Association of abnormal plasma bilirubin with aggressive HCC phenotype

PubMed Central

Carr, Brian I.; Guerra, Vito; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

2014-01-01

Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

Severe Methanol Poisoning with Supralethal Serum Formate Concentration: A Case Report

PubMed Central

Nurieva, Olga; Kotikova, Katerina

2015-01-01

Objective To present a case of survival without visual and central nervous system sequelae at a formate concentration of twice the reported lethal level. Clinical Presentation and Intervention This was a case of a 33-year-old man who ingested 1 liter of a toxic mixture of methanol and ethanol. Upon admission, he presented with anxiety, tachycardia and hypertension and had a serum formate level of 1,400 mg/l (normal range 0.9–2.1 mg/l), a methanol level of 806 mg/l (normal range 2–30 mg/l), an undetectable ethanol concentration and a normal lactate level. A 10% solution of ethanol and folinic acid was administered intravenously and two 8-hour sessions of intermittent hemodialysis were performed. The patient was discharged on the fifth day without sequelae of poisoning. The follow-up examinations 3 months and 2 years later revealed no damage to the basal ganglia. The patient had normal visual-evoked potential and findings on optical coherence tomography. The genetic analysis revealed a rare minor allele for the gene coding CYP2E1 enzyme of the microsomal ethanol oxidizing system. Conclusion The patient survived acute methanol poisoning without long-term sequelae despite a high serum level of formic acid upon admission. PMID:26380973

Low plasma PDGF-BB levels are associated with estradiol in postmenopausal osteoporosis: PDGF-BB mediated by estradiol in women.

PubMed

Tang, Lanhua; Xia, Zhuying; Luo, Zhongwei; Long, Haitao; Zhu, Yong; Zhao, Shushan

2017-08-01

Objective This study aimed to investigate the association between low plasma Platelet-derived growth factor-BB (PDGF-BB) levels and oestradiol in Postmenopausal osteoporosis (PMOP). Methods This prospective study measured plasma PDGF-BB and oestradiol levels in outpatients who were admitted to our hospital. Participants were screened and then allocated to three groups: normal young women, postmenopausal control, and PMOP. Additionally, Sprague-Dawley rats underwent either sham surgery or bilateral ovariectomy (OVX), and were divided into the following groups: sham, OVX, OVX + oestradiol, and OVX + PDGF-BB. Plasma oestradiol and PDGF-BB levels were measured using commercially available ELISA kits. Results A total of 121 participants, including 69 normal young women, 28 patients with primary PMOP, and 24 age-matched postmenopausal women were enrolled. Plasma oestradiol and PDGF-BB levels were lower in postmenopausal women, especially in PMOP ( P < 0.01). Pearson correlations analysis showed that PDGF-BB levels were positively correlated with oestradiol levels and inversely correlated with age ( P < 0.01). The OVX rat model showed that oestradiol replacement increased plasma PDGF-BB levels, while PDGF-BB systematic treatment had no effect on plasma oestradiol levels. Conclusions Plasma PDGF-BB levels are maintained by oestrogen in normal young women and play a major role in PMOP.

Gene Expression Profiling of Multiple Leiomyomata Uteri and Matched Normal Tissue from a Single Patient

PubMed Central

Dimitrova, Irina K.; Richer, Jennifer K.; Rudolph, Michael C.; Spoelstra, Nicole S.; Reno, Elaine M.; Medina, Theresa M.; Bradford, Andrew P.

2009-01-01

Objective To identify differentially expressed genes between fibroid and adjacent normal myometrium in an identical hormonal and genetic background. Design Array analysis of 3 leiomyomata and matched adjacent normal myometrium in a single patient. Setting University of Colorado Hospital. Patient(s) A single female undergoing medically indicated hysterectomy for symptomatic fibroids. Interventions(s) mRNA isolation and microarray analysis, reverse-transcriptase polymerase chain reaction, western blotting and immunohistochemistry. Main Outcome Measure(s) Changes in mRNA and protein levels in leiomyomata and matched normal myometrium. Result(s) Expression of 197 genes was increased and 619 decreased, significantly by at least 2 fold, in leiomyomata relative to normal myometrium. Expression profiles between tumors were similar and normal myometrial samples showed minimal variation. Changes in, and variation of, expression of selected genes were confirmed in additional normal and leiomyoma samples from multiple patients. Conclusion(s) Analysis of multiple tumors from a single patient confirmed changes in expression of genes described in previous, apparently disparate, studies and identified novel targets. Gene expression profiles in leiomyomata are consistent with increased activation of mitogenic pathways and inhibition of apoptosis. Down-regulation of genes implicated in invasion and metastasis, of cancers, was observed in fibroids. This expression pattern may underlie the benign nature of uterine leiomyomata and may aid in the differential diagnosis of leiomyosarcoma. PMID:18672237

Issues in characterizing resting energy expenditure in obesity and after weight loss

PubMed Central

Bosy-Westphal, Anja; Braun, Wiebke; Schautz, Britta; Müller, Manfred J.

2013-01-01

Limitations of current methods: Normalization of resting energy expenditure (REE) for body composition using the 2-compartment model fat mass (FM), and fat-free mass (FFM) has inherent limitations for the interpretation of REE and may lead to erroneous conclusions when comparing people with a wide range of adiposity as well as before and after substantial weight loss. Experimental objectives: We compared different methods of REE normalization: (1) for FFM and FM (2) by the inclusion of %FM as a measure of adiposity and (3) based on organ and tissue masses. Results were compared between healthy subjects with different degrees of adiposity as well as within subject before and after weight loss. Results: Normalizing REE from an “REE vs. FFM and FM equation” that (1) was derived in obese participants and applied to lean people or (2) was derived before weight loss and applied after weight loss leads to the erroneous conclusion of a lower metabolic rate (i) in lean persons and (ii) after weight loss. This is revealed by the normalization of REE for organ and tissue masses that was not significantly different between lean and obese or between baseline and after weight loss. There is evidence for an increasing specific metabolic rate of FFM with increasing %FM that could be explained by a higher contribution of liver, kidney and heart mass to FFM in obesity. Using “REE vs. FFM and FM equations” specific for different levels of adiposity (%FM) eliminated differences in REE before and after weight loss in women. Conