The evaluation of renal ischaemic damage: the value of CD10 monoclonal antibody staining and of biochemical assessments of tissue viability

PubMed Central

Tagboto, S; Griffiths, A Paul

2007-01-01

Background It is well recognised that there is often a disparity between the structural changes observed in the kidney following renal injury and the function of the organ. For this reason, we carried out studies to explore possible means of studying and quantifying the severity of renal ischaemic damage using a laboratory model. Methods To do this, freshly isolated rabbit kidney tissue was subjected to warm (37°C) or cold (1°C) ischaemia for 20 hours. Following this, the tissue was stained using Haematoxylin and Eosin (H+E), Periodic Schiff reagent (PAS) and the novel monoclonal antibody CD10 stain. Additionally, ischaemic damage to the kidneys was assessed by biochemical tests of tissue viability using formazan-based colorimetry. Results CD 10 antibody intensely stained the brush border of control kidney tissue with mild or no cytoplasmic staining. Cell injury was accompanied by a redistribution of CD10 into the lumen and cell cytoplasm. There was good correlation between a score of histological damage using the CD 10 monoclonal antibody stain and the biochemical assessment of viability. Similarly, a score of histological damage using traditional PAS staining correlated well with that using the CD10 antibody stain. In particular, the biochemical assay and the monoclonal antibody staining techniques were able to demonstrate the efficacy of Soltran (this solution is used cold to preserve freshly isolated human kidneys prior to transplantation) in preserving renal tissue at cold temperatures compared to other randomly selected solutions. Conclusion We conclude that the techniques described using the CD10 monoclonal antibody stain may be helpful in the diagnosis and assessment of ischaemic renal damage. In addition, biochemical tests of viability may have an important role in routine histopathological work by giving additional information about cellular viability which may have implications on the function of the organ. PMID:17531101

Evolution of ischemic damage and behavioural deficit over 6 months after MCAo in the rat: Selecting the optimal outcomes and statistical power for multi-centre preclinical trials

PubMed Central

Churilov, Leonid; Sidon, T. Kate; Aleksoska, Elena; Cox, Susan F.; Macleod, Malcolm R.; Howells, David W.

2017-01-01

Key disparities between the timing and methods of assessment in animal stroke studies and clinical trial may be part of the reason for the failure to translate promising findings. This study investigates the development of ischemic damage after thread occlusion MCAo in the rat, using histological and behavioural outcomes. Using the adhesive removal test we investigate the longevity of behavioural deficit after ischemic stroke in rats, and examine the practicality of using such measures as the primary outcome for future studies. Ischemic stroke was induced in 132 Spontaneously Hypertensive Rats which were assessed for behavioural and histological deficits at 1, 3, 7, 14, 21, 28 days, 12 and 24 weeks (n>11 per timepoint). The basic behavioural score confirmed induction of stroke, with deficits specific to stroke animals. Within 7 days, these deficits resolved in 50% of animals. The adhesive removal test revealed contralateral neglect for up to 6 months following stroke. Sample size calculations to facilitate the use of this test as the primary experimental outcome resulted in cohort sizes much larger than are the norm for experimental studies. Histological damage progressed from a necrotic infarct to a hypercellular area that cleared to leave a fluid filled cavity. Whilst absolute volume of damage changed over time, when corrected for changes in hemispheric volume, an equivalent area of damage was lost at all timepoints. Using behavioural measures at chronic timepoints presents significant challenges to the basic science community in terms of the large number of animals required and the practicalities associated with this. Multicentre preclinical randomised controlled trials as advocated by the MultiPART consortium may be the only practical way to deal with this issue. PMID:28182727

Experimental approach to IGF-1 therapy in CCl4-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency.

PubMed

Morales-Garza, Luis A; Puche, Juan E; Aguirre, Gabriel A; Muñoz, Úrsula; García-Magariño, Mariano; De la Garza, Rocío G; Castilla-Cortazar, Inma

2017-05-04

Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl 4 )-induced liver damage compared to healthy controls (Wt Igf +/+ ). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 +/- ). Three groups of 25 ± 5-week-old healthy male mice (Wt Igf +/+ ) were included in the protocol: untreated controls (Wt). Controls that received CCl 4 (Wt + CCl 4 ) and Wt + CCl 4 were treated subcutaneously with IGF-1 (2 µg/100 g body weight/day) for 10 days (Wt + CCl 4  + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1 +/- ) groups were studied: untreated Hz, Hz + CCl 4 , and Hz + CCl 4  + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean ± SEM. An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl 4  + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl 4 . Moreover, there was a correlation between MDA levels and the histological damage score (Pearson's r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series (healthy and IGF-1-deficient mice) with acute liver damage, suggesting that low doses of IGF-1, in acute liver damage, could be a feasible therapeutic option.

Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice

PubMed Central

Cui, Yi; Wei, Hongyun; Lu, Fanggen; Liu, Xiaowei; Liu, Deliang; Gu, Li; Ouyang, Chunhui

2016-01-01

Aim To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. Methods Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. Results The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. Conclusions Administration of an L. crispatus CCTCC M206119 supplement aggravated DSS-induced colitis. L. fermentum CCTCC M206110 proved to be effective at attenuating DSS-induced colitis. The potential probiotic effect of L. plantarum NCIMB8826 on UC has yet to be assessed. PMID:26840426

Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice.

PubMed

Cui, Yi; Wei, Hongyun; Lu, Fanggen; Liu, Xiaowei; Liu, Deliang; Gu, Li; Ouyang, Chunhui

2016-01-01

To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. Administration of an L. crispatus CCTCC M206119 supplement aggravated DSS-induced colitis. L. fermentum CCTCC M206110 proved to be effective at attenuating DSS-induced colitis. The potential probiotic effect of L. plantarum NCIMB8826 on UC has yet to be assessed.

Chronic viral hepatitis: the histology report.

PubMed

Guido, Maria; Mangia, Alessandra; Faa, Gavino

2011-03-01

In chronic viral hepatitis, the role of liver biopsy as a diagnostic test has seen a decline, paralleled by its increasing importance for prognostic purposes. Nowadays, the main indication for liver biopsy in chronic viral hepatitis is to assess the severity of the disease, in terms of both necro-inflammation (grade) and fibrosis (stage), which is important for prognosis and therapeutic management. Several scoring systems have been proposed for grading and staging chronic viral hepatitis and there is no a general consensus on the best system to be used in the daily practice. All scoring systems have their drawbacks and all may be affected by sampling and observer variability. Whatever the system used, a histological score is a reductive approach since damage in chronic viral hepatitis is a complex biological process. Thus, scoring systems are not intended to replace the detailed, descriptive, pathology report. In fact, lesions other than those scored for grading and staging may have clinical relevance and should be assessed and reported. This paper aims to provide a systematic approach to the interpretation of liver biopsies obtained in cases of chronic viral hepatitis, with the hope of helping general pathologists in their diagnostic practice. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

Xilei San Ameliorates Experimental Colitis in Rats by Selectively Degrading Proinflammatory Mediators and Promoting Mucosal Repair

PubMed Central

Hori, Kazutoshi; Wang, Shenglan; Kogure, Yoko; Fukunaga, Ken; Kashiwamura, Shinichiro; Yamamoto, Satoshi; Nakamura, Shiro; Li, Junxiang; Miwa, Hiroto; Noguchi, Koichi

2014-01-01

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC. PMID:25120575

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair.

PubMed

Hao, Yongbiao; Nagase, Kazuko; Hori, Kazutoshi; Wang, Shenglan; Kogure, Yoko; Fukunaga, Ken; Kashiwamura, Shinichiro; Yamamoto, Satoshi; Nakamura, Shiro; Li, Junxiang; Miwa, Hiroto; Noguchi, Koichi; Dai, Yi

2014-01-01

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.

In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis

PubMed Central

Hausmann, M; Obermeier, F; Paper, D H; Balan, K; Dunger, N; Menzel, K; Falk, W; Schoelmerich, J; Herfarth, H; Rogler, G

2007-01-01

Recently we demonstrated that in inflammatory bowel disease (IBD) macrophage-oxidative burst activity is increased and NADPH oxidase mRNA is induced. The herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced colitis model, in this study we have assessed whether systemic application of acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment with acteoside (120, 600 µg/mouse/day) was performed intraperitoneally. The colon lengths were determined. Colonic tissue was scored histologically (max. score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)-2 (final concentration 10 U/ml). After incubation for 24 h, IL-1β, IL-6, IL-12 tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in supernatants were analysed by the beadlyte® cytokine detection system. Histological scoring of colonic tissue revealed that application of acteoside was followed by a significantly improved histological score. In acute colitis the histological score was 3·2 with acteoside versus 5·2 with phosphate-buffered saline (PBS) (P < 0·02). In chronic colitis both 120 µg (3·3 versus 5·2) or 600 µg acteoside (3·0 versus 5·2) significantly ameliorated colitis (both P < 0·02). Stimulated MLN from mice with chronic DSS-induced colitis treated with acteoside showed a significant down-regulation of IFN-γ secretion (195 pg/ml with 600 µg acteoside versus 612 pg/ml with PBS, P < 0·02). Inhibition of oxidative burst activity with acteoside reduced mucosal tissue damage in DSS colitis and could be a therapeutic alternative for IBD treatment. Further studies of this agent are warranted. PMID:17437425

Lack of clinical and histological progression of chronic hepatitis C in individuals with true persistently normal ALT: the result of a 17-year follow-up.

PubMed

Nunnari, G; Pinzone, M R; Cacopardo, B

2013-04-01

Thirty to 40% of patients with chronic hepatitis C have persistently normal alanine aminotransferase (PNALT). Even though traditionally considered as healthy people, most PNALT carriers actually have some degree of clinical progression and histological liver damage. We evaluated the clinical and histological outcome of a 17-year follow-up on a cohort of patients with chronic HCV infection and PNALT. Between 1994 and 2011, 70 PNALTs and 55 Hyper-alanine aminotransferase (ALT) subjects underwent a clinical, biochemical, virological and histological follow-up. At the end of the follow-up, all patients were alive. In the PNALT group, none of the patients developed hepatic decompensation, while 14.5% of Hyper-ALTs were diagnosed as affected by decompensated cirrhosis. No significant variation of the Metavir grading and staging scores was observed among PNALTs by comparing pre- and post-follow-up liver specimens. On the contrary, a significant increase in both Metavir grading and staging scores was noticed within the Hyper-ALT group. Finally, the analysis of IL28B single-nucleotide polymorphism rs12979860 revealed no difference between Hyper-ALTs and PNALTs in terms of frequency of C/C genotype. In conclusion, progression of chronic hepatitis C among PNALTs is slow or even absent, because at the end of the 17-year follow-up histological and clinical parameters had not worsened significantly. © 2012 Blackwell Publishing Ltd.

Assessment of Histological Remission in Ulcerative Colitis: Discrepancies Between Daily Practice and Expert Opinion.

PubMed

Römkens, Tessa E H; Kranenburg, Pim; Tilburg, Arjan van; Bronkhorst, Carolien; Nagtegaal, Iris D; Drenth, Joost P H; Hoentjen, Frank

2018-03-28

Histological remission [HR] is a potential treatment target in ulcerative colitis [UC]. Limited 'real world' data are available on the reliability of histological scoring when assessing minimal histological inflammation. The aim of this study was to investigate the reliability of UC histological scores in colonic biopsies showing mucosal healing [MH] and limited histological inflammation, and to compare the 'daily practice' histological assessment with expert reviews by gastrointestinal [GI] pathologists. We performed a retrospective single-centre study. Colonic biopsies from UC patients with MH [Mayo score ≤ 1] were included. All biopsies assessed in daily practice were reassessed by three blinded GI pathologists using three histological scores (Geboes score [GS], Riley score [RS], Harpaz [Gupta] Index [HGI]) and a global visual scale [GVS]. We evaluated inter- and intra-observer variation between GI pathologists and correlations between scores including the initial histological assessment using Cronbach's alpha and Spearman rho analysis. In total, 270 biopsies from 39 UC patients were included. The inter-observer concordance for all histological indexes was substantial to almost perfect [GS 0.84; HGI 0.61; GVS 0.74, RS 0.91]. Correlation between the RS and GS was almost perfect [R = 0.86], but we found no correlation between the primary histological assessment and reassessment by GI pathologists. Current UC histological scores reliably assess limited histological inflammation in UC patients. The discrepancy between the initial histological assessment and the reassessment by dedicated GI pathologists suggests a gap between daily practice and academic expertise. This issue may limit the implementation of HR as a treatment target for UC in daily practice.

Hydroalcoholic extract of Brazilian red propolis exerts protective effects on acetic acid-induced ulcerative colitis in a rodent model.

PubMed

Barbosa Bezerra, Gislaine; de Menezes de Souza, Luana; Dos Santos, Adailma Santana; de Almeida, Grace Kelly Melo; Souza, Marília Trindade Santana; Santos, Sandra Lauton; Aparecido Camargo, Enilton; Dos Santos Lima, Bruno; de Souza Araújo, Adriano Antunes; Cardoso, Juliana Cordeiro; Gomes, Silvana Vieira Floresta; Gomes, Margarete Zanardo; de Albuquerque, Ricardo Luiz Cavalcanti

2017-01-01

Ulcerative colitis (UC) is a common intestinal inflammatory disease with an etiology that is not well understood. Although the anti-inflammatory and anti-oxidant effects of the hydroalcoholic extract of Brazilian red propolis (HERP) have been reported in various experimental models, its protective effect in models of UC have not been evaluated. The purpose of this study was to investigate the chemopreventive effect of hydroalcoholic extract of Brazilian red propolis (HERP) in acetic acid-induced colitis (AAIC) using a rodent model. The HERP was chemically characterised by HPLC/DAD analyses. Male rats were randomly assigned into four groups: sham, vehicle (with AAIC, treated with vehicle), P10 (with AAIC, treated with 10mg/kg HERP), and P100 (with AAIC, treated with 100mg/kg HERP). Treatments were performed for 7days, and colitis was induced on day seven. Animals were euthanized 24h after colitis induction and body weight, colon length, gross and histological scores, malondialdehyde (MDA) and myeloperoxidase (MPO) concentrations in colon tissue, and the immunohistochemical expression of inducible nitric oxide synthase (iNOS) were assessed. The major compounds found in HERP were liquiritigenin (68.8mg/g), formononetin (54.29mg/g), biochanin A (30.97mg/g), and daidzein (19.90mg/g). Rats treated with 10mg/kg HERP demonstrated significant decreases in MPO concentrations, gross and histological scores of tissue damage, and iNOS expression (p<0.05). Similarly, rats treated with 100mg/kg HERP demonstrated significant decreases in MPO levels (p<0.05) and histological scores of tissue damage (p<0.05). The results of this study indicate that oral administration of HERP attenuates AAIC in rats, which may be due to anti-inflammatory effects related to iNOS inhibition. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The effect of topical anesthetic hydration on the depth of thermal injury from the plasma skin regeneration device.

PubMed

Sanderson, Alicia R; Wu, Edward C; Liaw, Lih-Huei L; Garg, Rohit; Gangnes, Richard A

2014-02-01

The plasma skin regeneration (PSR) device delivers thermal energy to the skin by converting nitrogen gas to plasma. Prior to treatment, hydration of the skin is recommended as it is thought to limit the zone of thermal damage. However, there is limited data on optimal hydration time. This pilot study aims to determine the effect of topical anesthetic application time on the depth of thermal injury from a PSR device using histology. PSR (1.8 and 3.5 J) was performed after 0, 30, or 60 minutes of topical anesthetic application. Rhytidectomy was then performed and skin was fixed for histologic analysis. Four patients (two control and four treatment sites per patient) undergoing rhytidectomy were recruited for the study. Each patient served as his/her own control (no hydration). A scoring system for tissue injury was developed. Epidermal injury, the presence of vacuolization, blistering, damage to adnexal structures, and depth of dermal collagen changes were evaluated in over 1,400 high-power microscopy fields. There was a significant difference in the average thermal injury score, depth of thermal damage, and epidermal injury when comparing controls to 30 minutes of hydration (P = 0.012, 0.012, 0.017, respectively). There was no statistical difference between controls and 60 minutes of hydration or between 30 and 60 minutes of hydration. Epidermal vacuolization at low energy and patchy distribution of thermal injury was also observed. Topical hydration influences the amount of thermal damage when applied to skin for 30 minutes prior to treatment with the PSR device. There was a trend toward decreasing thermal damage at 60 minutes, and there was no difference between treatment for 30 or 60 minutes. The data suggest that application of topical anesthetic for a short period of time prior to treatment with the PSR device is cost-effective, safe, and may be clinically beneficial. © 2013 Wiley Periodicals, Inc.

Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat.

PubMed

Miampamba, M; Parr, E J; McCafferty, D M; Wallace, J L; Sharkey, K A

1998-03-01

We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry. When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC. Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.

Comparison of renal artery, soft tissue, and nerve damage after irrigated versus nonirrigated radiofrequency ablation.

PubMed

Sakakura, Kenichi; Ladich, Elena; Fuimaono, Kristine; Grunewald, Debby; O'Fallon, Patrick; Spognardi, Anna-Maria; Markham, Peter; Otsuka, Fumiyuki; Yahagi, Kazuyuki; Shen, Kai; Kolodgie, Frank D; Joner, Michael; Virmani, Renu

2015-01-01

The long-term efficacy of radiofrequency ablation of renal autonomic nerves has been proven in nonrandomized studies. However, long-term safety of the renal artery (RA) is of concern. The aim of our study was to determine if cooling during radiofrequency ablation preserved the RA while allowing equivalent nerve damage. A total of 9 swine (18 RAs) were included, and allocated to irrigated radiofrequency (n=6 RAs, temperature setting: 50°C), conventional radiofrequency (n=6 RAs, nonirrigated, temperature setting: 65°C), and high-temperature radiofrequency (n=6 RAs, nonirrigated, temperature setting: 90°C) groups. RAs were harvested at 10 days, serially sectioned from proximal to distal including perirenal tissues and examined after paraffin embedding, and staining with hematoxylin-eosin and Movat pentachrome. RAs and periarterial tissue including nerves were semiquantitatively assessed and scored. A total of 660 histological sections from 18 RAs were histologically examined by light microscopy. Arterial medial injury was significantly less in the irrigated radiofrequency group (depth of medial injury, circumferential involvement, and thinning) than that in the conventional radiofrequency group (P<0.001 for circumference; P=0.003 for thinning). Severe collagen damage such as denatured collagen was also significantly less in the irrigated compared with the conventional radiofrequency group (P<0.001). Nerve damage although not statistically different between the irrigated radiofrequency group and conventional radiofrequency group (P=0.36), there was a trend toward less nerve damage in the irrigated compared with conventional. Compared to conventional radiofrequency, circumferential medial damage in highest-temperature nonirrigated radiofrequency group was significantly greater (P<0.001). Saline irrigation significantly reduces arterial and periarterial tissue damage during radiofrequency ablation, and there is a trend toward less nerve damage. © 2014 American Heart Association, Inc.

Effect of mesalamine and prednisolone on TNBS experimental colitis, following various doses of orally administered iron.

PubMed

Triantafillidis, John K; Douvi, Georgia; Agrogiannis, George; Patsouris, Efstratios; Gikas, Aristofanis; Papalois, Apostolos E

2014-01-01

Experimental data suggest that oral iron (I.) supplementation can worsen colitis in animals. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M.) and Prednisolone (P.) on the severity of TNBS colitis following orally administered I. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor- α (t-TNF- α ) and tissue malondialdehyde (t-MDA) were estimated in all animal groups. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet) resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF- α levels (17.67 ± 4.92 versus 14.58 ± 5.71, P = 0.102), although it significantly reduced the t-MDA levels (5.79 ± 1.55 versus 3.67 ± 1.39, P = 0.000). Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet) did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF- α (16.57 ± 5.61 versus 14.65 ± 3.88, P = 0.296). However, M. significantly reduced the t-MDA levels (5.99 ± 1.37 versus 4.04 ± 1.41, P = 0.000). Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF- α levels (17.67 ± 4.92 versus 12.64 ± 3.97, P = 0.003) and the t-MDA levels (5.79 ± 1.54 versus 3.47 ± 1.21, P = 0.001). Administration of P on TNBS colitis after high I. supplementation resulted in a significant improvement of the overall histological score and three individual histological parameters and significantly reduced the levels of t-TNF- α (16.6 ± 5.6 versus 11.85 ± 1.3, P = 0.001). I. can induce colonic inflammation and aggravate TNBS colitis. M. and P. can significantly improve the inflammatory process in the colonic mucosa in TNBS colitis aggravated by orally administered I. P. has a stable anti-TNF- α effect. These findings suggest that the harmful.

Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats.

PubMed

Nicolau, Lucas A D; Carvalho, Nathalia S; Pacífico, Dvison M; Lucetti, Larisse T; Aragão, Karoline S; Véras, Leiz M C; Souza, Marcellus H L P; Leite, José R S A; Medeiros, Jand Venes R

2017-03-01

This study aimed to investigate the protective effect of epiisopiloturine hydrochloride (EPI), an imidazole alkaloid, on NAP-induced gastrointestinal damage in rats. Initially, rats were pretreated with 0.5% carboxymethylcellulose (vehicle) or EPI (3, 10 and 30mg/kg, p.o. or i.p., groups 3-5, respectively) twice daily, for 2days. After 1h, NAP (80mg/kg, p.o.) was given. The control group received only vehicle (group 1) or vehicle+naproxen (group 2). Rats were euthanized on 2nd day, 4h after NAP treatment. Stomachs lesions were measured. Samples were collected for histological evaluation and glutathione (GSH), malonyldialdehyde (MDA), myeloperoxidase (MPO), and cytokines levels. Moreover, gastric mucosal blood flow (GMBF) was evaluated. EPI pretreatment prevented NAP-induced macro and microscopic gastric damage with a maximal effect at 10mg/kg. Histological analysis revealed that EPI decreased scores of damage caused by NAP. EPI reduced MPO (3.4±0.3U/mg of gastric tissue) and inhibited changes in MDA (70.4±8.3mg/g of gastric tissue) and GSH (246.2±26.4mg/g of gastric tissue). NAP increased TNF-α levels, and this effect was reduced by EPI pretreatment. Furthermore, EPI increased GMBF by 15% compared with the control group. Our data show that EPI protects against NAP-induced gastric and intestinal damage by reducing pro-inflammatory cytokines, reducing oxidative stress, and increasing GMBF. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Macroscopic cartilage repair scoring of defect fill, integration and total points correlate with corresponding items in histological scoring systems - a study in adult sheep.

PubMed

Goebel, L; Orth, P; Cucchiarini, M; Pape, D; Madry, H

2017-04-01

To correlate osteochondral repair assessed by validated macroscopic scoring systems with established semiquantitative histological analyses in an ovine model and to test the hypothesis that important macroscopic individual categories correlate with their corresponding histological counterparts. In the weight-bearing portion of medial femoral condyles (n = 38) of 19 female adult Merino sheep (age 2-4 years; weight 70 ± 20 kg) full-thickness chondral defects were created (size 4 × 8 mm; International Cartilage Repair Society (ICRS) grade 3C) and treated with Pridie drilling. After sacrifice, 1520 blinded macroscopic observations from three observers at 2-3 time points including five different macroscopic scoring systems demonstrating all grades of cartilage repair where correlated with corresponding categories from 418 blinded histological sections. Categories "defect fill" and "total points" of different macroscopic scoring systems correlated well with their histological counterparts from the Wakitani and Sellers scores (all P ≤ 0.001). "Integration" was assessed in both histological scoring systems and in the macroscopic ICRS, Oswestry and Jung scores. Here, a significant relationship always existed (0.020 ≤ P ≤ 0.049), except for Wakitani and Oswestry (P = 0.054). No relationship was observed for the "surface" between histology and macroscopy (all P > 0.05). Major individual morphological categories "defect fill" and "integration", and "total points" of macroscopic scoring systems correlate with their corresponding categories in elementary and complex histological scoring systems. Thus, macroscopy allows to precisely predict key histological aspects of articular cartilage repair, underlining the specific value of macroscopic scoring for examining cartilage repair. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Intra- and inter-observer reliability of ten major histological scoring systems used for the evaluation of in vivo cartilage repair.

PubMed

Bonasia, Davide Edoardo; Marmotti, Antongiulio; Massa, Alessandro Domenico Felice; Ferro, Andrea; Blonna, Davide; Castoldi, Filippo; Rossi, Roberto

2015-09-01

In the last two decades, many surgical techniques have been described for articular cartilage repair. Reliable histological scoring systems are fundamental tools to evaluate new procedures. Several histological scoring systems have been described, and these can be divided in elementary and comprehensive scores, according to the number of sub-items. The aim of this study was to test the inter- and intra-observer reliability of ten main scores used for the histological evaluation of in vivo cartilage repair. The authors tested the starting hypothesis that elementary scores would show superior intra- and inter-observer reliability compared with comprehensive scores. Fifty histological sections obtained from the trochlea of New Zealand Rabbit and stained with Safranin-O fast green were used. The histological sections were analysed by 4 observers: 2 experienced in cartilage histology and 2 inexperienced. Histological evaluations were performed at time 1 and time 2, separated by a 30-day interval. The following scores were used: Mankin, O'Driscoll, Pineda, Wakitani, Fortier, Selleres, ICRS, ICRSII, Oswestry (OsScore) and modified O'Driscoll. Intra- and inter-observer reliability were evaluated for each score. In addition, the pavement-ceiling effect and the Bland-Altman Coefficient of Repeatability were then evaluated for each sub-item of every score. Intra-observer reliability was high for all observers in every score, even though the reliability was significantly lower for non-expert observers compared with expert counterparts. In terms of Coefficient of Repeatability, some scores performed better (O'Driscoll, Modified O'Driscoll and ICRSII) than others (Fortier, Seller). Inter-observer reliability was high for all observers in every score, but significantly lower for non-expert compared with expert observers. In expert hands, all the scores showed high intra- and inter-observer reliability, independently of the complexity. Although every score has advantages and disadvantages, ICRSII, O'Driscoll and Modified O'Driscoll scores should be preferred for the evaluation of in vivo cartilage repair in animal models.

Comparison of heat induced damage at the saphenofemoral junction after ablation with 1,470 nm laser or radiofrequency.

PubMed

Ozcinar, Evren; Cakici, Mehmet; Korun, Oktay; Han, Unsal; Kiziltepe, Ugursay

2017-03-01

The aim of this study was to evaluate the heat induced damage at the saphenofemoral junction level according to histopathological changes after radiofrequency or 1,470 nm radial tip laser ablation. Varicose vein segments of 6-10 mm in diameter were exposed to radiofrequency (Closure Fast catheter, 7 cm heat segment, one cycle, 15 seconds, 10 Watt, 120 °C) or laser ablation (1,470 nm radial tip, continuous wave, vein diameter: 6 cm/8 cm/10 cm-power: 10 Watt-pullback speed: 2.2 mm/s, 1.7 mm/s, 1.3 mm/s-LEED: 45J/cm, 60J/cm, 75J/cm-EFE 25J/cm 2 , respectively). Approximate 2 cm segments of the vein were left untreated, then histopathological examinations of the untouched segments (5 slices: level 1 - furthest segment, level 2 - nearest segment) for heat induced damage were performed. A total damage scoring system was established, including the presence of endothelial swelling, intimal thickening, cellular vacuolisation in the muscle layer, oedema in the tunica media, and extent of necrosis. At level 1, the furthest segment of the specimen, there was no significant difference between the laser and control group, while the total damage score of the radiofrequency group was significantly higher than the control group (p < 0.01). Radiofrequency group had higher total damage score compared to the laser group at level 1 (p < 0.01), 2 (p < 0.01), and 5 (p < 0.01); while no significant difference was observed at level 3 (p = 0.46) and 4 (p = 0.13). Significant heat induced damage may be seen even if the 2 cm segment of the vessel is left unablated. Radiofrequency ablation seems to cause more histological damage than laser ablation in this ex vivo study. Further in vivo studies are necessary, in order to validate these findings.

Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes

PubMed Central

Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K.; Vitalone, Matthew J.; Chen, Rong; Butte, Atul J.; Salvatierra, Oscar; Sarwal, Minnie M.

2015-01-01

The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy. PMID:21881554

Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.

PubMed

Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K; Vitalone, Matthew J; Chen, Rong; Butte, Atul J; Salvatierra, Oscar; Sarwal, Minnie M

2011-12-01

The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy.

Myristica fragrans seed extract protects against dextran sulfate sodium-induced colitis in mice.

PubMed

Kim, Hyojung; Bu, Youngmin; Lee, Beom-Joon; Bae, Jinhyun; Park, Sujin; Kim, Jinsung; Lee, Kyungjin; Cha, Jae-Myung; Ryu, Bongha; Ko, Seok-Jae; Han, Gajin; Min, Byungil; Park, Jae-Woo

2013-10-01

Nutmeg (seed of Myristica fragrans [MF]) is one of the most commonly used spices in the world and also a well-known herb for the treatment of various intestinal diseases, including colitis in traditional Korean medicine. The purpose of the current study was to investigate whether water extract of MF (MFE) can protect against dextran sulfate sodium (DSS) induced colitis in a mouse model. Colitis was induced by 5% DSS in balb/c mice. MFE (100, 300 or 1000 mg/kg) was orally administered to the mice twice a day for 7 days. Body weight, colon length, clinical score, and histological score were assessed to determine the effects on colitis. Proinflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were measured to investigate the mechanisms of action. MFE dose dependently inhibited the colon shortening and histological damage to the colon. However, it did not prevent weight loss. MFE also inhibited proinflammatory cytokines. The current results suggest that MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. Further investigation, including the exact mechanisms is needed.

The Effects of Ionizing Radiation and Hyperthermia on Mouse Spinal Cord.

NASA Astrophysics Data System (ADS)

Lo, Yeh-Chi

Assays were developed to quantify spinal cord damage in the mouse following radiation (X), hyperthermia (H) and their combination. The spinal cord (T_9-L _5) of C3Hf/Sed//Kam mice was irradiated with single (12-75 Gy) or fractionated doses (2 Gy to 23 Gy per fraction). Four arbitrary scales of neurological change were used. Findings for X were: (1) Radiation induces progressive damage, from mild to severe. (2) The latency to damage depended on the dose and the level of damage. Following doses around the ED50 (20-27 Gy), the onset of paralysis occurred between 6 and 8 months. (3) For the NSD equation, the exponent for N was 0.36-0.33 for mild to severe paralysis (score 1-3). Comparison of ED_{rm 50s} for 2 fractions separated by various intervals showed no time effect until 30-60 days. (4) If the data for higher doses per fraction were excluded (>10 Gy), the alpha/beta ratios were 3.5-5.6 for score 1-3. (5) Histological evidence of demyelination was evident at the time of paralysis. Using a water bath, the spinal cord was heated at 42.0 to 43.0^circC for 10-100 min. The results were: (1) Hyperthermia produces an acute reversible damage in the surviving mice. (2) No detectable late effects were seen up to 1.5 years. (3) A value of 0.48 for R in the thermal dose equation was found. (4) Heat lesions included neuronal and vascular damage, but this was seen only at high thermal dose. Mild thermal doses (42.5^circ C for 20-50 min.) were combined with single radiation doses ranging from 12 to 35 Gy in various sequences and time intervals. Findings were: (1) An acute and reversible potentiated damage (score 1) was found when H was given 5 min. before or 5 min., 7, 30, 60 and 150 days after X, but not in 7 days before or 1 day or 90 days after X. (2) An enhanced late effect was found when H was given 5 min. or 150 days after X. (3) Late effects were reduced when heat was given 5 min. or 1 day before or 1 day after X. (4) It seems that target cells (or targets within cells) for H and X may be different but may partially overlap. (5) Histological examination revealed both demyelination and vascular lesions in paralyzed animals. Comparison of human and the present data for paralysis following X, H and the combined treatment suggested that it may be possible to predict responses of humans using mouse data.

Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron

PubMed Central

Triantafillidis, John K.; Douvi, Georgia; Agrogiannis, George; Patsouris, Efstratios; Gikas, Aristofanis; Papalois, Apostolos E.

2014-01-01

Background. Experimental data suggest that oral iron (I.) supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M.) and Prednisolone (P.) on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α) and tissue malondialdehyde (t-MDA) were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet) resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67 ± 4.92 versus 14.58 ± 5.71, P = 0.102), although it significantly reduced the t-MDA levels (5.79 ± 1.55 versus 3.67 ± 1.39, P = 0.000). Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet) did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57  ± 5.61 versus 14.65 ± 3.88, P = 0.296). However, M. significantly reduced the t-MDA levels (5.99 ± 1.37 versus 4.04 ± 1.41, P = 0.000). Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67 ± 4.92 versus 12.64 ± 3.97, P = 0.003) and the t-MDA levels (5.79 ± 1.54 versus 3.47 ± 1.21, P = 0.001). Administration of P on TNBS colitis after high I. supplementation resulted in a significant improvement of the overall histological score and three individual histological parameters and significantly reduced the levels of t-TNF-α (16.6 ± 5.6 versus 11.85 ± 1.3, P = 0.001). Conclusion. I. can induce colonic inflammation and aggravate TNBS colitis. M. and P. can significantly improve the inflammatory process in the colonic mucosa in TNBS colitis aggravated by orally administered I. P. has a stable anti-TNF-α effect. These findings suggest that the harmful. PMID:24895596

Phototoxic effects of commercial photographic flash lamp on rat eyes.

PubMed

Inoue, Makoto; Shinoda, Kei; Ohde, Hisao; Tezuka, Keiji; Hida, Tetsuo

2006-11-01

To determine whether exposure of the cornea and retina of rats to flashes from a commercial photographic flash lamp is phototoxic. Sprague-Dawley rats were exposed to 10, 100, or 1,000 flashes of the OPTICAM 16M photographic flash lamp (Fujikoeki, Japan) placed 0.1, 1, or 3 m from the eyes. Corneal damage was assessed by a fluorescein staining score, and the retinal damage by eletroretinography (ERG) and histology before and 24 h after exposure. Exposure of the eyes to 1,000 flashes at 0.1 m increased the fluorescein staining score significantly (P = 0.009, the Mann-Whitney test). Scanning electron microscopy (SEM) of the cornea showed a detachment of the epithelial cells from the surface after this exposure. The amplitude of the a-wave was decreased significantly by 23.0% (P = 0.026) of the amplitude before the exposure, and the b-wave by 19.7% (P = 0.0478) following 1,000 flashes at 0.1 m but not by the other exposures. TUNEL-positive cells were present in the outer nuclear layer only after the extreme exposure, but no significant decrease in retinal thickness was seen under any condition. The fluorescein staining score and ERGs recovered to control levels within 1 week. Light exposure to a photographic flash lamp does not induce damage to the cornea and retina except when they are exposed to 1,000 flashes at 0.1 m.

Neuroprotective Effects of Cannabidiol in Hypoxic Ischemic Insult. The Therapeutic Window in Newborn Mice.

PubMed

Mohammed, Nagat; Ceprian, Maria; Jimenez, Laura; Pazos, M Ruth; Martínez-Orgado, Jose

2017-01-01

A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage. To test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage. 9-10 day-old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation). Then, CBD 1 mg/kg or vehicle were administered s.c. 15 min, or 1, 3, 6, 12, 18 or 24 h after the end of the HI insult. Seven days later brain damage was assessed using T2W Magnetic Resonance Imaging scan (ipsilateral hemisphere volume loss, IVHL) and histological studies: Nissl staining (neuropathological score), TUNEL staining (apoptotic damage) and immunohistochemistry with glial fibrillary acidic protein (astrocyte viability) or ionized calcium binding adaptor molecule (microglial activation). CBD administered up to 18 h after HI reduced IHVL and neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. In addition, CBD blunted the HI-induced increase in microglial population. When CBD administration was delayed 24 h, however, the neuroprotective effect was lost in terms of IHVL, apoptosis or astrogliosis reduction. CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evidence of cartilage repair by joint distraction in a canine model of osteoarthritis.

PubMed

Wiegant, Karen; Intema, Femke; van Roermund, Peter M; Barten-van Rijbroek, Angelique D; Doornebal, Arie; Hazewinkel, Herman A W; Lafeber, Floris P J G; Mastbergen, Simon C

2015-02-01

Knee osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage, bone, and synovial tissue changes that lead to pain and functional impairment. Joint distraction is a treatment that provides long-term improvement in pain and function accompanied by cartilage repair, as evaluated indirectly by imaging studies and measurement of biochemical markers. The purpose of this study was to evaluate cartilage tissue repair directly by histologic and biochemical assessments after joint distraction treatment. In 27 dogs, OA was induced in the right knee joint (groove model; surgical damage to the femoral cartilage). After 10 weeks of OA development, the animals were randomized to 1 of 3 groups. Two groups were fitted with an external fixator, which they wore for a subsequent 10 weeks (one group with and one without joint distraction), and the third group had no external fixation (OA control group). Pain/function was studied by force plate analysis. Cartilage integrity and chondrocyte activity of the surgically untouched tibial plateaus were analyzed 25 weeks after removal of the fixator. Changes in force plate analysis values between the different treatment groups were not conclusive. Features of OA were present in the OA control group, in contrast to the generally less severe damage after joint distraction. Those treated with joint distraction had lower macroscopic and histologic damage scores, higher proteoglycan content, better retention of newly formed proteoglycans, and less collagen damage. In the fixator group without distraction, similarly diminished joint damage was found, although it was less pronounced. Joint distraction as a treatment of experimentally induced OA results in cartilage repair activity, which corroborates the structural observations of cartilage repair indicated by surrogate markers in humans. Copyright © 2015 by the American College of Rheumatology.

Long-term native liver fibrosis in biliary atresia: development of a novel scoring system using histology and standard liver tests.

PubMed

Tomita, Hirofumi; Masugi, Yohei; Hoshino, Ken; Fuchimoto, Yasushi; Fujino, Akihiro; Shimojima, Naoki; Ebinuma, Hirotoshi; Saito, Hidetsugu; Sakamoto, Michiie; Kuroda, Tatsuo

2014-06-01

Although liver fibrosis is an important predictor of outcomes for biliary atresia (BA), postsurgical native liver histology has not been well reported. Here, we retrospectively evaluated postsurgical native liver histology, and developed and assessed a novel scoring system - the BA liver fibrosis (BALF) score for non-invasively predicting liver fibrosis grades. We identified 259 native liver specimens from 91 BA patients. Of these, 180 specimens, obtained from 62 patients aged ≥1 year at examination, were used to develop the BALF scoring system. The BALF score equation was determined according to the prediction of histological fibrosis grades by multivariate ordered logistic regression analysis. The diagnostic powers of the BALF score and several non-invasive markers were assessed by area under the receiver operating characteristic curve (AUROC) analyses. Natural logarithms of the serum total bilirubin, γ-glutamyltransferase, and albumin levels, and age were selected as significantly independent variables for the BALF score equation. The BALF score had a good diagnostic power (AUROCs=0.86-0.94, p<0.001) and good diagnostic accuracy (79.4-93.3%) for each fibrosis grade. The BALF score revealed a strong correlation with fibrosis grade (r=0.77, p<0.001), and was the preferable non-invasive marker for diagnosing fibrosis grades ⩾F2. In a serial liver histology subgroup analysis, 7/15 patients exhibited liver fibrosis improvement with BALF scores being equivalent to histological fibrosis grades of F0-1. In postsurgical BA patients aged ⩾1year, the BALF score is a potential non-invasive marker of native liver fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Assessment of the correlation between histological degeneration and radiological and clinical parameters in a series of patients who underwent lumbar disc herniation surgery].

PubMed

Munarriz, Pablo M; Paredes, Igor; Alén, José F; Castaño-Leon, Ana M; Cepeda, Santiago; Hernandez-Lain, Aurelio; Lagares, Alfonso

The use of histological degeneration scores in surgically-treated herniated lumbar discs is not common in clinical practice and its use has been primarily restricted to research. The objective of this study is to evaluate if there is an association between a higher grade of histological degeneration when compared with clinical or radiological parameters. Retrospective consecutive analysis of 122 patients who underwent single-segment lumbar disc herniation surgery. Clinical information was available on all patients, while the histological study and preoperative magnetic resonance imaging were also retrieved for 75 patients. Clinical variables included age, duration of symptoms, neurological deficits, or affected deep tendon reflex. The preoperative magnetic resonance imaging was evaluated using Modic and Pfirrmann scores for the affected segment by 2 independent observers. Histological degeneration was evaluated using Weiler's score; the presence of inflammatory infiltrates and neovascularization, not included in the score, were also studied. Correlation and chi-square tests were used to assess the association between histological variables and clinical or radiological variables. Interobserver agreement was also evaluated for the MRI variables using weighted kappa. No statistically significant correlation was found between histological variables (histological degeneration score, inflammatory infiltrates or neovascularization) and clinical or radiological variables. Interobserver agreement for radiological scores resulted in a kappa of 0.79 for the Pfirrmann scale and 0.65 for the Modic scale, both statistically significant. In our series of patients, we could not demonstrate any correlation between the degree of histological degeneration or the presence of inflammatory infiltrates when compared with radiological degeneration scales or clinical variables such as the patient's age or duration of symptoms. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

FREQUENCY CONTENT OF CARTILAGE IMPACT FORCE SIGNAL REFLECTS ACUTE HISTOLOGIC STRUCTURAL DAMAGE.

PubMed

Heiner, Anneliese D; Martin, James A; McKinley, Todd O; Goetz, Jessica E; Thedens, Daniel R; Brown, Thomas D

2012-10-01

The objective of this study was to determine if acute cartilage impact damage could be predicted by a quantification of the frequency content of the impact force signal. Osteochondral specimens excised from bovine lateral tibial plateaus were impacted with one of six impact energies. Each impact force signal underwent frequency analysis, with the amount of higher-frequency content (percent of frequency spectrum above 1 KHz) being registered. Specimens were histologically evaluated to assess acute structural damage (articular surface cracking and cartilage crushing) resulting from the impact. Acute histologic structural damage to the cartilage had higher concordance with the high-frequency content measure than with other mechanical impact measures (delivered impact energy, impact maximum stress, and impact maximum stress rate of change). This result suggests that the frequency content of an impact force signal, specifically the proportion of higher-frequency components, can be used as a quick surrogate measure for acute structural cartilage injury. Taking advantage of this relationship could reduce the time and expense of histological processing needed to morphologically assess cartilage damage, especially for purposes of initial screening when evaluating new impaction protocols.

Using Optical Coherence Tomography to Evaluate Skin Sun Damage and Precancer

PubMed Central

Korde, Vrushali R.; Bonnema, Garret T.; Xu, Wei; Krishnamurthy, Chetankumar; Ranger-Moore, James; Saboda, Kathylynn; Slayton, Lisa D.; Salasche, Stuart J.; Warneke, James A.; Alberts, David S.; Barton, Jennifer K.

2008-01-01

Background and Objectives Optical coherence tomography (OCT) is a depth resolved imaging modality that may aid in identifying sun damaged skin and the precancerous condition actinic keratosis (AK). Study Design/Materials and Methods OCT images were acquired of 112 patients at 2 sun protected and 2 sun exposed sites, with a subsequent biopsy. Each site received a dermatological evaluation, a histological diagnosis, and a solar elastosis (SE) score. OCT images were examined visually and statistically analyzed. Results Characteristic OCT image features were identified of sun protected, undiseased, sun damaged, and AK skin. A statistically significant difference (P < 0.0001) between the average attenuation values of skin with minimal and severe solar elastosis was observed. Significant differences (P < 0.0001) were also found between undiseased skin and AK using a gradient analysis. Using image features, AK could be distinguished from undiseased skin with 86% sensitivity and 83% specificity. Conclusion OCT has the potential to guide biopsies and provide non-invasive measures of skin sun damage and disease state, possibly increasing efficiency of chemopreventive agent trials. PMID:17960754

Evaluation of pre-implantation kidney biopsies: comparison of Banff criteria to a morphometric approach.

PubMed

Lopes, José António; Moreso, Francesc; Riera, Luis; Carrera, Marta; Ibernon, Meritxell; Fulladosa, Xavier; Grinyó, Josep Maria; Serón, Daniel

2005-04-01

Donor glomerulosclerosis, interstitial fibrosis, and fibrous intimal thickening correlate with graft outcome. We evaluate chronic lesions in donor biopsies according to Banff criteria and with a morphometric technique to ascertain their predictive value on graft outcome. We evaluated 77 cadaveric donor biopsies according to Banff criteria. Glomerulosclerosis was expressed as the percentage of global sclerotic glomeruli. The following morphometric parameters were obtained: cortical interstitial volume fraction (Vvint/c), cortical glomerular volume fraction (Vvglom/c), mean glomerular volume (Vg), mean and maximal intimal arterial volume fraction (Vvintima/art), and Vvintima/art of the largest artery. We evaluated the correlation of histologic lesions with delayed graft function, 3 months' glomerular filtration rate (GFR), and death-censored graft survival. Multivariate logistic regression showed that delayed graft function was associated with cv score [relative risk (RR) 4.2 and 95% CI 1.1 to 16.0) and glomerulosclerosis (RR 1.06 and 95% CI 1.01 to 1.13). Stepwise regression showed that Vvint/c and glomerulosclerosis were independent predictors of 3 months' GFR (R= 0.62, P= 0.0001). Repeated analysis not considering morphometric parameters showed that glomerulosclerosis, cv score and ci score were independent predictors of 3 months' GFR (R= 0.64, P= 0.0001). A donor chronic damage score was generated considering glomerulosclerosis, cv score and ci score. This score after adjusting for clinical variables was associated with 3 months' GFR (R= 0.71, P < 0.0001) and death-censored graft survival (RR 2.2 and 95% CI 1.3 to 3.7). Combined evaluation of donor glomerulosclerosis, chronic vascular and interstitial damage according to Banff criteria allows a precise prediction of graft outcome. Morphometric evaluation of donor biopsies does not improve the predictive value of semiquantitative grading.

FCG (FLIPI, Charlson comorbidity index, and histological grade) score is superior to FLIPI in advanced follicular lymphoma.

PubMed

Mihaljevic, Biljana; Jelicic, Jelena; Andjelic, Bosko; Antic, Darko; Markovic, Olivera; Petkovic, Ivan; Jovanovic, Maja Perunicic; Trajkovic, Goran; Bila, Jelena; Djurasinovic, Vladislava; Sretenovic, Aleksandra; Vukovic, Vojin; Smiljanic, Mihailo; Balint, Milena Todorovic

2016-12-01

The Follicular Lymphoma International Prognostic Index (FLIPI) is widely used in the identification of risk groups among follicular lymphoma (FL) patients. The aim of the present study was to evaluate the prognostic value of FLIPI combined with the Charlson comorbidity index (CCI) and histological grade of lymphoma. 224 newly diagnosed FL patients (median age 56 years) treated with immunochemotherapy were retrospectively analysed. Low FLIPI had 21.0 % of patients, intermediate 28.1 % and high 46.9 %. 50.9 % of patients had no comorbidities. Only 7.1 % of patients had a high CCI score (≥2), while 25.9 % of patients were histological grade 3. Parameters that influenced overall survival were evaluated using Cox regression analysis, in which CCI, FLIPI and histological grade (p < 0.05) retained prognostic significance. By combining these parameters, we have developed the FCG score, which incorporates FLIPI, CCI, and histological grade. This score defines three risk categories (low: 41.5 %; intermediate: 37.5 %; high: 13.4 %), associated with significantly different survival (p < 0.0001); this consequently improves discriminative power by 9.1 % compared to FLIPI. FCG score represents a possible new prognostic index, highlighting the role of the patient's clinical state and the histological characteristics of disease, as indicated by comorbidity index and histological grade of lymphoma.

Dexpanthenol attenuates lipid peroxidation and testicular damage at experimental ischemia and reperfusion injury.

PubMed

Etensel, Barlas; Ozkisacik, Sezen; Ozkara, Esra; Karul, Aslihan; Oztan, Onur; Yazici, Mesut; Gürsoy, Harun

2007-02-01

Prevention of tissue damage after testicular torsion caused by I/R injury is still a clinical and experimental problem. There are many experimental studies made with several chemicals in the literature for decreasing the effect of reactive oxygen species after ischemia and reperfusion. Dexpanthenol (Dxp) is the biologically active alcohol of pantothenic acid. Pantothenic acid increases the content of reduced glutathione, Coenzyme A and ATP in cell. We studied the effect of Dxp on lipid peroxidation and testicular damage. Forty adult rats were separated randomly into five groups: group Sh, Sham-operation; group TD, torsion-detorsion; group NS, torsion-normal saline-detorsion; group D, torsion-Dxp 250 mg/kg detorsion; group D2, torsion-Dxp 500 mg/kg detorsion group. Serum MDA levels were taken before detorsion, after torsion at the first and fifth minute and at the first hour. Tissue sample was taken at the first hour. The alterations of I/R injury on testis were histological graded. Serum MDA levels were significantly lower in group D2 compared to all groups. The histopathology score of group D2 was significantly lower than groups TD, NS and D. Histopathological score and serum MDA levels are strikingly compatible. Dxp attenuated lipid peroxidation and tissue damage at I/R injury. This effect depends on its antioxidant effect with increasingly reduced glutathione, Coenzyme A and ATP. The effect of Dxp on I/R injury has been shown for the first time in the experimental testicular torsion.

Biodosimetric quantification of short-term synchrotron microbeam versus broad-beam radiation damage to mouse skin using a dermatopathological scoring system

PubMed Central

Priyadarshika, R C U; Crosbie, J C; Kumar, B; Rogers, P A W

2011-01-01

Objectives Microbeam radiotherapy (MRT) with wafers of microscopically narrow, synchrotron generated X-rays is being used for pre-clinical cancer trials in animal models. It has been shown that high dose MRT can be effective at destroying tumours in animal models, while causing unexpectedly little damage to normal tissue. The aim of this study was to use a dermatopathological scoring system to quantify and compare the acute biological response of normal mouse skin with microplanar and broad-beam (BB) radiation as a basis for biological dosimetry. Method The skin flaps of three groups of mice were irradiated with high entrance doses (200 Gy, 400 Gy and 800 Gy) of MRT and BB and low dose BB (11 Gy, 22 Gy and 44 Gy). The mice were culled at different time-points post-irradiation. Skin sections were evaluated histologically using the following parameters: epidermal cell death, nuclear enlargement, spongiosis, hair follicle damage and dermal inflammation. The fields of irradiation were identified by γH2AX-positive immunostaining. Results The acute radiation damage in skin from high dose MRT was significantly lower than from high dose BB and, importantly, similar to low dose BB. Conclusion The integrated MRT dose was more relevant than the peak or valley dose when comparing with BB fields. In MRT-treated skin, the apoptotic cells of epidermis and hair follicles were not confined to the microbeam paths. PMID:21849367

Image Guided Focal Therapy for Magnetic Resonance Imaging Visible Prostate Cancer: Defining a 3-Dimensional Treatment Margin Based on Magnetic Resonance Imaging Histology Co-Registration Analysis.

PubMed

Le Nobin, Julien; Rosenkrantz, Andrew B; Villers, Arnauld; Orczyk, Clément; Deng, Fang-Ming; Melamed, Jonathan; Mikheev, Artem; Rusinek, Henry; Taneja, Samir S

2015-08-01

We compared prostate tumor boundaries on magnetic resonance imaging and radical prostatectomy histological assessment using detailed software assisted co-registration to define an optimal treatment margin for achieving complete tumor destruction during image guided focal ablation. Included in study were 33 patients who underwent 3 Tesla magnetic resonance imaging before radical prostatectomy. A radiologist traced lesion borders on magnetic resonance imaging and assigned a suspicion score of 2 to 5. Three-dimensional reconstructions were created from high resolution digitalized slides of radical prostatectomy specimens and co-registered to imaging using advanced software. Tumors were compared between histology and imaging by the Hausdorff distance and stratified by the magnetic resonance imaging suspicion score, Gleason score and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin. Three-dimensional software based registration with magnetic resonance imaging was done in 46 histologically confirmed cancers. Imaging underestimated tumor size with a maximal discrepancy between imaging and histological boundaries for a given tumor of an average ± SD of 1.99 ± 3.1 mm, representing 18.5% of the diameter on imaging. Boundary underestimation was larger for lesions with an imaging suspicion score 4 or greater (mean 3.49 ± 2.1 mm, p <0.001) and a Gleason score of 7 or greater (mean 2.48 ± 2.8 mm, p = 0.035). A simulated cylindrical treatment volume based on the imaging boundary missed an average 14.8% of tumor volume compared to that based on the histological boundary. A simulated treatment volume based on a 9 mm treatment margin achieved complete histological tumor destruction in 100% of patients. Magnetic resonance imaging underestimates histologically determined tumor boundaries, especially for lesions with a high imaging suspicion score and a high Gleason score. A 9 mm treatment margin around a lesion visible on magnetic resonance imaging would consistently ensure treatment of the entire histological tumor volume during focal ablative therapy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Total-Body Irradiation Produces Late Degenerative Joint Damage in Rats

PubMed Central

Hutchinson, Ian D.; Olson, John; Lindburg, Carl A.; Payne, Valerie; Collins, Boyce; Smith, Thomas L.; Munley, Michael T.; Wheeler, Kenneth T.; Willey, Jeffrey S.

2014-01-01

Purpose Premature musculoskeletal joint failure is a major source of morbidity among childhood cancer survivors. Radiation effects on synovial joint tissues of the skeleton are poorly understood. Our goal was to assess long-term changes in the knee joint from skeletally mature rats that received total-body irradiation while skeletal growth was ongoing. Materials and Methods 14 week-old rats were irradiated with 1, 3 or 7 Gy total-body doses of 18 MV x-rays. At 53 weeks of age, structural and compositional changes in knee joint tissues (articular cartilage, subchondral bone, and trabecular bone) were characterized using 7T MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and histology. Results T2 relaxation times of the articular cartilage were lower after exposure to all doses. Likewise, calcifications were observed in the articular cartilage. Trabecular bone microarchitecture was compromised in the tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3 and 7 Gy rats. Conclusions Late degenerative changes in articular cartilage and bone were observed after total body irradiation in adult rats exposed prior to skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential prognostic indicators of late radiation-induced joint damage. PMID:24885745

Antigen-specific immature dendritic cell vaccine ameliorates anti-dsDNA antibody-induced renal damage in a mouse model.

PubMed

Xia, Yumin; Jiang, Shan; Weng, Shenhong; Lv, Xiaochun; Cheng, Hong; Fang, Chunhong

2011-12-01

Dendritic cells (DCs) can inhibit immune response by clonal anergy when immature. Recent studies have shown that immature DCs (iDCs) may serve as a live cell vaccine after specific antigen pulse based on its potential of blocking antibody production. In this study, we aimed to investigate the effects of nuclear antigen-pulsed iDCs in the treatment of lupus-like renal damages induced by anti-dsDNA antibodies. iDCs were generated from haemopoietic stem cells in bone marrow and then pulsed in vitro with nuclear antigen. The iDC vaccine and corresponding controls were injected into mice with lupus-like renal damages. The evaluation of disease was monitored by biochemical parameters and histological scores. Anti-dsDNA antibody isotypes and T-lymphocyte-produced cytokines were analysed for elucidating therapeutic mechanisms. RESULTS; The mice treated with antigen-pulsed iDCs had a sustained remission of renal damage compared with those injected with non-pulsed iDCs or other controls, including decreased anti-dsDNA antibody level, less proteinuria, lower blood urea nitrogen and serum creatinine values, and improved histological evaluation. Analysis on isotypes of anti-dsDNA antibody showed that iDC vaccine preferentially inhibited the production of IgG3, IgG2b and IgG2a. Furthermore, administration of antigen-treated iDCs to mice resulted in significantly reduced IL-2, IL-4 and IL-12 and IFN-γ produced by T-memory cells. Conversely, the vaccination of antigen-pulsed mature DCs led to increased anti-dsDNA antibody production and an aggravation of lupus-like disease in the model. CONCLUSIONS; These results suggested the high potency of iDC vaccine in preventing lupus-like renal injuries induced by pathogenic autoantibodies.

Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

PubMed

Cheah, Ker Y; Howarth, Gordon S; Yazbeck, Roger; Wright, Tessa H; Whitford, Eleanor J; Payne, Caroline; Butler, Ross N; Bastian, Susan E P

2009-02-01

Mucositis is a common side-effect of high-dose chemotherapy regimens. Grape seed extract (GSE) represents a rich source of proanthocyanidins with the potential to decrease oxidative damage and inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of chemotherapy-induced mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by 5-Fluorouracil (5-FU). Cell viability was determined by neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received 5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for myeloperoxidase and sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by 5-FU (p < 0.01). Compared with 5-FU controls, GSE significantly reduced myeloperoxidase activity by 86% and 27% in the proximal jejunum (p < 0.001) and distal ileum (p < 0.05) respectively; decreased qualitative histological scores of damage (p < 0.05) in the proximal jejunum; increased villus height in the proximal jejunum (17%; p < 0.05) and distal ileum (50%; p < 0.01), and attenuated the 5-FU-induced reduction of mucosal thickness by 16% in the jejunum (p < 0.05) and 45% in the ileum (p < 0.01). GSE partially protected IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by 5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis.

Protective effects of melatonin and quercetin on experimental lung injury induced by carbon tetrachloride in rats.

PubMed

Taslidere, Elif; Esrefoglu, Mukaddes; Elbe, Hulya; Cetin, Asli; Ates, Burhan

2014-03-01

Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats. Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed. The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p < .001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p < .05). In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.

Effectiveness of sugammadex for cerebral ischemia/reperfusion injury.

PubMed

Ozbilgin, Sule; Yılmaz, Osman; Ergur, Bekir Ugur; Hancı, Volkan; Ozbal, Seda; Yurtlu, Serhan; Gunenc, Sakize Ferim; Kuvaki, Bahar; Kucuk, Burcu Ataseven; Sisman, Ali Rıza

2016-06-01

Cerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R) damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats. Copyright © 2016. Published by Elsevier Taiwan.

Assessing the Impact of Mechanical Damage on Full-Thickness Porcine and Human Skin Using an In Vitro Approach

PubMed Central

Builles, Nicolas; Frouin, Éric; Scott, Dan; Ramos, Jeanne; Marti-Mestres, Gilberte

2015-01-01

For most xenobiotics, the rates of percutaneous absorption are limited by diffusion through the horny layer of skin. However, percutaneous absorption of chemicals may seriously increase when the skin is damaged. The aim of this work was to develop an in vitro representative model of mechanically damaged skins. The epidermal barrier was examined following exposure to a razor, a rotating brush, and a microneedle system in comparison to tape-stripping which acted as a reference. Excised full-thickness skins were mounted on a diffusion chamber in order to evaluate the effect of injuries and to mimic physiological conditions. The transepidermal water loss (TEWL) was greatly increased when the barrier function was compromised. Measurements were made for all the damaged biopsies and observed histologically by microscopy. On human and porcine skins, the tape-stripping application (0 to 40 times) showed a proportional increase in TEWL which highlights the destruction of the stratum corneum. Similar results were obtained for all cosmetic instruments. This is reflected in our study by the nonsignificant difference of the mean TEWL scores between 30 strips and mechanical damage. For a specific appreciation, damaged skins were then selected to qualitatively evaluate the absorption of a chlorogenic acid solution using fluorescence microscopy. PMID:26247021

Erythropoietin and sildenafil protect against ischemia/reperfusion injury following testicular torsion in adult rats.

PubMed

Kostakis, Ioannis D; Zavras, Nick; Damaskos, Christos; Sakellariou, Stratigoula; Korkolopoulou, Penelope; Misiakos, Evangelos P; Tsaparas, Petros; Vaos, George; Karatzas, Theodoros

2017-06-01

Testicular torsion/detorsion causes severe tissue damage due to ischemia/reperfusion injury. The present study investigated the protective effect of erythropoietin and sildenafil against ischemia/reperfusion injury following unilateral testicular torsion/detorsion in adult rats. A total of 28 adult male rats were included, and were divided into the following groups: Group A (n=5), sham operated; groups B (n=5), C (n=5), D (n=5) and E (n=8), undergoing right testis torsion and detorsion after 90 min. Group B received no drug treatment. Rats in the groups C and D received low-dose (1,000 IU/kg) or high-dose (3,000 IU/kg) erythropoietin, while those in group E received sildenafil (0.7 mg/kg), through intraperitoneal injection after 60 min of torsion. The right testis was extracted 24 h after detorsion, and the tissue was subjected to histopathological examination and immunohistochemical assessment of cleaved caspase-3 expression. Histological alterations and the quality of spermatogenesis were scored according to the Cosentino and the Johnsen scoring systems, respectively. The results demonstrated normal testicular architecture in group A, while the other groups showed ischemic cellular damages, with the worst scores observed in group B. Groups D and E presented better scores compared with group C. Regarding the quality of spermatogenesis, the best scores were observed in group A, and the worst in group B. Groups C, D and E presented similar results, which were improved in comparison to group B, however, not compared to group A. Furthermore, cleaved caspase-3 levels were lower in groups A, D and E, with equal results observed. Group C had higher levels of cleaved caspase-3 compared with these groups, but lower than group B, which presented the highest cleaved caspase-3 levels. In conclusion, erythropoietin and sildenafil protect testis from ischemia/reperfusion injury by decreasing cellular damage and attenuating apoptosis.

Erythropoietin and sildenafil protect against ischemia/reperfusion injury following testicular torsion in adult rats

PubMed Central

Kostakis, Ioannis D.; Zavras, Nick; Damaskos, Christos; Sakellariou, Stratigoula; Korkolopoulou, Penelope; Misiakos, Evangelos P.; Tsaparas, Petros; Vaos, George; Karatzas, Theodoros

2017-01-01

Testicular torsion/detorsion causes severe tissue damage due to ischemia/reperfusion injury. The present study investigated the protective effect of erythropoietin and sildenafil against ischemia/reperfusion injury following unilateral testicular torsion/detorsion in adult rats. A total of 28 adult male rats were included, and were divided into the following groups: Group A (n=5), sham operated; groups B (n=5), C (n=5), D (n=5) and E (n=8), undergoing right testis torsion and detorsion after 90 min. Group B received no drug treatment. Rats in the groups C and D received low-dose (1,000 IU/kg) or high-dose (3,000 IU/kg) erythropoietin, while those in group E received sildenafil (0.7 mg/kg), through intraperitoneal injection after 60 min of torsion. The right testis was extracted 24 h after detorsion, and the tissue was subjected to histopathological examination and immunohistochemical assessment of cleaved caspase-3 expression. Histological alterations and the quality of spermatogenesis were scored according to the Cosentino and the Johnsen scoring systems, respectively. The results demonstrated normal testicular architecture in group A, while the other groups showed ischemic cellular damages, with the worst scores observed in group B. Groups D and E presented better scores compared with group C. Regarding the quality of spermatogenesis, the best scores were observed in group A, and the worst in group B. Groups C, D and E presented similar results, which were improved in comparison to group B, however, not compared to group A. Furthermore, cleaved caspase-3 levels were lower in groups A, D and E, with equal results observed. Group C had higher levels of cleaved caspase-3 compared with these groups, but lower than group B, which presented the highest cleaved caspase-3 levels. In conclusion, erythropoietin and sildenafil protect testis from ischemia/reperfusion injury by decreasing cellular damage and attenuating apoptosis. PMID:28587411

Relation between histological prostatitis and lower urinary tract symptoms and erectile function.

PubMed

Mizuno, Taiki; Hiramatsu, Ippei; Aoki, Yusuke; Shimoyama, Hirofumi; Nozaki, Taiji; Shirai, Masato; Lu, Yan; Horie, Shigeo; Tsujimura, Akira

2017-09-01

Chronic prostatitis (CP) significantly worsens a patient's quality of life (QOL), but its etiology is heterogeneous. Although the inflammatory process must be associated with CP symptoms, not all patients with benign prostatic hyperplasia and histological prostatitis complain of CP symptoms. The relation between the severity of histological inflammation and lower urinary tract symptoms (LUTS) and erectile function is not fully understood. This study comprised 26 men with suspected prostate cancer but with no malignant lesion by pathological examination of prostate biopsy specimens. LUTS were assessed by several questionnaires including the International Prostate Symptom Score (IPSS), QOL index, Overactive Bladder Symptom Score (OABSS), and the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), and erectile function was assessed by the Sexual Health Inventory for Men. Prostate volume (PV) measured by transabdominal ultrasound, maximum flow rate by uroflowmetry, and serum concentration of prostate-specific antigen were also evaluated. All data collections were performed before prostate biopsy. Histological prostatitis was assessed by immunohistochemical staining with anti-CD45 antibody as the Quick score. The relation between the Quick score and several factors was assessed by Pearson correlation coefficient and a multivariate linear regression model after adjustment for PV. The Pearson correlation coefficient showed a correlation between the Quick score and several factors including PV, IPSS, QOL index, OABSS, and NIH-CPSI. A multivariate linear regression model after adjustment for PV showed only the NIH-CPSI to be associated with the Quick score. The relation between the Quick score and each domain score of the NIH-CPSI showed only the subscore of urinary symptoms to be an associated factor. We found a correlation only between histological prostatitis and LUTS, but not erectile dysfunction. Especially, the subscore of urinary symptoms (residual feeling and urinary frequency) was associated with histological prostatitis.

Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage.

PubMed

Sheen, Jiunn-Ming; Huang, Li-Tung; Hsieh, Chih-Sung; Chen, Chih-Cheng; Wang, Jia-Yi; Tain, You-Lin

2010-08-01

Cholestatic liver disease may result in progressive end-stage liver disease and other extrahepatic complications. We explored the temporal progression of bile duct ligation (BDL)-induced cholestasis in developing rats, focusing on brain cognition and liver and kidney pathology, to elucidate whether these findings were associated with asymmetric dimethylarginine and oxidative stress alterations. Three groups of young male Sprague-Dawley rats were studied: one group underwent laparotomy (sham), another group underwent laparotomy and BDL for 2 weeks (BDL2), and a third group underwent laparotomy and BDL for 4 weeks (BDL4). The effect of BDL on liver was represented by transforming growth factor beta1 levels and histology activity index scores, which were worse in the BDL4 rats than in the BDL2 rats. BDL4 rats also exhibited more severe spatial memory deficits than BDL2 rats. In addition, renal injury was more progressive in BDL4 rats than in BDL2 rats because BDL4 rats displayed higher Cr levels, elevated tubulointerstitial injury scores, neutrophil gelatinase-associated lipocalin, and symmetric dimethylarginine levels. Our findings highlight the fact that young BDL rats exhibit similar trends of progression of liver, kidney, and brain damage. Further studies are needed to better delineate the nature of progression of organ damage in young cholestatic rats. Copyright 2010 Elsevier Inc. All rights reserved.

The reproducibility and predictive value on outcome of renal biopsies from expanded criteria donors.

PubMed

Azancot, M Antonieta; Moreso, Francesc; Salcedo, Maite; Cantarell, Carme; Perello, Manel; Torres, Irina B; Montero, Angeles; Trilla, Enric; Sellarés, Joana; Morote, Joan; Seron, Daniel

2014-05-01

Reproducibility and predictive value on outcome are the main criteria to evaluate the utility of histological scores. Here we analyze the reproducibility of donor biopsy assessment by different on-call pathologists and the retrospective evaluation by a single renal pathologist blinded to clinical outcomes. We also evaluate the predictive value on graft outcome of both evaluations. A biopsy was performed in donors with any of the following: age≥55 years, hypertension, diabetes, creatinine>1.5 mg/dl, or stroke. Glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal thickening, and arteriolar hyalinosis evaluated according to the Banff criteria were added to obtain a chronic score. Biopsies were classified as mild (≥3), intermediate (4-5), or advanced (6-7) damage, and unacceptable (≥8) for transplantation of 127 kidneys biopsied. Weighted κ value between both readings was 0.41 (95% CI: 0.28-0.54). Evaluation of biopsies by the renal pathologist was significantly and independently associated with estimated 12-month glomerular filtration rate and a significant composite outcome variable, including death-censored graft survival and time to reach an estimated glomerular filtration rate<30 ml/min per 1.73 m2. Thus, there was no association between readings of on-call pathologists and outcome. The lack of association between histological scores obtained by the on-call pathologists and graft outcome suggests that a specific training on renal pathology is recommended to optimize the use of kidneys retrieved from expanded criteria donors.

Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury

PubMed Central

Boyce, Mary K.; Trumble, Troy N.; Carlson, Cathy S.; Groschen, Donna M.; Merritt, Kelly A.; Brown, Murray P.

2013-01-01

Objective Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). Methods An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. Results Osteochondral fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P=0.0012), while joint circumference (P<0.0001) and effusion scores (P<0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Conclusion Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery. PMID:23467035

Ameliorative effect of propolis on the cadmium-induced reproductive toxicity in male albino rats.

PubMed

Çilenk, Kübra Tuğçe; Öztürk, İsmet; Sönmez, Mehmet Fatih

2016-10-01

Propolis is a potent antioxidant and a free radical scavenger. The present study aimed to investigate protective effects of propolis extract on cadmium-induced testicular damage, apoptosis, HIF-1α expression and toxicity in rat's testis tissue. A total of 32 male rats were equally divided into four study groups namely, control, Cd (1mg/kg/day), Cd+propolis (50mg/kg/day) and propolis. The rats were decapitated under ketamine anesthesia and their testes tissues were removed. Serum testosterone, tissue malondialdehyde and HIF-1α levels, HIF-1α expression, apoptosis and histopathological damage scores were then compared. In the Cd group, the diameters of seminiferous tubules, tubular biopsy score of Johnsen and serum testosterone levels were decreased compared control group, but tissue HIF-1α and tissue MDA levels was higher than control group. The immunoreactivity of HIF-1α and the number of apoptotic cells were increased in Cd group. Furthermore, the propolis treated group showed an improved histological appearance in the Cd group. Thus, the results suggest that propolis acts as a potent protective agent against Cd-induced testicular toxicity in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Climbing Bloom's taxonomy pyramid: Lessons from a graduate histology course.

PubMed

Zaidi, Nikki B; Hwang, Charles; Scott, Sara; Stallard, Stefanie; Purkiss, Joel; Hortsch, Michael

2017-09-01

Bloom's taxonomy was adopted to create a subject-specific scoring tool for histology multiple-choice questions (MCQs). This Bloom's Taxonomy Histology Tool (BTHT) was used to analyze teacher- and student-generated quiz and examination questions from a graduate level histology course. Multiple-choice questions using histological images were generally assigned a higher BTHT level than simple text questions. The type of microscopy technique (light or electron microscopy) used for these image-based questions did not result in any significant differences in their Bloom's taxonomy scores. The BTHT levels for teacher-generated MCQs correlated positively with higher discrimination indices and inversely with the percent of students answering these questions correctly (difficulty index), suggesting that higher-level Bloom's taxonomy questions differentiate well between higher- and lower-performing students. When examining BTHT scores for MCQs that were written by students in a Multiple-Choice Item Development Assignment (MCIDA) there was no significant correlation between these scores and the students' ability to answer teacher-generated MCQs. This suggests that the ability to answer histology MCQs relies on a different skill set than the aptitude to construct higher-level Bloom's taxonomy questions. However, students significantly improved their average BTHT scores from the midterm to the final MCIDA task, which indicates that practice, experience and feedback increased their MCQ writing proficiency. Anat Sci Educ 10: 456-464. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Treatment of collagenase-induced osteoarthritis with a viral vector encoding TSG-6 results in ectopic bone formation.

PubMed

Broeren, Mathijs G A; Di Ceglie, Irene; Bennink, Miranda B; van Lent, Peter L E M; van den Berg, Wim B; Koenders, Marije I; Blaney Davidson, Esmeralda N; van der Kraan, Peter M; van de Loo, Fons A J

2018-01-01

Tumor necrosis factor-inducible gene 6 (TSG-6) has anti-inflammatory and chondroprotective effects in mouse models of inflammatory arthritis. Because cartilage damage and inflammation are also observed in osteoarthritis (OA), we determined the effect of viral overexpression of TSG-6 in experimental osteoarthritis. Bone marrow-derived cells were differentiated to multinucleated osteoclasts in the presence of recombinant TSG-6 or after transduction with a lentiviral TSG-6 expression vector. Multi-nucleated osteoclasts were analyzed after tartrate resistant acid phosphatase staining and resorption activity was determined on dentin slices. Collagenase-induced osteoarthritis (CIOA) was induced in C57BL/6 mice after intra-articular injection of an adenoviral TSG-6 or control luciferase expression vector. Inflammation-related protease activity was measured using bioluminescent Prosense probes. After a second adenovirus injection, cartilage damage was assessed in histological sections stained with Safranin-O. Ectopic bone formation was scored in X-ray images of the affected knees. TSG-6 did not inhibit the formation of multi-nucleated osteoclasts, but caused a significant reduction in the resorption activity on dentin slices. Adenoviral TSG-6 gene therapy in CIOA could not reduce the cartilage damage compared to the luciferase control virus and no significant difference in inflammation-related protease activity was noted between the TSG-6 and control treated group. Instead, X-ray analysis and histological analysis revealed the presence of ectopic bone formation in the TSG-6 treated group. Gene therapy based on the expression of TSG-6 could not provide cartilage protection in experimental osteoarthritis, but instead resulted in increased ectopic bone formation.

Sister chromatid exchange rate and alkaline comet assay scores in patients with ovarian cancer.

PubMed

Baltaci, Volkan; Kayikçioğlu, Fulya; Alpas, Idil; Zeyneloğlu, Hulusi; Haberal, Ali

2002-01-01

Sister chromatid exchange (SCE) frequencies were studied in patients with different types of ovarian malignancies and in healthy volunteers. The level of DNA damage in patients with ovarian malignancy and control subjects has also been studied by alkaline single cell gel electrophoresis (SCGE), also known as the comet assay. Peripheral blood was collected from 30 patients after histological confirmation of malignancy and 20 healthy female volunteers. The cells were evaluated according to their grade of damage. We found that the sister chromatid exchange frequencies of cancer cases were significantly greater than that of controls (P < 0.001). The frequency of exchange in chromosomal groups A, B, and C, which include chromosomes 1-12, was higher than that of the other chromosomal groups in both groups. Comparison of the results of the alkaline comet assay in patient and control subjects showed a significant difference in the number of damaged cells. The frequency of limited migrated and extensive migrated cells in the women with ovarian malignancies was higher than that of control women (P < 0.001). SCE and SCGE can be used successfully to monitor DNA damage in women with ovarian cancer.

Extracts from Hericium erinaceus relieve inflammatory bowel disease by regulating immunity and gut microbiota.

PubMed

Diling, Chen; Xin, Yang; Chaoqun, Zheng; Jian, Yang; Xiaocui, Tang; Jun, Chen; Ou, Shuai; Yizhen, Xie

2017-10-17

Hericium erinaceus (HE), a traditional edible mushroom, is known as a medicine food homology to ameliorate gastrointestinal diseases. To investigate whether HE is clinically effective in alleviating inflammatory bowel disease (IBD), HE extracts (polysaccharide, alcoholic extracts and whole extracts were prepared using solvent extraction methods) were administrated for 2 weeks in rats with IBD induced by trinitro-benzene-sulfonic acid (TNBS) enema (150 mg/kg). Significant clinical and histological changes in IBD rats were identified, including damage activity, common morphous and tissue damage index scores in colonic mucosa and myeloperoxidase (MPO) activity. The damage activity, common morphous and tissue damage index scores in colonic mucosa ( P <0.05) were improved, MPO activities were decreased. Inflammatory factors were also differentially expressed in colonic mucosa in IBD rats, including serum cytokines, Foxp3 and interleukin (IL)-10 were increased while NF-κB p65 and tumor necrosis factor (TNF)-α were decreased ( P <0.05), and T cells were activated ( P <0.05), especially in the alcohol extracts-treated group. We also found that the structure of gut microbiota of the H. erinaceus extracts-treated groups changed significantly by compared with the model group. Further studies revealed that the polysaccharides in HE extracts may play a prebiotic role, whereas the alcoholic extracts show bactericidin-like and immunomodulatory effects. Taken together, we demonstrated that H. erinaceus extracts could promote the growth of beneficial gut bacteria and improve the host immunity in vivo IBD model, which shows clinical potential in relieving IBD by regulating gut microbiota and immune system.

Extracts from Hericium erinaceus relieve inflammatory bowel disease by regulating immunity and gut microbiota

PubMed Central

Diling, Chen; Xin, Yang; Chaoqun, Zheng; Jian, Yang; Xiaocui, Tang; Jun, Chen; Ou, Shuai; Yizhen, Xie

2017-01-01

Hericium erinaceus (HE), a traditional edible mushroom, is known as a medicine food homology to ameliorate gastrointestinal diseases. To investigate whether HE is clinically effective in alleviating inflammatory bowel disease (IBD), HE extracts (polysaccharide, alcoholic extracts and whole extracts were prepared using solvent extraction methods) were administrated for 2 weeks in rats with IBD induced by trinitro-benzene-sulfonic acid (TNBS) enema (150 mg/kg). Significant clinical and histological changes in IBD rats were identified, including damage activity, common morphous and tissue damage index scores in colonic mucosa and myeloperoxidase (MPO) activity. The damage activity, common morphous and tissue damage index scores in colonic mucosa (P <0.05) were improved, MPO activities were decreased. Inflammatory factors were also differentially expressed in colonic mucosa in IBD rats, including serum cytokines, Foxp3 and interleukin (IL)-10 were increased while NF-κB p65 and tumor necrosis factor (TNF)-α were decreased (P <0.05), and T cells were activated (P <0.05), especially in the alcohol extracts-treated group. We also found that the structure of gut microbiota of the H. erinaceus extracts-treated groups changed significantly by compared with the model group. Further studies revealed that the polysaccharides in HE extracts may play a prebiotic role, whereas the alcoholic extracts show bactericidin-like and immunomodulatory effects. Taken together, we demonstrated that H. erinaceus extracts could promote the growth of beneficial gut bacteria and improve the host immunity in vivo IBD model, which shows clinical potential in relieving IBD by regulating gut microbiota and immune system. PMID:29156761

Endometrial vs. cervical cancer: development and pilot testing of a magnetic resonance imaging (MRI) scoring system for predicting tumor origin of uterine carcinomas of indeterminate histology.

PubMed

Bourgioti, Charis; Chatoupis, Konstantinos; Panourgias, Evangelia; Tzavara, Chara; Sarris, Kyrillos; Rodolakis, Alexandros; Moulopoulos, Lia Angela

2015-10-01

To report discriminant MRI features between cervical and endometrial carcinomas and to design an MRI- scoring system, with the potential to predict the origin of uterine cancer (cervix or endometrium) in histologically indeterminate cases. Dedicated pelvic MRIs of 77 patients with uterine tumors involving both cervix and corpus were retrospectively analyzed by two experts in female imaging. Seven MRI tumor characteristics were statistically tested for their discriminant ability for tumor origin compared to final histology: tumor location, perfusion pattern, rim enhancement, depth of myometrial invasion, cervical stromal integrity, intracavitary mass, and retained endometrial secretions. Kappa values were estimated to assess the levels of inter-rater reliability. On the basis of positive likelihood ratio values, an MRI-score was assigned. K value was excellent for most of the imaging criteria. Using ROC curve analysis, the estimated optimal cut-off for the MRI-scoring system was 4 with 96.6% sensitivity and 100% specificity. Using a ≥4 cut-off for cervical cancers and <4 for endometrial cancers, 97.4% of the patients were correctly classified. 2/58 patients with cervical cancer had MRI score <4 and none of the patients with endometrial cancer had MRI score >4. The area under curve of the MRI-scoring system was 0.99 (95% CI 0.98-1.00). When the MRI-score was applied to 20/77 patients with indeterminate initial biopsy and to 5/26 surgically treated patients with erroneous pre-op histology, all cases were correctly classified. The produced MRI-scoring system may be a reliable problem-solving tool for the differential diagnosis of cervical vs. endometrial cancer in cases of equivocal histology.

Diagnostic Dilemma for Low Viremia with Significant Fibrosis; Is HBV DNA Threshold Level a Good Indicator for Predicting Liver Damage?

PubMed

Yenilmez, Ercan; Çetinkaya, Rıza Aytaç; Tural, Ersin

2018-05-04

The most important difficulties about management of hepatitis B are still determining the liver damage and the right time to start antiviral therapy. To reveal the role of hepatitis B virus DNA threshold level for prediction of liver fibrosis and inflammation in young-aged hepatitis B e antigen negative chronic hepatitis B patients. Diagnostic accuracy study. A total of 273 hepatitis B e antigen negative young chronic hepatitis B patients with any hepatitis B virus DNA levels between 2008 and 2016, who had liver biopsy after at least 6 months follow up period, enrolled in this retrospective study. We created two groups as case and control, cases with hepatitis B virus DNA levels below 2.000 IU/mL and controls with hepatitis B virus DNA levels over 2.000 IU/mL. Having histological activity index ≥4 or/and fibrosis scores ≥2 were defined as significant histological abnormality. Then, we analyzed the relationship between these groups. We showed that significant fibrosis may occur in one third of young chronic hepatitis B patients with low viremia (30.2%, n=42/139 in cases, %55.2, n=74/134 in controls). Among the 42 cases with low viremia and significant fibrosis, 21.4% had alanine aminotransferase level between 40-59 U/L, 42.8% had alanine aminotransferase level between 60-79 U/L, and 35.7% had alanine aminotransferase level over 80 U/L. There was weak correlation between hepatitis B virus DNA threshold level and fibrosis score (p=0.000, rho=0.253). The optimum serum hepatitis B virus DNA threshold level in our study for predicting significant fibrosis was 1293 IU/mL (p=0.00, AUC: 0.657±0.034). The optimum alanine aminotransferase threshold level for predicting significant histological activity index and fibrosis was 64.5 and 59.5 U/L, respectively. The sensitivity and the specificity of 1293 vs 2000 IU/mL hepatitis B virus DNA threshold with 60 U/L alanine aminotransferase threshold level for predicting F≥2 fibrosis score were similar (sensitivity: 0.43 and 0.38, respectively; specificity: 0.76 and 0.77, respectively). Significant fibrosis may occur even in young cases with low viremia. It is not possible to define a single threshold hepatitis B virus DNA level for differentiating inactive carriers from patients with hepatitis B e antigen-negative chronic hepatitis. Diagnostic accuracy of hepatitis B virus DNA with alanine aminotransferase thresholds for the prediction of significant fibrosis is weak.

Histologic damage of lung allografts according to magnitude of acute rejection in the re-isotransplant model.

PubMed

Marui, Tsutomu; Iwata, Hisashi; Shirahashi, Koyo; Matsumoto, Shinsuke; Mizuno, Yoshimasa; Matsui, Masafumi; Takemura, Hirofumi

2008-06-01

Graft damage due to acute rejection has been reported as one of the risk factors in the chronic stage of cardiac and renal allografts. This study was designed to elucidate the histologic changes of grafts after ongoing acute allograft rejection was discontinued in models of lung re-isotransplantation. WKAH rat lungs were orthotopically transplanted into F344 recipients. Three days (3A group) and 5 days (5A group) after the first allotransplantation, the grafts were re-isotransplanted back into the WKAH rats (3RA and 5RA groups, respectively). Five days (5I group) after the first isotransplantation, the grafts were re-isotransplanted back into the WKAH rats (5RI group). The grafts were removed 30 and 60 days after re-isotransplantation and assessed histologically. Typical acute allograft rejection developed in the 3A and 5A groups, and the changes were reduced after re-isotransplantation, although they remained significantly greater in the 5RA group than in the 3RA and 5RI groups. For intimal hyperplasia, the graft score 60 days after re-isotransplantation in the 5RA group was significantly higher than in the 5RI and 3RA groups. The changes in airway inflammation were significantly greater in the 5RA group than in the 3RA and 5RI groups at 60 days. Peribronchiolar fibrosis was significantly more frequent in the 5RA and 3RA groups than in the 5RI group. Acute rejection and airway inflammation corresponded to the magnitude of rejection before retransplantation. Significant intimal hyperplasia developed in severe acute rejection, and peribronchiolar fibrosis occurred after the first acute rejection.

Effects of cryoanalgesia on post-thoracotomy pain and on the structure of intercostal nerves: a human prospective randomized trial and a histological study.

PubMed

Moorjani, N; Zhao, F; Tian, Y; Liang, C; Kaluba, J; Maiwand, M O

2001-09-01

The choice of analgesia in the management of post-thoracotomy pain remains controversial. Although several alternative forms of post-thoracotomy analgesia exist, all have their disadvantages. Cryoanalgesia, localized freezing of intercostal nerves, has been reported to have variable effectiveness and an incidence of long-term cutaneous sensory changes. We carried out an animal study to assess the reversibility of histological changes induced by cryoanalgesia and a prospective randomized trial to compare the effectiveness of cryoanalgesia with conventional analgesia (parenteral opiates). In six anaesthetized dogs, intercostal nerves were exposed to a varying duration of cryo-application (30, 60, 90 and 120 s). The nerves were biopsied and examined histologically at regular intervals over the following 6 months. In the clinical study, 200 consecutive patients undergoing thoracotomy were randomized to cryoanalgesia and conventional (parenteral opiates) analgesia groups. Postoperative pain scores, respiratory function tests and use of opiate analgesia were measured for the two groups. Following application of the cryoprobe, degeneration and fragmentation of the axons was evident with associated inflammatory changes. As the endoneurium remained intact, axonal regeneration took place after the resolution of axonal swelling. Over the course of weeks, recovery of the intercostal nerve occurred and was complete after 1 month for the 30 and 60 s groups. For nerves exposed to longer durations of cryoanalgesia, the time taken for complete recovery was proportionally increased. Clinically, there was a statistically significant (P<0.05) improvement in postoperative pain scores and use of opiate analgesia and an improvement (P>0.05) in respiratory function tests for patients in the cryoanalgesia group. The previously suggested cutaneous sensory changes resolved within 6 months with complete restoration of function. We suggest that cryoanalgesia be considered as a simple, inexpensive, long-term form of post-thoracotomy pain relief, which does not cause any long-term histological damage to intercostal nerves.

Complex and elementary histological scoring systems for articular cartilage repair.

PubMed

Orth, Patrick; Madry, Henning

2015-08-01

The repair of articular cartilage defects is increasingly moving into the focus of experimental and clinical investigations. Histological analysis is the gold standard for a valid and objective evaluation of cartilaginous repair tissue and predominantly relies on the use of established scoring systems. In the past three decades, numerous elementary and complex scoring systems have been described and modified, including those of O'Driscoll, Pineda, Wakitani, Sellers and Fortier for entire defects as well as those according to the International Cartilage Repair Society (ICRS-I/II) for osteochondral tissue biopsies. Yet, this coexistence of different grading scales inconsistently addressing diverse parameters may impede comparability between reported study outcomes. Furthermore, validation of these histological scoring systems has only seldom been performed to date. The aim of this review is (1) to give a comprehensive overview and to compare the most important established histological scoring systems for articular cartilage repair, (2) to describe their specific advantages and pitfalls, and (3) to provide valid recommendations for their use in translational and clinical studies of articular cartilage repair.

Post-fertilization effect of bilateral primary testicular damage induced by unilateral cryptorchidism in the rat model.

PubMed

Tsounapi, P; Honda, M; Dimitriadis, F; Shimizu, S; Hikita, K; Muraoka, K; Sejima, T; Saito, M; Tomita, S; Sofikitis, N; Takenaka, A

2016-03-01

Cryptorchidism, a common anomaly of the male genitalia, affects 2-4% of male infants. The post-fertilization effects of unilateral cryptorchidism model in the rat and the effects of antioxidant treatment were investigated. Six-week-old male Wistar rats were randomly separated into four groups. Unilateral cryptorchidism was induced in the right testis of three groups. One group was treated with saline intraperitoneally (i.p.) (Crypto), one group was treated with taurine (500 mg/kg, i.p.; Tau), and another group was treated with sivelestat (15 mg/kg i.p.; Siv). The control group was treated with saline i.p. The treatment was daily for 8 weeks. Five days before sacrifice, mating studies were performed. Body, testicular, and epididymal weights were recorded. Malondialdehyde (MDA) levels in the seminal vesicular fluid (SVF) were measured. Testicular levels of MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined bilaterally. TUNEL assay was used to examine DNA fragmentation bilaterally. Histological examination and the Johnsen score were used to evaluate morphological testicular alterations. The Crypto group demonstrated significantly lower right testicular and epididymal weights, significantly increased SVF-MDA levels, testicular MDA and 8-OHdG levels, and the apoptotic score bilaterally compared to the controls. Furthermore, histological evaluation revealed significantly reduced spermatogenesis and mild injury to the cryptorchid testes compared to the control. Treatment with both taurine and sivelestat significantly reduced SVF-MDA levels, testicular MDA, 8-OHdG, and apoptosis bilaterally compared to the Crypto group. Antioxidant treatment was unable to ameliorate spermatogenesis. Newborns delivered by females that mated with Crypto-males had significantly lower body weight compared with the respective animals from the control, Tau and Siv groups. The present study demonstrated that unilateral cryptorchidism-induced testicular damage can significantly affect the contralateral testis as well having further deleterious post-fertilization effect on the development of newborns. Treatment with antioxidants can partially improve the testicular damage bilaterally with beneficial effects for the newborns. © 2016 American Society of Andrology and European Academy of Andrology.

Histological evaluations and inflammatory responses of different dental implant abutment materials: A human histology pilot study.

PubMed

Sampatanukul, Teeratida; Serichetaphongse, Pravej; Pimkhaokham, Atiphan

2018-04-01

Improvements of soft tissue to the abutment surface results in more stable peri-implant conditions, however, few human histological studies have compared soft tissue responses around different abutment materials. To describe the peri-implant tissue around 3 abutment materials; titanium, zirconia, and gold alloy, over an 8-week healing period. Fifteen edentulous sites were treated with implants. Eight weeks later, peri-implant tissue was harvested and processed using a nonseparation resin embedded technique. The tissue attachment characteristics were assessed at clinical stages using the gingival index (GI) score, surgical stage (surgical score), and histological stage (histological attachment percentage). Additionally, the inflammatory responses were evaluated using inflammatory extent and inflammatory cellularity grades. Nonparametrical statistics were used to describe the GI and surgical scores, and analytical statistics were used to analyze the histological attachment percentages as well as the inflammatory extent and cellularity grades amongst the 3 groups. There were no statistically significant differences among the groups for GI score (P = .071) and surgical score (P = .262). Titanium and zirconia exhibited nearly similar mean histological attachment percentages while gold alloy had a significantly lower percentage (P = .004). For the inflammatory extent and cellularity grades, the odds of being one grade higher for gold alloy abutment was 5.18 and 17.8 times that of titanium abutment, respectively. However, for the zirconia abutment, the odds were 0.87 and 7.5 times higher than the titanium group. The tissue around the gold alloy abutments resulted in worse attachment conditions compared with the titanium and zirconia abutments. Inflammation tended to be higher in the tissue around the gold alloy abutments than the titanium and zirconia abutments. © 2017 Wiley Periodicals, Inc.

Protective Effect of Camellia Oil (Camellia oleifera Abel.) against Ethanol-Induced Acute Oxidative Injury of the Gastric Mucosa in Mice.

PubMed

Tu, Pang-Shuo; Tung, Yu-Tang; Lee, Wei-Ting; Yen, Gow-Chin

2017-06-21

Camellia oil, a common edible oil in Taiwan and China, has health effects for the gastrointestinal tract in folk medicine, and it contains abundant unsaturated fatty acids and phytochemicals. However, the preventive effect of camellia oil on ethanol-induced gastric ulcers remains unclear. This study was aimed to evaluate the preventive effect of camellia oil on ethanol-induced gastric injury in vitro and in vivo as well as its mechanisms of action. In an in vitro study, our results showed that pretreatment of RGM-1 cells with camellia oil enhanced the migration ability as well as increased heat shock protein expression and reduced apoptotic protein expression. In animal experiments, mice pretreated with camellia oil effectively showed improved ethanol-induced acute injury of the gastric muscosa and oxidative damage through the enhancement of antioxidant enzyme activities and heat shock protein and PGE 2 production, as well as the suppression of lipid peroxidation, apoptosis-related proteins, pro-inflammatory cytokines, and NO production. Histological injury score and hemorrhage score in ethanol-induced gastric mucosal damage dramatically elevated from the control group (0.00 ± 0.0) to 3.40 ± 0.7 and 2.60 ± 0.5, respectively. However, treatments with camellia oil or olive oil (2 mL/kg bw) and lansoprazole (30 mg/kg bw) showed significant decreases in elevation of injury score and hemorrhage score (p < 0.05). Therefore, camellia oil has the potential to ameliorate ethanol-induced acute gastric mucosal injury through the inhibition of inflammation and oxidative stress.

OLGA- and OLGIM-based staging of gastritis using narrow-band imaging magnifying endoscopy.

PubMed

Saka, Akiko; Yagi, Kazuyoshi; Nimura, Satoshi

2015-11-01

As atrophic gastritis and intestinal metaplasia as a result of Helicobacter pylori are considered risk factors for gastric cancer, it is important to assess their severity. In the West, the operative link for gastritis assessment (OLGA) and operative link for gastric intestinal metaplasia assessment (OLGIM) staging systems based on biopsy have been widely adopted. In Japan, however, narrow-band imaging (NBI)-magnifying endoscopic diagnosis of gastric mucosal inflammation, atrophy, and intestinal metaplasia has been reported to be fairly accurate. Therefore, we investigated the practicality of NBI-magnifying endoscopy (NBI-ME) for gastritis staging. We enrolled 55 patients, in whom NBI-ME was used to score the lesser curvature of the antrum (antrum) and the lesser curvature of the lower body (corpus). The NBI-ME score classification was established from images obtained beforehand, and then biopsy specimens taken from the observed areas were scored according to histological findings. The NBI-ME and histology scores were then compared. Furthermore, we assessed the NBI-ME and histology stages using a combination of scores for the antrum and corpus, and divided the stages into two risk groups: low and high. The degree to which the stage assessed by NBI-ME approximated that assessed by histology was then ascertained. Degree of correspondence between the NBI-ME and histology scores was 69.1% for the antrum and 72.7% for the corpus, and that between the high- and low-risk groups was 89.1%. Staging of gastritis using NBI-ME approximates that based on histology, and would be a practical alternative to the latter. © 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

Interphalangeal Osteoarthritis Radiographic Simplified (iOARS) score: a radiographic method to detect osteoarthritis of the interphalangeal finger joints based on its histopathological alterations.

PubMed

Sunk, Ilse-Gerlinde; Amoyo-Minar, Love; Stamm, Tanja; Haider, Stefanie; Niederreiter, Birgit; Supp, Gabriela; Soleiman, Afschin; Kainberger, Franz; Smolen, Josef S; Bobacz, Klaus

2014-11-01

To develop a radiographic score for assessment of hand osteoarthritis (OA) that is based on histopathological alterations of the distal (DIP) and proximal (PIP) interphalangeal joints. DIP and PIP joints were obtained from corpses (n=40). Plain radiographies of these joints were taken. Joint samples were prepared for histological analysis; cartilage damage was graded according to the Mankin scoring system. A 2×2 Fisher's exact test was applied to define those radiographic features most likely to be associated with histological alterations. Receiver operating characteristic curves were analysed to determine radiographic thresholds. Intraclass correlation coefficients (ICC) estimated intra- and inter-reader variability. Spearman's correlation was applied to examine the relationship between our score and histopathological changes. Differences between groups were determined by a Student's t test. The Interphalangeal Osteoarthritis Radiographic Simplified (iOARS) score is presented. The score is based on histopathological changes of DIP and PIP joints and follows a simple dichotomy whether OA is present or not. The iOARS score relies on three equally ranked radiographic features (osteophytes, joint space narrowing and subchondral sclerosis). For both DIP and PIP joints, the presence of one x-ray features reflects interphalangeal OA. Sensitivity and specificity for DIP joints were 92.3% and 90.9%, respectively, and 75% and 100% for PIP joints. All readers were able to reproduce their own readings in DIP and PIP joints after 4 weeks. The overall agreement between the three readers was good; ICCs ranged from 0.945 to 0.586. Additionally, outcomes of the iOARS score in a hand OA cohort revealed a higher prevalence of interphalangeal joint OA compared with the Kellgren and Lawrence score. The iOARS score is uniquely based on histopathological alterations of the interphalangeal joints in order to reliably determine OA of the DIP and PIP joints radiographically. Its high specificity and sensitivity together with the dichotomous approach renders the iOARS score reliable, fast to perform and easy to apply. This tool may not only be valuable in daily clinical practice but also in clinical and epidemiological trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Climbing Bloom's Taxonomy Pyramid: Lessons from a Graduate Histology Course

ERIC Educational Resources Information Center

Zaidi, Nikki B.; Hwang, Charles; Scott, Sara; Stallard, Stefanie; Purkiss, Joel; Hortsch, Michael

2017-01-01

Bloom's taxonomy was adopted to create a subject-specific scoring tool for histology multiple-choice questions (MCQs). This Bloom's Taxonomy Histology Tool (BTHT) was used to analyze teacher- and student-generated quiz and examination questions from a graduate level histology course. Multiple-choice questions using histological images were…

Protective Effect of Anthocyanins Extract from Blueberry on TNBS-Induced IBD Model of Mice

PubMed Central

Wu, Lin-Hua; Xu, Zeng-Lai; Dong, Di; He, Shan-An; Yu, Hong

2011-01-01

This study was carried out to evaluate the protective effect of anthocyanins extract of blueberry on trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) model of mice. The study employed female C57BL/6 mice (n = 50), and colitis was induced by intracolonic injection of 0.5 mg of TNBS dissolved in 50% ethanol–phosphate buffered solution. The mice were divided into five groups (n = 10): vehicle, TNBS control and anthocyanins groups that received different doses of anthocyanins extract (10, 20 and 40 mg kg−1) daily for 6 days. Both increase in body weight and diarrhea symptoms were monitored each day. After 6 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay (NO, myeloperoxidase (MPO), interleukin (IL)-12, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ). The results showed that the anthocyanins extract of blueberry rendered strong protection against TNBS-induced colonic damage at a dosage of 40 mg kg−1. When compared with the control, anthocyanins extract significantly prevented loss of body weight and ameliorated the scores of diarrhea, morphology and histology. Treatment with anthocyanins extract restored IL-10 excretion, as well as caused reduction in the levels of NO, MPO, IL-12, TNF-α and IFN-γ. Our research revealed the protective effect of anthocyanins extract from blueberry on TNBS-induced experimental colitis in mice, as well as examined whether high levels of dietary blueberries would lower the risk or have protective effects on human IBD, which may require further investigation. PMID:21785630

Micro-fractional ablative skin resurfacing with two novel erbium laser systems.

PubMed

Dierickx, Christine C; Khatri, Khalil A; Tannous, Zeina S; Childs, James J; Cohen, Richard H; Erofeev, Andrei; Tabatadze, David; Yaroslavsky, Ilya V; Altshuler, Gregory B

2008-02-01

Fractional ablation offers the potential benefits of full-surface ablative skin resurfacing while minimizing adverse effects. The purpose of this study was to evaluate the safety, damage profile, and efficacy of erbium fractional lasers. Histology from animal and human skin as well as clinical evaluations were conducted with erbium YAG (2,940 nm) and erbium YSGG (2,790 nm) fractional lasers varying pulse width, microbeam (microb) energy, number of passes, and stacking of pulses. Single-pulse treatment parameters from 1 to 12 mJ per 50-70 microm diameter microbeam and 0.25-5 milliseconds pulse widths produced microcolumns of ablation with border coagulation of up to 100 microm width and 450 microm depth. Stacking of pulses generated deeper microcolumns. Clinical observations and in vivo histology demonstrate rapid re-epithelization and limited adverse side effects. Facial treatments were performed in the periorbital and perioral areas using 1-8 passes of single and stacked pulses. Treatments were well-tolerated and subjects could resume their normal routine in 4 days. A statistically significant reduction in wrinkle scores at 3 months was observed for both periorbital and perioral wrinkles using blinded grading. For periorbital treatments of four passes or more, over 90% had > or =1 score wrinkle reduction (0-9 scale) and 42% had > or =2. For perioral wrinkles, over 50% had substantial improvements (> or =2). The clinical observations and histology findings demonstrate that micro-fractional ablative treatment with 2,790 and 2,940 nm erbium lasers resulted in safe and effective wrinkle reduction with minimal patient downtime. The depth and width of the ablated microcolumns and varying extent of surrounding coagulation can be controlled and used to design new treatment procedures targeted for specific indications and areas such as moderate to severe rhytides and photodamaged skin.

Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury.

PubMed

Boyce, M K; Trumble, T N; Carlson, C S; Groschen, D M; Merritt, K A; Brown, M P

2013-05-01

Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. OC fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P = 0.0012), while joint circumference (P < 0.0001) and effusion scores (P < 0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Histologic structure of red nile tilapia fish (Oreochromis nilloticus Var.) gill which is exposed to lead acetate

NASA Astrophysics Data System (ADS)

Utami, N. R.; Widiyaningrum, P.; Iswari, R. S.

2018-03-01

Fish is a water biota commonly used as the bioindicator of water pollution level. One of the animals which are recommended by EPA as the test species is red Nile Tilapia fish (Oreochromis niloticus var). The purpose of this research is to get the value of LC50-96 hours in the toxicity test toward the fishes which are exposed to lead acetate with some details identification of the gills damage by gill histologic structure examination together with the determination of the lead concentration which caused the destruction. Sixty fish were used in the preliminary test to detect the threshold concentration (LC0-48 h); whereas 120 fish were used in the toxicity test to get the mortality level of fish up to 50% in 96 h. Finally, for treatment test, there were 80 fish which were exposed to lead acetate in the concentration of 0 ppm, 259.51 ppm, 291.94 ppm and 324.38 ppm. All the treatment tests were given for four weeks. The data were collected at the end of the 4th week, and then, the description of the fish gill histology structure was done. The histology observation of the fishes gill detected some damages in the form of edema (0% -25%), lamellar fusion (1% -75%), hyperplasia (0% -50%), epithelial lifting (0% -50%), and necrosis (0% -50%). The results indicate that administration of lead acetate accelerates moderate damage to the red Nile tilapia fish gill structure. The greatest level of damage is lamellar fusion, while the other decline damages are edema, hyperplasia, epithelial lifting, and necrosis. Furthermore, it can be concluded that LC50-96 hours value in the lead acetate toxicity test of red Nile tilapia fish is 324,38 ppm with some histologic structure damage in the gill the fishes.

Optimizing utilization of kidneys from deceased donors over 60 years: five-year outcomes after implementation of a combined clinical and histological allocation algorithm.

PubMed

Pierobon, Elisa Sefora; Sefora, Pierobon Elisa; Sandrini, Silvio; Silvio, Sandrini; De Fazio, Nicola; Nicola, De Fazio; Rossini, Giuseppe; Giuseppe, Rossini; Fontana, Iris; Iris, Fontana; Boschiero, Luigino; Luigino, Boschiero; Gropuzzo, Maria; Maria, Gropuzzo; Gotti, Eliana; Eliana, Gotti; Donati, Donato; Donato, Donati; Minetti, Enrico; Enrico, Minetti; Gandolfo, Maria Teresa; Teresa, Gandolfo Maria; Brunello, Anna; Anna, Brunello; Libetta, Carmelo; Carmelo, Libetta; Secchi, Antonio; Antonio, Secchi; Chiaramonte, Stefano; Stefano, Chiaramonte; Rigotti, Paolo; Paolo, Rigotti

2013-08-01

This 5 year observational multicentre study conducted in the Nord Italian Transplant programme area evaluated outcomes in patients receiving kidneys from donors over 60 years allocated according to a combined clinical and histological algorithm. Low-risk donors 60-69 years without risk factors were allocated to single kidney transplant (LR-SKT) based on clinical criteria. Biopsy was performed in donors over 70 years or 60-69 years with risk factors, allocated to Single (HR-SKT) or Dual kidney transplant (HR-DKT) according to the severity of histological damage. Forty HR-DKTs, 41 HR-SKTs and 234 LR-SKTs were evaluated. Baseline differences generally reflected stratification and allocation criteria. Patient and graft (death censored) survival were 90% and 92% for HR-DKT, 85% and 89% for HR-SKT, 88% and 87% for LR-SKT. The algorithm appeared user-friendly in daily practice and was safe and efficient, as demonstrated by satisfactory outcomes in all groups at 5 years. Clinical criteria performed well in low-risk donors. The excellent outcomes observed in DKTs call for fine-tuning of cut-off scores for allocation to DKT or SKT in high-risk patients. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

Histological examination of drill sites in bovine rib bone after grinding in vitro with eight different devices.

PubMed

Draenert, F G; Mathys, R; Ehrenfeld, M; Draenert, Y; Draenert, K

2007-10-01

The way in which bone is processed may affect the quality of the specimen and how much information may be gleaned on histological examination. We investigated eight widely used rasps and drills and compared the results. All large chip cutters damaged the bed and marrow of the bone. The tool that caused the least damage was the wet grinding diamond tool.

Improvement of small intestinal microcirculation by postconditioning after lower limb ischemia.

PubMed

Turóczi, Zsolt; Fülöp, András; Czigány, Zoltán; Varga, Gabriella; Rosero, Oliver; Tökés, Tünde; Kaszaki, József; Lotz, Gábor; Harsányi, László; Szijártó, Attila

2015-03-01

Major lower limb vascular surgeries may result in severe, remote injury of the gastrointestinal system, which has high mortality rates. Postconditioning is a technique with potential capability of reducing remote gastrointestinal complications. Our aim was to assess the remote macro- and micro-hemodynamic changes of the small intestine following an infrarenal aortic occlusion and to evaluate the effects of postconditioning on these alterations. Rats underwent 3h of infrarenal aortic occlusion followed by 4h of reperfusion. In one group, postconditioning was applied. Blood pressure, superior mesenteric artery flow and mucosal microcirculation of the duodenum, jejunum and ileum were assessed. Samples were taken from each intestinal segment for histological examinations. Superior mesenteric artery flow, as well as microcirculation of the duodenum, jejunum and ileum showed significant impairment in the IR group, while histological damage was significantly worsened. Postconditioning was able to limit flow reduction in all three small bowel segments and in the superior mesenteric artery, and was able to significantly reduce histological damage. Strong negative correlation was found between microcirculatory values and histological damage. Microcirculatory impairment might be responsible for remote intestinal injury following infrarenal aortic occlusion. Postconditioning was able to reduce this remote intestinal damage. Copyright © 2015 Elsevier Inc. All rights reserved.

Zero-Time Renal Transplant Biopsies: A Comprehensive Review.

PubMed

Naesens, Maarten

2016-07-01

Zero-time kidney biopsies, obtained at time of transplantation, are performed in many transplant centers worldwide. Decisions on kidney discard, kidney allocation, and choice of peritransplant and posttransplant treatment are sometimes based on the histological information obtained from these biopsies. This comprehensive review evaluates the practical considerations of performing zero-time biopsies, the predictive performance of zero-time histology and composite histological scores, and the clinical utility of these biopsies. The predictive performance of individual histological lesions and of composite scores for posttransplant outcome is at best moderate. No single histological lesion or composite score is sufficiently robust to be included in algorithms for kidney discard. Dual kidney transplantation has been based on histological assessment of zero-time biopsies and improves outcome in individual patients, but the waitlist effects of this strategy remain obscure. Zero-time biopsies are valuable for clinical and translational research purposes, providing insight in risk factors for posttransplant events, and as baseline for comparison with posttransplant histology. The molecular phenotype of zero-time biopsies yields novel therapeutic targets for improvement of donor selection, peritransplant management and kidney preservation. It remains however highly unclear whether the molecular expression variation in zero-time biopsies could become a better predictor for posttransplant outcome than donor/recipient baseline demographic factors.

Matriptase Induction of Metalloproteinase‐Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms

PubMed Central

Wilkinson, David J.; Habgood, Angela; Lamb, Heather K.; Thompson, Paul; Hawkins, Alastair R.; Désilets, Antoine; Leduc, Richard; Steinmetzer, Torsten; Hammami, Maya; Lee, Melody S.; Craik, Charles S.; Watson, Sharon; Lin, Hua; Milner, Jennifer M.

2017-01-01

Objective To assess the ability of matriptase, a type II transmembrane serine proteinase, to promote aggrecan loss from the cartilage of patients with osteoarthritis (OA) and to determine whether its inhibition can prevent aggrecan loss and cartilage damage in experimental OA. Methods Aggrecan release from human OA cartilage explants and human stem cell–derived cartilage discs was evaluated, and cartilage‐conditioned media were used for Western blotting. Gene expression was analyzed by real‐time polymerase chain reaction. Murine OA was induced by surgical destabilization of the medial meniscus, and matriptase inhibitors were administered via osmotic minipump or intraarticular injection. Cartilage damage was scored histologically and aggrecan cleavage was visualized immunohistochemically using specific neoepitope antibodies. Results The addition of soluble recombinant matriptase promoted a time‐dependent release of aggrecan (and collagen) from OA cartilage, which was sensitive to metalloproteinase inhibition and protease‐activated receptor 2 antagonism. Although engineered human (normal) cartilage discs failed to release aggrecan following matriptase addition, both matrix metalloproteinase– and aggrecanase‐mediated cleavages of aggrecan were detected in human OA cartilage. Additionally, while matriptase did not directly degrade aggrecan, it promoted the accumulation of low‐density lipoprotein receptor–related protein 1 (LRP‐1) in conditioned media of the OA cartilage explants. Matriptase inhibition via neutralizing antibody or small molecule inhibitor significantly reduced cartilage damage scores in murine OA, which was associated with reduced generation of metalloproteinase‐mediated aggrecan cleavage. Conclusion Matriptase potently induces the release of metalloproteinase‐generated aggrecan fragments as well as soluble LRP‐1 from OA cartilage. Therapeutic targeting of matriptase proteolytic activity reduces metalloproteinase activity, further suggesting that this serine proteinase may have potential as a disease‐modifying therapy in OA. PMID:28464560

Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on cadmium-induced testicular toxicity.

PubMed

El-Neweshy, M S; El-Maddawy, Z K; El-Sayed, Y S

2013-12-01

Cadmium (Cd) is a well-known testicular toxicant. This study was designed to explore the long-term effects of a single low dose of Cd on spermatogenesis, and testicular dysfunction and oxidative stress, and the therapeutic potential of date palm pollen extract (DPP) in averting such reproductive damage. Adult male Wistar rats received a single intraperitoneal injection of CdCl2 (0 or 1 mg kg(-1) ). Twenty-four hours later, they started receiving DPP (0 or 40 mg kg(-1) ) orally, once daily for 56 consecutive days. Cd exposure caused significant reproductive damage via reduced weight of the reproductive organs, which includes spermatological damage (decreased sperm count and motility and increased rates of sperm abnormalities), increased oxidative stress (increased malondialdehyde and decreased reduced glutathione levels), histological alterations (necrosis, inefficient to completely arrest spermatogenesis and a reduced Johnsen's score) and decreased serum testosterone level. DPP restored spermatogenesis and attenuated the toxic effects of Cd on the reproductive system to the levels observed in the control animals. These findings support the hypothesis that the testis is particularly sensitive to Cd, which can cause testicular damage and infertility. Treatment with DPP can ameliorate the deleterious effects of Cd, probably by activating testicular endocrine and antioxidant systems. © 2012 Blackwell Verlag GmbH.

Gastroprotective properties of cashew gum, a complex heteropolysaccharide of Anacardium occidentale, in naproxen-induced gastrointestinal damage in rats.

PubMed

Carvalho, Nathalia S; Silva, Mônica M; Silva, Renan O; Nicolau, Lucas A D; Sousa, Francisca Beatriz M; Damasceno, Samara R B; Silva, Durcilene A; Barbosa, André L R; Leite, José Roberto S A; Medeiros, Jand Venes R

2015-05-01

Long-term use nonsteroidal anti-inflammatory drug is associated with gastrointestinal (GI) lesion formation. The aim of this study was to investigate the protective activity of cashew gum (CG), a complex heteropolysaccharide extracted from Anacardium occidentale on naproxen (NAP)-induced GI damage. Male Wistar rats were pretreated with vehicle or CG (1, 3, 10, and 30 mg/kg, p.o.) twice daily for 2 days; after 1 h, NAP (80 mg/kg, p.o.) was administered. The rats were euthanized on the 2nd day of treatment, 4 h after NAP administration. Stomach lesions were measured using digital calipers. The medial small intestine was used for the evaluation of macroscopic lesion scores. Samples of the stomach and the intestine were used for histological evaluation, and assays for glutathione (GSH), malonyldialdehyde (MDA), and myeloperoxidase (MPO). Additional rats were used to measure gastric mucus and secretion. Pretreatment with CG reduced the macroscopic and microscopic damage induced by NAP. CG significantly attenuated NAP-induced alterations in MPO, GSH, and MDA levels. Furthermore, CG returned adherent mucus levels to normal values. These results suggest that CG has a protective effect against GI damage via mechanisms that involve the inhibition of inflammation and increasing the amount of adherent mucus in mucosa. © 2015 Wiley Periodicals, Inc.

[Therapeutic effect of human mesenchymal stem cells in skin after radiation damage].

PubMed

Bensidhoum, Morad; Gobin, Stéphanie; Chapel, Alain; Lemaitre, Gilles; Bouet, Stéphan; Waksman, Gilles; Thierry, Dominique; Martin, Michèle T

2005-01-01

Over 50% of all cancer patients presently receive radiotherapy at one stage in their treatment course. Inevitably skin is one of the most frequently damaged tissue due to its localization and constant turn-over. Our present goal is to reduce radiation-induced complications in human skin through stem cell therapy, particulary in human epidermis. Mesenchymal Stem Cells (MSCs) have been shown to be multipotent cells able to engraft in many tissues after injury. Herein, we isolated human MSCs and tested their capability to improve skin wound healing after irradiation. This potential was assessed in NOD/SCID mice which received 30 Gy locally on the thigh. This dose caused within 3 weeks local epidermis necrosis which was repaired within 13 weeks. MSCs were intravenously injected in irradiated mice 24 hours after exposure. Clinical scoring throughout 6 weeks gave indications that human MSCs reduced the extent of damage and accelerated the wound healing process. We show by quantitative qPCR and histological studies the presence of human MSCs derived cells into the scar. Human MSCs homed to the damaged skin and participated to the wound healing process. These results open prospects for cellular therapy by MSCs in irradiated epithelial tissues and could be extended to the whole general field of cutaneous cicatrization, particularly after burns.

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

PubMed Central

dos Santos, G.C.; Parra, E.R.; Stegun, F.W.; Cirqueira, C.S.; Capelozzi, V.L.

2013-01-01

Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures. PMID:24270907

Comparison of ferromagnetic induction and bipolar electrosurgery and suction in corticotomies in pig cerebrum.

PubMed

Bowers, Christian A; Burns, Greg; Salzman, Karen; McGill, Lawrence; MacDonald, Joel D

2015-04-01

The effects of newer energy-based surgical dissection and coagulation modalities on cerebral tissue have not been investigated. Several instruments have been developed to address the limitations of traditional electrosurgical instruments in the nervous system. We compared the effects of standard bipolar electrocautery and suction (BPS) with those of a new ferromagnetic induction (FMI) device in corticotomies of pig cerebral tissue as assessed by magnetic resonance imaging (MRI) and histological analysis. Three adult pigs underwent bilateral corticotomies (3 cm long×1 cm deep) using both FMI and BPS. The acute cerebral tissue edema created by each method was measured on coronal volumetric T2-weighted MRI sequences immediately after surgery. A lateral thermal "damage index" was calculated by dividing the width of the visible T2 tissue edema by the measured depth. The radiographic damage indices with each method were compared statistically. Histological analysis of each incision was conducted to compare the extent of tissue damage. MRI showed that the mean radiographic damage index of each corticotomy was significantly lower with the FMI (0.30 ± 0.02 (0.28-0.32)) than with the BPS method (0.54 ± 0.11 (0.42-0.64)) (p = 0.02). Histological analysis suggested a correlation with the radiographic findings as the FMI tissue samples demonstrated less adjacent tissue damage than BPS. FMI appeared to cause less adjacent tissue damage than the BPS method in pig cerebral tissue based on quantitative radiographic and qualitative histological analysis. Future studies are needed to investigate the clinical implications of energy-based surgical dissection on cerebral tissue. Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Hepatoprotective activity of dried- and fermented-processed virgin coconut oil.

PubMed

Zakaria, Z A; Rofiee, M S; Somchit, M N; Zuraini, A; Sulaiman, M R; Teh, L K; Salleh, M Z; Long, K

2011-01-01

The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study.

Hepatoprotective Activity of Dried- and Fermented-Processed Virgin Coconut Oil

PubMed Central

Zakaria, Z. A.; Rofiee, M. S.; Somchit, M. N.; Zuraini, A.; Sulaiman, M. R.; Teh, L. K.; Salleh, M. Z.; Long, K.

2011-01-01

The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study. PMID:21318140

A simple behavioral test for locomotor function after brain injury in mice.

PubMed

Tabuse, Masanao; Yaguchi, Masae; Ohta, Shigeki; Kawase, Takeshi; Toda, Masahiro

2010-11-01

To establish a simple and reliable test for assessing locomotor function in mice with brain injury, we developed a new method, the rotarod slip test, in which the number of slips of the paralytic hind limb from a rotarod is counted. Brain injuries of different severity were created in adult C57BL/6 mice, by inflicting 1-point, 2-point and 4-point cryo-injuries. These mice were subjected to the rotarod slip test, the accelerating rotarod test and the elevated body swing test (EBST). Histological analyses were performed to assess the severity of the brain damage. Significant and consistent correlations between test scores and severity were observed for the rotarod slip test and the EBST. Only the rotarod slip test detected the mild hindlimb paresis in the acute and sub-acute phase after injury. Our results suggest that the rotarod slip test is the most sensitive and reliable method for assessing locomotor function after brain damage in mice. Copyright © 2010 Elsevier Ltd. All rights reserved.

Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment.

PubMed

Bar-Yehuda, S; Rath-Wolfson, L; Del Valle, L; Ochaion, A; Cohen, S; Patoka, R; Zozulya, G; Barer, F; Atar, E; Piña-Oviedo, S; Perez-Liz, G; Castel, D; Fishman, P

2009-10-01

Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A(3) adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model. OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 microg/kg given twice daily) was initiated. The A(3) adenosine receptor antagonist MRS1220 (100 microg/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O-fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses. CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-kappaB signaling pathway, resulting in down-regulation of tumor necrosis factor alpha. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes. CF101 deregulated the NF-kappaB signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA.

Non-alcoholic fatty liver disease - histological scoring systems: a large cohort single-center, evaluation study.

PubMed

Rastogi, Archana; Shasthry, Saggere Muralikrishna; Agarwal, Ayushi; Bihari, Chhagan; Jain, Priyanka; Jindal, Ankur; Sarin, Shiv

2017-11-01

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease. Till date, liver biopsy remains the gold standard for identification and quantification of the wide histological spectra of NAFLD. Histological scorings are very useful and widely applied for the diagnosis and management in clinical trials and follow-up studies of non-alcoholic steatohepatitis (NASH). However, in view of scarce published literature, there is a need to evaluate them in large cohort of NAFLD. This study was aimed to evaluate the two histological scoring systems (NAS-CRN, SAF) in the diagnosis of NAFLD and to assess the role of histological characteristics as injury markers in NAFLD. Retrospective histological study of liver biopsies of 1000 patients diagnosed as NAFLD, between 2010 and 2016, was conducted. Histopathologic evaluation and semiquantiative scoring based on NAS-CRN and SAF algorithm and their correlation with serum aminotransferase and fibrosis were performed. Liver biopsies were classified according to the NAS-CRN scoring, as NAS <3 (not NASH) in 72 (7.2%), NAS 3-4 (borderline NASH) in 310 (31%), and NAS ≥5 (definite NASH) in 618 (61.8%), and SAF classified 117 (11.7%) not NASH and 883 (88.3%) definite NASH. There was excellent concordance for definite NASH and not NASH; however, 88.06% of borderline NASH was classified as NASH by SAF. 76.39% by NAS and 78.63% by SAF algorithm who were diagnosed as not NASH showed the presence of fibrosis; however, higher stages of fibrosis were significantly more prevalent in definite NASH, excluding burnt-out cirrhosis. Serum ALT was significantly associated with increasing stages of fibrosis (p < 0.001) and the three categories (not NASH, borderline NASH, and definite NASH) when classified as with/without fibrosis (p < 0.001). Steatosis of higher grades, more ballooned cells, and more foci of Lobular Inflammation were found in significantly higher proportion of patients with NASH (p < 0.001), with higher fibrosis stages (p < 0.001) and higher serum ALT levels (p < 0.001). NAFLD classifications based on histological scoring NAS-CRN and SAF algorithm are concordant for the category of definite NASH and not NASH, while borderline NASH shows discrepant interpretation. There was highly significant correlation between the NAS and SAF categories with high grades of histological characteristics, with serum ALT and with higher stages of fibrosis. Exclusion of fibrosis is a limitation with both scores. © 2017 APMIS. Published by John Wiley & Sons Ltd.

High-intensity focused ultrasound for potential treatment of polycystic ovary syndrome: toward a noninvasive surgery.

PubMed

Shehata, Islam A; Ballard, John R; Casper, Andrew J; Hennings, Leah J; Cressman, Erik; Ebbini, Emad S

2014-02-01

To investigate the feasibility of using high-intensity focused ultrasound (HIFU), under dual-mode ultrasound arrays (DMUAs) guidance, to induce localized thermal damage inside ovaries without damage to the ovarian surface. Laboratory feasibility study. University-based laboratory. Ex vivo canine and bovine ovaries. DMUA-guided HIFU. Detection of ovarian damage by ultrasound imaging, gross pathology, and histology. It is feasible to induce localized thermal damage inside ovaries without damage to the ovarian surface. DMUA provided sensitive imaging feedback regarding the anatomy of the treated ovaries and the ablation process. Different ablation protocols were tested, and thermal damage within the treated ovaries was histologically characterized. The absence of damage to the ovarian surface may eliminate many of the complications linked to current laparoscopic ovarian drilling (LOD) techniques. HIFU may be used as a less traumatic tool to perform LOD. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Are the consequences of neonatal hypoxia-ischemia dependent on animals' sex and brain lateralization?

PubMed

Sanches, E F; Arteni, N S; Scherer, E B; Kolling, J; Nicola, F; Willborn, S; Wyse, A T S; Netto, C A

2013-04-24

Hypoxia-ischemia on 3-day-old rats (HIP3) allows the investigation of HI damage in the immature brain. HIP3 is characterized for neurological disabilities caused by white matter injury. This study investigates the relationship between animals' sex and injured hemisphere on HIP3 consequences. Male and female Wistar rats had their right or left common carotid artery occluded under halotane anesthesia and exposed to 8% O2 for 1.5 h. Control rats received sham surgery and exposure to 1.5 h of room air in isolation of their mothers. Sex and injured hemisphere influence in Na+/K+ -ATPase activity 24h after lesion: females and the right brain hemispheres showed decreased enzymatic activity after HIP3. Cognitive impairment was observed in step-down inhibitory avoidance, in which females HIP3 left injured were the most damaged. Histological analysis showed a trend to white matter damage in females left injured without hemispherical nor hippocampal volume decrease in HIP3 rats at postnatal day 21. However, at PND90, hemisphere and sex effects were noted in hemispherical volume and myelination: left brain hemisphere and the females evidenced higher histological damage. Our results points to an increased resistance of male rats and right brain hemisphere to support the impairment caused in Na+/K+ -ATPase activity early after HIP3, and evidencing more discrete behavioral impairments and histological damage at adulthood. Present data adds new evidence of distinct effects of brain lateralization and sex vulnerability on biochemical, behavioral and histological parameters after hypoxia-ischemia. Copyright © 2013 Elsevier B.V. All rights reserved.

The effect of forced exercise on knee joints in Dio2(-/-) mice: type II iodothyronine deiodinase-deficient mice are less prone to develop OA-like cartilage damage upon excessive mechanical stress.

PubMed

Bomer, Nils; Cornelis, Frederique M F; Ramos, Yolande F M; den Hollander, Wouter; Storms, Lies; van der Breggen, Ruud; Lakenberg, Nico; Slagboom, P Eline; Meulenbelt, Ingrid; Lories, Rik J L

2016-03-01

To further explore deiodinase iodothyronine type 2 (DIO2) as a therapeutic target in osteoarthritis (OA) by studying the effects of forced mechanical loading on in vivo joint cartilage tissue homeostasis and the modulating effect herein of Dio2 deficiency. Wild-type and C57BL/6-Dio2(-/-) -mice were subjected to a forced running regime for 1 h per day for 3 weeks. Severity of OA was assessed by histological scoring for cartilage damage and synovitis. Genome-wide gene expression was determined in knee cartilage by microarray analysis (Illumina MouseWG-6 v2). STRING-db analyses were applied to determine enrichment for specific pathways and to visualise protein-protein interactions. In total, 158 probes representing 147 unique genes showed significantly differential expression with a fold-change ≥1.5 upon forced exercise. Among these are genes known for their association with OA (eg, Mef2c, Egfr, Ctgf, Prg4 and Ctnnb1), supporting the use of forced running as an OA model in mice. Dio2-deficient mice showed significantly less cartilage damage and signs of synovitis. Gene expression response upon exercise between wild-type and knockout mice was significantly different for 29 genes. Mice subjected to a running regime have significant increased cartilage damage and synovitis scores. Lack of Dio2 protected against cartilage damage in this model and was reflected in a specific gene expression profile, and either mark a favourable effect in the Dio2 knockout (eg, Gnas) or an unfavourable effect in wild-type cartilage homeostasis (eg, Hmbg2 and Calr). These data further support DIO2 activity as a therapeutic target in OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Spermidine rescues proximal tubular cells from oxidative stress and necrosis after ischemic acute kidney injury.

PubMed

Kim, Jinu

2017-10-01

Kidney ischemia and reperfusion injury (IRI) is associated with a high mortality rate, which is attributed to tubular oxidative stress and necrosis; however, an effective approach to limit IRI remains elusive. Spermidine, a naturally occurring polyamine, protects yeast cells against aging through the inhibition of oxidative stress and necrosis. In the present study, spermidine supplementation markedly attenuated increases in plasma creatinine concentration and tubular injury score after IRI. In addition, exogenous spermidine potently inhibited oxidative stress, especially lipid peroxidation after IRI in kidneys and exposure to hydrogen peroxide in kidney proximal tubular cells, suppressing plasma membrane disruption and necrosis. Consistent with spermidine supplementation, upregulation of ornithine decarboxylase (ODC) in human kidney proximal tubular cells significantly diminished lipid peroxidation and necrosis induced by hydrogen peroxide-induced injury. Conversely, ODC deficiency significantly enhanced lipid peroxidation and necrosis after exposure to hydrogen peroxide. Finally, small interfering RNA-mediated ODC inhibition induced functional and histological damage in kidneys as well as it increased lipid hydroperoxide levels after IRI. In conclusion, these data suggest that spermidine level determines kidney proximal tubular damage through oxidative stress and necrosis induced by IRI, and this finding provides a novel target for prevention of tubular damage induced by IRI.

Histological alterations in gills of Macrobrachium amazonicum juveniles exposed to ammonia and nitrite.

PubMed

Dutra, Fabrício Martins; Rönnau, Milton; Sponchiado, Dircelei; Forneck, Sandra Carla; Freire, Carolina Arruda; Ballester, Eduardo Luis Cupertino

2017-06-01

Aquaculture has shown great growth in the last decades. Due to the restrictions on water use, production systems are becoming increasingly more intensive, raising concerns about the production water quality. Macrobrachium amazonicum is among the freshwater prawn species with favorable characteristics for production and possibility of intensification. Nitrogen compounds such as ammonia and nitrite affect the health of aquatic organisms since they quickly reach toxic concentrations. These compounds can also cause damage to the gill structure, leading to hypoxia in tissues, affecting acid-base balance, osmoregulation (salt absorption) and ammonia excretion, decreasing the immune capacity of the animal and, in extreme cases, cause death. The aim of this study was to assess histological changes in the gills of Macrobrachium amazonicum juveniles subjected to different concentrations of total ammonia and nitrite. The prawns were subjected to different concentrations of those compounds and their gills were removed and preserved for histological analysis. The gills were assessed for changes according to the Organ Index (I org ) and, for each change, an importance factor (w) was attributed according to the degree of reversibility and applied according to the degree of extension or frequency of the damage. The damage to the gills in the treatments with 100% mortality, both for ammonia and nitrite, corresponded to the high occurrence of progressive, regressive, circulatory, and inflammation damages. The other treatments (which caused less mortality) had mainly inflammation and regressive damages, whose occurrence increased according to the increase in ammonia and nitrite concentration. The histological analysis confirmed that the higher the total ammonia and nitrite concentrations, the larger the damages caused to the gill structure and that lower nitrite concentrations caused similar damages to those caused by higher total ammonia concentrations, which reflects the lower capacity M. amazonicum has to tolerate nitrite. Copyright © 2017 Elsevier B.V. All rights reserved.

T2* mapping of hip joint cartilage in various histological grades of degeneration.

PubMed

Bittersohl, B; Miese, F R; Hosalkar, H S; Herten, M; Antoch, G; Krauspe, R; Zilkens, C

2012-07-01

To evaluate T2* values in various histological severities of osteoarthritis (OA). Magnetic resonance imaging (MRI) and T2* mapping including a three-dimensional (3D) double-echo steady-state (DESS) sequence for morphological cartilage assessment and a 3D multiecho data image combination (MEDIC) sequence for T2* mapping were conducted in 21 human femoral head specimens with varying severities of OA. Subsequently, histological assessment was undertaken in all specimens to correlate the observations of T2* mapping with histological analyses. According to the Mankin score, four grades of histological changes were determined: grade 0 (Mankin scores of 0-4), grade I (scores of 5-8), grade II (scores of 9-10), and grade III (scores of 11-14). For reliability assessment, cartilage T2* measurements were repeated after 4 weeks in 10 randomly selected femoral head specimens. T2* values decreased significantly with increasing cartilage degeneration (total P-values <0.001) ranging from 36.3 ± 4.3 ms in grade 0 regions to 22.8 ± 4.3 ms in regions with grade III changes. Pearson correlation analysis proved a fair correlation between T2* values and Mankin score (correlation coefficient = -0.362) that was statistically significant (P-value <0.001). Intra-class correlation (ICC) analysis demonstrated high intra-observer reproducibility for the T2* measurement (ICC: 0.949, P < 0.001). Given the advantages of the T2* mapping technique with no need for contrast medium, high image resolution and ability to perform 3D biochemically sensitive imaging, T2* mapping may be a strong addition to the currently evolving era of cartilage biochemical imaging. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Comparison of first-intention healing of carbon dioxide laser, 4.0-MHz radiosurgery, and scalpel incisions in ball pythons (Python regius).

PubMed

Hodshon, Rebecca T; Sura, Patricia A; Schumacher, Juergen P; Odoi, Agricola; Steeil, James C; Newkirk, Kim M

2013-03-01

To evaluate first-intention healing of CO(2) laser, 4.0-MHz radiowave radiosurgery (RWRS), and scalpel incisions in ball pythons (Python regius). 6 healthy adult ball pythons. A skin biopsy sample was collected, and 2-cm skin incisions (4/modality) were made in each snake under anesthesia and closed with surgical staples on day 0. Incision sites were grossly evaluated and scored daily. One skin biopsy sample per incision type per snake was obtained on days 2, 7, 14, and 30. Necrotic and fibroplastic tissue was measured in histologic sections; samples were assessed and scored for total inflammation, histologic response (based on the measurement of necrotic and fibroplastic tissues and total inflammation score), and other variables. Frequency distributions of gross and histologic variables associated with wound healing were calculated. Gross wound scores were significantly greater (indicating greater separation of wound edges) for laser incisions than for RWRS and scalpel incisions at all evaluated time points. Necrosis was significantly greater in laser and RWRS incisions than in scalpel incision sites on days 2 and 14 and days 2 and 7, respectively; fibroplasia was significantly greater in laser than in scalpel incision sites on day 30. Histologic response scores were significantly lower for scalpel than for other incision modalities on days 2, 14, and 30. In snakes, skin incisions made with a scalpel generally had less necrotic tissue than did CO(2) laser and RWRS incisions. Comparison of the 3 modalities on the basis of histologic response scores indicated that use of a scalpel was preferable, followed by RWRS and then laser.

Correlation Between Magnetic Resonance Imaging-Based Evaluation of Extramural Vascular Invasion and Prognostic Parameters of T3 Stage Rectal Cancer.

PubMed

Yu, Jing; Huang, Dong-Ya; Xu, Hui-Xin; Li, Yang; Xu, Qing

2016-01-01

The aim of this study was to analyze the correlation between magnetic resonance imaging-based extramural vascular invasion (EMVI) and the prognostic clinical and histological parameters of stage T3 rectal cancers. Eighty-six patients with T3 stage rectal cancer who received surgical resection without neoadjuvant therapy were included. Magnetic resonance imaging-based EMVI scores were determined. Correlations between the scores and pretreatment carcinoembryonic antigen levels, tumor differentiation grade, nodal stage, and vascular endothelial growth factor expression were analyzed using Spearman rank coefficient analysis. Magnetic resonance imaging-based EMVI scores were statistically different (P = 0.001) between histological nodal stages (N0 vs N1 vs N2). Correlations were found between magnetic resonance imaging-based EMVI scores and tumor histological grade (rs = 0.227, P = 0.035), histological nodal stage (rs = 0.524, P < 0.001), and vascular endothelial growth factor expression (rs = 0.422; P = 0.016). Magnetic resonance imaging-based EMVI score is correlated with prognostic parameters of T3 stage rectal cancers and has the potential to become an imaging biomarker of tumor aggressiveness. Magnetic resonance imaging-based EMVI may be useful in helping the multidisciplinary team to stratify T3 rectal cancer patients for neoadjuvant therapies.

HISTOLOGICAL AND BIOCHEMICAL ANALYSIS OF MECHANICAL AND THERMAL BIOEFFECTS IN BOILING HISTOTRIPSY LESIONS INDUCED BY HIGH INTENSITY FOCUSED ULTRASOUND

PubMed Central

Wang, Yak-Nam; Khokhlova, Tatiana; Bailey, Michael; Hwang, Joo Ha; Khokhlova, Vera

2013-01-01

Recent studies have shown that shock wave heating and millisecond boiling in high intensity focused ultrasound (HIFU) fields can result in mechanical fractionation or emulsification of tissue - named boiling histotripsy. Visual observations of the change in color and contents indicated that the degree of thermal damage in the emulsified lesions can be controlled by varying the parameters of the exposure. The goal of this work was to examine thermal and mechanical effects in boiling histotripsy lesions using histological and biochemical analysis. The lesions were induced in ex vivo bovine heart and liver using a 2-MHz single-element transducer operating at duty factors of 0.005–0.01, pulse durations of 5–500 ms, and in situ shock amplitude of 73 MPa. Mechanical and thermal damage to tissue was evaluated histologically using conventional staining techniques (H&E and NADH-diphorase). Thermal effects were quantified by measuring denaturation of salt soluble proteins in the treated region. According to histology, the lesions that visually appeared as a liquid, contained no cellular structures larger than a cell nucleus and had a very sharp border of 1–2 cells. Both histology and protein analysis showed that lesions obtained with short pulses (< 10 ms) did not contain any thermal damage. Increasing the pulse duration resulted in an increase in thermal damage. However, both protein analysis and NADH-diaphorase staining showed less denaturation than visually observed as whitening of tissue. The number of HIFU pulses delivered per exposure did not change the lesion shape or the degree of thermal denaturation, whereas the size of the lesion showed a saturating behaviour thus suggesting optimal exposure duration. This study confirmed that boiling histotripsy offers an effective, predictable way to non-invasively fractionate tissue into subcellular fragments with or without inducing thermal damage. PMID:23312958

Histological evaluation of the equine larynx after unilateral laser-assisted ventriculocordectomy.

PubMed

Robinson, P; Williams, K J; Sullins, K E; Arnoczky, S P; Stick, J A; Robinson, N E; de Feijter-Rupp, H; Derksen, F J

2007-05-01

Trans-endoscopic laser surgery, such as unilateral laser-assisted ventriculocordectomy (LVC), has gained popularity in the treatment of RLN because a laryngotomy incision or general anaesthesia are not required. However, removal of the vocal fold and ventricle takes considerable laser energy and could cause collateral tissue damage, including injury to the adjacent laryngeal cartilages. To document the histological effects of laser surgery on laryngeal tissues in horses that have undergone LVC for the treatment of laryngeal hemiplegia (LH). Six horses were used: 4 with experimentally induced LH that had subsequently undergone LVC 6 months prior to euthanasia; and, 2 horses were used as controls. One of the control horses with naturally occurring LH was used to study the effect of neuropathy alone, whereas the other was subjected to euthanasia immediately following LVC to evaluate the acute effect of laser surgery. Using a band saw, each larynx was sectioned transversely at 5 mm intervals and evaluated histologically. Acutely, LVC caused thermal damage to adjacent soft tissues but did not affect the histology of the laryngeal cartilages. Six months after LVC, laryngeal cartilages were histologically normal and there was squamous metaplasia of the repaired laryngeal mucosa, resulting in restitution of the mucosal integrity. Using a diode laser in contact fashion at 20 W, LVC can be used to remove the laryngeal vocal fold and ventricle without causing laryngeal cartilage damage. Laryngeal chondritis is an unlikely consequence of LVC.

Exosomes Derived from Dendritic Cells Treated with Schistosoma japonicum Soluble Egg Antigen Attenuate DSS-Induced Colitis

PubMed Central

Wang, Lifu; Yu, Zilong; Wan, Shuo; Wu, Feng; Chen, Wei; Zhang, Beibei; Lin, Datao; Liu, Jiahua; Xie, Hui; Sun, Xi; Wu, Zhongdao

2017-01-01

Exosomes are 30–150 nm small membrane vesicles that are released into the extracellular medium via cells that function as a mode of intercellular communication. Dendritic cell (DC)-derived exosomes modulate immune responses and prevent the development of autoimmune diseases. Moreover, Schistosoma japonicum eggs show modulatory effects in a mouse model of colitis. Therefore, we hypothesized that exosomes derived from DCs treated with S. japonicum soluble eggs antigen (SEA; SEA-treated DC exosomes) would be useful for treating inflammatory bowel disease (IBD). Exosomes were purified from the supernatant of DCs treated or untreated with SEA and identified via transmission electron microscopy, western blotting and NanoSight. Acute colitis was induced via the administration of dextran sulfate sodium (DSS) in drinking water (5.0%, wt/vol). Treatment with exosomes was conducted via intraperitoneal injection (i.p.; 50 μg per mouse) from day 0 to day 6. Clinical scores were calculated based on weight loss, stool type, and bleeding. Colon length was measured as an indirect marker of inflammation, and colon macroscopic characteristics were determined. Body weight loss and the disease activity index of DSS-induced colitis mice decreased significantly following treatment with SEA-treated DC exosomes. Moreover, the colon lengths of SEA-treated DC exosomes treated colitis mice improved, and their mean colon macroscopic scores decreased. In addition, histologic examinations and histological scores showed that SEA-treated DC exosomes prevented colon damage in acute DSS-induced colitis mice. These results indicate that SEA-treated DC exosomes attenuate the severity of acute DSS-induced colitis mice more effectively than DC exosomes. The current work suggests that SEA-treated DC exosomes may be useful as a new approach to treat IBD. PMID:28959207

[Histomorphology of the liver by damage with phenolisatine-containing laxatives (Recurrent chronic cholangiohepatitis)].

PubMed

Lüders, C J; Riske, W E; Henning, H; Vogel, H M

1975-01-01

In the case of 36 female patients who were anamnestically known to have taken laxatives, semiquantitative histological investigations with laparoscopically obtained liver needle biopsies were effected after the exposition with preparations containing phenolisatine. The time gap until exposition was 12 to 24 h (16 cases), 48 h (8 cases), 72 to 96 h (4 cases) and 7 to 14 days (4 cases). The histological result after the exposition is an acute cholangiolitis of the allergic-hyperergic type with edema and a dense eosinophile infiltration of the portal fields with destruction of the epithelium of preformed bile ducts and portally proliferated ductles. In addition, the parenchyma of the liver shows a pleomorphism of the cells in form and colour with a cellular edema and with disseminated acidophilic necroses and necrobioses of the individual cells as well as with little reactive proliferation of the Kupffer's cell. After a period of 8 days the acute process has more or less subsided. Also, in the majority of cases there are histological signs of an aggressive chronic hepatitis of type IIa, partially in the active stage with piece-meal necroses and partially stabilized or in the process of healing. A transition to the picture of hepatitic cirrhosis is possible. In serious cases the picture of a chronic non-purulent destructive cholangitis can be simulated by the hepatocellular and canalicular damage. Thirty-one bioptic pre-examinations from the same results, whereby the acute cholangiolitical exacerbation can be attributed to an exposition of the patients themselves. The clinical picture of the phenolisatine damage in its entirety is induced by medication and is described as a recurrent chronic cholangiohepatitis. Similarities exist between the liver damages caused by chlorpromazine and arsphenamine. When medication is discontinued, the morphologic substrate recedes leaving behind an inactive fibrosis or cirrhosis. The formal and known causal pathogenetic connections are discussed with regard to this clinically important liver disease. Guidelines are then given for histological diagnosis of this damage caused by medication. 14% of the female patients with a histological picture of aggressive chronic hepatitis and hepatitic cirrhosis are affected by this type of liver damage.

Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model

PubMed Central

de Morais Lima, Gedson Rodrigues; Machado, Flavia Danniele Frota; Périco, Larissa Lucena; de Faria, Felipe Meira; Luiz-Ferreira, Anderson; Souza Brito, Alba Regina Monteiro; Pellizzon, Cláudia Helena; Hiruma-Lima, Clélia Akiko; Tavares, Josean Fechine; Barbosa Filho, José Maria; Batista, Leônia Maria

2017-01-01

AIM To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd). METHODS Inflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were evaluated. RESULTS Both Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-α and IL-1β. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide dismutase. CONCLUSION The data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease. PMID:28293082

The Effect of Metformin and Standard Therapy Versus Standard Therapy Alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial

DTIC Science & Technology

2009-01-01

histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA - IR scores, serum...BMI through diet and exercise significantly improved HOMA - IR scores, serum aminotransferases and liver histology. 15. SUBJECT TERMS 16. SECURITY...insulin resistance (or HOMA - IR ) score was calculated using the formula: fasting insulin (mIU/ml) fasting glu- cose (mg/dl)/405 [Matthews et al. 1985

Effects of PEG-PLA-nano Artificial Cells Containing Hemoglobin on Kidney Function and Renal Histology in Rats

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology. PMID:18979292

The relationship between histological prostatitis and lower urinary tract symptoms and sexual function.

PubMed

Kumsar, Sukru; Kose, Osman; Aydemir, Huseyin; Halis, Fikret; Gokce, Ahmet; Adsan, Oztug; Akkaya, Zeynep Kahyaoglu

2016-01-01

This prospective analysis assessed the effect of histological prostatitis on lower urinary tract functions and sexual function. The patients were separated into two groups as histologically observed prostatitis (Group A) and no prostatitis (Group B) according to the biopsy outcomes. International prostate symptom score, international index of erectile function-5 scores, maximal and average flow rate, and residual urine volumes were compared statistically between groups. There was no significant difference (P>0.05) in baseline age (t=0.64), body mass index value (t=0.51), prostate volume (t=0.87), prostate-specific antigen levels (t=0.43), maximal (t=0.84) and average flow rate (t=0.59), and post-void residual urine volume (t=0.71). Mean international prostate symptom score in patients with prostatitis was numerically but not significantly higher than that in those without prostatitis (t=0.794, P=0.066). Mean international index of erectile function-5 score in the prostatitis group was significantly lower than that in those without prostatitis (t=1.854, P=0.013). Histological prostatitis notably affected sexual function of patients and may serve as a major risk factor for sexual dysfunction while having little effect on lower urinary tract symptoms.

Disease modifying anti-rheumatic activity of the alkaloid montanine on experimental arthritis and fibroblast-like synoviocytes.

PubMed

Farinon, Mirian; Clarimundo, Vanessa S; Pedrazza, Graziele P R; Gulko, Pércio S; Zuanazzi, José A S; Xavier, Ricardo M; de Oliveira, Patricia G

2017-03-15

Montanine is an alkaloid isolated from Rhodophiala bifida bulb with potential anti-arthritic activity. In this context, we evaluated whether montanine has a disease modifying anti-rheumatic activity in two arthritis models and its effect in vitro on lymphocyte proliferation and on invasiveness of fibroblast-like synoviocytes (FLS). Antigen-induced arthritis (AIA) was performed in Balb/C mice with methylated bovine serum albumin, and nociception and leukocytes migration into the knee joint were evaluated. Collagen-induced arthritis (CIA) was performed in DBA/1J mice, and arthritis development and severity were assessed by clinical and histological scoring and articular nociception. Montanine was administered intraperitoneally twice a day. Lymphocyte proliferation stimulated by concanavalin A in 48h was performed with MTT assay, while FLS invasion in 24h was assayed in a Matrigel-coated transwell system. Administration of montanine decreased nociception (P<0.001) and leukocyte articular migration (P<0.001) in mice with AIA. In mice with CIA, treatment with montanine reduced severity of arthritis and joint damage assessed by clinical (P<0.001) and histological (P<0.05) scores and ameliorated articular nociception (P<0.05). In vitro, montanine inhibited lymphocyte proliferation stimulated with ConA (P<0.001) and decreased FLS invasion (P<0.05) by 54%, with an action independent of cytotoxicity. Our findings suggest that montanine can be further explored as an innovative pharmacological approach for autoimmune diseases such as arthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlation between ICDAS and histology: Differences between stereomicroscopy and microradiography with contrast solution as histological techniques

PubMed Central

Campos, Samara de Azevedo Gomes; Vieira, Maria Lúcia Oliveira

2017-01-01

Detection of occlusal caries with visual examination using ICDAS correlates strongly with histology under stereomicroscopy (SM), but dentin aspects under SM are ambiguous regarding mineral content. Thus, our aim was to test two null hypotheses: SM and microradiography result in similar correlations between ICDAS and histology; SM and microradiography result in similar positive (PPV) and negative predictive values (NPV) of ICDAS cut-off 1–2 (scores 0–2 as sound) with histological threshold D3 (demineralization in the inner third of dentin). Occlusal surfaces of extracted permanent teeth (n = 115) were scored using ICDAS. Undemineralized ground sections were histologically scored using both SM without contrast solution and microradiography after immersion in Thoulet’s solution 1.47 for 24 h (MRC). Correlation between ICDAS and histology differed from SM (0.782) to MRC (0.511) (p = 0.0002), with a large effect size “q” of 0.49 (95% CI: 0.638/0.338). For ICDAS cut-off 1–2 and D3, PPV from MRC (0.56) was higher than that from SM (0.28) (p< 0.00001; effect size h = 0.81), and NPV from MRC (0.72) was lower than that from SM (1,00) (p < 0.00001; effect size h = 1.58). In conclusion, SM overestimated the correlation between ICDAS and lesion depth, and underestimated the number of occlusal surfaces with ICDAS cut-off 1–2 and deep dentin demineralization. PMID:28841688

The effects of the Er:YAG laser on trabecular bone micro-architecture: Comparison with conventional dental drilling by micro-computed tomographic and histological techniques

PubMed Central

Zeitouni, Jihad; Clough, Bret; Zeitouni, Suzanne; Saleem, Mohammed; Al Aisami, Kenan; Gregory, Carl

2017-01-01

Background: The use of lasers has become increasingly common in the field of medicine and dentistry, and there is a growing need for a deeper understanding of the procedure and its effects on tissue. The aim of this study was to compare the erbium-doped yttrium aluminium garnet (Er:YAG) laser and conventional drilling techniques, by observing the effects on trabecular bone microarchitecture and the extent of thermal and mechanical damage. Methods: Ovine femoral heads were employed to mimic maxillofacial trabecular bone, and cylindrical osteotomies were generated to mimic implant bed preparation. Various laser parameters were tested, as well as a conventional dental drilling technique. The specimens were then subjected to micro-computed tomographic (μCT) histomorphometic analysis and histology. Results: Herein, we demonstrate that mCT measurements of trabecular porosity provide quantitative evidence that laser-mediated cutting preserves the trabecular architecture and reduces thermal and mechanical damage at the margins of the cut. We confirmed these observations with histological studies. In contrast with laser-mediated cutting, conventional drilling resulted in trabecular collapse, reduction of porosity at the margin of the cut and histological signs of thermal damage. Conclusions: This study has demonstrated, for the first time, that mCT and quantification of porosity at the margin of the cut provides a quantitative insight into damage caused by bone cutting techniques. We further show that with laser-mediated cutting, the marrow remains exposed to the margins of the cut, facilitating cellular infiltration and likely accelerating healing. However, with drilling, trabecular collapse and thermal damage is likely to delay healing by restricting the passage of cells to the site of injury and causing localized cell death. PMID:29416849

Glycogen synthase kinase-3 beta inhibition reduces secondary damage in experimental spinal cord trauma.

PubMed

Cuzzocrea, Salvatore; Genovese, Tiziana; Mazzon, Emanuela; Crisafulli, Concetta; Di Paola, Rosanna; Muià, Carmelo; Collin, Marika; Esposito, Emanuela; Bramanti, Placido; Thiemermann, Christoph

2006-07-01

Glycogen synthase kinase-3 (GSK-3) has recently been identified as an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and plays an important role in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3beta inhibition on the degree of experimental spinal cord trauma induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury (SCI) in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a potent and selective GSK-3beta inhibitor, significantly reduced the degree of 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase activity); 3) inducible nitric-oxide synthase, nitrotyrosine, and cyclooxygenase-2 expression; and 4) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and Bax and Bcl-2 expression). In a separate set of experiments, TDZD-8 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with TDZD-8 reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Effect of thalidomide on signal transduction pathways and secondary damage in experimental spinal cord trauma.

PubMed

Genovese, Tiziana; Mazzon, Emanuela; Esposito, Emanuela; Di Paola, Rosanna; Caminiti, Rocco; Meli, Rosaria; Bramanti, Placido; Cuzzocrea, Salvatore

2008-09-01

TNF-alpha seems to play a central role in the inflammatory process of spinal cord injury. We tested the neuroprotective effects of thalidomide, an immunomodulatory agent that inhibits TNF-alpha production, which have not been investigated so far. The aim of our study was to evaluate the therapeutic efficacy of thalidomide in an experimental model of spinal cord trauma, which was induced by the application of vascular clips (force of 24 g) to the dura via a 4-level T5 to T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production that is followed by recruitment of other inflammatory cells, production of a range of inflammation mediators, tissue damage, apoptosis, and disease. Thalidomide treatment significantly reduced the degree of: 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase evaluation); 3) iNOS, nitrotyrosine, lipid peroxidation, and cytokine expression (TNF-alpha and IL-1beta); 4) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, and Bax and Bcl-2 expression); and 5) nuclear factor-kappaB activation. In a separate set of experiments, we have also clearly demonstrated that thalidomide significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with thalidomide reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Aprikalim a potassium adenosine triphosphate channel opener reduces neurologic injury in a rabbit model of spinal cord ischemia.

PubMed

Lozos, Vasileios A; Toumpoulis, Ioannis K; Agrogiannis, Georgios; Giamarellos-Bourboulis, Evangelos J; Chamogeorgakis, Themistocles P; Rizos, Ioannis K; Patsouris, Efstratios S; Anagnostopoulos, Constantine E; Rokkas, Chris K

2013-01-01

Potassium adenosine triphosphate (KATP) channel openers have been involved in the enhancement of ischemic tolerance in various tissues. The purpose of the present study is to evaluate the effects of aprikalim, a specific KATP channel opener, on spinal cord ischemic injury. Fifty-four rabbits were randomly assigned to three groups: group 1 (n = 18, sham operation), group 2 (n = 18, 30 min of normothermic aortic cross-clamping) and group 3 (n = 18, aprikalim 100 μg/kg was administered 15 min before 30 min of normothermic aortic cross-clamping). Neurologic evaluation was performed according to the modified Tarlov scale. Six animals from each group were sacrificed at 24, 48 and 168 h postoperatively. The lumbar spinal cords were harvested and examined histologically. The motor neurons were counted and the histologic lesions were scored (0-3, 3: normal). Group 3 (aprikalim group) had better Tarlov scores compared to group 2 at all-time points (P < 0.025). The histologic changes were proportional to the Tarlov scores and group 3 had better functional outcome as compared to group 2 at 168 h (number of neurons: 21.2 ± 4.9 vs. 8.0 ± 2.7, P < 0.001 and histologic score: 1.67 ± 1.03 vs. 0.50 ± 0.55, P = 0.03). Although aprikalim exhibited improved effect on clinical and histologic neurologic outcome when compared to normothermic spinal cord ischemia, animals in group 3 had worse Tarlov score, reduced number of motor neurons and worse histologic score when compared to group 1 (sham operation) at 168 h (P = 0.003, P = 0.001 and P = 0.019 respectively). Aprikalim reduces the severity of spinal cord ischemic injury in a rabbit model of spinal cord ischemia. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

A Sulfated-Polysaccharide Fraction from Seaweed Gracilaria birdiae Prevents Naproxen-Induced Gastrointestinal Damage in Rats

PubMed Central

Silva, Renan O.; Santana, Ana Paula M.; Carvalho, Nathalia S.; Bezerra, Talita S.; Oliveira, Camila B.; Damasceno, Samara R. B.; Chaves, Luciano S.; Freitas, Ana Lúcia P.; Soares, Pedro M. G.; Souza, Marcellus H. L. P.; Barbosa, André Luiz R.; Medeiros, Jand-Venes R.

2012-01-01

Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation. PMID:23342384

A sulfated-polysaccharide fraction from seaweed Gracilaria birdiae prevents naproxen-induced gastrointestinal damage in rats.

PubMed

Silva, Renan O; Santana, Ana Paula M; Carvalho, Nathalia S; Bezerra, Talita S; Oliveira, Camila B; Damasceno, Samara R B; Chaves, Luciano S; Freitas, Ana Lúcia P; Soares, Pedro M G; Souza, Marcellus H L P; Barbosa, André Luiz R; Medeiros, Jand-Venes R

2012-12-01

Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group-vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.

Evaluation of clinical and histologic factors associated with survival time in dogs with stage II splenic hemangiosarcoma treated by splenectomy and adjuvant chemotherapy: 30 cases (2011-2014).

PubMed

Moore, Antony S; Rassnick, Kenneth M; Frimberger, Angela E

2017-09-01

OBJECTIVE To determine histologic and clinical factors associated with survival time in dogs with stage II splenic hemangiosarcoma treated by splenectomy and a chemotherapy protocol in which an anthracycline was alternated with lomustine. DESIGN Retrospective case series. ANIMALS 30 dogs with stage II splenic hemangiosarcoma. PROCEDURES Medical records of 3 facilities were reviewed to identify dogs treated for stage II splenic hemangiosarcoma between June 2011 and October 2014. Information collected included signalment, disease staging data, whether anemia was present, date of splenectomy, chemotherapy protocol, adverse effects, and date of death or last follow-up. Histologic slides were reviewed and scored by pathologists. Associations between variables of interest and survival data were evaluated statistically. RESULTS Median survival time for all dogs was 158 days (range, 55 to 560 days), and the 1-year survival rate was 16%. On multivariate analysis, only the histologically determined mitotic score was significantly associated with survival time. The median survival time of 292 days for dogs with a mitotic score of 0 (< 11 mitoses/10 hpf; n = 9) was significantly longer than that for dogs with higher scores (indicating higher mitotic rates); the 1-year survival rate for these dogs was 42%. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that future studies should take histologic factors, particularly mitotic rate, as well as tumor stage into account when assessing treatment effects on survival time of dogs with splenic hemangiosarcoma.

Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys.

PubMed

Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean P; Loomba, Rohit; Brunt, Elizabeth M; Chen, Yii-Der Ida; Goodarzi, Mark O; Taylor, Kent D; Yates, Katherine P; Tonascia, James; Rotter, Jerome I

2017-11-01

To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7 -07 ). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9 -07 ). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Infrared fiber optic probe evaluation of degenerative cartilage correlates to histological grading.

PubMed

Hanifi, Arash; Bi, Xiaohong; Yang, Xu; Kavukcuoglu, Beril; Lin, Ping Chang; DiCarlo, Edward; Spencer, Richard G; Bostrom, Mathias P G; Pleshko, Nancy

2012-12-01

Osteoarthritis (OA), a degenerative cartilage disease, results in alterations of the chemical and structural properties of tissue. Arthroscopic evaluation of full-depth tissue composition is limited and would require tissue harvesting, which is inappropriate in daily routine. Fourier transform infrared (FT-IR) spectroscopy is a modality based on molecular vibrations of matrix components that can be used in conjunction with fiber optics to acquire quantitative compositional data from the cartilage matrix. To develop a model based on infrared spectra of articular cartilage to predict the histological Mankin score as an indicator of tissue quality. Comparative laboratory study. Infrared fiber optic probe (IFOP) spectra were collected from nearly normal and more degraded regions of tibial plateau articular cartilage harvested during knee arthroplasty (N = 61). Each region was graded using a modified Mankin score. A multivariate partial least squares algorithm using second-derivative spectra was developed to predict the histological modified Mankin score. The partial least squares model derived from IFOP spectra predicted the modified Mankin score with a prediction error of approximately 1.4, which resulted in approximately 72% of the Mankin-scored tissues being predicted correctly and 96% being predicted within 1 grade of their true score. These data demonstrate that IFOP spectral parameters correlate with histological tissue grade and can be used to provide information on tissue composition. Infrared fiber optic probe studies have significant potential for the evaluation of cartilage tissue quality without the need for tissue harvest. Combined with arthroscopy, IFOP analysis could facilitate the definition of tissue margins in debridement procedures.

The relationship between histological prostatitis and lower urinary tract symptoms and sexual function

PubMed Central

Kumsar, Sukru; Kose, Osman; Aydemir, Huseyin; Halis, Fikret; Gokce, Ahmet; Adsan, Oztug; Akkaya, Zeynep Kahyaoglu

2016-01-01

ABSTRACT This prospective analysis assessed the effect of histological prostatitis on lower urinary tract functions and sexual function. The patients were separated into two groups as histologically observed prostatitis (Group A) and no prostatitis (Group B) according to the biopsy outcomes. International prostate symptom score, international index of erectile function-5 scores, maximal and average flow rate, and residual urine volumes were compared statistically between groups. There was no significant difference (P>0.05) in baseline age (t=0.64), body mass index value (t=0.51), prostate volume (t=0.87), prostate-specific antigen levels (t=0.43), maximal (t=0.84) and average flow rate (t=0.59), and post-void residual urine volume (t=0.71). Mean international prostate symptom score in patients with prostatitis was numerically but not significantly higher than that in those without prostatitis (t=0.794, P=0.066). Mean international index of erectile function-5 score in the prostatitis group was significantly lower than that in those without prostatitis (t=1.854, P=0.013). Histological prostatitis notably affected sexual function of patients and may serve as a major risk factor for sexual dysfunction while having little effect on lower urinary tract symptoms. PMID:27286118

Score of liver ultrasonography predicts treatment-related severe neutropenia and neutropenic fever in induction chemotherapy with docetaxel for locally advanced head and neck cancer patients with normal serum transamines.

PubMed

Wang, Ting-Yao; Chen, Wei-Ming; Yang, Lan-Yan; Chen, Chao-Yu; Chou, Wen-Chi; Chen, Yi-Yang; Chen, Chih-Cheng; Lee, Kuan-Der; Lu, Chang-Hsien

2016-11-01

Induction chemotherapy with docetaxel improved outcome in advanced head and neck squamous cell carcinoma (HNSCC) patients, but docetaxel was not recommended in liver dysfunction patients for treatment toxicities. Severe neutropenic events (SNE) including severe neutropenia (SN) and febrile neutropenia (FN) still developed in these patients with normal serum transaminases. Ultrasonography (US) fibrotic score represented degree of hepatic parenchymal damage and showed good correlation to fibrotic changes histologically. This study aims to evaluate the association of US fibrotic score with docetaxel treatment-related SNE in advanced HNSCC patients with normal serum transaminases. Between 1 January 2011 and 31 December 2013, a total of 47 advanced HNSCC patients treated with induction docetaxel were enrolled. The clinical features were collected to assess predictive factors for SNE. The patients were divided into two groups by the US fibrotic score with a cutoff value of 7. The Mann-Whitney U test and logistic regression method were used for the risk factor analysis. The background, treatment, and response were similar in both groups except for lower lymphocyte and platelet count in patients with higher US score. Twenty-seven patients (51 %) developed grade 3/4 neutropenia, and more SNE developed in patients with US score ≧7. In multivariate analysis, only US score ≥7 was independent predictive factor for developing SN (hazard ratio 7.71, p = 0.043) and FN (hazard ratio 20.95, p = 0.008). US score ≥7 is an independent risk factor for SNE in advanced HNSCC patients treated with induction docetaxel. US score could be used for risk prediction of docetaxel-related SNE.

Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and antiinflammatory mechanisms.

PubMed

Palla, Amber Hanif; Iqbal, Najeeha Talat; Minhas, Khurram; Gilani, Anwarul-Hassan

2016-09-01

New treatments for inflammatory bowel disease are of interest due to high rate of remission failure. Natural products have been effective in IBD therapeutics as they have multiple constituents. The aim of the present study was to evaluate the effect of Flaxseed extract (Fs.Cr) on ulcerative colitis and identify the possible mechanisms involved. Colitis was induced by intrarectal administration of 6% AA in BALB/c mice. Colonic mucosal damage was assessed after 24h by calculating disease activity index (DAI), macroscopic and histological damage scores, biochemical measurement of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total glutathione activities. Since cytokines are involved in exacerbating inflammatory cascade with emerging role of innate immune cytokines in IBD therapeutics, we hence assessed the effect on the levels of TNF-α, IFN-γ and IL-17, at 6, 12 and 24h by ELISA. Fs.Cr ameliorated the severity of AA colitis as evident by improved DAI, macroscopic damage and the histopathological scores along with restoration of goblet cells. Fs.Cr decreased MDA and MPO activities and enhanced antioxidant activity compared to the AA group. Finally, Fs.Cr in doses (300 and 500mg/kg) decreased TNF-α and IFN-γ levels at all time points with simultaneous increase in IL-17 levels at 24h as compared to the AA group. These results suggest that Fs.Cr ameliorates the severity of AA colitis by reducing goblet cell depletion, scavenging oxygen-derived free radicals, reduce neutrophil infiltration that may be attributed due to decreasing IFN-γ and TNF-α and increasing IL-17 levels. Copyright © 2016. Published by Elsevier B.V.

Hepatic ischemia/reperfusion injury is diminished by atorvastatin in Wistar rats.

PubMed

Cámara-Lemarroy, Carlos Rodrigo; Guzmán-de la Garza, Francisco Javier; Alarcón-Galván, Gabriela; Cordero-Pérez, Paula; Muñoz-Espinosa, Linda; Torres-González, Liliana; Fernández-Garza, Nancy Esthela

2014-04-01

Temporal occlusion of the hepatoduodenal ligament (HDL) is often used during liver surgeries in order to reduce blood loss, resulting in ischemia/reperfusion injury (I/R). The aim of the study was to investigate the effects of atorvastatin (ATOR) on hepatic I/R injury and on serum levels of tumor necrosis factor-alpha (TNF-α), endothelin-1 (ET-1), antithrombin III (ATIII) and intracellular adhesion molecule-1 (ICAM-1). Liver ischemia was induced in Wistar rats by clamping the HDL for 60 min, followed by either 60 or 180 min reperfusion. Rats received either vehicle or 10 mg/kg ATOR before hepatic I/R. Control group received sham surgery. Livers were examined for histological damage and serum AST, ALT, TNF-α, ET-1, ATIII and ICAM-1 concentrations were measured. After I/R, AST and ALT were significantly elevated, ATIII levels were significantly depleted, both TNF-α and ICAM-1 levels increased and ET-1 was significantly elevated (at 180 min). ATOR pretreatment attenuated these alterations and diminished histological injury scores. Our results show that ATOR protects the liver from I/R injury. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

Laser-Induced Thermal Damage of Skin

DTIC Science & Technology

1977-12-01

identify by block number) Skin Burns Skin Model Laser Effects \\Thermal Predictions 20 ABSTRACT (Continue on reverse side it necessary and identify by...block number) A computerized model was developed for predicting thermal damage of skin by laser exposures. Thermal, optical, and physiological data are...presented for the model. Model predictions of extent of irreversible damage were compared with histologic determinations of the extent of damage

A Preclinical Assessment of Early Continuous Passive Motion and Treadmill Therapeutic Exercises for Generating Chondroprotective Effects After Anterior Cruciate Ligament Rupture.

PubMed

Chang, Nai-Jen; Lee, Kuan-Wei; Chu, Chih-Jou; Shie, Ming-You; Chou, Pei-Hsi; Lin, Chih-Chan; Liang, Peir-In

2017-08-01

Anterior cruciate ligament (ACL) injury is a well-known risk factor for the development of posttraumatic osteoarthritis (PTOA). However, whether using continuous passive motion (CPM) with or without additional treadmill exercise (TRE) in early ACL injury might provide chondroprotective effects and further decrease the risk of PTOA has yet to be determined. CPM may offer an enhanced chondroprotective effect, but TRE may attenuate that effect due to the mechanical stress on the joint and inflammatory cytokines in the joint. Controlled laboratory study. Thirty adult New Zealand White male rabbits were randomly allocated to sedentary (SED), CPM, TRE, or CPM+TRE groups. Each rabbit underwent an ACL transection (ACLT) on the right knee, with the contralateral knee used as an internal control (sham). The 4 joint surfaces (ie, medial and lateral femoral condyles and tibial plateaus) were evaluated 4 weeks after surgery for gross appearance, histological characteristics, and quantitative osteoarthritis (OA) scores. Overall, at the end of testing, the CPM group experienced the best protective therapeutic effects in all compartments. In gross appearance, CPM resulted in normal articular surfaces, while the TRE and SED groups exhibited surface abrasion. Histological analysis showed significant differences in articular cartilage status. The CPM group had significantly better histological OA scores ( P < .01), corresponding to the smoothest cartilage surface and sound chondrocyte and collagen arrangement. This group also showed abundant glycosaminoglycan (GAG) content and a sound growth microenvironment, with significantly lower expression levels of the inflammatory cytokine tumor necrosis factor α and the apoptotic marker caspase 3. In contrast, the TRE and SED groups showed several features of damage: distinct graded cartilage abrasion; damaged collagen fibers, corresponding to noticeable collagen type X (osteoarthritic cartilage); reduced cartilage thickness; fewer cartilaginous cells; and the appearance of chondrocyte clusters. These groups also showed loss of GAG, corresponding to higher levels of inflammatory cytokines and apoptosis of articular chondrocytes. Furthermore, the CPM+TRE group displayed visible pathological changes in the superficial cartilage, indicating that early loading exercise may contribute to osteoarthritis. The sham treatment showed no difference in the changes in all compartments between groups. Immediate CPM therapy produces a superior in situ microenvironment for reducing the occurrence of PTOA after ACL injury without reconstruction in rabbits. These data suggest that immediate application of CPM therapy may be necessary to create a sound microenvironment in joints and possibly to decrease the risk of PTOA without or while awaiting ACL reconstruction. In contrast, both early active loading exercise and inactivity lead to the development of PTOA.

MR enterography-histology comparison in resected pediatric small bowel Crohn disease strictures: can imaging predict fibrosis?

PubMed

Barkmeier, Daniel T; Dillman, Jonathan R; Al-Hawary, Mahmoud; Heider, Amer; Davenport, Matthew S; Smith, Ethan A; Adler, Jeremy

2016-04-01

Crohn disease is a chronic inflammatory condition that can lead to intestinal strictures. The presence of fibrosis within strictures alters optimal management but is not reliably detected by current imaging methods. To correlate the MRI features of surgically resected small-bowel strictures in pediatric Crohn disease with histological inflammation and fibrosis scoring. We included children with Crohn disease who had symptomatic small-bowel strictures requiring surgical resection and had preoperative MR enterography (MRE) within 3 months of surgery (n = 20). Two blinded radiologists reviewed MRE examinations to document stricture-related findings. A pediatric pathologist scored stricture histological specimens for fibrosis (0-4) and inflammation (0-4). MRE findings were correlated with histological data using Spearman correlation (ρ) and exact logistic regression analysis. There was significant positive correlation between histological bowel wall fibrosis and inflammation in resected strictures (ρ = 0.55; P = 0.01). Confluent transmural histological fibrosis was associated with pre-stricture upstream small-bowel dilatation >3 cm at univariate (odds ratio [OR] = 51.7; 95% confidence interval [CI]: 7.6- > 999.9; P = 0.0002) and multivariate (OR = 43.4; 95% CI: 6.1- > 999.9; P = 0.0006, adjusted for age) analysis. The degree of bowel wall T2-weighted signal intensity failed to correlate with histological bowel wall fibrosis or inflammation (P-values >0.05). There were significant negative correlations between histological fibrosis score and patient age at resection (ρ = -0.48, P = 0.03), and time from diagnosis to surgery (ρ = -0.73, P = 0.0002). Histological fibrosis and inflammation co-exist in symptomatic pediatric Crohn disease small-bowel strictures and are positively correlated. Pre-stenotic upstream small-bowel dilatation greater than 3 cm is significantly associated with confluent transmural fibrosis.

Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka.

PubMed

Nanayakkara, Shanika; Komiya, Toshiyuki; Ratnatunga, Neelakanthi; Senevirathna, S T M L D; Harada, Kouji H; Hitomi, Toshiaki; Gobe, Glenda; Muso, Eri; Abeysekera, Tilak; Koizumi, Akio

2012-05-01

Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.

Acute liver damage and ecstasy ingestion.

PubMed Central

Ellis, A J; Wendon, J A; Portmann, B; Williams, R

1996-01-01

Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted but subsequently died, histological examination showing widespread microvesicular fatty change. Four patients presented with acute liver failure without hyperthermia. All four fulfilled criteria for transplantation, one died before a donor organ became available, and two died within one month post-transplantation of overwhelming sepsis. Histological examination showed submassive lobular collapse. Two patients presented with abdominal pain and jaundice and recovered over a period of three weeks; histological examination showed a lobular hepatitis with cholestasis. Patients developing jaundice or with evidence of hepatic failure particularly encephalopathy and prolongation of the international normalised ratio, or both, whether or not preceded by hyperthermia, should be referred to a specialised liver unit as liver transplantation probably provides the only chance of recovery. Images Figure 1 Figure 2 Figure 3 PMID:8675102

Bilayer Implants

PubMed Central

Schagemann, Jan C.; Rudert, Nicola; Taylor, Michelle E.; Sim, Sotcheadt; Quenneville, Eric; Garon, Martin; Klinger, Mathias; Buschmann, Michael D.; Mittelstaedt, Hagen

2016-01-01

Objective To compare the regenerative capacity of 2 distinct bilayer implants for the restoration of osteochondral defects in a preliminary sheep model. Methods Critical sized osteochondral defects were treated with a novel biomimetic poly-ε-caprolactone (PCL) implant (Treatment No. 2; n = 6) or a combination of Chondro-Gide and Orthoss (Treatment No. 1; n = 6). At 19 months postoperation, repair tissue (n = 5 each) was analyzed for histology and biochemistry. Electromechanical mappings (Arthro-BST) were performed ex vivo. Results Histological scores, electromechanical quantitative parameter values, dsDNA and sGAG contents measured at the repair sites were statistically lower than those obtained from the contralateral surfaces. Electromechanical mappings and higher dsDNA and sGAG/weight levels indicated better regeneration for Treatment No. 1. However, these differences were not significant. For both treatments, Arthro-BST revealed early signs of degeneration of the cartilage surrounding the repair site. The International Cartilage Repair Society II histological scores of the repair tissue were significantly higher for Treatment No. 1 (10.3 ± 0.38 SE) compared to Treatment No. 2 (8.7 ± 0.45 SE). The parameters cell morphology and vascularization scored highest whereas tidemark formation scored the lowest. Conclusion There was cell infiltration and regeneration of bone and cartilage. However, repair was incomplete and fibrocartilaginous. There were no significant differences in the quality of regeneration between the treatments except in some histological scoring categories. The results from Arthro-BST measurements were comparable to traditional invasive/destructive methods of measuring quality of cartilage repair. PMID:27688843

Superior cerebral protection with profound hypothermia during circulatory arrest.

PubMed

Gillinov, A M; Redmond, J M; Zehr, K J; Troncoso, J C; Arroyo, S; Lesser, R P; Lee, A W; Stuart, R S; Reitz, B A; Baumgartner, W A

1993-06-01

The optimal temperature for cerebral protection during hypothermic circulatory arrest is not known. This study was undertaken to test the hypothesis that deeper levels of cerebral hypothermia (< 10 degrees C) confer better protection against neurologic injury during prolonged hypothermic circulatory arrest ("colder is better"). Twelve male dogs (20 to 25 kg) were placed on closed-chest cardiopulmonary bypass via femoral artery and femoral/external jugular vein. Using surface and core cooling, tympanic membrane temperature was lowered to 18 degrees to 20 degrees C (deep hypothermia, n = 6) or 5 degrees to 7 degrees C (profound hypothermia, n = 6). After 2 hours of hypothermic circulatory arrest, animals were rewarmed to 35 degrees to 37 degrees C on cardiopulmonary bypass. All were mechanically ventilated and monitored in an intensive care unit setting for 20 hours. Neurologic assessment was performed every 12 hours using a species-specific behavior scale that yielded a neurodeficit score ranging from 0% to 100%, where 0 = normal and 100% = brain dead. After 72 hours, animals were sacrificed and examined histologically for neurologic injury. Histologic injury scores were assigned to each animal (range, 0 [normal] to 100 [severe injury]). At the end of the observation period, profoundly hypothermic animals had better neurologic function (neurodeficit score, 5.7% +/- 4.0%) compared with deeply hypothermic animals (neurodeficit score, 41% +/- 9.3%; p < 0.006). Every animal had histologic evidence of neurologic injury, but profoundly hypothermic animals had significantly less injury (histologic injury score, 19.2 +/- 1.2 versus 48.3 +/- 1.5; p < 0.0001).

Chronic Glaucoma in Dogs: Relationships Between Histologic Lesions and the Gonioscopic Diagnosis of Pectinate Ligament Dysplasia.

PubMed

Bauer, B S; Sandmeyer, L S; Philibert, H; Feng, C X; Grahn, B H

2016-11-01

Pectinate ligament dysplasia (PLD) is a common cause of canine glaucoma and the definitive clinical diagnosis is based on gonioscopy. Although the histologic lesions of PLD have been described, it has not been determined whether these changes are specific for PLD or if similar histologic changes can develop as a consequence of secondary glaucoma. The filtration angles of 61 enucleated canine globes with chronic glaucoma were evaluated with light microscopy by 3 examiners who were masked to the clinical history, signalment, and gonioscopic results. A histologic diagnosis of PLD versus non-PLD was determined by each examiner based on previously reported morphologic criteria and compared with the clinical gonioscopic diagnosis. Of the 61 enucleated glaucomatous eyes, 40 were clinically diagnosed with PLD. For all 3 examiners, a histologic diagnosis of PLD corresponded poorly with the clinical diagnosis of PLD (range of kappa score: 0.149-0.269; range of AUC: 0.592-0.621). There was no difference between examiners in their ability to correctly diagnose PLD histologically (P = .978). A fair degree of agreement was noted among examiners in obtaining their suspected histologic diagnosis of PLD (kappa score 0.256). No individual or sets of histologic ICA features were consistent with clinical PLD. The results indicate the histologic ICA changes proposed to be characteristic of PLD are also noted in canine globes affected with chronic secondary glaucoma. Therefore, using routine histologic evaluation, a histologic diagnosis of PLD is not possible in the face of chronic canine glaucoma. © The Author(s) 2016.

Hyaluronic acid injections protect patellar tendon from detraining-associated damage.

PubMed

Frizziero, Antonio; Salamanna, Francesca; Giavaresi, Gianluca; Ferrari, Andrea; Martini, Lucia; Marini, Marina; Veicsteinas, Arsenio; Maffulli, Nicola; Masiero, Stefano; Fini, Milena

2015-09-01

Having previously demonstrated that detraining affects patellar tendon (PT) proteoglycan content and collagen fiber organization, we undertook the present study with two aims: to improve knowledge on the adaptation of PT and its enthesis to detraining from a histological and histomorphometric point of view, and to investigate the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained PT may reduce and limit detrained associated-damage. Twenty-four male Sprague-Dawley rats were divided into 3 groups: Untrained (n=6), Trained (n=6) (10 wks-treadmill) and Detrained (n=12). In the detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Structure and morphology of PTs (modified Movin score, tear density, collagen type I and III) and enthesis (cell morphology, chondrocyte cluster formation, tidemark integrity, matrix staining and vascularization) were evaluated. The left PT and enthesis of the Detrained groups showed altered structure and morphology with the highest Movin score values, the highest percentage of collagen III and the lowest of collagen I; the lowest score values were observed in the Trained and Detrained-HA groups. Detrained-NaCl PTs showed the highest collagen III and the lowest collagen I values with respect to Detrained-HA PTs. This study strengthens previously published data showing the alteration in tendon and enthesis morphology due to discontinuation of training, and provides new data showing that treatment with HA is effective in the maintenance of the structural properties of PT and enthesis in Detrained rats. Such beneficial effects could play a significant role in the management of conservative and rehabilitation strategies in athletes that change type, intensity and duration of training.

Repeated mild traumatic brain injury can cause acute neurologic impairment without overt structural damage in juvenile rats.

PubMed

Meconi, Alicia; Wortman, Ryan C; Wright, David K; Neale, Katie J; Clarkson, Melissa; Shultz, Sandy R; Christie, Brian R

2018-01-01

Repeated concussion is becoming increasingly recognized as a serious public health concern around the world. Moreover, there is a greater awareness amongst health professionals of the potential for repeated pediatric concussions to detrimentally alter the structure and function of the developing brain. To better study this issue, we developed an awake closed head injury (ACHI) model that enabled repeated concussions to be performed reliably and reproducibly in juvenile rats. A neurological assessment protocol (NAP) score was generated immediately after each ACHI to help quantify the cumulative effects of repeated injury on level of consciousness, and basic motor and reflexive capacity. Here we show that we can produce a repeated ACHI (4 impacts in two days) in both male and female juvenile rats without significant mortality or pain. We show that both single and repeated injuries produce acute neurological deficits resembling clinical concussion symptoms that can be quantified using the NAP score. Behavioural analyses indicate repeated ACHI acutely impaired spatial memory in the Barnes maze, and an interesting sex effect was revealed as memory impairment correlated moderately with poorer NAP score performance in a subset of females. These cognitive impairments occurred in the absence of motor impairments on the Rotarod, or emotional changes in the open field and elevated plus mazes. Cresyl violet histology and structural magnetic resonance imaging (MRI) indicated that repeated ACHI did not produce significant structural damage. MRI also confirmed there was no volumetric loss in the cortex, hippocampus, or corpus callosum of animals at 1 or 7 days post-ACHI. Together these data indicate that the ACHI model can provide a reliable, high throughput means to study the effects of concussions in juvenile rats.

2D and 3D MOCART scoring systems assessed by 9.4 T high-field MRI correlate with elementary and complex histological scoring systems in a translational model of osteochondral repair.

PubMed

Goebel, L; Zurakowski, D; Müller, A; Pape, D; Cucchiarini, M; Madry, H

2014-10-01

To compare the 2D and 3D MOCART system obtained with 9.4 T high-field magnetic resonance imaging (MRI) for the ex vivo analysis of osteochondral repair in a translational model and to correlate the data with semiquantitative histological analysis. Osteochondral samples representing all levels of repair (sheep medial femoral condyles; n = 38) were scanned in a 9.4 T high-field MRI. The 2D and adapted 3D MOCART systems were used for grading after point allocation to each category. Each score was correlated with corresponding reconstructions between both MOCART systems. Data were next correlated with corresponding categories of an elementary (Wakitani) and a complex (Sellers) histological scoring system as gold standards. Correlations between most 2D and 3D MOCART score categories were high, while mean total point values of 3D MOCART scores tended to be 15.8-16.1 points higher compared to the 2D MOCART scores based on a Bland-Altman analysis. "Defect fill" and "total points" of both MOCART scores correlated with corresponding categories of Wakitani and Sellers scores (all P ≤ 0.05). "Subchondral bone plate" also correlated between 3D MOCART and Sellers scores (P < 0.001). Most categories of the 2D and 3D MOCART systems correlate, while total scores were generally higher using the 3D MOCART system. Structural categories "total points" and "defect fill" can reliably be assessed by 9.4 T MRI evaluation using either system, "subchondral bone plate" using the 3D MOCART score. High-field MRI is valuable to objectively evaluate osteochondral repair in translational settings. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Rabbit Trochlear Model of Osteochondral Allograft Transplantation

PubMed Central

To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A

2011-01-01

Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft–host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host–graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host–graft bone interface available for analysis. PMID:22330350

Can Mesenchymal Stem Cells Reverse Chronic Stress-Induced Impairment of Wound Healing Following Traumatic Injury?

PubMed Central

Gore, Amy V.; Bible, Letitia E.; Livingston, David H.; Mohr, Alicia M.; Sifri, Ziad C.

2015-01-01

Intro One week following unilateral lung contusion (LC), rat lungs demonstrate full histologic recovery. When animals undergo LC plus the addition of chronic restraint stress (CS), wound healing is significantly delayed. Mesenchymal stem cells (MSC) are pluripotent cells capable of immunomodulation that have been the focus of much research in wound healing and tissue regeneration. We hypothesize that the addition of MSCs will improve wound healing in the setting of CS. Methods Male Sprague-Dawley rats (n=6-7/group) were subjected to LC/CS with or without the injection of MSCs. MSCs were given as a single IV dose of 5 × 106 cells in 1mL IMDM media at the time of LC. Rats were subjected to two hours of restraint stress on days 1-6 following LC. Seven days following injury, rats were sacrificed and lungs examined for histologic evidence of wound healing using a well-established histologic lung injury score (LIS) to grade injury. LIS examines inflammatory cells/high power field (hpf) averaged over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity with scores ranging from 0 (normal) to 11 (highly damaged). Peripheral blood was analyzed by flow cytometry for the presence of T-regulatory (C4+CD25+FoxP3+) cells. Data analyzed by ANOVA followed by Tukey’s multiple comparison test, expressed as mean ± SD. Results As previously shown, seven days following isolated LC, LIS has returned to 0.83 ± 0.41, with a subscore of zero for inflammatory cells/hpf. The addition of CS results in a LIS score of 4.4 ± 2.2, with a subscore of 1.9 ± 0.7 for inflammatory cells/hpf. Addition of MSC to LC/CS decreased LIS score to 1.7 ± 0.8 with a subscore of zero for inflammatory cells/hpf. Furthermore, treatment of animals undergoing LC/CS with MSCs increased the %T-regulatory cells by 70% in animals undergoing LC/CS alone (12.9 ± 2.4% vs 6.2 ± 1.3%) Conclusion Stress-induced impairment of wound healing is reversed by addition of MSCs given at the time of injury in this rat lung contusion model. This improvement in lung healing is associated with a decrease in the number of inflammatory cells and an increase in the number of T regulatory cells. Further study into the mechanisms by which MSCs hasten wound healing is warranted. PMID:25807405

Curcumin improves regulatory T cells in gut-associated lymphoid tissue of colitis mice

PubMed Central

Zhao, Hai-Mei; Xu, Rong; Huang, Xiao-Ying; Cheng, Shao-Min; Huang, Min-Fang; Yue, Hai-Yang; Wang, Xin; Zou, Yong; Lu, Ai-Ping; Liu, Duan-Yong

2016-01-01

AIM: To explore the probable pathway by which curcumin (Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells (DCs). METHODS: Experimental colitis was induced by administering 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Forty male C57BL/6 mice were randomly divided into four groups: normal, TNBS + Cur, TNBS + mesalazine (Mes) and TNBS groups. The mice in the TNBS + Cur and TNBS +Mes groups were treated with Cur and Mes, respectively, while those in the TNBS group were treated with physiological saline for 7 d. After treatment, the curative effect of Cur was evaluated by colonic weight, colonic length, weight index of the colon, and histological observation and score. The levels of CD4+CD25+Foxp3+ T cells (Treg cells) and costimulatory molecules of DCs were measured by flow cytometry. Also, related cytokines were analyzed by enzyme-linked immunosorbent assay. RESULTS: Cur alleviated inflammatory injury of the colonic mucosa, decreased colonic weigh and histological score, and restored colonic length. The number of Treg cells was increased, while the secretion of TNF-α, IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules (CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur. CONCLUSION: Cur potentially modulates activation of DCs to enhance the suppressive functions of Treg cells and promote the recovery of damaged colonic mucosa in inflammatory bowel disease. PMID:27340353

Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice.

PubMed

Cattaruzza, Fiore; Johnson, Cali; Leggit, Alan; Grady, Eileen; Schenk, A Katrin; Cevikbas, Ferda; Cedron, Wendy; Bondada, Sandhya; Kirkwood, Rebekah; Malone, Brian; Steinhoff, Martin; Bunnett, Nigel; Kirkwood, Kimberly S

2013-06-01

Chronic pancreatitis (CP) is a devastating disease characterized by persistent and uncontrolled abdominal pain. Our lack of understanding is partially due to the lack of experimental models that mimic the human disease and also to the lack of validated behavioral measures of visceral pain. The ligand-gated cation channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis and sustained pancreatic pain. We induced CP by injecting the chemical agent trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis, into the pancreatic duct of C57BL/6 trpa1(+/+) and trpa1(-/-) mice. Chronic inflammatory changes and pain behaviors were assessed after 2-3 wk. TNBS injection caused marked pancreatic fibrosis with increased collagen-staining intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic stellate cell activation, and these changes were reflected by increased histological damage scores. TNBS-injected animals showed mechanical hypersensitivity during von Frey filament probing of the abdomen, decreased daily voluntary wheel-running activity, and increased immobility scores during open-field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal to von Frey filament probing, suggesting central sensitization. Inflammatory changes and pain indexes were significantly reduced in trpa1(-/-) mice. In conclusion, we have characterized in mice a model of CP that resembles the human condition, with marked histological changes and behavioral measures of pain. We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain.

Studies in fat grafting: Part III. Fat grafting irradiated tissue--improved skin quality and decreased fat graft retention.

PubMed

Garza, Rebecca M; Paik, Kevin J; Chung, Michael T; Duscher, Dominik; Gurtner, Geoffrey C; Longaker, Michael T; Wan, Derrick C

2014-08-01

Following radiation therapy, skin becomes fibrotic and can present a difficult problem for reconstructive surgeons. There is an increasing belief that fat grafting under irradiated skin can reverse the damage caused by radiation. The present study evaluated the effect of fat grafting on irradiated skin, along with fat graft quality and retention rates in irradiated tissue. Nine adult Crl:NU-Foxn1 CD-1 mice underwent 30-Gy external beam irradiation of the scalp. Four weeks after irradiation, scalp skin from irradiated and nonirradiated mice was harvested and compared histologically for dermal thickness, collagen content, and vascular density. Human fat grafts were then injected in the subcutaneous plane of the scalp. Skin assessment was performed in the irradiated group at 2 and 8 weeks after grafting, and fat graft retention was measured at baseline and every 2 weeks up to 8 weeks after grafting using micro-computed tomography. Finally, fat graft samples were explanted at 8 weeks, and quality scoring was performed. Fat grafting resulted in decreased dermal thickness, decreased collagen content, and increased vascular density in irradiated skin. Computed tomographic analysis revealed significantly decreased fat graft survival in the irradiated group compared with the nonirradiated group. Histologic scoring of explanted fat grafts demonstrated no difference in quality between the irradiated and nonirradiated groups. Fat grafting attenuates dermal collagen deposition and vessel depletion characteristic of radiation fibrosis. Although fat graft retention rates are significantly lower in irradiated than in nonirradiated tissue, the quality of retained fat between the groups is similar.

Anti-inflammatory effects and mechanisms of vagal nerve stimulation combined with electroacupuncture in a rodent model of TNBS-induced colitis.

PubMed

Jin, Haifeng; Guo, Jie; Liu, Jiemin; Lyu, Bin; Foreman, Robert D; Yin, Jieyun; Shi, Zhaohong; Chen, Jiande D Z

2017-09-01

The purpose of this study was to determine the effects and mechanisms of vagal nerve stimulation (VNS) and additive effects of electroacupuncture (EA) on colonic inflammation in a rodent model of IBD. Chronic inflammation in rats was induced by intrarectal TNBS (2,4,6-trinitrobenzenesulfonic acid). The rats were then treated with sham ES (electrical stimulation), VNS, or VNS + EA for 3 wk. Inflammatory responses were assessed by disease activity index (DAI), macroscopic scores and histological scores of colonic tissues, plasma levels of TNFα, IL-1β, and IL-6, and myeloperoxidase (MPO) activity of colonic tissues. The autonomic function was assessed by the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. It was found that 1 ) the area under curve (AUC) of DAI was substantially decreased with VNS + EA and VNS, with VNS + EA being more effective than VNS ( P < 0.001); 2 ) the macroscopic score was 6.43 ± 0.61 in the sham ES group and reduced to 1.86 ± 0.26 with VNS ( P < 0.001) and 1.29 ± 0.18 with VNS + EA ( P < 0.001); 3 ) the histological score was 4.05 ± 0.58 in the sham ES group and reduced to 1.93 ± 0.37 with VNS ( P < 0.001) and 1.36 ± 0.20 with VNS + EA ( P < 0.001); 4 ) the plasma levels of TNFα, IL-1β, IL-6, and MPO were all significantly decreased with VNS and VNS + EA compared with the sham ES group; and 5 ) autonomically, both VNS + EA and VNS substantially increased vagal activity and decreased sympathetic activity compared with sham EA ( P < 0.001, P < 0.001, respectively). In conclusion, chronic VNS improves inflammation in TNBS-treated rats by inhibiting proinflammatory cytokines via the autonomic mechanism. Addition of noninvasive EA to VNS may enhance the anti-inflammatory effect of VNS. NEW & NOTEWORTHY This is the first study to address and compare the effects of vagal nerve stimulation (VNS), electrical acupuncture (EA) and VNS + EA on TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced colitis in rats. The proposed chronic VNS + EA, VNS, and EA were shown to decrease DAI and ameliorate macroscopic and microscopic damages in rats with TNBS-induced colitis via the autonomic pathway. The addition of EA to VNS provided a significant effect on the behavioral assessment of inflammation (DAI, CMDI, and histological score) but not on cytokines or mechanistic measurements, suggesting an overall systemic effect of EA.View this article's corresponding video summary at https://youtu.be/-rEz6HMkErM.

[Inter-observes agreement of Ishak and Metavir scores in histological evaluation of chronic viral hepatitis B and C].

PubMed

Rammeh, Soumaya; Khadra, Hajer Ben; Znaidi, Nadia Sabbegh; Romdhane, Neila Attia; Najjar, Taoufik; Bouzaidi, Slim; Zermani, Rachida

2014-01-01

Many classification systems are currently used for histological evaluation of the severity of chronic viral hepatitis, including the Ishak and Metavir scores, but there is not a consensus classification. The objective of this work was to study the intra and inter-observers agreement of these two scores in the histopathological analysis of liver biopsies in patients with chronic viral hepatitis B or C. Fifty nine patients were included in the study, 26 had chronic hepatitis C and 33 had chronic hepatitis B. To investigate the inter-observers agreement, the liver biopsies were analyzed separately by two pathologists without prior consensus reading. The two pathologists conducted then a consensual reading before reviewing all cases independently. Cohen's kappa coefficient was calculated and in case of asymmetry Spearman's rho coefficient. Before the consensus reading, the agreement was moderate for the analysis of histological activity with both scores (Metavir: kappa=0.41, Ishak: rho=0.58). For the analysis of fibrosis, the agreement was good with both scores (Metavir: kappa=0.61, Ishak: rho=0.86). The consensus reading has improved the reproducibility of the activity that has become good with both scores (Metavir: kappa=0.77, Ishak: rho=0.76). For fibrosis improvement was observed with the Ishak score which agreement became excellent (kappa=0.81). In conclusion, we recommend in routine practice, a combined score: Metavir for activity and Ishak for fibrosis and to make a double reading for each biopsy.

Macroscopic Rotator Cuff Tendinopathy and Histopathology Do Not Predict Repair Outcomes of Rotator Cuff Tears.

PubMed

Sethi, Paul M; Sheth, Chirag D; Pauzenberger, Leo; McCarthy, Mary Beth R; Cote, Mark P; Soneson, Emma; Miller, Seth; Mazzocca, Augustus D

2018-03-01

Numerous studies have identified factors that may affect the chances of rotator cuff healing after surgery. Intraoperative tendon quality may be used to predict healing and to determine type of repair and/or consideration of augmentation. There are no data that correlate how gross tendon morphology and degree of tendinopathy affect patient outcome or postoperative tendon healing. Purpose/Hypothesis: The purposes of this study were to (1) compare the gross appearance of the tendon edge during arthroscopic rotator cuff repair with its histological degree of tendinopathy and (2) determine if gross appearance correlated with postoperative repair integrity. The hypothesis was that gross (macroscopic) tendon with normal thickness, no delamination, and elastic tissue before repair would have a correlation with low Bonar scores, higher postoperative American Shoulder and Elbow Surgeons (ASES) scores, and increased rates of postoperative tendon healing on ultrasound. Cross-sectional study; Level of evidence, 3. A total of 105 patients undergoing repair of medium-size (1-3 cm) full-thickness rotator cuff tears were enrolled in the study. Intraoperatively, the supraspinatus tendon was rated on thickness, fraying, and stiffness. Tendon tissue was recovered for histological analysis based on the Bonar scoring system. Postoperative ASES and ultrasound assessment of healing were obtained 1 year after repair. Correlation between gross appearance of the tendon and rotator cuff histology was determined. Of the 105 patients, 85 were followed the study to completion. The mean age of the patients was 61.6 years; Bonar score, 7.5; preoperative ASES score, 49; and postoperative ASES score, 86. Ninety-one percent of repairs were intact on ultrasound. Gross appearance of torn rotator cuff tendon tissue did not correlate with histological appearance. Neither histological (Bonar) score nor gross appearance correlated with multivariate analysis of ASES score, postoperative repair status, or demographic data. The degree of tendinopathy did not correlate with morphological appearance of the tendon. Neither of these parameters correlated with healing or patient outcome. This study suggests that the degree of tendinopathy, unlike muscle atrophy, may not be predictive of outcomes and that, on appearance, poor quality tendon has adequate healing capacity. Therefore, abnormal gross tendon appearance should not affect the repair effort or technique.

Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan.

PubMed

Akuta, Norio; Kawamura, Yusuke; Arase, Yasuji; Suzuki, Fumitaka; Sezaki, Hitomi; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Suzuki, Yoshiyuki; Ikeda, Kenji; Kumada, Hiromitsu

2016-05-23

It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.

Bone marrow stimulation of the medial femoral condyle produces inferior cartilage and bone repair compared to the trochlea in a rabbit surgical model.

PubMed

Chen, Hongmei; Chevrier, Anik; Hoemann, Caroline D; Sun, Jun; Picard, Genevieve; Buschmann, Michael D

2013-11-01

The influence of the location of cartilage lesions on cartilage repair outcome is incompletely understood. This study compared cartilage and bone repair in medial femoral condylar (MFC) versus femoral trochlear (TR) defects 3 months after bone marrow stimulation in mature rabbits. Intact femurs from adult rabbits served as controls. Results from quantitative histomorphometry and histological scoring showed that bone marrow stimulation produced inferior soft tissue repair in MFC versus TR defects, as indicated by significantly lower % Fill (p = 0.03), a significant increase in collagen type I immunostaining (p < 0.00001) and lower O'Driscoll scores (p < 0.05). 3D micro-CT analysis showed that repaired TR defects regained normal un-operated values of bone volume fraction, trabecular thickness, and trabecular number, whereas in MFC defects the repaired bone architecture appeared immature and less dense compared to intact un-operated MFC controls (p < 0.0001). Severe medial meniscal damage was found in 28% of operated animals and was strongly correlated with (i) low cartilage defect fill, (ii) incomplete bone repair in MFC, and (iii) with a more posterior defect placement in the weight-bearing region. We conclude that the location of cartilage lesions influences cartilage repair, with better outcome in TR versus MFC defects in rabbits. Meniscal degeneration is associated with cartilage damage. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Cadmium-induced oxidative stress and histological damage in the myocardium. Effects of a soy-based diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferramola, Mariana L.; Pérez Díaz, Matías F.F.; Honoré, Stella M.

Cd exposure has been associated to an augmented risk for cardiovascular disease. We investigated the effects of 15 and 100 ppm of Cd on redox status as well as histological changes in the rat heart and the putative protective effect of a soy-based diet. Male Wistar rats were separated into 6 groups and treated during 60 days as follows: groups (1), (2) and (3) were fed a casein-based diet; groups (4), (5) and (6), a soy-based diet; (1) and (4) were given tap water; (2) and (5) tap water containing 15 ppm of Cd{sup 2+}; and (3) and (6) tapmore » water containing 100 ppm of Cd{sup 2+}. Serum lipid peroxides increased and PON-1 activity decreased in group (3). Lipoperoxidation also increased in the heart of all intoxicated groups; however protein oxidation only augmented in (3) and reduced glutathione levels diminished in (2) and (3). Catalase activity increased in groups (3) and (6) while superoxide dismutase activity increased only in (6). Glutathione peroxidase activity decreased in groups (3) and (6). Nrf2 expression was higher in groups (3) and (6), and MTI expression augmented in (3). Histological examination of the heart tissue showed the development of hypertrophic and fusion of cardiomyocytes along with foci of myocardial fiber necrosis. The transmission electron microscopy analysis showed profound ultra-structural damages. No protection against tissue degeneration was observed in animals fed the soy-based diet. Our findings indicate that even though the intake of a soy-based diet is capable of ameliorating Cd induced oxidative stress, it failed in preventing cardiac damage. -- Highlights: ► Cd intoxication produces extracellular and ultrastructural damage in the myocardium. ► The intake of a soy-based diet ameliorated Cd-induced oxidative stress. ► Cd-induced myocardial damage wasn't prevented by the intake of a soy-based diet. ► Cd-induced myocardial degeneration may not be caused by oxidative stress generation. ► Histology evaluation is needed to establish the extent of Cd-induced cardiac damage.« less

Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice.

PubMed

O'Keefe, Lena M; Doran, Sarah J; Mwilambwe-Tshilobo, Laetitia; Conti, Lisa H; Venna, Venugopal R; McCullough, Louise D

2014-03-01

Social isolation prior to stroke leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression. Copyright © 2013 Elsevier B.V. All rights reserved.

Osteochondral Biopsy Analysis Demonstrates That BST-CarGel Treatment Improves Structural and Cellular Characteristics of Cartilage Repair Tissue Compared With Microfracture

PubMed Central

Méthot, Stéphane; Changoor, Adele; Tran-Khanh, Nicolas; Hoemann, Caroline D.; Stanish, William D.; Restrepo, Alberto; Shive, Matthew S.; Buschmann, Michael D.

2016-01-01

Objective The efficacy and safety of BST-CarGel, a chitosan-based medical device for cartilage repair, was compared with microfracture alone at 1 year during a multicenter randomized controlled trial (RCT) in the knee. The quality of repair tissue of osteochondral biopsies collected from a subset of patients was compared using blinded histological assessments. Methods The international RCT evaluated repair tissue quantity and quality by 3-dimensional quantitative magnetic resonance imaging as co-primary endpoints at 12 months. At an average of 13 months posttreatment, 21/41 BST-CarGel and 17/39 microfracture patients underwent elective second look arthroscopies as a tertiary endpoint, during which ICRS (International Cartilage Repair Society) macroscopic scoring was carried out, and osteochondral biopsies were collected. Stained histological sections were evaluated by blinded readers using ICRS I and II histological scoring systems. Collagen organization was evaluated using a polarized light microscopy score. Results BST-CarGel treatment resulted in significantly better ICRS macroscopic scores (P = 0.0002) compared with microfracture alone, indicating better filling, integration, and tissue appearance. Histologically, BST-CarGel resulted in a significant improvement of structural parameters—Surface Architecture (P = 0.007) and Surface/Superficial Assessment (P = 0.042)—as well as cellular parameters—Cell Viability (P = 0.006) and Cell Distribution (P = 0.032). No histological parameters were significantly better for the microfracture group. BST-CarGel treatment also resulted in a more organized repair tissue with collagen stratification more similar to native hyaline cartilage, as measured by polarized light microscopy scoring (P = 0.0003). Conclusion Multiple and independent analyses in this biopsy substudy demonstrated that BST-CarGel treatment results in improved structural and cellular characteristics of repair tissue at 1 year posttreatment compared with microfracture alone, supporting previously reported results by quantitative magnetic resonance imaging. PMID:26958314

Ultrasound definition of tendon damage in patients with rheumatoid arthritis. Results of a OMERACT consensus-based ultrasound score focussing on the diagnostic reliability.

PubMed

Bruyn, George A W; Hanova, Petra; Iagnocco, Annamaria; d'Agostino, Maria-Antonietta; Möller, Ingrid; Terslev, Lene; Backhaus, Marina; Balint, Peter V; Filippucci, Emilio; Baudoin, Paul; van Vugt, Richard; Pineda, Carlos; Wakefield, Richard; Garrido, Jesus; Pecha, Ondrej; Naredo, Esperanza

2014-11-01

To develop the first ultrasound scoring system of tendon damage in rheumatoid arthritis (RA) and assess its intraobserver and interobserver reliability. We conducted a Delphi study on ultrasound-defined tendon damage and ultrasound scoring system of tendon damage in RA among 35 international rheumatologists with experience in musculoskeletal ultrasound. Twelve patients with RA were included and assessed twice by 12 rheumatologists-sonographers. Ultrasound examination for tendon damage in B mode of five wrist extensor compartments (extensor carpi radialis brevis and longus; extensor pollicis longus; extensor digitorum communis; extensor digiti minimi; extensor carpi ulnaris) and one ankle tendon (tibialis posterior) was performed blindly, independently and bilaterally in each patient. Intraobserver and interobserver reliability were calculated by κ coefficients. A three-grade semiquantitative scoring system was agreed for scoring tendon damage in B mode. The mean intraobserver reliability for tendon damage scoring was excellent (κ value 0.91). The mean interobserver reliability assessment showed good κ values (κ value 0.75). The most reliable were the extensor digiti minimi, the extensor carpi ulnaris, and the tibialis posterior tendons. An ultrasound reference image atlas of tenosynovitis and tendon damage was also developed. Ultrasound is a reproducible tool for evaluating tendon damage in RA. This study strongly supports a new reliable ultrasound scoring system for tendon damage. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease.

PubMed

Sundaram, Shikha S; Sokol, Ronald J; Capocelli, Kelley E; Pan, Zhaoxing; Sullivan, Jillian S; Robbins, Kristen; Halbower, Ann C

2014-04-01

To determine whether obstructive sleep apnea (OSA) and/or nocturnal hypoxemia are associated with the severity of liver injury in patients with pediatric nonalcoholic fatty liver disease (NAFLD). Obese children aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic, clinical, and laboratory data were collected, polysomnography was performed, and liver histology was scored. Subjects were divided into those with OSA/hypoxemia and those without OSA/hypoxemia for analysis. Of 25 subjects with NAFLD, OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 ± 1.9 years; 68% male; 88% Hispanic; mean body mass index z-score, 2.3 ± 0.3). Subjects with and without OSA/hypoxemia had similar levels of serum aminotransferases, serum lipids, and inflammatory and insulin resistance markers. Although there were no differences between groups in the histological severity of steatosis, inflammation, ballooning degeneration, NAFLD activity score, or histological grade, subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation ≤90% was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04), aspartate aminotransferase level (r = 0.56; P = .004), and alanine aminotransferase level (r = 0.44; P = .03). Moderate OSA/hypoxemia is common in pediatric patients with biopsy-proven NAFLD. OSA and the severity/duration of hypoxemia are associated with biochemical and histological measures of NAFLD severity. Copyright © 2014 Mosby, Inc. All rights reserved.

The inflammation-based Glasgow Prognostic Score predicts survival in patients with cervical cancer.

PubMed

Polterauer, Stephan; Grimm, Christoph; Seebacher, Veronika; Rahhal, Jasmin; Tempfer, Clemens; Reinthaller, Alexander; Hefler, Lukas

2010-08-01

The Glasgow Prognostic Score (GPS) is known to reflect the degree of tumor-associated cachexia and inflammation and is associated with survival in various malignancies. We investigated the value of the GPS in patients with cervical cancer. We included 244 consecutive patients with cervical cancer in our study. The pretherapeutic GPS was calculated as follows: patients with elevated C-reactive protein serum levels (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2, and patients with 1 or no abnormal value were allocated a score of 1 or 0, respectively. The association between GPS and survival was evaluated by univariate log-rank tests and multivariate Cox regression models. The GPS was correlated with clinicopathologic parameters as shown by performing chi2 tests. In univariate analyses, GPS (P < 0.001, P < 0.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001, P < 0.001), and lymph node involvement (P < 0.001, P < 0.001), but not patients' age (P = 0.2, P = 0.07), histological grade (P = 0.08, P = 0.1), and histological type (P = 0.8, P = 0.9), were associated with disease-free and overall survival, respectively. In a multivariate analysis GPS (P = 0.03, P = 0.04), FIGO stage (P = 0.006, P = 0.006), and lymph node involvement (P = 0.003, P = 0.002), but not patients' age (P = 0.5, P = 0.5), histological grade (P = 0.7, P = 0.6), and histological type (P = 0.4, P = 0.6) were associated with disease-free and overall survival, respectively. The GPS was associated with FIGO stage (P < 0.001) and histological grade (P = 0.02). The GPS can be used as an inflammation-based predictor for survival in patients with cervical cancer.

The OARSI Histopathology Initiative - Recommendations for Histological Assessments of Osteoarthritis in the Guinea Pig

PubMed Central

Kraus, Virginia B; Huebner, Janet L.; DeGroot, Jeroen; Bendele, Alison

2010-01-01

Objective This review focuses on the criteria for assessing osteoarthritis (OA) in the guinea pig at the macroscopic and microscopic levels, and recommends particular assessment criteria to assist standardization in the conduct and reporting of preclinical trails in guinea pig models of OA. Methods A review was conducted of all OA studies from 1958 until the present that utilized the guinea pig. The PubMed database was originally searched August 1, 2006 using the following search terms: guinea pig and osteoarthritis. We continued to check the database periodically throughout the process of preparing this chapter and the final search was conducted January 7, 2009. Additional studies were found in a review of abstracts from the OsteoArthritis Research Society International (OARSI) conferences, Orthopaedic Research Society (ORS) conferences, and literature related to histology in other preclinical models of OA reviewed for relevant references. Studies that described or used systems for guinea pig joint scoring on a macroscopic, microscopic, or ultrastructural basis were included in the final comprehensive summary and review. General recommendations regarding methods of OA assessment in the guinea pig were derived on the basis of a comparison across studies and an inter-rater reliability assessment of the recommended scoring system. Results A histochemical-histological scoring system (based on one first introduced by H. Mankin) is recommended for semi-quantitative histological assessment of OA in the guinea pig, due to its already widespread adoption, ease of use, similarity to scoring systems used for OA in humans, its achievable high inter-rater reliability, and its demonstrated correlation with synovial fluid biomarker concentrations. Specific recommendations are also provided for histological scoring of synovitis and scoring of macroscopic lesions of OA. Conclusions As summarized herein, a wealth of tools exist to aid both in the semi-quantitative and quantitative assessment of OA in the guinea pig and provide a means of comprehensively characterizing the whole joint organ. In an ongoing effort at standardization, we recommend specific criteria for assessing the guinea pig model of OA as part of an OARSI initiative, termed herein the OARSI-HISTOgp recommendations. PMID:20864022

Antioxidant response of ridgetail white prawn Exopalaemon carinicauda to harmful dinoflagellate Prorocentrum minimum exposure and its histological change

NASA Astrophysics Data System (ADS)

Mu, Cuimin; Ren, Xianyun; Ge, Qianqian; Wang, Jiajia; Li, Jian

2017-04-01

The dinoflagellate Prorocentrum minimum, one of the most widespread red tide causing species, affects marine aquaculture and ecosystems worldwide. In this study, ridgetail white prawn Exopalaemon carinicauda were exposed to P. minimum cells (5 × 104 cells mL-1) to investigate its harmful effects on the shrimp. Antioxidant activities and histological changes were used as indicators of health status of the shrimp. In 72 hours, the mortality of E. carinicauda was not affected, but its antioxidant response and histology were statistically different from those of control. Elevated superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities and depressed catalase (CAT) activity were observed in gill; while increased SOD, glutathione S-transferase (GST), CAT activities and modulated GPX activity were observed in hepatopancreas. Thus, antioxidant activities in gill and hepatopancreas seem to respond differentially to harmful alga exposure. Increased malondialdehyde (MDA) content in early a few hours indicates the damage of the antioxidant defense system. Although MDA content recovered to a low level thereafter, a series of histological abnormalities including accumulation or infiltration of hemocytes, tissue lesions and necrosis were discovered in gill and hepatopancreas. Exposure to P. minimum induced sublethal effects on E. carinicauda, including temporary oxidative damage and histological injury.

Manual resurfacing and trichloroacetic acid for the treatment of patients with widespread actinic damage. Clinical and histologic observations.

PubMed

Cooley, J E; Casey, D L; Kauffman, C L

1997-05-01

A facial resurfacing regimen combining manual abrasion of the skin and 25% trichloroacetic acid has been reported to produce excellent results, but the histologic depth of injury produced by this technique has not been studied. To describe our experience with this technique treating patients with extensive actinic damage and to determine the histologic depth of injury produced. We treated 40 patients using manual resurfacing and trichloroacetic acid, primarily for widespread actinic keratoses. Resurfacing tools included silicone carbide sandpaper, drywall screen, electrocautery tip cleaners, abrasive pads, scalpel blades, and curettes. Four patients underwent sequential biopsies to evaluate the depth of wounding using this technique. Manual resurfacing combined with trichloroacetic acid consistently produced excellent cosmetic results and nearly complete eradication of actinic keratoses. Histologically, treated areas showed replacement of the dermal elastotic band by newly formed collagen, a significantly deeper level of wounding than the Jessner's/35% trichloroacetic acid peel. There was no evidence for foreign body granulomas clinically or histologically as a result of the abrasive materials. The deeper level of this peel explains the improved cosmetic outcome and greater eradication of actinic keratoses. This treatment is particularly well suited for patients with extensive photodamage and widespread actinic keratoses.

The effects of staged intra-articular injection of cultured autologous mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in caprine model.

PubMed

Nam, Hui Yin; Karunanithi, Puvanan; Loo, Wagner Cheng; Naveen, Sangeetha; Chen, Hui; Hussin, Paisal; Chan, Lucy; Kamarul, Tunku

2013-09-20

Treatment of chondral injuries remains a major issue despite the many advances made in cartilage repair techniques. Although it has been postulated that the use of marrow stimulation in combination with cell-based therapy may provide superior outcome, this has yet to be demonstrated. A pilot study was thus conducted to determine if bone marrow derived mesenchymal stromal cells (BM-MSCs) have modulatory effects on the repair outcomes of bone marrow stimulation (BMS) techniques. Two full-thickness chondral 5 mm diameter defects were created in tandem on the medial condyle of left stifle joints of 18 Boer caprine (N = 18). Goats were then divided equally into three groups. Simultaneously, bone marrow aspirates were taken from the iliac crests from the goats in Group 1 and were sent for BM-MSC isolation and expansion in vitro. Six weeks later, BMS surgery, which involves subchondral drilling at the defect sites, was performed. After two weeks, the knees in Group 1 were given autologous intra-articular BM-MSCs (N = 6). In Group 2, although BMS was performed there were no supplementations provided. In Group 3, no intervention was administered. The caprines were sacrificed after six months. Repairs were evaluated using macroscopic assessment through the International Cartilage Repair Society (ICRS) scoring, histologic grading by O'Driscoll score, biochemical assays for glycosaminoglycans (GAGs) and gene expressions for aggrecan, collagen II and Sox9. Histological and immunohistochemical analyses demonstrated hyaline-like cartilage regeneration in the transplanted sites particularly in Group 1. In contrast, tissues in Groups 2 and 3 demonstrated mainly fibrocartilage. The highest ICRS and O'Driscoll scorings was also observed in Group 1, while the lowest score was seen in Group 3. Similarly, the total GAG/total protein as well as chondrogenic gene levels were expressed in the same order, that is highest in Group 1 while the lowest in Group three. Significant differences between these 3 groups were observed (P <0.05). This study suggests that supplementing intra-articular injections of BM-MSCs following BMS knee surgery provides superior cartilage repair outcomes.

Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury.

PubMed

Spieth, Peter M; Carvalho, Alysson R; Pelosi, Paolo; Hoehn, Catharina; Meissner, Christoph; Kasper, Michael; Hübler, Matthias; von Neindorff, Matthias; Dassow, Constanze; Barrenschee, Martina; Uhlig, Stefan; Koch, Thea; de Abreu, Marcelo Gama

2009-04-15

Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Critchley, J.A.J.H.; Beeley, J.M.; Clark, R.J.

1990-04-01

Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. The authors evaluated NAC and methylprednisolone in two rats models of inhalation injury: 40-hr exposure to >97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). Themore » increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. They caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.« less

[Mesenteric flow in an experimental model of ischaemia-reperfusion in rats].

PubMed

Cáceres, F; Castañon, M; Lerena, J; Cusi, V; Badosa, J; Morales, L

2014-03-01

Maintained acute occlusion followed by reperfusion of the superior mesenteric artery (SMA) in a few hours can trigger irreversible bowel damage. The aim of the study was to determine the changes in mesenteric flow measured by colour Doppler Ultrasound and correlating with histological lesions in an experimental model of ischaemia-reperfusion. Three groups of Sprague-Dawley 17 day-old rats were studied (control, ischemia and reperfusion). The model used was ischaemia-reperfusion over the SMA. Intra-abdominal ultrasound was then performed. The parameters recorded were: Maximum systolic velocity (MSV), pulsatility index (PI), resistance (RI) and systole-diastole (S/D). The histological variables were: intestinal lesion (Wallace/Keenan-Chiu scale), morphometrics (mean villus height [MVH]), and goblet cells. The Spearman (rs) correlation was used. The MSV in the reperfusion group was 74.3 cm/s, the PI 7.33 and S/D 25.75 in the SMA, which were higher than the controls (41.35 cm/s; 3.12 and 12.45, respectively). A direct association (P<.01) was found between MSV, PI and S/D regarding: Wallace/Kennan scoring system (rs = 0.655; rs = 0.593; rs = 0.63) and the Chiu (rs = 0.569; rs = 0.522; rs = 0.47). While the correlation was the reverse (P<.01) when associated with the MVH (rs = -0,495; rs = -0,452; rs = -0,459) and goblet cells of the colon (rs = -0,525; rs = -0,45; rs = -0,518). The reperfusion phase increased mesenteric flow expressed by the MSV and PI and could significantly predict the potential bowel damage at macroscopic and microscopic level. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury.

PubMed

Zhang, Shu-xin; Huang, Fengfa; Gates, Mary; White, Jason; Holmberg, Eric G

2010-08-30

Intrathecal infusion has been widely used to directly deliver drugs or neurotrophins to a lesion site following spinal cord injury. Evidence shows that intrathecal infusion is efficient for 7 days but is markedly reduced after 14 days, due to time dependent occlusion. In addition, extensive fibrotic scarring is commonly observed with intrathecal infusion. These anomalies need to be clearly elucidated in histology. In the present study, all adult Long-Evans rats received a 25 mm contusion injury on spinal cord T10 produced using the NYU impactor device. Immediately after injury, catheter tubing with an outer diameter of 0.38 mm was inserted through a small dural opening at L3 into the subdural space with the tubing tip positioned near the injury site. The tubing was connected to an Alzet mini pump, which was filled with saline solution and was placed subcutaneously. Injured rats without tubing served as control. Rats were behaviorally tested for 6 weeks using the BBB locomotor rating scale and histologically assessed for tissue scarring. Six weeks later, we found that the intrathecal tubing caused extensive scarring and inflammation, related to neutrophils, macrophages and plasma cells. The tubing's tip was occluded by scar tissue and inflammatory cells. The scar tissue surrounding the tubing consists of 20-70 layers of fibroblasts and densely compacted collagen fibers, seriously compressing and damaging the cord tissue. BBB scores of rats with intrathecal tubing were significantly lower than control rats (p<0.01) from 2 weeks after injury, implying serious impairment of functional recovery caused by the scarring. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia.

PubMed

Figueira, R L; Gonçalves, F L; Simões, A L; Bernardino, C A; Lopes, L S; Castro E Silva, O; Sbragia, L

2016-06-23

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

PubMed Central

Figueira, R.L.; Gonçalves, F.L.; Simões, A.L.; Bernardino, C.A.; Lopes, L.S.; Castro e Silva, O.; Sbragia, L.

2016-01-01

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers. PMID:27356106

Joint distraction attenuates osteoarthritis by reducing secondary inflammation, cartilage degeneration and subchondral bone aberrant change.

PubMed

Chen, Y; Sun, Y; Pan, X; Ho, K; Li, G

2015-10-01

Osteoarthritis (OA) is a progressive joint disorder. To date, there is not effective medical therapy. Joint distraction has given us hope for slowing down the OA progression. In this study, we investigated the benefits of joint distraction in OA rat model and the probable underlying mechanisms. OA was induced in the right knee joint of rats through anterior cruciate ligament transaction (ACLT) plus medial meniscus resection. The animals were randomized into three groups: two groups were treated with an external fixator for a subsequent 3 weeks, one with and one without joint distraction; and one group without external fixator as OA control. Serum interleukin-1β level was evaluated by ELISA; cartilage quality was assessed by histology examinations (gross appearance, Safranin-O/Fast green stain) and immunohistochemistry examinations (MMP13, Col X); subchondral bone aberrant changes was analyzed by micro-CT and immunohistochemistry (Nestin, Osterix) examinations. Characters of OA were present in the OA group, contrary to in general less severe damage after distraction treatment: firstly, IL-1β level was significantly decreased; secondly, cartilage degeneration was attenuated with lower histologic damage scores and the lower percentage of MMP13 or Col X positive chondrocytes; finally, subchondral bone abnormal change was attenuated, with reduced bone mineral density (BMD) and bone volume/total tissue volume (BV/TV) and the number of Nestin or Osterix positive cells in the subchondral bone. In the present study, we demonstrated that joint distraction reduced the level of secondary inflammation, cartilage degeneration and subchondral bone aberrant change, joint distraction may be a strategy for slowing OA progression. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Prophylactic effects of Lonicera japonica extract on dextran sulphate sodium-induced colitis in a mouse model by the inhibition of the Th1/Th17 response.

PubMed

Park, Jae-Woo; Bae, Hyunsu; Lee, Gihyun; Hong, Beom-Gi; Yoo, Hye Hyun; Lim, Sung-Jig; Lee, Kyungjin; Kim, Jinsung; Ryu, Bongha; Lee, Beom-Joon; Bae, Jinhyun; Lee, Hyejung; Bu, Youngmin

2013-01-28

Inflammatory bowel diseases (IBD) are chronically relapsing inflammatory disorders of the intestine. Although some therapeutic agents, including steroids, are available for the treatment of IBD, these agents have limited use. Therefore, dietary supplements have emerged as possible interventions for IBD. Japanese honeysuckle flower, the flower of Lonicera japonica, is a well-known dietary supplement and has been used to prevent or treat various inflammatory diseases. In the present study, we investigated the effects of L. japonica on experimental murine colitis. Colitis was induced by 5 % dextran sulphate sodium (DSS) in Balb/c mice. The water extract of L. japonica (LJE) at doses of 20, 100 or 500 mg/kg was orally administered to mice twice per day for 7 d. Body weight, colon length and a histological damage score were assessed to determine the effects on colitis. Cytokine profiles were assessed to examine the effects on helper T (Th) cell-related immunological responses. In addition, CD4⁺CD25⁺Foxp3⁺T cells were analysed in vivo and in vitro for investigating the effects on regulatory T (Treg) cells. LJE showed dose-dependent inhibitory effects against colon shortening, weight loss and histological damage. LJE down-regulated IL-1β, TNF-α, interferon-γ, IL-6, IL-12 and IL-17. However, LJE did not show any significant effects on IL-10, IL-23, transforming growth factor-β1 and Treg cell populations. In conclusion, LJE showed protective effects against DSS-induced colitis via the Th1/Th17 pathway and not via Treg cell-related mechanisms.

The oxidative damage and disbalance of calcium homeostasis in brain of chicken induced by selenium deficiency.

PubMed

Xu, Shi-Wen; Yao, Hai-Dong; Zhang, Jian; Zhang, Zi-Wei; Wang, Jin-Tao; Zhang, Jiu-Li; Jiang, Zhi-Hui

2013-02-01

Dietary selenium (Se) deficiency can influence the function of the brain. Our objective was to investigate the effects of Se deficiency on oxidative damage and calcium (Ca) homeostasis in brain of chicken. In the present study, 1-day-old chickens were fed either a commercial diet (as control group) with 0.15 mg/kg Se or a Se-deficient diet (as L group) with 0.033 mg/kg Se for 75 days. Then, brain injury biomarkers were examined, including histological analysis, ultrastructure assay, and apoptosis assay. We also examined the effect of Se deficiency on the Se-containing antioxidative enzyme glutathione peroxidase (GSH-Px), the level of glutathione (GSH), and the Ca homeostasis in brain of chicken. The results showed that the levels of Se and GSH and activity of GSH-Px are seriously reduced by 33.8-96 % (P < 0.001), 24.51-27.84 % (P < 0.001), and 20.70-64.24 % (P < 0.01), respectively. In the present study, we also perform histological analysis and ultrastructure assay and find that Se deficiency caused disorganized histological structure, damage to the mitochondria, fusion of nuclear membrane and nucleus shrinkage, higher apoptosis rate (P < 0.001), and increase of Ca homeostasis (P < 0.05 or P < 0.01 or P < 0.001) in the brain of chicken. In conclusion, the results demonstrated that Se deficiency induced oxidative damage and disbalance of Ca homeostasis in the brain of chicken. Similar to mammals, chickens brain is also extremely susceptible to oxidative damage and selenium deficiency.

A BEHAVIORAL AND HISTOLOGICAL COMPARISON OF FLUID PERCUSSION INJURY AND CONTROLLED CORTICAL IMPACT INJURY TO THE RAT SENSORIMOTOR CORTEX

PubMed Central

Peterson, Todd C.; Maass, William R.; Anderson, Jordan R.; Anderson, Gail D.; Hoane, Michael R.

2015-01-01

Our primary goal was to evaluate the behavioral and histological outcome of fluid percussion injury (FPI) and cortical contusion injury (CCI) to the sensorimotor cortex (SMC). The SMC has been used to evaluate neuroplasticity following CCI, but has not been extensively examined with FPI. In both the CCI and FPI models, a mechanical force of 4 mm in diameter was applied over the SMC, allowing for a direct comparison to measure the relative rates of histology and recovery of function in these models. Gross behavioral deficits were found on the sensory task (tactile adhesive removal task) and multiple motor assessments (forelimb asymmetry task, forelimb placing task, and rotorod). These sensorimotor deficits occurred in the absence of cognitive deficits in the water maze. The CCI model creates focal damage with a localized injury wheras the FPI model creates a more diffuse injury causing widespread damage. Both behavioral and histological deficits ensued following both models of injury to the SMC. The neuroplastic changes and ease at which damage to this area can be measured behaviorally make this an excellent location to assess traumatic brain injury (TBI) treatments. No injury model can completely mimic the full spectrum of human TBI and any potential treatments should be validated across both focal and diffuse injury models. Both of these injury models to the SMC produce severe and enduring behavioral deficits, which are ideal for evaluating treatment options. PMID:26275924

Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

PubMed Central

Sartori, Massimo; Andorno, Silvano; Rossini, Angelo; Boldorini, Renzo; Bozzola, Cristina; Carmagnola, Stefania; Piano, Mario Del; Albano, Emanuele

2010-01-01

AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to, or unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin ≤ 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by at least one point reduction in the staging score or, in case of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

PubMed

Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

2015-11-01

Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with normal or mildly elevated ALT.

Meniscus Induced Cartilaginous Damage and Non-linear Gross Anatomical Progression of Early-stage Osteoarthritis in a Canine Model

PubMed Central

Kahn, David; Mittelstaedt, Daniel; Matyas, John; Qu, Xiangui; Lee, Ji Hyun; Badar, Farid; Les, Clifford; Zhuang, Zhiguo; Xia, Yang

2016-01-01

Background: The predictable outcome of the anterior cruciate ligament transection (ACLT) canine model, and the similarity to naturally occurring osteoarthritis (OA) in humans, provide a translatable method for studying OA. Still, evidence of direct meniscus-induced cartilaginous damage has not been identified, and gross-anatomical blinded scoring of early-stage OA has not been performed. Objective: A gross anatomical observation and statistical analysis of OA progression to determine meniscus induced cartilaginous damage, to measure the macroscopic progression of OA, and to address matters involving arthroscopic and surgical procedures of the knee. Method: Unblinded assessment and blinded scoring of meniscal, tibial, femoral, and patellar damage were performed for control and at four time points following unilateral ACLT: 3-week (N=4), 8-week (N=4), 12-week (N=5), and 25-week (N=4). Mixed-model statistics illustrates damage (score) progression; Wilcoxon rank-sum tests compared time-point scores; and Wilcoxon signed-rank tests compared ACLT and contralateral scores, and meniscus and tibia scores. Result: Damage was manifest first on the posterior aspect of the medial meniscus and subsequently on the tibia and femur, implying meniscal damage can precede, coincide with, and aggravate cartilage damage. Damage extent varied chronologically and was dependent upon the joint component. Meniscal damage was evident at 3 weeks and progressed through 25-weeks. Meniscal loose bodies corresponded to tibial cartilage damage location and extent through 12 weeks, followed by cartilage repair activity after complete meniscal degeneration. Conclusion: This study provides additional information for understanding OA progression, identifying OA biomarkers, and arthroscopic and meniscectomy procedures. PMID:28144379

A Prospective Study of the Impact of Current Poverty, History of Poverty, and Exiting Poverty on Accumulation of Disease Damage in Systemic Lupus Erythematosus.

PubMed

Yelin, Edward; Trupin, Laura; Yazdany, Jinoos

2017-08-01

To estimate the effect of current poverty, number of years in poverty, and exiting poverty on disease damage accumulation in systemic lupus erythematosus (SLE). For this study, 783 patients with SLE were followed up from 2003 to 2015 through annual structured interviews. Respondents were categorized in each year by whether they had a household income of ≤125% of the US federal poverty level. Linear and logistic regression analyses were used to assess the impact of poverty in 2009, number of years in poverty between 2003 and 2009, and permanent exits from poverty as of 2009 on the extent of disease damage (according to the Brief Index of Lupus Damage [BILD] score) or accumulation of a clinically meaningful increase in disease damage (defined as a minimum 2-point increase in the BILD damage score) by 2015. After adjustment for sociodemographic features, health care characteristics, and health behaviors, poverty in 2009 was associated with an increased level of accumulated disease damage in 2015 (mean difference in BILD damage score between poor and non-poor 0.62 points, 95% confidence interval [95% CI] 0.25-0.98) and increased odds of a clinically important increase in damage (odds ratio [OR] 1.67, 95% CI 0.98-2.85). Being poor in every year between 2003 and 2009 was associated with greater damage (mean change in BILD score 2.45, 95% CI 1.88-3.01) than being poor for one-half or more of those years (mean change in BILD score 1.45, 95% CI 0.97-1.93), for fewer than one-half of those years (mean change in BILD score 1.49, 95% CI 1.10-1.88), or for none of those years (mean change in BILD score 1.34, 95% CI 1.20-1.49). Those exiting poverty permanently had similar increases in disease damage (mean change in BILD score 1.30, 95% CI 0.90-1.69) as those who were never in poverty (mean change in BILD score 1.36, 95% CI 1.23-1.50) but much less damage than those who remained in poverty (mean change in BILD score 1.98, 95% CI 1.59-2.38). The effects of current poverty, "dose" of poverty, and exiting poverty suggest that poverty plays a critical role in the accumulation of damage in patients with SLE. © 2017, American College of Rheumatology.

[Values and limits in fine needle aspiration in the diagnosis of Warthin tumour of the parotid gland].

PubMed

Righi, A; Foschini, M P

2006-12-01

Recent paper state that cytological diagnosis of Warthin Tumour of the parotid gland is poorly reproducible and that aspiration procedures damage the tumoral tissue as to make difficult the histological diagnosis. Aim of the present study is to review cytological sampling performed with fine needle sampling without aspiration and to compare them with the relative surgical specimens in order to determine the value of fine needle aspiration in the diagnosis of Warthin Tumour and to quantify' the damage in histological tissue. All cases with cytological and/or histological diagnosis of Warthin Tumour during the period 1/1/98 to 30/6/04 were retrieved. In all cases both cytological and histological slides were reviewed and compared. In all cases fine needle aspiration (FNA) was performed according to the technique described by Zajdela et al. in 1987. A cytologic sample was considered diagnostic when there were in the same sample mucoid substance, lymphocytes scattered with a range of maturation and oncocytes organized in flat sheets of cells. 38 cases were selected corresponding to 37 patients (1 case of Warthin Tumour bilateral): all tumors were localized in the parotid gland. Fine needle sampling were 43. Nine cytological sample (20.9%) were inadequate. Sensitivity and specificity, in the preent series, had the same value, being 97.1%. A spectrum of histologic alterations were observed in 30/38 cases (79%). These alterations were squamous metaplasia (7 cases), acute and chronic hemorrhage and inflammation with multinucleated giant cells (26 cases) and granulation tissue with subsequent fibrosis (24 cases). In all cases the histologic alterations from fine needle were focal, limited to less than 20% of the tumoral area (first category of Batsakis 'classification), and did not prevent the histologic diagnosis of Warthin Tumour. These data suggest that fine needle aspiration without aspiration is a valuable tool for the per-operative diagnosis of Warthin Tumour. In addition it creates only minor histological changes, that always allow the histological diagnosis.

Cartilage regeneration by selected chondrogenic clonal mesenchymal stem cells in the collagenase-induced monkey osteoarthritis model.

PubMed

Jiang, Li; Ma, Anlun; Song, Lijun; Hu, Yanxin; Dun, Hao; Daloze, Pierre; Yu, Yonglin; Jiang, Jianyuan; Zafarullah, Muhammad; Chen, Huifang

2014-11-01

Osteoarthritis (OA) is the most common form of arthritis, in which cartilage is irreversibly degraded, causing severe pain and disability. Current therapeutic strategies cannot repair damaged cartilage. We evaluated the repair potential of selected chondrogenic clonal MSCs (sC-MSCs) by delivering them into the injured cartilage site in a collagenase-induced OA model in Cynomolgus monkeys. In vitro characterization showed that the isolated monkey sC-MSCs and polyclonal MSCs (P-MSCs) expressed mesenchymal stem cell markers and could differentiate into chondrocytes. The articular cartilage lesions in animals were treated with normal saline (NS), autologous P-MSCs and sC-MSCs, respectively, by direct delivery. The clinical parameters, radiographic images, histological and immunohistochemical examinations at weeks 8, 16 and 24 post-treatment demonstrated that the abrasions of articular cartilage were significantly improved and repaired by MSC-based treatment, particularly in the sC-MSC-treated group, which displayed consistently higher histological scores than those of other groups. In summary, treatment with sC-MSCs can effectively improve the healing of cartilage lesions in the Cynomolgus monkey collagenase-induced OA model. Due to the genetic proximity of monkey and human, the therapeutic strategy presented in this study will have broad applications in clinical practice. Copyright © 2013 John Wiley & Sons, Ltd.

Curative effect of Terminalia chebula extract on acetic acid-induced experimental colitis: role of antioxidants, free radicals and acute inflammatory marker.

PubMed

Gautam, M K; Goel, Shalini; Ghatule, R R; Singh, A; Nath, G; Goel, R K

2013-10-01

The present study has evaluated the healing effects of extract of dried fruit pulp of Terminalia chebula (TCE) on acetic acid (AA)-induced colitis in rats. TCE (600 mg/kg) showed healing effects against AA-induced colonic damage score and weight when administered orally daily for 14 days. TCE was further studied for its effects on various physical (mucus/blood in stool and stool frequency, food and water intake and body weight changes), histology, antibacterial activity and free radicals (NO and LPO), antioxidants (SOD, CAT and GSH) and myeloperoxidase in colonic tissue. Intra-colonic AA administration increased colonic mucosal damage and inflammation, mucus/bloody diarrhoea, stool frequency, but decreased body weight which were reversed by TCE and sulfasalazine (SS, positive control) treatments. TCE showed antibacterial activity and both TCE and SS enhanced the antioxidants, but decreased free radicals and myeloperoxidase activities affected in acetic acid-induced colitis. TCE indicated the presence of active principles with proven antioxidants, anti-inflammatory, immunomodulatory, and free radical scavenging and healing properties. Thus, TCE seemed to be safe and effective in healing experimental colitis.

Thermal Damage Done to Bone by Burring and Sawing With and Without Irrigation in Knee Arthroplasty.

PubMed

Tawy, Gwenllian F; Rowe, Philip J; Riches, Philip E

2016-05-01

Heat from bone resecting tools used in knee surgery can induce thermal osteonecrosis, potentially causing aseptic implant loosening. This study compared oscillating saws to burrs in terms of temperature generation and histologic damage. Use of irrigation to reduce bone temperature was also investigated. Temperatures were recorded during sawing and burring with or without irrigation (uncooled or cooled). Histologic analyses were then carried out. Differences between groups were tested statistically (α = 0.05). On average, burring produced higher temperatures than sawing (P < .001). When uncooled irrigation was used, bone temperatures were significantly lower in sawed bone than in burred bone (P < .001). Irrigation lowered temperatures and thermal damage depths and increased osteocyte viability (P < .001). These results suggest that irrigating bone during resection could prevent osteonecrosis onset. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

PubMed

Whittaker, Alexandra L; Lymn, Kerry A; Wallace, Georgia L; Howarth, Gordon S

2016-01-01

Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis.

PubMed

Hayami, Tadashi; Zhuo, Ya; Wesolowski, Gregg A; Pickarski, Maureen; Duong, Le T

2012-06-01

To investigate the disease modifying effects of cathepsin K (CatK) inhibitor L-006235 compared to alendronate (ALN) in two preclinical models of osteoarthritis (OA). Skeletally mature rabbits underwent sham or anterior cruciate ligament transection (ACLT)-surgery and were treated with L-006235 (L-235, 10 mg/kg or 50 mg/kg, p.o., daily) or ALN (0.6 mg/kg, s.c., weekly) for 8-weeks. ACLT joint instability was also induced in CatK(-/-) versus wild type (wt) mice and treated for 16-weeks. Changes in cartilage degeneration, subchondral bone volume and osteophyte area were determined by histology and μ-CT. Collagen type I helical peptide (HP-I), a bone resorption marker and collagen type II C-telopeptide (CTX-II), a cartilage degradation marker were measured. L-235 (50 mg/kg) and ALN treatment resulted in significant chondroprotective effects, reducing CTX-II by 60% and the histological Mankin score for cartilage damage by 46% in the ACLT-rabbits. Both doses of L-235 were more potent than ALN in protecting against focal subchondral bone loss, and reducing HP-I by 70% compared to vehicle. L-235 (50 mg/kg) and ALN significantly reduced osteophyte formation in histomorphometric analysis by 55%. The Mankin score in ACLT-CatK(-/-) mice was ~2.5-fold lower than the ACLT-wt mice and was not different from sham-CatK(-/-). Osteophyte development was not different among the groups. Inhibition of CatK provides significant benefits in ACLT-model of OA, including: 1) protection of subchondral bone integrity, 2) protection against cartilage degradation and 3) reduced osteophytosis. Preclinical evidence supports the role of CatK as a potential therapeutic target for the treatment of OA. Copyright © 2012 Elsevier Inc. All rights reserved.

Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation.

PubMed

Saito, Kosuke; Tamaki, Tetsuro; Hirata, Maki; Hashimoto, Hiroyuki; Nakazato, Kenei; Nakajima, Nobuyuki; Kazuno, Akihito; Sakai, Akihiro; Iida, Masahiro; Okami, Kenji

2015-01-01

Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2-8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks.

Structural and functional correlations in stable renal allografts.

PubMed

Fulladosa, Xavier; Moreso, Francesc; Torras, Joan; Hueso, Miquel; Grinyó, Josep M; Serón, Daniel

2003-05-01

Renal functional reserve (RFR) has been proposed as a surrogate marker of renal mass, but its significance in well-functioning renal transplants is controversial. Thus, we used early protocol biopsies to analyze structural and functional correlations in stable grafts. We studied 32 cyclosporine (CsA)-treated stable cadaveric transplants at 5 months. Biopsies were evaluated according to Banff criteria and histomorphometry. Inulin and p-aminohippurate clearances were used to calculate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). RFR after an amino acid infusion (RFR-AA) and after a combined amino acid and dopamine infusion (RFR-AA-DOPA) was evaluated. Baseline GFR was 54 +/- 16 mL/min/1.73 m2, and ERPF was 219 +/- 55 mL/min/1.73 m2. RFR-AA was 9% +/- 13%, and RFR-AA-DOPA was 22% +/- 20%. RFR-AA correlated with CsA dose (R = 0.39; P = 0.02), whereas RFR-AA-DOPA correlated with CsA dose (R = 0.36; P = 0.04) and CsA levels (R = 0.40; P = 0.02). The only histological parameter associated with RFR was the presence of arteriolar hyalinosis (AH). Patients showing an AH score of 1 or greater (n = 7) had lower RFR-AA (0% +/- 9% versus 11% +/- 13%; P = 0.02) and lower RFR-AA-DOPA (9% +/- 17% versus 26% +/- 19%; P = 0.03). Multivariate analysis showed that an AH score of 1 or greater, but not CsA dose or levels, was associated with RFR-AA (R = 0.42; P = 0.01). RFR-AA-DOPA was associated with hyaline arteriolar damage (R = 0.43; P = 0.01), as well as CsA levels (R = 0.54; P = 0.006). The presence of AH is the only histological parameter associated with impaired RFR in well-functioning grafts.

Resistive index and chronic allograft nephropathy evaluated in protocol biopsies as predictors of graft outcome.

PubMed

Vallejos, Augusto; Alperovich, Gabriela; Moreso, Francesc; Cañas, Concepcion; de Lama, M Eugenia; Gomà, Montserrat; Fulladosa, Xavier; Carrera, Marta; Hueso, Miguel; Grinyó, Josep M; Serón, Daniel

2005-11-01

The presence of chronic allograft nephropathy (CAN) in protocol biopsies is negatively associated with graft survival. Although recent studies have indicated that the resistive index (RI) is a predictor of graft failure, it does not correlate with CAN in stable grafts. We therefore studied the relationship between RI and CAN and examined the predictive value of both parameters on graft outcome. Included were patients transplanted between 1997 and 2002 and who had protocol biopsies and RI determinations. Renal lesions were blindly evaluated according to Banff 97 criteria. Mean glomerular volume, cortical interstitial volume fraction and intimal arterial volume fraction were estimated using a point counting technique. RI was determined before biopsy in at least two different renal locations. The outcome variable was defined as graft failure or a 30% serum creatinine increase between protocol biopsy and last follow-up. Eighty-seven patients were included. RI correlated with recipient age (R = 0.52, P < 0.0001), diastolic blood pressure (R = -0.36, P = 0.0006), pulse pressure index (R = 0.27, P = 0.009) and g-score for histological glomerulitis (rho = 0.30, P = 0.0054), but there were no correlations between RI and chronic Banff scores or any morphometric parameter. The presence of CAN (relative risk, 3.5; 95% confidence interval 1.2-10.2; P = 0.02) but not RI was associated with the outcome variable. RI was associated with surrogate measures of vascular compliance such as recipient age and pulse pressure index but not with chronic allograft damage, even when it was evaluated by histomorphometry. Our results indicate that histology may be superior to RI in predicting graft function deterioration, at least in patients with stable renal function.

Effects of gadolinium-based MRI contrast agents on liver tissue.

PubMed

Mercantepe, Tolga; Tümkaya, Levent; Çeliker, Fatma Beyazal; Topal Suzan, Zehra; Çinar, Seda; Akyildiz, Kerimali; Mercantepe, Filiz; Yilmaz, Adnan

2018-04-01

MRI with contrast is often used clinically. However, recent studies have reported a high accumulation of gadolinium-based contrast agents (GBCAs) in kidney, liver, and spleen tissues in several mouse models. To compare the effects on liver tissue of gadolinium-based MRI contrast agents in the light of biochemical and histopathological evaluation. Institutional Review Board (IRB)-approved controlled longitudinal study. In all, 32 male Sprague-Dawley rats were divided into a healthy control group subjected to no procedure (Group 1), a sham group (Group 2), a gadodiamide group (Group 3), and a gadoteric acid group (Group 4). Not applicable. Liver tissues removed at the end of the fifth week and evaluated pathologically (scored Knodell's histological activity index [HAI] method by two histopathologists) immunohistochemical (caspase-3 and biochemical tests (AST, ALT, TAS, TOS, and OSI method by Erel et al) were obtained. Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by the Tamhane test, and one-way analysis of variance (ANOVA) followed by Turkey's HSD test. An increase was observed in histological activity scores in sections from rats administered gadodiamide and gadoteric acid, and in caspase-3, AST and ALT values (P < 0.05). In contrast, we determined no change in TOS (P = 0.568 and P = 0.094, respectively), TAS (P = 0.151 and P = 0.055, respectively), or OSI (P = 0.949 and P = 0.494, respectively) values. These data suggest that gadodiamide and gadoteric acid trigger hepatocellular necrosis and apoptosis by causing damage in hepatocytes, although no change occurs in total antioxidant and antioxidant capacity. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Interferon-alpha-induced changes in metallothionein expression in liver biopsies from patients with chronic hepatitis C.

PubMed

Nagamine, Takeaki; Suzuki, Keiji; Kondo, Toshihiko; Nakazato, Kyomi; Kakizaki, Satoru; Takagi, Hitoshi; Nakajima, Katuyuki

2005-08-01

An association between reactive oxygen species and liver damage has been postulated in the course of hepatitis C virus (HCV) infection. Metallothionein (MT), induced by HCV core protein and interferon (IFN), plays a role in scavenging free radicals. MT expression in liver biopsies obtained from 21 patients with chronic HCV infection before and after IFN-alpha therapy was investigated. Changes in Knodell histological activity index (HAI) scores, MT protein levels (immunohistochemistry), MT-I and MT-II messenger (m)RNA expression levels (in situ hybridization) and proliferating cell nuclear antigen (PCNA) labelling index were determined and compared in serial liver specimens. MT staining was clustered around the portal tracts with inflammatory cells and fibrosis. The pattern of MT protein before IFN-alpha therapy was similar in all patients, but was higher in IFN-sustained responders than in nonresponders after IFN-alpha therapy. HAI scores and PCNA labelling indexes were significantly reduced after IFN-alpha therapy. MT-II mRNA expression correlated positively with PCNA index before therapy and with HAI scores after therapy (P<0.05). No correlation was found between MT-I mRNA and HAI scores or PCNA index. The findings indicate that IFN-alpha-induced hepatic MT may participate in the therapeutic effects of IFN-alpha for HCV. In addition, MT-II mRNA expression may be involved in cell proliferation in the livers of patients with chronic HCV infection.

Intra- and inter-observer agreement in histological assessment of canine soft tissue sarcoma.

PubMed

Yap, F W; Rasotto, R; Priestnall, S L; Parsons, K J; Stewart, J

2017-12-01

The diagnosis of canine soft tissue sarcoma (STS) is based on histological assessment. Assessment of criteria such as, degree of differentiation, necrosis score and mitotic score, gives rise to a final tumour grade, which is important in the recommendation of treatment and prognosis of patients. Previously diagnosed cases of STS were independently assessed by three board-certified veterinary pathologists. Participating pathologists were blinded to the original results. For the intra-observer study, the cases were assessed by a single pathologist six months apart and slides were randomized between readings. For the inter-observer study, the whole case series was assessed by a single pathologist before being passed onto the next pathologist. Intraclass correlation coefficient (ICC) and Fleiss's Kappa (ƙ) for the intra- (single observer) and inter-observer agreement. Strong agreement was observed for the intra-observer assessment in necrosis score, mitotic score, total score and tumour grading (ICC between 0.78 to 0.91). The intra-observer agreement for differentiation score was rated perfect (ICC 1.00). The agreement between pathologists for the diagnosis and grading of canine STS was moderate (ƙ = 0.60 and 0.43 respectively). Histological assessment of canine STS had high reproducibility by an individual pathologist. The agreement of diagnosis and grading of canine STS was moderate between pathologists. Future studies are required to investigate further assessment criteria to improve the specificity of STS diagnosis and the accuracy of the STS grading in dogs. © 2017 John Wiley & Sons Ltd.

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaefer, Inga-Marie; Hornick, Jason L.; Barysauskas, Constance M.

Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportionalmore » hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.« less

Pressure threshold for shock wave induced renal hemorrhage.

PubMed

Mayer, R; Schenk, E; Child, S; Norton, S; Cox, C; Hartman, C; Cox, C; Carstensen, E

1990-12-01

Studies were performed with an interest in determining a pressure threshold for extracorporeal shock wave induced renal damage. Histological evidence of intraparenchymal hemorrhage was used as an indicator of tissue trauma. Depilated C3H mice were anesthetized and placed on a special frame to enhance visualization and treatment of the kidneys in situ. A Wolf electrohydraulic generator and 9 French probe designed for endoscopic use were utilized to expose the kidneys to 10 double spherically divergent shock waves. Measurements of the shock waves revealed two positive pressure peaks of similar magnitude for each spark discharge. The kidneys were exposed to different peak pressures by choice of distance from the spark source and were removed immediately after treatment for histologic processing. A dose response was noted with severe corticomedullary damage apparent following 15 to 20 MPa shocks. Hemorrhage was more apparent in the medulla where evidence of damage could be seen following pressures as low as three to five MPa. When a latex membrane was interposed to prevent possible collapse of the initial bubble from the spark source against the skin surface, histological evaluation revealed substantial reduction of severe tissue damage associated with the highest pressures tested, 20 MPa. However, the threshold level for evidence of hemorrhage remained about three to five MPa. Hydrophonic measurements indicated that the membrane allowed transmission of the acoustic shock waves and suggested that collapse of the bubble generated by electrohydraulic probes may have local effects due to a cavitation-like mechanism.

Analysis of Arg-Gly-Asp mimetics and soluble receptor of tumour necrosis factor as therapeutic modalities for concanavalin A induced hepatitis in mice.

PubMed Central

Bruck, R; Shirin, H; Hershkoviz, R; Lider, O; Kenet, G; Aeed, H; Matas, Z; Zaidel, L; Halpern, Z

1997-01-01

BACKGROUND/AIMS: It has been shown that synthetic non-peptidic analogues of Arg-Gly-Asp, a major cell adhesive ligand of extracellular matrix, prevented an increase in serum aminotransferase activity, as a manifestation of concanavalin A induced liver damage in mice. This study examined the effects of an Arg-Gly-Asp mimetic on liver histology and cytokine release in response to concanavalin A administration, and the efficacy of soluble receptor of tumour necrosis factor (TNF) alpha in preventing hepatitis in this model of liver injury. METHODS: Mice were pretreated with either the Arg-Gly-Asp mimetic SF-6,5 or recombinant soluble receptor of TNF alpha before their inoculation with 10 mg/kg concanavalin A. Liver enzymes, histology, and the serum values of TNF alpha and interleukin (IL)6 were examined. RESULTS: The histopathological damage in the liver, and the concanavalin A induced release of TNF alpha and IL6 were significantly inhibited by the synthetic Arg-Gly-Asp mimetic (p < 0.001). Liver injury, manifested by the increase in serum aminotransferase and cytokines, as well as by histological manifestations of hepatic damage, was effectively prevented by pretreatment of the mice with the soluble TNF receptor (p < 0.001). CONCLUSIONS: This study confirms the efficacy of a synthetic Arg-Gly-Asp mimetic and soluble TNF receptor in the prevention of immune mediated liver damage in mice. Images PMID:9155591

Comparison of epidermal/dermal damage between the long-pulsed 1064 nm Nd:YAG and 755 nm alexandrite lasers under relatively high fluence conditions: quantitative and histological assessments.

PubMed

Lee, Ju Hwan; Park, So Ra; Jo, Jeong Ho; Park, Sung Yun; Seo, Young Kwon; Kim, Sung Min

2014-07-01

The purpose of this study was to compare degrees of epidermal/dermal tissue damage quantitatively and histologically after laser irradiation, to find ideal treatment conditions with relatively high fluence for skin rejuvenation. A number of recent studies have evaluated the clinical efficacy and safety of therapeutic lasers under relatively low fluence conditions. We transmitted the long-pulsed 1064 nm Nd:YAG and 755 nm Alexandrite lasers into pig skin according to different fluences and spot diameters, and estimated epidermal/dermal temperatures. Pig skin specimens were stained with hematoxylin and eosin for histological assessments. The fluence conditions comprised 26, 30, and 36 J/cm2, and the spot diameter conditions were 5, 8, and 10 mm. Pulse duration was 30 ms for all experiments. Both lasers produced reliable thermal damage on the dermis without any serious epidermal injuries, under relatively high fluence conditions. The 1064 nm laser provided more active fibrous formations than the 755 nm laser, while higher risks for tissue damages simultaneously occurred. The ideal treatment conditions for skin rejuvenation were 8 mm diameter with 30 J/cm2 and 10 mm diameter with 26 J/cm2 for the 1064 nm laser, and 8 mm diameter with 36 J/cm2 and 10 mm diameter with 26 J/cm2 for the 755 nm laser.

Using synchrotron X-ray phase-contrast micro-computed tomography to study tissue damage by laser irradiation.

PubMed

Robinson, Alan M; Stock, Stuart R; Soriano, Carmen; Xiao, Xianghui; Richter, Claus-Peter

2016-11-01

The aim of this study was to determine if X-ray micro-computed tomography could be used to locate and characterize tissue damage caused by laser irradiation and to describe its advantages over classical histology for this application. A surgical CO 2 laser, operated in single pulse mode (100 milliseconds) at different power settings, was used to ablate different types of cadaveric animal tissues. Tissue samples were then harvested and imaged with synchrotron X-ray phase-contrast and micro-computed tomography to generate stacks of virtual sections of the tissues. Subsequently, Fiji (ImageJ) software was used to locate tissue damage, then to quantify volumes of laser ablation cones and thermal coagulation damage from 3D renderings of tissue image stacks. Visual comparisons of tissue structures in X-ray images with those visible by classic light microscopy histology were made. We demonstrated that micro-computed tomography could be used to rapidly identify areas of surgical laser ablation, vacuolization, carbonization, and thermally coagulated tissue. Quantification and comparison of the ablation crater, which represents the volume of ablated tissue, and the thermal coagulation zone volumes were performed faster than we could by classical histology. We demonstrated that these procedures can be performed on fresh hydrated and non-sectioned plastic embedded tissue. We demonstrated that the application of non-destructive micro-computed tomography to the visualization and analysis of laser induced tissue damage without tissue sectioning is possible. This will improve evaluation of new surgical lasers and their corresponding effect on tissues. Lasers Surg. Med. 48:866-877, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

NADH fluorescence imaging and the histological impact of cortical spreading depolarization during the acute phase of subarachnoid hemorrhage in rats.

PubMed

Shimizu, Tomohisa; Hishikawa, Tomohito; Nishihiro, Shingo; Shinji, Yukei; Takasugi, Yuji; Haruma, Jun; Hiramatsu, Masafumi; Kawase, Hirokazu; Sato, Sachiko; Mizoue, Ryoichi; Takeda, Yoshimasa; Sugiu, Kenji; Morimatsu, Hiroshi; Date, Isao

2018-01-01

OBJECTIVE Although cortical spreading depolarization (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH) in clinical settings, the pathogenicity of CSD is unclear. The aim of this study is to elucidate the effects of loss of membrane potential on neuronal damage during the acute phase of SAH. METHODS Twenty-four rats were subjected to SAH by the perforation method. The propagation of depolarization in the brain cortex was examined by using electrodes to monitor 2 direct-current (DC) potentials and obtaining NADH (reduced nicotinamide adenine dinucleotide) fluorescence images while exposing the parietal-temporal cortex to ultraviolet light. Cerebral blood flow (CBF) was monitored in the vicinity of the lateral electrode. Twenty-four hours after onset of SAH, histological damage was evaluated at the DC potential recording sites. RESULTS Changes in DC potentials (n = 48 in total) were sorted into 3 types according to the appearance of ischemic depolarization in the entire hemisphere following induction of SAH. In Type 1 changes (n = 21), ischemic depolarization was not observed during a 1-hour observation period. In Type 2 changes (n = 13), the DC potential demonstrated ischemic depolarization on initiation of SAH and recovered 80% from the maximal DC deflection during a 1-hour observation period (33.3 ± 15.8 minutes). In Type 3 changes (n = 14), the DC potential displayed ischemic depolarization and did not recover during a 1-hour observation period. Histological evaluations at DC potential recording sites showed intact tissue at all sites in the Type 1 group, whereas in the Type 2 and Type 3 groups neuronal damage of varying severity was observed depending on the duration of ischemic depolarization. The duration of depolarization that causes injury to 50% of neurons (P 50 ) was estimated to be 22.4 minutes (95% confidence intervals 17.0-30.3 minutes). CSD was observed in 3 rats at 6 sites in the Type 1 group 5.1 ± 2.2 minutes after initiation of SAH. On NADH fluorescence images CSD was initially observed in the anterior cortex; it propagated through the entire hemisphere in the direction of the occipital cortex at a rate of 3 mm/minute, with repolarization in 2.3 ± 1.2 minutes. DC potential recording sites that had undergone CSD were found to have intact tissue 24 hours later. Compared with depolarization that caused 50% neuronal damage, the duration of CSD was too short to cause histological damage. CONCLUSIONS CSD was successfully visualized using NADH fluorescence. It propagated from the anterior to the posterior cortex along with an increase in CBF. The duration of depolarization in CSD (2.3 ± 1.2 minutes) was far shorter than that causing 50% neuronal damage (22.4 minutes) and was not associated with histological damage in the current experimental setting.

Association of office-based frailty score with hypertensive end organ damage in the J-SHIPP cross-sectional study.

PubMed

Tabara, Yasuharu; Kohara, Katsuhiko; Ochi, Masayuki; Okada, Yoko; Ohara, Maya; Nagai, Tokihisa; Igase, Michiya

2016-08-01

Frailty, a geriatric syndrome reflecting a state of reduced physiological reserve and increased vulnerability, is an independent risk factor for cardiovascular morbidity and mortality. However, the relationship between frailty and hypertensive end-organ damage is not fully established. We performed a cross-sectional study to investigate the association between frailty and end-organ damage in 1125 apparently healthy middle-aged to elderly subjects. We performed a simple frailty (SF) score that was easily obtainable in the office, in combination with low hand grip power and short one-leg standing (OLS) time. The association between SF score and hypertensive end-organ damage and other frailty-related parameters was evaluated. Odds ratio of SF score 1 to score 0 for the presence of hypertension was 1.9 [1.4-2.5, p<.0001] and that of SF score 2 was 3.3 [2.1-5.3, p<.0001]. SF score was also significantly associated with brachial-ankle pulse wave velocity (baPWV) and central pulse pressure (PP2). SF score was significantly associated with higher frailty index calculated from 21 parameters, lower cognitive test score, % vital capacity, skeletal muscle mass, and thigh muscle cross-sectional area. SF score was positively associated with stage of brain white matter hyperintenisty, plasma levels of B-type natriuretic peptide, and urinary protein excretion, even after correction for confounding parameters including baPWV and PP2. These findings indicate that frailty is significantly associated with end-organ damage in elderly subjects. SF score may be a useful clinical tool to identify frail subjects and advanced end-organ damage in elderly subjects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position.

PubMed

Fioretto, José Roberto; Klefens, Susiane Oliveira; Pires, Rafaelle Fernandes; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; Bonatto, Rossano César; Moraes, Marcos Aurélio; Ronchi, Carlos Fernando

2017-01-01

To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation.

Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position

PubMed Central

Fioretto, José Roberto; Klefens, Susiane Oliveira; Pires, Rafaelle Fernandes; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; Bonatto, Rossano César; Moraes, Marcos Aurélio; Ronchi, Carlos Fernando

2017-01-01

Objective To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Methods Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Results Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. Conclusion High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation. PMID:29236845

The effects of high-dose methotrexate on the development of cartilage lesions in a lapine model of osteoarthrosis.

PubMed

Neidel, J; Schroers, B; Sintermann, F

1998-01-01

To determine whether systemic administration of methotrexate (MTX) can prevent joint destruction in experimental osteoarthrosis (OA) in rabbits, the disorder was induced unilaterally in the knee joints of 40 rabbits by partial medial meniscectomy and sectioning of the medial collateral and both cruciate ligaments. A sham operation (arthrotomy only) was performed in another four animals. Effects on the cartilage of the femoral condyles were studied after 6 and 12 weeks. Twelve weeks after induction, femoral and tibial osteophyte formation was demonstrated on radiographs in all cases. Marked cartilage damage was found histologically (median Mankin score 10 vs 1 for non-operated controls; P < 0.05, Wilcoxon test). Cartilage proteoglycan (GAG) content (dye binding assay) was reduced in operated joints [63 +/- 8 (mean +/- SEM) vs 75 +/- 6 micrograms chondroitin sulfate/mg cartilage wet weight], and the leukocyte count in the joints was elevated (226 +/- 14 vs 7 +/- 3 leukocytes per microliter joint aspirate after injection of 0.5 ml saline solution; both P < 0.05, Wilcoxon test). The rate of GAG synthesis was unchanged (ex vivo labelling with 35S-sulfate). Treatment with MTX (30 mg x kg body weight-1 x week-1 i.m., starting 12 h postoperatively) reduced cartilage damage (median Mankin score 8 vs 10 for placebo, P < 0.05, Mann-Whitney U-test), but had no significant effect on the other parameters tested. No significant MTX effects were observed on cartilage from nonoperated joints. Our data indicate that MTX may have a limited therapeutic effect in experimental OA in the rabbit.

Magnetic resonance imaging detection of multiple ischemic injury produced in an adult rat model of minor stroke followed by mild transient cerebral ischemia.

PubMed

Tuor, Ursula I; Qiao, Min

2017-04-01

To determine whether cumulative brain damage produced adjacent to a minor stroke that is followed by a mild transient ischemia is detectable with MRI and histology, and whether acute or chronic recovery between insults influences this damage. A minor photothrombotic (PT) stroke was followed acutely (1-2 days) or chronically (7 days) by a mild transient middle cerebral artery occlusion (tMCAO). MRI was performed after each insult, followed by final histology. The initial PT produced small hyperintense T 2 and DW infarct lesions and peri-lesion regions of scattered necrosis and modestly increased T 2 . Following tMCAO, in a slice and a region adjacent to the PT, a region of T 2 augmentation was observed when recovery between insults was acute but not chronic. Within the PT slice, a modest region of exacerbated T 2 change proximate to the PT was also observed in the chronic group. Corresponding histological changes within regions of augmented T 2 included increased vacuolation and cell death. Within regions adjacent to an experimental minor stroke, a recurrence of a mild transient cerebral ischemia augmented T 2 above increases produced by tMCAO alone, reflecting increased damage in this region. Exacerbation appeared broader with acute versus chronic recovery between insults.

Chemical changes demonstrated in cartilage by synchrotron infrared microspectroscopy in an antibody-induced murine model of rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Croxford, Allyson M.; Selva Nandakumar, Kutty; Holmdahl, Rikard; Tobin, Mark J.; McNaughton, Don; Rowley, Merrill J.

2011-06-01

Collagen antibody-induced arthritis develops in mice following passive transfer of monoclonal antibodies (mAbs) to type II collagen (CII) and is attributed to effects of proinflammatory immune complexes, but transferred mAbs may react directly and damagingly with CII. To determine whether such mAbs cause cartilage damage in vivo in the absence of inflammation, mice lacking complement factor 5 that do not develop joint inflammation were injected intravenously with two arthritogenic mAbs to CII, M2139 and CIIC1. Paws were collected at day 3, decalcified, paraffin embedded, and 5-μm sections were examined using standard histology and synchrotron Fourier-transform infrared microspectroscopy (FTIRM). None of the mice injected with mAb showed visual or histological evidence of inflammation but there were histological changes in the articular cartilage including loss of proteoglycan and altered chondrocyte morphology. Findings using FTIRM at high lateral resolution revealed loss of collagen and the appearance of a new peak at 1635 cm-1 at the surface of the cartilage interpreted as cellular activation. Thus, we demonstrate the utility of synchrotron FTIRM for examining chemical changes in diseased cartilage at the microscopic level and establish that arthritogenic mAbs to CII do cause cartilage damage in vivo in the absence of inflammation.

Investigating histological aspects of scars in children.

PubMed

Westra, I; Verhaegen, P D H M; Ibrahim Korkmaz, H; Braam, K I; Kaspers, G J L; Niessen, H W M; Niessen, F B

2017-05-02

Very little is known about histological aspects of paediatric scars and the possible role of the immune system during their formation. In this study, the histology thoracic scars caused by the placement of an implantable central venous access device in children who underwent treatment for cancer was assessed. The amount and type of collagen, the collagen orientation, the type of elastic fibres, the vascularsation, and the count of neutrophils, macrophages, and lymphocytes were analysed. The severity of scarring was assessed using the Vancouver scar scale (VSS). To evaluate the role of the immune system on scar severity and histology, the scars of children suffering from acute lymphoblastic leukaemia (ALL) were compared with the scars of children suffering from other types of childhood cancer. Our results showed an extremely random orientation of the collagen fibres of the paediatric scars with a mean collagen orientation index of 0.22 (standard deviation (SD) 0.10, zero indicating a perfectly random orientation and a perfectly parallel orientation). A lower collagen orientation index was seen in scars with a lower VSS score (VSS score <3: 0.19 versus VSS score ≥3 0.29, p=0.037). A higher total VSS score, resembling a worse scar, was assessed to the scars in the non-ALL group compared with the children with ALL (mean ALL: 0.91 (0-3) versus mean non-ALL: 2.50 (0-6), p=0.037). To our knowledge, this is the first study investigating a wide array of histological aspects in paediatric scars. Compared with adult scars, an extremely random collagen orientation was found (0.22 in children versus 0.41 and 0.46 adult normotrophic and hypertrophic scars, respectively). A lower collagen orientation index was found in scars with a lower VSS score. In addition, less severe scarring was measured in children suffering from ALL compared with children suffering from other types of childhood cancer. This suggests that the immune system could play a role in the development of aberrant scarring and should be a target for future research.

A chicken intestinal ligated loop model to study the virulence of Clostridium perfringens isolates recovered from antibiotic-free chicken flocks.

PubMed

Parent, Eric; Archambault, Marie; Charlebois, Audrey; Bernier-Lachance, Jocelyn; Boulianne, Martine

2017-04-01

Necrotic enteritis (NE) is a major problem in antibiotic-free (ABF) chicken flocks and specific strains of Clostridium perfringens are known to induce NE. The objective of this study was to develop a chicken intestinal ligated loop model in order to compare the virulence of various C. perfringens strains recovered from consecutive ABF flocks with and without NE. Intestinal loops were surgically prepared in 10 anaesthetized specific-pathogen-free chickens and alternately inoculated with C. perfringens isolates or brain heart infusion (BHI) media. Histological lesion scoring was performed for each loop. All strains from NE-affected flocks induced histological lesions compatible with NE whereas inoculation of loops with a commensal C. perfringens strain or BHI did not. Among inoculated strains, CP0994 (netB-positive and cpb2-positive) and CP-2003-1256 (netB-positive) demonstrated mean histological lesion scores significantly higher (P < 0.01) than those obtained with a commensal strain or BHI whereas strain CP1073 (netB-negative and cpb2-positive) induced intestinal lesions without significantly higher scores. In loops where villi were colonized by Gram-positive rods, significantly higher (P < 0.01) mean histological lesion scores were observed. This result supports the hypothesis that colonization of the intestinal mucosa by C. perfringens is a critical step in the pathogenesis of NE. Finally, we demonstrated the importance of controlling virulent C. perfringens strains in ABF chicken flocks as a highly virulent strain can be present in consecutive flocks with NE and possibly affect multiple flocks.

Adenocarcinoma predominant pattern subtyping and nuclear grading in cytology: Is there a role in prognostication of advanced pulmonary adenocarcinomas?

PubMed

Nambirajan, A; Kaur, H; Jangra, K; Kaur, K; Madan, K; Mathur, S R; Iyer, V K; Jain, D

2018-04-01

Primary lung adenocarcinomas (ADs) show varied architectural patterns, and pattern-based subtyping of ADs is currently recommended due to prognostic implications. Predicting AD patterns on cytology is challenging; however, cytological nuclear features appear to correlate with histological grade and survival in early stage lung ADs. The feasibility and value of AD pattern prediction and nuclear grading on cytology in advanced lung ADs is not known. We aimed to predict patterns and analyse nuclear features on cytology and evaluate their role in prognostication. One-hundred patients of Stage III/IV lung AD with available matched cytology and histology samples were included. Cyto-patterns based on cell arrangement patterns (flat sheets vs three-dimensional clusters vs papillae) and cyto-nuclear score based on nuclear features (size, shape, contour), nucleoli (macronucleoli vs prominent vs inconspicuous), and nuclear chromatin were determined, and correlated with predominant histological-pattern observed on the matched small biopsy and outcome. Higher cyto-nuclear scores were observed with high-grade histo-patterns (solid, micropapillary and cribriform), while the predicted cyto-patterns did not correspond to the predominant pattern on histology in 77% cases. Highest cyto-histo agreement was observed for solid pattern (72%). High grade histo-patterns and cyto-nuclear scores > 3 showed a trend towards inferior survival (not significant). Nuclear grade scoring on cytology is simple to perform, and is predictive of high grade patterns. Its inclusion in routine reporting of cytology samples of lung ADs may be valuable. © 2018 John Wiley & Sons Ltd.

Suppression of dextran sulfate sodium-induced colitis in mice by radon inhalation.

PubMed

Nishiyama, Yuichi; Kataoka, Takahiro; Yamato, Keiko; Taguchi, Takehito; Yamaoka, Kiyonori

2012-01-01

The enhanced release of reactive oxygen species from activated neutrophils plays important role in the pathogenesis of inflammatory bowel disease. We previously reported that radon inhalation activates antioxidative functions in various organs of mice. In this study, we examined the protective effects of radon inhalation on dextran sulfate sodium- (DSS) induced colitis in mice which were subjected to DSS for 7 days. Mice were continuously treated with air only (sham) or radon at a concentration of 2000 Bq/m³ from a day before DSS administration to the end of colitis induction. In the results, radon inhalation suppressed the elevation of the disease activity index score and histological damage score induced by DSS. Based on the changes in tumor necrosis factor-alpha in plasma and myeloperoxidase activity in the colon, it was shown that radon inhalation suppressed DSS-induced colonic inflammation. Moreover, radon inhalation suppressed lipid peroxidation of the colon induced by DSS. The antioxidant level (superoxide dismutase and total glutathione) in the colon after DSS administration was significantly higher in mice treated with radon than with the sham. These results suggested that radon inhalation suppressed DSS-induced colitis through the enhancement of antioxidative functions in the colon.

Suppression of Dextran Sulfate Sodium-Induced Colitis in Mice by Radon Inhalation

PubMed Central

Nishiyama, Yuichi; Kataoka, Takahiro; Yamato, Keiko; Taguchi, Takehito; Yamaoka, Kiyonori

2012-01-01

The enhanced release of reactive oxygen species from activated neutrophils plays important role in the pathogenesis of inflammatory bowel disease. We previously reported that radon inhalation activates antioxidative functions in various organs of mice. In this study, we examined the protective effects of radon inhalation on dextran sulfate sodium- (DSS) induced colitis in mice which were subjected to DSS for 7 days. Mice were continuously treated with air only (sham) or radon at a concentration of 2000 Bq/m3 from a day before DSS administration to the end of colitis induction. In the results, radon inhalation suppressed the elevation of the disease activity index score and histological damage score induced by DSS. Based on the changes in tumor necrosis factor-alpha in plasma and myeloperoxidase activity in the colon, it was shown that radon inhalation suppressed DSS-induced colonic inflammation. Moreover, radon inhalation suppressed lipid peroxidation of the colon induced by DSS. The antioxidant level (superoxide dismutase and total glutathione) in the colon after DSS administration was significantly higher in mice treated with radon than with the sham. These results suggested that radon inhalation suppressed DSS-induced colitis through the enhancement of antioxidative functions in the colon. PMID:23365486

Acute damage threshold for infrared neural stimulation of the cochlea: functional and histological evaluation.

PubMed

Goyal, Vinay; Rajguru, Suhrud; Matic, Agnella I; Stock, Stuart R; Richter, Claus-Peter

2012-11-01

This article provides a mini review of the current state of infrared neural stimulation (INS), and new experimental results concerning INS damage thresholds. INS promises to be an attractive alternative for neural interfaces. With this method, one can attain spatially selective neural stimulation that is not possible with electrical stimulation. INS is based on the delivery of short laser pulses that result in a transient temperature increase in the tissue and depolarize the neurons. At a high stimulation rate and/or high pulse energy, the method bears the risk of thermal damage to the tissue from the instantaneous temperature increase or from potential accumulation of thermal energy. With the present study, we determined the injury thresholds in guinea pig cochleae for acute INS using functional measurements (compound action potentials) and histological evaluation. The selected laser parameters for INS were the wavelength (λ = 1,869 nm), the pulse duration (100 μs), the pulse repetition rate (250 Hz), and the radiant energy (0-127 μJ/pulse). For up to 5 hr of continuous irradiation at 250 Hz and at radiant energies up to 25 μJ/pulse, we did not observe any functional or histological damage in the cochlea. Functional loss was observed for energies above 25 μJ/pulse and the probability of injury to the target tissue resulting in functional loss increased with increasing radiant energy. Corresponding cochlear histology from control animals and animals exposed to 98 or 127 μJ/pulse at 250 Hz pulse repetition rate did not show a loss of spiral ganglion cells, hair cells, or other soft tissue structures of the organ of Corti. Light microscopy did not reveal any structural changes in the soft tissue either. Additionally, microcomputed tomography was used to visualize the placement of the optical fiber within the cochlea. Copyright © 2012 Wiley Periodicals, Inc.

Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced lung injury.

PubMed

Lange, Matthias; Cox, Robert A; Enkhbaatar, Perenlei; Whorton, Elbert B; Nakano, Yoshimitsu; Hamahata, Atsumori; Jonkam, Collette; Esechie, Aimalohi; von Borzyskowski, Sanna; Traber, Lillian D; Traber, Daniel L

2011-05-01

Inhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, lung lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, lung lymph flow, and lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.

Systematic review with meta-analysis: the significance of histological disease severity in lean patients with nonalcoholic fatty liver disease.

PubMed

Sookoian, S; Pirola, C J

2018-01-01

Current evidence suggests that lean and obese patients with nonalcoholic fatty liver disease (NAFLD) share an altered metabolic and cardiovascular profile. However, there is an incomplete understanding of the natural history of "lean-NAFLD." Indeed, an unanswered question is whether lean (BMI ≤ 25 Kg/m 2 ) NAFLD-patients are protected from severe histological outcomes. To perform a meta-analysis with the goal of providing a quantitative estimation of the magnitude of fibrosis, as well as histological features associated with the disease severity, in lean versus overweight/obese-NAFLD patients. Through a systematic search up to July 2017, we identified eight studies that compared histological outcomes in lean (n = 493) versus overweight/obese (n = 2209) patients. Relative to lean-NAFLD, overweight/obese-NAFLD patients showed significantly (P = .032) higher fibrosis scores; the observed difference in means between the two groups, which is the absolute difference between the mean value of fibrosis score [0-4] ± standard error, was 0.28 ± 0.13. The risk of having nonalcoholic steatohepatitis-NASH (OR 0.58 95% CI 0.34-0.97) was significantly lower in lean-NAFLD (n = 322) than in overweight/obese-NAFLD (n = 1357), P = .04. Relative to lean-NAFLD, overweight/obese-NAFLD patients also have significantly greater NAFLD activity (difference in means ± SE: 0.58 ± 0.16, P = .0004) and steatosis (difference in means ± SE: 0.23 ± 0.07, P = .002) scores. Lean-NAFLD patients tend to show less severe histological features as compared to overweight/obese-NAFLD patients. Subsequent longitudinal assessment is needed to understand the clinical impact of these findings; however, the significant ~ 25% increment of mean fibrosis score in overweight/obese patients suggests that obesity could predict a worse long-term prognosis. © 2017 John Wiley & Sons Ltd.

Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology.

PubMed

Sánchez, Mikel; Anitua, Eduardo; Azofra, Juan; Prado, Roberto; Muruzabal, Francisco; Andia, Isabel

2010-04-01

To investigate whether the application of a particular platelet-rich plasma preparation rich in growth factors (PRGF) during anterior cruciate ligament (ACL) surgery gives a potential advantage for better tendon graft ligamentization. This study included 37 volunteers who underwent either conventional (control group, n = 15) or PRGF-assisted (n = 22) ACL reconstruction with an autogenous hamstring and required second-look arthroscopy to remove hardware or loose bodies, treat meniscal tears or plica syndrome, or resect cyclops lesions at 6 to 24 months after ACL surgery. The gross morphologies of the grafts were evaluated on second-look arthroscopy by use of the full arthroscopic score (0 to 4 points) to evaluate graft thickness and apparent tension (0 to 2 points) plus synovial coverage (0 to 2 points). At the same time, biopsy specimens were harvested uniformly from the grafted tendons. In these specimens the histologic transformation of the tendon graft to ACL-like tissue was evaluated by use of the Ligament Tissue Maturity Index, and a score to assess the progression of new connective tissue enveloping the graft was created by use of 3 criteria previously used to characterize changes during ligament healing: cellularity, vascularity, and collagen properties. The overall arthroscopic evaluation of PRGF-treated grafts showed an excellent rating in 57.1% of the knees (score of 4) and a fair rating in 42.9% (score of 2 or 3). In contrast, evaluation of untreated grafts showed an excellent rating in 33.3% of the knees, a fair rating in 46.7%, and a poor rating in 20% (score of 0 or 1). Overall, arthroscopic evaluations were not statistically different between PRGF and control groups (P = .051). PRGF treatment influenced the histologic characteristics of the tendon graft, resulting in tissue that was more mature than in controls (P = .024). Histologically evident newly formed connective tissue enveloping the graft was present in 77.3% of PRGF-treated grafts and 40% of controls. The appearance of the connective tissue envelope changed with increasing time from surgery. On the basis of the histologic findings, we suggest that the remodeling of PRGF-treated grafts involves the formation of synovial-like tissue enveloping the graft. This tissue is eventually integrated in the remodeled tendon graft, conferring a similar appearance to the normal ACL. The use of PRGF influenced the histologic characteristics of tendon grafts, resulting in more remodeling compared with untreated grafts. We have shown temporal histologic changes during the 6- to 24-month postoperative period of graft maturation, with newly formed connective tissue enveloping most grafts treated with PRGF. Level III, case-control study. Copyright 2010 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery.

PubMed

Kockelkoren, Remko; Vos, Annelotte; Van Hecke, Wim; Vink, Aryan; Bleys, Ronald L A W; Verdoorn, Daphne; Mali, Willem P Th M; Hendrikse, Jeroen; Koek, Huiberdina L; de Jong, Pim A; De Vis, Jill B

2017-01-01

Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. First, CT features of the score were circularity (absent, dot(s), <90°, 90-270° or 270-360°), thickness (absent, ≥1.5mm, or <1.5mm), and morphology (indistinguishable, irregular/patchy or continuous). A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification.

[Evaluation of sphincter damage degree with anal endosonography for children with fecal incontinence].

PubMed

Sun, Xiaobing; Li, Dianguo; Wang, Ruoyi; Sun, Xiaogang; Liu, Qian

2014-03-01

To evaluate the application of anal endosonography in the morphology of internal anal sphincter (IAS), external anal sphincter (EAS) and puborectalis (PR) in order to provide necessary information for analysis of the etiology of fecal incontinence and formulation of the therapeutic schedule. From December 2010 to November 2012, 18 children of anorectal malformation (n=14) or Hirschsprung's disease(n=4) with fecal incontinence received anal endosonography. The morphology of IAS, EAS and PR was observed. The damage of anal sphincter was classified according to Starck criteria. Anorectal mamometry and anal clinical score were measured simultaneously. Spearman analysis was performed to examine the correlation of anal sphincter damage with anorectal mamometric score and anal clinical score. According to Starck criteria, anal sphincter damage was small in 11 children, moderate in 6, and severe in 1. PR damage was found in 4 cases. Starck score was positively correlated with manometric score(P<0.05), while not correlated with anal clinical score(P>0.05). Anal endosonography can clearly display the morphology of IAS, EAS and PR, and their integrity and damage degree. It is a very valuable technique to evaluate the anal sphincter of the children with fecal incontinence, which however can not reflect the function of anal sphincter and anal continence thoroughly.

Exsanguination cardiac arrest in rats treated by 60 min, but not 75 min, emergency preservation and delayed resuscitation is associated with intact outcome.

PubMed

Drabek, Tomas; Stezoski, Jason; Garman, Robert H; Han, Fei; Henchir, Jeremy; Tisherman, Samuel A; Stezoski, S William; Kochanek, Patrick M

2007-10-01

Emergency preservation and resuscitation (EPR) is a new approach for resuscitation of exsanguination cardiac arrest (CA) victims to buy time for surgical hemostasis. EPR uses a cold aortic flush to induce deep hypothermic preservation, followed by resuscitation with cardiopulmonary bypass (CPB). We previously reported that 20 min of EPR was feasible with intact outcome. In this report, we tested the limits for EPR in rats. Adult male isoflurane-anesthetized rats were subjected to rapid hemorrhage (12.5 ml over 5 min), followed by esmolol/KCl-induced CA and 1 min of no-flow. EPR was then induced by perfusion with 270 ml of ice-cold Plasma-Lyte to decrease body temperature to 15 degrees C. After 60 min (n=7) or 75 min (n=7) of EPR, resuscitation was attempted with CPB over 60 min, blood transfusion, correction of acid-base balance and electrolyte disturbances, and mechanical ventilation for 2h. Survival, overall performance category (OPC: 1=normal, 5=death), neurological deficit score (NDS), and histological damage score (HDS) were assessed in survivors on day 3. While all rats after 60 min EPR survived, only two out of seven rats after 75 min EPR survived (p<0.05). All rats after 60 min EPR achieved OPC 1 and normal NDS by day 3. Survivors after 75 min EPR achieved best OPC 3 (p<0.05 vs. 60 min EPR). HDS of either brain or individual viscera was not statistically different after 60 versus 75 min EPR, except for kidneys (0+/-0 vs. 1.9+/-1.3, respectively; p<0.05), with a strong trend toward greater injury in all extracerebral organs in the 75-min EPR group (p<0.06). Histological findings were dominated by cardiac lesions observed in both groups and acute renal tubular and liver necrosis in the 75-min EPR group. In conclusion, we have shown that 60 min of EPR after exsanguination CA is associated with survival and favorable neurological outcome, while 75 min of EPR results in significant mortality and neurological damage in survivors. Surprisingly, extracerebral lesions predominated at 75-min EPR group. This model should serve as a screening model both for testing new pharmacological adjuncts to improve survival after exsanguination CA, and for elucidating the underlying mechanisms of ischemia/reperfusion injury.

Selective retinal therapy with a continuous line scanning laser

NASA Astrophysics Data System (ADS)

Paulus, Yannis M.; Jain, ATul; Gariano, Ray F.; Nomoto, Hiroyuki; Schuele, Georg; Sramek, Christopher; Charalel, Resmi; Palanker, Daniel

2010-02-01

This study evaluates the effects of exposure duration, beam diameter, and power on the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser. A 532 nm laser (PASCALTM) with retinal beam diameters of 40 and 66 μm was applied to 60 eyes of 30 Dutch-Belted rabbits. Retinal exposure duration varied from 15 to 60 μs. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography (FA). RPE flatmounts were evaluated with live-dead fluorescent assay (LD). Histological analysis was performed at 1 hour, 1 and 3 days, 1 and 2 weeks, and 1 and 2 months following laser treatment. Ophthalmoscopic visibility (OV) of the lesions corresponded to photoreceptor damage on histological analysis at 1 hour. In subvisible lesions, FA and LD yielded similar thresholds of RPE damage. The ratios of the threshold of rupture and of OV to FA visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Above the threshold of OV, histology showed focal RPE damage and photoreceptor loss at one day without inner retinal effects. By one week, continuity of photoreceptor and RPE layers was restored. By 1 month, photoreceptors appeared normal while hypertrophy and hyperpigmentation of the RPE persisted. Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors. The damage zone in the photoreceptor layer is quickly filled-in, likely due to photoreceptor migration from adjacent zones. Continuous scanning laser can treat large retinal areas within standard eye fixation time.

Comparison of Epidermal/Dermal Damage Between the Long-Pulsed 1064 nm Nd:YAG and 755 nm Alexandrite Lasers Under Relatively High Fluence Conditions: Quantitative and Histological Assessments

PubMed Central

Lee, Ju Hwan; Park, So Ra; Jo, Jeong Ho; Park, Sung Yun; Seo, Young Kwon

2014-01-01

Abstract Objective: The purpose of this study was to compare degrees of epidermal/dermal tissue damage quantitatively and histologically after laser irradiation, to find ideal treatment conditions with relatively high fluence for skin rejuvenation. Background data: A number of recent studies have evaluated the clinical efficacy and safety of therapeutic lasers under relatively low fluence conditions. Methods: We transmitted the long-pulsed 1064 nm Nd:YAG and 755 nm Alexandrite lasers into pig skin according to different fluences and spot diameters, and estimated epidermal/dermal temperatures. Pig skin specimens were stained with hematoxylin and eosin for histological assessments. The fluence conditions comprised 26, 30, and 36 J/cm2, and the spot diameter conditions were 5, 8, and 10 mm. Pulse duration was 30 ms for all experiments. Results: Both lasers produced reliable thermal damage on the dermis without any serious epidermal injuries, under relatively high fluence conditions. The 1064 nm laser provided more active fibrous formations than the 755 nm laser, while higher risks for tissue damages simultaneously occurred. Conclusions: The ideal treatment conditions for skin rejuvenation were 8 mm diameter with 30 J/cm2 and 10 mm diameter with 26 J/cm2 for the 1064 nm laser, and 8 mm diameter with 36 J/cm2 and 10 mm diameter with 26 J/cm2 for the 755 nm laser. PMID:24992273

Histologic scoring of gastritis and gastric cancer in mouse models.

PubMed

Rogers, Arlin B

2012-01-01

Histopathology is a defining endpoint in mouse models of experimental gastritis and gastric adenocarcinoma. Presented here is an overview of the histology of gastritis and gastric cancer in mice experimentally infected with Helicobacter pylori or H. felis. A modular histopathologic scoring scheme is provided that incorporates relevant disease-associated changes. Whereas the guide uses Helicobacter infection as the prototype challenge, features may be applied to chemical and genetically engineered mouse models of stomach cancer as well. Specific criteria included in the combined gastric histologic activity index (HAI) include inflammation, epithelial defects, oxyntic atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia or neoplasia. Representative photomicrographs accompany descriptions for each lesion grade. Differentiation of genuine tumor invasion from pseudoinvasion is highlighted. A brief comparison of normal rodent versus human stomach anatomy and physiology is accompanied by an introduction to mouse-specific lesions including mucous metaplasia and eosinophilic droplets (hyalinosis). In conjunction with qualified pathology support, this guide is intended to assist research scientists, postdoctoral fellows, graduate students, and medical professionals from affiliated disciplines in the interpretation and histologic grading of chronic gastritis and gastric carcinoma in mouse models.

Sex Difference in Susceptibility and Resistance to Noise-Induced Hearing Loss in Chinchillas

DTIC Science & Technology

2000-10-01

Estradiol assays Blood samples were collected from deeply anesthetized chinchillas prior to cochlear histology. The blood samples were centrifuged to...pattern of hearing loss and cochlear damage for male and female chinchillas Gender differences have been reported in susceptibility to NIHL, both...Given the results of physiological testing (IC-EVPs and CDPs), the results of cochlear histology were somewhat surprising (see McFadden et al., 1999

Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis.

PubMed

Lin, Runhua; Zhang, Chong; Zheng, Jiaxuan; Tian, Dongping; Lei, Zhijin; Chen, Donglin; Xu, Zexin; Su, Min

2016-04-26

Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis.

Exploring cartilage damage in gout using 3-T MRI: distribution and associations with joint inflammation and tophus deposition.

PubMed

Popovich, I; Dalbeth, N; Doyle, A; Reeves, Q; McQueen, F M

2014-07-01

Few imaging studies have investigated cartilage in gout. Magnetic resonance imaging (MRI) can image cartilage damage and also reveals other features of gouty arthropathy. The objective was to develop and validate a system for quantifying cartilage damage in gout. 3-T MRI scans of the wrist were obtained in 40 gout patients. MRI cartilage damage was quantified using an adaptation of the radiographic Sharp van der Heijde score. Two readers scored cartilage loss at 7 wrist joints: 0 (normal), 1 (partial narrowing), 2 (complete narrowing) and concomitant osteoarthritis was recorded. Bone erosion, bone oedema and synovitis were scored (RAMRIS) and tophi were assessed. Correlations between radiographic and MRI cartilage scores were investigated, as was the reliability of the MRI cartilage score and its associations. The GOut MRI Cartilage Score (GOMRICS) was highly correlated with the total Sharp van der Heijde (SvdH) score and the joint space narrowing component (R = 0.8 and 0.71 respectively, p < 0.001). Reliability was high (intraobserver, interobserver ICCs = 0.87 [0.57-0.97], 0.64 [0.41-0.79] respectively), and improved on unenhanced scans; interobserver ICC = 0.82 [0.49-0.95]. Cartilage damage was predominantly focal (82% of lesions) and identified in 40 out of 280 (14%) of joints. Cartilage scores correlated with bone erosion (R = 0.57), tophus size (R = 0.52), and synovitis (R = 0.55), but not bone oedema scores. Magnetic resonance imaging can be used to investigate cartilage in gout. Cartilage damage was relatively uncommon, focal, and associated with bone erosions, tophi and synovitis, but not bone oedema. This emphasises the unique pathophysiology of gout.

Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis

PubMed Central

Milici, Anthony J; Kudlacz, Elizabeth M; Audoly, Laurent; Zwillich, Samuel; Changelian, Paul

2008-01-01

Introduction CP-690550 is a small molecule inhibitor of Janus kinase 3 (JAK3), a critical enzyme in the signaling pathway of multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are important in various T cell functions including development, activation and homeostasis. The purpose of this study was to evaluate CP-690550 in murine collagen-induced (CIA) and rat adjuvant-induced (AA) models of rheumatoid arthritis (RA). Methods CIA and AA were induced using standard protocols and animals received the JAK3 inhibitor via osmotic mini-pump infusion at doses ranging from 1.5–15 mg/kg/day following disease induction. Arthritis was assessed by clinical scores in the CIA models and paw swelling monitored using a plethysmometer in the AA model until study conclusion, at which time animals were killed and evaluated histologically. Results CP-690550 dose-dependently decreased endpoints of disease in both RA models with greater than 90% reduction observed at the highest administered dose. An approximate ED50 of approximately 1.5 mg/kg/day was determined for the compound based upon disease endpoints in both RA models examined and corresponds to CP-690550 serum levels of 5.8 ng/ml in mice (day 28) and 24 ng/ml in rats (day 24). The compound also reduced inflammatory cell influx and joint damage as measured histologically. Animals receiving a CP-690550 dose of 15 mg/k/d showed no histological evidence of disease. Conclusion The efficacy observed with CP-690550 in CIA and AA suggests JAK3 inhibition may represent a novel therapeutic target for the treatment of RA. PMID:18234077

Bisphenol A exposure and healing effects of Adiantum capillus-veneris L. plant extract (APE) in bisphenol A-induced reproductive toxicity in albino rats.

PubMed

Yousaf, Balal; Amina; Liu, Guijian; Wang, Ruwei; Qadir, Abdul; Ali, Muhammad Ubaid; Kanwal, Qudsia; Munir, Bushra; Asmatullah; Abbas, Zaigham

2016-06-01

The current study presents the bisphenol A exposure and the ameliorative effects of Adiantum capillus-veneris on testicular toxicity induced by bisphenol A. Adult male albino rats were divided into five groups of five animals each: A (control), B (vehicle control), C (toxic), D (protective), and E (ameliorative) were served distilled water, olive oil, bisphenol A (BPA) at 100 mg/kg body weight, A. capillus-veneris plant extract at 25 mg/kg body weight, and BPA + A. capillus-veneris, respectively. All of the doses were administered orally for 15 days, and the rats were then sacrificed. Blood samples for the testosterone assay and both testes were collected for histological examination. The body weight, paired testes weight, relative tissue weight index, Johnsen scoring of tubules, and level of serum testosterone decreased in BPA-treated rats. Similarly, histological examination of the testes in BPA-treated animals revealed a lower number of Leydig cells, an irregular basement membrane, sloughing of germinal layers, vacuolization, a lower number of spermatocytes, and debris in the lumen. However, co-administration of A. capillus-veneris with BPA increased the total antioxidative capacity (330.82 ± 22.46 μmol/mg protein) of the testes and restored the serum testosterone level (1.70 ng/ml); histological features showed restoration in the stages of spermatogenesis. Conclusively, A. capillus-veneris plant extract overcomes the estrogenic effects of BPA on the reproductive system of rats and protects rats' testes against BPA-induced injury/damage via an antioxidative mechanism that appears to be conciliated.

Use of a 3-Telsa magnet to perform delayed gadolinium-enhanced magnetic resonance imaging of the distal interphalangeal joint of horses with and without naturally occurring osteoarthritis.

PubMed

Bischofberger, Andrea S; Fürst, Anton E; Torgerson, Paul R; Carstens, Ann; Hilbe, Monika; Kircher, Patrick

2018-03-01

OBJECTIVE To characterize delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) features of healthy hyaline cartilage of the distal interphalangeal joint (DIPJ) of horses, to determine whether dGEMRIC can be used to differentiate various stages of naturally occurring osteoarthritis of the DIPJ, and to correlate relaxation times determined by dGEMRIC with the glycosaminoglycan concentration, water content, and macroscopic and histologic findings of hyaline cartilage of DIPJs with and without osteoarthritis. SAMPLE 1 cadaveric forelimb DIPJ from each of 12 adult warmblood horses. PROCEDURES T1-weighted cartilage relaxation times were obtained for predetermined sites of the DIPJ before (T1 preGd ) and after (T1 postGd ) intra-articular gadolinium administration. Corresponding cartilage sites underwent macroscopic, histologic, and immunohistochemical evaluation, and cartilage glycosaminoglycan concentration and water content were determined. Median T1 preGd and T1 postGd were correlated with macroscopic, histologic, and biochemical data. Mixed generalized linear models were created to evaluate the effects of cartilage site, articular surface, and macroscopic and histologic scores on relaxation times. RESULTS 122 cartilage specimens were analyzed. Median T1 postGd was lower than the median T1 preGd for normal and diseased cartilage. Both T1 preGd and T1 postGd were correlated with macroscopic and histologic scores, whereby T1 preGd increased and T1 postGd decreased as osteoarthritis progressed. There was topographic variation of T1 preGd and T1 postGd within the DIPJ. Cartilage glycosaminoglycan concentration and water content were significantly correlated with T1 preGd and macroscopic and histologic scores but were not correlated with T1 postGd . CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dGEMRIC relaxation times varied for DIPJs with various degrees of osteoarthritis. These findings may help facilitate early detection of osteoarthritis.

Simultaneous evaluation of lymphocyte subpopulations in the liver and in peripheral blood mononuclear cells of HCV-infected patients: relationship with histological lesions

PubMed Central

PERNOLLET, M; JOUVIN-MARCHE, E; LEROY, V; VIGAN, I; ZARSKI, J -P; MARCHE, P N

2002-01-01

Intrahepatic lymphocytes are believed to be involved in the immunopathogenesis of hepatitis C virus (HCV) infection and the evolution of HCV-induced hepatitis. In the present study, we examined the three main intrahepatic lymphocyte subsets, namely CD3+CD56− conventional T lymphocytes, CD3+CD56+ natural T (NT) lymphocytes and CD3−CD56+ natural killer (NK) lymphocytes in HCV-infected patients. The proportion of each lymphocyte subset was evaluated both in liver biopsies and in samples of peripheral blood lymphocytes (PBL) by flow cytometry in 21 patients with histologically proven chronic hepatitis C. Simultaneously, alanine aminotransferase (ALT) levels, viral load and histological lesions were assessed. Neither NT nor NK populations correlated with any biochemical, viral or histological parameters. Furthermore, Vα24+ NT lymphocytes showed no preferential enrichment in the liver of HCV-infected patients. Regarding conventional T lymphocytes, a highly significant linear correlation was found between intrahepatic CD3+CD56− T lymphocytes and the Knodell score, a numerical score for assessing histological activity and fibrosis (r = 0·715, P < 0·0001) and more specifically with the periportal necrosis parameter, which is the main lesion of chronic hepatitis C. In addition, analysis of the peripheral compartment revealed a high correlation between values of CD3+CD56− lymphocytes and both Knodell score (r = 0·624, P = 0·003) and serum ALT levels and again with periportal necrosis. The strong correlation between the proportion of peripheral CD3+CD56− conventional T lymphocytes and the severity of hepatic lesions leads us to propose that evaluation of this accessible peripheral population could be used as an indicator test for the severity of histological lesions in chronic hepatitis C. Abbreviations: PMID:12452844

Non-destructive electromechanical assessment (Arthro-BST) of human articular cartilage correlates with histological scores and biomechanical properties.

PubMed

Sim, S; Chevrier, A; Garon, M; Quenneville, E; Yaroshinsky, A; Hoemann, C D; Buschmann, M D

2014-11-01

The hand-held Arthro-BST™ device is used to map electromechanical properties of articular cartilage. The purpose of the study was to evaluate correlation of electromechanical properties with histological, biochemical and biomechanical properties of cartilage. Electromechanical properties (quantitative parameter (QP)) of eight human distal femurs were mapped manually ex vivo using the Arthro-BST (1 measure/site, 5 s/measure, 3209 sites). Osteochondral cores were then harvested from different areas on the femurs and assessed with the Mankin histological score. Prior to histoprocessing, cores were tested in unconfined compression. A subset of the cores was analyzed with polarized light microscopy (PLM) to assess collagen structure. Biochemical assays were done on additional cores to obtain water content and glycosaminoglycan (GAG) content. The QP corresponding to each core was calculated by averaging all QPs collected within 6 mm of the core center. The electromechanical QP correlated strongly with both the Mankin score and the PLM score (r = 0.73, P < 0.0001 and r = -0.70, P < 0.0001 respectively) thus accurately reflecting tissue quality and collagen architecture. Electromechanical QP also correlated strongly with biomechanical properties including fibril modulus (r = -0.76, P < 0.0001), matrix modulus (r = -0.69, P < 0.0001), and log of permeability (r = 0.72, P < 0.0001). The QP correlated weakly with GAG per wet weight and with water content (r = -0.50, P < 0.0003 and r = 0.39, P < 0.006 respectively). Non-destructive electromechanical QP measurements correlate strongly with histological scores and biomechanical parameters providing a rapid and reliable assessment of articular cartilage quality. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Influence of semi-quantitative oestrogen receptor expression on adjuvant endocrine therapy efficacy in ductal and lobular breast cancer - a TEAM study analysis.

PubMed

van de Water, Willemien; Fontein, Duveken B Y; van Nes, Johanna G H; Bartlett, John M S; Hille, Elysée T M; Putter, Hein; Robson, Tammy; Liefers, Gerrit-Jan; Roumen, Rudi M H; Seynaeve, Caroline; Dirix, Luc Y; Paridaens, Robert; Kranenbarg, Elma Meershoek-Klein; Nortier, Johan W R; van de Velde, Cornelis J H

2013-01-01

Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated. Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5 years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n=235); ER-rich (7; n=1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse. Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95%confidence interval (CI) 0.67-1.03)), and ILC (HR 0.69 (95%CI 0.45-1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95%CI 0.56-0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32-4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p=0.003). Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression. Copyright © 2012 Elsevier Ltd. All rights reserved.

The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney

PubMed Central

Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

2017-01-01

Objective: Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger (Zingiber officinale) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. Materials and Methods: The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Results: Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. Conclusion: In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron. PMID:29299437

The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney.

PubMed

Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

2017-01-01

Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger ( Zingiber officinale ) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron.

Distinct enzyme profiles in patients with cryptogenic cirrhosis reflect heterogeneous causes with different outcomes after liver transplantation (OLT): a long-term documentation before and after OLT.

PubMed

Berg, Thomas; Neuhaus, Ruth; Klein, Reinhild; Leder, Korinna; Lobeck, Hartmut; Bechstein, Wolf-Otto; Müller, Andrea R; Wiedenmann, Bertram; Hopf, Uwe; Berg, Peter A; Neuhaus, Peter

2002-09-27

Sound information is lacking about the clinical presentation of cryptogenic cirrhosis and its outcome after orthotopic liver transplantation (OLT). Among 856 patients who have been transplanted at our center, 40 patients had no evidence of any known etiologies and were therefore defined as suffering from cryptogenic cirrhosis. Their median follow-up period before OLT was 78 months (range, 1-264), and after OLT 97 months (range, 1-132). Laboratory and histological data were evaluated according to features being compatible either with a toxic, hepatitic, or cholestatic condition. The clinical and histological findings differed specifically between these three groups. The toxic-like group (GGT 4-18 x upper limit of normal [ULN]) expressed significantly higher IgA levels, had histologically more often fatty liver changes, and risk factors for non-alcoholic steatohepatitis predominated (56% compared with 3% in the other groups, P=0.01). The hepatitic-like group (ALT 2-18 x ULN) showed histologically features of chronic hepatitis or hepatitic cirrhosis, and only among these patients a median International Autoimmune Hepatitis (IAH) score of 13 was found suggesting autoimmune hepatitis (AiH). In the cholestatic group (AP 2-8 x ULN) histology was compatible with a non-toxic inflammatory process but IAH score excluded AiH in all. After OLT, actuarial graft and patients survival was 90% at 5 years. Mild or moderate graft hepatitis occurred in 9 patients (23%) and was significantly associated with a pre-OLT IAH score >or= 10 (P =0.008). This study provides arguments that cryptogenic cirrhosis is a heterogeneous disease in which autoimmune mechanisms might be predominately involved and being responsible for recurrence of chronic liver disease observed in some instances after OLT.

Effect of endoscopic forceps on quality of duodenal mucosal biopsy in healthy dogs.

PubMed

Goutal-Landry, C M; Mansell, J; Ryan, K A; Gaschen, F P

2013-01-01

Limited data exist regarding influence of endoscopic forceps on duodenal mucosal biopsy quality and adequacy for histologic examination/assessment in dogs. Hypothesizing that larger forceps would procure superior specimens, we evaluated effect of 6 disposable forceps on duodenal biopsy weight, depth, crush artifact, and adequacy for histologic examination/assessment. Seventeen healthy adult dogs. Prospective study. Two operators each obtained 4 duodenal specimens from each dog with each forceps. Lightest sample discarded. One pathologist evaluated blindly other 3 specimens. A total of 612 specimens evaluated. Results analyzed by one-way ANOVA of forceps effects with dog as blocking factor. Posthoc pairwise comparisons examined with Tukey's test when indicated. Biopsies performed with large capacity forceps heavier (10.56 ± 0.90 and 11.6 ± 0.62 mg (mean ± SD) versus 5.55 ± 0.53 to 8.61 ± 0.49; P < .0001) and adequacy for histologic examination/assessment superior to standard oval and 'pediatric' (scores 2.52 ± 0.41 and 2.58 ± 0.37 versus 2.08 ± 0.33 and 2.14 ± 0.29; P < .0001). No statistically significant difference in depth scores. Large capacity forceps with spike associated with less crush artifact than all smaller forceps (scores 1.19 ± 0.16 versus 1.38 ± 0.21 to 1.52 ± 0.21; P < .0001). In same size forceps, presence of spike had no effect on crush artifact and adequacy for histologic examination/assessment (P < .0001). Large capacity forceps are superior, providing higher quality and greater numbers of samples achieving adequacy for histologic examination/assessment. Choice of endoscopic biopsy forceps for duodenal samples influences sample volume and diagnostic utility. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Pilot investigation of the correlation between histological and clinical effects of infrared fractional resurfacing lasers.

PubMed

Walgrave, Susan; Zelickson, Brian; Childs, James; Altshuler, Gregory; Erofeev, Andrei; Yaroslavsky, Ilya; Kist, David; Counters, Jeff

2008-11-01

Yucatan Black pig skin was treated with a 1,540-nm erbium (Er):glass laser (Lux1540, 15 and 30 mJ) and two 1,550-nm Er-doped fiber lasers (Fraxel SR750 and SR1500, 8, 10, and 12 mJ). Histologic sections were examined to determine the depth of damage and to correlate subjects' clinical response. Concurrently, six subjects with photodamaged skin received three split-face and ipsilateral dorsal hand treatments with the 1,540-nm Er:glass laser on one side and one of the 1,550-nm Er-doped lasers (Fraxel SR750) on the other. The 1,550-nm Er-doped lasers, using lower fluences and higher densities, produced shallower micro-columns than the 1,540-nm Er:glass device at higher fluences and lower densities (mean depths 250-275 microm vs 425-525 microm, respectively). Blinded assessors found greater overall improvement in pigmentation with the 1,550-nm Er-doped laser and better overall improvement in texture with the 1,540-nm Er:glass laser. Greater densities of shallower damage columns at lower energies may better improve pigmentation, whereas deeper injuries, using higher energies and moderate densities, may better improve texture. This pilot study did not compare similar fluences and histologic damage between the two systems, and newer available systems allow for greater depth of penetration.

Automated detection of insect-damaged sunflower seeds by X-ray imaging

USDA-ARS?s Scientific Manuscript database

The development of insect-resistant sunflowers is hindered by the lack of a quick and effective method for scoring samples in terms of insect damage. The current method for scoring insect damage, which involves manual inspection of seeds for holes bored into the shell, is tedious, requiring approxi...

CURCUMIN IN COMBINATION WITH TRIPLE THERAPY REGIMES AMELIORATES OXIDATIVE STRESS AND HISTOPATHOLOGIC CHANGES IN CHRONIC GASTRITIS-ASSOCIATED HELICOBACTER PYLORI INFECTION.

PubMed

Judaki, Arezu; Rahmani, Asghar; Feizi, Jalil; Asadollahi, Khairollah; Hafezi Ahmadi, Mohammad Reza

2017-01-01

Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (P<0.05 for both). Triple therapy group in combination with Curcumin significantly decreased all active, chronic and endoscopic inflammation scores of patients compared to the baseline and triple therapy group (P<0.05 for both). The eradication rate by triple therapy + curcumin was significantly increased compared to triple therapy alone (P<0.05). Curcumin can be a useful supplement to improve chronic inflammation and prevention of carcinogenic changes in patients with chronic gastritis associated by H. pylori.

Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.

PubMed

Lucero, Yalda; Oyarzún, Amaya; O'Ryan, Miguel; Quera, Rodrigo; Espinosa, Nelly; Valenzuela, Romina; Simian, Daniela; Alcalde, Elisa; Arce, Claudio; Farfán, Mauricio J; Vergara, Alejandra F; Gajardo, Iván; Mendez, Jocelyn; Carrasco, Jorge; Errázuriz, Germán; Gonzalez, Mónica; Ossa, Juan C; Maiza, Eduardo; Perez-Bravo, Francisco; Castro, Magdalena; Araya, Magdalena

2017-01-01

HIGHLIGHTS What is already known about this subject?Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive. H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. pylori (and the effect of their virulence factors) in CD have not yet completely elucidated.What are the new findings? cagA + H. pylori strains are associated to milder histological damage in infected CD patients.In active-CD patients the presence of cagA + H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA + infected potential-CD individuals.How might it impact on clinical practice in the foreseeable future?The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients. Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD) remain elusive. Helicobacter pylori (Hp) chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA + strains) in CD is unclear. Objective: To assess the relationship between gastric Hp infection ( cagA + strains) and duodenal histological damage in patients with CD. Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/ cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-β expression in duodenal lamina propria were analyzed. Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30-40%), but cagA + strains were more common in infected potential-CD than in active-CD (10/11 vs. 4/10; p = 0.020) and non-CD (10/20; p = 0.025). Among active-CD patients, Foxp3 positivity was significantly higher in subjects with cagA + Hp+ compared to cagA- Hp+ ( p < 0.01) and Hp- ( p < 0.01). In cagA+ Hp+ individuals, Foxp3 positivity was also higher comparing active- to potential-CD ( p < 0.01). TGF-β expression in duodenum was similar in active-CD with cagA + Hp+ compared to Hp- and was significantly downregulated in cagA + potential-CD subjects compared to other groups. Conclusion: Hp infection rates were similar among individuals with/without CD, but infection with cagA + strains was associated with milder histological damage in celiac patients infected by Hp, and in active-CD cases with higher expression of T-reg markers. Results suggest that infection by cagA + Hp may be protective for CD progression, or conversely, that these strains are prone to colonize intestinal mucosa with less severe damage.

Impact of virtual microscopy with conventional microscopy on student learning in dental histology.

PubMed

Hande, Alka Harish; Lohe, Vidya K; Chaudhary, Minal S; Gawande, Madhuri N; Patil, Swati K; Zade, Prajakta R

2017-01-01

In dental histology, the assimilation of histological features of different dental hard and soft tissues is done by conventional microscopy. This traditional method of learning prevents the students from screening the entire slide and change of magnification. To address these drawbacks, modification in conventional microscopy has evolved and become motivation for changing the learning tool. Virtual microscopy is the technique in which there is complete digitization of the microscopic glass slide, which can be analyzed on a computer. This research is designed to evaluate the effectiveness of virtual microscopy with conventional microscopy on student learning in dental histology. A cohort of 105 students were included and randomized into three groups: A, B, and C. Group A students studied the microscopic features of oral histologic lesions by conventional microscopy, Group B by virtual microscopy, and Group C by both conventional and virtual microscopy. The students' understanding of the subject was evaluated by a prepared questionnaire. The effectiveness of the study designs on knowledge gains and satisfaction levels was assessed by statistical assessment of differences in mean test scores. The difference in score between Groups A, B, and C at pre- and post-test was highly significant. This enhanced understanding of the subject may be due to benefits of using virtual microscopy in teaching histology. The augmentation of conventional microscopy with virtual microscopy shows enhancement of the understanding of the subject as compared to the use of conventional microscopy and virtual microscopy alone.

Ozonized sunflower oil reduces oxidative damage induced by indomethacin in rat gastric mucosa.

PubMed

Zamora, Z; González, R; Guanche, D; Merino, N; Menéndez, S; Hernández, F; Alonso, Y; Schulz, S

2008-01-01

This study was carried out in order to investigate the potential cytoprotective effects of ozonized sunflower oil (OSO) in the damage of rat gastric mucosa induced by indomethacin and also to elucidate the role of reactive oxygen species (ROS), lipid peroxidation and some constituents of antioxidant defense such as superoxide dismutase (SOD) and catalase (CAT) in these effects. The gastric damage was induced by indomethacin (20 mg/kg) as solution in 0.5% sodium bicarbonate and given intragastrically. Three hours later OSO (4, 12 and 24 mg/kg) and cimetidine 25 mg/kg were administered also by oral route. Four hours thereafter the rats were killed and the stomachs were removed for biochemical analysis and histological study. The gastric ulcer index was reduced by OSO and cimetidine. OSO also reduced TBARS concentration, but it increased SOD activity in gastric mucosa homogenates. In contrast, CAT activity was not significantly modified the treatment. Histological study confirmed the cytoprotective effects of OSO in rat gastric mucosa damaged by indomethacin. It was concluded that cytoprotective effects of OSO in rat gastric mucosa are mediated at least partially by upregulation of the antioxidant system and mainly SOD.

Histological scoring and associated risk factors of non-alcoholic fatty liver disease.

PubMed

Majid, N; Ali, Z; Rahman, M R; Akhter, A; Rajib, R C; Ahmad, F; Sharmin, S; Akond, A K; Huq, N

2013-10-01

Non alcoholic steatohepatitis is a hepatic disorder with histological features of alcohol induced liver disease that occurs in individual who do not consume significant alcohol. Liver biopsy is an important part of the evaluation in term of both grade & stage. A cross sectional study was carried out in the department of Pathology, Dhaka Medical College, Dhaka & department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2007 to June 2009. Total 55 adult subjects of both sex were included on the basis of predefined inclusion & exclusion criteria in this study to evaluate the histological pattern of non alcoholic fatty liver disease (NAFLD) and its correlation with risk factors. Liver biopsy was done and H & E and Masson's Trichrome stain slides were examined to evaluate the grade and stage of NAFLD. Scoring and semiquantitative assessment of steatosis and NAFLD severity was done according to Kleiner scale known as NAFLD activity score (NAS). The results of Pearson correlation showed only BMI and triglyceride level significantly correlated with NAS score. The results of Spearman's rank correlation showed that BMI, central obesity, triglyceridaemia and age significantly correlated with staging of fibrosis. The results of multiple regression analysis showed that variation of NAS depend on BMI and triglyceride level. The study also revealed that risk factors contributed about 29% risk for the occurrence of non alcoholic steatohepatitis.

Effects of indigo naturalis on colonic mucosal injuries and inflammation in rats with dextran sodium sulphate-induced ulcerative colitis.

PubMed

Wang, Yunliang; Liu, Lijuan; Guo, Yi; Mao, Tangyou; Shi, Rui; Li, Junxiang

2017-08-01

The effects of indigo naturalis (IN), which is a traditional Chinese herbal formulation, have been clinically demonstrated in treating refractory ulcerative colitis (UC). The present study aimed to verify the effects and mechanisms of IN in experimental UC rats. A total of 48 male Sprague-Dawley rats were randomly divided into six groups: Chow, model, high-dose IN, medium-dose IN, low-dose IN and mesalazine (a bowel-specific aminosalicylate drug) groups. The models were administered 3.5% dextran sodium sulphate solution for 7 days. The treatment groups were administered IN or mesalazine and then sacrificed and sampled on day 8. Disease activity index (DAI), histological damage score (HDS) and myeloperoxidase (MPO) activity were used to evaluate the severity of UC. Colon and serum cytokines were detected using liquid-phase chip technology and the expression of occludin protein in colonic mucosa was assessed by immunohistochemistry and western blot analysis. The results indicated that the oral administration of IN may reduce DAI, HDS and MPO activity. IN also reduced the expression of inflammatory cytokines and increased the expression of colonic mucosal repair-related cytokines and occludin protein. These results highlight the potential of IN as a therapeutic agent for treating UC through its action of inflammation control and colonic mucosal damage repair.

Methylene blue dyeing of cellular nuclei during salpingoscopy, a new in-vivo method to evaluate vitality of tubal epithelium.

PubMed

Marconi, G; Quintana, R

1998-12-01

The Fallopian tube can be damaged by different noxious substances that may change cellular ultrastructure and function. Alteration of the cell membrane allows the passage of certain aniline dyes, which can stain the nucleus. A total of 310 Fallopian tubes from 163 patients who underwent a surgical or diagnostic laparoscopy during fertility studies was analysed by salpingoscopy. Cellular nuclei were stained by injection of 20 ml of a 10% solution of methylene blue in saline solution (NaCl 10%) through the cervical cannula prior to salpingoscopy. Evaluation of nuclear staining with methylene blue, adhesions, vascular alterations, and the flattening of folds in relation to pregnancy outcome was undertaken. Quantification of salpingoscopic findings was carried out according to a score. Flattening of folds and vascular alterations showed no difference in the pregnant and non-pregnant groups. On the other hand, adhesions and nuclear dyeing were significantly greater in the non-pregnant group (adhesions 13.6 versus 26.8%, P < 0.004, and nuclear dyeing: 25 versus 41.7%, P < 0.009, pregnant versus non-pregnant). Methylene blue dye is a new tool to evaluate in vivo cyto-histological tubal damage, and is a useful and simple method to provide a prognosis of salpingean function.

The protective effect of dexmedetomidine in a rat ex vivo lung model of ischemia-reperfusion injury.

PubMed

Zhou, Yan; Zhou, Xinqiao; Zhou, Wenjuan; Pang, Qingfeng; Wang, Zhiping

2018-01-01

To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), 78 kDa glucose-regulated protein (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured, respectively. The introduction of Dex attenuated the post-ischemia-reperfusion lung damage and MDA level, improved lung histology, W/D ratio, lung injury scores and SOD activity. Decreased mRNA and protein levels of GRP78 and CHOP compared with the IR group were observed after Dex treatment. The effect of Dex was dosage-dependence and a high dose of Dex (10 nM) was shown to confer the strongest protective effect against lung damage (P<0.05). Yohimbine, an α2 receptor antagonist, significantly reversed the protective effect of Dex in lung tissues (P<0.05). Dex reduced ischemia-reperfusion injury in rat ex vivo lungs.

An entirely automated method to score DSS-induced colitis in mice by digital image analysis of pathology slides

PubMed Central

Kozlowski, Cleopatra; Jeet, Surinder; Beyer, Joseph; Guerrero, Steve; Lesch, Justin; Wang, Xiaoting; DeVoss, Jason; Diehl, Lauri

2013-01-01

SUMMARY The DSS (dextran sulfate sodium) model of colitis is a mouse model of inflammatory bowel disease. Microscopic symptoms include loss of crypt cells from the gut lining and infiltration of inflammatory cells into the colon. An experienced pathologist requires several hours per study to score histological changes in selected regions of the mouse gut. In order to increase the efficiency of scoring, Definiens Developer software was used to devise an entirely automated method to quantify histological changes in the whole H&E slide. When the algorithm was applied to slides from historical drug-discovery studies, automated scores classified 88% of drug candidates in the same way as pathologists’ scores. In addition, another automated image analysis method was developed to quantify colon-infiltrating macrophages, neutrophils, B cells and T cells in immunohistochemical stains of serial sections of the H&E slides. The timing of neutrophil and macrophage infiltration had the highest correlation to pathological changes, whereas T and B cell infiltration occurred later. Thus, automated image analysis enables quantitative comparisons between tissue morphology changes and cell-infiltration dynamics. PMID:23580198

Prostatic vascular damage induced by cigarette smoking as a risk factor for recovery after holmium laser enucleation of the prostate (HoLEP)

PubMed Central

Gu, Meng; Chen, Yanbo; Cai, Zhikang; Chen, Qi; Wang, Zhong

2017-01-01

Purpose To evaluate the relationship between prostatic vessel changes induced by cigarette smoking and the perioperative outcome of holmium laser enucleation of the prostate (HoLEP). Materials and Methods A total of 268 postoperative patients with benign prostatic hyperplasia (BPH) were prospectively analysed in our department. They were divided into two groups (smokers and non-smokers) according to smoking history. Transrectal colour Doppler ultrasound was performed to evaluate the prostate vascular changes. Pathologically, HE staining, CD31 and CD34 were analysed in prostatic section chips. Furthermore, postoperative outcomes were determined during a 6-month follow-up period. Results The preoperative prostate volume was significantly decreased in smoking patients (P = 0.04). CPI was significantly lower in smoking BPH patients (P < 0.01), whereas RI was significantly increased in smokers compared with non-smokers (P < 0.01). Histological assays revealed elevated CD34 in the smoking BPH individuals presenting an increased number of microvessels. The HoLEP duration was increased in smokers. Interestingly, we identified significantly increased overactive bladder syndrome score (OABSS) and decreased Qmax in smoking individuals during the 6-month follow-up with no difference being observed preoperatively. However, no significant difference between the groups was observed for the International Prostate Symptom Score (IPSS). Conclusions The significantly lower CPI and higher RI values in smoking BPH patients indicated the presence of considerable vascular damage in these subjects. Moreover, cigarette smoking extended the surgical duration and prolonged the recovery period of overactive bladder (OAB) syndrome. Thus, integrated treatment should be suggested for various BPH individuals. PMID:27732940

Effects of the Soluble Fiber Complex PolyGlycopleX® on Glucose Homeostasis and Body Weight in Young Zucker Diabetic Rats

PubMed Central

Grover, Gary James; Koetzner, Lee; Wicks, Joan; Gahler, Roland J.; Lyon, Michael R.; Reimer, Raylene A.; Wood, Simon

2011-01-01

Dietary fiber can reduce insulin resistance, body weight, and hyperlipidemia depending on fiber type, water solubility, and viscosity. PolyGlycopleX® (PGX®) is a natural, novel water soluble, non-starch polysaccharide complex that with water forms a highly viscous gel compared to other naturally occurring dietary fiber. We determined the effect of dietary PGX® vs. cellulose and inulin on the early development of insulin resistance, body weight, hyperlipidemia, and glycemia-induced tissue damage in young Zucker diabetic rats (ZDFs) in fasted and non-fasted states. ZDFs (5 weeks old) were fed a diet containing 5% (wgt/wgt) cellulose, inulin, or PGX® for 8 weeks. Body weight, lipids, insulin, and glucose levels were determined throughout the study and homeostasis model assessment (HOMA) was used to measure insulin sensitivity throughout the study in fasted animals. At study termination, insulin sensitivity (oral glucose tolerance test, OGTT) and kidney, liver, and pancreatic histopathology were determined. Body weight and food intake were significantly reduced by PGX® vs. inulin and cellulose. Serum insulin in fasted and non-fasted states was significantly reduced by PGX® as was non-fasted blood glucose. Insulin resistance, measured as a HOMA score, was significantly reduced by PGX® in weeks 5 through 8 as well as terminal OGTT scores in fed and fasted states. Serum total cholesterol was also significantly reduced by PGX®. PGX® significantly reduced histological kidney and hepatic damage in addition to reduced hepatic steatosis and cholestasis. A greater mass of pancreatic β-cells was found in the PGX® group. PGX® therefore may be a useful dietary additive in the control of the development of the early development of the metabolic syndrome. PMID:21922008

Cardioprotective role of tadalafil against cisplatin-induced cardiovascular damage in rats.

PubMed

Saleh, Rasha M; Awadin, Walaa F; El-Shafei, Reham A; Elseady, Yousef Y; Wehaish, Faheim E; Elshal, Mohamed F

2015-10-15

The present study investigated the possible cardioprotective effect of tadalafil (Tad) on cisplatin (CDDP)-induced cardiac and vascular damages in rats. A total number of seventy two healthy male albino rats initially weighting between 200 and 220 g were used and randomly divided into four groups,18 rats in each. The control group received no treatment; CDDP group received a single dose of CDDP (4 mg/kg) intraperitoneal (i.p.) per week for 4 weeks the duration of the experiment; Tad group received 0.4 mg/kg BW Tad i.p. daily and Tad +CDDP group received 0.4 mg/kg BW Tad i.p. +4 mg/kg BW CDDP i.p. The results showed that Tad was able to decrease blood pressure, heart rate, levels of serum cardiac troponin (cTn-I), malondialdehyde (MDA) and increased levels of reduced glutathione (GSH) and nitric oxide (NO) in the heart homogenate sample from CDDP treated rats. Semi-quantitative analysis showed that Tad was able to decrease the histopathological scores of cardiac muscular hyalinzation and fibrosis in three sacrifices in CDDP treated rats. CDDP treated rats showed significantly increased thickening in wall of aorta with an irregular luminal layer of endothelial cell linings in three sacrifices when it was compared to other groups. Moreover, immunohistochemical labeling of α- smooth muscle actin (α-SMA) in aorta revealed significant lower scores in Tad +CDDP group when they were compared to CDDP group. In conclusion, Tad alone did not induce any harmful effects on blood pressure, selective antioxidant, peroxidation markers or cardiac histology, in addition, Tad has a cardio-protective role against CDDP. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of the Soluble Fiber Complex PolyGlycopleX on Glucose Homeostasis and Body Weight in Young Zucker Diabetic Rats.

PubMed

Grover, Gary James; Koetzner, Lee; Wicks, Joan; Gahler, Roland J; Lyon, Michael R; Reimer, Raylene A; Wood, Simon

2011-01-01

Dietary fiber can reduce insulin resistance, body weight, and hyperlipidemia depending on fiber type, water solubility, and viscosity. PolyGlycopleX(®) (PGX(®)) is a natural, novel water soluble, non-starch polysaccharide complex that with water forms a highly viscous gel compared to other naturally occurring dietary fiber. We determined the effect of dietary PGX(®) vs. cellulose and inulin on the early development of insulin resistance, body weight, hyperlipidemia, and glycemia-induced tissue damage in young Zucker diabetic rats (ZDFs) in fasted and non-fasted states. ZDFs (5 weeks old) were fed a diet containing 5% (wgt/wgt) cellulose, inulin, or PGX(®) for 8 weeks. Body weight, lipids, insulin, and glucose levels were determined throughout the study and homeostasis model assessment (HOMA) was used to measure insulin sensitivity throughout the study in fasted animals. At study termination, insulin sensitivity (oral glucose tolerance test, OGTT) and kidney, liver, and pancreatic histopathology were determined. Body weight and food intake were significantly reduced by PGX(®) vs. inulin and cellulose. Serum insulin in fasted and non-fasted states was significantly reduced by PGX(®) as was non-fasted blood glucose. Insulin resistance, measured as a HOMA score, was significantly reduced by PGX(®) in weeks 5 through 8 as well as terminal OGTT scores in fed and fasted states. Serum total cholesterol was also significantly reduced by PGX(®). PGX(®) significantly reduced histological kidney and hepatic damage in addition to reduced hepatic steatosis and cholestasis. A greater mass of pancreatic β-cells was found in the PGX(®) group. PGX(®) therefore may be a useful dietary additive in the control of the development of the early development of the metabolic syndrome.

Does Surface Topography Play a Role in Taper Damage in Head-neck Modular Junctions?

PubMed

Pourzal, Robin; Hall, Deborah J; Ha, Nguyen Q; Urban, Robert M; Levine, Brett R; Jacobs, Joshua J; Lundberg, Hannah J

2016-10-01

There are increasing reports of total hip arthroplasty failure subsequent to modular taper junction corrosion. The surfaces of tapers are machined to have circumferential machining marks, resulting in a surface topography of alternating peaks and valleys on the scale of micrometers. It is unclear if the geometry of this machined surface topography influences the degree of fretting and corrosion damage present on modular taper junctions or if there are differences between modular taper junction material couples. (1) What are the differences in damage score and surface topography between CoCr/CoCr and CoCr/Ti modular junctions? (2) How are initial surface topography, flexural rigidity, taper angle mismatch, and time in situ related to visual taper damage scores for CoCr/CoCr couples? (3) How are initial surface topography, flexural rigidity, taper angle mismatch, and time in situ related to visual taper damage scores for CoCr/Ti couples? Damage on stem and head tapers was evaluated with a modified Goldberg score. Differences in damage scores were determined between a group of 140 CoCr/CoCr couples and 129 CoCr/Ti couples using a chi-square test. For a subgroup of 70 retrievals, selected at random, we measured five variables, including initial stem taper machining mark height and spacing, initial head taper roughness, flexural rigidity, and taper angle mismatch. All retrievals were obtained at revision surgeries. None were retrieved as a result of metal-on-metal failures or were recalled implants. Components were chosen so there was a comparable number of each material couple and damage score. Machining marks around the circumference of the tapers were measured using white light interferometry to characterize the initial stem taper surface topography in terms of the height of and spacing between machining mark peaks as well as initial head taper roughness. The taper angle mismatch was assessed with a coordinate measuring machine. Flexural rigidity was determined based on measurements of gross taper dimensions and material properties. Differences of median or mean values of all variables between material couples were determined (Wilcoxon rank-sum tests and t-tests). The effect of all five variables along with time in situ on stem and head taper damage scores was tested with a multiple regression model. With 70 retrievals, a statistical power of 0.8 could be achieved for the model. Damage scores were different between CoCr/CoCr and CoCr/Ti modular taper junction material couples. CoCr/CoCr stem tapers were less likely to be mildly damaged (11%, p = 0.006) but more likely to be severely damaged (4%, p = 0.02) than CoCr/Ti stem tapers (28% and 1%, respectively). CoCr/CoCr couples were less likely to have moderately worn head tapers (7% versus 17%, p = 0.003). Stem taper machining mark height and spacing and head taper roughness were 11 (SD 3), 185 (SD 46), and 0.57 (SD 0.5) for CoCr/CoCr couples and 10 (SD 3), 170 (SD 56), and 0.64 (SD 0.4) for CoCr/Ti couples, respectively. There was no difference (p = 0.09, p = 0.1, p = 0.16, respectively) for either factor between material couples. Larger stem taper machining mark heights (p = 0.001) were associated with lower stem taper damage scores, and time in situ (p = 0.006) was associated with higher stem taper damage scores for CoCr/CoCr material couples. Stem taper machining marks that had higher peaks resulted in slower damage progression over time. For CoCr/Ti material couples, head taper roughness was associated with higher stem (p = 0.001) and head taper (p = 0.003) damage scores, and stem taper machining mark height, but not time in situ, was associated with lower stem taper damage scores (p = 0.007). Stem taper surface topography was related to damage scores on retrieved head-neck modular junctions; however, it affected CoCr/CoCr and CoCr/Ti couples differently. A taper topography of circumferential machining marks with higher peaks appears to enable slower damage progression and, subsequently, a reduction of the reported release of corrosion products. This may be of interest to implant designers and manufacturers in an effort to reduce the effects of metal release from modular femoral components.

Assessment of Biomarkers Associated with Joint Injury and Subsequent Post-Traumatic Arthritis

DTIC Science & Technology

2014-10-01

using a modified Mankin score, synovial inflammation using a modified synovitis score with semi-quantitative scales, and osteophyte score6-10...Parametric analyses were performed for bone morphological measures and histological assessment. Subchondral bone thickening was significantly increased in...Soder S, Eger W, Diemtar T, Aigner T. Feb 2003. Osteophyte development-- molecular characterization of differentiation stages. Osteoarthritis

Performance on the Frontal Assessment Battery is sensitive to frontal lobe damage in stroke patients.

PubMed

Kopp, Bruno; Rösser, Nina; Tabeling, Sandra; Stürenburg, Hans Jörg; de Haan, Bianca; Karnath, Hans-Otto; Wessel, Karl

2013-11-16

The Frontal Assessment Battery (FAB) is a brief battery of six neuropsychological tasks designed to assess frontal lobe function at bedside [Neurology 55:1621-1626, 2000]. The six FAB tasks explore cognitive and behavioral domains that are thought to be under the control of the frontal lobes, most notably conceptualization and abstract reasoning, lexical verbal fluency and mental flexibility, motor programming and executive control of action, self-regulation and resistance to interference, inhibitory control, and environmental autonomy. We examined the sensitivity of performance on the FAB to frontal lobe damage in right-hemisphere-damaged first-ever stroke patients based on voxel-based lesion-behavior mapping. Voxel-based lesion-behavior mapping of FAB performance revealed that the integrity of the right anterior insula (BA13) is crucial for the FAB global composite score, for the FAB conceptualization score, as well as for the FAB inhibitory control score. Furthermore, the FAB conceptualization and mental flexibility scores were sensitive to damage of the right middle frontal gyrus (MFG; BA9). Finally, the FAB inhibitory control score was sensitive to damage of the right inferior frontal gyrus (IFG; BA44/45). These findings indicate that several FAB scores (including composite and item scores) provide valid measures of right hemispheric lateral frontal lobe dysfunction, specifically of focal lesions near the anterior insula, in the MFG and in the IFG.

Performance on the Frontal Assessment Battery is sensitive to frontal lobe damage in stroke patients

PubMed Central

2013-01-01

Background The Frontal Assessment Battery (FAB) is a brief battery of six neuropsychological tasks designed to assess frontal lobe function at bedside [Neurology 55:1621-1626, 2000]. The six FAB tasks explore cognitive and behavioral domains that are thought to be under the control of the frontal lobes, most notably conceptualization and abstract reasoning, lexical verbal fluency and mental flexibility, motor programming and executive control of action, self-regulation and resistance to interference, inhibitory control, and environmental autonomy. Methods We examined the sensitivity of performance on the FAB to frontal lobe damage in right-hemisphere-damaged first-ever stroke patients based on voxel-based lesion-behavior mapping. Results Voxel-based lesion-behavior mapping of FAB performance revealed that the integrity of the right anterior insula (BA13) is crucial for the FAB global composite score, for the FAB conceptualization score, as well as for the FAB inhibitory control score. Furthermore, the FAB conceptualization and mental flexibility scores were sensitive to damage of the right middle frontal gyrus (MFG; BA9). Finally, the FAB inhibitory control score was sensitive to damage of the right inferior frontal gyrus (IFG; BA44/45). Conclusions These findings indicate that several FAB scores (including composite and item scores) provide valid measures of right hemispheric lateral frontal lobe dysfunction, specifically of focal lesions near the anterior insula, in the MFG and in the IFG. PMID:24237624

Laser-induced cartilage damage: an ex-vivo model using confocal microscopy

NASA Astrophysics Data System (ADS)

Frenz, Martin; Zueger, Benno J.; Monin, D.; Weiler, C.; Mainil-Varlet, P. M.; Weber, Heinz P.; Schaffner, Thomas

1999-06-01

Although there is an increasing popularity of lasers in orthopedic surgery, there is a growing concern about negative side effects of this therapy e.g. prolonged restitution time, radiation damage to adjacent cartilage or depth effects like bone necrosis. Despite case reports and experimental investigations over the last few years little is known about the extent of acute cartilage damage induced by different lasers types and energies. Histological examination offers only limited insights in cell viability and metabolism. Ho:YAG and Er:YAG lasers emitting at 2.1 micrometer and 2.94 micrometer, respectively, are ideally suited for tissue treatment because these wavelengths are strongly absorbed in water. The Purpose of the present study is to evaluate the effect of laser type and energy on chondrocyte viability in an ex vivo model. Free running Er:YAG (E equals 100 and 150 mJ) and Ho:YAG (E equals 500 and 800 mJ) lasers were used at different energy levels using a fixed pulse length of 400 microseconds. The energy was delivered at 8 Hz through optical fibers. Fresh bovine hyaline cartilage samples were mounted in a water bath at room temperature and the fiber was positioned at 30 degree and 180 degree angles relative to the tissue surface. After laser irradiation the samples were assessed by a life-dead cell viability test using a confocal microscope and by standard histology. Thermal damage was much deeper with Ho:YAG (up to 1800 micrometer) than with the Er:YAG laser (up to 70 micrometer). The cell viability test revealed a damage zone about twice the one determined by standard histology. Confocal microscopy is a powerful tool for assessing changes in tissue structure after laser treatment. In addition this technique allows to quantify these alterations without necessitating time consuming and expensive animal experiments.

The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

PubMed Central

Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

2015-01-01

Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

Contributions of HLA haplotypes, IL8 level and Toxoplasma gondii infection in defining celiac disease's phenotypes.

PubMed

Rostami-Nejad, Mohammad; Hejazi, Seyed Hossein; Peña, Amado Salvador; Asadzadeh-Aghdaei, Hamid; Rostami, Kamran; Volta, Umberto; Zali, Mohammad Reza

2018-05-18

It is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease's phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection. In this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013-14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification. High levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities. CD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD's phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.

Sympathetic block by metal clips may be a reversible operation.

PubMed

Thomsen, Lars L; Mikkelsen, Rasmus T; Derejko, Miroslawa; Schrøder, Henrik D; Licht, Peter B

2014-12-01

Thoracoscopic sympathectomy is now used routinely to treat patients with disabling primary hyperhidrosis or facial blushing. Published results are excellent, but side effects, such as compensatory sweating, are also very frequent. The surgical techniques used and the levels of targeting the sympathetic chain vary tremendously. Most surgeons transect or resect the sympathetic chain, but application of a metal clip that blocks transmission of nerve impulses in the sympathetic chain is used increasingly worldwide. This approach offers potential reversibility if patients regret surgery, but the question of reversibility remains controversial. Two recent experimental studies found severe histological signs of nerve damage 4-6 weeks after clip removal, but they only used conventional histopathological staining methods. Thoracoscopic clipping of the sympathetic trunk was performed in adult sheep, and the clip was removed thoracoscopically after 7 days. Following another 4 weeks (n = 6) or 12 weeks (n = 3), the sympathetic trunks were harvested and analysed by conventional and specific nerve tissue immunohistochemical stains (S100, neurofilament protein and synaptophysin). The contralateral sympathetic chains were used as controls. Conventional and immunohistochemical stains demonstrated severe signs of neural damage on the operated side 4 weeks after clip removal. After 12 weeks, these changes had decreased markedly and conventional histology had almost normalized. Conventional and immunohistochemical stains confirmed that application of metal clips to the sympathetic chain caused severe histological damage in the sympathetic trunk that remained visible 4 weeks after clip removal. However, after 12 weeks, these signs of damage had clearly decreased, which suggests in theory that application of metal clips to the sympathetic chain is a reversible procedure if only the observation period is prolonged. Further studies with longer periods between application and removal as well as investigations of nerve conduction should be encouraged, because we do not know whether histological reversibility at cellular level translates into physiological reversibility and possible correlation of nerve trauma with the duration of the applied clip. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Curative effect of Amorphophallus paeoniifolius tuber on experimental hemorrhoids in rats.

PubMed

Dey, Yadu Nandan; Wanjari, Manish M; Kumar, Dharmendra; Lomash, Vinay; Jadhav, Ankush D

2016-11-04

Amorphophallus paeoniifolius (Dennst.) Nicolson (Family- Araceae) is a crop of south East Asian origin. In India, its tuber is widely used in ethnomedicinal practices by different tribes for the treatment of piles (hemorrhoids). The present study evaluated the effect of methanolic and aqueous extract of Amorphophallus paeoniifolius tuber on croton oil induced hemorrhoids in rats. The methanolic extract was standardized with the major phenolic compound, betulinic acid, by HPLC. The hemorrhoids were induced by applying 6% croton oil preparation in the ano-rectal region. Rats were orally administered methanolic and aqueous extract at doses of 250 and 500mg/kg, each for 7 days. Pilex (200mg/kg) was used as reference anti-hemorrhoidal drug. Hemorrhoids were assessed on eighth day by measuring hemorrhoidal and biochemical parameters along with histology of ano-rectal tissue. Croton oil application caused induction of hemorrhoids as indicated by significant (p<0.001) increase in plasma exudation of Evans blue in ano-rectal tissue, macroscopic severity score and ano-rectal coefficient as compared to normal rats. It significantly (p<0.001) elevated lactate dehydrogenase and cytokines (TNF-α and IL-6) levels in serum and increased myeloperoxidase activity and lipid peroxidation in ano-rectal tissue along with marked histological damage as compared to normal rats. Treatment with tuber extracts and pilex significantly (p<0.05-p<0.001) ameliorated Evans blue exudation, hemorrhoidal parameters and other biochemical parameters with attenuation of tissue damage compared to hemorrhoid control rats. The results indicate that tuber extracts exhibited curative action on hemorrhoids. The aqueous extract showed more pronounced effect than methanolic extract. The effects may be attributed to anti-inflammatory and antioxidant properties. Results indicate that tuber of Amorphophallus paeoniifolius exhibited curative action on hemorrhoids through anti-inflammatory and antioxidant properties. The study validates the ethnomedicinal use of tuber in hemorrhoids and implicates its therapeutic potential as an anti-hemorrhoidal agent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of architectural and histopathological biomarkers in the intestine of brown trout (Salmo trutta Linnaeus, 1758) challenged with environmental pollution.

PubMed

Barišić, Josip; Filipović Marijić, Vlatka; Mijošek, Tatjana; Čož-Rakovac, Rozelindra; Dragun, Zrinka; Krasnići, Nesrete; Ivanković, Dušica; Kružlicová, Dáša; Erk, Marijana

2018-06-14

In the present study novel histopathological approach, using fish intestine as a sensitive bioindicator organ of pollution impact in the freshwater ecosystem, was proposed. Histopathological alterations were compared between native brown trout (Salmo trutta Linnaeus, 1758) from the reference (Krka River spring) and pollution impacted location (influence of technological/municipal wastewaters and agricultural runoff near the Town of Knin) of the karst Krka River in Croatia. In brown trout from both locations, severe parasitic infestation with acanthocephalan species Dentitruncus trutae was found, enabling evaluation of acanthocephalan infestation histopathology, which indicated parasite tissue reaction in a form of inflammatory, necrotic and hyperplastic response that extended throughout lamina epithelialis mucosae, lamina propria, and lamina muscularis mucosae. New semi-quantitative histological approach was proposed in order to foresee alterations classified in three reaction patterns: control tissue appearance, moderate (progressive) tissue impairment and severe (regressive and inflammatory) tissue damage. The most frequent progressive alteration was hyperplasia of epithelium on the reference site, whereas the most frequent regressive alterations were atrophy and necrosis seen on the polluted site. Furthermore, histopathological approach was combined with micromorphological and macromorphological assessment as an additional indicator of pollution impact. Among 15 observed intestinal measures, two biomarkers of intestinal tissue damage were indicated as significant, height of supranuclear space (hSN) and number of mucous cells over 100 μm fold distance of intestinal mucosa (nM), which measures were significantly lower in fish from polluted area compared to the reference site. Obtained results indicated that combined histological and morphological approach on fish intestinal tissue might be used as a valuable biological tool for assessing pollution impact on aquatic organisms. Therefore, semi quantitative scoring and multiparametric morphological assessment of intestinal tissue lesion magnitude should become a common approach to handle environmental pollution impact. Copyright © 2018 Elsevier B.V. All rights reserved.

Induced hypothermia reduces the hepatic inflammatory response in a swine multiple trauma model.

PubMed

Fröhlich, Matthias; Hildebrand, Frank; Weuster, Matthias; Mommsen, Philipp; Mohr, Juliane; Witte, Ingo; Raeven, Pierre; Ruchholtz, Steffen; Flohé, Sascha; van Griensven, Martijn; Pape, Hans-Christoph; Pfeifer, Roman

2014-06-01

Mild therapeutic hypothermia following trauma has been introduced in several studies to reduce the posttraumatic inflammation and organ injury. In this study, we analyzed the effects of induced mild hypothermia (34°C) on the inflammation of the shock organs liver and kidney. In a porcine model of multiple trauma including blunt chest trauma, liver laceration, and hemorrhagic shock followed by fluid resuscitation, the influence of induced hypothermia on hepatic and renal damage and organ-specific inflammation were evaluated. A total of 40 pigs were randomly assigned to four groups, which were sham (anesthesia only) or trauma groups receiving either hypothermia or normothermia. The parameters analyzed were laboratory parameters (aspartate transaminase [AST], lactate dehydrogenase, urea, creatinine) as well as hepatic and renal cytokine expression determined by real-time polymerase chain reaction (interleukin 6 [IL-6], IL-8). Blinded analysis of histologic changes in the liver and kidney was performed. Fifteen and a half hours following combined trauma, hepatic cytokine expression and liver damage were significantly increased in animals with normothermia compared with the respective sham group. Hypothermia, however, resulted in a fivefold reduced hepatic expression of IL-8 (mean ± SE, 2.4 ± 1.3; p = 0.01) when compared with the normothermic trauma group (IL-8, 12.8 ± 4.7). Accordingly, granulocyte infiltration and a histologic, semiquantitative score for liver injury were significantly higher in the normothermic trauma group. Serum AST levels raised significantly after trauma and normothermia compared with the respective sham group, while AST levels showed no difference from the sham groups in the hypothermic trauma group. In contrast, neither trauma nor hypothermia influenced the expression of IL-6 and IL-8 and tissue injury in the kidney. Therapeutic hypothermia seems to attenuate the hepatic inflammatory response and the associated liver injury after severe trauma. Therefore, induced hypothermia might represent a potential therapeutic strategy to avoid posttraumatic organ dysfunction.

Histological validation of near-infrared reflectance multispectral imaging technique for caries detection and quantification

NASA Astrophysics Data System (ADS)

Salsone, Silvia; Taylor, Andrew; Gomez, Juliana; Pretty, Iain; Ellwood, Roger; Dickinson, Mark; Lombardo, Giuseppe; Zakian, Christian

2012-07-01

Near infrared (NIR) multispectral imaging is a novel noninvasive technique that maps and quantifies dental caries. The technique has the ability to reduce the confounding effect of stain present on teeth. The aim of this study was to develop and validate a quantitative NIR multispectral imaging system for caries detection and assessment against a histological reference standard. The proposed technique is based on spectral imaging at specific wavelengths in the range from 1000 to 1700 nm. A total of 112 extracted teeth (molars and premolars) were used and images of occlusal surfaces at different wavelengths were acquired. Three spectral reflectance images were combined to generate a quantitative lesion map of the tooth. The maximum value of the map at the corresponding histological section was used as the NIR caries score. The NIR caries score significantly correlated with the histological reference standard (Spearman's Coefficient=0.774, p<0.01). Caries detection sensitivities and specificities of 72% and 91% for sound areas, 36% and 79% for lesions on the enamel, and 82% and 69% for lesions in dentin were found. These results suggest that NIR spectral imaging is a novel and promising method for the detection, quantification, and mapping of dental caries.

Histological validation of near-infrared reflectance multispectral imaging technique for caries detection and quantification.

PubMed

Salsone, Silvia; Taylor, Andrew; Gomez, Juliana; Pretty, Iain; Ellwood, Roger; Dickinson, Mark; Lombardo, Giuseppe; Zakian, Christian

2012-07-01

Near infrared (NIR) multispectral imaging is a novel noninvasive technique that maps and quantifies dental caries. The technique has the ability to reduce the confounding effect of stain present on teeth. The aim of this study was to develop and validate a quantitative NIR multispectral imaging system for caries detection and assessment against a histological reference standard. The proposed technique is based on spectral imaging at specific wavelengths in the range from 1000 to 1700 nm. A total of 112 extracted teeth (molars and premolars) were used and images of occlusal surfaces at different wavelengths were acquired. Three spectral reflectance images were combined to generate a quantitative lesion map of the tooth. The maximum value of the map at the corresponding histological section was used as the NIR caries score. The NIR caries score significantly correlated with the histological reference standard (Spearman's Coefficient=0.774, p<0.01). Caries detection sensitivities and specificities of 72% and 91% for sound areas, 36% and 79% for lesions on the enamel, and 82% and 69% for lesions in dentin were found. These results suggest that NIR spectral imaging is a novel and promising method for the detection, quantification, and mapping of dental caries.

Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis

PubMed Central

Tian, Dongping; Lei, Zhijin; Chen, Donglin; Xu, Zexin; Su, Min

2016-01-01

Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis. PMID:27028857

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats.

PubMed

Kasote, D M; Badhe, Y S; Zanwar, A A; Hegde, M V; Deshmukh, K K

2012-07-01

to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats. Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl(4) in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl(4) intoxication. Hepatic lipid peroxidation elevated by CCl(4) intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl(4) -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl(4) -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). EPC-BF possesses the significant hepatoprotective activity against CCl(4) induced liver damage, which could be mediated through increase in antioxidant defenses.

Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs.

PubMed

Weiss, Steven M; Dahlstrom, Jane E; Saint, David A

2013-12-01

The cardiac persistent sodium current (IN aP ) presents a novel target for cardiac ischaemic protection. Herein we investigated the effects of the IN aP blocker riluzole in a pig model of regional myocardial ischaemia. Landrace or Large White pigs were subjected to 3 h ligation of the left anterior descending coronary artery (LAD). Pigs received either saline (500 mL/h, i.v.) throughout the experiment (control; n = 7) or riluzole (2 mg/kg in 2 mL propylene glycol in 100 mL saline, i.v.; RIL; n = 7) between 15 and 5 min prior to ligation. The arrhythmia score was calculated in 5 min epochs. Myocardial damage was assessed using epicardial image analysis and histological sectioning. In the control group, all seven pigs developed premature ventricular contractions (PVC), seven developed non-sustained arrhythmias and six of seven developed sustained arrhythmias. Of the sustained arrhythmias, 23 of 28 instances were initiated by R-on-T extrasytoles (extrasystoles within the vulnerable period that can trigger re-entrant arrhythmias). In the RIL group, all seven pigs developed PVC, six of seven developed non-sustained arrhythmias and only three developed sustained arrhythmias, of which two of five instances were R-on-T initiated. The riluzole-treated pigs exhibited less myocardial damage than pigs in the control group (65% smaller surface area (P = 0.008) on gross epicardial inspection, 51% less oedema (P = 0.01), 53% less fibre waviness (P = 0.029) assessed by haematoxylin and eosin staining and 79% fewer fragmented nuclei (P = 0.009) assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling). In conclusion, riluzole significantly reduced Phase 2 (the period associated with irreversible damage) ischaemic R-on-T triggered and non-R-on-T arrhythmias and myocardial damage occurring during the 3 h period of regional ischaemia. © 2013 Wiley Publishing Asia Pty Ltd.

Corneal and skin laser exposures from 1540-nm laser pulses

NASA Astrophysics Data System (ADS)

Johnson, Thomas E.; Mitchell, Michael A.; Rico, Pedro J.; Fletcher, David J.; Eurell, Thomas E.; Roach, William P.

2000-06-01

Mechanisms of tissue damage are investigated for skin and cornea exposures from 1540 nm ('eye safe') laser single pulses of 0.8 milli-seconds. New skin model data point out the advantages of using the Yucatan mini-pig versus the Yorkshire pig for in-vivo skin laser exposures. Major advantages found include similarities in thickness and melanin content when compared with human skin. Histology from Yucatan mini-pig skin exposures and the calculation of an initial ED50 threshold indicate that the main photon tissue interaction may not be solely due to water absorption. In-vitro corneal equivalents compared well with in-vivo rabbit cornea exposure under similar laser conditions. In-vivo and in-vitro histology show that initial energy deposition leading to damage occurs intrastromally, while epithelial cells show no direct injury due to laser light absorption.

Experimental scleral cross-linking increases glaucoma damage in a mouse model

PubMed Central

Kimball, Elizabeth C.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary E.; Oglesby, Ericka N.; Oveson, Brian C.; Quigley, Harry A.

2014-01-01

The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model. CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure—strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice. PMID:25285424

Essential fatty acid supplementation in chronic hepatitis B.

PubMed

Jenkins, A P; Green, A T; Thompson, R P

1996-08-01

Dietary supplementation with essential fatty acids and polyunsaturated lecithin may improve biochemical and histological parameters in liver disease. Ten patients with serological and histological evidence of chronic hepatitis B received capsules of the polyunsaturated fatty acid-rich evening primrose oil in a dose of 4 g daily for 12 months, while a matched group received liquid paraffin capsules as a placebo. Compared to the placebo group, the patients receiving evening primrose oil showed no improvement in either biochemical or histological indices of liver damage, or in the rate of loss of circulating e antigen. Dietary, supplementation with this dose of essential fatty acids is unlikely to be of benefit in chronic hepatitis B.

Selenium Alleviates Oxidative Stress and Lung Damage Induced by Aluminum Chloride in Adult Rats: Biochemical and Histological Approach.

PubMed

Ghorbel, Imen; Elwej, Awatef; Chaabane, Mariem; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Zeghal, Najiba

2017-03-01

Our study pertains to the potential ability of selenium, used as a nutritional supplement, to alleviate oxidative stress induced by aluminum chloride in the lung tissue. Rats have received during 21 days either aluminum chloride (AlCl 3 ) (400 ppm) via drinking water, AlCl 3 associated with Na 2 SeO 3 (0.5 mg/kg of diet), or only Na 2 SeO 3 . Exposure of rats to AlCl 3 induced lung oxidative stress with an increase of malondialdehyde, hydrogen peroxide, and protein carbonyls levels. An alteration of lactate dehydrogenase activities and antioxidant redox status, enzymatic (catalase, superoxide dismutase, and glutathione peroxidase), and non-enzymatic (non-protein thiols, glutathione, metallothionein, and vitamin C) was also observed. These biochemical modifications were substantiated by histopathological data showing alveolar edema, a large number of hemosiderin-laden macrophages, and emphysema. Se supplementation attenuated the levels of oxidative stress by restoring antioxidant state and improved lung histological damage. Our results revealed that Se, a trace element with antioxidant properties, was effective in preventing lung damage.

Nuclear morphometry in histological specimens of canine prostate cancer: Correlation with histological subtypes, Gleason score, methods of collection and survival time.

PubMed

Di Donato, Guido; Laufer-Amorim, Renée; Palmieri, Chiara

2017-10-01

Ten normal prostates, 22 benign prostatic hyperplasia (BPH) and 29 prostate cancer (PC) were morphometrically analyzed with regard to mean nuclear area (MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND), coefficient of variation of the nuclear area (NACV), mean nuclear diameter maximum (MDx), mean nuclear diameter minimum (MDm), mean nuclear form ellipse (MNFe) and form factor (FF). The relationship between nuclear morphometric parameters and histological type, Gleason score, methods of sample collection, presence of metastases and survival time of canine PC were also investigated. Overall, nuclei from neoplastic cells were larger, with greater variation in nuclear size and shape compared to normal and hyperplastic cells. Significant differences were found between more (small acinar/ductal) and less (cribriform, solid) differentiated PCs with regard to FF (p<0.05). MNA, MNP, MND, MDx, and MDm were significantly correlated with the Gleason score of PC (p<0.05). MNA, MNP, MDx and MNFe may also have important prognostic implications in canine prostatic cancer since negatively correlated with the survival time. Biopsy specimens contained nuclei that were smaller and more irregular in comparison to those in prostatectomy and necropsy specimens and therefore factors associated with tissue sampling and processing may influence the overall morphometric evaluation. The results indicate that nuclear morphometric analysis in combination with Gleason score can help in canine prostate cancer grading, thus contributing to the establishment of a more precise prognosis and patient's management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Failure to obtain an autoimmune response following cryosurgery to the normal rat liver.

PubMed Central

Townell, N H; Tsantoulas, D; Holborow, E J; Hobbs, K E

1980-01-01

Smooth muscle antibody (SMA) and anti-liver-specific lipoprotein (anti-LSP) responses were investigated following five different freeze thaw regimes to the normal rat liver. The livers were examined histologically for evidence of autoimmune liver disease. No SMA or anti-LSP was found in any animal and on histological examination the unfrozen part of all livers was normal. It is concluded that cryosurgical damage to the liver is unlikely to provoke an autoimmune response. PMID:7460392

Late post-AVR progression of bicuspid aortopathy: link to hemodynamics.

PubMed

Naito, Shiho; Gross, Tatiana; Disha, Kushtrim; von Kodolitsch, Yskert; Reichenspurner, Hermann; Girdauskas, Evaldas

2017-05-01

The ascending aortic dilatation may progress after aortic valve replacement (AVR) in bicuspid aortic valve (BAV) patients. Our aim was to evaluate rheological flow patterns and histological characteristics of the aneurysmal aorta in BAV patients at the time of reoperative aortic surgery. 13 patients (mean age: 42 ± 9 years, 10 (77%) male) with significant progression of proximal aortopathy after isolated AVR surgery for BAV disease (i.e., 16.7 ± 8.1 years post-AVR) were identified by cardiac phase-contrast cine magnetic resonance imaging (MRI) in our hospital. A total of nine patients (69%) underwent redo aortic surgery. Based on the MRI data, the aortic area of the maximal flow-induced stress (jet sample) and the opposite site (control sample) were identified and corresponding samples were collected intraoperatively. Histological sum-score values [i.e. aortic wall changes were graded based on a summation of seven histological criteria (each scored from 0 to 3)] were compared between these samples. Mean proximal aortic diameter at MRI follow-up was 55 ± 6 mm (range 47-66mm). Preoperative cardiac MRI demonstrated eccentric systolic flow pattern directed towards right-lateral/right posterior wall of the proximal aorta in 9/13 (69%) patients. Histological sum-score values were significantly higher in the jet sample vs control sample (i.e., 8.3 ± 3.8 vs 5.6 ± 2.4, respectively, p = 0.04). Hemodynamic factors may still be involved in the late progression of bicuspid aortopathy even after isolated AVR surgery for BAV disease.

Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients

PubMed Central

Lucero, Yalda; Oyarzún, Amaya; O'Ryan, Miguel; Quera, Rodrigo; Espinosa, Nelly; Valenzuela, Romina; Simian, Daniela; Alcalde, Elisa; Arce, Claudio; Farfán, Mauricio J.; Vergara, Alejandra F.; Gajardo, Iván; Mendez, Jocelyn; Carrasco, Jorge; Errázuriz, Germán; Gonzalez, Mónica; Ossa, Juan C.; Maiza, Eduardo; Perez-Bravo, Francisco; Castro, Magdalena; Araya, Magdalena

2017-01-01

HIGHLIGHTS What is already known about this subject?Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive.H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. pylori (and the effect of their virulence factors) in CD have not yet completely elucidated.What are the new findings?cagA+ H. pylori strains are associated to milder histological damage in infected CD patients.In active-CD patients the presence of cagA+ H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA+ infected potential-CD individuals.How might it impact on clinical practice in the foreseeable future?The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients. Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD) remain elusive. Helicobacter pylori (Hp) chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA+ strains) in CD is unclear. Objective: To assess the relationship between gastric Hp infection (cagA+ strains) and duodenal histological damage in patients with CD. Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-β expression in duodenal lamina propria were analyzed. Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30–40%), but cagA+ strains were more common in infected potential-CD than in active-CD (10/11 vs. 4/10; p = 0.020) and non-CD (10/20; p = 0.025). Among active-CD patients, Foxp3 positivity was significantly higher in subjects with cagA+ Hp+ compared to cagA- Hp+ (p < 0.01) and Hp- (p < 0.01). In cagA+ Hp+ individuals, Foxp3 positivity was also higher comparing active- to potential-CD (p < 0.01). TGF-β expression in duodenum was similar in active-CD with cagA+ Hp+ compared to Hp- and was significantly downregulated in cagA+ potential-CD subjects compared to other groups. Conclusion: Hp infection rates were similar among individuals with/without CD, but infection with cagA+ strains was associated with milder histological damage in celiac patients infected by Hp, and in active-CD cases with higher expression of T-reg markers. Results suggest that infection by cagA+ Hp may be protective for CD progression, or conversely, that these strains are prone to colonize intestinal mucosa with less severe damage. PMID:28879170

Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation

PubMed Central

Saito, Kosuke; Tamaki, Tetsuro; Hirata, Maki; Hashimoto, Hiroyuki; Nakazato, Kenei; Nakajima, Nobuyuki; Kazuno, Akihito; Sakai, Akihiro; Iida, Masahiro; Okami, Kenji

2015-01-01

Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2–8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks. PMID:26372044

Actinic comedonal plaque.

PubMed

Eastern, J S; Martin, S

1980-12-01

Solitary plaques developed on the sun-exposed and damaged skin of five elderly, fair-skinned individuals. The lesions, erythematous to bluish confluent nodules and plaques with a cribriform appearance and comedone-like structures, presented a distinctive histologic picture of dilated, keratin-filled follicles within a matrix of amorphous, damaged collagen. We believe these cases demonstrate a distinct entity within the realm of actinic dermatoses, for which the name "actinic comedonal plaque" seems appropriate.

Coconut water vinegar ameliorates recovery of acetaminophen induced liver damage in mice.

PubMed

Mohamad, Nurul Elyani; Yeap, Swee Keong; Beh, Boon-Kee; Ky, Huynh; Lim, Kian Lam; Ho, Wan Yong; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

2018-06-25

Coconut water has been commonly consumed as a beverage for its multiple health benefits while vinegar has been used as common seasoning and a traditional Chinese medicine. The present study investigates the potential of coconut water vinegar in promoting recovery on acetaminophen induced liver damage. Mice were injected with 250 mg/kg body weight acetaminophen for 7 days and were treated with distilled water (untreated), Silybin (positive control) and coconut water vinegar (0.08 mL/kg and 2 mL/kg body weight). Level of oxidation stress and inflammation among treated and untreated mice were compared. Untreated mice oral administrated with acetaminophen were observed with elevation of serum liver profiles, liver histological changes, high level of cytochrome P450 2E1, reduced level of liver antioxidant and increased level of inflammatory related markers indicating liver damage. On the other hand, acetaminophen challenged mice treated with 14 days of coconut water vinegar were recorded with reduction of serum liver profiles, improved liver histology, restored liver antioxidant, reduction of liver inflammation and decreased level of liver cytochrome P450 2E1 in dosage dependent level. Coconut water vinegar has helped to attenuate acetaminophen-induced liver damage by restoring antioxidant activity and suppression of inflammation.

A comparative MRI study of cartilage damage in gout versus rheumatoid arthritis.

PubMed

Popovich, Ivor; Lee, Arier C L; Doyle, Anthony; McHaffie, Alexandra; Clarke, Andrew; Reeves, Quentin; Dalbeth, Nicola; McQueen, Fiona M

2015-08-01

Magnetic resonance imaging (MRI) is useful for detecting joint inflammation and damage in the inflammatory arthropathies. This study aimed to investigate MRI cartilage damage and its associations with joint inflammation in patients with gout compared with a group with rheumatoid arthritis (RA). Forty patients with gout and 38 with seropositive RA underwent 3T-MRI of the wrist with assessment of cartilage damage at six carpal sites, using established scoring systems. Synovitis and bone oedema (BME) were graded according to Rheumatoid Arthritis MRI Scoring System criteria. Cartilage damage was compared between the groups adjusting for synovitis and disease duration using logistic regression analysis. Compared with RA, there were fewer sites of cartilage damage and lower total damage scores in the gout group (P = 0.02 and 0.003), adjusting for their longer disease duration and lesser degree of synovitis. Cartilage damage was strongly associated with synovitis in both conditions (R = 0.59, P < 0.0001 and R = 0.52, P = 0.0045 respectively) and highly correlated with BME in RA (R = 0.69, P < 0.0001) but not in gout (R = 0.095, P = 0.56). Cartilage damage is less severe in gout than in RA, with fewer sites affected and lower overall scores. It is associated with synovitis in both diseases, likely indicating an effect of pro-inflammatory cytokine production on cartilage integrity. However, the strong association between cartilage damage and BME observed in RA was not identified in gout. This emphasizes differences in the underlying pathophysiology of joint damage in these two conditions. © 2015 The Royal Australian and New Zealand College of Radiologists.

Prognostic significance of pulmonary lymphangioleiomyomatosis histologic score.

PubMed

Matsui, K; Beasley, M B; Nelson, W K; Barnes, P M; Bechtle, J; Falk, R; Ferrans, V J; Moss, J; Travis, W D

2001-04-01

Correlations were made between clinical and follow-up data and histopathologic findings in 105 women (mean age +/- standard deviation, 38.3 +/- 9.0 years) with pulmonary lymphangioleiomyomatosis (LAM). The actuarial survival (to pulmonary transplantation or death) of the patients from the time of lung biopsy was 85.1% and 71.0% after 5 and 10 years respectively. The histologic severity of LAM, graded as a LAM histologic score (LHS), was determined on the basis of semiquantitative estimation of the percentage of tissue involvement by the two major features of LAM: the cystic lesions and the infiltration by abnormal smooth muscle cells (LAM cells) in each case: LHS-1, <25%; LHS-2, 25% to 50%; and LHS-3, >50%. Analysis using the Kaplan-Meier method revealed significant differences in survival for patients with LHS-1, -2, and -3 (p = 0.01). The 5-and 10-year survivals were 100% and 100% for LHS-1, 81.2% and 74.4% for LHS-2, and 62.8% and 52.4% for LHS-3. Increased degrees of accumulation of hemosiderin in macrophages also were associated with higher LHS scores (p = 0.029) and a worse prognosis (p = 0.0012). Thus, the current study suggests that the LHS may provide a basis for determining the prognosis of LAM.

Fecal Calprotectin in Ileal Crohn's Disease: Relationship with Magnetic Resonance Enterography and a Pathology Score.

PubMed

Cerrillo, Elena; Beltrán, Belén; Pous, Salvador; Echarri, Ana; Gallego, Jose Carlos; Iborra, Marisa; Pamies, Jose; Nos, Pilar

2015-07-01

Magnetic resonance enterography (MRE) is an effective method of assessing small bowel Crohn's disease (CD). Fecal calprotectin (FC) correlates well with endoscopic disease activity. We aimed to evaluate the correlation between FC and disease activity according to MRE and surgical pathology in small bowel CD. One hundred twenty consecutive patients with ileal CD who underwent MRE assessment were included. Clinical data, C-reactive protein and FC, radiological and histological variables were obtained. Clinical activity was evaluated by the Harvey-Bradshaw Index and FC by enzyme-linked immunosorbent assay. MRE activity was assessed by means of the Magnetic Resonance Index of Activity score. Chiorean's score was used to grade pathological inflammation in surgical specimens. Seventy-five patients (62.5%) were in clinical remission (Harvey-Bradshaw Index < 5) and 45 (37.5%) had active disease (Harvey-Bradshaw Index ≥ 5). The Magnetic Resonance Index of Activity score was significantly associated with FC levels (P < 0.01), with a moderate overall correlation (Spearman's r = 0.56, P < 0.001). FC reflected MRE inflammatory activity with an area under the receiver operating characteristic curve of 0.914 (confidence interval, 0.849-0.958; P < 0.001). A cutoff value of 166.50 μg/g had 90% sensitivity, 74% specificity, 89% positive predictive value, and 76% negative predictive value for diagnosis of inflammation. Twenty-eight of 120 patients were operated. Surgical pathology showed a good agreement with FC for moderate (P = 0.03) and severe (P = 0.01) Chiorean's index. No relationship was detected for C-reactive protein. FC correlates with the degree of MRE inflammatory activity and with surgical pathology damage in ileal CD. Thus, FC could be a surrogate marker of disease control used to select patients for MRE assessment and therapeutic adjustment.

Linked color imaging improves the visibility of colorectal polyps: a video study

PubMed Central

Yoshida, Naohisa; Naito, Yuji; Murakami, Takaaki; Hirose, Ryohei; Ogiso, Kiyoshi; Inada, Yutaka; Dohi, Osamu; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Handa, Osamu; Konishi, Hideyuki; Siah, Kewin Tien Ho; Yagi, Nobuaki; Fujita, Yasuko; Kishimoto, Mitsuo; Yanagisawa, Akio; Itoh, Yoshito

2017-01-01

Background/study aim  Linked color imaging (LCI) by a laser endoscope (Fujifilm Co, Tokyo, Japan) is a novel narrow band light observation. In this study, we aimed to investigate whether LCI could improve the visibility of colorectal polyps using endoscopic videos. Patients and methods  We prospectively recorded videos of consecutive polyps 2 – 20 mm in size diagnosed as neoplastic polyps. Three videos, white light (WL), blue laser imaging (BLI)-bright, and LCI, were recorded for each polyp by one expert. After excluding inappropriate videos, all videos were evaluated in random order by two experts and two non-experts according to a published polyp visibility score from four (excellent visibility) to one (poor visibility). Additionally, the relationship between polyp visibility scores in LCI and various clinical characteristics including location, size, histology, morphology, and preparation were analyzed compared to WL and BLI-bright. Results  We analyzed 101 colorectal polyps (94 neoplastic) in 66 patients (303 videos). The mean polyp size was 9.0 ± 8.1 mm and 54 polyps were non-polypoid. The mean polyp visibility scores for LCI (2.86 ± 1.08) were significantly higher than for WL and BLI-bright (2.53 ± 1.15, P  < 0.001; 2.73 ± 1.47, P  < 0.041). The ratio of poor visibility (score 1 and 2) was significantly lower in LCI for experts and non-experts (35.6 %, 33.6 %) compared with WL (49.6 %, P  = 0.015, 50.5 %, P  = 0.046). The polyp visibility scores for LCI were significantly higher than those for WL for all of the factors. With respect to the comparison between BLI-bright and WL, the polyp visibility scores for BLI-bright were not higher than WL for right-sided location, < 10 mm size, sessile serrated adenoma and polyp histology, and poor preparation. For those characteristics, LCI improved the lesions with right-sided location, SSA/P histology, and poor preparation significantly better than BLI. Conclusions  LCI improved polyp visibility compared to WL for both expert and non-expert endoscopists. It is useful for improving polyp visibility in any location, any size, any morphology, any histology, and any preparation level. PMID:28596985

Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score.

PubMed

Kutikov, Alexander; Smaldone, Marc C; Egleston, Brian L; Manley, Brandon J; Canter, Daniel J; Simhan, Jay; Boorjian, Stephen A; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2011-08-01

Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available. All patients in the cohort underwent either partial or radical nephrectomy. The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Histological change and heat shock protein 70 expression in different tissues of Japanese flounder Paralichthys olivaceus in response to elevated temperature

NASA Astrophysics Data System (ADS)

Liu, Yifan; Ma, Daoyuan; Xiao, Zhizhong; Xu, Shihong; Wang, Yanfeng; Wang, Yufu; Xiao, Yongshuang; Song, Zongcheng; Teng, Zhaojun; Liu, Qinghua; Li, Jun

2015-01-01

High temperature influences the homeostasis of fish. We investigated the effects of elevated temperature on tissues of Japanese flounder ( Paralichthys olivaceus) by analyzing the histology and heat shock protein 70 ( hsp70) expression of fish reared in warm conditions. In this study, temperature was increased at 1±0.5°C/day starting at 24±0.5°C, and was kept at that temperature for 5 days before the next rise. After raising temperature at the rate up to 32±0.5°C, tissue samples from midgut, spleen, stomach, liver, muscle, gill, heart, trunk kidney and brain were collected for histological analysis and mRNA assay. Almost all the tissues showed changes in morphological structure and hsp70 level at 32±0.5°C. Histological assessment of the tissues indicated that the gill had the most serious damage, including highly severe epithelial lifting and edema, curved tips and hyperemia at the ending of the lamellars, desquamation and necrosis. The next most severe damage was found in liver and kidney. The hsp70 levels in all the tissues first increased and then decreased. The gut, stomach, muscle, heart, and brain had the highest expressions in 6 h, whereas the spleen, liver, gill and kidney had the highest expressions in 2 h. Therefore, tissues with the most significant lesions (especially gill and liver) responded much earlier (2 h) in hsp70 expression than other tissues, and these tissues demonstrated the most marked histological disruption and elevated mRNA levels, making them ideal candidates for further studies on the thermal physiology of this species.

Reality of the G-spot and its relation to female circumcision and vaginal surgery.

PubMed

Thabet, Saeed Mohamad Ahmad

2009-10-01

To clarify the reality of the G-spot anatomically, functionally and histologically, and to determine the possible effect of female circumcision and anterior vaginal wall surgery on the integrity and function of the G-spot. A controlled descriptive and comparative cohort prospective study was conducted at Kasr El Aini School of Medicine, Cairo University, Cairo, Egypt, of 50 uncircumcised and 125 circumcised women with small to moderate anterior vaginal wall descent. Preoperative sexual examination was performed to map the site of the G-spot and other anatomical landmarks on the anterior vaginal wall and to verify the associated circumcision state. Pre- and postoperative sexual assessment and histological examination of different mapped sites in the anterior vagina were also conducted. Histological findings, results of the anatomical and sexual mapping of the anterior vaginal wall and sexual scores were recorded. The G-spot was proved functionally in 144 (82.3%) of women and anatomically in 95 (65.9%). The latter appeared as two small flaccid balloon-like masses on either side of the lower third of the urethra and were named 'the sexual bodies of the G-spot'. These bodies were significantly detected in all histo-positive cases in the circumcised women and in the uncircumcised women who had small or average clitorises. The G-spot was also proved histologically in 47.4% of all cases and was formed of epithelial, glandular and erectile tissue. Sex scores were significantly higher in the histo-positive cases with sexual bodies but significantly dropped after anterior vaginal wall surgery. In contrast, female circumcision rarely alters the scores. The G-spot is functional reality in 82.3% of women, an anatomical reality in 54.3% and a histological reality in 47.4%. Anterior vaginal wall surgery usually affects the G-spot and female sexuality, but female circumcision rarely affects them.

Prospective In Vivo Comparison of Damaged and Healthy-Appearing Articular Cartilage Specimens in Patients With Femoroacetabular Impingement: Comparison of T2 Mapping, Histologic Endpoints, and Arthroscopic Grading.

PubMed

Ho, Charles P; Surowiec, Rachel K; Frisbie, David D; Ferro, Fernando P; Wilson, Katharine J; Saroki, Adriana J; Fitzcharles, Eric K; Dornan, Grant J; Philippon, Marc J

2016-08-01

To describe T2 mapping values in arthroscopically determined International Cartilage Repair Society (ICRS) grades in damaged and healthy-appearing articular cartilage waste specimens from arthroscopic femoroacetabular impingement (FAI) treatment. Furthermore, we sought to compare ICRS grades of the specimens with biochemical, immunohistochemistry and histologic endpoints and assess correlations with T2 mapping. Twenty-four patients were prospectively enrolled, consecutively, between December 2011 and August 2012. Patients were included if they were aged 18 years or older and met criteria that followed the clinical indications for arthroscopy to treat FAI. Patients with prior hip trauma including fracture or dislocation or who have undergone prior hip surgery were excluded. All patients received a preoperative sagittal T2 mapping scan of the hip joint. Cartilage was graded intraoperatively using the ICRS grading system, and graded specimens were collected as cartilage waste for histologic, biochemical, and immunohistochemistry analysis. Forty-four cartilage specimens (22 healthy-appearing, 22 damaged) were analyzed. Median T2 values were significantly higher among damaged specimens (55.7 ± 14.9 ms) than healthy-appearing specimens (49.3 ± 12.3 ms; P = .043), which was most exaggerated among mild (grade 1 or 2) defects where the damaged specimens (58.1 ± 16.4 ms) were significantly higher than their paired healthy-appearing specimens (48.7 ± 15.4 ms; P = .026). Severely damaged specimens (grade 3 or 4) had significantly lower cumulative H&E than their paired healthy-appearing counterparts (P = .02) but was not statistically significant among damaged specimens with mild (grade 1 or 2) defects (P = .198). Among healthy-appearing specimens, median T2 and the percentage of collagen fibers oriented parallel were significantly correlated (rho = 0.425, P = .048). This study outlines the potential for T2 mapping to identify early cartilage degeneration in patients undergoing arthroscopy to treat FAI. Findings in ICRS grade 1 and 2 degeneration corresponded to an increase in T2 values. Further biochemical evaluation revealed a significant difference between healthy-appearing cartilage and late degeneration in cumulative H&E as well as significantly lower percentage of collagen fibers oriented parallel and a higher percentage of collagen fibers oriented randomly when considering all grades of cartilage damage. Level II, prospective comparative study. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Longitudinal diffusion tensor magnetic resonance imaging study of radiation-induced white matter damage in a rat model.

PubMed

Wang, Silun; Wu, Ed X; Qiu, Deqiang; Leung, Lucullus H T; Lau, Ho-Fai; Khong, Pek-Lan

2009-02-01

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular) correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in lambda(//) and lambda( perpendicular). DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

Carbon dioxide laser ablation with immediate autografting in a full-thickness porcine burn model.

PubMed Central

Glatter, R D; Goldberg, J S; Schomacker, K T; Compton, C C; Flotte, T J; Bua, D P; Greaves, K W; Nishioka, N S; Sheridan, R L

1998-01-01

OBJECTIVE: To compare the long-term clinical and histologic outcome of immediate autografting of full-thickness burn wounds ablated with a high-power continuous-wave CO2 laser to sharply débrided wounds in a porcine model. SUMMARY BACKGROUND DATA: Continuous-wave CO2 lasers have performed poorly as tools for burn excision because the large amount of thermal damage to viable subeschar tissues precluded successful autografting. However, a new technique, in which a high-power laser is rapidly scanned over the eschar, results in eschar vaporization without significant damage to underlying viable tissues, allowing successful immediate autografting. METHODS: Full-thickness paravertebral burn wounds measuring 36 cm2 were created on 11 farm swine. Wounds were ablated to adipose tissue 48 hours later using either a surgical blade or a 150-Watt continuous-wave CO2 laser deflected by an x-y galvanometric scanner that translated the beam over the tissue surface, removing 200 microm of tissue per scan. Both sites were immediately autografted and serially evaluated clinically and histologically for 180 days. RESULTS: The laser-treated sites were nearly bloodless. The mean residual thermal damage was 0.18+/-0.05 mm. The mean graft take was 96+/-11% in manual sites and 93+/-8% in laser sites. On postoperative day 7, the thickness of granulation tissue at the graft-wound bed interface was greater in laser-debrided sites. By postoperative day 180, the manual and laser sites were histologically identical. Vancouver scar assessment revealed no differences in scarring at postoperative day 180. CONCLUSIONS: Long-term scarring, based on Vancouver scar assessments and histologic evaluation, was equivalent at 6 months in laser-ablated and sharply excised sites. Should this technology become practical, the potential clinical implications include a reduction in surgical blood loss without sacrifice of immediate engraftment rates or long-term outcome. Images Figure 1. Figure 2. Figure 3. Figure 4. PMID:9712572

The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus.

PubMed

Salphale, P; Danda, D; Chandrashekar, L; Peter, D; Jayaseeli, N; George, R

2011-12-01

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a newly described tool used to assess the activity of and damage caused by cutaneous lupus erythematosus (CLE). There is a paucity of data on CLASI from the Indian subcontinent. We sought to determine the applicability of CLASI in specific lesions of CLE in patients with systemic lupus erythematosus (SLE) attending a tertiary care hospital in India. In this prospective, cross-sectional study, 93 patients of SLE with cutaneous lesions were recruited. CLASI activity and damage scores of lupus erythematosus (LE)-specific skin lesions were done in 75 patients with SLE. The mean CLASI activity score was 15.4 ± 9.4 (range 0-39) and the mean damage score was 6.87 ± 7.75 (range 0-30). Higher mean CLASI activity scores were seen in patients with a combination of acute, subacute and chronic CLE and in those with widespread lesions. Patients with longstanding disease and long duration of skin lesions had higher damage scores. This study shows that CLASI is an effective tool to assess cutaneous activity of LE-specific lesions, and the damage caused by them, in Indian patients.

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients.

PubMed

Kaihan, Ahmad Baseer; Yasuda, Yoshinari; Katsuno, Takayuki; Kato, Sawako; Imaizumi, Takahiro; Ozeki, Takaya; Hishida, Manabu; Nagata, Takanobu; Ando, Masahiko; Tsuboi, Naotake; Maruyama, Shoichi

2017-12-01

The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

Hepatoprotective activity of sea cucumber Phyllophorus sp. extract in carp (Cyprinus carpio)

NASA Astrophysics Data System (ADS)

Sulmartiwi, Laksmi; Triastuti, Juni; Andriyono, Sapto; Umami, Mardiah Rahma

2017-02-01

Many procedures continuously in aquaculture and scientific research like tagging and vaccinating cause pain, involving damaging tissue and also cause stress responses in fish. Stress responses in fish influence liver because liver have vital role to supply energy and metabolism. Histology alteration in liver is caused by stress response like changes of vacuolation hepatocyte and characteristic colour. Triterpenoid was known had hepatoprotective activity. One of marine organism contained triterpenoid was sea cucumber. Result of research showed that liver tissue in fish with injected acetic acid 5 % (in upper lip) as pain stimulus have histopathology damages such as pyknosis (medium damage level) and oedema (heavy damage level) after 8 hour injection. Injected Lidocaine 1mg/fish as analgesic drug have histopathology damages such as oedema (heavy damages level), necrosis and pyknosis (low damages level). Injected acetic acid 5 % (in upper lip) and ethanolic extract of sea cucumber Phyllophorus sp. dose 5 mg/50 gr body weight shown histopathology damages such as necrosis, edema (medium damage level) and pyknosis (low damage level).

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis.

PubMed

Oh, Sa-Rang; Ok, Seon; Jung, Tae-Sung; Jeon, Sang-Ok; Park, Ji-Min; Jung, Ji-Wook; Ryu, Deok-Seon

2017-09-01

To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE 2 , COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting. Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE 2 in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment. The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

A polarized light microscopy method for accurate and reliable grading of collagen organization in cartilage repair.

PubMed

Changoor, A; Tran-Khanh, N; Méthot, S; Garon, M; Hurtig, M B; Shive, M S; Buschmann, M D

2011-01-01

Collagen organization, a feature that is critical for cartilage load bearing and durability, is not adequately assessed in cartilage repair tissue by present histological scoring systems. Our objectives were to develop a new polarized light microscopy (PLM) score for collagen organization and to test its reliability. This PLM score uses an ordinal scale of 0-5 to rate the extent that collagen network organization resembles that of young adult hyaline articular cartilage (score of 5) vs a totally disorganized tissue (score of 0). Inter-reader reliability was assessed using Intraclass Correlation Coefficients (ICC) for Agreement, calculated from scores of three trained readers who independently evaluated blinded sections obtained from normal (n=4), degraded (n=2) and repair (n=22) human cartilage biopsies. The PLM score succeeded in distinguishing normal, degraded and repair cartilages, where the latter displayed greater complexity in collagen structure. Excellent inter-reader reproducibility was found with ICCs for Agreement of 0.90 [ICC(2,1)] (lower boundary of the 95% confidence interval is 0.83) and 0.96 [ICC(2,3)] (lower boundary of the 95% confidence interval is 0.94), indicating the reliability of a single reader's scores and the mean of all three readers' scores, respectively. This PLM method offers a novel means for systematically evaluating collagen organization in repair cartilage. We propose that it be used to supplement current gold standard histological scoring systems for a more complete assessment of repair tissue quality. Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

In vivo longitudinal MRI and behavioral studies in experimental spinal cord injury.

PubMed

Sundberg, Laura M; Herrera, Juan J; Narayana, Ponnada A

2010-10-01

Comprehensive in vivo longitudinal studies that include multi-modal magnetic resonance imaging (MRI) and a battery of behavioral assays to assess functional outcome were performed at multiple time points up to 56 days post-traumatic spinal cord injury (SCI) in rodents. The MRI studies included high-resolution structural imaging for lesion volumetry, and diffusion tensor imaging (DTI) for probing the white matter integrity. The behavioral assays included open-field locomotion, grid walking, inclined plane, computerized activity box performance, and von Frey filament tests. Additionally, end-point histology was assessed for correlation with both the MRI and behavioral data. The temporal patterns of the lesions were documented on structural MRI. DTI studies showed significant changes in white matter that is proximal to the injury epicenter and persisted to day 56. White matter in regions up to 1 cm away from the injury epicenter that appeared normal on conventional MRI also exhibited changes that were indicative of tissue damage, suggesting that DTI is a more sensitive measure of the evolving injury. Correlations between DTI and histology after SCI could not be firmly established, suggesting that injury causes complex pathological changes in multiple tissue components that affect the DTI measures. Histological evidence confirmed a significant decrease in myelin and oligodendrocyte presence 56 days post-SCI. Multiple assays to evaluate aspects of functional recovery correlated with histology and DTI measures, suggesting that damage to specific white matter tracts can be assessed and tracked longitudinally after SCI.

Focal Defects of the Knee Articular Surface: Evidence of a Regenerative Potential Pattern in Osteochondritis Dissecans and Degenerative Lesions

PubMed Central

Gabusi, Elena; Manferdini, Cristina; Paolella, Francesca; Gambari, Laura; Mariani, Erminia

2017-01-01

The surgical treatment of knee articular focal lesions may offer heterogeneous clinical results. Osteochondritis dissecans (OCD) lesions showed to heal better than degenerative lesions (DL) but the underlying biological reasons are unknown. We evaluated the basal histological and immunohistochemical characteristics of these lesions analyzing a series of osteochondral fragments from young patients with similar age but presenting different etiology. Osteochondral tissue samples were stained with Safranin O and graded using a histological score. Markers of mesenchymal progenitor cells (CD146), osteoclasts (tartrate-resistant acid phosphatase, TRAP), and vessels (CD34) were evaluated. Histological score showed a higher degeneration of both cartilage and bone compartments in OCD compared to DL fragments. Only CD146-positive cells were found at the same percentage in cartilage compartment of both DL and OCD patients. By contrast, in the bone compartment a significantly higher percentage of CD146, TRAP, and CD34 markers was found in OCD compared to DL patients. These data showed distinct histological characteristics of osteochondral focal lesions located in the same anatomical region but having a different etiology. The higher percentages of these markers in OCD than in DL, mainly associated with a high bone turnover, could help to explain the higher clinical healing potential of OCD patients. PMID:28770227

Does placental inflammation relate to brain lesions and volume in preterm infants?

PubMed

Reiman, Milla; Kujari, Harry; Maunu, Jonna; Parkkola, Riitta; Rikalainen, Hellevi; Lapinleimu, Helena; Lehtonen, Liisa; Haataja, Leena

2008-05-01

To evaluate the association between histologic inflammation of placenta and brain findings in ultrasound examinations and regional brain volumes in magnetic resonance imaging in very-low-birth-weight (VLBW) or in very preterm infants. VLBW or very preterm infants (n = 121) were categorized into 3 groups according to the most pathologic brain finding on ultrasound examinations until term. The brain magnetic resonance imaging performed at term was analyzed for regional brain volumes. The placentas were analyzed for histologic inflammatory findings. Histologic chorioamnionitis on the fetal side correlated to brain lesions in univariate but not in multivariate analyses. Low gestational age was the only significant risk factor for brain lesions in multivariate analysis (P < .0001). Histologic chorioamnionitis was not associated with brain volumes in multivariate analyses. Female sex, low gestational age, and low birth weight z score correlated to smaller volumes in total brain tissue (P = .001, P = .0002, P < .0001, respectively) and cerebellum (P = .047, P = .003, P = .001, respectively). In addition, low gestational age and low-birth-weight z score correlated to a smaller combined volume of basal ganglia and thalami (P = .0002). Placental inflammation does not appear to correlate to brain lesions or smaller regional brain volumes in VLBW or in very preterm infants at term age.

Assessment of Cochlear Damage after Microwave Irradiation.

DTIC Science & Technology

1988-02-26

dosimetry measurements. Mr. Thomas J. Watkins, Washington Uni- versity School of Medicine provided excellent technical assis- tance throughout the study... MATERIAL AND METHODS Subjects.................................................. 6 Microwave Exposure....................................... 6 Histological...Processing.................................. 9 Microscopic Evaluation................................... 9 RESU LTS Dosimetry

Heart Alterations after Domoic Acid Administration in Rats

PubMed Central

Vieira, Andres C.; Cifuentes, José Manuel; Bermúdez, Roberto; Ferreiro, Sara F.; Castro, Albina Román; Botana, Luis M.

2016-01-01

Domoic acid (DA) is one of the best known marine toxins, causative of important neurotoxic alterations. DA effects are documented both in wildlife and experimental assays, showing that this toxin causes severe injuries principally in the hippocampal area. In the present study we have addressed the long-term toxicological effects (30 days) of DA intraperitoneal administration in rats. Different histological techniques were employed in order to study DA toxicity in heart, an organ which has not been thoroughly studied after DA intoxication to date. The presence of DA was detected by immunohistochemical assays, and cellular alterations were observed both by optical and transmission electron microscopy. Although histological staining methods did not provide any observable tissue damage, transmission electron microscopy showed several injuries: a moderate lysis of myofibrils and loss of mitochondrial conformation. This is the first time the association between heart damage and the presence of the toxin has been observed. PMID:26978401

A review of the physiological and histological effects of laser osteotomy.

PubMed

Rajitha Gunaratne, G D; Khan, Riaz; Fick, Daniel; Robertson, Brett; Dahotre, Narendra; Ironside, Charlie

2017-01-01

Osteotomy is the surgical cutting of bone. Some obstacles to laser osteotomy have been melting, carbonisation and subsequent delayed healing. New cooled scanning techniques have resulted in effective bone cuts without the strong thermal side effects, which were observed by inappropriate irradiation techniques with continuous wave and long pulsed lasers. With these new techniques, osteotomy gaps histologically healed with new bone formation without any noticeable or minimum thermal damage. No significant cellular differences in bone healing between laser and mechanical osteotomies were noticed. Some studies even suggest that the healing rate may be enhanced following laser osteotomy compared to conventional mechanical osteotomy. Additional research is necessary to evaluate different laser types with appropriate laser setting variables to increase ablation rates, with control of depth, change in bone type and damage to adjacent soft tissue. Laser osteotomy has the potential to become incorporated into the armamentarium of bone surgery.

Analysis of surface damage in retrieved carbon fiber-reinforced and plain polyethylene tibial components from posterior stabilized total knee replacements.

PubMed

Wright, T M; Rimnac, C M; Faris, P M; Bansal, M

1988-10-01

The performance of carbon fiber-reinforced ultra-high molecular weight polyethylene was compared with that of plain (non-reinforced) polyethylene on the basis of the damage that was observed on the articulating surfaces of retrieved tibial components of total knee prostheses. Established microscopy techniques for subjectively grading the presence and extent of surface damage and the histological structure of the surrounding tissues were used to evaluate twenty-six carbon fiber-reinforced and twenty plain polyethylene components that had been retrieved after an average of twenty-one months of implantation. All of the tibial components were from the same design of total knee replacement. The two groups of patients from whom the components were retrieved did not differ with regard to weight, the length of time that the component had been implanted, the radiographic position and angular alignment of the component, the original diagnosis, or the reason for removal of the component. The amounts and types of damage that were observed did not differ for the two materials. For both materials, the amount of damage was directly related to the length of time that the component had been implanted. The histological appearance of tissues from the area around the component did not differ for the two materials, except for the presence of fragments of carbon fiber in many of the samples from the areas around carbon fiber-reinforced components.

The ELGAN study of the brain and related disorders in extremely low gestational age newborns.

PubMed

O'Shea, T M; Allred, E N; Dammann, O; Hirtz, D; Kuban, K C K; Paneth, N; Leviton, A

2009-11-01

Extremely low gestational age newborns (ELGANs) are at increased risk for structural and functional brain abnormalities. To identify factors that contribute to brain damage in ELGANs. Multi-center cohort study. We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites; 1201 (80%) survived to 2 years corrected age. Information about exposures and characteristics was collected by maternal interview, from chart review, microbiologic and histological examination of placentas, and measurement of proteins in umbilical cord and early postnatal blood spots. Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions, on protocol cranial ultrasound scans; head circumference and developmental outcomes at 24 months adjusted age, i.e., cerebral palsy, mental and motor scales of the Bayley Scales of Infant Development, and a screen for autism spectrum disorders. ELGAN Study publications thus far provide evidence that the following are associated with ultrasongraphically detected white matter damage, cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor premature rupture of membranes, or cervical insufficiency; recovery of microorganisms in the placenta parenchyma, including species categorized as human skin microflora; histological evidence of placental inflammation; lower gestational age at delivery; greater neonatal illness severity; severe chronic lung disease; neonatal bacteremia; and necrotizing enterocolitis. In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our study is the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma.

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats

PubMed Central

Kasote, D. M.; Badhe, Y. S.; Zanwar, A. A.; Hegde, M. V.; Deshmukh, K. K.

2012-01-01

Objective: to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats. Materials and Methods: Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl4 in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. Results: EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl4 intoxication. Hepatic lipid peroxidation elevated by CCl4 intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl4 -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl4 -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). Conclusion: EPC-BF possesses the significant hepatoprotective activity against CCl4 induced liver damage, which could be mediated through increase in antioxidant defenses. PMID:22923966

Histology, fusion status, and outcome in metastatic rhabdomyosarcoma: A report from the Children's Oncology Group.

PubMed

Rudzinski, Erin R; Anderson, James R; Chi, Yueh-Yun; Gastier-Foster, Julie M; Astbury, Caroline; Barr, Frederic G; Skapek, Stephen X; Hawkins, Douglas S; Weigel, Brenda J; Pappo, Alberto; Meyer, William H; Arnold, Michael A; Teot, Lisa A; Parham, David M

2017-12-01

Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) has historically been of prognostic and therapeutic importance. However, classification has been complicated by shifting histologic criteria required for an ARMS diagnosis. Children's Oncology Group (COG) studies after IRS-IV, which included the height of this diagnostic shift, showed both an increased number of ARMS and an increase in the proportion of fusion-negative ARMS. Following diagnostic standardization and histologic re-review of ARMS cases enrolled during this era, analysis of low-risk (D9602) and intermediate-risk (D9803) rhabdomyosarcoma (RMS) studies showed that fusion status rather than histology best predicts prognosis for patients with RMS. This analysis remains to be completed for patients with high-risk RMS. We re-reviewed cases on high-risk COG studies D9802 and ARST0431 with an enrollment diagnosis of ARMS. We compared the event-free survival (EFS) and overall survival by histology, PAX-FOXO1 fusion, and clinical risk factors (Oberlin score) for patients with metastatic RMS using the log-rank test. Histology re-review resulted in reclassification as ERMS for 12% of D9802 cases and 5% of ARST0431 cases. Fusion-negative RMS had a superior EFS to fusion-positive RMS; however, poorer outcome for metastatic RMS was most related to clinical risk factors including age, primary site, and number of metastatic sites. In contrast to low- or intermediate-risk RMS, in metastatic RMS, clinical risk factors have the most impact on patient outcome. PAX-FOXO1 fusion is more common in patients with a high Oberlin score, but fusion status is not an independent biomarker of prognosis. © 2017 Wiley Periodicals, Inc.

Strong association of insulin-like growth factor 1 receptor expression with histologic grade, subtype, and HPV status in penile squamous cell carcinomas: a tissue microarray study of 112 cases.

PubMed

Faraj, Sheila F; Gonzalez-Roibon, Nilda; Munari, Enrico; Sharma, Rajni; Burnett, Arthur L; Cubilla, Antonio L; Netto, George J; Chaux, Alcides

2017-06-01

Insulin-like growth factor-1 receptor (IGF1R) plays a key role in cell growth and transformation. It is overexpressed in several solid tumors. This study evaluates IGF1R immunoexpression in penile squamous cell carcinoma (SCC). Four tissue microarrays were built from formalin-fixed, paraffin-embedded blocks of 112 penile SCC from Paraguay. Membranous IGF1R expression was evaluated by immunohistochemistry using two different approaches. An H-score was calculated in each spot (stain intensity by extent), and a median score per tumor was obtained. The second approach consisted of a score similar to the scoring system that was used for evaluating HER2 immunoexpression. For each case, the highest category obtained at any spot was used for statistical analyses. IGF1R expression was compared by histologic subtype, grade, and human papillomavirus (HPV) status. Median H-score was 22.5. The distribution of IGF1R expression by HER2 approach was as follows: 0 in 33.0% cases, 1+ in 46.4%, 2+ in 14.3%, and 3+ in 6.2%. IGF1R H-scores were associated with basaloid and warty/basaloid subtypes (p = 0.0026) and higher grade (p = 0.00052). Although weaker when using the HER2 approach, the association of IGF1R expression with subtype (p = 0.015) and grade (p = 0.015) remained significant. Furthermore, there was an association between IGF1R expression by HER2 approach and HPV status (p = 0.012). IGF1R was expressed in about two thirds of penile SCC cases, showing a strong positive association with histologic grade, subtype, and HPV status. Considering that grade is a predictor of outcome IGF1R expression may have prognostic relevance and could point to a potential role for IGF1R inhibitors in treating penile SCC.

A comparison between modified Alvarado score and RIPASA score in the diagnosis of acute appendicitis.

PubMed

Singla, Anand; Singla, Satpaul; Singh, Mohinder; Singla, Deeksha

2016-12-01

Acute appendicitis is a common but elusive surgical condition and remains a diagnostic dilemma. It has many clinical mimickers and diagnosis is primarily made on clinical grounds, leading to the evolution of clinical scoring systems for pin pointing the right diagnosis. The modified Alvarado and RIPASA scoring systems are two important scoring systems, for diagnosis of acute appendicitis. We prospectively compared the two scoring systems for diagnosing acute appendicitis in 50 patients presenting with right iliac fossa pain. The RIPASA score correctly classified 88 % of patients with histologically confirmed acute appendicitis compared with 48.0 % with modified Alvarado score, indicating that RIPASA score is more superior to Modified Alvarado score in our clinical settings.

Subperiosteal preparation using a new piezoelectric device: a histological examination.

PubMed

Stoetzer, Marcus; Magel, Anja; Kampmann, Andreas; Lemound, Juliana; Gellrich, Nils-Claudius; von See, Constantin

2014-01-01

Subperiosteal preparation using a periosteal elevator leads to disturbances of local immunohistochemistry and periosteal histology due to a microtrauma. Usually soft-tissue damage can be considerably reduced by using piezoelectric technology. For this reason, the effects of a novel piezoelectric device on immunohistochemistry and periosteal histology were examined and compared to conventional preparation of the periosteum using a periosteal elevator. Lewis rats were randomly assigned to one of five groups (n=50). Subperiosteal preparation was performed using either a piezoelectric device or a periosteal elevator. Immunohistochemical and histological analyses were performed immediately after preparation as well as three and eight days postoperatively. A statistical analysis of the histological colouring was performed offline using analysis of variance (ANOVA) on ranks (p<0.05). At all times, immunohistochemical and histological analysis demonstrated a significantly more homogenous tissue structure in the group of rats that underwent piezosurgery than in the group of rats that underwent treatment with a periosteal elevator. The use of a piezoelectric device for subperiosteal preparation is associated with more harmonious immunohistochemical and histological results for the periosteum than the use of a conventional periosteal elevator. As a result, piezoelectric devices can be expected to have a positive effect primarily on soft tissue, in particular of the periosteal as well as on surrounding tissues.

Pulpo-dentin complex response after direct capping with self-etch adhesive systems.

PubMed

Nowicka, Alicja; Parafiniuk, Miroslaw; Lipski, Mariusz; Lichota, Damian; Buczkowska-Radlinska, Jadwiga

2012-01-01

The purpose of the present study was to evaluate morphologically the response of feline teeth pulp to direct pulp capping with two different self-etch adhesive systems. Twenty-four cavities in feline teeth were mechanically exposed and assigned to one of two experimental groups: AdheSE + Tetric Ceram (the ASE group), or Adper Prompt L-Pop + Filtek Supreme (the APLP group). There was also a control group Dycal Ca(OH)(2) liner + Amalgam (the CH group eight teeth), and six teeth were used as an intact control group. The animals were sacrificed after 40 days. The teeth were removed and processed for standard histological evaluation, using a scoring system for inflammatory cell response, pulp tissue disorganisation, reparative tissue formation, and the presence of bacteria. Statistical analysis revealed no significant differences between the ASE and APLP self-etching resin systems during the observation period. The majority of the specimens presented inflammatory pulp response with tissue disorganisation and a lack of dentinal bridge formation. CH capping resulted in a significantly smaller inflammatory pulp response and a considerably higher incidence of reparative dentin formation. ASE and APLP were comparably effective as direct pulp capping materials, but their application resulted in significantly greater pulp tissue damage than CH capping. Further in vivo human studies are necessary to determine which adhesive resin systems should be clinically used for direct pulp capping without incurring severe damage to the pulpal tissue.

Effects of indigo naturalis on colonic mucosal injuries and inflammation in rats with dextran sodium sulphate-induced ulcerative colitis

PubMed Central

Wang, Yunliang; Liu, Lijuan; Guo, Yi; Mao, Tangyou; Shi, Rui; Li, Junxiang

2017-01-01

The effects of indigo naturalis (IN), which is a traditional Chinese herbal formulation, have been clinically demonstrated in treating refractory ulcerative colitis (UC). The present study aimed to verify the effects and mechanisms of IN in experimental UC rats. A total of 48 male Sprague-Dawley rats were randomly divided into six groups: Chow, model, high-dose IN, medium-dose IN, low-dose IN and mesalazine (a bowel-specific aminosalicylate drug) groups. The models were administered 3.5% dextran sodium sulphate solution for 7 days. The treatment groups were administered IN or mesalazine and then sacrificed and sampled on day 8. Disease activity index (DAI), histological damage score (HDS) and myeloperoxidase (MPO) activity were used to evaluate the severity of UC. Colon and serum cytokines were detected using liquid-phase chip technology and the expression of occludin protein in colonic mucosa was assessed by immunohistochemistry and western blot analysis. The results indicated that the oral administration of IN may reduce DAI, HDS and MPO activity. IN also reduced the expression of inflammatory cytokines and increased the expression of colonic mucosal repair-related cytokines and occludin protein. These results highlight the potential of IN as a therapeutic agent for treating UC through its action of inflammation control and colonic mucosal damage repair. PMID:28781623

The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide-Induced Cystitis in Rats

PubMed Central

Moraes, Janaína P.; Pereira, Denyson S.; Matos, Alexandre S.; Santana, Danielle G.; Santos, Cliomar A.; Estevam, Charles S.; Fakhouri, Ricardo; de Lucca Junior, Waldecy; Camargo, Enilton A.

2013-01-01

Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400 mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx − were also evaluated. Treatment with EECp (100–400 mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx − induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100 mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats. PMID:24348180

Thiopental attenuates hypoxic changes of electrophysiology, biochemistry, and morphology in rat hippocampal slice CA1 pyramidal cells.

PubMed

Wang, T; Raley-Susman, K M; Wang, J; Chambers, G; Cottrell, J E; Kass, I S

1999-11-01

Thiopental has been shown to protect against cerebral ischemic damage; however, it has undesirable side effects. We have examined how thiopental alters histological, physiological, and biochemical changes during and after hypoxia. These experiments should enable the discovery of agents that share some of the beneficial effects of thiopental. We made intracellular recordings and measured ATP, sodium, potassium, and calcium concentrations from CA1 pyramidal cells in rat hippocampal slices subjected to 10 minutes of hypoxia with and without 600 micromol/L thiopental. Thiopental delayed the time until complete depolarization (21+/-3 versus 11+/-2 minutes for treated versus untreated slices, respectively) and attenuated the level of depolarization at 10 minutes of hypoxia (-33+/-6 versus -12+/-5 mV). There was improved recovery of the resting potential after 10 minutes of hypoxia in slices treated with thiopental (89% versus 31% recovery). Thiopental attenuated the changes in sodium (140% versus 193% of prehypoxic concentration), potassium (62% versus 46%), and calcium (111% versus 197%) during 10 minutes of hypoxia. There was only a small effect on ATP (18% versus 8%). The percentage of cells showing clear histological damage was decreased by thiopental (45% versus 71%), and thiopental improved protein synthesis after hypoxia (75% versus 20%). Thiopental attenuates neuronal depolarization, an increase in cellular sodium and calcium concentrations, and a decrease in cellular potassium and ATP concentrations during hypoxia. These effects may explain the reduced histological, protein synthetic, and electrophysiological damage to CA1 pyramidal cells after hypoxia with thiopental.

PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging.

PubMed

den Hartog, A G; Bovens, S M; Koning, W; Hendrikse, J; Pasterkamp, G; Moll, F L; de Borst, G J

2011-02-01

In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk.

IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture.

PubMed

Lara-Diaz, V J; Castilla-Cortazar, I; Martín-Estal, I; García-Magariño, M; Aguirre, G A; Puche, J E; de la Garza, R G; Morales, L A; Muñoz, U

2017-05-01

Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1 +/- , and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.

PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging

PubMed Central

den Hartog, A.G; Bovens, S.M; Koning, W; Hendrikse, J; Pasterkamp, G; Moll, F.L; de Borst, G.J

2011-01-01

Introduction: In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. Study objective: The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. Design: We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. Discussion: We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk. PMID:22294972

FKBP12 deficiency reduces strength deficits after eccentric contraction-induced muscle injury

PubMed Central

Corona, Benjamin T.; Rouviere, Clement; Hamilton, Susan L.; Ingalls, Christopher P.

2008-01-01

Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from excitation-contraction uncoupling. FKBP12 is a 12-kDa binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca2+ release channel [ryanodine receptor (RyR1)] and plays an important role in excitation-contraction coupling. To assess the effects of FKBP12 deficiency on muscle injury and recovery, we measured anterior crural muscle (tibialis anterior and extensor digitorum longus muscles) strength in skeletal muscle-specific FKBP12-deficient and wild-type (WT) mice before and after a single bout of 150 eccentric contractions, as well as before and after the performance of six injury bouts. Histological damage of the tibialis anterior muscle was assessed after injury. Body weight and peak isometric and eccentric torques were lower in FKBP12-deficient mice compared with WT mice. There were no differences between FKBP12-deficient and WT mice in preinjury peak isometric and eccentric torques when normalized to body weight, and no differences in the relative decreases in eccentric torque with a single or multiple injury bouts. After a single injury bout, FKBP12-deficient mice had less initial strength deficits and recovered faster (especially females) than WT mice, despite no differences in the degree of histological damage. After multiple injury bouts, FKBP12-deficient mice recovered muscle strength faster than WT mice and exhibited significantly less histological muscle damage than WT mice. In summary, FKBP12 deficiency results in less initial strength deficits and enhanced recovery from single (especially females) and repeated bouts of injury than WT mice. PMID:18511525

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study.

PubMed

Riis, R G C; Gudbergsen, H; Simonsen, O; Henriksen, M; Al-Mashkur, N; Eld, M; Petersen, K K; Kubassova, O; Bay Jensen, A C; Damm, J; Bliddal, H; Arendt-Nielsen, L; Boesen, M

2017-02-01

To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA). Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R 2 ). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3). 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R 2 -value obtained in Model 1 was R 2  = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R 2  = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R 2  = 0.71. DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Performance of brain-damaged and non-brain-damaged institutionalized children on the Minnesota Percepto-Diagnostic Test.

PubMed

Holland, J M; Fuller, G B; Barth, C E

1982-01-01

Examined the performance of 64 children on the Minnesota Percepto-Diagnostic test (MPD) who were diagnosed as either Brain-Damaged (BD) or emotionally impaired Non-Brain-Damaged (NBD). There were 31 children in the NBD group and 33 in the BD group. The MPD T-score and Actuarial Table significantly differentiated between the two groups. Seventy-four percent of the combined BD-NBD groups were identified correctly. Additional discriminant analysis on this sample yielded combined BD-NBD groups classification rates that ranged from 77% with the MPD variables Separation of Circle-Diamond (SPCD), Distortion of Circle-Diamond (DCD) and Distortion of Dots (DD) to 83% with the WISC-R three IQ scores plus the MPD T-score, SPCD and DD. The MPD T-score and Actuarial Table (MPD Two-Step Diagnosis) appeared to generalize to other populations more readily than discriminant analysis formulae, which tend to be sensitive to the samples from which they are derived.

Revisiting the role of pathological analysis in transarterial chemoembolization-treated hepatocellular carcinoma after transplantation

PubMed Central

Vasuri, Francesco; Malvi, Deborah; Rosini, Francesca; Baldin, Pamela; Fiorentino, Michelangelo; Paccapelo, Alexandro; Ercolani, Giorgio; Pinna, Antonio Daniele; Golfieri, Rita; Morselli-Labate, Antonio Maria; Grigioni, Walter Franco; D’Errico-Grigioni, Antonia

2014-01-01

AIM: To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification. METHODS: We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected. We finally considered 11 histological variables for each patient: total number of nodules, number of viable nodules, size of the major nodule, size of the major viable nodule, occurrence of microscopic vascular invasion, maximum Edmondson's grade, clear cell/sarcomatous changes, and the residual neoplastic volume. Survival data were computed by means of the Kaplan-Meier procedure and analyzed by means of the Cox proportional hazards model. The multivariate linear regression and a k-means cluster analysis were also used in order to compute the standardized histological score. RESULTS: The total number of nodules, the residual neoplastic volume (the total volume of all evaluated nodules minus the necrotic portion) and the microvascular invasion entered the Cox multivariate hazard model with HCC recurrence as dependent variable. The histological score was therefore computed and a cluster analysis sorted recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates and 1.6%, 11.1% and 38.5% of tumor-related mortality respectively at the end of follow-up. CONCLUSION: The histological score allows a reliable stratification of HCC recurrence risk, especially in those recipients found out to be beyond the Milan criteria after orthotopic liver transplantation (OLT). PMID:25309084

Lung tissue remodelling in MCT-induced pulmonary hypertension: a proposal for a novel scoring system and changes in extracellular matrix and fibrosis associated gene expression.

PubMed

Franz, Marcus; Grün, Katja; Betge, Stefan; Rohm, Ilonka; Ndongson-Dongmo, Bernadin; Bauer, Reinhard; Schulze, P Christian; Lichtenauer, Michael; Petersen, Iver; Neri, Dario; Berndt, Alexander; Jung, Christian

2016-12-06

Pulmonary hypertension (PH) is associated with vasoconstriction and remodelling. We studied lung tissue remodelling in a rat model of PH with special focus on histology and extracellular matrix (ECM) remodelling. After induction of PH by monocrotaline, lung tissue was analysed histologically, by gene expression analysis and immunofluorescence labelling of ED-A domain containing fibronectin (ED-A+ Fn), B domain containing tenascin-C (B+ Tn-C) as well as alpha-smooth muscle actin (α-SMA). Serum concentrations of ED-A+ Fn were determined by ELISA. Systolic right ventricular pressure (RVPsys) values were significantly elevated in PH (n = 18; 75 ± 26.4 mmHg) compared to controls (n = 10; 29 ± 19.3 mmHg; p = 0.015). The histological sum-score was significantly increased in PH (8.0 ± 2.2) compared to controls (2.5 ± 1.6; p < 0.001). Gene expression analysis revealed relevant induction of several key genes of extracellular matrix remodelling. Increased protein deposition of ED-A+ Fn but not of B+ Tn-C and α-SMA in lung tissue was found in PH (2.88 ± 3.19 area%) compared to controls (1.32 ± 0.16 area%; p = 0.030). Serum levels of ED-A+ Fn were significantly higher in PH (p = 0.007) positively correlating with RVPsys (r = 0.618, p = 0.019). We here present a novel histological scoring system to assess lung tissue remodelling in PH. Gene expression analysis revealed induction of candidate genes involved in collagen matrix turnover, fibrosis and vascular remodelling. The stable increased tissue deposition of ED-A+ Fn in PH as well as its dynamics in serum suggests a role as a promising novel biomarker and potential therapeutic target.

Immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck squamous cell carcinoma.

PubMed

de Andrade, Ana Luiza Dias Leite; Ferreira, Stefânia Jeronimo; Ferreira, Sonia Maria Soares; Ribeiro, Camila Maria Beder; Freitas, Roseana de Almeida; Galvão, Hébel Cavalcanti

2015-10-01

The epidermal growth factor receptor (EGFR) and the extracellular matrix metalloproteinase inducer (EMMPRIN) have been identified as oncologically important targets. This study aimed to evaluate the immunoexpression of EGFR and EMMPRIN in a series of cases of head and neck squamous cell carcinoma (HNSCC). Forty-five cases of HNSCC were selected for this study and evaluated with anti-EGFR and anti-EMMPRIN antibodies. The percentage of positive cells was determined assessing to the following categories: score 1 (staining in 0-50% of cells), score 2 (staining in 51-75% of cells), and score 3 (staining in >75% of cells). Immunostaining intensity was graded according to the following parameters: score 1 (absent/weak expression) and score 2 (strong expression). For EGFR, a predominance of high median scores was observed in cases of both histological grades of malignancy and in different clinical stages (p>0.05). For EMMPRIN, a statistically significant difference was observed between the histological grades of malignancy (p=0.030). Regarding the immunostaining intensity of EMMPRIN, it was observed a predominance of score 1 in cases with stages I/II, whereas most cases with stages III/IV presented score 2 (p=0.032). Considering the anatomical location, most cases of buccal floor presented higher median score of EMMPRIN in comparison with the other sites (p=0.015). These findings suggest that both proteins are potential targets for cancer therapy and EMMPRIN can be used as a prognostic marker of a more aggressive biological behavior in patients with HNSCC. Copyright © 2015 Elsevier GmbH. All rights reserved.

Corneal staining patterns in vernal keratoconjunctivitis: the new VKC-CLEK scoring scale.

PubMed

Leonardi, Andrea; Lazzarini, Daniela; La Gloria Valerio, Alvise; Scalora, Tania; Fregona, Iva

2018-01-24

To propose a new scoring system in the assessment of ocular surface epithelial damage in vernal keratoconjunctivitis (VKC). 25 consecutive patients with VKC (50 eyes) were evaluated using the Quality of Life in children with VKC (QUICK) questionnaire and objective clinical measures: fluorescein and lissamine green staining and cornea confocal microscopy (Heidelberg Retina Tomography 3). Oxford, Van Bljsterweld and a new system, the VKC-Collaborative Longitudinal Evaluation of Keratoconus study (CLEK) (VKC-CLEK) scores, were used to evaluate the epithelial damage after staining. Mean Oxford and VKC-CLEK scores were significantly different after fluorescein staining (P<0.001), but significantly correlated (P<0.001; r=0.649). The same data were obtained comparing Van Bljsterweld and VKC-CLEK after lissamine green staining (P<0.001; r=0.760). In patient with limbal VKC, a statistically significant difference was found comparing new VKC-CLEK scores and Oxford or Van Bljsterweld scores (P<0.001), but not in tarsal VKC. A statistically superior concordance was found between QUICK and VKC-CLEK scores compared with standard staining scores values (P<0.001). Oxford and Van Bijsterveld scores are not adequate for the evaluation of the epithelial damage in patients with limbal VKC because the staining patterns considered for these tests do not correspond to the staining patterns in patients with VKC. We propose a new scoring system, VKC-CLEK, to better evaluate both limbal and tarsal epithelial damage in patients with VKC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Is 'virtual histology' the next step after the 'virtual autopsy'? Magnetic resonance microscopy in forensic medicine.

PubMed

Thali, M J; Dirnhofer, R; Becker, R; Oliver, W; Potter, K

2004-10-01

The study aimed to validate magnetic resonance microscopy (MRM) studies of forensic tissue specimens (skin samples with electric injury patterns) against the results from routine histology. Computed tomography and magnetic resonance imaging are fast becoming important tools in clinical and forensic pathology. This study is the first forensic application of MRM to the analysis of electric injury patterns in human skin. Three-dimensional high-resolution MRM images of fixed skin specimens provided a complete 3D view of the damaged tissues at the site of an electric injury as well as in neighboring tissues, consistent with histologic findings. The image intensity of the dermal layer in T2-weighted MRM images was reduced in the central zone due to carbonization or coagulation necrosis and increased in the intermediate zone because of dermal edema. A subjacent blood vessel with an intravascular occlusion supports the hypothesis that current traveled through the vascular system before arcing to ground. High-resolution imaging offers a noninvasive alternative to conventional histology in forensic wound analysis and can be used to perform 3D virtual histology.

Which cartilage is regenerated, hyaline cartilage or fibrocartilage? Non-invasive ultrasonic evaluation of tissue-engineered cartilage.

PubMed

Hattori, K; Takakura, Y; Ohgushi, H; Habata, T; Uematsu, K; Takenaka, M; Ikeuchi, K

2004-09-01

To investigate ultrasonic evaluation methods for detecting whether the repair tissue is hyaline cartilage or fibrocartilage in new cartilage regeneration therapy. We examined four experimental rabbit models: a spontaneous repair model (group S), a large cartilage defect model (group L), a periosteal graft model (group P) and a tissue-engineered cartilage regeneration model (group T). From the resulting ultrasonic evaluation, we used %MM (the maximum magnitude of the measurement area divided by that of the intact cartilage) as a quantitative index of cartilage regeneration. The results of the ultrasonic evaluation were compared with the histological findings and histological score. The %MM values were 61.1 +/- 16.5% in group S, 29.8 +/- 15.1% in group L, 36.3 +/- 18.3% in group P and 76.5 +/- 18.7% in group T. The results showed a strong similarity to the histological scoring. The ultrasonic examination showed that all the hyaline-like cartilage in groups S and T had a high %MM (more than 60%). Therefore, we could define the borderline between the two types of regenerated cartilage by the %MM.

A preclinical study testing "Focused multiple laser beams," a new concept of irradiation with the 1064-nm Nd:YAG laser for skin rejuvenation.

PubMed

Horiguchi, Masatoshi; Miyata, Nariaki; Mizuno, Hiroshi

2017-04-01

In order to avoid epidermal heat damage, we developed a novel irradiation method termed "Focused multiple laser beams (FMLB)," which allows long-pulse neodymium:yttrium aluminum garnet (Nd:YAG) laser beams to be irradiated from several directions in a concentric fashion followed by focusing into the dermis without epidermal damage. This study aimed to assess whether FMLB achieves the desired dermal improvement without epidermal damage. The dorsal skin of New Zealand White rabbits was irradiated with FMLB. Macroscopic and histological analyses were performed after 1 hour and 1, 2, 3 and 4 weeks. Real-time PCR analysis of type I and III collagen expression was performed at two and four weeks. Control groups exhibited skin ulcers which were healed with scar formation whereas FMLB groups remained intact macroscopically. Histologically, FMLB group showed increase in dermal thickness at four weeks while the epidermis remained intact. Real-time PCR demonstrated that both type I and III collagen increased at two weeks but decreased at four weeks. FMLB can deliver the target laser energy to the dermis without significantly affecting the epidermis.

Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective study on long-term outcome with propensity score analysis

PubMed Central

De Angelis, Carmine; Di Maio, Massimo; Crispo, Anna; Giuliano, Mario; Schettini, Francesco; Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Cinausero, Marika; Riccardi, Ferdinando; Ciancia, Giuseppe; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Arpino, Grazia

2017-01-01

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome. PMID:29348868

A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer.

PubMed

Kelly, Karen; Kittelson, John; Franklin, Wilbur A; Kennedy, Timothy C; Klein, Catherine E; Keith, Robert L; Dempsey, Edward C; Lewis, Marina; Jackson, Mary K; Hirsch, Fred R; Bunn, Paul A; Miller, York E

2009-05-01

No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without alpha tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus alpha tocopherol (13-cis RA/alpha toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to observations/13-cis RA/13-cis RA/alpha toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/alpha toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36-2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, -0.18; 95% confidence interval, -1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The addition of alpha tocopherol did not affect toxicity.

A Randomized Phase II Chemoprevention Trial of 13-CIS Retinoic Acid with Or without α Tocopherol or Observation in Subjects at High Risk for Lung Cancer

PubMed Central

Kelly, Karen; Kittelson, John; Franklin, Wilbur A.; Kennedy, Timothy C.; Klein, Catherine E.; Keith, Robert L.; Dempsey, Edward C.; Lewis, Marina; Jackson, Mary K.; Hirsch, Fred R.; Bunn, Paul A.; Miller, York E.

2011-01-01

No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without α tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus α tocopherol (13-cis RA/α toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment “failure” defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to obervations/13-cis RA/13-cis RA/α toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/α toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36–2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, −0.18; 95% confidence interval, −1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The addition of α tocopherol did not affect toxicity. PMID:19401528

Comparison of acoustic radiation force impulse imaging (ARFI) to liver biopsy histologic scores in the evaluation of chronic liver disease: A pilot study.

PubMed

Haque, Mazhar; Robinson, Charlotte; Owen, David; Yoshida, Eric M; Harris, Alison

2010-01-01

Acoustic Radiation Force Impulse Imaging (ARFI) is a novel non invasive technique studying the localized mechanical properties of tissue by utilising short, high intensity acoustic pulses (shear wave pulses) to assess the mechanical response (tissue displacement), providing a measure of tissue elasticity. The aim of this study is to investigate the feasibility of ARFI imaging as a non-invasive method for the assessment of liver fibrosis compared to liver biopsy scores. A prospective blind comparison study of ARFI elastography (Virtual Touch Imaging., ACUSON S2000 Ultrasound Unit, Siemens, Mountain View CA) in a consecutive series of patients who underwent liver biopsy for assessment of fibrosis in chronic liver disease. ARFI shear-wave propagation velocity was measured in meters per second. Mean ARFI velocities were compared with both Batts-Ludwig (F0 to F4) and Modified Ishak scores (F0 to F4) for fibrosis in liver biopsy findings. Twenty-one patients with chronic liver disease (Hepatitis C (HCV) =16, Hepatitis B (HBV) = 1, both HCV and HBV = 1 Alcoholic liver disease (ALD) = 1, others = 2) underwent ARFI and liver biopsy on the same day. The Spearman correlation coefficients between the median values of the ARFI measurements and the histological fibrosis stage of the Modified Ishak score and Batts-Lud- (3) wig score were both highly significant (p < 0.01) with rho = 0.69 and rho = 0.72 respectively. The median ARFI (total 180 replications; minimum 5, maximum 10 measurements per patients) velocities for our study population range from 0.92 to 4.17 m/sec. Areas under the receiver operating characteristic curve for the accuracy of ARFI imaging was 1.00 and 0.35, for the diagnosis of moderate fibrosis (histologic fibrosis stage, F (3) 2) and 0.85 and 0.85 respectively for Ishak and Batts-Ludwig score, for the diagnosis of cirrhosis. ARFI imaging has a strong correlation with the fibrosis stage of both Batts-Ludwig and shak score in chronic liver disease. It.s accuracy in prediction of severe fibrosis and cirrhosis is maximal in comparison with earlier stages.

Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo.

PubMed

Brillant, Nathalie; Elmasry, Mohamed; Burton, Neal C; Rodriguez, Josep Monne; Sharkey, Jack W; Fenwick, Stephen; Poptani, Harish; Kitteringham, Neil R; Goldring, Christopher E; Kipar, Anja; Park, B Kevin; Antoine, Daniel J

2017-10-01

The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention. Perturbation of liver function and cellular viability was assessed in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122, HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a 60% partial hepatectomy model as a situation of defined hepatic functional mass loss to compared acetaminophen-induced changes to. Integration of these mechanistic markers correlated with histological features of APAP hepatotoxicity in a time-dependent manner. They accurately reflected the onset and recovery from hepatotoxicity compared to traditional biomarkers and also reported the efficacy of NAC with high sensitivity. ICG clearance kinetics correlated with histological scores for acute liver damage for APAP (i.e. 3h timepoint; r=0.90, P<0.0001) and elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6h timepoint; r=0.70, P=0.005) and HMGB1 (e.g. 6h timepoint; r=0.56, P=0.04). For the first time we report the utility of this non-invasive longitudinal imaging approach to provide direct visualisation of the liver function coupled with mechanistic biomarkers, in the same animal, allowing the investigation of the toxicological and pharmacological aspects of APAP-ILI and hepatic regeneration. Copyright © 2017. Published by Elsevier Inc.

Longitudinal study of esophageal mucosal damage after esophagectomy and gastric interposition: relationship between reflux-related mucosal injury and Notch signaling

PubMed Central

Yuan, Yong; Tong, Tie-Jun; Zeng, Xiao-Xi; Yang, Yu-Shang; Wang, Zhi-Qiang; Wang, Yun-Cang; Gou, Jun-He

2017-01-01

Background Esophagectomy with gastric interposition could serve as a good human reflux model to study the molecular pathogenesis of esophageal mucosal damage induced by gastroesophageal reflux. This study was to investigate the role of Notch signaling in reflux injury of esophageal mucosa. Methods Patients undergoing Ivor-Lewis esophagectomy for early stage esophageal squamous cell carcinoma were included. Follow-ups were scheduled at 6, 18, 36 and 48 months postoperatively, including reflux symptom assessment, endoscopic and histological evaluation of esophageal mucosal damage. The expressions of Notch1 and its downstream target gene Hes1 were evaluated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). Results Forty-four out of 48 patients completed four follow-ups. Injuries of esophageal remnant confirmed by endoscopical and histological examinations were both more often with a longer postoperative period (P<0.05). The mRNA expression levels of Notch1 and Hes1 were decreased in a time-dependent manner after operation (P<0.001). Notch1 and Hes1 mRNA levels were significantly higher in normal squamous mucosa than in esophagitis, and higher in esophagitis than in metaplasia (P<0.05). Immunohistochemical study also demonstrated a similar protein expression pattern. Samples with endoscopic evidence of mucosal damage exhibited lower expression of Notch1 mRNA levels as compared to biopsies without visualized damage (P=0.035). Conclusions This is the first longitudinal study on Notch signaling in human esophagectomy model, our preliminary findings suggest decreased Notch signaling might be involved in the development of mucosa damage caused by gastroesophageal reflux. PMID:29312733

Subacute Fluoxetine Reduces Signs of Hippocampal Damage Induced by a Single Convulsant Dose of 4-Aminopyridine in Rats.

PubMed

Shiha, Ahmed A; de la Rosa, Rubén Fernández; Delgado, Mercedes; Pozo, Miguel A; García-García, Luis

2017-01-01

Epilepsy is a central disorder associated with neuronal damage and brain hypometabolism. It has been reported that antidepressant drugs show anticonvulsant and neuroprotective effects in different animal models of seizures and epilepsy. The purpose of this study was to investigate the eventual short-term brain impairment induced by a single low convulsant dose of the potassium channel blocker 4-aminopyridine (4-AP) and the eventual neuroprotective effects exerted by fluoxetine, a prototypical selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI). In vivo 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and several histological assessments were carried out in adult male rats after i.p. administration of 3 mg/kg 4-AP for evaluating eventual brain metabolism impairment and signs of hippocampal damage. We also evaluated the effects of a short-term fluoxetine treatment (10 mg/kg, i.p. for 7 days) in this seizure model. [18F]FDG PET analysis revealed no changes in the regional brain metabolism on day 3 after 4-AP injection. The histological assessments revealed signs of damage in the hippocampus, a brain area usually affected by seizures. Thus, reactive gliosis and a significant increase in the expression of caspase-9 were found in the aforementioned brain area. By contrast, we observed no signs of neurodegeneration or neuronal death. Regarding the effects of fluoxetine, this SSRI showed beneficial neurologic effects, since it significantly increased the seizure latency time and reduced the abovementioned 4-AP-induced hippocampal damage markers. Overall, our results point to SSRIs and eventually endogenous 5-HT as neuroprotective agents against convulsant-induced hippocampal damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Influence of the ICDAS e-learning program for occlusal caries detection on dental students.

PubMed

Diniz, Michele B; Lima, Luciana Monti; Santos-Pinto, Lourdes; Eckert, George J; Zandoná, Andrea G Ferreira; de Cássia Loiola Cordeiro, Rita

2010-08-01

The aim of this study was to evaluate the influence of ICDAS training in a group of dental students for occlusal caries detection in permanent teeth. Premolars and molars (N=104) with occlusal surfaces varying from ICDAS scores 0 to 6 were cleaned, one occlusal site per tooth was selected, and a photograph taken to identify the site. Eight senior dental students examined the teeth twice with a one-week interval between examinations during each of two phases: before and after the ICDAS e-learning program. Teeth were histologically assessed for caries extension. Intraclass correlation coefficients for intra- and interexaminer repeatability were high, both before (0.75 and 0.72, respectively) and after e-learning (0.82 and 0.78, respectively). The ICDAS scores decreased significantly from before to after e-learning (p=0.0001). Correlation between ICDAS scores and histology scores was moderate (0.57 before e-learning and 0.61 after). Although the ROC curve shows an improvement in the use of the ICDAS scoring after e-learning, the difference was not significant (p=0.10). Specificity of the ICDAS scores significantly improved after e-learning (77 percent vs. 36 percent), and sensitivity was reduced slightly after e-learning (87 percent vs. 92 percent). The ICDAS e-learning program improved the performance of the diagnostic skills of the investigated students for the detection of occlusal caries lesions.

Evaluation of gastric histology in children and adolescents with Helicobacter pylori gastritis using the Update Sydney System.

PubMed

Langner, Marini; Machado, Rodrigo Strehl; Patrício, Francy R S; Kawakami, Elisabete

2009-01-01

Although Helicobacter pylori infection is prevalent in our country, there are few studies evaluating the associated histological abnormalities in children. To evaluate the histological features of the gastric mucosa in children and adolescents with Helicobacter pylori gastritis. One hundred and thirty two gastric biopsies from 22 symptomatic patients infected with H. pylori (14F/8M, median age 10 y 5 mo, age range 2 y 11 mo to 16 y 9 mo) were evaluated. Evaluated gastric regions included: antrum (lesser and greater curvature), corpus (lesser and greater curvature), incisura angularis and fundus. Histological examination was performed according to the Updated Sydney System, and regional scores for polymorphonuclear and mononuclear cell infiltrate as well as bacterial density were generated. Fifteen (68.2%) patients presented H. pylori-chronic active gastritis, six (27.3%) presented antrum-predominant H. pylori-chronic active gastritis, and one (4.5%) presented corpus-predominant H. pylori-chronic active gastritis. Polymorphonuclear cell infiltrate and mononuclear cell infiltrate were observed in 93.9% and 98.5% of the biopsy specimens, respectively. Higher histological scores for polymorphonuclear infiltrate, mononuclear infiltrate, and bacterial density were observed in the gastric antrum. Intestinal metaplasia and gastric atrophy were not identified in any patient. Lymphoid aggregates and lymphoid follicles were observed in the gastric antrum of three (13.6%) and seven (31.8%) patients, respectively, but they were not related to antral nodularity. Chronic active gastritis was observed in all patients with H. pylori infection. However, antral or corporeal predominance was not observed in most patients.

Combined Adiponectin Deficiency and Resistance in Obese Patients: Can It Solve Part of the Puzzle in Nonalcoholic Steatohepatitis.

PubMed

Salman, Ahmed; Hegazy, Mona; AbdElfadl, Soheir

2015-06-15

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, nonalcoholic steatohepatitis (NASH) and fibrosis in obese patients identifies the risk group with increased incidence of liver-related deaths. To clarify the role of serum adiponectin and its receptor liver gene expression in the progression of liver damage in NAFLD. Fifty four (54) obese patients with NAFLD preliminary diagnosed by liver ultra-sound were recruited. Full medical history, anthropometric measurement, biochemical studies, serum adiponectin level, liver biopsy for histological examination and NAS score to identify NASH patients, and assessment of adiponectin receptor gene expression by RT-PCR, were conducted for each patients. Fifteen ages matched average weight healthy adult had been chosen as a control for serum adiponectin level. According to NAS score, patients were divided into non- NASH (8 patients), and NASH (46 patients). Serum adiponectin level was significantly lower in NAFLD patients compared to normal participants (p < 0.004). Serum adiponectin level was lower in NASH patients (4.437 ± 2.569 ng/dl in NASH vs. 5.138 ± 2.841 ng/dl in non-NASH). Adiponectin receptor liver gene expression was lower in NASH patients (0.8459 ± 0.4671 vs. 1.0688 ± 0.3965 in non-NASH). Both adiponectin deficiency and resistance had a role in progression of simple liver steatosis to severe injury in obese patients.

Tissue response to five commercially available peritoneal adhesion barriers-A systematic histological evaluation.

PubMed

Schmitt, Volker H; Mamilos, Andreas; Schmitt, Christine; Neitzer-Planck, Constanze N E; Rajab, Taufiek K; Hollemann, David; Wagner, Willi; Krämer, Bernhard; Hierlemann, Helmut; James Kirkpatrick, C; Brochhausen, Christoph

2018-02-01

Separating wounded serosa by physical barriers is the only clinically approved adjunct for postoperative adhesion prevention. Since the optimal adhesion barrier has not been found, it is essential to improve our pathogenic understanding of adhesion formation and to compare the effects of different barrier materials on tissue and cells. Wistar rats underwent standardized peritoneal damage and were treated either with Seprafilm, Adept, Intercoat, Spraygel, SupraSeal or remained untreated as a control. 14 days postoperatively, the lesions were explanted and histomorphologically analyzed using the European ISO score to evaluate material implants. Striking differences between the material groups were present regarding the inflammation, fibrosis, and foreign body reaction. According to the ISO score, Intercoat and Spraygel were considered as nonirritating to tissue. Adept, Seprafilm, and SupraSeal were assessed as mild-irritating materials. Interestingly, the most effective material in adhesion prevention revealed moderate inflammation accompanied by minor fibrosis. The degree of inflammation to barrier materials does not predict the efficacy in the prevention of adhesions. Histopathological investigations are crucial to improve our understanding of the cellular mechanisms during adhesion formation and elucidate the tissue response to material approaches used in adhesion prevention. This will lead to improved antiadhesive strategies and the development of functional barrier biomaterials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 598-609, 2018. © 2017 Wiley Periodicals, Inc.

An experimental study on the impacts of inspiratory and expiratory muscles activities during mechanical ventilation in ARDS animal model

PubMed Central

Zhang, Xianming; Du, Juan; Wu, Weiliang; Zhu, Yongcheng; Jiang, Ying; Chen, Rongchang

2017-01-01

In spite of intensive investigations, the role of spontaneous breathing (SB) activity in ARDS has not been well defined yet and little has been known about the different contribution of inspiratory or expiratory muscles activities during mechanical ventilation in patients with ARDS. In present study, oleic acid-induced beagle dogs’ ARDS models were employed and ventilated with the same level of mean airway pressure. Respiratory mechanics, lung volume, gas exchange and inflammatory cytokines were measured during mechanical ventilation, and lung injury was determined histologically. As a result, for the comparable ventilator setting, preserved inspiratory muscles activity groups resulted in higher end-expiratory lung volume (EELV) and oxygenation index. In addition, less lung damage scores and lower levels of system inflammatory cytokines were revealed after 8 h of ventilation. In comparison, preserved expiratory muscles activity groups resulted in lower EELV and oxygenation index. Moreover, higher lung injury scores and inflammatory cytokines levels were observed after 8 h of ventilation. Our findings suggest that the activity of inspiratory muscles has beneficial effects, whereas that of expiratory muscles exerts adverse effects during mechanical ventilation in ARDS animal model. Therefore, for mechanically ventilated patients with ARDS, the demands for deep sedation or paralysis might be replaced by the strategy of expiratory muscles paralysis through epidural anesthesia. PMID:28230150

Hepatic damage in newborns from female rats exposed to the pesticide derivative ethylenethiourea.

PubMed

Lemos, Patrícia Veruska Ribeiro Barbosa; Martins, José Luiz; Lemos, Sidney Pereira Pinto; Santos, Fernando Leandro dos; Silva, Sílvio Romero Gonçalves e

2012-12-01

To evaluate hepatic morphological-histological abnormalities in newborns from female rats exposed to ethylenethiourea. A randomized study was conducted on fifty-five newborn Wistar rats were studied: 34 in the experimental group, whose mothers had been exposed to 1% ethylenethiourea; and 21 in the control group, whose mothers had received 0.9% physiological solution. The solution was administered via gavage on the 11(th) day of gestation. Cesarean section was performed on the 20(th) day of gestation. The newborns' livers were examined and any morphological-histological abnormalities were registered. The presence of megakaryocytes was quantified in 50 microscope fields, as the total number of these cells per mm(2). The entire experimental group presented abnormalities of embryonic formation, with musculoskeletal anomalies, digestive system anomalies, hepatic congestion and friability, hydrops and delayed intrauterine growth. The histopathological analysis showed that morphological-histological hepatic destructuring had occurred in all entire experimental with removal of the hepatic trabeculae and severe hepatic megakaryocytosis. The mean megakaryocyte density ranged from 107.9 to 114.2 per mm(2), and it was eight times greater than in the control group, thus characterizing a situation of extramedullary hematopoiesis. The fetal exposure to ethylenethiourea caused hepatic damage characterized by severe extramedullary hematopoiesis.

Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.

PubMed

Quintana, Harry Karmouty; Cannet, Catherine; Zurbruegg, Stefan; Blé, François-Xavier; Fozard, John R; Page, Clive P; Beckmann, Nicolau

2006-12-01

Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase-induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases.

Barbiturate euthanasia solution-induced tissue artifact in nonhuman primates.

PubMed

Grieves, J L; Dick, E J; Schlabritz-Loutsevich, N E; Butler, S D; Leland, M M; Price, S E; Schmidt, C R; Nathanielsz, P W; Hubbard, G B

2008-06-01

Barbiturate euthanasia solutions are a humane and approved means of euthanasia. Overdosing causes significant tissue damage in a variety of laboratory animals. One hundred seventeen non-human primates (NHP) representing 7 species including 12 fetuses euthanized for humane and research reasons by various vascular routes with Euthasol, Sodium Pentobarbital, Fatal Plus, Beuthanasia D, or Euthanasia 5 were evaluated for euthanasia-induced tissue damage. Lungs and livers were histologically graded for hemolysis, vascular damage, edema, and necrosis. Severity of tissue damage was analyzed for differences on the basis of agent, age, sex, dose, and injection route. Severity of tissue damage was directly related to dose and the intracardiac injection route, but did not differ by species, sex, and agent used. When the recommended dose of agent was used, tissue damage was generally reduced, minimal, or undetectable. Barbiturate-induced artifacts in NHPs are essentially the same as in other laboratory species.

Epidermal growth factor receptor (EGFR) is overexpressed in high-grade dysplasia and adenocarcinoma of the esophagus and may represent a biomarker of histological progression in Barrett's esophagus (BE).

PubMed

Cronin, James; McAdam, Elizabeth; Danikas, Antonios; Tselepis, Chris; Griffiths, Paul; Baxter, John; Thomas, Linzi; Manson, James; Jenkins, Gareth

2011-01-01

The assessment of cancer risk in patients with Barrett's esophagus (BE) is currently fraught with difficulty. The current gold standard method of assessing cancer risk is histological assessment, with the appearance of high-grade dysplasia (HGD) as the key event monitored. Sampling error during endoscopy limits the usefulness of this approach, and there has been much recent interest in supplementing histological assessment with molecular markers, which may aid in patient stratification. No molecular marker has been yet validated to accurately correlate with esophageal histological progression. Here, we assessed the suitability of several membranous proteins as biomarkers by correlating their abundance with histological progression. In all, 107 patient samples, from 100 patients, were arranged on a tissue microarray (TMA) and represented the various stages of histological progression in BE. This TMA was probed with antibodies for eight receptor proteins (mostly membranous). Epidermal growth factor receptor (EGFR) staining was found to be the most promising biomarker identified with clear increases in staining accompanying histological progression. Further, immunohistochemistry was performed using the full-tissue sections from BE, HGD, and adenocarcinoma tissues, which confirmed the stepwise increase in EGFR abundance. Using a robust H-score analysis, EGFR abundance was shown to increase 13-fold in the adenocarcinoma tissues compared to the BE tissues. EGFR was "overexpressed" in 35% of HGD specimens and 80% of adenocarcinoma specimens when using the H-score of the BE patients (plus 3 s.d.) as the threshold to define overexpression. EGFR staining was also noted to be higher in BE tissues adjacent to HGD/adenocarcinoma. Western blotting, although showing more EGFR protein in the adenocarcinomas compared to the BE tissue, was highly variable. EGFR overexpression was accompanied by aneuploidy (gain) of chromosome 7, plus amplification of the EGFR locus. Finally, the bile acid deoxycholic acid (DCA) (at neutral and acidic pH) and acid alone was capable of upregulating EGFR mRNA in vitro, and in the case of neutral pH DCA, this was NF-κB dependent. EGFR is overexpressed during the histological progression in BE tissues and hence may be useful as a biomarker of histological progression. Furthermore, as EGFR is a membranous protein expressed on the luminal surface of the esophageal mucosa, it may also be a useful target for biopsy guidance during endoscopy.

FEM modeling and histological analyses on thermal damage induced in facial skin resurfacing procedure with different CO2 laser pulse duration

NASA Astrophysics Data System (ADS)

Rossi, Francesca; Zingoni, Tiziano; Di Cicco, Emiliano; Manetti, Leonardo; Pini, Roberto; Fortuna, Damiano

2011-07-01

Laser light is nowadays routinely used in the aesthetic treatments of facial skin, such as in laser rejuvenation, scar removal etc. The induced thermal damage may be varied by setting different laser parameters, in order to obtain a particular aesthetic result. In this work, it is proposed a theoretical study on the induced thermal damage in the deep tissue, by considering different laser pulse duration. The study is based on the Finite Element Method (FEM): a bidimensional model of the facial skin is depicted in axial symmetry, considering the different skin structures and their different optical and thermal parameters; the conversion of laser light into thermal energy is modeled by the bio-heat equation. The light source is a CO2 laser, with different pulse durations. The model enabled to study the thermal damage induced into the skin, by calculating the Arrhenius integral. The post-processing results enabled to study in space and time the temperature dynamics induced in the facial skin, to study the eventual cumulative effects of subsequent laser pulses and to optimize the procedure for applications in dermatological surgery. The calculated data where then validated in an experimental measurement session, performed in a sheep animal model. Histological analyses were performed on the treated tissues, evidencing the spatial distribution and the entity of the thermal damage in the collageneous tissue. Modeling and experimental results were in good agreement, and they were used to design a new optimized laser based skin resurfacing procedure.

Interventional Vitamin C A Strategy for Attenuation of Coagulopathy and Inflammation in Hemorrhagic Trauma and Shock

DTIC Science & Technology

2016-10-01

evident in liver and kidney sections. Treatment with VitC (200mg/kg) was associated with a lower degree of histological tissue injury and a...significantly reduced ALI score. Treatment with VitC also reduced the expression of pro-inflammatory mediators in lungs, liver and kidneys . In addition, VitC...Euthasol IV  Tissue samples (lung, liver and kidney ) obtained for histology and molecular characterization Definitive trial conducted: Eight (8

The interrupted learner: How distractions during live and video lectures influence learning outcomes.

PubMed

Zureick, Andrew H; Burk-Rafel, Jesse; Purkiss, Joel A; Hortsch, Michael

2017-11-27

New instructional technologies have been increasingly incorporated into the medical school learning environment, including lecture video recordings as a substitute for live lecture attendance. The literature presents varying conclusions regarding how this alternative experience impacts students' academic success. Previously, a multi-year study of the first-year medical histology component at the University of Michigan found that live lecture attendance was positively correlated with learning success, while lecture video use was negatively correlated. Here, three cohorts of first-year medical students (N = 439 respondents, 86.6% response rate) were surveyed in greater detail regarding lecture attendance and video usage, focusing on study behaviors that may influence histology learning outcomes. Students who reported always attending lectures or viewing lecture videos had higher average histology scores than students who employed an inconsistent strategy (i.e., mixing live attendance and video lectures). Several behaviors were negatively associated with histology performance. Students who engaged in "non-lecture activities" (e.g., social media use), students who reported being interrupted while watching the lecture video, or feeling sleepy/losing focus had lower scores than their counterparts not engaging in these behaviors. This study suggests that interruptions and distractions during medical learning activities-whether live or recorded-can have an important impact on learning outcomes. Anat Sci Educ 00: 000-000. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Primary central chondrosarcoma of long bone, limb girdle and trunk: Analysis of 174 cases by numerical scoring on histology

PubMed Central

Nakashima, Yasuaki; Mano, Masayuki; Tomita, Yasuhiko; Nagasaki, Ikumitsu; Kubo, Toshikazu; Araki, Nobuhito; Haga, Hironori; Toguchida, Junya; Ueda, Takafumi; Sakuma, Toshiko; Imahori, Masaya; Morii, Eiichi; Yoshikawa, Hideki; Tsukamoto, Yoshitane; Futani, Hiroyuki; Wakasa, Kenichi; Hoshi, Manabu; Hamada, Shinshichi; Takeshita, Hideyuki; Inoue, Takeshi; Aono, Masanari; Kawabata, Kenji; Murata, Hiroaki; Katsura, Kanade; Urata, Yoji; Ueda, Hideki; Yanagisawa, Akio

2015-01-01

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15–80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5‐year and 10‐year disease‐specific survival (DSS) rates [follow‐up: 1–258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS. PMID:26126783

Microwave Processing for Sample Preparation to Evaluate Mitochondrial Ultrastructural Damage in Hemorrhagic Shock

NASA Astrophysics Data System (ADS)

Josephsen, Gary D.; Josephsen, Kelly A.; Beilman, Greg J.; Taylor, Jodie H.; Muiler, Kristine E.

2005-12-01

This is a report of the adaptation of microwave processing in the preparation of liver biopsies for transmission electron microscopy (TEM) to examine ultrastructural damage of mitochondria in the setting of metabolic stress. Hemorrhagic shock was induced in pigs via 35% total blood volume bleed and a 90-min period of shock followed by resuscitation. Hepatic biopsies were collected before shock and after resuscitation. Following collection, biopsies were processed for TEM by a rapid method involving microwave irradiation (Giberson, 2001). Samples pre- and postshock of each of two animals were viewed and scored using the mitochondrial ultrastructure scoring system (Crouser et al., 2002), a system used to quantify the severity of ultrastructural damage during shock. Results showed evidence of increased ultrastructural damage in the postshock samples, which scored 4.00 and 3.42, versus their preshock controls, which scored 1.18 and 1.27. The results of this analysis were similar to those obtained in another model of shock (Crouser et al., 2002). However, the amount of time used to process the samples was significantly shortened with methods involving microwave irradiation.

Attenuation of intestinal ischemia-reperfusion-injury by β-alanine: a potentially glycine-receptor mediated effect.

PubMed

Brencher, Lisa; Verhaegh, Rabea; Kirsch, Michael

2017-05-01

Acute mesenteric ischemia is often caused by embolization of the mesenteric arterial circulation. Coherent intestinal injury due to ischemia and following reperfusion get visible on macroscopic and histologic level. In previous studies, application of glycine caused an ameliorated intestinal damage after ischemia-reperfusion in rats. Because we speculated that glycine acted here as a signal molecule, we investigated whether the glycine-receptor agonist β-alanine evokes the same beneficial effect in intestinal ischemia-reperfusion. β-alanine (10, 30, and 100 mg/kg) was administered intravenously. Ischemia/reperfusion of the small intestine was initiated by occluding and reopening the superior mesenteric artery in rats. After 90 min of ischemia and 120 min of reperfusion, the intestine was analyzed with regard to macroscopic and histologic tissue damage, the activity of the saccharase, and accumulation of macrophages. In addition, systemic parameters and metabolic ones (e.g., acid-base balance, electrolytes, and blood glucose) were measured at certain points in time. All three dosages of β-alanine did not change systemic parameters but prevent from hyponatremia during the period of reperfusion. Most importantly, application of 100-mg β-alanine clearly diminished intestinal tissue damage, getting visible on macroscopic and histologic level. In addition, I/R-mediated decrease of saccharase activity and accumulation of macrophages in the small intestine were ameliorated. The present study demonstrated that β-alanine was a potent agent to ameliorate I/R-induced injury of the small intestine. Due to its diminishing effect on the accumulation of macrophages, β-alanine is strongly expected to mediate its beneficial effect via glycine receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of organochlorines and metals on wild fish living in a tropical hydroelectric reservoir: bioaccumulation and histopathological biomarkers.

PubMed

Paulino, Marcelo Gustavo; Benze, Tayrine Paschoaletti; Sadauskas-Henrique, Helen; Sakuragui, Marise Margareth; Fernandes, João Batista; Fernandes, Marisa Narciso

2014-11-01

This study evaluates the contaminants in water and their bioaccumulation in the gills and liver of two ecologically distinct fish species, Astyanax fasciatus and Pimelodus maculatus, living in the reservoir of the Furnas hydroelectric power station located in Minas Gerais in the southeastern Brazil. The histological alterations in these organs are also examined. Water and fish were collected in June and December from five sites (site 1: FU10, site 2: FU20, site 3: FU30, site 4: FU40 and site 5: FU50) in the reservoir, and agrochemicals and metals selected based on their use in the field crops surrounding the reservoir were analyzed in the water and in the fish gills and livers. The concentrations of the organochlorines aldrin/dieldrin, endosulfan and heptachlor/heptachlor epoxide as well as the metals copper, chromium, iron and zinc in the gills and livers of both fish species were higher in June than in December; the liver accumulated higher concentrations of contaminants than the gills. The organochlorine metolachlor was detected only in the liver. The histological pattern of changes was similar in both species with regard to contaminant accumulation in the gills and liver. Fish from FU10, the least contaminated site, exhibited normal gill structure and moderate to heavy liver damage. Fish collected at FU20 to FU50, which were contaminated with organochlorines and metals, showed slight to moderate gill damage in June and irreparable liver damage in the livers in June and December. The histological changes in the gills and liver were suitable to distinguishing contaminated field sites and are therefore useful biomarkers for environmental contamination representing a biological end-point of exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

Longitudinal in vivo microcomputed tomography of mouse lungs: No evidence for radiotoxicity

PubMed Central

Vande Velde, Greetje; De Langhe, Ellen; Poelmans, Jennifer; Bruyndonckx, Peter; d'Agostino, Emiliano; Verbeken, Erik; Bogaerts, Ria; Himmelreich, Uwe

2015-01-01

Before microcomputed tomography (micro-CT) can be exploited to its full potential for longitudinal monitoring of transgenic and experimental mouse models of lung diseases, radiotoxic side effects such as inflammation or fibrosis must be considered. We evaluated dose and potential radiotoxicity to the lungs for long-term respiratory-gated high-resolution micro-CT protocols. Free-breathing C57Bl/6 mice underwent four different retrospectively respiratory gated micro-CT imaging schedules of repeated scans during 5 or 12 wk, followed by ex vivo micro-CT and detailed histological and biochemical assessment of lung damage. Radiation exposure, dose, and absorbed dose were determined by ionization chamber, thermoluminescent dosimeter measurements and Monte Carlo calculations. Despite the relatively large radiation dose delivered per micro-CT acquisition, mice did not show any signs of radiation-induced lung damage or fibrosis when scanned weekly during 5 and up to 12 wk. Doubling the scanning frequency and once tripling the radiation dose as to mimic the instant repetition of a failed scan also stayed without detectable toxicity after 5 wk of scanning. Histological analyses confirmed the absence of radiotoxic damage to the lungs, thereby demonstrating that long-term monitoring of mouse lungs using high-resolution micro-CT is safe. This opens perspectives for longitudinal monitoring of (transgenic) mouse models of lung diseases and therapeutic response on an individual basis with high spatial and temporal resolution, without concerns for radiation toxicity that could potentially influence the readout of micro-CT-derived lung biomarkers. This work further supports the introduction of micro-CT for routine use in the preclinical pulmonary research field where postmortem histological approaches are still the gold standard. PMID:26024893

The protective effect of pomegranate juice in paracetamol-induced acute hepatotoxicity in rats

PubMed Central

Çalışkan, Duygu; Koca, Tuğba; Doğuç, Duygu Kumbul; Özgöçmen, Meltem; Akçam, Mustafa

2016-01-01

Aim: Being the most commonly used antipyretic and analgesic, paracetamol is one of the most common causes of childhood poisoning in the world and maintains its importance also in our country. Paracetamol poisoning is one of the most common causes of liver failure. This study aimed to investigate if pomegranate juice had protective effect in acute liver toxicity related with paracetamol. Material and Methods: A total of 36 Wistar-Albino rats were divided into four groups as the paracetamol group (3 000 mg/kg paracetamol), the pomegranate juice + paracetamol group (1.5 mL pomegranate juice plus 3 000 mg/kg paracetamol), the pomegranate juice group (1.5 mL pomegranate juice) and the control group (1.5 mL distilled water). Pomegranate juice and distilled water were administered for eight days. Paracetamol was administered on day 8. The level of thiobarbituric acid reactive substances, as an oxidative marker, was measured in the blood and liver tissue on day 9. In addition, liver tissues were evaluated histologically (in terms of increased connective tissue, granular degeneration, mononuclear cell infiltration, necrotic cells and vascular congestion). Results: The liver tissue and blood thiobarbituric acid reactive substances levels were found to be significantly lower in the pomegranate juice + paracetamol group compared to the paracetamol group (p<0.05). Histologically, structural changes related with damage were observed in both the paracetamol group and pomegranate juice + paracetamol group. The extent of damage was statistically significantly lower in the pomegranate juice + paracetamol group (p<0.001). Conclusions: Our results related with oxidative and histologic evaluation showed that pomegranate juice might have a preventive effect in paracetamol-induced acute liver damage. PMID:27489463

The protective effect of pomegranate juice in paracetamol-induced acute hepatotoxicity in rats.

PubMed

Çalışkan, Duygu; Koca, Tuğba; Doğuç, Duygu Kumbul; Özgöçmen, Meltem; Akçam, Mustafa

2016-06-01

Being the most commonly used antipyretic and analgesic, paracetamol is one of the most common causes of childhood poisoning in the world and maintains its importance also in our country. Paracetamol poisoning is one of the most common causes of liver failure. This study aimed to investigate if pomegranate juice had protective effect in acute liver toxicity related with paracetamol. A total of 36 Wistar-Albino rats were divided into four groups as the paracetamol group (3 000 mg/kg paracetamol), the pomegranate juice + paracetamol group (1.5 mL pomegranate juice plus 3 000 mg/kg paracetamol), the pomegranate juice group (1.5 mL pomegranate juice) and the control group (1.5 mL distilled water). Pomegranate juice and distilled water were administered for eight days. Paracetamol was administered on day 8. The level of thiobarbituric acid reactive substances, as an oxidative marker, was measured in the blood and liver tissue on day 9. In addition, liver tissues were evaluated histologically (in terms of increased connective tissue, granular degeneration, mononuclear cell infiltration, necrotic cells and vascular congestion). The liver tissue and blood thiobarbituric acid reactive substances levels were found to be significantly lower in the pomegranate juice + paracetamol group compared to the paracetamol group (p<0.05). Histologically, structural changes related with damage were observed in both the paracetamol group and pomegranate juice + paracetamol group. The extent of damage was statistically significantly lower in the pomegranate juice + paracetamol group (p<0.001). Our results related with oxidative and histologic evaluation showed that pomegranate juice might have a preventive effect in paracetamol-induced acute liver damage.

Early detection of osteoarthritis in rabbits using MRI with a double-contrast agent.

PubMed

Onishi, Okihiro; Ikoma, Kazuya; Kido, Masamitsu; Kabuto, Yukichi; Ueshima, Keiichiro; Matsuda, Ken-Ichi; Tanaka, Masaki; Kubo, Toshikazu

2018-03-13

Articular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent. We induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T 2 -calculated images were obtained before and after contrast agent injection into the knee. The signal intensity ratio (SIR) values on the proton density-weighted images were calculated by dividing the signal intensity of the articular cartilage by that of joint fluid. Six rabbits were examined using MRI at 2 (designated 2-w OA) and 4 weeks (4-w OA) after the operation. Histological examination was performed 4 weeks after the operation. One rabbit was histologically examined 2 weeks after the operation. The control consisted of six rabbits that were not subjected to the operation. The SIR values, T 2 values and the thicknesses of the cartilage of the 2-w OA, 4-w OA and the control before and after contrast agent injection were analyzed. The Mankin score and OARSI (Osteoarthritis Research Society International) score were used for the histological evaluation. Significant differences in the SIR and T 2 values of the medial and lateral condyles of the femur were found between the control and the 4-w OA only after contrast agent injection. No significant differences were found in the SIR and T 2 values before contrast agent injection between the control, the 2-w OA and 4-w OA. The thickness of the articular cartilage revealed no significant differences. In the histological assessment, the Mankin score and OARSI score sequentially increased from the control to the 4-w OA. We evaluated the SIR and T 2 values of the knees in a rabbit OA model and a control model using a new double-contrast agent. MRI with this agent enabled OA detection earlier than using conventional MRI.

Histopathological Validation of the Surface-Intermediate-Base Margin Score for Standardized Reporting of Resection Technique during Nephron Sparing Surgery.

PubMed

Minervini, Andrea; Campi, Riccardo; Kutikov, Alexander; Montagnani, Ilaria; Sessa, Francesco; Serni, Sergio; Raspollini, Maria Rosaria; Carini, Marco

2015-10-01

The surface-intermediate-base margin score is a novel standardized reporting system of resection techniques during nephron sparing surgery. We validated the surgeon assessed surface-intermediate-base score with microscopic histopathological assessment of partial nephrectomy specimens. Between June and August 2014 data were prospectively collected from 40 consecutive patients undergoing nephron sparing surgery. The surface-intermediate-base score was assigned to all cases. The score specific areas were color coded with tissue margin ink and sectioned for histological evaluation of healthy renal margin thickness. Maximum, minimum and mean thickness of healthy renal margin for each score specific area grade (surface [S] = 0, S = 1 ; intermediate [I] or base [B] = 0, I or B = 1, I or B = 2) was reported. The Mann-Whitney U and Kruskal-Wallis tests were used to compare the thickness of healthy renal margin in S = 0 vs 1 and I or B = 0 vs 1 vs 2 grades, respectively. Maximum, minimum and mean thickness of healthy renal margin was significantly different among score specific area grades S = 0 vs 1, and I or B = 0 vs 1, 0 vs 2 and 1 vs 2 (p <0.001). The main limitations of the study are the low number of the I or B = 1 and I or B = 2 samples and the assumption that each microscopic slide reflects the entire score specific area for histological analysis. The surface-intermediate-base scoring method can be readily harnessed in real-world clinical practice and accurately mirrors histopathological analysis for quantification and reporting of healthy renal margin thickness removed during tumor excision. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Correlation between systolic transvalvular flow and proximal aortic wall changes in bicuspid aortic valve stenosis.

PubMed

Girdauskas, Evaldas; Rouman, Mina; Disha, Kushtrim; Scholle, Thorsten; Fey, Beatrix; Theis, Bernhard; Petersen, Iver; Borger, Michael A; Kuntze, Thomas

2014-08-01

The purpose of this study was to analyse the correlation between preoperative systolic transvalvular flow patterns and proximal aortic wall lesions in patients undergoing surgery for bicuspid aortic valve (BAV) stenosis. A total of 48 consecutive patients with BAV stenosis (mean age 58 ± 9 years, 65% male) underwent aortic valve replacement (AVR) ± proximal aortic surgery from January 2012 through February 2013. Preoperative cardiac phase-contrast cine magnetic resonance imaging (MRI) assessment was performed in all patients in order to detect the area of maximal flow-induced stress in the proximal aorta. Based on these MRI data, two aortic wall samples (i.e. area of the maximal stress (jet sample) and the opposite aortic wall (control sample)) were collected during AVR surgery. Aortic wall changes were graded based on a summation of seven histological criteria (each scored from 0 to 3). Histological sum score (0-21) was separately calculated and compared between the two aortic samples (i.e. jet sample vs control sample). An eccentric transvalvular flow jet hitting the proximal aortic wall could be identified in all 48 (100%) patients. The mean histological sum score was significantly higher in the jet sample vs control sample areas of the aorta (i.e. 4.1 ± 1.8 vs 2.2 ± 1.5, respectively) (P = 0.02). None of the patients had a higher sum score value in the control sample. Our study demonstrates a strong correlation between the systolic pattern of the transvalvular flow jet and asymmetric proximal aortic wall changes in patients undergoing AVR for BAV stenosis. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Prognostic Value of Non-Invasive Fibrosis and Steatosis Tools, Hepatic Venous Pressure Gradient (HVPG) and Histology in Nonalcoholic Steatohepatitis.

PubMed

Sebastiani, Giada; Alshaalan, Rasha; Wong, Philip; Rubino, Maria; Salman, Ayat; Metrakos, Peter; Deschenes, Marc; Ghali, Peter

2015-01-01

Non-invasive diagnostic methods for liver fibrosis predict clinical outcomes in viral hepatitis and nonalcoholic fatty liver disease (NAFLD). We specifically evaluated prognostic value of non-invasive fibrosis methods in nonalcoholic steatohepatitis (NASH) against hepatic venous pressure gradient (HVPG) and liver histology. This was a retrospective cohort study of 148 consecutive patients who met the following criteria: transjugular liver biopsy with HVPG measurement; biopsy-proven NASH; absence of decompensation; AST-to-Platelets Ratio Index (APRI), fibrosis-4 (FIB-4), NAFLD fibrosis score, ultrasound, hepatic steatosis index and Xenon-133 scan available within 6 months from biopsy; a minimum follow-up of 1 year. Outcomes were defined by death, liver transplantation, cirrhosis complications. Kaplan-Meier and Cox regression analyses were employed to estimate incidence and predictors of outcomes, respectively. Prognostic value was expressed as area under the curve (AUC). During a median follow-up of 5 years (interquartile range 3-8), 16.2% developed outcomes, including 7.4% who died or underwent liver transplantation. After adjustment for age, sex, diabetes, the following fibrosis tools predicted outcomes: HVPG >10mmHg (HR=9.60; 95% confidence interval [CI] 3.07-30.12), histologic fibrosis F3-F4 (HR=3.14; 1.41-6.95), APRI >1.5 (HR=5.02; 1.6-15.7), FIB-4 >3.25 (HR=6.33; 1.98-20.2), NAFLD fibrosis score >0.676 (HR=11.9; 3.79-37.4). Prognostic value was as follows: histologic fibrosis stage, AUC=0.85 (95% CI 0.76-0.93); HVPG, AUC=0.81 (0.70-0.91); APRI, AUC=0.89 (0.82-0.96); FIB-4, AUC=0.89 (0.83-0.95); NAFLD fibrosis score, AUC=0.79 (0.69-0.91). Neither histologic steatosis nor non-invasive steatosis methods predicted outcomes (AUC<0.50). Non-invasive methods for liver fibrosis predict outcomes of patients with NASH. They could be used for serial monitoring, risk stratification and targeted interventions.

Juvenile- and adult-onset systemic lupus erythematosus: a comparative study in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

PubMed

Torrente-Segarra, Vicenç; Salman Monte, Tarek Carlos; Rúa-Figueroa, Iñigo; Sánchez-Alonso, Fernando; López-Longo, Francisco Javier; Galindo-Izquierdo, María; Calvo-Alén, Jaime; Olivé-Marqués, Alejandro; Ibañez-Ruán, Jesús; Horcada, Loreto; Sánchez-Atrio, Ana; Montilla, Carlos; Melero González, Rafael Benito; Díez-Álvarez, Elvira; Martinez-Taboada, Victor; Andreu, José Luis; Fernández-Berrizbeitia, Olaia; Hernández-Beriain, José Ángel; Gantes, Marian; Hernández-Cruz, Blanca; Pecondón-Español, Ángela; Marras, Carlos; Bonilla, Gema; Pego-Reigosa, José M

2017-01-01

We aimed to describe juvenile-onset systemic lupus erythematosus (jSLE) features and to establish its differences compared to adult-onset SLE (aSLE) from a large national database. Data from patients (≥4 ACR criteria) included in Spanish Society of Rheumatology Lupus Registry (RELESSER) were analysed. Sociodemographic, clinical, serological, activity, treatment, cumulative damage, comorbidities and severity data were collected. Patients with disease onset <18 years were described and compared to those with disease onset ≥18 years. We reviewed 3,428 aSLE patients (89.6% women) and 484 jSLE patients (89.8% girls), 93% Caucasian (both groups). Mean age at diagnosis was 38.1±14 and 16.6±6.3 years (p<0.001) and mean age at the end of follow-up was 48.8±14.3 and 31.5±30 years (p<0.001), respectively. jSLE showed significantly more clinical (including lymphadenopathy, fever, malar rash, mucosal ulcers, pericarditis, pleuritis, Raynaud's phenomenon, lupus nephritis, recurrent nephritis, histologic nephritis changes, thrombocytopenia, haemolytic anaemia, thrombotic thrombocytopenic purpura, seizures, lupus headache and organic brain syndrome) and immunological (a-dsDNA and a-Sm antibodies, hypocomplementaemia) involvement than did aSLE, except for secondary Sjögren's syndrome, a-Ro antibodies, fibromyalgia and osteoporosis. jSLE also showed more SLE family history, longer diagnosis delay, higher SLEDAI and Katz scores, but lower Charlson scores than aSLE. Several specific domains were more frequently involved in SLICC/ACR DI in jSLE. jSLE patients more frequently underwent all SLE-related treatment and procedures, as well as dialysis and kidney transplantations. jSLE shares many clinical and serological features with aSLE. However, jSLE patients typically manifested more activity, severity, cumulative damage in certain areas, than their aSLE counterparts.

A novel multi-target ligand (JM-20) protects mitochondrial integrity, inhibits brain excitatory amino acid release and reduces cerebral ischemia injury in vitro and in vivo.

PubMed

Nuñez-Figueredo, Yanier; Ramírez-Sánchez, Jeney; Hansel, Gisele; Simões Pires, Elisa Nicoloso; Merino, Nelson; Valdes, Odalys; Delgado-Hernández, René; Parra, Alicia Lagarto; Ochoa-Rodríguez, Estael; Verdecia-Reyes, Yamila; Salbego, Christianne; Costa, Silvia L; Souza, Diogo O; Pardo-Andreu, Gilberto L

2014-10-01

We previously showed that JM-20, a novel 1,5-benzodiazepine fused to a dihydropyridine moiety, possessed an anxiolytic profile similar to diazepam and strong neuroprotective activity in different cell models relevant to cerebral ischemia. Here, we investigated whether JM-20 protects against ischemic neuronal damage in vitro and in vivo. The effects of JM-20 were evaluated on hippocampal slices subjected to oxygen and glucose deprivation (OGD). For in vivo studies, Wistar rats were subjected 90 min of middle cerebral artery occlusion (MCAo) and oral administration of JM-20 at 2, 4 and 8 mg/kg 1 h following reperfusion. Twenty-four hours after cerebral blood flow restoration, neurological deficits were scored, and the infarct volume, histopathological changes in cortex, number of hippocampal and striatal neurons, and glutamate/aspartate concentrations in the cerebrospinal fluid were measured. Susceptibility to brain mitochondrial swelling, membrane potential dissipation, H2O2 generation, cytochrome c release, Ca2+ accumulation, and morphological changes in the organelles were assessed 24 h post-ischemia. In vitro, JM-20 (1 and 10 μM) administered during reperfusion significantly reduced cell death in hippocampal slices subjected to OGD. In vivo, JM-20 treatment (4 and 8 mg/kg) significantly decreased neurological deficit scores, edema formation, total infarct volumes and histological alterations in different brain regions. JM-20 treatment also protected brain mitochondria from ischemic damage, most likely by preventing Ca2+ accumulation in organelles. Moreover, an 8-mg/kg JM-20 dose reduced glutamate and aspartate concentrations in cerebrospinal fluid and the deleterious effects of MCAo even when delivered 8 h after blood flow restoration. These results suggest that in rats, JM-20 is a robust neuroprotective agent against ischemia/reperfusion injury with a wide therapeutic window. Our findings support the further examination of potential clinical JM-20 use to treat acute ischemic stroke. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

PubMed Central

Francescato, H.D.C.; Chierice, J.R.A.; Marin, E.C.S.; Cunha, F.Q.; Costa, R.S.; Silva, C.G.A.; Coimbra, T.M.

2012-01-01

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg−1·day−1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein−1·h−1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation. PMID:22331137

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin.

PubMed

Francescato, H D C; Chierice, J R A; Marin, E C S; Cunha, F Q; Costa, R S; Silva, C G A; Coimbra, T M

2012-03-01

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects.

PubMed

Sekiya, Ichiro; Muneta, Takeshi; Horie, Masafumi; Koga, Hideyuki

2015-07-01

Transplantation of mesenchymal stem cells (MSCs) is one possible strategy to achieve articular cartilage repair. We previously reported that synovial MSCs were highly proliferative and able to undergo chondrogenesis. We also found that placing a suspension of synovial MSCs on a cartilage defect for 10 minutes promoted cartilage repair in rabbit and pig models. However, the in vivo efficacy of this approach has not been tested clinically. We asked whether transplantation of synovial MSCs improves (1) MRI features, (2) histologic features, and (3) clinical evaluation scores in patients with cartilage defects in the knee? Patients with a symptomatic single cartilage lesion of the femoral condyle were indicated for inclusion in our study, and between April 2008 and April 2011, 10 patients were enrolled in this study. All patients completed followups of 3 years or more. The average followup period was 52 months (range, 37-80 months). Synovial MSCs were expanded with 10% autologous human serum for 14 days after digestion. For transplantation, the patient was positioned so that the cartilage defect was facing upward, and synovial MSC suspension was placed on the cartilage defect with a syringe under arthroscopic control. The defect with the applied suspension then was held in the upward position for 10 minutes. Five patients underwent concomitant ACL reconstructions, among whom two had meniscus suturing performed simultaneously. For MRI quantification, the cartilage defect was scored from 0 to 5. Second-look arthroscopy was performed for four patients and biopsy specimens were evaluated histologically. Clinical outcome was assessed using the Lysholm score and Tegner Activity Level Scale at final followup. Comparisons of MRI and Lysholm scores before and after treatment for each patient were analyzed using the Wilcoxon signed-rank test. MRI score (median ± 95% CI) was 1.0 ± 0.3 before and 5.0 ± 0.7 after, and increased after treatment in each patient (p = 0.005). Second-look arthroscopy in four patients showed that the cartilage defect appeared to be qualitatively better in all cases. Histologic analyses showed hyaline cartilage in three patients and fibrous cartilage in one at the deep zone. The Lysholm score (median ± 95% CI) was 76 ± 7 before and 95 ± 3 after, and increased after treatment in each patient (p = 0.005). The Tegner Activity Level Scale did not decrease after treatment in each patient. For this small initial case series, transplantation of synovial MSCs was effective in terms of MRI score, qualitative histology, and Lysholm score. The use of synovial MSCs has an advantage in that the cells can be prepared at passage 0 in only 14 days. Transplantation of synovial MSCs may be less invasive than mosaicplasty and autologous chondrocyte implantation. To conclusively show the effectiveness of this treatment requires comparative studies, especially with more established arthroscopic procedures, such as marrow stimulation techniques. Level IV, therapeutic study.

Hurricane Harvey: Infrastructure Damage Assessment of Texas' Central Gulf Coast Region

NASA Astrophysics Data System (ADS)

Mooney, W. D.; Fovenyessy, S.; Patterson, S. F.

2017-12-01

We report a detailed ground-based damage survey for Hurricane Harvey, the first major hurricane to make landfall along the central Texas coast since the 1970 Category 3 Hurricane Celia. Harvey, a Category 4 storm, made landfall near Rockport, Texas on August 25th, 2017 at 10 PM local time. From September 2nd to 5th we visited Rockport and 22 nearby cities to assess the severity of the damage. Nearly all damage observed occurred as a direct result of the hurricane-force winds, rather than a storm surge. This observation is in contrast to the severe damage caused by both high winds and a significant storm surge, locally 3 to 5 m in height, in the 2013 Category 5 Hurricane Haiyan, that devastated the Philippines. We have adopted a damage scale and have given an average damage score for each of the areas investigated. Our damage contour map illustrates the areal variation in damage. The damage observed was widespread with a high degree of variability. Different types of damage included: (1) fallen fences and utility poles; (2) trees with branches broken or completely snapped in half; (3) business signs that were either partially or fully destroyed; (4) partially sunken or otherwise damaged boats; (5) and sheet metal sheds either completely or partially destroyed. There was also varying degrees of damage to both residential and commercial structures. Many homes had (6) roof damage, ranging from minor damage to complete destruction of the roof and second story, and (7) siding damage, where parts or whole sections of the homes siding had been removed. The area that had the lowest average damage score was Corpus Christi, and the areas that had the highest average damage score was both Fulton and Holiday Beach. There is no simple, uniform pattern of damage distribution. Rather, the damage was scattered, revealing hot spots of areas that received more damage than the surrounding area. However, when compared to the NOAA wind swath map, all of the damage was contained within the zone of highest wind speed.

Early Outcomes in Children With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

PubMed

Morishita, Kimberly A; Moorthy, Lakshmi N; Lubieniecka, Joanna M; Twilt, Marinka; Yeung, Rae S M; Toth, Mary B; Shenoi, Susan; Ristic, Goran; Nielsen, Susan M; Luqmani, Raashid A; Li, Suzanne C; Lee, Tzielan; Lawson, Erica F; Kostik, Mikhail M; Klein-Gitelman, Marisa; Huber, Adam M; Hersh, Aimee O; Foell, Dirk; Elder, Melissa E; Eberhard, Barbara A; Dancey, Paul; Charuvanij, Sirirat; Benseler, Susanne M; Cabral, David A

2017-07-01

To characterize the early disease course in childhood-onset antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the 12-month outcomes in children with AAV. Eligible subjects were children entered into the Pediatric Vasculitis Initiative study who were diagnosed before their eighteenth birthday as having granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss), or ANCA-positive pauci-immune glomerulonephritis. The primary outcome measure was achievement of disease remission (Pediatric Vasculitis Activity Score [PVAS] of 0) at 12 months with a corticosteroid dosage of <0.2 mg/kg/day. Secondary outcome measures included the rates of inactive disease (PVAS of 0, with any corticosteroid dosage) and rates of improvement at postinduction (4-6 months after diagnosis) and at 12 months, presence of damage at 12 months (measured by a modified Pediatric Vasculitis Damage Index [PVDI]; score 0 = no damage, score 1 = one damage item present), and relapse rates at 12 months. In total, 105 children with AAV were included in the study. The median age at diagnosis was 13.8 years (interquartile range 10.9-15.8 years). Among the study cohort, 42% of patients achieved remission at 12 months, 49% had inactive disease at postinduction (4-6 months), and 61% had inactive disease at 12 months. The majority of patients improved, even if they did not achieve inactive disease. An improvement in the PVAS score of at least 50% from time of diagnosis to postinduction was seen in 92% of patients. Minor relapses occurred in 12 (24%) of 51 patients after inactive disease had been achieved postinduction. The median PVDI damage score at 12 months was 1 (range 0-6), and 63% of patients had ≥1 PVDI damage item scored as present at 12 months. This is the largest study to date to assess disease outcomes in pediatric AAV. Although the study showed that a significant proportion of patients did not achieve remission, the majority of patients responded to treatment. Unfortunately, more than one-half of this patient cohort experienced damage to various organ systems early in their disease course. © 2017, American College of Rheumatology.

The Localized Scleroderma Cutaneous Assessment Tool: responsiveness to change in a pediatric clinical population.

PubMed

Kelsey, Christina E; Torok, Kathryn S

2013-08-01

Lack of agreement on how to accurately capture disease outcomes in localized scleroderma (LS) has hindered the development of efficacious treatment protocols. The LS Cutaneous Assessment Tool (LoSCAT), consisting of the modified LS Skin Severity Index (mLoSSI) and the LS Damage Index, has potential for use in clinical trials. The goal of this article is to further evaluate the clinical responsiveness of the LoSCAT. Based on the modifiable nature of disease activity versus damage, we expected the mLoSSI to be responsive to change. At 2 study visits, a physician completed the LoSCAT and Physician Global Assessment (PGA) of Disease Activity and of Disease Damage for 29 patients with LS. Spearman correlations were used to examine the relationships between the change in the LoSCAT and the PGA scores. To evaluate contrasted group validity, patients were grouped according to disease activity classification and change scores of groups were compared. Minimal clinically important differences were calculated and compared with the standard error of measurement. Change in the mLoSSI score correlated strongly with change in the PGA of Disease Activity score, whereas change in the LS Damage Index score correlated weakly with change in the PGA of Disease Damage score. The mLoSSI and PGA of Disease Activity exhibited contrasted group validity. Minimal clinically important differences for the activity measures were greater than the respective standard errors of measurement. Only 2 study visits were included in analysis. This study gives further evidence that the LoSCAT, specifically the mLoSSI, is a responsive, valid measure of activity in LS and should be used in future treatment studies. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Evaluating the effectiveness of flood damage mitigation measures by the application of Propensity Score Matching

NASA Astrophysics Data System (ADS)

Hudson, P.; Botzen, W. J. W.; Kreibich, H.; Bubeck, P.; Aerts, J. C. J. H.

2014-01-01

The employment of damage mitigation measures by individuals is an important component of integrated flood risk management. In order to promote efficient damage mitigation measures, accurate estimates of their damage mitigation potential are required. That is, for correctly assessing the damage mitigation measures' effectiveness from survey data, one needs to control for sources of bias. A biased estimate can occur if risk characteristics differ between individuals who have, or have not, implemented mitigation measures. This study removed this bias by applying an econometric evaluation technique called Propensity Score Matching to a survey of German households along along two major rivers major rivers that were flooded in 2002, 2005 and 2006. The application of this method detected substantial overestimates of mitigation measures' effectiveness if bias is not controlled for, ranging from nearly € 1700 to € 15 000 per measure. Bias-corrected effectiveness estimates of several mitigation measures show that these measures are still very effective since they prevent between € 6700-14 000 of flood damage. This study concludes with four main recommendations regarding how to better apply Propensity Score Matching in future studies, and makes several policy recommendations.

Evaluating the effectiveness of flood damage mitigation measures by the application of propensity score matching

NASA Astrophysics Data System (ADS)

Hudson, P.; Botzen, W. J. W.; Kreibich, H.; Bubeck, P.; Aerts, J. C. J. H.

2014-07-01

The employment of damage mitigation measures (DMMs) by individuals is an important component of integrated flood risk management. In order to promote efficient damage mitigation measures, accurate estimates of their damage mitigation potential are required. That is, for correctly assessing the damage mitigation measures' effectiveness from survey data, one needs to control for sources of bias. A biased estimate can occur if risk characteristics differ between individuals who have, or have not, implemented mitigation measures. This study removed this bias by applying an econometric evaluation technique called propensity score matching (PSM) to a survey of German households along three major rivers that were flooded in 2002, 2005, and 2006. The application of this method detected substantial overestimates of mitigation measures' effectiveness if bias is not controlled for, ranging from nearly EUR 1700 to 15 000 per measure. Bias-corrected effectiveness estimates of several mitigation measures show that these measures are still very effective since they prevent between EUR 6700 and 14 000 of flood damage per flood event. This study concludes with four main recommendations regarding how to better apply propensity score matching in future studies, and makes several policy recommendations.

Salutary effect of pre-treatment with an Nrf2 inducer on ischemia reperfusion injury in the rat liver.

PubMed

Masuda, Yuichi; Vaziri, Nosratola D; Takasu, Chie; Li, Shiri; Robles, Lourdes; Pham, Christine; Le, Aimee; Vo, Kelly; Farzaneh, Seyed H; Stamos, Michael J; Ichii, Hirohito

2014-01-01

Ischemia-reperfusion injury (IRI) is a common phenomenon occurring during liver surgery, transplantation, and trauma. IRI causes oxidative stress which plays a critical role in causing organ damage. The Nrf2 is the master regulator of numerous genes, encoding antioxidant, detoxifying, and cytoprotective molecules. Nrf2 dysfunction has been implicated in the pathogenesis of several inflammatory disorders, cancer, and aging. This study was undertaken to investigate the effect of Nrf2 pathway activator (dh404) on warm liver IRI in a rodent model. Ten Sprague-Dawley rats were treated with dh404 or vehicle. Dh404 was dissolved in sesame oil and was given orally (1.5mg/kg) the night before and 5 hours before procedures. Rat livers were subjected to 60 minutes of 70% ischemia followed by 3 hours of reperfusion. Serum ALT and Malondialdehyde (MDA) were determined and liver tissue was processed for histological examination, and determination of apoptosis, myeloperoxidase (MPO) activity, ADP/ATP ratio, and expressions of Nrf2, eNOS, anti-oxidant enzymes, and inflammatory mediators. Serum ALT and MDA levels and tissue MPO activity were significantly lower, expression of the anti-oxidant enzyme, glutamate cysteine ligase were significantly higher, whereas expression of NFkB and COX-2 was unchanged in the dh404-treated group. Although the total Suzuki histology score did not differ significantly, the extent of sinusoidal congestion, vacuolization, and apoptosis was significantly reduced in the dh404 treated compared to the untreated group (P<0.01). Pre-treatment with dh404 resulted in partial attenuation of hepatic ischemia reperfusion injury in rats.

Milrinone-induced postconditioning reduces hepatic ischemia-reperfusion injury in rats: the roles of phosphatidylinositol 3-kinase and nitric oxide.

PubMed

Toyoda, Tomomi; Tosaka, Shinya; Tosaka, Reiko; Maekawa, Takuji; Cho, Sungsam; Eguchi, Susumu; Nakashima, Masahiro; Sumikawa, Koji

2014-01-01

Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR) injury. Milrinone, a phosphodiesterase 3 inhibitor, has been reported to exhibit preconditioning properties against hepatic IR injury; however, its PostC properties remain unknown. This study investigated whether milrinone has PostC properties against hepatic IR injury and the roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS). Male Wistar rats were separated into six groups: (1) group S: animals that underwent sham operation without ischemia, (2) group C: ischemia followed by reperfusion with no other intervention, (3) group M: milrinone administered immediately after reperfusion, (4) group MW: wortmannin, a PI3K inhibitor, injected before milrinone administration, (5) group MN: l-NAME, a NOS inhibitor, injected before milrinone administration, and (6) group MD, milrinone administered 30 min after reperfusion. Except for group S, all groups underwent 1 h of warm ischemia of median and left lateral lobes, followed by 5 h of reperfusion. Biochemical liver function analysis and histologic examination were performed. Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, histologic damage scores, and apoptotic rate in group M were significantly lower than those in group C. The inhibition of PI3K or NOS prevented this protective effect. Milrinone administered 30 min after reperfusion did not show obvious protective effects. Milrinone-induced PostC protects against hepatic IR injury when it is administered immediately after reperfusion, and PI3K and NOS may play an important role in this protective effect. Copyright © 2014 Elsevier Inc. All rights reserved.

Protective effects of silymarin against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice.

PubMed

Bektur, Nuriye Ezgi; Sahin, Erhan; Baycu, Cengiz; Unver, Gonul

2016-04-01

This study was designed to estimate protective effects of silymarin on acetaminophen (N-acetyl-p-aminophenol, paracetamol; APAP)-induced hepatotoxicity and nephrotoxicity in mice. Treatment of mice with overdose of APAP resulted in the elevation of aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) levels in serum, liver, and kidney nitric oxide (NO) levels and significant histological changes including decreased body weight, swelling of hepatocytes, cell infiltration, dilatation and congestion, necrosis and apoptosis in liver, and dilatation of Bowman's capsular space and glomerular capillaries, pale-stained tubules epithelium, cell infiltration, and apoptosis in kidney. Posttreatment with silymarin 1 h after APAP injection for 7 days, however, significantly normalized the body weight, histological damage, serum ALT, AST, BUN, SCr, and tissue NO levels. Our observation suggested that silymarin ameliorated the toxic effects of APAP-induced hepatotoxicity and nephrotoxicity in mice. The protective role of silymarin against APAP-induced damages might result from its antioxidative and anti-inflammatory effects. © The Author(s) 2013.

Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

PubMed

Mukhopadhyay, Sanjay; Parambil, Joseph G

2012-10-01

Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Photodynamic damage to cartilage and synovial tissue grafted on a chick's chorioallantoic membrane

NASA Astrophysics Data System (ADS)

Fisher, M.; Nahir, A. M.; Kimel, Sol

1997-09-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints causing pain deformities and disability. The highly vascular inflamed synovium has aggressive and destructive characteristics, it invades, erodes and gradually destroys cartilage and underlying bone. Photodynamic therapy (PDT) was performed using the chick chorioallantoic membrane (CAM) model to investigate the vitality of synovium and cartilage implanted on the CAM. Synovium, obtained from human patients, was grafted onto the CAM; gross microscopy and histology proved its vitality 7 days post grafting. Cartilage obtained from rabbit knee joint was also maintained on the CAM for 7 days. Its vitality was demonstrated by histology and by measuring metabolic and enzymatic activity of cartilage cells (chondrocytes) as well as the collagen and proteoglycans content. Selective PDT was performed using aluminum phthalocyanine tetrasulfonate (AlPcS4), a hydrophilic compound, soluble in biological solutions, as a photosensitizer. After irradiation with a diode laser (lambda equals 670 nm, 10 mW) damage was observed in vascularized synovium grafts, whereas avascular cartilage remained intact.

Subchronic exposure to kalach 360 SL-induced endocrine disruption and ovary damage in female rats.

PubMed

Hamdaoui, Latifa; Naifar, Manel; Rahmouni, Fatma; Harrabi, Bahira; Ayadi, Fatma; Sahnoun, Zouheir; Rebai, Tarek

2018-02-01

Kalach 360 SL (KL), glyphosate (G) surfactant-based herbicides, is a systemic herbicide effective against weeds. It was applied in agriculture in Tunisia and throughout the world, which can represent a risk to non-target organisms. The aim of this study was to investigate the morphological and biochemical aspects of ovary injury after exposure to KL. Female Wistar rats were divided into three groups: group 1 was used as a control; group 2 orally received 0.07 ml of KL, (126 mg of G/kg) and group 3 orally received 0.175 ml of KL (315 mg of G/kg) each day for 60 days. The subchronic exposure of KL induces impaired folliculogenesis, ovary development, decreased oestrogen secretion, promoted oxidative stress and impairments of ovary histological aspects. Histological finding shows necrosis cell, vacuolisation of follicles, dissociated oocytes and granulosa cell, associated with several atretic follicles. We conclude that KL induces endocrine disruption and ovary damage in female rats.

Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia.

PubMed

Wiard, R P; Dickerson, M C; Beek, O; Norton, R; Cooper, B R

1995-03-01

Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of lamotrigine, a novel antiepileptic drug that inhibits the release of glutamate in vitro, with both behavioral and histological measures of global ischemia in gerbils. The common carotid arteries of gerbils were occluded for either 5, 10, or 15 minutes. Twenty-one days after reperfusion, gerbils were tested for impairments in a spatial memory task (Morris water maze). After water maze testing the animals were killed, and damage to hippocampal pyramidal cells was assessed. The effect of lamotrigine on the behavioral and histological outcome of either 5 or 15 minutes of global ischemia was evaluated. Bilateral occlusion of the common carotid arteries for 5 minutes resulted in severe degeneration of hippocampal CA1 and CA2 pyramidal cells. Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion. Gerbils subjected to 5 minutes of ischemic insult were not impaired in their ability to solve a spatial memory task 21 days after cerebral ischemia. However, gerbils subjected to 10 and 15 minutes of carotid artery occlusion showed significant impairment in their ability to solve a water maze task. Lamotrigine significantly protected against the cognitive deficits associated with 15 minutes of cerebral ischemia. Histologically, increased durations of cerebral ischemia resulted in a progressive loss of CA1, CA2, and CA3 pyramidal cells. Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus. Lamotrigine also reduced the mortality associated with 15 minutes of ischemia. Lamotrigine had neuroprotective effects in a gerbil model of global cerebral ischemia. Lamotrigine protected gerbils against behavioral deficits resulting from 15 minutes of carotid occlusion and also prevented histological damage resulting from 5 and 15 minutes of global cerebral ischemia.

Varus knee osteoarthritis: Elevated synovial CD15 counts correlate with inferior biomechanical properties of lateral-compartment cartilage.

PubMed

Koller, Ulrich; Waldstein, Wenzel; Krenn, Veit; Windhager, Reinhard; Boettner, Friedrich

2018-03-01

The study analyzed the influence of synovitis on the histological and biomechanical properties of lateral-compartment cartilage. In a prospective cohort study, 84 patients (100 knees) with varus deformity of the knee were included. Osteochondral samples from the distal lateral femur underwent biomechanical and histologic analysis. Synovial tissue was sampled for histological (chronic synovitis score) and immunohistochemical evaluation of the degree of synovitis. CD15 (neutrophils), Ki-67 (dividing cells), and CD68 (macrophages) were tested in all synovial samples. While the histological synovitis score did not correlate with the degree of cartilage degeneration (histological OARSI grades), both CD15 (r s  = 0.297, p = 0.006) and Ki-67 (r s  = 0.249, p = 0.023) correlated with histological OARSI grades. There was a weak negative correlation of CD15 with biomechanical properties of cartilage of the distal lateral femur (aggregate modulus (Ha): r s  = -0.125; p = 0.257; dynamic modulus (DM): r s  = -0.216; p = 0.048). No correlations were observed for Ki-67 and CD68. In addition, biomechanical properties were inferior in knees with a CD15 of >8/high power field compared to knees with a CD15 of ≤8/high power field (Ha: p = 0.031, d = 0.46; DM: p = 0.005, d = 0.68). The study demonstrates an association of increased inflammatory activity with advanced cartilage degeneration. Lateral-compartment cartilage in knees with elevated synovial CD15 counts has a reduced ability to withstand compressive loads. CD15 might serve as an indicator for inferior biomechanical cartilage properties. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:841-846, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Etiological involvement of Helicobacter pylori in "reflux" gastritis after gastrectomy.

PubMed

Nagahata, Y; Kawakita, N; Azumi, Y; Numata, N; Yano, M; Saitoh, Y

1996-10-01

"Reflux" gastritis after gastrectomy is associated with various symptoms that are often detrimental to the patients' quality of life. However, prevention of the reflux does not always bring relief from the symptoms of gastritis. Helicobacter pylori (H. pylori) is now considered one of the most important pathogenetic factors in gastritis. The association between H. pylori infection and reflux gastritis after gastrectomy was investigated in the present study. In total, 115 patients who had undergone gastrectomy were entered in this study. Five biopsy specimens from the gastric remnant were taken during upper GI endoscopy. One specimen was examined pathohistologically, and the remaining four were examined for H. pylori infection. The histological degree of gastritis was determined according to the score system of Rauws et al. Forty-six patients (40%) demonstrated H. pylori infection in their stomachs. The prevalence of the infection was significantly higher in patients with conventional gastrectomy than in those with subtotal gastrectomy. The prevalence of H. pylori infection was significantly lower in patients who had undergone gastrectomy more than 4 yr ago. The histological gastritis score in patients with H. pylori infection was significantly higher than in those without H. pylori infection. Furthermore, the eradication of H. pylori in patients with both serious gastritis symptoms and no bile reflux improved the symptoms and significantly decreased the histological gastritis score. The results suggest that H. pylori is a factor in the pathogenesis of reflux gastritis after gastrectomy.

Comparison of histological effects of polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats

PubMed Central

Karahan, Nazım; Arslan, İlyas; Orak, Müfit; Midi, Ahmet; Yücel, İstemi

2017-01-01

Aim: The histological effects of intra-articular polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats were investigated. Methods: Thirty rats were divided into three groups, i.e. polydeoxyribonucleic acid group, hyaluronic acid group and saline group. Osteoarthritis of the knee joints of the rats were induced by acl- transection. The polydeoxyribonucleic group was injected with 100 µg (0.05 cc) polydeoxyribonucleic acid. The hyaluronic acid group was injected with 100 µg (0.05 cc) hyaluronic acid, and the saline group was injected with 50 µl (0.05 cc) of 0.9% sodium chloride solution. All of the rats were sacrificed on day 29 and the right knee joints were prepared, and evaluated histologically by Mankin classification. Findings: The differences in total Mankin scores between the three groups were statistically significant (P < 0.01). The differences in total Mankin scores between the polydeoxyribonucleic acid group and the hyaluronic acid group were statistically significant (P < 0.01). The differences in total Mankin scores between hyaluronic acid group and saline group were statistically significant (P < 0.01). Tidemark continuity in all the specimens of the polydeoxyribonucleic acid group was noteworthy. Conclusion: The present study shows that more chondroprotective effect and less degeneration was observed with intra-articularly delivered polydeoxyribonucleic acid compared to hyaluronic acid and saline solution in the experimentally induced osteoarthritis of the knee joints of rats.

Relationships between traumatic symptoms and environmental damage conditions among children 8 months after the 2011 Japan earthquake and tsunami.

PubMed

Usami, Masahide; Iwadare, Yoshitaka; Kodaira, Masaki; Watanabe, Kyota; Aoki, Momoko; Katsumi, Chiaki; Matsuda, Kumi; Makino, Kazunori; Iijima, Sonoko; Harada, Maiko; Tanaka, Hiromi; Sasaki, Yoshinori; Tanaka, Tetsuya; Ushijima, Hirokage; Saito, Kazuhiko

2012-01-01

To evaluate relationships between traumatic symptoms and environmental damage conditions among children who survived the 2011 Great East Japan Earthquake and Tsunami. The subjects were 12,524 children in kindergartens, elementary schools, and junior high schools in Ishinomaki City, Miyagi Prefecture, Japan. The Post Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-completion questionnaire on traumatic symptoms, was distributed to the children and a questionnaire regarding environmental damage conditions affecting the children was distributed to their teachers. Of 12,524 questionnaires distributed, an effective response was obtained from 11,692 (93.3%). The PTSSC-15 score was significantly higher in females than in males among 4(th) to 6(th) grade students in elementary schools and among junior high school students. In terms of traumatic symptoms and environmental damage conditions, with the exception of kindergartners, children who had their houses damaged or experienced separation from family members had a significantly higher PTSSC-15 score than children who did not experience environmental damage. Except for kindergartners and 4(th)- to 6(th)-grade elementary school students, children who experienced evacuation had a significantly higher PTSSC-15 score. This study demonstrated relationships between traumatic symptoms and environmental damage conditions in children who had suffered from the disaster. Factors examined in studying the relationship between environmental damage conditions and traumatic symptoms were gender, age, house damage, evacuation experience, and bereavement experience. It was critical not only to examine the traumatic symptoms of the children but also to collect accurate information about environmental damage conditions.

Relationships between Traumatic Symptoms and Environmental Damage Conditions among Children 8 Months after the 2011 Japan Earthquake and Tsunami

PubMed Central

Usami, Masahide; Iwadare, Yoshitaka; Kodaira, Masaki; Watanabe, Kyota; Aoki, Momoko; Katsumi, Chiaki; Matsuda, Kumi; Makino, Kazunori; Iijima, Sonoko; Harada, Maiko; Tanaka, Hiromi; Sasaki, Yoshinori; Tanaka, Tetsuya; Ushijima, Hirokage; Saito, Kazuhiko

2012-01-01

Background To evaluate relationships between traumatic symptoms and environmental damage conditions among children who survived the 2011 Great East Japan Earthquake and Tsunami. Methods The subjects were 12,524 children in kindergartens, elementary schools, and junior high schools in Ishinomaki City, Miyagi Prefecture, Japan. The Post Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-completion questionnaire on traumatic symptoms, was distributed to the children and a questionnaire regarding environmental damage conditions affecting the children was distributed to their teachers. Of 12,524 questionnaires distributed, an effective response was obtained from 11,692 (93.3%). Results The PTSSC-15 score was significantly higher in females than in males among 4th to 6th grade students in elementary schools and among junior high school students. In terms of traumatic symptoms and environmental damage conditions, with the exception of kindergartners, children who had their houses damaged or experienced separation from family members had a significantly higher PTSSC-15 score than children who did not experience environmental damage. Except for kindergartners and 4th- to 6th-grade elementary school students, children who experienced evacuation had a significantly higher PTSSC-15 score. Conclusions This study demonstrated relationships between traumatic symptoms and environmental damage conditions in children who had suffered from the disaster. Factors examined in studying the relationship between environmental damage conditions and traumatic symptoms were gender, age, house damage, evacuation experience, and bereavement experience. It was critical not only to examine the traumatic symptoms of the children but also to collect accurate information about environmental damage conditions. PMID:23209817

Remote histology learning from static versus dynamic microscopic images.

PubMed

Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

2016-05-06

Histology is the study of microscopic structures in normal tissue sections. Curriculum redesign in medicine has led to a decrease in the use of optical microscopes during practical classes. Other imaging solutions have been implemented to facilitate remote learning. With advancements in imaging technologies, learning material can now be digitized. Digitized microscopy images can be presented in either a static or dynamic format. This study of remote histology education identifies whether dynamic pictures are superior to static images for the acquisition of histological knowledge. Test results of two cohorts of second-year Bachelor in Medicine students at Ghent University were analyzed in two consecutive academic years: Cohort 1 (n = 190) and Cohort 2 (n = 174). Students in Cohort 1 worked with static images whereas students in Cohort 2 were presented with dynamic images. ANCOVA was applied to study differences in microscopy performance scores between the two cohorts, taking into account any possible initial differences in prior knowledge. The results show that practical histology scores are significantly higher with dynamic images as compared to static images (F (1,361) = 15.14, P < 0.01), regardless of student's gender and performance level. Several reasons for this finding can be explained in accordance with cognitivist learning theory. Since the findings suggest that knowledge construction with dynamic pictures is stronger as compared to static images, dynamic images should be introduced in a remote setting for microscopy education. Further implementation within a larger electronic learning management system needs to be explored in future research. Anat Sci Educ 9: 222-230. © 2015 American Association of Anatomists. © 2015 American Association of Anatomists.

Different histological status of gastritis in superficial adenocarcinoma of the esophagogastric junction.

PubMed

Yamada, Masayoshi; Kushima, Ryoji; Oda, Ichiro; Mojtahed, Kaveh; Nonaka, Satoru; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Matsubara, Akiko; Taniguchi, Hirokazu; Sekine, Shigeki; Saito, Yutaka; Shimoda, Tadakazu

2014-01-01

Although many gastric cancers arise in chronic gastritis, the association between adenocarcinoma of the esophagogastric junction and the status of background gastritis remains unclear. We aim to investigate the histological status of gastritis in the background fundic gland mucosa of adenocarcinoma of the esophagogastric junction. The present study included 121 consecutive patients with superficial adenocarcinoma of the esophagogastric junction obtained by surgical and/or endoscopic resection. We re-evaluated the histogenesis of adenocarcinoma of the esophagogastric junction, including the background fundic gland mucosa using the Updated Sydney System. The prevalence of histologic atrophic gastric mucosa with gastritis (positive gastritis), non-atrophic gastric mucosa without gastritis (negative gastritis) and Barrett's adenocarcinoma was examined. Histologic-positive gastritis was found in 67 (55%) of all patients, in 24 (38%) of 63 Barrett's adenocarcinoma patients and in 43 (74%) of 58 non-Barrett's adenocarcinoma patients (P < 0.01). A higher female ratio in non-Barrett's adenocarcinoma with gastritis patients `and younger age in non-Barrett's adenocarcinoma without gastritis patients were shown. There were no differences in clinicopathological features related to the gastritis status in Barrett's adenocarcinoma patients. Reflux esophagitis was observed in most (81%) of all patients, and 32 (74%) of the non-Barrett's adenocarcinoma with gastritis patients. In the 67 positive gastritis patients, the mean Updated Sydney System scores of glandular atrophy and intestinal metaplasia were 1.45 and 1.10, respectively, and these scores were higher in the non-Barrett's adenocarcinoma patients than in the Barrett's adenocarcinoma patients. This study suggests that about half of the patients with adenocarcinoma of the esophagogastric junction harbor histological gastritis. Adenocarcinoma of the esophagogastric junction is considered to be a heterogeneous entity, including Barrett's esophagus-related, positive gastritis-related, and Barrett's esophagus and gastritis-unrelated adenocarcinoma of the esophagogastric junction.

Protective effect of alpha glucosyl hesperidin (G-hesperidin) on chronic vanadium induced testicular toxicity and sperm nuclear DNA damage in male Sprague Dawley rats.

PubMed

Vijaya Bharathi, B; Jaya Prakash, G; Krishna, K M; Ravi Krishna, C H; Sivanarayana, T; Madan, K; Rama Raju, G A; Annapurna, A

2015-06-01

The study was conducted to evaluate the vanadium-induced testicular toxicity and its effect on sperm parameters, sperm nuclear DNA damage and histological alterations in Sprague Dawley rats and to assess the protective effect of G-hesperidin against this damage. Treatment of rats with vanadium at a dose of 1 mg kg bw(-1) for 90 days resulted in significant reduction in serum testosterone levels, sperm count and motility. Further, a parallel increase in abnormal sperm morphology and adverse histopathological changes in testis was also associated with vanadium administration when compared to normal control. Moreover, sperm chromatin dispersion assay revealed that vanadium induces sperm nuclear DNA fragmentation. A marked increase in testicular malondialdehyde levels and decreased activity of antioxidant enzymes such as superoxide dismutase and catalase indicates vanadium-induced oxidative stress. Co-administration of G-hesperidin at a dose of 25 and 50 mg kg bw(-1) significantly attenuated the sperm parameters and histological changes by restoring the antioxidant levels in rat testis. These results suggested that vanadium exposure caused reduced bioavailability of androgens to the tissue and increased free radical formation, thereby causing structural and functional changes in spermatozoa. G-hesperidin exhibited antioxidant effect by protecting the rat testis against vanadium-induced oxidative damage, further ensures antioxidant potential of bioflavonoids. © 2014 Blackwell Verlag GmbH.

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease

PubMed Central

Varsani, Hemlata; Charman, Susan C; Li, Charles K; Marie, Suely K N; Amato, Anthony A; Banwell, Brenda; Bove, Kevin E; Corse, Andrea M; Emslie-Smith, Alison M; Jacques, Thomas S; Lundberg, Ingrid E; Minetti, Carlo; Nennesmo, Inger; Rushing, Elisabeth J; Sallum, Adriana M E; Sewry, Caroline; Pilkington, Clarissa A; Holton, Janice L; Wedderburn, Lucy R

2015-01-01

Objectives To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. Methods 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers’ ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. Results Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. Conclusions The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM. PMID:24064003

Let thy left brain know what thy right brain doeth: Inter-hemispheric compensation of functional deficits after brain damage.

PubMed

Bartolomeo, Paolo; Thiebaut de Schotten, Michel

2016-12-01

Recent evidence revealed the importance of inter-hemispheric communication for the compensation of functional deficits after brain damage. This review summarises the biological consequences observed using histology as well as the longitudinal findings measured with magnetic resonance imaging methods in brain damaged animals and patients. In particular, we discuss the impact of post-stroke brain hyperactivity on functional recovery in relation to time. The reviewed evidence also suggests that the proportion of the preserved functional network both in the lesioned and in the intact hemispheres, rather than the simple lesion location, determines the extent of functional recovery. Hence, future research exploring longitudinal changes in patients with brain damage may unveil potential biomarkers underlying functional recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Generalized bone loss as a predictor of three-year radiographic damage in African American patients with recent-onset rheumatoid arthritis.

PubMed

Zhang, Jie; Redden, David T; McGwin, Gerald; Callahan, Leigh F; Smith, Edwin A; Alarcón, Graciela S; Moreland, Larry W; van der Heijde, Désirée M; Brown, Elizabeth E; Arnett, Donna K; Mikuls, Ted R; Bridges, S Louis

2010-08-01

To examine the association between baseline bone mineral density (BMD) and radiographic damage at 3 years of disease duration in a longitudinal cohort of African Americans with recent-onset rheumatoid arthritis (RA). African American RA patients with a disease duration of <2 years (n = 141) were included in the study. All patients underwent baseline BMD measurements (femoral neck and/or lumbar spine) using dual x-ray absorptiometry. T scores were calculated using normative data from the general population of African Americans. Patients were categorized as having osteopenia/osteoporosis (T score less than or equal to -1) or as being healthy. Hand and wrist radiographs, obtained at baseline and at 3 years of disease duration, were scored using the modified Sharp/van der Heijde method. The association between baseline BMD and total radiographic score at 3 years of disease was examined using multivariable negative binomial regression. At baseline, the mean age and the mean disease duration were 52.4 years and 14.8 months, respectively; 85.1% of the patients were women. The average total radiographic scores at baseline and at 3 years of disease were 2.4 and 5.7, respectively. In the final reduced multivariable model, adjusting for age, sex, anti-cyclic citrullinated peptide antibody positivity, and the presence of radiographic damage at baseline, the total radiographic score at 3 years disease in patients with osteopenia/osteoporosis of the femoral neck was twice that in patients with normal bone density, and the difference was statistically significant (P = 0.0084). No association between lumbar spine osteopenia/osteoporosis and radiographic score was found. Our findings suggest that reduced generalized BMD may be a predictor of future radiographic damage and support the hypothesis that radiographic damage and reduced generalized BMD in RA patients may share a common pathogenic mechanism.

The effect of asymptomatic histological prostatitis on sexual function and lower urinary tract symptoms.

PubMed

Urkmez, Ahmet; Yuksel, Ozgur Haki; Uruc, Fatih; Akan, Serkan; Yildirim, Caglar; Sahin, Aytac; Verit, Ayhan

2016-05-01

Prostatitis affects 10-14% of men of all ages and ethnicities. More than 50% of the men experience episodes of prostatitis at one time of their lives. Patients with CP typically have longlasting genitourinary/pelvic pain and obstructive and/or irritative voiding symptoms. Sexual dysfunction and psychological symptoms are frequently added to these symptoms. We also investigated the relationship between sexual functions, and lower urinary system symptoms, and asymptomatic histological prostatitis detected on transrectal ultrasound-guided (TRUS) biopsy performed with the indication of high PSA levels. Sixty cases compliant with the study criteria among patients who underwent prostate biopsies between September 2014 and June 2015 with the indication of higher PSA levels were included in the study. All patients were requested to complete IIEF-5 and IPSS forms one day previously. Based on histological analysis of biopsy materials, the patients were allocated into groups of BPH (simple BPH without histological prostatitis) (n:30) and histological chronic prostatitis (combination of BPH and histological prostatitis) (n:30). Mean age of the cases was 65.73±5.01 (range, 56-75 yrs) years. PSA levels ranged between 4-15 ng/ml. A statistically significant intergroup difference was not found regarding mean age, BMIs, PSA levels, incidence rates of hypertension and coronary artery disease (p>0.05). Prostate volumes of the HCP group were higher than those of the BPH group , with statistically significant differences (p:0.001; p<0.01). Questionnaire forms of the patients included in the study were statistically evaluated, and mean IPSS score of the HCP group was found to be higher when compared with that of the BPH group, with statistically significant differences. (p:0.016; p<0.05). However mean IIEF score of the BPH group was higher than that of the HCP group, with statistically significant differences (p:0.039; p<0.05). These findings suggested the presence of a correlation between chronic inflammation and lower urinary tract symptoms (LUTS). In addition, statistically significant lower IIEF values in patients with histological chronic prostatitis relative to those without suggested negative effects of even asymptomatic inflammation on sexual functions and mechanism of erection.

Ovarian histology and follicular score in female rats treated with nandrolone decanoate and submitted to physical effort.

PubMed

Cherici Camargo, Isabel Cristina; Barreiros de Souza, Roberta; de Fátima Paccola Mesquita, Suzana; Chuffa, L G A; Frei, F

2009-09-01

The study was conducted to analyze the histology of the ovaries of adults rats treated with steroids, and submitted or not to physical effort. The control group consisted of females submitted to physical effort and sedentary females, both of which received a physiological solution of 0.9% saline. Treated females, sedentary or not, received 6 mg/kg of body weight of nandrolone decanoate. The steroid and physiological solution were administered intraperitoneally, with a single injection per week for 4 consecutive weeks. The applied physical effort was swimming (20 minutes daily, 5 days/week, for the 4 weeks of treatment). Serial sections (5 mum) of ovaries were prepared for histological evaluation and follicular score. The weight of ovaries and hypophysis, the number of antral and atretic follicles, and the area of corpus luteum were all affected by the steroids. In the ovaries of the control groups, well-developed corpus luteum was observed. In the treated groups, the cortical stroma was occupied by ovarian interstitial tissue. The females treated with steroids presented estral acyclicity. The use of nandrolone decanoate, whether associated with physical effort or not, affected the morphological pattern of the ovaries.

Effect of vitamin E on reversibility of renal function following discontinuation of colistin in rats: Histological and biochemical investigations.

PubMed

Ghlissi, Zohra; Hakim, Ahmed; Mnif, Hela; Kallel, Rim; Zeghal, Khaled; Boudawara, Tahiya; Sahnoun, Zouheir

2018-01-01

This study was carried out to evaluate spontaneous renal regeneration after stopping colistin methanesulfonate (CMS), which induces tubular damage, and the curative effect of Vitamin E (vit E) in rats. Animals were given the following: sterile saline (n = 6), 300,000 IU/kg/ day of CMS (n = 24), or 450,000 IU/kg/day of CMS (n = 24) for seven days. Each CMS group was subdivided into four subgroups (n = 6) and sacrificed as follows: (i) 12 h after stopping CMS, (ii) two weeks after stopping CMS, (iii) two weeks after stopping treatment with vit E, and (iv) two weeks after stopping treatment with olive oil. Subsequently, plasma creatinine (pCr), urine N-acetyl-b-D-glucosaminidase (NAG), renal tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GSH), and renal histology were tested. CMS-induced tubular damage increased the NAG and MDA levels and decreased the SOD and GSH activities. After two weeks of stopping CMS, there was no significant renal recovery. However, treatment with vit E improved tubular regeneration and reduced the biochemical impairments. Two weeks might not be long enough for significant spontaneous renal regeneration. Improvement of renal parameters by vit E could be explained by the reduction of oxidative stress damage.

Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract

PubMed Central

THAM, CHING S.; CHAKRAVARTHI, SRIKUMAR; HALEAGRAHARA, NAGARAJA; DE ALWIS, RANJIT

2013-01-01

Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis. PMID:23403524

Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract.

PubMed

Tham, Ching S; Chakravarthi, Srikumar; Haleagrahara, Nagaraja; DE Alwis, Ranjit

2013-02-01

Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis.

Berberine attenuates oxidative stress and hepatocytes apoptosis via protecting mitochondria in blunt snout bream Megalobrama amblycephala fed high-fat diets.

PubMed

Lu, Kang-Le; Wang, Li-Na; Zhang, Ding-Dong; Liu, Wen-Bin; Xu, Wei-Na

2017-02-01

High-fat diets may have favorable effects on growth and cost, but high-fat diets often induce excessive fat deposition, resulting in liver damage. This study aimed to identify the hepatoprotective of a Chinese herb (berberine) for blunt snout bream (Megalobrama amblycephala). Fish were fed with a normal diet (LFD, 5 % fat), high-fat diet (HFD, 15 % fat) or berberine-supplemented diets (BSD, 15 % fat with berberine 50 or 100 mg/kg level) for 8 weeks. After the feeding, histology, oxidative status and mitochondrial function of liver were assessed. The results showed that HFD caused fat accumulation, oxidative stress and apoptosis in hepatocytes of fish. Hepatocytes in HFD group appeared to be hypertrophied, with larger liver cells diameter than these of LFD group. Berberine-supplemented diets could attenuate oxidative stress and hepatocytes apoptosis. HFD induced the decreasing mitochondrial complexes activities and bulk density and surface area density. Berberine improved function of mitochondrial respiratory chain via increasing the complex activities. Moreover, the histological results showed that berberine has the potential to repair mitochondrial ultrastructural damage and elevate the density in cells. In conclusion, our study demonstrated that berberine has attenuated liver damage induced by the high fat mainly via the protection for mitochondria.

Efficacy of retinol palmitate eye drops for dry eye in rabbits with lacrimal gland resection

PubMed Central

Odaka, Akito; Toshida, Hiroshi; Ohta, Toshihiko; Tabuchi, Nobuhito; Koike, Daisuke; Suto, Chikako; Murakami, Akira

2012-01-01

Purpose We examined the efficacy of retinol palmitate (VApal) for dry eyes using dry eye model rabbits whose lacrimal glands were resected. Materials and methods After alkaline injury on keratoconjunctival epithelium, VApal eye drops were administered 6 times a day for 7 days. The efficacy of VApal was also compared with that of 0.1% hyaluronic acid eye drops. Results The fluorescein staining and rose bengal scores showed a significant decrease compared with the score in the vehicle group at 7 days (P < 0.05) in the 1000 IU/mL VApal group and at both 3 days (P < 0.05) and 7 days (P < 0.01) in the 1500 IU/mL VApal group. Histological examination revealed recovery of the corneal epithelium, and PAS staining disclosed the recovery of mucin-producing lower palpebral conjunctival goblet cells after 7 days in the 1500 IU/mL VApal group compared with the vehicle group. Results from impression cytology showed a significant increase in density of conjunctival goblet cells compared with that in the vehicle group after 7 days in the 1000 IU/mL VApal group and after 3 and 7 days in the 1500 IU/mL VApal group. There were no significant changes in tear flow in either group. Topical application of VApal at 1500 IU/mL showed greater improvement than 0.1% hyaluronic acid in both fluorescein and rose bengal score and in the density of conjunctival goblet cells. Conclusion It is suggested that VApal is effective for the improvement of keratoconjunctival epithelial damage associated with tear abnormalities, such as dry eyes. PMID:23055683

Melatonin attenuates lung ischaemia-reperfusion injury via inhibition of oxidative stress and inflammation.

PubMed

Wang, Ming-Liang; Wei, Chun-Hua; Wang, Wen-Dong; Wang, Jia-Shun; Zhang, Jun; Wang, Jian-Jun

2018-05-01

Lung ischaemia-reperfusion injury is a complex pathophysiological process due to the production of reactive oxygen species and the generation of inflammatory reaction. We investigated the protective effects and the corresponding mechanism of melatonin (MT), a potent free-radical scavenger, on lung injury induced by ischaemia-reperfusion in a mouse model. Adult male C57BL/6J mice (n = 30) were randomly and equally allocated into 5 groups: sham controls, IR, IR + 10 mg/kg MT, IR + 20 mg/kg MT and IR + 30 mg/kg MT. Lung ischaemia-reperfusion injury was induced by thoracotomy followed by clamping of the left hilum for 1 h and subsequent reperfusion for 2 h. Histological scoring analysis showed that lung parenchymal damage was ameliorated in the melatonin pretreatment groups when compared with the IR group, with the IR + 20 mg/kg MT group showing the strongest effect among the melatonin pretreatment groups. Wet-to-dry weight ratio, detection of malondialdehyde, protein expressions of inflammatory factors (tumour necrosis factor-α, interleukin-1β, NF-κB and IKK-γ) and apoptotic factors (cleaved caspase-3 and Bax/Bcl-2), as well as TUNEL assay showed changes similar to those of the lung injury scores in all groups. In contrast, the examination of superoxide dismutase showed a pattern contrary to that of the lung injury score in all groups. In addition, immunohistochemistry staining showed that the expressions of the antioxidants glutathione peroxidase and glutathione reductase were increased in the melatonin pretreatment groups. This study demonstrated that melatonin pretreatment attenuated lung ischaemia-reperfusion injury via inhibition of oxidative stress, inflammation and apoptosis.

Role of zinc in chronic gastritis.

PubMed

Marjanović, Ksenija; Dovhanj, Jasna; Kljaić, Ksenija; Sakić, Katarina; Kondza, Goran; Tadzić, Refmir; Vcev, Aleksandar

2010-06-01

Oxidative stress occurs in inflammation of gastric mucosa. The role of zinc in modulating oxidative stress has recently been recognized. Zn deficiency results in an increased sensitivity to oxidative stress and have a higher risk of musoca damage in inflammation. The aim of this study was to determine wheather chronic inflammation affects on the concentration of Zn2+ ions in gastric mucosa of patients with chronic gastritis. Forthy-three patients with chronic gastitis were enrolled. Patients were endoscoped. Histology and scoring of gastritis was performed following the guidelines of the updated Sydney system. Endoscopic finding of mucosa were scored according to a Lanza scoring system. The diagnosis of Helicobacter pylori (H. pylori) infection, histopathologic changes, intensity of inflammation and zinc concentration were determined from biopsies of gastric mucosa. The atomic absorption spectrophotometer was used to determine tissue concentrations of zinc. Twenty of 43 patients with chronic gastritis were uninfected by H. pylori. There was no statistically significant difference in tissue concentrations of zinc between H. pylori-positive and H. pylori-negative patients. From those infected patients 53.3% had chronic active gastritis. There was no statistically significant difference in tissue concentrations of zinc between patients with chronic active gastritis and patients with chronic inactive gastritis (p = 0.966). Zn in antrum showed positive correlation with density of H. pylori in antrum (Spearman' rho = 0.481, p = 0.020), negative correlation with density of H. pylori in corpus (Spearman' rho = -0.492, p = 0.017) and with zinc in corpus (Spearman' rho = 0.631, p =0.001). Tissue concentration of zinc was not affected by chronic inflammation of gastric mucosa in patients with chronic gastritis.

Mangiferin attenuates DSS colitis in mice: Molecular docking and in vivo approach.

PubMed

Somani, Sahil; Zambad, Shitalkumar; Modi, Ketan

2016-06-25

Inflammation, oxidative stress and altered mucosal barrier permeability are potential etiopathological or triggering factors for inflammatory bowel disease (IBD). In this study, the therapeutic potential of Mangiferin was investigated in vivo in mouse model of colitis and also attempts were made to understand mechanistic insights of Mangiferin in IBD. In present study, colitis was induced by administration of 5% DSS for 11 days, followed by 3 days of DSS free period. On day 14, animals were sacrificed and colon tissues were taken for biochemical and histological analysis. Therapeutic treatment with Mangiferin after colitis induction (i.e. day 5) ameliorated symptoms of colitis (presence of blood in stools, body weight loss and diarrhea) as evidenced by reduced DAI score, attenuated the levels of catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO). It also decreased the colonic pro-inflammatory mediators tumor necrosis factor (TNF-α), interleukin 1β (IL-1β) levels, matrix metalloproteinase-9 (MMP-9) activity and histopathological score. Molecular docking of Mangiferin against TNF-α and MMP-9 was evaluated using GLIDE software. Mangiferin demonstrated the glide score of -8.04 kcal/mol for TNF-α and -9.97 kcal/mol for MMP-9, which indicated its binding potential with TNF-α and MMP-9. In conclusion, Mangiferin reduces colonic damage in a murine model of colitis, alleviates the oxidative and inflammatory events partly through directly influencing the activity of TNF-α and MMP-9 and therefore might have therapeutic usefulness in the management of inflammatory bowel disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Exploring the ameliorative potential of probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum on dextran sodium sulphate induced colitis in mice.

PubMed

Jadhav, Sagar R; Shandilya, Umesh Kr; Kansal, Vinod K

2013-02-01

Conventional medical therapies for ulcerative colitis (UC) are still limited due to the adverse side effects like dose-dependent diarrhoea and insufficient potency to keep in remission for long-term periods. So, new alternatives that provide more effective and safe therapies for ulcerative colitis are constantly being sought. In the present study, probiotic LaBb Dahi was selected for investigation of its therapeutic effect on DSS-induced colitis model in mice. LaBb Dahi was prepared by co-culturing Dahi culture of Lactococci along with selected strain of Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3 in buffalo milk. Four groups of mice (12 each) were fed for 17 d with buffalo milk (normal control), buffalo milk plus DSS (Colitis control), Dahi plus DSS, and LaBb Dahi plus DSS, respectively, with basal diet. The disease activity scores, weight loss, organ weight, colon length, myeloperoxidase (MPO) and β-glucoronidase activity was assessed, and the histopathological picture of the colon of mice was studied. All colitis control mice evidenced significant increase in MPO, β-glucoronidase activity and showed high disease activity scores along with histological damage to colonic tissue. Feeding with LaBb Dahi offered significant reduction in MPO activity, β-glucoronidase activity and improved disease activity scores. We found significant decline in length of colon, organ weight and body weight in colitis induced controls which were improved significantly by feeding LaBb Dahi. The present study suggests that LaBb Dahi can be used as a potential nutraceutical intervention to combat UC related changes and may offer effective adjunctive treatment for management of UC.

Association Between Genetic Variation in FOXO3 and Reductions in Inflammation and Disease Activity in Inflammatory Polyarthritis

PubMed Central

Viatte, Sebastien; Lee, James C.; Fu, Bo; Espéli, Marion; Lunt, Mark; De Wolf, Jack N. E.; Wheeler, Lily; Reynolds, John A.; Castelino, Madhura; Symmons, Deborah P. M.; Lyons, Paul A.

2016-01-01

Objective Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte‐driven inflammation through a transforming growth factor β1–dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis. Methods Collagen‐induced arthritis, the most commonly used mouse model of RA, was used to assess how Foxo3 contributes to arthritis severity. Using clinical, serologic, and biochemical methods, the arthritis that developed in mice carrying a loss‐of‐function mutation in Foxo3 was compared with that which occurred in littermate controls. The association of rs12212067 with nonradiographic measures of RA severity, including the C‐reactive protein level, the swollen joint count, the tender joint count, the Disease Activity Score in 28 joints, and the Health Assessment Questionnaire score, were modeled longitudinally in a large prospective cohort of patients with early RA. Results Loss of Foxo3 function resulted in more severe arthritis in vivo (both clinically and histologically) and was associated with higher titers of anticollagen antibodies and interleukin‐6 in the blood. Similarly, rs12212067 (a single‐nucleotide polymorphism that increases FOXO3 transcription) was associated with reduced inflammation, both biochemically and clinically, and with lower RA activity scores. Conclusion Consistent with its known role in restraining inflammatory responses, FOXO3 limits the severity of in vivo arthritis and, through genetic variation that increases its transcription, is associated with reduced inflammation and disease activity in RA patients, effects that result in less radiographic damage. PMID:27214848

Depressive disorder may be associated with raphe nuclei lesions in patients with brainstem infarction.

PubMed

Numasawa, Yoshiyuki; Hattori, Takaaki; Ishiai, Sumio; Kobayashi, Zen; Kamata, Tomoyuki; Kotera, Minoru; Ishibashi, Satoru; Sanjo, Nobuo; Mizusawa, Hidehiro; Yokota, Takanori

2017-04-15

Depression is a common symptom after stroke, but its neural substrates remain unclear. The ascending serotonergic system originates from the raphe nuclei in the brainstem. We hypothesized that depressive disorder due to brainstem infarction is associated with damage to the raphe nuclei. We prospectively enrolled 19 patients who had the first-ever acute isolated brainstem infarction in an observational cross-sectional study. All patients were evaluated by using the Montgomery Åsberg Depression Rating Scale (MADRS), the clinician-rated version of Apathy Evaluation Scale (AES-C) and Mini-Mental State Examination (MMSE). Depressive disorder was diagnosed according to DSM-5 and MADRS score of 12 or greater. Diffusion tensor imaging and proton density-weighted images were used to identify damage in the raphe nuclei. Accordingly, patients were classified into either the raphe-nuclei-damaged or intact group. Prevalence of depressive disorder and the MADRS, AES-C, and MMSE scores were compared between the two groups. Depressive disorder was more frequent in the damaged group (n=6) than in the intact group (n=13) (83% vs. 15%; P=0.01). MADRS scores were higher in the damaged group than in the intact group (mean±1 SD, 17.5±7.9 vs. 7.0±4.4; P=0.002), whereas the AES-C and MMSE scores did not differ between groups. We did not assess the damage to the ascending projection fibers from the raphe nuclei. Our results suggest that damage to the raphe nuclei underlies depressive disorder due to brainstem infarction, possibly via serotonergic denervation. Copyright © 2017 Elsevier B.V. All rights reserved.

Possible protective effect of royal jelly against cyclophosphamide induced prostatic damage in male albino rats; a biochemical, histological and immuno-histo-chemical study.

PubMed

Abdel-Hafez, Sara Mohammed Naguib; Rifaai, Rehab Ahmed; Abdelzaher, Walaa Yehia

2017-06-01

Almost all the chemotherapy treat many cancer types effectively, but it leads to severe side effects. Chemotherapy like cyclophosphamide (CP) not works only on the active cells, such as cancer cells, but also acts on the healthy cells. Royal jelly (RJ) was reported to have a lot of therapeutic effects besides being an anti-oxidant and anti-cancer agent. The purpose of this study was to assess the possible protective role of RJ in ameliorating the toxic effects of CP overdose in the rat prostatic tissue. The rats were separated into 4 groups; control group, RJ group, CP group and RJ with CP group. Prostatic specimens were processed for biochemical, histological and immune-histo-chemical studies. The mean area fractions of eNOS and Bax expression were measured in all groups, and statistical analysis was carried out. The results showed that in CP treated group, there were marked biological changes in the form of significant increase in prostatic malondialdehyde (MDA) and C - reactive protein (CRP). Additionally there was a significant decrease in glutathione peroxidase (GPx) in prostatic tissue if compared with the control group. Furthermore, the histological changes showed marked acinar and stromal prostatic degeneration. Most prostatic acini showed less PAS reaction and more (eNOS and Bax) expression if compared with the control group. Concomitant administration of RJ with CP revealed a noticeable amelioration of these biochemical and histological changes. In conclusion, RJ provided biochemical and histo-pathological improvement in CP induced prostatic tissue toxicity. These findings revealed that this improvement was associated with a decrease in the tissue oxidative damage and apoptosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The Role of Calcium in Ameliorating the Oxidative Stress of Fluoride in Rats.

PubMed

Mohamed, N E

2016-03-01

The present study was carried out to investigate the effects of fluoride toxicity on some biochemical, hormonal, and histological parameters of female rats and the protective role of calcium against such effects. Adult female albino rats were divided into five groups; control group received distilled water for 60 days, calcium group received calcium carbonate with dose of 50 mg/kg three times per week for 60 days, fluoride group received sodium fluoride with dose of 20 mg/kg three times per week for 60 days, calcium + fluoride group received calcium carbonate (50 mg/kg) then after 2 h received sodium fluoride (20 mg/kg) three times per week for 60 days, and fluoride + calcium group received sodium fluoride (20 mg/kg) three times per week for 30 days then received calcium carbonate (50 mg/kg) three times per week for another 30 days. The results showed that the levels of thiobarbituric acid reactive substances, urea, creatinine, alkaline phosphatase, triiodothyronine, thyroxine, parathormone, phosphorous, magnesium, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transferase were significantly increased in rats treated with fluoride while serum estradiol, calcium, and organ glutathione were significantly decreased. The histological examination of the femur bone revealed that fluoride treatment induced thinning of bone trabeculae with wilding of marrow space, demineralization, and loss of trabeculae interconnections. Also, the histological examination of hepatic and renal tissues of fluoride-treated rats showed some damages in these tissues while administration of calcium carbonate for 30 or 60 days during fluoride treatment minimized such damages. It could be concluded that administration of calcium to female rats can ameliorate the hazardous effects of fluoride observed in the biochemical, hormonal, and histological parameters.

Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury.

PubMed

Osna, Natalia A; Feng, Dan; Ganesan, Murali; Maillacheruvu, Priya F; Orlicky, David J; French, Samuel W; Tuma, Dean J; Kharbanda, Kusum K

2016-10-14

To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.

Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury

PubMed Central

Osna, Natalia A; Feng, Dan; Ganesan, Murali; Maillacheruvu, Priya F; Orlicky, David J; French, Samuel W; Tuma, Dean J; Kharbanda, Kusum K

2016-01-01

AIM To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. METHODS Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. CONCLUSION To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage. PMID:27784962

Glutamine prevents gastric oxidative stress in an animal model of portal hypertension gastropathy.

PubMed

Marques, Camila; Mauriz, José L; Simonetto, Douglas; Marroni, Claudio A; Tuñon, María J; González-Gallego, Javier; Marrón, Norma P

2011-01-01

Portal hypertension (PHI) is a clinical syndrome characterized by increases of the blood flow and/or of the vascular resistance in the portal system. A direct consequence of PHI can appearance different lesions on the gastric mucosa and submucosa, cumulatively termed portal hypertensive gastropathy (PHG). To investigate the effects of glutamine on oxidative stress in an experimental model of PHG induced by partial portal vein ligation (PPVL). Portal pressure, transaminase and alkaline phosphatase activity were quantified. Gastric tissue damage was assessed by histological analysis. Oxidative stress was measured by quantification of cytosolic concentration of thiobarbituric acid reactive substances (TBARS), hydroperoxide-initiated chemiluminescence (QL), and nitric oxide (NO) production. Moreover, activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were analyzed. Transaminase and alkaline phosphatase activities were not significantly modified by PPVL, indicating absence of liver injury. Histological analysis of gastric sections showed a lost of normal architecture, with edema and vasodilatation. TBARS, QL, and NO production were significantly increased in PPVL animals. A reduction of SOD activity was found. Glutamine administration markedly alleviated histological abnormalities and oxidative stress, normalized SOD activity, and blocked NO overproduction. Our results confirm that the use of molecules with antioxidant capacity can provide protection of the gastric tissue in portal hypertension. Glutamine treatment can be useful to reduce the oxidative damage induced by PHI on gastric tissue.

Betanin attenuates carbon tetrachloride (CCl4)-induced liver injury in common carp (Cyprinus carpio L.).

PubMed

Han, Junyan; Gao, Cheng; Yang, Shaobin; Wang, Jun; Tan, Dehong

2014-06-01

This study investigates the protective effect of betanin against liver injury induced by carbon tetrachloride (CCl4) in common carp (Cyprinus carpio L.). The fish were treated with 1, 2, and 4 % betanin in fodder throughout the experiment. After 20 days of treatment, the fish were intraperitoneally injected with 20 % (v/v in peanut oil) CCl4 at a volume of 0.5 mL/kg body weight. The fish were killed 3 days after CCl4 intoxication, and then, histological and biochemical assays were performed. Results showed that CCl4-induced liver CYP2E1 activity, oxidative stress, and injury, as indicated by the depleted glycogen storage, increased serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) activities and liver histological damage. Compared with the CCl4 control group, the betanin-treated groups exhibited reduced CYP2E1 activity, decreased malondialdehyde level, increased liver antioxidative capacity (increased glutathione level and superoxide dismutase and catalase activities), increased liver glycogen storage, and reduced serum AST/ALT activities, with significant differences in the 2 and 4 % groups (p < 0.05). Histological assay further confirmed the protective effect of betanin. In conclusion, betanin attenuates CCl4-induced liver damage in common carp. Moreover, the inhibition of CYP2E1 activity and oxidative stress may have significant roles in the protective effect of betanin.

Histopathological study of perilesional skin in patients diagnosed with nonmelanoma skin cancer.

PubMed

Apalla, Z; Calzavara-Pinton, P; Lallas, A; Argenziano, G; Kyrgidis, A; Crotti, S; Facchetti, F; Monari, P; Gualdi, G

2016-01-01

Epidemiological and clinical data suggest that actinic damage to the skin is an important predictor of skin carcinogenesis. To investigate the association of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with sun-damage alterations seen by histopathology. In the current prospective study, perilesional skin of SCC or BCC lesions was evaluated for presence of alterations associated with chronic photodamage. Presence of scarring, perineural/perivascular invasion, haemorrhage/haemorrhagic crust, ulceration/erosion and margin involvement were also assessed. Of 6038 included lesions, 4523 (74.9%) were BCCs and 1515 (25.1%) were SCCs. Presence of actinic damage was five times more frequent in SCC than in BCC (OR = 5.29, 95% CI 4.44-6.00, P < 0.001), and diagnosis of SCC was twice as common in photo-exposed than nonphoto-exposed body sites (OR = 2.34, 95% CI 2.03-2.70, P < 0.001). There were twofold higher odds for actinic damage in SCC compared with Bowen disease (OR = 2.015, 95% CI 1.55-2.61, P < 0.001). Assessing the different BCC histological subtypes, we found that nodular BCC had at least twofold higher odds (OR = 2.63, 95% CI 2.09-3.32), infiltrative BCC had 48% higher odds (OR = 1.487, 95% CI 1.18-1.87) and basosquamous BCC had fourfold higher odds (OR = 4.10, 95% CI 3.01-5.57) of having actinic damage compared with superficial BCC. Histological verification of ultraviolet-associated alterations in the perilesional skin in patients with NMSC in our study confirms the aetiopathogenic link between sun exposure and epithelial carcinogenesis on a histopathological basis. This correlation was stronger for SCCs than for BCCs. © 2015 British Association of Dermatologists.

Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect.

PubMed

Marotta, F; Barreto, R; Wu, C C; Naito, Y; Gelosa, F; Lorenzetti, A; Yoshioka, M; Fesce, E

2005-01-01

The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.

Laser solder welding of articular cartilage: tensile strength and chondrocyte viability.

PubMed

Züger, B J; Ott, B; Mainil-Varlet, P; Schaffner, T; Clémence, J F; Weber, H P; Frenz, M

2001-01-01

The surgical treatment of full-thickness cartilage defects in the knee joint remains a therapeutic challenge. Recently, new techniques for articular cartilage transplantation, such as mosaicplasty, have become available for cartilage repair. The long-term success of these techniques, however, depends not only on the chondrocyte viability but also on a lateral integration of the implant. The goal of this study was to evaluate the feasibility of cartilage welding by using albumin solder that was dye-enhanced to allow coagulation with 808-nm laser diode irradiation. Conventional histology of light microscopy was compared with a viability staining to precisely determine the extent of thermal damage after laser welding. Indocyanine green (ICG) enhanced albumin solder (25% albumin, 0.5% HA, 0.1% ICG) was used for articular cartilage welding. For coagulation, the solder was irradiated through the cartilage implant by 808-nm laser light and the tensile strength of the weld was measured. Viability staining revealed a thermal damage of typically 500 m in depth at an irradiance of approximately 10 W/cm(2) for 8 seconds, whereas conventional histologies showed only half of the extent found by the viability test. Heat-bath investigations revealed a threshold temperature of minimum 54 degrees C for thermal damage of chondrocytes. Efficient cartilage bonding was obtained by using bovine albumin solder as adhesive. Maximum tensile strength of more than 10 N/cm(2) was achieved. Viability tests revealed that the thermal damage is much greater (up to twice) than expected after light microscopic characterization. This study shows the feasibility to strongly laser weld cartilage on cartilage by use of a dye-enhanced albumin solder. Possibilities to reduce the range of damage are suggested. Copyright 2001 Wiley-Liss, Inc.

A Short-Term Biological Indicator for Long-Term Kidney Damage after Radionuclide Therapy in Mice

PubMed Central

Pellegrini, Giovanni; Siwowska, Klaudia; Haller, Stephanie; Antoine, Daniel J.; Schibli, Roger; Kipar, Anja; Müller, Cristina

2017-01-01

Folate receptor (FR)-targeted radionuclide therapy using folate radioconjugates is of interest due to the expression of the FR in a variety of tumor types. The high renal accumulation of radiofolates presents, however, a risk of radionephropathy. A potential option to address this challenge would be to use radioprotectants, such as amifostine. Methods for early detection of kidney damage that—in this case—cannot be predicted based on dose estimations, would facilitate the development of novel therapies. The aim of this study was, therefore, to assess potentially changing levels of plasma and urine biomarkers and to determine DNA damage at an early stage after radiofolate application. The identification of an early indicator for renal damage in mice would be useful since histological changes become apparent only several months after treatment. Mice were injected with different quantities of 177Lu-folate (10 MBq, 20 MBq and 30 MBq), resulting in mean absorbed kidney doses of ~23 Gy, ~46 Gy and ~69 Gy, respectively, followed by euthanasia two weeks (>85% of the mean renal radiation dose absorbed) or three months later. Whereas all investigated biomarkers remained unchanged, the number of γ-H2AX-positive nuclei in the renal cortex showed an evident dose-dependent increase as compared to control values two weeks after treatment. Comparison with the extent of kidney injury determined by histological changes five to eight months after administration of the same 177Lu-folate activities suggested that the quantitative assessment of double-strand breaks can be used as a biological indicator for long-term radiation effects in the kidneys. This method may, thus, enable faster assessment of radiopharmaceuticals and protective measures by preventing logistically challenging long-term investigations to detect kidney damage. PMID:28635637

Detection of vesicant-induced upper airway mucosa damage in the hamster cheek pouch model using optical coherence tomography.

PubMed

Hammer-Wilson, Marie J; Nguyen, Vi; Jung, Woong-Gyu; Ahn, Yehchen; Chen, Zhongping; Wilder-Smith, Petra

2010-01-01

Hamster cheek pouches were exposed to 2-chloroethyl ethyl sulfide [CEES, half-mustard gas (HMG)] at a concentration of 0.4, 2.0, or 5.0 mg/ml for 1 or 5 min. Twenty-four hours post-HMG exposure, tissue damage was assessed by both stereomicrography and optical coherence tomography (OCT). Damage that was not visible on gross visual examination was apparent in the OCT images. Tissue changes were found to be dependent on both HMG concentration and exposure time. The submucosal and muscle layers of the cheek pouch tissue showed the greatest amount of structural alteration. Routine light microscope histology was performed to confirm the OCT observations.

Finite element model of thermal processes in retinal photocoagulation

NASA Astrophysics Data System (ADS)

Sramek, Christopher; Paulus, Yannis M.; Nomoto, Hiroyuki; Huie, Phil; Palanker, Daniel

2009-02-01

Short duration (< 20 ms) pulses are desirable in patterned scanning laser photocoagulation to confine thermal damage to the photoreceptor layer, decrease overall treatment time and reduce pain. However, short exposures have a smaller therapeutic window (defined as the ratio of rupture threshold power to that of light coagulation). We have constructed a finite-element computational model of retinal photocoagulation to predict spatial damage and improve the therapeutic window. Model parameters were inferred from experimentally measured absorption characteristics of ocular tissues, as well as the thresholds of vaporization, coagulation, and retinal pigment epithelial (RPE) damage. Calculated lesion diameters showed good agreement with histological measurements over a wide range of pulse durations and powers.

In Vivo Wear Performance of Cobalt-Chromium Versus Oxidized Zirconium Femoral Total Knee Replacements.

PubMed

Gascoyne, Trevor C; Teeter, Matthew G; Guenther, Leah E; Burnell, Colin D; Bohm, Eric R; Naudie, Douglas R

2016-01-01

This study examines the damage and wear on the polyethylene (PE) inserts from 52 retrieved Genesis II total knee replacements to identify differences in tribological performance between matched pairs of cobalt-chromium (CoCr) and oxidized zirconium (OxZr) femoral components. Observer damage scoring and microcomputed tomography were used to quantify PE damage and wear, respectively. No significant differences were found between CoCr and OxZr groups in terms of PE insert damage, surface penetration, or wear. No severe damage such as cracking or delamination was noted on any of the 52 PE inserts. Observer damage scoring did not correlate with penetrative or volumetric PE wear. The more costly OxZr femoral component does not demonstrate clear tribological benefit over the standard CoCr component in the short term with this total knee replacement design. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of anosognosia in persons with frontal lobe damage: clinical utility of the Mayo-Portland Adaptability Inventory (MPAI).

PubMed

Murrey, G J; Hale, F M; Williams, J D

2005-08-10

To determine if the Mayo-Portland Adaptability Inventory (MPAI) demonstrates clinical utility in differentiating between persons with severe TBI and frontal lobe damage/anosognosia and persons with mild TBI and no frontal lobe damage. Forty-three persons with TBI and documented frontal lobe damage (mean age = 34; mean time since injury = 5.2 years) and 69 persons with mild TBI and no frontal lobe damage (mean age = 34.3; mean time since injury = 4.8 4.8 years). MPAI. Total inventory and select sub-category difference scores were significantly greater in the frontal lobe group than in the non-frontal lobe group. However, as expected, there was no significant difference between the two groups on the mobility sub-category difference scores. The MPAI appears to be potentially clinically useful in assessing for frontal lobe damage and associated anosognosia in patients with TBI.

Low protein and high-energy diet: a possible natural cause of fatty liver hemorrhagic syndrome in caged White Leghorn laying hens.

PubMed

Rozenboim, I; Mahato, J; Cohen, N A; Tirosh, O

2016-03-01

Fatty liver hemorrhagic syndrome (FLHS) is a metabolic condition of chicken and other birds caused by diverse nutritional, hormonal, environmental, and metabolic factors. Here we studied the effect of different diet composition on the induction of FLHS in single comb White Leghorn (WL) Hy-line laying hens. Seventy six (76) young WL (26 wks old) laying hens and 69 old hens (84 wks old) of the same breed were each divided into 4 treatment groups and provided 4 different diet treatments. The diet treatments included: control (C), 17.5% CP, 3.5% fat (F); normal protein, high fat (HF), 17.5% CP, 7% F; low protein, normal fat (LP), 13% CP, 3.5% F; and low protein, high fat (LPHF), 13% CP, 6.5% F. The diets containing high fat also had a higher ME of 3,000 kcal/kg of feed while the other 2 diets with normal fat had a regular lower amount of ME (2750 kcal/kg). Hen-day egg production (HDEP), ADFI, BW, egg weight, plasma enzymes indicating liver damage (alkaline phosphatase [ALP], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT]), liver and abdominal fat weight, liver color score (LCS), liver hemorrhagic score (LHS), liver fat content (LFC), liver histological examination, lipid peroxidation product in the liver, and genes indicating liver inflammation were evaluated. HDEP, ADFI, BW, and egg weight were significantly decreased in the LPHF diet group, while egg weight was also decreased in the LP diet group. In the young hens (LPHF group), ALP was found significantly higher at 30 d of diet treatment and was numerically higher throughout the experiment, while AST was significantly higher at 105 d of treatment. LCS, LHS, and LFC were significantly higher in young hens on the LPHF diet treatment. A liver histological examination shows more lipid vacuolization in the LPHF treatment diet. HF or LP alone had no significant effect on LFC, LHS, or LCS. We suggest that LP in the diet with higher ME from fat can be a possible natural cause for predisposing laying hens to FLHS. © 2016 Poultry Science Association Inc.

Primary central chondrosarcoma of long bone, limb girdle and trunk: Analysis of 174 cases by numerical scoring on histology.

PubMed

Konishi, Eiichi; Nakashima, Yasuaki; Mano, Masayuki; Tomita, Yasuhiko; Nagasaki, Ikumitsu; Kubo, Toshikazu; Araki, Nobuhito; Haga, Hironori; Toguchida, Junya; Ueda, Takafumi; Sakuma, Toshiko; Imahori, Masaya; Morii, Eiichi; Yoshikawa, Hideki; Tsukamoto, Yoshitane; Futani, Hiroyuki; Wakasa, Kenichi; Hoshi, Manabu; Hamada, Shinshichi; Takeshita, Hideyuki; Inoue, Takeshi; Aono, Masanari; Kawabata, Kenji; Murata, Hiroaki; Katsura, Kanade; Urata, Yoji; Ueda, Hideki; Yanagisawa, Akio

2015-09-01

The aims of this study were: (i) to elucidate clinicopathological characteristics of pcCHS of long bones (L), limb girdles (LG) and trunk (T) in Japan; (ii) to investigate predictive pathological findings for outcome of pcCHS of L, LG and T, objectively; and (iii) to elucidate a discrepancy of grade between biopsy and resected specimens. Clinicopathological profiles of 174 pcCHS (79 male, 95 female), of L, LG, and T were retrieved. For each case, a numerical score was given to 18 pathological findings. The average age was 50.5 years (15-80 years). Frequently involved sites were femur, humerus, pelvis and rib. The 5-year and 10-year disease-specific survival (DSS) rates [follow-up: 1-258 months (average 65.5)] were 87.0% and 80.4%, respectively. By Cox hazards analysis on pathological findings, age, sex and location, histologically higher grade and older age were unfavorable predictors, and calcification was a favorable predictor in DSS. The histological grade of resected specimen was higher than that of biopsy in 37.7% (26/69 cases). In conclusion, higher histological grade and older age were predictors for poor, but calcification was for good prognosis. Because there was a discrepancy in grade between biopsy and resected specimens, comprehensive evaluation is necessary before definitive operation for pcCHS. © 2015 The Authors. Pathology International published by Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats.

PubMed

Diefenbeck, M; Schrader, C; Gras, F; Mückley, T; Schmidt, J; Zankovych, S; Bossert, J; Jandt, K D; Völpel, A; Sigusch, B W; Schubert, H; Bischoff, S; Pfister, W; Edel, B; Faucon, M; Finger, U

2016-09-01

Implant related infection is one of the most feared and devastating complication associated with the use of orthopaedic implant devices. Development of anti-infective surfaces is the main strategy to prevent implant contamination, biofilm formation and implant related osteomyelitis. A second concern in orthopaedics is insufficient osseointegration of uncemented implant devices. Recently, we reported on a macroporous titanium-oxide surface (bioactive TiOB) which increases osseointegration and implant fixation. To combine enhanced osseointegration and antibacterial function, the TiOB surfaces were, in addition, modified with a gentamicin coating. A rat osteomyelitis model with bilateral placement of titanium alloy implants was employed to analyse the prophylactic effect of gentamicin-sodiumdodecylsulfate (SDS) and gentamicin-tannic acid coatings in vivo. 20 rats were randomly assigned to four groups: (A) titanium alloy; PBS inoculum (negative control), (B) titanium alloy, Staphylococcus aureus inoculum (positive control), (C) bioactive TiOB with gentamicin-SDS and (D) bioactive TiOB plus gentamicin-tannic acid coating. Contamination of implants, bacterial load of bone powder and radiographic as well as histological signs of implant-related osteomyelitis were evaluated after four weeks. Gentamicin-SDS coating prevented implant contamination in 10 of 10 tibiae and gentamicin-tannic acid coating in 9 of 10 tibiae (infection prophylaxis rate 100% and 90% of cases, respectively). In Group (D) one implant showed colonisation of bacteria (swab of entry point and roll-out test positive for S. aureus). The interobserver reliability showed no difference in the histologic and radiographic osteomyelitis scores. In both gentamicin coated groups, a significant reduction of the histological osteomyelitis score (geometric mean values: C = 0.111 ± 0.023; D = 0.056 ± 0.006) compared to the positive control group (B: 0.244 ± 0.015; p < 0.05) was observed. The radiographic osteomyelitis scores confirmed these histological findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Histologic Grading of Prostatic Adenocarcinoma Can Be Further Optimized: Analysis of the Relative Prognostic Strength of Individual Architectural Patterns in 1275 Patients From the Canary Retrospective Cohort.

PubMed

McKenney, Jesse K; Wei, Wei; Hawley, Sarah; Auman, Heidi; Newcomb, Lisa F; Boyer, Hilary D; Fazli, Ladan; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Tretiakova, Maria S; Vakar-Lopez, Funda; Carroll, Peter R; Cooperberg, Matthew R; Gleave, Martin E; Lance, Raymond S; Lin, Dan W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Feng, Ziding; Brooks, James D

2016-11-01

Histologic grading remains the gold standard for prognosis in prostate cancer, and assessment of Gleason score plays a critical role in active surveillance management. We sought to optimize the prognostic stratification of grading and developed a method of recording and studying individual architectural patterns by light microscopic evaluation that is independent of standard Gleason grade. Some of the evaluated patterns are not assessed by current Gleason grading (eg, reactive stromal response). Individual histologic patterns were correlated with recurrence-free survival in a retrospective postradical prostatectomy cohort of 1275 patients represented by the highest-grade foci of carcinoma in tissue microarrays. In univariable analysis, fibromucinous rupture with varied epithelial complexity had a significantly lower relative risk of recurrence-free survival in cases graded as 3+4=7. Cases having focal "poorly formed glands," which could be designated as pattern 3+4=7, had lower risk than cribriform patterns with either small cribriform glands or expansile cribriform growth. In separate multivariable Cox proportional hazard analyses of both Gleason score 3+3=6 and 3+4=7 carcinomas, reactive stromal patterns were associated with worse recurrence-free survival. Decision tree models demonstrate potential regrouping of architectural patterns into categories with similar risk. In summary, we argue that Gleason score assignment by current consensus guidelines are not entirely optimized for clinical use, including active surveillance. Our data suggest that focal poorly formed gland and cribriform patterns, currently classified as Gleason pattern 4, should be in separate prognostic groups, as the latter is associated with worse outcome. Patterns with extravasated mucin are likely overgraded in a subset of cases with more complex epithelial bridges, whereas stromogenic cancers have a worse outcome than conveyed by Gleason grade alone. These findings serve as a foundation to facilitate optimization of histologic grading and strongly support incorporating reactive stroma into routine assessment.

Histological features of pseudotumor-like tissues from metal-on-metal hips.

PubMed

Campbell, Pat; Ebramzadeh, Edward; Nelson, Scott; Takamura, Karren; De Smet, Koen; Amstutz, Harlan C

2010-09-01

Pseudotumor-like periprosthetic tissue reactions around metal-on-metal (M-M) hip replacements can cause pain and lead to revision surgery. The cause of these reactions is not well understood but could be due to excessive wear, or metal hypersensitivity or an as-yet unknown cause. The tissue features may help distinguish reactions to high wear from those with suspected metal hypersensitivity. We therefore examined the synovial lining integrity, inflammatory cell infiltrates, tissue organization, necrosis and metal wear particles of pseudotumor-like tissues from M-M hips revised for suspected high wear related and suspected metal hypersensitivity causes. Tissue samples from 32 revised hip replacements with pseudotumor-like reactions were studied. A 10-point histological score was used to rank the degree of aseptic lymphocytic vasculitis-associated lesions (ALVAL) by examination of synovial lining integrity, inflammatory cell infiltrates, and tissue organization. Lymphocytes, macrophages, plasma cells, giant cells, necrosis and metal wear particles were semiquantitatively rated. Implant wear was measured with a coordinate measuring machine. The cases were divided into those suspected of having high wear and those suspected of having metal hypersensitivity based on clinical, radiographic and retrieval findings. The Mann-Whitney test was used to compare the histological features in these two groups. The tissues from patients revised for suspected high wear had a lower ALVAL score, fewer lymphocytes, but more macrophages and metal particles than those tissues from hips revised for pain and suspected metal hypersensitivity. The highest ALVAL scores occurred in patients who were revised for pain and suspected metal hypersensitivity. Component wear was lower in that group. Pseudotumor-like reactions can be caused by high wear, but may also occur around implants with low wear, likely because of a metal hypersensitivity reaction. Histologic features including synovial integrity, inflammatory cell infiltrates, tissue organization, and metal particles may help differentiate these causes. Painful hips with periprosthetic masses may be caused by high wear, but if this can be ruled out, metal hypersensitivity should be considered.

The relation of microdamage to fracture and material property degradation in human cortical bone tissue

NASA Astrophysics Data System (ADS)

Akkus, Ozan

This dissertation investigates the relation of microdamage to fracture and material property degradation of human cortical bone tissue. Fracture resistance and fatigue crack growth of microcracks were examined experimentally and material property degradation was examined through theoretical modeling. To investigate the contribution of microdamage to static fracture resistance, fracture toughness tests were conducted in the transverse and longitudinal directions to the osteonal orientation of normal bone tissue. Damage accumulation was monitored by acoustic emission during testing and was spatially observed by histological observation following testing. The results suggested that the propagation of the main crack involved weakening of the tissue by diffuse damage at the fracture plane and by formation of linear microcracks away from the fracture plane for the transverse specimens. For the longitudinal specimens, growth of the main crack occurred in the form of separations at lamellar interfaces. Acoustic emission results supported the histological observations. To investigate the contribution of ultrastructure to static fracture resistance, fracture toughness tests were conducted after altering the collagen phase of the bone tissue by gamma radiation. A significant decrease in the fracture toughness, Work-to-Fracture and the amount damage was observed due to irradiation in both crack growth directions. For cortical bone irradiated at 27.5kGy, fracture toughness is reduced due to the inhibition of damage formation at and near the crack tip. Microcrack fatigue crack growth and arrest were investigated through observations of surface cracks during cyclic loading. At the applied cyclic stresses, the microcracks propagated and arrested in less than 10,000 cycles. In addition, the microcracks were observed not to grow beyond a length of 150mum and a DeltaK of 0.5MNm-3/2, supporting a microstructural barrier concept. Finally, the contribution of linear microcracks to material property degradation was examined by developing a theoretical micromechanical damage model. The model was compared to experimentally induced damage in bone tissue. The percent contribution of linear microcracks to the total degradation was predicted to be less than 5%, indicating that diffuse damage or an unidentified form of damage is primarily responsible for material property degradation in human cortical bone tissue.

In field damage of high and low cyanogenic cassava due to a generalist insect herbivore Cyrtomenus bergi (Hemiptera: Cydnidae).

PubMed

Riis, Lisbeth; Bellotti, Anthony Charles; Castaño, Oscar

2003-12-01

The hypothesis that cyanogenic potential in cassava roots deters polyphagous insects in the field is relevant to current efforts to reduce or eliminate the cyanogenic potential in cassava. To test this hypothesis, experiments were conducted in the field under natural selection pressure of the polyphagous root feeder Cyrtomenus bergi Froeschner (Hemiptera: Cydnidae). A number of cassava varieties (33) as well as 13 cassava siblings and their parental clone, each representing a determined level of cyanogenic potential (CNP), were scored for damage caused by C. bergi and related to CNP and nonglycosidic cyanogens, measured as hydrogen cyanide. Additionally, 161 low-CNP varieties (< 50 ppm hydrogen cyanide, fresh weight) from the cassava germplasm core collection at Centro Internacional de Agricultura Tropical (CIAT) were screened for resistance/tolerance to C. bergi. Low root damage scores were registered at all levels of CNP. Nevertheless, CNP and yield (or root size) partly explained the damage in cassava siblings (r2 = 0.82) and different cassava varieties (r2 = 0.42), but only when mean values of damage scores were used. This relation was only significant in one of two crop cycles. A logistic model describes the underlying negative relation between CNP and damage. An exponential model describes the underlying negative relation between root size and damage. Damage, caused by C. bergi feeding, released nonglycosidic cyanogens, and an exponential model fits the underlying positive relation. Fifteen low-CNP clones were selected for potential resistance/tolerance against C. bergi.

Standardization of an in vitro Model for Evaluating the Bioavailability of Topically Applied Compounds on Damaged Skin: Application to Sunscreen Analysis.

PubMed

Jacques-Jamin, Carine; Jeanjean-Miquel, Corinne; Domergue, Anaïs; Bessou-Touya, Sandrine; Duplan, Hélène

2017-01-01

Information is lacking on the dermal penetration of topically applied formulations on in vitro skin models, under conditions where the stratum corneum (SC) is damaged. Therefore, we have developed a standardized in vitro barrier-disrupted skin model using tape stripping. Different tape stripping conditions were evaluated using histology, transepidermal water loss, infrared densitometry, and caffeine absorption. The effects of tape stripping were comparable using pig and human skin. Optimized conditions were used to test the effect of SC damage and UV irradiation on the absorption of an UV filter combination present in a sunscreen. The bioavailability of the filters was extremely low regardless of the extent of skin damage, suggesting bioavailability would not be increased if the consumer applied the sunscreen to sun-damaged skin. This standardized in vitro methodology using pig or human skin for damaged skin will add valuable information for the safety assessment of topically applied products. © 2017 S. Karger AG, Basel.

Spatial Statistics for Segmenting Histological Structures in H&E Stained Tissue Images.

PubMed

Nguyen, Luong; Tosun, Akif Burak; Fine, Jeffrey L; Lee, Adrian V; Taylor, D Lansing; Chennubhotla, S Chakra

2017-07-01

Segmenting a broad class of histological structures in transmitted light and/or fluorescence-based images is a prerequisite for determining the pathological basis of cancer, elucidating spatial interactions between histological structures in tumor microenvironments (e.g., tumor infiltrating lymphocytes), facilitating precision medicine studies with deep molecular profiling, and providing an exploratory tool for pathologists. This paper focuses on segmenting histological structures in hematoxylin- and eosin-stained images of breast tissues, e.g., invasive carcinoma, carcinoma in situ, atypical and normal ducts, adipose tissue, and lymphocytes. We propose two graph-theoretic segmentation methods based on local spatial color and nuclei neighborhood statistics. For benchmarking, we curated a data set of 232 high-power field breast tissue images together with expertly annotated ground truth. To accurately model the preference for histological structures (ducts, vessels, tumor nets, adipose, etc.) over the remaining connective tissue and non-tissue areas in ground truth annotations, we propose a new region-based score for evaluating segmentation algorithms. We demonstrate the improvement of our proposed methods over the state-of-the-art algorithms in both region- and boundary-based performance measures.

Removal of Chronic Intravascular Blood Clots using Liquid Plasma

NASA Astrophysics Data System (ADS)

Jung, Jae-Chul; Choi, Myeong; Koo, Il; Yu, Zengqi; Collins, George

2011-10-01

An electrical embolectomy device for removing chronic intravascular blood clots using liquid plasma under saline environment was demonstrated. We employed a proxy experimental blood clot model of deep vein thrombosis (DVT) and actual equine blood clot. Thermal damage to contiguous tissue and the collagen denaturing via the plasma irradiation were investigated by histological analysis using birefringence of the tissue and verified by FT-IR spectroscopic study, respectively, which showed the high removal rate up to 2 mm per minute at room temperature and small thermal damage less than 200 μm.

The efficacy of intra-articular hyaluronan injection after the microfracture technique for the treatment of articular cartilage lesions.

PubMed

Strauss, Eric; Schachter, Aaron; Frenkel, Sally; Rosen, Jeffrey

2009-04-01

Although the exact mechanism of action has yet to be elucidated, recent animal studies have demonstrated chondroprotective and anti-inflammatory properties of hyaluronic acid viscosupplementation. Intra-articular hyaluronic acid after microfracture improves the quality of the repair leading to a more hyaline-like repair tissue with better defect fill and adjacent area integration. Controlled laboratory study. Full-thickness cartilage defects were created in the weightbearing area of the medial femoral condyle in 36 female New Zealand White rabbits. The defects were then treated with surgical microfracture. Eighteen rabbits formed the 3-month cohort and the other 18 formed the 6-month cohort. Within each cohort, 6 rabbits were randomly assigned to receive 3 weekly injections of hyaluronic acid (group A), 5 weekly injections (group B), or control injections of normal saline (group C). At 3 and 6 months postmicrofracture, the animals were sacrificed and the operative knee harvested. Repair tissue was assessed blinded- both grossly, using a modified component of the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment scoring scale, and histologically, using the modified O'Driscoll histological cartilage scoring system. Comparisons were made with respect to gross and histologic findings between treatment groups at each time point. Effects of each treatment type were also evaluated longitudinally by comparing the 3-month results with the 6-month results. Statistical analysis was performed using unpaired Student t tests with significance defined as P < .05. At 3 months, gross and histologic evaluation of the repair tissue demonstrated that the 3-injection group had significantly better fill of the defects and more normal appearing, hyaline-like tissue than controls (a mean ICRS score of 1.92 vs 1.26; P < .05 and a mean modified O'Driscoll score of 10.3 vs 7.6; P < .02). Specimens treated with 5 weekly injections were not significantly improved compared with controls. At 6 months, the mean gross appearance and histologic scores between the 3 specimen cohorts were not significantly different. However, examination of the entire operative knee demonstrated a significantly greater extent of degenerative changes (synovial inflammation and osteophyte formation) in the control group than in both hyaluronic acid treatment groups (P < .05). Supplementing the microfracture technique with 3 weekly injections of intra-articular hyaluronic acid had a positive effect on the repair tissue that formed within the chondral defect at the early follow-up time point. This improvement was not found for the 3-injection group at 6 months or for the 5-injection group at either time point. Additionally, hyaluronic acid supplementation had a possible chondroprotective and anti-inflammatory effect, limiting the development of degenerative changes within the knee joint. The adjunctive use of hyaluronic acid appears to hold promise in the treatment of chondral injuries and warrants further investigation.

Histologic evaluation of laser lipolysis comparing continuous wave vs pulsed lasers in an in vivo pig model.

PubMed

Levi, Jessica R; Veerappan, Anna; Chen, Bo; Mirkov, Mirko; Sierra, Ray; Spiegel, Jeffrey H

2011-01-01

To evaluate acute and delayed laser effects of subdermal lipolysis and collagen deposition using an in vivo pig model and to compare histologic findings in fatty tissue after continuous wave diode (CW) vs pulsed laser treatment. Three CW lasers (980, 1370, and 1470 nm) and 3 pulsed lasers (1064, 1320, and 1440 nm) were used to treat 4 Göttingen minipigs. Following administration of Klein tumescent solution, a laser cannula was inserted at the top of a 10 × 2.5-cm rectangle and was passed subdermally to create separate laser "tunnels." Temperatures at the surface and at intervals of 4-mm to 20-mm depths were recorded immediately after exposure and were correlated with skin injury. Full-thickness cutaneous biopsy specimens were obtained at 1 day, 1 week, and 1 month after exposure and were stained with hematoxylin-eosin and trichrome stain. Qualitative and semiquantitative histopathologic evaluations were performed with attention to vascular damage, lipolysis, and collagen deposition. Skin surface damage occurred at temperatures exceeding 46°C. Histologic examination at 1 day after exposure showed hemorrhage, fibrous collagen fiber coagulation, and adipocyte damage. Adipocytes surrounded by histiocytes, a marker of lipolysis, were present at 1 week and 1 month after exposure. Collagen deposition in subdermal fatty tissue and in reticular dermis of some specimens was noted at 1 week and had increased at 1 month. Tissue treated with CW laser at 1470 nm demonstrated greater hemorrhage and more histiocytes at damage sites than tissue treated with pulsed laser at 1440 nm. There was a trend toward more collagen deposition with pulsed lasers than with CW lasers, but this was not statistically significant. Histopathologic comparison between results of CW laser at 980 nm vs pulsed laser at 1064 nm showed the same trend. Hemorrhage differences may result from pulse duration variations. A theoretical calculation estimating temperature rise in vessels supported this hypothesis. Pulsed lasers with higher peak powers provided better hemostatic effects than CW lasers. The degree of lipolysis depended on wavelength, laser power, and energy density. Subdermal laser irradiation can stimulate collagen deposition in subdermal tissue and reticular dermis.

Blood-Brain Barrier: Real-time Feedback-controlled Focused Ultrasound Disruption by Using an Acoustic Emissions–based Controller

PubMed Central

Hynynen, Kullervo

2012-01-01

Purpose: To determine if focused ultrasound disruption of the blood-brain barrier (BBB) can be safely controlled by using real-time modulation of treatment pressures on the basis of acoustic emissions from the exposed microbubbles. Materials and Methods: All experiments were performed with the approval of the institutional animal care committee. Transcranial focused ultrasound (551.5 kHz, 10-msec bursts, 2-Hz pulse repetition frequency, 2 minute sonication) in conjunction with circulating microbubbles was applied in 86 locations in 27 rats to disrupt the BBB. Acoustic emissions captured during each burst by using a wideband polyvinylidene fluoride hydrophone were analyzed for spectral content and used to adjust treatment pressures. Pressures were increased incrementally after each burst until ultraharmonic emissions were detected, at which point the pressure was reduced to a percentage of the pressure required to induce the ultraharmonics and was maintained for the remainder of the sonication. Disruption was evaluated at contrast material–enhanced T1-weighted magnetic resonance (MR) imaging. Mean enhancement was calculated by averaging the signal intensity at the focus over a 3 × 3-pixel region of interest and comparing it with that in nonsonicated tissue. Histologic analysis was performed to determine the extent of damage to the tissue. Statistical analysis was performed by using Student t tests. Results: For sonications resulting in BBB disruption, the mean peak pressure was 0.28 MPa ± 0.05 (standard deviation) (range, 0.18–0.40 MPa). By using the control algorithm, a linear relationship was found between the scaling level and the mean enhancement on T1-weighted MR images after contrast agent injection. At a 50% scaling level, mean enhancement of 19.6% ± 1.7 (standard error of the mean) was achieved without inducing damage. At higher scaling levels, histologic analysis revealed gross tissue damage, while at a 50% scaling level, no damage was observed at high-field-strength MR imaging or histologic examination 8 days after treatment. Conclusion: This study demonstrates that acoustic emissions can be used to actively control focused ultrasound exposures for the safe induction of BBB disruption. © RSNA, 2012 PMID:22332065

The Cutaneous Assessment Tool (CAT): Development and Reliability in Juvenile Idiopathic Inflammatory Myopathy

PubMed Central

Huber, Adam M.; Dugan, Elizabeth M.; Lachenbruch, Peter A.; Feldman, Brian M.; Perez, Maria D.; Zemel, Lawrence S.; Lindsley, Carol B.; Rennebohm, Robert M.; Wallace, Carol A.; Passo, Murray H.; Reed, Ann M.; Bowyer, Suzanne L.; Ballinger, Susan H.; Miller, Frederick W.; Rider, Lisa G.

2007-01-01

Objectives Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater reliability of the CAT, and the frequency of lesions endorsed in a large population of juvenile IIM patients. Methods The CAT includes 10 activity, 4 damage and 7 combined lesions. Thirty-two photographic slides depicting IIM skin lesions were assessed by 11 raters. One hundred and twenty three children were assessed by 11 pediatric rheumatologists at ten centers. Inter-rater reliability was assessed using simple agreements and intra-class correlation coefficients (ICC). Results Simple agreements in recognizing lesions as present or absent were generally high (0.5 – 1.0). ICC's for CAT lesions were moderate (0.4 – 0.75) in both slides and real patients. ICC's for the CAT activity and damage scores were 0.71 and 0.81, respectively. CAT activity scores ranged from 0 – 44 (median 7, potential range 0 – 96) and CAT damage scores ranged from 0 – 13 (median 1, potential range 0 – 22). The most common cutaneous lesions endorsed were periungual capillary loop changes (63%), Gottron's papules/sign (53%), heliotrope rash (49%) and malar/facial erythema (49%). Conclusions Total CAT activity and damage scores have moderate to good reliability. Assessors generally agree on the presence of a variety of cutaneous lesions. The CAT is a promising, semi-quantitative tool to comprehensively assess skin disease activity and damage in IIM. PMID:17890275

The RIPASA score is sensitive and specific for the diagnosis of acute appendicitis in a western population.

PubMed

Malik, Muhammad Usman; Connelly, Tara M; Awan, Faisal; Pretorius, Frederik; Fiuza-Castineira, Constantino; El Faedy, Osama; Balfe, Paul

2017-04-01

The definitive diagnosis of acute appendicitis (AA) requires histopathological examination. Various clinical diagnostic scoring systems attempt to reduce negative appendectomy rates. The most commonly used in Western Europe and the USA is the Alvarado score. The Raja Isteri Pengiran Anak Saleha appendicitis (RIPASA) score achieves better sensitivity and specificity in Asian and Middle Eastern populations. We aimed to determine the diagnostic accuracy of the RIPASA score in Irish patients with AA. All patients who presented to our institution with right iliac fossa pain and clinically suspected AA between January 1 and December 31, 2015, were indentified from our hospital inpatient enquiry database and retrospectively studied. Operating theatre records and histology reports confirmed those who underwent a non-elective operative procedure and the presence or absence of AA. SPSS version 22 was used for statistical analysis. Standard deviation is provided where appropriate. Two hundred eight patients were included in the study (106/51% male, mean age 22.7 ± 9.2 years). One hundred thirty-five (64.9%) had histologically confirmed AA (mean symptom duration = 36.19 ± 15.90 h). At a score ≥7.5, the previously determined score most likely associated with AA in Eastern populations, the RIPASA scoring system demonstrated a sensitivity of 85.39%, specificity of 69.86%, positive predictive value of 84.06%, negative predictive value of 72.86% and diagnostic accuracy of 80% in our cohort. The RIPASA score is a useful tool to aid in the diagnosis of acute appendicitis in the Irish population. A score of ≥7.5 provides sensitivity and specificity exceeding that previously documented for the Alvarado score in Western populations. WHAT DOES THIS PAPER ADD TO THE LITERATURE?: This is the first study evaluating the utility of the RIPASA score in predicting acute appendicitis in a Western population. At a value of 7.5, a cut-off score suggestive of appendicitis in the Eastern population, RIPASA demonstrated a high-sensitivity, specificity, positive predictive value and diagnostic accuracy in our cohort and was more accurate than the commonly used Alvarado score.

Radiographic readings for asbestosis: misuse of science--validation of the ILO classification.

PubMed

Miller, Albert

2007-01-01

Radiographic readings for pneumoconiosis (both asbestosis and silicosis), even those using the International Labour Office (ILO) Classification, have received widespread negative coverage in the media and strong judicial rebuke. The medical literature over the past 90 years was reviewed for the relationships between radiographic severity (standardized as the ILO profusion score) and indices of exposure to silica or asbestos, tissue burden of silica particles or asbestos fibers, histologic fibrosis, various measurements of pulmonary function and mortality. Evidence from many different disciplines has demonstrated that the ILO profusion score correlates with occupational exposure, dust burden in the lung, histologic fibrosis and, more recently, with physiologic impairment and mortality. The ILO Classification has therefore been validated as a scientific tool. Its fraudulent misuse by "hired-gun" physicians, attorneys and elements of the compensation system to falsify claims of asbestosis and/or silicosis (often in the same claimant) must be condemned. (c) 2006 Wiley-Liss, Inc.

Expression and significance of Ki-67 in lung cancer.

PubMed

Folescu, Roxana; Levai, Codrina Mihaela; Grigoraş, Mirela Loredana; Arghirescu, Teodora Smaranda; Talpoş, Ioana Cristina; Gîndac, Ciprian Mihai; Zamfir, Carmen Lăcrămioara; Poroch, Vladimir; Anghel, Mirella Dorina

2018-01-01

Ki-67 parameter is a proliferation marker in malignant tumors. The increased proliferation activity and the decreased prognosis in lung cancer determined us to investigate different parameters connected to the tumor's aggression, such as cellularity, Ki-67 positivity rate, and proliferating cell nuclear antigen (PCNA). We evaluated the proliferative activity in 62 primary lung tumors by determining the cell's percentage of Ki-67 and immunoreactive PCNA (using MIB-1 and PCNA monoclonal antibodies), classifying Ki-67 and PCNA immunoreactivity into three score groups. The results obtained emphasized a linkage between Ki-67 score with the histological tumor subtype, tumor cellularity and degree of differentiation and with other proliferation immunohistochemistry (IHC) markers, such as p53 cellular tumor antigen. The tumor's cellularity, the Ki-67 positivity rate and PCNA, together with the clinical stage and the histological differentiation bring extra pieces of useful information in order to anticipate the evolution and the prognosis of lung cancer.

Novel diagnostic techniques for celiac disease.

PubMed

Kurppa, Kalle; Taavela, Juha; Saavalainen, Päivi; Kaukinen, Katri; Lindfors, Katri

2016-07-01

The diagnosis of celiac disease has long been based on the demonstration of gluten-induced small-bowel mucosal damage. However, due to the constantly increasing disease prevalence and limitations in the histology-based criteria there is a pressure towards more serology-based diagnostics. The serological tools are being improved and new non-invasive methods are being developed, but the constantly refined endoscopic and histologic techniques may still prove helpful. Moreover, growing understanding of the disease pathogenesis has led researchers to suggest completely novel approaches to celiac disease diagnostics regardless of disease activity. In this review, we will elucidate the most recent development and possible future innovations in the diagnostic techniques for celiac disease.

Monitoring of DNA breakage in embryonic stages of the African catfish Clarias gariepinus (Burchell, 1822) after exposure to lead nitrate using alkaline comet assay.

PubMed

Osman, Alaa G M; Mekkawy, Imam A; Verreth, Johan; Wuertz, Sven; Kloas, Werner; Kirschbaum, Frank

2008-12-01

Increasing lead contamination in Egyptian ecosystems and high lead concentrations in food items have raised concern for human health and stimulated studies on monitoring ecotoxicological impact of lead-caused genotoxicity. In this work, the alkaline comet assay was modified for monitoring DNA strand breakage in sensitive early life stages of the African catfish Clarias gariepinus. Following exposure to 100, 300, and 500 microg/L lead nitrate, DNA strand breakage was quantified in embryos at 30, 48, 96, 144, and 168 h post-fertilization (PFS). For quantitative analysis, four commonly used parameters (tail % DNA, %TDNA; head % DNA, %HDNA; tail length, TL; tail moment, TM) were analyzed in 96 nuclei (in triplicates) at each sampling point. The parameter %TDNA revealed highest resolution and lowest variation. A strong correlation between lead concentration, time of exposure, and DNA strand breakage was observed. Here, genotoxicity detected by comet assay preceded the manifested malformations assessed with conventional histology. Qualitative evaluation was carried out using five categories are as follows: undamaged (%TDNA < or = 10%), low damaged (10% < %TDNA < or = 25%), median damaged (25 < %TDNA < or = 50%), highly damaged (50 < %TDNA < or = 75%), and extremely damaged (%TDNA > 75%) nuclei confirming a dose and time-dependent shift towards increased frequencies of highly and extremely damaged nuclei. A protective capacity provided by a hardened chorion is a an interesting finding in this study as DNA damage in the prehatching stages 30 h-PFS and 48 h-PFS was low in all treatments (qualitative and quantitative analyses). These results clearly show that the comet assay is a sensitive tool for the detection of genotoxicity in vulnerable early life stages of the African catfish and is a method more sensitive than histological parameters for monitoring genotoxic effects. 2008 Wiley Periodicals, Inc.

Histopathology of ventilator-associated pneumonia (VAP) and its clinical implications.

PubMed

Torres, A; Fábregas, N; Arce, Y; López-Boado, M A

1999-01-01

Ventilator-associated pneumonia (VAP) is a diffuse polymicrobial and dynamic process, with heterogeneous distribution of lesions, showing different degrees of histological evolution predominating in the dependent lung zones, in which microbiology and histology can be dissociated. This might explain why blind endobronchial techniques to collect respiratory secretions have similar accuracy compared to visually guided samples, explaining the difficulties in validating any methods for its diagnosis. In the clinical setting the association of acute lung injury (ALI) and pneumonia is controversial. However, it is rare to detect diffuse alveolar damage (DAD) in absence of histological signs of pneumonia, probably evidencing that ALI favors the development of pneumonia. Histopathologically, it is difficult to distinguish initial and resolution phases of DAD from pneumonia and vice versa. On the other hand, there is a clear relationship between antimicrobial treatment and the decreased lung bacterial burden which strengthens the importance of distal airway sampling before starting antibiotic therapy.

Delayed gastric emptying does not normalize after gluten withdrawal in adult celiac disease.

PubMed

Usai-Satta, Paolo; Oppia, Francesco; Scarpa, Mariella; Giannetti, Cristiana; Cabras, Francesco

2016-08-01

Objective Delayed gastric emptying has been frequently detected in patients with untreated celiac disease. According to several studies, gluten withdrawal showed to be effective in normalizing the gastric emptying rate. The aim of this study was to evaluate the gastric emptying rate of solids in patients with celiac disease before and after a gluten-free diet. Methods Twelve adult patients with celiac disease (age range 20-57 years) and 30 healthy controls (age range 30-54 years) underwent a (13)C-octanoic acid breath test to measure gastric emptying. Half emptying time (t1/2) and lag phase (tlag) were calculated. After at least 12 months of a gluten-free diet, celiac patients underwent a new (13)C-octanoic acid breath test. A symptom score was utilized to detect dyspeptic and malabsorption symptoms in all the patients. Results The gastric motility parameters, t1/2 and tlag, were significantly longer in patients than in controls. On a gluten-free diet, surprisingly, the gastric emptying did not normalize despite an improvement of symptom score. No significant correlation between abnormal gastric emptying and specific symptom patterns, anthropometric parameters or severity of histological damage was found. Conclusions This finding supports the hypothesis that gluten-driven mucosal inflammation might determine motor abnormalities by affecting smooth muscle contractility or impairing gut hormone function. The persistence of these abnormalities on a gluten free diet suggests the presence of a persistent low-grade mucosal inflammation with a permanent perturbation of the neuro-immunomodulatory regulation.

The impact of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature terminology in the routine diagnosis of thyroid tumours.

PubMed

Jaconi, M; Manzoni, M; Pincelli, A I; Giardini, V; Scardilli, M; Smith, A; Fellegara, G; Pagni, F

2017-12-01

Due to the recent proposal of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice. A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically-treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III-IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC-like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1). In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC-like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low-risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations. © 2017 John Wiley & Sons Ltd.

Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: an experimental study in rabbits.

PubMed

Athanasiou, Vasilis T; Papachristou, Dionysios J; Panagopoulos, Andreas; Saridis, Alkis; Scopa, Chrisoula D; Megas, Panagiotis

2010-01-01

Different types of bone-graft substitutes have been developed and are on the market worldwide to eliminate the drawbacks of autogenous grafting. This experimental animal study was undertaken to evaluate the different histological properties of various bone graft substitutes utilized in this hospital. Ninety New Zealand white rabbits were divided into six groups of 15 animals. Under general anesthesia, a 4.5 mm-wide hole was drilled into both the lateral femoral condyles of each rabbit, for a total of 180 condyles for analysis. The bone defects were filled with various grafts, these being 1) autograft, 2) DBM crunch allograft (Grafton), 3) bovine cancellous bone xenograft (Lubboc), 4) calcium phosphate hydroxyapatite substitute (Ceraform), 5) calcium sulfate substitute (Osteoset), and 6) no filling (control). The animals were sacrificed at 1, 3, and 6 months after implantation and tissue samples from the implanted areas were processed for histological evaluation. A histological grading scale was designed to determine the different histological parameters of bone healing. The highest histological grades were achieved with the use of cancellous bone autograft. Bovine xenograft (Lubboc) was the second best in the histological scale grading. The other substitutes (Grafton, Ceraform, Osteoset) had similar scores but were inferior to both allograft and xenograft. Bovine xenograft showed better biological response than the other bone graft substitutes; however, more clinical studies are necessary to determine its overall effectiveness.

Pelvic pain in endometriosis: painkillers or sport to alleviate symptoms?

PubMed

Koppan, A; Hamori, J; Vranics, I; Garai, J; Kriszbacher, I; Bodis, J; Rebek-Nagy, G; Koppan, M

2010-06-01

To assess potential individual factors influencing quality of life and pain scores of patients suffering from histologically confirmed endometriosis. Study using a questionnaire among patients of reproductive age undergoing laparoscopy with a presumed diagnosis of endometriosis. Details of fertility, previous treatments and quality of life, sexual activity, as well as linear pain scores for several symptoms, were recorded. Details of intraoperative findings were also collected and only those data were used where endometriosis was intraoperatively and histologically proven. A questionnaire before surgery gathered information from women on the following groups of variables: age, marital status, education, reproductive and medical history including previous pregnancies and parity, knowledge of accompanying pelvic disorders, regular sport activity, as well as general quality of life estimates including self-image. Pelvic pain was scored using a visual analogue scale. Data were statistically evaluated. Eighty-one patients complaining about persistent pelvic pain were later intraoperatively and histologically proven to have endometriosis. Thirty-one of them (38.2%) reported regular sport as part of their daily life schedule while 50 of them (61.8%) performed no physical activity at all. Fourteen patients among regular exercisers and 33 patients among those without physical activity reported the effectiveness of painkillers for pelvic pain, corresponding to 45.1% and 66% of these subgroups, respectively (difference statistically significant, p<0.05). Based on our results, we can conclude, that taking painkillers might be less effective among endometriosis patients performing regular daily sport activities, and, thus it might impose them to an unnecessary burden of possible side-effects.

Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial.

PubMed

Bomhof, Marc R; Parnell, Jill A; Ramay, Hena R; Crotty, Pam; Rioux, Kevin P; Probert, Chris S; Jayakumar, Saumya; Raman, Maitreyi; Reimer, Raylene A

2018-05-19

In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. This trial was registered at Clinicaltrials.com as NCT03184376.

Effects of ozone (O3) therapy on cisplatin-induced ototoxicity in rats.

PubMed

Koçak, Hasan Emre; Taşkın, Ümit; Aydın, Salih; Oktay, Mehmet Faruk; Altınay, Serdar; Çelik, Duygu Sultan; Yücebaş, Kadir; Altaş, Bengül

2016-12-01

The aim of this study is to investigate the effect of rectal ozone and intratympanic ozone therapy on cisplatin-induced ototoxicity in rats. Eighteen female Wistar albino rats were included in our study. External auditory canal and tympanic membrane examinations were normal in all rats. The rats were randomly divided into three groups. Initially, all the rats were tested with distortion product otoacoustic emissions (DPOAE), and emissions were measured normally. All rats were injected with 5-mg/kg/day cisplatin for 3 days intraperitoneally. Ototoxicy had developed in all rats, as confirmed with DPOAE after 1 week. Rectal and intratympanic ozone therapy group was Group 1. No treatment was administered for the rats in Group 2 as the control group. The rats in Group 3 were treated with rectal ozone. All the rats were tested with DPOAE under general anesthesia, and all were sacrificed for pathological examination 1 week after ozone administration. Their cochleas were removed. The outer hair cell damage and stria vascularis damage were examined. In the statistical analysis conducted, a statistically significant difference between Group 1 and Group 2 was observed in all frequencies according to the DPOAE test. In addition, between Group 2 and Group 3, a statistically significant difference was observed in the DPOAE test. However, a statistically significant difference was not observed between Group 1 and Group 3 according to the DPOAE test. According to histopathological scoring, the outer hair cell damage score was statistically significantly high in Group 2 compared with Group 1. In addition, the outer hair cell damage score was also statistically significantly high in Group 2 compared with Group 3. Outer hair cell damage scores were low in Group 1 and Group 3, but there was no statistically significant difference between these groups. There was no statistically significant difference between the groups in terms of stria vascularis damage score examinations. Systemic ozone gas therapy is effective in the treatment of cell damage in cisplatin-induced ototoxicity. The intratympanic administration of ozone gas does not have any additional advantage over the rectal administration.

Accuracy of ultrasound in the detection of liver fibrosis in chronic viral hepatitis.

PubMed

D'Onofrio, Mirko; Martone, Enrico; Brunelli, Silvia; Faccioli, Niccolò; Zamboni, Giulia; Zagni, Irene; Fattovich, Giovanna; Pozzi Mucelli, Roberto

2005-10-01

To assess the accuracy of ultrasonography (US) in the identification and grading of hepatic fibrosis in patients afflicted with chronic viral liver disease, compared to histological examination as a gold standard. We prospectively studied 105 patients (32 F, 73 M) affected by chronic viral liver disease in 36 months. Patients were studied with B-mode US and then underwent US-guided liver biopsy. All the patients were studied with conventional US with a Sequoia 512, 6.0 (Acuson, Mountain View CA, USA). We evaluated the following US parameters: liver margins, parenchymal echotexture, portal vein caliber and spleen diameter. The four B-mode US parameters were used for the US grading (from 0 to 4). Scheuer's grading (from 0 to 4) was used for the histological score. Grades 3 and 4 were considered as positive for fibrosis. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated in the case of absence, positivity of one or all the US parameters. The correlation between US and histological scores was evaluated with Spearman's test. At histology seventy-seven patients (73%) had absent grade 0 (1 patient; 1%), low-moderate grade 1 (35 patients; 33%) or grade 2 (41 patients; 39%) liver fibrosis. Twenty-eight patients (27%) had severe grade 3 (16 patients; 15%) or grade 4 (12 patients; 11%) fibrosis. In the case of absence of US parameters sensitivity was 32%, specificity 32%, positive predictive value 15%, negative predictive value 57% and accuracy 32%. In the case of positivity of at least one of the US parameters the values were 68%, 68%, 43%, 84% and 69%. In the case of presence of all the US signs the results were 25%, 100%, 100%, 79% and 80%. None of the 77 patients with a healthy liver or with low-grade fibrosis was positive for all the US parameters. All the patients positive for all of the ultrasonographic parameters had high-grade fibrosis or cirrhosis at liver biopsy. Correlation between B-mode and histological scores was not statistically significant (Rs=0.45; p=0.0001). US identification of liver fibrosis in chronic liver disease is possible with 25% sensitivity, 100% specificity, 100% positive predictive value and 79% negative predictive value, with an 80% diagnostic accuracy.

Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniels, Thomas B.; Brown, Paul D., E-mail: Brown.paul@mayo.edu; Felten, Sara J.

2011-09-01

Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-riskmore » group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.« less

A clinically feasible treatment protocol for magnetic resonance-guided high-intensity focused ultrasound ablation in the liver.

PubMed

Wijlemans, Joost W; de Greef, Martijn; Schubert, Gerald; Bartels, Lambertus W; Moonen, Chrit T W; van den Bosch, Maurice A A J; Ries, Mario

2015-01-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) allows for noninvasive thermal ablation under real-time temperature imaging guidance. The purpose of this study was to assess the feasibility and safety of MR-HIFU ablation of liver tissue in a clinically acceptable setting. The experimental protocol was designed with a clinical ablation procedure of a small malignant tumor in mind; the procedures were performed within a clinically feasible time frame and care was taken to avoid adverse events. The main outcome was the size and quality of the ablated liver tissue volume on imaging and histology. Secondary outcomes were safety and treatment time. Healthy pigs (n = 10) under general anesthesia were positioned on a clinical MR-HIFU system, which consisted of an HIFU tabletop with a skin cooling system integrated into a 1.5-T MR scanner. A liver tissue volume was ablated with multiple sonication cells (4 × 4 × 10 mm, 450 W). Both MR thermometry and sonication were respiratory-gated using a pencil beam navigator on the diaphragm. Contrast-enhanced T1-weighted (CE-T1w) imaging was performed for treatment evaluation. Targeted total treatment time was 3 hours. The abdominal wall, liver, and adjacent organs were inspected postmortem for thermal damage. Ablated tissue volumes were processed for cell viability staining. The ablated volumes were analyzed using MR imaging, MR thermometry, and cell viability histology. Eleven volume ablations were performed in 10 animals, resulting in a median nonperfused volume (NPV) on CE-T1w imaging of 1.6 mL (interquartile range [IQR], 0.8-2.3; range, 0.7-3.0). Cell viability histology showed a damaged volume of 1.5 mL (IQR, 1.1-1.8; range, 0.7-2.3). The NPV was confluent in 10 of the 11 cases. The ablated tissue volume on cell viability histology was confluent in all 9 available cases. In all cases, there was a good correspondence between the aspects of the NPV on CE-T1w and the ablated volume on cell viability histology. Two treatment-related adverse events occurred: 1 animal had a 7-mm skin burn and 1 animal showed evidence of thermal damage on the surface of the spleen. Median ablation time was 108 minutes (IQR, 101-120; range, 96-181 minutes) and median total treatment time was 180 minutes (IQR, 165-224; 130-250 minutes). Our results demonstrate the feasibility and safety of MR-HIFU ablation of liver tissue volumes. The imaging data and cell viability histology show, for the first time, that confluent ablation volumes can be achieved with motion-gated ablation and MR guidance. These results were obtained using a readily available MR-HIFU system with only minor modifications, within a clinically acceptable time frame, and with only minor adverse events. This shows that this technique is sufficiently reliable and safe to initiate a clinical trial.

Histological comparison of alendronate, calcium hydroxide and formocresol in amputated rat molar.

PubMed

Cengiz, S Burcak; Batirbaygil, Yildiz; Onur, Mehmet Ali; Atilla, Pergin; Asan, Esin; Altay, Nil; Cehreli, Zafer C

2005-10-01

The purpose of this study was to evaluate the potential of alendronate sodium (ALN), a biphosohonate to stimulate hard tissue formation in pulpotomized (amputated) rat molars. Two commonly used pulpotomy materials, calcium hydroxide (CH) and formocresol (FC) were utilized for comparisons. Histological evaluations were performed by observers blinded to treatment allocation on days 7, 15, 30 and 60, followed by statistical analysis of selected histological criteria. In all evaluation periods, hard tissue deposition was evident along the radicular dentin in ALN and CH groups. In days 30 and 60, the latter two groups showed no differences in inflammatory cell response and hard tissue deposition scores (P > 0.05). ALN appears to be capable of maintaining pulpal vitality, while promoting hard tissue formation, similar to CH.

Nerve Ultrasound Predicts Treatment Response in Chronic Inflammatory Demyelinating Polyradiculoneuropathy-a Prospective Follow-Up.

PubMed

Härtig, Florian; Ross, Marlene; Dammeier, Nele Maria; Fedtke, Nadin; Heiling, Bianka; Axer, Hubertus; Décard, Bernhard F; Auffenberg, Eva; Koch, Marilin; Rattay, Tim W; Krumbholz, Markus; Bornemann, Antje; Lerche, Holger; Winter, Natalie; Grimm, Alexander

2018-04-01

As reliable biomarkers of disease activity are lacking, monitoring of therapeutic response in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains a challenge. We sought to determine whether nerve ultrasound and electrophysiology scoring could close this gap. In CIDP patients (fulfilling EFNS/PNS criteria), we performed high-resolution nerve ultrasound to determine ultrasound pattern sum scores (UPSS) and predominant echotexture nerve conduction study scores (NCSS) as well as Medical Research Council sum scores (MRCSS) and inflammatory neuropathy cause and treatment disability scores (INCAT) at baseline and after 12 months of standard treatment. We retrospectively correlated ultrasound morphology with nerve histology when available. 72/80 CIDP patients featured multifocal nerve enlargement, and 35/80 were therapy-naïve. At baseline, clinical scores correlated with NCSS (r 2  = 0.397 and r 2  = 0.443, p < 0.01), but not or hardly with UPSS (Medical Research Council sum scores MRCSS r 2  = 0.013, p = 0.332; inflammatory neuropathy cause and treatment disability scores INCAT r 2  = 0.053, p = 0.048). Longitudinal changes in clinical scores, however, correlated significantly with changes in both UPSS and NCSS (r 2  = 0.272-0.414, p < 0.0001). Combining nerve/fascicle size with echointensity and histology at baseline, we noted 3 distinct classes: 1) hypoechoic enlargement, reflecting active inflammation and onion bulbs; 2) nerve enlargement with additional hyperechogenic fascicles/perifascicular tissue in > 50% of measured segments, possibly reflecting axonal degeneration; and 3) almost no enlargement, reflecting "burned-out" or "cured" disease without active inflammation. Clinical improvement after 12 months was best in patients with pattern 1 (up to 75% vs up to 43% in pattern 2/3, Fisher's exact test p < 0.05). Nerve ultrasound has additional value not only for diagnosis, but also for classification of disease state and may predict treatment response.

Computational model of retinal photocoagulation and rupture

NASA Astrophysics Data System (ADS)

Sramek, Christopher; Paulus, Yannis M.; Nomoto, Hiroyuki; Huie, Phil; Palanker, Daniel

2009-02-01

In patterned scanning laser photocoagulation, shorter duration (< 20 ms) pulses help reduce thermal damage beyond the photoreceptor layer, decrease treatment time and minimize pain. However, safe therapeutic window (defined as the ratio of rupture threshold power to that of light coagulation) decreases for shorter exposures. To quantify the extent of thermal damage in the retina, and maximize the therapeutic window, we developed a computational model of retinal photocoagulation and rupture. Model parameters were adjusted to match measured thresholds of vaporization, coagulation, and retinal pigment epithelial (RPE) damage. Computed lesion width agreed with histological measurements in a wide range of pulse durations and power. Application of ring-shaped beam profile was predicted to double the therapeutic window width for exposures in the range of 1 - 10 ms.

Possible risk factors associated with greater damage in systemic lupus erythematosus patients: an Egyptian multicenter study.

PubMed

Hammad, M; Eissa, M; Fathi, S

2016-08-01

Systemic lupus erythematosus (SLE) is a prototypic multisystem autoimmune disorder. The total damage in a patient with SLE may result from SLE itself or from any other pathologic process. The aim of this study was to assess risk factors of greater damage in a sample of Egyptian SLE patients. This Egyptian multicenter retrospective study included 100 SLE patients: 64 patients from Cairo University Hospitals and 36 patients from Zagazig University Hospitals. The Systemic Lupus International Collaborative Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (ACR-DI) was used to document the damage in each patient. The total SLICC/ACR-DI score ranged from 0 to 8. A higher DI score was found in hypertensive patients, compared to normotensive patients; and among those with positive anti-phospholipid antibodies, compared to those with negative anti-phospholipid antibodies. This difference was statistically significant (p < 0.01). Also, a higher DI score was found in cyclophosphamide users, compared to non-users; and in those with proteinuria and seizures, compared to those without; and the difference was statistically significant (p < 0.05). There was a significant positive correlation between the DI and patient age (p < 0.05). Damage in SLE cannot be prevented completely, as SLE disease is considered an aggressive disease treated by aggressive medications, but rheumatologists should try to minimize damage as much as possible to maintain the patients' health, functioning and general wellbeing. © The Author(s) 2016.

Rotator cuff healing after continuous subacromial bupivacaine infusion: an in vivo rabbit study

PubMed Central

FRIEL, NICOLE A.; WANG, VINCENT M.; SLABAUGH, MARK A.; WANG, FANCHIA; CHUBINSKAYA, SUSAN; COLE, BRIAN J.

2013-01-01

Background The objective of this study was to evaluate the effects of continuous subacromial bupivacaine infusion on supraspinatus muscle and rotator cuff tendon healing via gross, biomechanical, and histologic analyses. Methods Thirty-three New Zealand White rabbits underwent unilateral supraspinatus transection and rotator cuff repair (RCR). Rabbits were assigned to 1 of 3 groups: (1)RCR only, (2)RCR with continuous saline infusion for 48 hours, or (3)RCR with continuous 0.25% bupivacaine with epinephrine (1:200,000) infusion for 48 hours. Rabbits were sacrificed at either 2 (for histologic assessment) or 8 weeks post-operatively (for biomechanical and histologic assessment). Results Tensile testing showed significantly higher load to failure in intact tendons compared to repaired tendons (p<0.01); however, no statistical differences were detected among RCR only, RCR Saline, and RCR Bupivacaine groups. Histologically, the enthesis of repaired tendons showed increased cellularity and disorganized collagen fibers compared to intact tendons, with no differences between treatment groups. Muscle histology demonstrated scattered degenerative muscle fibers at 2 weeks in both RCR Saline and RCR Bupivacaine, but no degeneration was noted at 8 weeks. Conclusions The healing supraspinatus tendons exposed to bupivacaine infusion showed similar histologic and biomechanical characteristics compared to untreated and saline infused RCR groups. Muscle histology showed fiber damage at 2 weeks for both the saline and bupivacaine treated groups, with no apparent disruption at 8 weeks, suggesting a recovery process. Therefore, subacromial bupivacaine infusion in this rabbit rotator cuff model does not appear to impair muscle or tendon following acute injury and repair. Level Of Evidence Basic science study PMID:22818894

Collaborative Testing in Practical Laboratories: An Effective Teaching-Learning Method in Histology.

PubMed

Guo, Yuping; Li, Enzhong

2016-01-01

This article presents an experimental teaching and learning program used in histology with first-year students in the second term in the Faculty of Biology at Huanghuai University, China. Eighty-six students were divided randomly into two groups (n=43 per group). Tests were conducted at the end of each practical laboratory (10 laboratories in total) in which collaborative testing was used in the experimental group and traditional testing in the control group. To assess achievement, a final examination in histology was carried out at the end of the course. To determine students' attitude to the teaching styles, a questionnaire survey was conducted at the end of the term. Results showed that students preferred the collaborative testing format. In the experimental group, students' scores were significantly higher than those of students in the control group in final examinations. These findings indicate that collaborative testing enhances student learning and understanding of the material taught, and suggest that collaborative testing is an effective teaching-learning method in histology.

Functional Assessment of Laser Irradiation

DTIC Science & Technology

1988-03-01

1 Diagram of the Plexiglas restraint device used during laser exposure and acuity testing ........................................... 4 FIGURE 2...8 FIGURE 6 Spectral sensitivity curves for rhesus, human trichromat, and protonomalous human tested under similar...luminance, wavelength and logical means (fundoscopic or histologic verification contrast of test targets have yielded various damac of tissue damage) or can

Efficacy of clade 2.3.2 H5 commercial vaccines in protecting chickens from clade 2.3.4.4 H5N8 highly pathogenic avian influenza infection.

PubMed

Yuk, Seong-Su; Erdene-Ochir, T O; Kwon, Jung-Hoon; Noh, Jin-Yong; Hong, Woo-Tack; Jeong, Jei-Hyun; Jeong, Sol; Gwon, Gyeong-Bin; Shin, Jong-Il; Sur, Jung-Hyang; Song, Chang-Seon

2017-03-01

Emerging clade 2.3.4.4 of the highly pathogenic avian influenza (HPAI) virus strain H5N8, which had been detected sporadically in domestic poultry in China, started to affect wild birds and poultry in South Korea in 2014. The virus was spread to Germany, Italy, the Netherlands, United Kingdom, and even United States by migratory birds. Here, we tested currently used commercial clade 2.3.2 H5 vaccines to evaluate mortality, clinical signs, virus shedding, and histological damage after experimental infection of chickens with the clade 2.3.4.4 HPAI H5N8 virus. Although the vaccination protected chickens from death, it failed to prevent chickens from shedding the virus and from tissue damage according to histological examination. These results suggest that the use of appropriate vaccines that match the currently epidemic HPAI virus is recommended, and continuous HPAI surveillance and testing of currently used commercial vaccines should be performed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Absence of histological changes after the administration of a continuous intrathecal clonidine in Wistar rats.

PubMed

Guevara-López, Uriah; Aldrete, J Antonio; Covarrubias-Gómez, Alfredo; Hernández-Pando, Rogelio E; López-Muñoz, Francisco J

2009-01-01

The administration of epidural and spinal clonidine has demonstrated an antinociceptive effect in animals and humans. For that reason, its spinal administration has been proposed as an adjuvant in chronic pain management. However, there is limited information about its possible neurotoxic effect after its continuous neuraxial administration. Twelve male Wistar rats were randomly divided into two groups. Using an osmotic mini-pump a continuous infusion of intrathecal clonidine, (21.4 micrograms/day, Group A) or saline solution (Group B), was administered for 14 consecutive days. For evaluating the neurological damage a neuropathological analysis of the spinal cord was performed by light microscopy. Neurohistopathologic examination of the spinal cord specimens failed to show evidence of neurotoxic damage in either group. These findings showed that continuous intrathecal administration of clonidine did not produce evidence of histological neurotoxicity; therefore it is possible that continuous administration of intrathecal clonidine might be a safe option for treatment of chronic intractable pain; however, further investigations are necessary for evaluating diverse doses and periods of time, and to define its possible behavioral effects.

NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

PubMed

Nickolas, Thomas L; Forster, Catherine S; Sise, Meghan E; Barasch, Nicholas; Solá-Del Valle, David; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

2012-09-01

The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 μg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 μg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.

Efficacy of Gold Nanoparticles against Nephrotoxicity Induced by Schistosoma mansoni Infection in Mice.

PubMed

Dkhil, Mohamed A; Khalil, Mona F; Bauomy, Amira A; Diab, Marwa Sm; Al-Quraishy, Saleh

2016-11-01

In this study, the ameliorative effects of gold nanoparticles (gold NP) on the renal tissue damage in Schistosoma mansoni (S. mansoni)-infected mice was investigated. High-resolution transmission electron microscopy was used for the characterization of NP. The gold NP at concentrations of 250, 500, and 1000 μg/kg body weight were inoculated into S. mansoni-infected mice. The parasite caused alterations in the histological architecture. Furthermore, it induced a significant reduction in the renal glutathione levels; however, the levels of nitric oxide and malondialdehyde were significantly elevated. The parasite also managed to downregulate KIM-1, NGAL, MCP-1, and TGF-β mRNA expression in infected animals. Notably, gold NP treatment in mice reduced the extent of histological impairment and renal oxidative damage. Gold NP were able to regulate gene expression impaired by S. Mansoni infection. The curative effect of gold NP against renal toxicity in S. mansoni-infected mice is associated with their role as free radical scavengers. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model.

PubMed

Huang, Tzou-Chi; Tsai, Shinn-Shyong; Liu, Li-Fang; Liu, Yu Lin; Liu, Hung-Jen; Chuang, Kuo Pin

2010-09-07

To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC). BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in colonic sections were detected by immunohistochemistry. There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-alpha were also decreased in AL-treated groups. We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC.

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

PubMed

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

Simplified Radiographic Damage Index for Affected Joints in Chronic Gouty Arthritis

PubMed Central

2016-01-01

The aim of this study was to develop and validate a new radiographic damage scoring method (DAmagE index of GoUt; DAEGU) in chronic gout using plain radiography. Two independent observers scored foot x-rays from 15 patients with chronic gout according to the DAEGU method and the modified Sharp/van der Heijde (SvdH) method. The 10 metatarsophalangeal (MTP) and 2 interphalangeal (IP) joints of the first toes of both feet were scored to assess the degrees of erosion and joint space narrowing (JSN). The intraobserver and interobserver reliabilities were analyzed by calculating the intraclass correlation coefficient (ICC) and minimal detectable change (MDC). The correlation between the DAEGU and SvdH methods was analyzed by calculating the Spearman's rho correlation coefficients and Kappa coefficients. The DAEGU method was found to be highly reproducible (0.945–0.987 for the intraobserver and 0.993–0.996 for the interobserver ICC values). The erosion, JSN, and total scores exhibited strong positive correlations between the DAEGU and SvdH methods and also within each method (r = 0.860–0.969, P < 0.001 for all parameters). The DAEGU and SvdH methods were in very good agreement as determined by Kappa coefficient analysis [0.732 (0.387–1.000) for erosion and 1.000 (1.000–1.000) for JSN]. In conclusion, this study revealed that DAEGU method was a reliable and feasible tool in the assessment of radiographic damage in chronic gout. The DAEGU method may provide a more easy assessment of structural damage in chronic gout in the real clinical practice. PMID:26955246

Evaluation of Single-Impact-Induced Cartilage Degeneration by Optical Coherence Tomography

PubMed Central

de Bont, Florence; Brill, Nicolai; Schmitt, Robert; Tingart, Markus; Pufe, Thomas; Jahr, Holger; Nebelung, Sven

2015-01-01

Posttraumatic osteoarthritis constitutes a major cause of disability in our increasingly elderly population. Unfortunately, current imaging modalities are too insensitive to detect early degenerative changes of this disease. Optical coherence tomography (OCT) is a promising nondestructive imaging technique that allows surface and subsurface imaging of cartilage, at near-histological resolution, and is principally applicable in vivo during arthroscopy. Thirty-four macroscopically normal human cartilage-bone samples obtained from total joint replacements were subjected to standardized single impacts in vitro (range: 0.25 J to 0.98 J). 3D OCT measurements of impact area and adjacent tissue were performed prior to impaction, directly after impaction, and 1, 4, and 8 days later. OCT images were assessed qualitatively (DJD classification) and quantitatively using established parameters (OII, Optical Irregularity Index; OHI, Optical Homogeneity Index; OAI, Optical Attenuation Index) and compared to corresponding histological sections. While OAI and OHI scores were not significantly changed in response to low- or moderate-impact energies, high-impact energies significantly increased mean DJD grades (histology and OCT) and OII scores. In conclusion, OCT-based parameterization and quantification are able to reliably detect loss of cartilage surface integrity after high-energy traumatic insults and hold potential to be used for clinical screening of early osteoarthritis. PMID:26229959

Mesenchymal stem cells promote hard-tissue repair after direct pulp capping.

PubMed

Obeid, Maram; Saber, Shehab El Din Mohamed; Ismael, Alaa El Din; Hassanien, Ehab

2013-05-01

The aim of this study was to investigate the potential of autologous mesenchymal bone marrow stem cells (BMSCs) to promote hard-tissue formation after direct pulp capping procedures. Bone marrow was aspirated from the iliac crest of healthy dogs of nonspecific race. Mononuclear cells were obtained using the Histopaque (Sigma-Aldrich, St Louis, MO) protocol and cultured for 21 days. Direct pulp capping procedures were performed in posterior teeth, and then mineral trioxide aggregate (MTA), hydroxyapatite/tricalcium phosphate, or BMSCs were used as direct pulp capping agents. After 3 months, animals were sacrificed, and jaw segments were processed for radiographic examination using cone-beam computed tomography scanning and histologic examination to assess the formation of a hard-tissue barrier according to a scoring system. The longitudinal and cross-sectional radiophotographs and histologic sections confirmed the formation of an evident calcific barrier after direct pulp capping with MTA and BMSCs. Statistical analysis of the scores given for radiographic and histologic calcific bridge formation showed that both MTA and BMSCs had a comparable tendency to produce a hard-tissue barrier that was significantly higher than hydroxyapatite tricalcium phosphate (P < .05). Autologous mesenchymal BMSCs were able to promote hard-tissue formation after direct pulp capping procedures. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Histopathological assessment of OASIS Ultra on critical-sized wound healing: a pilot study.

PubMed

Yeh, Daniel Dante; Nazarian, Rosalynn M; Demetri, Leah; Mesar, Tomaz; Dijkink, Suzan; Larentzakis, Andreas; Velmahos, George; Sadik, Karim Walid

2017-06-01

Dermatopathologists assess wounds secondary to trauma, infection, or oncologic resection that can be challenging to reconstruct. OASIS Ultra, an extracellular matrix, has been described for use in chronic and burn wounds. The aim of this pilot study is to assess wound healing in post-traumatic and infective wounds treated with OASIS using histological markers of repair. Adults with traumatic, infective or iatrogenic wound defects with size precluding primary closure were eligible. Half the wound was randomly assigned to receive OASIS plus standard therapy; the other half received standard of care (SOC) therapy. During dressing changes, standardized-scale photographs were taken and biopsies obtained. Histologic sections were reviewed for degree of acute inflammation and extent of tissue repair. Neutrophils, edema, hemorrhage, necrosis, fibroblasts, collagen density and neovascularization were semi-quantitatively assessed. Forty-four skin biopsies from 7 patients with 10 acute wounds met eligibility criteria. Histologically, OASIS samples demonstrated improved acute inflammation scores compared to SOC. No patients experienced OASIS-related complications. OASIS-treated wound halves trended toward more wound contraction and improved tissue repair. Our scoring system aids histopathological wound assessment. Treatment of critical-sized, post-traumatic, acute wounds with OASIS resulted in decreased inflammation, and potentially more advanced wound healing, compared to SOC. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy.

PubMed

Marin, Evelyn Cristina Santana; Balbi, Ana Paula Coelho; Francescato, Heloísa Della Coletta; Alves da Silva, Cleonice Giovanini; Costa, Roberto Silva; Coimbra, Terezila M

2008-01-01

Adult rats submitted to perinatal salt overload presented renin-angiotensin system (RAS) functional disturbances. The RAS contributes to the renal development and renal damage in a 5/6 nephrectomy model. The aim of the present study was to analyze the renal structure and function of offspring from dams that received a high-salt intake during pregnancy and lactation. We also evaluated the influence of the prenatal high-salt intake on the evolution of 5/6 nephrectomy in adult rats. A total of 111 sixty-day-old rat pups from dams that received saline or water during pregnancy and lactation were submitted to 5/6 nephrectomy (nephrectomized) or to a sham operation (sham). The animals were killed 120 days after surgery, and the kidneys were removed for immunohistochemical and histological analysis. Systolic blood pressure (SBP), albuminuria, and glomerular filtration rate (GFR) were evaluated. Increased SBP, albuminuria, and decreased GFR were observed in the rats from dams submitted to high-sodium intake before surgery. However, there was no difference in these parameters between the groups after the 5/6 nephrectomy. The scores for tubulointerstitial lesions and glomerulosclerosis were higher in the rats from the sham saline group compared to the same age control rats, but there was no difference in the histological findings between the groups of nephrectomized rats. In conclusion, our data showed that the high-salt intake during pregnancy and lactation in rats leads to structural changes in the kidney of adult offspring. However, the progression of the renal lesions after 5/6 nephrectomy was similar in both groups.

Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates.

PubMed

Ma, Anlun; Jiang, Li; Song, Lijun; Hu, Yanxin; Dun, Hao; Daloze, Pierre; Yu, Yonglin; Jiang, Jianyuan; Zafarullah, Muhammad; Chen, Huifang

2013-07-01

Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys. MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively. Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups. Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects. Copyright © 2013 Elsevier B.V. All rights reserved.

Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model

PubMed Central

Shin, Seung Kak; Cho, Jae Hee; Kim, Eui Joo; Kim, Eun-Kyung; Park, Dong Kyun; Kwon, Kwang An; Chung, Jun-Won; Kim, Kyoung Oh; Kim, Yoon Jae

2017-01-01

AIM To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model. METHODS An acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured. RESULTS In DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2’-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells (P < 0.05). CONCLUSION Rosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease. PMID:28740344

Duodenal histopathology and laboratory deficiencies related to bone metabolism in coeliac disease.

PubMed

Posthumus, Lotte; Al-Toma, Abdul

2017-08-01

Coeliac disease (CD) is a chronic immune-mediated small intestine enteropathy precipitated by gluten in genetically predisposed individuals. Adult presentation is often atypical and malabsorption of vitamins and minerals is common, with a consequent disturbance of bone metabolism. We aim to evaluate laboratory deficiencies related to bone metabolism and the relationship between severity of histological damage and degree of bone mass loss at diagnosis of CD. A retrospective cross-sectional study of 176 adult coeliac patients was carried out. All patients fulfilled the histopathological criteria for CD. Biochemical data were analysed (calcium/phosphate/alkaline-phosphatase/vitamin D/parathormone). Duodenal histology was classified according to the Marsh classification. Bone mass density (BMD) at the lumbar and femoral regions measured by dual X-ray absorptiometry. A P-value of less than 0.05 was considered significant. No correlation was found between the presence of gastrointestinal symptoms and the Marsh histopathological stage (P>0.05). Vitamin D deficiency was most common (44.5%), whereas only 5.7% had hypocalcaemia. Calcium was lower (P<0.05) and parathormone was higher (P=0.01) in patients with Marsh III. These patients had lower lumbar T-score (P<0.05). Although low BMD occurred in all age groups, most osteoporotic patients were aged 45-49 years (81.8%). A multiple regression analysis showed that the Marsh histopathological stage could be a predictor of lower lumbar BMD (r=0.322, B=-1.146, P<0.05). Laboratory deficiencies and decreased BMD could be severe and unrelated to the presence of gastrointestinal symptoms. At diagnosis, the Marsh histopathological stage could predict the occurrence of low BMD, which carries a risk of developing into osteoporosis. In coeliac patients older than 30 years, evaluation of bone biomarkers and dual X-ray absorptiometry examination should be considered.

Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats.

PubMed

Di Paola, Rosanna; Fusco, Roberta; Impellizzeri, Daniela; Cordaro, Marika; Britti, Domenico; Morittu, Valeria Maria; Evangelista, Maurizio; Cuzzocrea, Salvatore

2016-12-12

Osteoarthritis (OA) is a degenerative joint disease produced by a cascade of events that can ultimately lead to joint damage. The aim of this study was to evaluate the effect of adelmidrol, a synthetic palmitoylethanolamide analogue, combined with hyaluronic acid on pain severity and modulation of the inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. OA was induced by intra-articular injection of MIA in the knee joint. On day 21 post-MIA administration, the knee joint was analyzed. Rats subjected to OA were treated by intra-articular injection of adelmidrol in combination with sodium hyaluronate at different doses and time points after MIA induction. Limb nociception was assessed by the paw withdrawal latency and threshold measurement. Samples were examined macroscopically, histologically, and by immunohistochemistry. At day 21 post-MIA injection, the MIA + solvent and MIA + 1.0% sodium hyaluronate groups showed irregularities and fibrillation in the surface layer, a decrease in blood cells and multilayering in transition and radial zones, no pannus formation, and modified Mankin scores significantly higher than sham knees. The combination of hyaluronic acid and adelmidrol dose-dependently (adelmidrol 0.6% + 1.0% sodium hyaluronate and adelmidrol 2% + 1.0% sodium hyaluronate) reduced the histological alterations induced by MIA. Moreover, degeneration of articular cartilage, mast cell infiltration, and pro-inflammatory cytokine and chemokine plasma levels were significantly downregulated by treatment with a combination of hyaluronic acid and adelmidrol at the above doses. Our results clearly demonstrate that the combination of hyaluronic acid and adelmidrol improves the signs of OA induced by MIA.

Effect of Lactobacillus plantarum LP-Onlly on gut flora and colitis in interleukin-10 knockout mice.

PubMed

Xia, Yang; Chen, Hong-Qi; Zhang, Min; Jiang, Yan-Qun; Hang, Xiao-Min; Qin, Huan-Long

2011-02-01

Probiotics are used in the therapy of inflammatory bowel disease. This study aimed to determine the effects of probiotic Lactobacillus plantarum LP-Onlly (LP) on gut flora and colitis in interleukin-10 knockout (IL-10(-/-) ) mice, a model of spontaneous colitis. IL-10(-/-) and wild-type mice were used at 8 weeks of age and LP by gavage was administered at a dose of 10(9) cells/day per mice for 4 weeks. Mice were maintained for another one week without LP treatment. The colonic tissues were collected for histological and ultrastructural analysis at death after 4 weeks treatment of LP, and the feces were collected at 1-week intervals throughout the experiment for the analysis of gut flora and LP using selective culture-based techniques. Compared with control mice, IL-10(-/-) mice developed a severe intestinal inflammation and tissue damage, and had an abnormal composition of gut microflora. LP administration attenuated colitis with the decreased inflammatory scoring and histological injury in the colon of IL-10(-/-) mice. In addition, LP administration increased the numbers of beneficial total bifidobacteria and lactobacilli, and decreased the numbers of potential pathogenic enterococci and Clostridium perfringens, although the decrease of coliforms was not significant after LP treatment in IL-10(-/-) mice. Oral administration of LP was effective in the treatment of colitis, with the direct modification of gut microflora in IL-10(-/-) mice. This probiotic strain could be used as a potential adjuvant in the therapy of inflammatory bowel disease, although further studies are required in human. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Enhancement of Wound Healing by the Traditional Chinese Medicine Herbal Mixture Sophora flavescens in a Rat Model of Perianal Ulceration

PubMed Central

XU, XIAOPING; LI, XIAOHUA; ZHANG, LEI; LIU, ZHAOHUI; PAN, YUAN; CHEN, DONG; BIN, DONGHUA; DENG, QUN; SUN, YU; HOFFMAN, M. ROBERT; YANG, ZHIJIAN; YUAN, HONG

2017-01-01

Background/Aim: Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. Materials and Methods: A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E2 (PGE2) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. Results: Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. Conclusion: CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE2 and IL-8 may be involved in the mechanism of enhanced wound-healing. PMID:28652418

Enhancement of Wound Healing by the Traditional Chinese Medicine Herbal Mixture Sophora flavescens in a Rat Model of Perianal Ulceration.

PubMed

Xu, Xiaoping; Li, Xiaohua; Zhang, Lei; Liu, Zhaohui; Pan, Yuan; Chen, Dong; Bin, Donghua; Deng, Qun; Sun, Y U; Hoffman, Robert M; Yang, Zhijian; Yuan, Hong

2017-01-01

Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E 2 (PGE 2 ) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE 2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE 2 and IL-8 may be involved in the mechanism of enhanced wound-healing. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

1'-Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells.

PubMed

Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao

2016-09-25

1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ethmoid Histopathology Does Not Predict Olfactory Outcomes after Endoscopic Sinus Surgery

PubMed Central

Soler, Zachary M.; Sauer, David A.; Mace, Jess C.; Smith, Timothy L.

2010-01-01

BACKGROUND Histologic inflammation correlates with the degree of baseline olfactory dysfunction in patients with chronic rhinosinusitis (CRS), however factors associated with improvement in olfactory status after endoscopic sinus surgery (ESS) remain elusive. OBJECTIVE Our purpose was to compare histopathologic findings in CRS patients with olfactory loss and evaluate whether inflammatory markers can predict long-term olfactory improvement after ESS. METHODS Adult (≥18 years) patients with CRS were prospectively enrolled after electing ESS due to failed medical management. Mucosal tissue specimens were collected at the time of surgery and underwent pathlogic review in a blinded fashion. Subjects completed the 40-item Smell Identification Test (SIT) preoperatively and at least 6 months postoperatively. Multivariate logistic regression was used to identify histologic factors associated with postoperative improvement in SIT score. RESULTS The final cohort was comprised of 101 patients with a mean follow-up of 16.7 ± 6.0 months. Mean mucosal eosinophil count was higher in patients with hyposmia and anosmia (p<0.001). Patients with preoperative anosmia were more likely to have greater severity of BM thickening compared to subjects with hyposmia or normosmia (p=0.021). In patients with olfactory dysfunction, 54.7% reported olfactory improvement of at least 4 points on postoperative SIT scores. After controlling for nasal polyposis, histologic variables were not associated with postoperative improvement in olfaction. CONCLUSIONS Patients with severe olfactory dysfunction were more likely to have mucosal eosinophilia and basement membrane thickening on ethmoid histopathologic examination compared to normosmics. The presence of specific histologic inflammatory findings did not however predict olfactory improvement after surgery. PMID:20819467

Histologic findings in protocol biopsies performed in stable renal allografts under different immunosuppressive schedules.

PubMed

Moreso, F; Alperovich, G; Fulladosa, X; Gil-Vernet, S; Ibernon, M; Carrera, M; Castelao, A M; Hueso, M; Grinyo, J M; Serón, D

2003-08-01

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions. Histologic findings in protocol biopsies have been related to graft outcome. We evaluated histologic lesions observed in protocol biopsies performed in patients under different immunosuppression therapies. From June 1988 a protocol biopsy was performed at approximately 4 months in patients who fulfilled the following criteria: serum creatinine <300 micromol/L; stable renal function; and proteinuria <1 g/d. Histologic lesions were graded according to 1997 Banff criteria. For the present study we considered the following groups according to immunosuppressive schedule: (i) induction therapy with polyclonal or monoclonal antilymphocytic antibodies associated with cyclosporine and prednisone (n=201); (ii) cyclosporine, mycophenolate mofetil, and prednisone (n=127); and (iii) tacrolimus, mycophenolate mofetil, and prednisone (n=51). On protocol biopsy patients treated with tacrolimus displayed a lower acute score (0.61+/-1.01 vs 1.24+/-1.23 in group I, 1.28+/-1.41 in group II; P<.0001) and a higher proportion of normal biopsies (57.1% vs 41.9% in group I, 45.1% in group II; P=.016). A similar proportion of chronic lesions (chronic score of group I: 1.30+/-1.56; group II: 1.34+/-1.80; group III: 1.51+/-0.95; P=NS) was observed in the three groups. Protocol biopsies displayed fewer acute lesions in patients treated with tacrolimus. This result suggests that the efficacy of new immunosuppression schedules can be evaluated using the protocol biopsy as a surrogate marker of graft outcome.

NK1.1+ cells promote sustained tissue injury and inflammation after trauma with hemorrhagic shock.

PubMed

Chen, Shuhua; Hoffman, Rosemary A; Scott, Melanie; Manson, Joanna; Loughran, Patricia; Ramadan, Mostafa; Demetris, Anthony J; Billiar, Timothy R

2017-07-01

Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1 + cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1 + cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1 + cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1 + cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut. © Society for Leukocyte Biology.

Characterization of Retinal Vascular and Neural Damage in a Novel Model of Diabetic Retinopathy.

PubMed

Weerasekera, Lakshini Y; Balmer, Lois A; Ram, Ramesh; Morahan, Grant

2015-06-01

Diabetic retinopathy (DR) is a major cause of blindness globally. Investigating the underlying mechanisms of DR would be aided by a suitable mouse model that developed key features seen in the human disease, and did so without carrying genetic modifications. This study was undertaken to produce such a model. Our panel of Collaborative Cross strains was screened for DR-like features after induction of diabetes by intravenous injection with alloxan or streptozotocin. Both flat-mounted whole-retina and histologic sections were studied for the presence of retinal lesions. Progression of DR was also studied by histologic examination of the retinal vascular and neural structure at various time points after diabetes onset. In addition, microarray investigations were conducted on retinas from control and diabetic mice. Features of DR such as degenerated pericytes, acellular capillaries, minor vascular proliferation, gliosis of Müller cells, and loss of ganglion cells were noted as early as day 7 in some mice. These lesions became more evident with time. After 21 days of diabetes, severe vascular proliferation, microaneurysms, preretinal damage, increased Müller cell gliosis, and damage to the outer retina were all obvious. Microarray studies found significant differential expression of multiple genes known to be involved in DR. The FOT_FB strain provides a useful model to investigate the pathogenesis of DR and to develop treatments for this vision-threatening disease.

Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized [1-(13)C]pyruvate.

PubMed

Josan, Sonal; Billingsley, Kelvin; Orduna, Juan; Park, Jae Mo; Luong, Richard; Yu, Liqing; Hurd, Ralph; Pfefferbaum, Adolf; Spielman, Daniel; Mayer, Dirk

2015-12-01

To facilitate diagnosis and staging of liver disease, sensitive and non-invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized (13)C-pyruvate to assess metabolic parameters in a CCl4 model of liver damage in rats. Dynamic 3D (13)C chemical shift imaging data from a volume covering kidney and liver were acquired from 8 control and 10 CCl4-treated rats. At 12 time points at 5 s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine, and lactate. These measurements were compared with standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl4-treated but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with these results, metabolic imaging revealed an increased alanine/pyruvate ratio in liver of CCl4-treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl4-treated compared with control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using (13)C-pyruvate can be a successful tool to non-invasively assess liver damage in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Comparison of a combination diode laser and radiofrequency device (Polaris) and a long-pulsed 1064-nm Nd:YAG laser (Lyra) on leg telangiectases. Histologic and immunohistochemical analysis.

PubMed

Prieto, Victor; Zhang, Peter; Sadick, Neil S

2006-12-01

Several devices have been proposed for the treatment of leg telangiectases. For most of these devices the histologic changes induced in the dermis are not well characterized. Three volunteers with class I-II red and blue 0.1-2.0 mm leg telangiectases were treated with the Lyra (Laserscope, San Jose, CA, USA) and the Polaris (Syneron Medical Ltd, Yokneam, Israel) devices to the left and right legs, respectively. Two 3-mm punches were taken from either site 7 days after treatment. The specimens were routinely processed and also stained for elastic tissue and collagen tissue. After treatment, specimens treated with both the Polaris and the Lyra showed intermediate-sized vessels with complete thrombosis and extensive hemorrhage in both the dermis and subcutis. The overlying epidermis also evidenced damage characterized as focal full-thickness necrosis. Special stains confirmed the damage to the vessels. All other skin structures were morphologically unremarkable. An average of 50-75% clinical clearing occurred using both modalities of a single treatment session. Our study confirms that both devices result in severe damage to small, intermediate-sized vessels, thus explaining the reported clinical improvement of leg telangiectases. The expression of hsp70 in the dermal vessels and overlying epidermis is consistent with a direct thermal effect delivered by either device.

Double Pass 595 nm Pulsed Dye Laser Does Not Enhance the Efficacy of Port Wine Stains Compared with Single Pass: A Randomized Comparison with Histological Examination.

PubMed

Yu, Wenxin; Zhu, Jiafang; Wang, Lizhen; Qiu, Yajing; Chen, Yijie; Yang, Xi; Chang, Lei; Ma, Gang; Lin, Xiaoxi

2018-03-27

To compare the efficacy and safety of double-pass pulsed dye laser (DWL) and single-pass PDL (SWL) in treating virgin port wine stain (PWS). The increase in the extent of vascular damage attributed to the use of double-pass techniques for PWS remains inconclusive. A prospective, side-by-side comparison with a histological study for virgin PWS is still lacking. Twenty-one patients (11 flat PWS, 10 hypertrophic PWS) with untreated PWS underwent 3 treatments at 2-month intervals. Each PWS was divided into three treatment sites: SWL, DWL, and untreated control. Chromametric and visual evaluation of the efficacy and evaluation of side effects were conducted 3 months after final treatment. Biopsies were taken at the treated sites immediately posttreatment. Chromametric and visual evaluation suggested that DWL sites showed no significant improvement compared with SWL (p > 0.05) in treating PWS. The mean depth of photothermal damage to the vessels was limited to a maximum of 0.36-0.41 mm in both SWL and DWL sides. Permanent side effects were not observed in any patients. Double-pass PDL does not enhance PWS clearance. To improve the clearance of PWS lesions, either the depth of laser penetration should be increased or greater photothermal damage to vessels should be generated.

Hepatic fat quantification using the two-point Dixon method and fat color maps based on non-alcoholic fatty liver disease activity score.

PubMed

Hayashi, Tatsuya; Saitoh, Satoshi; Takahashi, Junji; Tsuji, Yoshinori; Ikeda, Kenji; Kobayashi, Masahiro; Kawamura, Yusuke; Fujii, Takeshi; Inoue, Masafumi; Miyati, Tosiaki; Kumada, Hiromitsu

2017-04-01

The two-point Dixon method for magnetic resonance imaging (MRI) is commonly used to non-invasively measure fat deposition in the liver. The aim of the present study was to assess the usefulness of MRI-fat fraction (MRI-FF) using the two-point Dixon method based on the non-alcoholic fatty liver disease activity score. This retrospective study included 106 patients who underwent liver MRI and MR spectroscopy, and 201 patients who underwent liver MRI and histological assessment. The relationship between MRI-FF and MR spectroscopy-fat fraction was used to estimate the corrected MRI-FF for hepatic multi-peaks of fat. Then, a color FF map was generated with the corrected MRI-FF based on the non-alcoholic fatty liver disease activity score. We defined FF variability as the standard deviation of FF in regions of interest. Uniformity of hepatic fat was visually graded on a three-point scale using both gray-scale and color FF maps. Confounding effects of histology (iron, inflammation and fibrosis) on corrected MRI-FF were assessed by multiple linear regression. The linear correlations between MRI-FF and MR spectroscopy-fat fraction, and between corrected MRI-FF and histological steatosis were strong (R 2  = 0.90 and R 2  = 0.88, respectively). Liver fat variability significantly increased with visual fat uniformity grade using both of the maps (ρ = 0.67-0.69, both P < 0.001). Hepatic iron, inflammation and fibrosis had no significant confounding effects on the corrected MRI-FF (all P > 0.05). The two-point Dixon method and the gray-scale or color FF maps based on the non-alcoholic fatty liver disease activity score were useful for fat quantification in the liver of patients without severe iron deposition. © 2016 The Japan Society of Hepatology.

O-GlcNAcylation in oral squamous cell carcinoma.

PubMed

Kongkaew, Tassaporn; Aung, Win Pa Pa; Supanchart, Chayarop; Makeudom, Anupong; Langsa-Ard, Sarawat; Sastraruji, Thanapat; Chaiyarit, Ponlatham; Krisanaprakornkit, Suttichai

2018-03-01

Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading. Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFR tyr1173 , and anti-phosphorylated-Akt ser473 antibodies following standard immunohistochemistry. The immunohistochemical (IHC) score was determined using the Fromowitz standard. Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody. The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFR tyr1173 and phosphorylated-Akt ser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively). Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFR tyr1173 and phosphorylated-Akt ser473 (P < .01 and P < .001, respectively). The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading. Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Health Effects of Exposure to Water-Damaged New Orleans Homes Six Months After Hurricanes Katrina and Rita

PubMed Central

Cummings, Kristin J.; Cox-Ganser, Jean; Riggs, Margaret A.; Edwards, Nicole; Hobbs, Gerald R.; Kreiss, Kathleen

2008-01-01

Objectives. We investigated the relation between respiratory symptoms and exposure to water-damaged homes and the effect of respirator use in posthurricane New Orleans, Louisiana. Methods. We randomly selected 600 residential sites and then interviewed 1 adult per site. We created an exposure variable, calculated upper respiratory symptom (URS) and lower respiratory symptom (LRS) scores, and defined exacerbation categories by the effect on symptoms of being inside water-damaged homes. We used multiple linear regression to model symptom scores (for all participants) and polytomous logistic regression to model exacerbation of symptoms when inside (for those participating in clean-up). Results. Of 553 participants (response rate=92%), 372 (68%) had participated in clean-up; 233 (63%) of these used a respirator. Respiratory symptom scores increased linearly with exposure (P<.05 for trend). Disposable-respirator use was associated with lower odds of exacerbation of moderate or severe symptoms inside water-damaged homes for URS (odds ratio (OR)=.51; 95% confidence interval (CI)=0.24, 1.09) and LRS (OR=0.33; 95% CI=0.13, 0.83). Conclusions. Respiratory symptoms were positively associated with exposure to water-damaged homes, including exposure limited to being inside without participating in clean-up. Respirator use had a protective effect and should be considered when inside water-damaged homes regardless of activities undertaken. PMID:18381997

Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

PubMed Central

Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

2006-01-01

AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage.

PubMed

Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

2006-07-21

To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

The effect of nonablative laser energy on joint capsular properties. An in vitro histologic and biochemical study using a rabbit model

NASA Technical Reports Server (NTRS)

Hayashi, K.; Thabit, G. 3rd; Vailas, A. C.; Bogdanske, J. J.; Cooley, A. J.; Markel, M. D.

1996-01-01

The purpose of this study was to evaluate the effect of laser energy at nonablative levels on joint capsular histologic and biochemical properties in an in vitro rabbit model. The medial and lateral portions of the femoropatellar joint capsule from both stifles of 12 mature New Zealand White rabbits were used. Specimens were divided into three treatment groups (5 watts, 10 watts, and 15 watt) and one control group using a randomized block design. Specimens were placed in a 37 degrees bath of lactated Ringer's solution and laser energy was applied using a holmium:yttrium-aluminum-garnet laser in four transverse passes across the tissue at a velocity of 2 mm/sec with the handpiece set 1.5 mm from the synovial surface. Histologic analysis revealed thermal alteration of collagen (fusion) and fibroblasts (pyknosis) at all energy densities, with higher laser energy causing significantly greater morphologic changes over a larger area (P < 0.05). Application of laser energy did not significantly alter the biochemical parameters evaluated, including type I collagen content and nonreducible crosslinks (P > 0.05). This study demonstrated that nonablative laser energy caused significant thermal damage to the joint capsular tissue in an energy-dependent fashion, but type I collagen content and nonreducible crosslinks (P > 0.05). This study demonstrated that nonablative laser energy caused significant thermal damage to the joint capsular tissue in an energy-dependent fashion, but type I Collagen content and nonreducible corsslinks were not significantly altered.

Immunephenotype of glomerular and interstitial infiltrating cells in protocol renal allograft biopsies and histological diagnosis.

PubMed

Moreso, F; Seron, D; O'Valle, F; Ibernon, M; Gomà, M; Hueso, M; Cruzado, J M; Bestard, O; Duarte, V; del Moral, R García; Grinyó, J M

2007-12-01

Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 +/- 117), SCR (202 +/- 145), IF/TA (208 +/- 151) and IF/TA + SCR (307 +/- 180 cells/mm(2)), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23-7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

Effects of vertebral column distraction on transcranial electrical stimulation-motor evoked potential and histology of the spinal cord in a porcine model.

PubMed

Yang, Jae Hyuk; Suh, Seung Woo; Modi, Hitesh N; Ramani, Easwar T; Hong, Jae Young; Hwang, Jin Ho; Jung, Woon Yong

2013-05-01

Spinal cord injury can occur following surgical procedures for correction of scoliosis and kyphosis, as these procedures produce lengthening of the vertebral column. The objective of this study was to cause spinal cord injury by vertebral column distraction and evaluate the histological changes in the spinal cord in relationship to the pattern of recovery from the spinal cord injury. Global osteotomy of all three spinal columns was performed on the ninth thoracic vertebra of sixteen pigs. The osteotomized vertebra was distracted until transcranial electrical stimulation-motor evoked potential (TES-MEP) signals disappeared or decreased by >80% compared with the baseline amplitude; this was defined as spinal cord injury. The distraction distance at which spinal cord injury occurred was measured, the distraction was released, and the TES-MEP recovery pattern was observed. A wake-up test was performed, two days of observations were made, and histological changes were evaluated in relationship to the recovery pattern. Spinal cord injury developed at a distraction distance of 20.2 ± 4.7 mm, equivalent to 3.6% of the thoracolumbar spinal length, and the distraction distance was correlated with the thoracolumbar spinal length (r = 0.632, p = 0.009). No animals exhibited complete recovery according to TES-MEP testing, eleven exhibited incomplete recovery, and five exhibited no recovery. During the two days of observation, all eleven animals with incomplete recovery showed positive responses to sensory and motor tests, whereas none of the five animals with no recovery had positive responses. On histological evaluation, three animals that exhibited no recovery all showed complete severance of nerve fibers (axotomy), whereas six animals that exhibited incomplete recovery all showed partial white-matter injury. Parallel distraction of approximately 3.6% of the thoracolumbar length after global osteotomy resulted in spinal cord injury and histological evidence of spinal cord damage. The pattern of recovery from the spinal cord injury after release of the distraction was consistent with the degree of axonal damage. Axotomy was observed in animals that exhibited no recovery on TES-MEP, and only hemorrhagic changes in the white matter were observed in animals that exhibited incomplete recovery.

Near-infared hyperspectral imaging of teeth for dental caries detection

NASA Astrophysics Data System (ADS)

Zakian, Christian; Pretty, Iain; Ellwood, Roger

2009-11-01

Near-infrared (NIR) is preferred for caries detection compared to visible light imaging because it exhibits low absorption by stain and deeper penetration into teeth. Hyperspectral images from 1000 to 2500 nm have been obtained for a total of 12 extracted teeth (premolars and molars) with different degrees of natural lesion. Analysis of the reflectance spectra suggests that light scattering by porous enamel and absorption by water in dentin can be used to quantify the lesion severity and generate a NIR caries score. Teeth were ground for histological examination after the measurements. The NIR caries score obtained correlates significantly (Spearman's correlation of 0.89, p<0.01) with the corresponding histological score. Results yield a sensitivity of >99% and a specificity of 87.5% for enamel lesions and a sensitivity of 80% and a specificity >99% for dentine lesions. The nature of the technique offers significant advantages, including the ability to map the lesion distribution rather than obtaining single-point measurements, it is also noninvasive, noncontact, and stain insensitive. These results suggest that NIR spectral imaging is a potential clinical technique for quantitative caries diagnosis and can determine the presence of occlusal enamel and dentin lesions.

Near-infrared hyperspectral imaging of teeth for dental caries detection.

PubMed

Zakian, Christian; Pretty, Iain; Ellwood, Roger

2009-01-01

Near-infrared (NIR) is preferred for caries detection compared to visible light imaging because it exhibits low absorption by stain and deeper penetration into teeth. Hyperspectral images from 1000 to 2500 nm have been obtained for a total of 12 extracted teeth (premolars and molars) with different degrees of natural lesion. Analysis of the reflectance spectra suggests that light scattering by porous enamel and absorption by water in dentin can be used to quantify the lesion severity and generate a NIR caries score. Teeth were ground for histological examination after the measurements. The NIR caries score obtained correlates significantly (Spearman's correlation of 0.89, p<0.01) with the corresponding histological score. Results yield a sensitivity of >99% and a specificity of 87.5% for enamel lesions and a sensitivity of 80% and a specificity >99% for dentine lesions. The nature of the technique offers significant advantages, including the ability to map the lesion distribution rather than obtaining single-point measurements, it is also noninvasive, noncontact, and stain insensitive. These results suggest that NIR spectral imaging is a potential clinical technique for quantitative caries diagnosis and can determine the presence of occlusal enamel and dentin lesions.

Effects of chronic copper exposure during early life in rhesus monkeys.

PubMed

Araya, Magdalena; Kelleher, Shannon L; Arredondo, Miguel A; Sierralta, Walter; Vial, María Teresa; Uauy, Ricardo; Lönnerdal, Bo

2005-05-01

Whether infants regulate copper absorption and the potential effects of excess copper in early life remain poorly defined. The objective of the study was to assess copper retention, liver copper content, and liver function in infant rhesus monkeys fed infant formula containing 6.6 mg Cu/L. From birth to 5 mo of age, infant rhesus monkeys were fed formula that was supplemented with copper (0.6 mg Cu/L; n = 5) or not supplemented (n = 4). In all animals, weight and crown-rump length (by anthropometry), hemoglobin, hematocrit, plasma ceruloplasmin activity, and zinc and copper concentrations were measured monthly (birth to 6 mo) and at 8 and 12 mo. When the animals were 1, 5, and 8 mo old, liver copper and metallothionein concentrations, liver histology (by light and electron microscopy), and the number of Kupffer cells were assessed, and 67Cu retention was measured. Liver function was assessed by measurement of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activities and protein, albumin, bilirubin, and blood urea nitrogen concentrations. 67Cu retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with approximately 75% in controls at age 2 mo. At age 8 mo, 67Cu retention was 22.9% in copper-treated animals and 31.5% in controls. Liver histology remained normal by light microscopy, with mild ultrastructural signs of cell damage at 5 mo. Liver copper concentration was 4711, 1139, and 498 microg/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microg/g at 2 mo in controls. Measurements could not be completed in all animals. No clinical evidence of copper toxicity was observed. Copper absorption was down-regulated; increases in liver copper content at ages 1 and 5 mo did not result in histologic damage. Ultrastructural changes at age 5 mo could signal early cellular damage.

Transcriptomics, metabolomics and histology indicate that high-carbohydrate diet negatively affects the liver health of blunt snout bream (Megalobrama amblycephala).

PubMed

Prisingkorn, Wassana; Prathomya, Panita; Jakovlić, Ivan; Liu, Han; Zhao, Yu-Hua; Wang, Wei-Min

2017-11-09

Global trend of the introduction of high levels of relatively cheap carbohydrates to reduce the amount of costly protein in the aquatic animal feed production has affected the aquaculture of an economically important cyprinid fish, blunt snout bream (Megalobrama amblycephala). This dietary shift has resulted in increased prevalence of metabolic disorders, often causing economic losses. High dietary intake of carbohydrates, associated with obesity, is one of the major causes of non-alcoholic fatty liver disease (NAFLD) in humans. We have conducted an eight-week feeding trial to better understand how a high-carbohydrate diet (HCBD) affects the liver health in this fish. Hepatosomatic index and lipid content were significantly (P < 0.05) higher in the HCBD group. Histology results also suggested pathological changes in the livers of HCBD group, with excessive lipid accumulation and indication of liver damage. Metabolomics and serum biochemistry analyses showed that a number of metabolites indicative of liver damage were increased in the HCBD group. This group also exhibited low levels of betaine, which is a metabolite crucial for maintaining the healthy liver functions. Transcriptomic and qPCR analyses indicated that HCBD had a strong impact on the expression of a large number of genes associated with the NAFLD and insulin signalling pathways, which may lead to the development of insulin resistance in hepatocytes, pathological liver changes, and eventually the NAFLD. Transcriptomics, metabolomics and histology results all indicate early symptoms of liver damage. However whether these would actually lead to the development of NAFLD after a longer period of time, remains inconclusive. Additionally, a very high number of upregulated genes in the HCBD group associated with several neurodegenerative diseases is a strong indication of neurodegenerative changes caused by the high-carbohydrate diet in blunt snout bream. This suggests that fish might present a good model to study neurodegenerative changes associated with high-carbohydrate diet in humans.

Effects of Korean Red Ginseng extract on busulfan-induced dysfunction of the male reproductive system.

PubMed

Jung, Seok-Won; Kim, Hyeon-Joong; Lee, Byung-Hwan; Choi, Sun-Hye; Kim, Hyun-Sook; Choi, Yang-Kyu; Kim, Joon Yong; Kim, Eun-Soo; Hwang, Sung-Hee; Lim, Kwang Yong; Kim, Hyoung-Chun; Jang, Minhee; Park, Seong Kyu; Cho, Ik-Hyun; Nah, Seung-Yeol

2015-07-01

Anticancer agents induce a variety of adverse effects when administered to cancer patients. Busulfan is a known antileukemia agent. When administered for treatment of leukemia in young patients, busulfan could cause damage to the male reproductive system as one of its adverse effects, resulting in sterility. We investigated the effects of Korean Red Ginseng extract (KRGE) on busulfan-induced damage and/or dysfunction of the male reproductive system. We found that administration of busulfan to mice: decreased testis weight; caused testicular histological damage; reduced the total number of sperm, sperm motility, serum testosterone concentration; and eventually, litter size. Preadministration of KRGE partially attenuated various busulfan-induced damages to the male reproductive system. These results indicate that KRGE has a protective effect against busulfan-induced damage to the male reproduction system. The present study shows a possibility that KRGE could be applied as a useful agent to prevent or protect the male reproductive system from the adverse side effects induced by administration of anticancer agents such as busulfan.

Modified stoke ankylosing spondylitis spinal score as an outcome measure to assess the impact of treatment on structural progression in ankylosing spondylitis.

PubMed

van der Heijde, Désirée; Braun, Jürgen; Deodhar, Atul; Baraliakos, Xenofon; Landewé, Robert; Richards, Hanno B; Porter, Brian; Readie, Aimee

2018-05-30

In ankylosing spondylitis (AS), structural damage that occurs as a result of syndesmophyte formation and ankylosis of the vertebral column is irreversible. Structural damage is currently assessed by conventional radiography and scoring systems that reliably assess radiographic structural damage are needed to capture the differential effects of drugs on structural damage progression. The validity of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) as a primary outcome measure in evaluating the effect of AS treatments on radiographic progression rates was assessed in this review. The mSASSS has not been used, to date, as a primary outcome measure in a prospective randomized controlled clinical trial of biologic therapy in AS. This review of the medical literature confirmed that the mSASSS is the most validated and widely used method for assessing radiographic progression in AS, correlating with worsening measures of disease signs and symptoms, spinal mobility and physical function, with a 2-year interval being required to ensure sufficient sensitivity to change.

Organizational strategy influence on visual memory performance after stroke: cortical/subcortical and left/right hemisphere contrasts.

PubMed

Lange, G; Waked, W; Kirshblum, S; DeLuca, J

2000-01-01

To examine how organizational strategy at encoding influences visual memory performance in stroke patients. Case control study. Postacute rehabilitation hospital. Stroke patients with right hemisphere damage (n = 20) versus left hemisphere damage (n = 15), and stroke patients with cortical damage (n = 11) versus subcortical damage (n = 19). Organizational strategy scores, recall performance on the Rey-Osterrieth Complex Figure (ROCF). Results demonstrated significantly greater organizational impairment and less accurate copy performance (i.e., encoding of visuospatial information on the ROCF) in the right compared to the left hemisphere group, and in the cortical relative to the subcortical group. Organizational strategy and copy accuracy scores were significantly related to each other. The absolute amount of immediate and delayed recall was significantly associated with poor organizational strategy scores. However, relative to the amount of visual information originally encoded, memory performances did not differ between groups. These findings suggest that visual memory impairments after stroke may be caused by a lack of organizational strategy affecting information encoding, rather than an impairment in memory storage or retrieval.

Impact of storage conditions on electromechanical, histological and histochemical properties of osteochondral allografts.

PubMed

Mickevicius, Tomas; Pockevicius, Alius; Kucinskas, Audrius; Gudas, Rimtautas; Maciulaitis, Justinas; Noreikaite, Aurelija; Usas, Arvydas

2015-10-23

Osteochondral allograft transplantation has a good clinical outcome, however, there is still debate on optimization of allograft storage protocol. Storage temperature and nutrient medium composition are the most critical factors for sustained biological activity of grafts before implantation. In this study, we performed a time-dependent in vitro experiment to investigate the effect of various storage conditions on electromechanical, histological and histochemical properties of articular cartilage. Osteochondral grafts derived from goat femoral condyles were frozen at -70 °C or stored at 4 °C and 37 °C in the medium supplemented with or without insulin-like growth factor-1 (IGF-1). After 14 and 28 days the cartilage samples were quantitatively analysed for electromechanical properties, glycosaminoglycan distribution, histological structure, chondrocyte viability and apoptosis. The results were compared between the experimental groups and correlations among different evaluation methods were determined. Storage at -70 °C and 37 °C significantly deteriorated cartilage electromechanical, histological and histochemical properties. Storage at 4 °C maintained the electromechanical quantitative parameter (QP) and glycosaminoglycan expression near the normal levels for 14 days. Although hypothermic storage revealed reduced chondrocyte viability and increased apoptosis, these parameters were superior compared with the storage at -70 °C and 37 °C. IGF-1 supplementation improved the electromechanical QP, chondrocyte viability and histological properties at 37 °C, but the effect lasted only 14 days. Electromechanical properties correlated with the histological grading score (r = 0.673, p < 0.001), chondrocyte viability (r = -0.654, p < 0.001) and apoptosis (r = 0.416, p < 0.02). In addition, apoptosis correlated with glycosaminoglycan distribution (r = -0.644, p < 0.001) and the histological grading score (r = 0.493, p = 0.006). Our results indicate that quality of allografts is better preserved at currently established 4 °C storage temperature. Storage at -70 °C or at 37 °C is unable to maintain cartilage function and metabolic activity. IGF-1 supplementation at 37 °C can enhance chondrocyte viability and improve electromechanical and histological properties of the cartilage, but the impact persists only 14 days. The correlations between cartilage electromechanical quantitative parameter (QP) and metabolic activity were detected. Our findings indicate that non-destructive assessment of cartilage by Arthro-BST is a simple and reliable method to evaluate allograft quality, and could be routinely used before implantation.

Histology Verification Demonstrates That Biospectroscopy Analysis of Cervical Cytology Identifies Underlying Disease More Accurately than Conventional Screening: Removing the Confounder of Discordance

PubMed Central

Gajjar, Ketan; Ahmadzai, Abdullah A.; Valasoulis, George; Trevisan, Júlio; Founta, Christina; Nasioutziki, Maria; Loufopoulos, Aristotelis; Kyrgiou, Maria; Stasinou, Sofia Melina; Karakitsos, Petros; Paraskevaidis, Evangelos; Da Gama-Rose, Bianca; Martin-Hirsch, Pierre L.; Martin, Francis L.

2014-01-01

Background Subjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation. Methods Within a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn’s test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease. Results Conventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening. Scores plots of IR spectra exhibit marked crossover of spectral points between different cytological categories. Although, significant differences between spectral bands in different categories are noted, crossover samples point to the potential for poor specificity and hampers the development of biospectroscopy as a diagnostic tool. However, when histology-based categories are used to conduct analyses, the scores plot of IR spectra exhibit markedly better segregation. Conclusions Histology demonstrates that ATR-FTIR spectroscopy of liquid-based cytology identifies the presence of underlying atypia or disease missed in conventional cytology screening. This study points to an urgent need for a future biospectroscopy study where categories are based on such histology. It will allow for the validation of this approach as a screening tool. PMID:24404130

Antioxidant Protective Effect of Honey in Cigarette Smoke-Induced Testicular Damage in Rats

PubMed Central

Mohamed, Mahaneem; Sulaiman, Siti Amrah; Jaafar, Hasnan; Sirajudeen, Kuttulebbai Nainamohamed Salam

2011-01-01

Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis. PMID:22016605

Antioxidant protective effect of honey in cigarette smoke-induced testicular damage in rats.

PubMed

Mohamed, Mahaneem; Sulaiman, Siti Amrah; Jaafar, Hasnan; Sirajudeen, Kuttulebbai Nainamohamed Salam

2011-01-01

Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis.

Wistar rats immature testicular tissue vitrification and heterotopic grafting.

PubMed

Benvenutti, Larissa; Salvador, Rafael Alonso; Til, David; Senn, Alfred Paul; Tames, David Rivero; Amaral, Nicole Louise Lângaro; Amaral, Vera Lúcia Lângaro

2018-04-25

To evaluate the efficiency of two vitrification protocols for rat immature testicular tissue and heterotopic transplantation. Twenty-four pre-pubertal Wistar rats were divided into three groups (n=8). After orchiectomy, testicular fragments (3mm) from Groups 1 and 2 were vitrified with different cryoprotectant concentration solutions, using sterile inoculation loops as support. After warming up, the fragments were submitted to cell viability assessment by Trypan blue and histological evaluation. Vitrified (Groups 1 and 2) and fresh (Group 3) fragments were grafted to the animals periauricular region. After 8 weeks of grafting, the implant site was histologically analyzed. The viability recovery rate from Group 1 (72.09%) was higher (p=0.02) than that from Group 2 (59.19%). Histological analysis showed similar tubular integrity between fresh fragments from Groups 1 and 3. Group 2 samples presented lower tubular integrity. We ran histological analyses in the grafts from the Groups. In all groups, it was possible to see the implant site, however, no fragment of testicular tissue or signs of inflammation were histologically found in most samples from Groups 1 and 3. In one sample from Group 2, we found degenerated seminiferous tubules with necrosis and signs of an inflammatory process. In another sample from Group 2, we found seminiferous tubules in the implant site. The vitrification of pre-pubertal testicular tissue of rats showed little damage to cell viability through histological analysis when we used cryoprotectants in a lower concentration. Heterotopic transplantation could not preserve the structural organization of the testicular tissue.

Asymmetric Macular Structural Damage Is Associated With Relative Afferent Pupillary Defects in Patients With Glaucoma

PubMed Central

Gracitelli, Carolina P. B.; Tatham, Andrew J.; Zangwill, Linda M.; Weinreb, Robert N.; Abe, Ricardo Y.; Diniz-Filho, Alberto; Paranhos, Augusto; Baig, Saif; Medeiros, Felipe A.

2016-01-01

Purpose We examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma. Methods A cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression. Results There was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R2 = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R2 = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R2 = 0.350, P < 0.001) and SAP MD (R2 = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness. Conclusions Objective assessment of pupillary responses using a pupillometer was associated with asymmetric macular structural damage in patients with glaucoma. PMID:27064394

Mechanical and histological characterization of trachea tissue subjected to blast-type pressures

NASA Astrophysics Data System (ADS)

Butler, B. J.; Bo, C.; Tucker, A. W.; Jardine, A. P.; Proud, W. G.; Williams, A.; Brown, K. A.

2014-05-01

Injuries to the respiratory system can be a component of polytrauma in blast-loading injuries. Tissues located at air-liquid interfaces, including such tissues in the respiratory system, are particularly vulnerable to damage by blast overpressures. There is a lack of information about the mechanical and cellular responses that contribute to the damage of this class of tissues subjected to the high strain rates associated with blast loading. Here, we describe the results of dynamic blast-like pressure loading tests at high strain rates on freshly harvested ex vivo trachea tissue specimens.

Assessment of Biomarkers Associated with Joint Injury and Subsequent Post-Traumatic Arthritis

DTIC Science & Technology

2014-10-01

synovitis score with semi-quantitative scales, and osteophyte score6-10. Parametric analyses were performed for bone morphological measures and...histological assessment. Subchondral bone thickening was significantly increased in the C57BL/6 mice compared to the MRL/MpJ mice in the medial femur (p...biochemical and metabolic data. J Bone Joint Surg Am. 53:523-537. 10. Gelse K, Soder S, Eger W, Diemtar T, Aigner T. Feb 2003. Osteophyte development

Long-term results of biopsy-guided selection and allocation of kidneys from older donors in older recipients.

PubMed

Fernández-Lorente, L; Riera, L; Bestard, O; Carrera, M; Gomà, M; Porta, N; Torras, J; Melilli, E; Gil-Vernet, S; Grinyó, J M; Cruzado, J M

2012-10-01

In our old-for-old program, we discard or allocate older extended criteria donor kidneys to single (SKT) or dual kidney transplantation (DKT) depending on histological Remuzzi's score in recipients older than 60 years. Here, we analyze the long-term results of this program and try to identify independent predictors of patient and graft survival. Between December 1996 and January 2008, we performed 115 SKT and 88 DKT. Discard rate was 15%. Acute rejection incidence was higher in SKT than in DKT (22.6% vs. 11.4%, p = 0.04). Renal function was better in DKT than in SKT up to 5 years after transplantation. Surgical complications were frequent in DKT. Ten-year cumulative graft survival was significantly lower in the SKT group (31% vs. 53%, p = 0.03). In SKT, histological score 4 provided similar graft survival than 3 or less, whereas in DKT score 4, 5 or 6 displayed similar outcome. Finally, independent predictors of graft survival were history of major adverse cardiac event and 1-year serum creatinine, rather than SKT or DKT. In conclusion, this biopsy-guided old-for-old strategy resulted in acceptable long-term graft survival. Our results suggest that DKT should be considered for scores of 5 or 6 only. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Relationship between areas of popliteal cysts and radiological damage in rheumatoid arthritis and in osteoarthritis.

PubMed

Manganelli, P; Salaffi, F; Nervetti, A; Chierici, P; Ferraccioli, G F; Ambanelli, U

1987-01-01

Fifty-five patients, (30 Rheumatoid Arthritis (RA) and 25 Osteoarthritis (OA], with knee synovial effusion and popliteal cysts, visualized through arthrograms, were studied. A relationship was sought between radiological findings and area of the cysts, measured through a millimeter grid. Ten radiological parameters were graded and summed up to obtain a "total knee score". A "total geode score" was also obtained by scoring, separately, the geodes. In addition two specific indexes were used--for comparison--the erosive index, modified after Berens and Lin, in RA and the Kelligren's index in OA. In RA a statistically significant, inverse correlation was found between the x-ray scores and the area of the cysts, while such a relationship was not observed in OA. However, only a third of the cysts accounted for the inverse relationship in RA. Furthermore, two control groups of RA and OA patients revealed a striking association between degree of radiological damage and frequency of popliteal cysts. Therefore, the hypothesis that popliteal cysts might have a protective effect against the articular-bone damage in RA, can be held only in few cases.

Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

PubMed Central

Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

2016-01-01

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC’s efficacy and mechanism of action. Results: ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. Conclusions: ARC treatment confers neuroprotection of brain tissue through anti-inflammatory and anti-apoptotic effects in a mouse model of SWI. These results suggest a new strategy for promoting neuronal survival and function after CED to improve long-term patient outcome. PMID:27445818

Protective effects of dexpanthenol in an experimental model of necrotizing enterocolitis.

PubMed

Karadag, Ahmet; Ozdemir, Ramazan; Kurt, Ahmet; Parlakpinar, Hakan; Polat, Alaadin; Vardi, Nigar; Taslidere, Elif; Karaman, Abdurrahman

2015-07-01

In pathogenesis of necrotizing enterocolitis (NEC), both oxidative stress and inflammation are considerable risk factors. The study was designed to evaluate whether administration of dexpanthenol (Dxp) is able to attenuate intestinal injury through the antioxidant and antiinflammatory mechanisms in a neonatal rat model of NEC. Forty newborn pups divided into four groups were included in the study: control, control+Dxp, NEC, and NEC+Dxp. NEC was induced by hyperosmolar formula and additionally the pups were exposed to hypoxia/hyperoxia and cold stress. They were sacrificed on postnatal day four, and their intestinal tissues were analyzed biochemically and histopathologically. Dxp caused a significant decrease in intestinal damage as determined by the histological score, villus height and number of goblet cells in NEC groups (p<0.0001). Tissue malondialdehyde, total oxidant status, and oxidative stress indexes levels were higher in the NEC group than in the control and control+Dxp groups (p<0.001). These values were reduced in the pups treated with Dxp (p≤0.004). Superoxide dismutase, glutathione peroxidase, and reduced glutathione activities were significantly reduced in the NEC group compared to the others (p<0.005). Treatment with Dxp significantly reduced elevations in tissue homogenate levels of tumor necrosis factor-α and interleukin-1β in the NEC+Dxp group (p=0.002 and p=0.01, respectively). Dexpanthenol seems to have antiinflammatory and antioxidant properties. Prophylaxis with Dxp has a potential to reduce the severity of intestinal damage in NEC in the animals. Copyright © 2015 Elsevier Inc. All rights reserved.

8-oxo-7,8-dihydroguanine level - the DNA oxidative stress marker - recognized by fluorescence image analysis in sporadic uterine adenocarcinomas in women.

PubMed

Postawski, Krzysztof; Przadka-Rabaniuk, Dorota; Piersiak, Tomasz

2013-01-01

In the case of carcinogenesis in human endometrium no information exists on tissue concentration of 8-oxo-7,8-dihydroguanine, the DNA oxidative stress marker This was the main reason to undertake the investigation of this DNA modification in human uterine estrogen-dependent tissue cancers. In order to estimate the level of oxidative damage, 8-oxo-7,8-dihydroguanine was determined directly in cells of tissue microscope slides using OxyDNA Assay Kit, Fluorometric. Cells were investigated under confocal microscope. Images of individual cells were captured by computer-interfaced digital photography and analyzed for fluorescence intensities (continuous inverted 8-bit gray-scale = 0 [black]-255 [white]). Fluorescence scores were calculated for each of 13 normal endometrial samples and 31 uterine adenocarcinoma specimens. Finally the level of the oxidative stress marker was also analyzed according to histological and clinical features of the neoplasms. The obtained data revealed that: 8-oxo-7,8-dihydroguanine levels were higher in uterine adenocarcinomas than in normal endometrial samples (48,32 vs. 38,64; p<0,001); in contrast to normal endometrium there was no correlation between age and DNA oxidative modification content in uterine cancer; highest mean fluorescence intensity was recognized in G2 endometrial adenocarcinomas; level of 8-oxo-7,8-dihydroguanine does not depend on Body Mass Index (BMI) and cancer uterine wall infiltration or tumor FIGO stage. Our study indicates that accumulation of the oxidized DNA base may contribute to the development of endometrial neoplasia, however oxidative DNA damage does not seem to increase with tumor progression.

Human umbilical cord-derived mesenchymal stem cells reduce monosodium iodoacetate-induced apoptosis in cartilage

PubMed Central

Chang, Yu-Hsun; Wu, Kun-Chi; Liu, Hwan-Wun; Chu, Tang-Yuan; Ding, Dah-Ching

2018-01-01

Objective: The present study investigated the therapeutic potential and underlying mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) on joint cartilage destruction induced by monosodium iodoacetate (MIA) in mice. Materials and Methods: HUCMSCs were tested for mesenchymal stem cell (MSC) characteristics including surface markers by flow cytometry and mesoderm differentiation (adipogenesis, osteogenesis, and chondrogenesis). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Western blot assay were used to evaluate MIA-induced chondrocyte apoptosis. In the in vivo study, 18 mice were divided into three groups (n = 6 each); normal saline (control), MIA-treated, and MIA-treated/HUCMSC-transplantation. Rota-Rods tests were used to evaluate MIA-induced cartilage destruction behaviors in mice. Histological changes in the mice cartilage were examined by immunohistochemistry. Results: HUCMSCs had an immunophenotype similar to bone marrow-derived MSCs and were able to differentiate into adipocytes, osteocytes, and chondrocytes. Conditioned medium of the HUCMSCs exhibited an anti-apoptotic effect and inhibited expression of caspase 3 in MIA-treated chondrocytes. HUCMSC transplantation assisted in recovery from movement impairment (from 30% on day 7 to 115% on day 14) and in regeneration and repair of cartilage damaged by MIA. (International Cartilage Repair Society score: 3.8 in the MIA group vs. 10.2 in the HUCMSC-treated group); HUCMSC transplantation ameliorated cartilage apoptosis through the caspase 3 pathway in MIA-induced cartilage destruction in mice. Conclusion: Taken together, these observations suggest that HUCMSC transplantation appears to be effective in protecting cartilage from MIA damage. PMID:29875586

Synergistic Effects of Electroacupuncture and Mesenchymal Stem Cells on Intestinal Ischemia/Reperfusion Injury in Rats.

PubMed

Geng, Yanxia; Chen, Dong; Zhou, Jiang; Lu, Jun; Chen, Mingqi; Zhang, Haidong; Wang, Xing

2016-08-01

Electroacupuncture (EA) and transplantation of bone marrow mesenchymal stem cells (MSCs) are both promising therapeutic applications for intestinal disorders. The current study examined their combined effect on rat intestinal ischemia/reperfusion (I/R) injury and the possible mechanism. Five groups were performed: con group (shame operation),I/R group (model group), MSC group (I/R + MSC), EA group (I/R + EA), and combined group (I/R + MSC + EA). Intestinal histological damage, crypt cell proliferation degree, mucosal cytokines expression, and levels of inflammation factors were studied for each group. Compared with the I/R group, crypt cell proliferation index and mucosal mRNA concentration of SDF-1, CXCR4, EGF, EGFR in MSC group and EA group were significantly increased, with mucosal NF-кBp65 and serum inflammation factor (TNF-α, IL-6) levels significantly decreased. Above all of these indicators except NF-кBp65 were improved more notably in combined group than the other two treatment groups. Chiu's score was only ameliorated remarkably in the combined group. The combined treatment of MSC transplantion and electroacupuncture could protect intestinal mucosal barrier from I/R injury.

[Limb remote ischemic preconditioning attenuates liver ischemia reperfusion injury by activating autophagy via modulating PPAR-γ pathway].

PubMed

Ruan, Wei; Liu, Qing; Chen, Chan; Li, Suobei; Xu, Junmei

2016-09-28

To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms.
 Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min-
reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC.
 At the end of reperfusion, liver injury was significantly increased (increases in Suzike's injury score, AST and ALT release), concomitant with elevated oxidative stress (increases in MDA formation, MPO activity, as well as the decrease in SOD activity) and inflammation (increases in TNF-α and IL-6 levels, decrease in IL-10 content). RIPC improved liver function and reduced histologic damage, accompanied by the increased PPAR-γ activation and autophagosome formation as well as the reduced autophagosome clearance. The beneficial effects of RIPC were markedly attenuated by T0070907, an inhibitor of PPAR-γ.
 RIPC exerts the protective effects on liver by activation of autophagy via PPAR-γ.

Prevention of Intraabdominal Adhesions by Local and Systemic Administration of Immunosuppressive Drugs

PubMed Central

Peker, Kemal; Inal, Abdullah; Sayar, Ilyas; Sahin, Murat; Gullu, Huriye; Inal, Duriye Gul; Isik, Arda

2013-01-01

Background: Intraperitoneal adhesion formation is a serious postsurgical issue. Adhesions develop after damage to the peritoneum by surgery, irradiation, infection or trauma. Objectives: Using a rat model, we compared the effectiveness of systemic and intraperitoneally administered common immunosuppressive drugs for prevention of postoperative intraperitoneal adhesions. Materials and Methods: Peritoneal adhesions were induced in 98 female Wistar-Albino rats by cecal abrasion and peritoneal excision. Rats were randomly separated into seven groups, each containing fourteen rats, and the standard experimental model was applied to all of rats. 14 days later, rats were euthanized, intraperitoneal adhesions were scored and tissues were examined histologically using hematoxylin/eosin and Masson’s trichrome staining. Results: Throughout the investigation, no animal died during or after surgery. In all of experimental groups, decrease in fibrosis was statistically significant. Decrease in fibrosis was most prominently in intraperitoneal tacrolimus group (P = 0.000), and decrease was least in intraperitoneal cyclosporine group (P = 0.022). Vascular proliferation was significantly decreased in all experimental groups (P < 0.05) except for systemic tacrolimus group (P = 0.139). Most prominent reduction in vascular proliferation was in intraperitoneal tacrolimus group (P = 0.000). Conclusions: Administration of immunosuppressive drugs is effective for prevention of intraperitoneal adhesions. PMID:24693396

Autologous Bone Plug Supplemented With Autologous Chondrocyte Implantation in Osteochondral Defects of the Knee.

PubMed

Bhattacharjee, Atanu; McCarthy, Helen S; Tins, Bernhard; Roberts, Sally; Kuiper, J H; Harrison, Paul E; Richardson, James B

2016-05-01

Structural and functional outcome of bone graft with first- or second-generation autologous chondrocyte implantation (ACI) in treating cartilage and subchondral bone defect has not been reported previously. To evaluate the outcome of simultaneous transplantation of an autologous bone plug with first- or second-generation ACI for restoration of concomitant subchondral bone and full-thickness cartilage defect in the femoral condyle of the knee. Case series; Level of evidence, 4. Seventeen patients (mean ± SD age, 27 ± 7 years; range, 17-40 years)-12 with osteochondritis dissecans (International Cartilage Repair Society [ICRS] grades 3 and 4) and 5 with an isolated osteochondral defect (ICRS grade 4)-had the defect reconstructed with implantation of a unicortical autologous bone graft combined with ACI (the OsPlug technique). Functional outcome was assessed with Lysholm scores obtained preoperatively and at 1 and 5 years postoperatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART score (magnetic resonance observation of cartilage repair tissue), and ICRS II histology score. Formation of a subchondral lamina and lateral integration of the bone grafts were evaluated from magnetic resonance imaging scans. The mean defect size was 4.5 ± 2.6 cm(2) (range, 1-9 cm(2)), and the mean depth was 11.3 ± 5 mm (range, 5-18 mm). The preoperative Lysholm score improved from 45 (interquartile range [IQR], 24; range, 16-79) to 77 (IQR, 28; range, 41-100) at 1 year (P = .001) and 70 (IQR, 35; range, 33-91) at 5 years (P = .009). The mean OAS of the repair site was 6.2 (range, 0-9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22 (range, 20-85) at 2.6 ± 1.8 years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft, as assessed on magnetic resonance imaging scan, and a low OAS were significantly associated with a poor Lysholm score and failure. A total of 3 patients had treatment failure, with 1 requiring total knee replacement at 5 years (Lysholm score of 33 at failure) and the other 2 requiring further surgical intervention because of persistent symptoms at 2 and 4 years, respectively (both had Lysholm score of 45 at failure). The Lysholm score in these patients before failure were still noted to be higher than at the preoperative level. The OsPlug technique shows significant improvement of functional outcome for up to 5 years in patients with high-grade osteochondritis dissecans or osteochondral defect. This is the first report describing association of bone graft integration with functional outcome after such a procedure. It also demonstrates histologic evidence of integration of the repair cartilage with the underlying bone graft. © 2016 The Author(s).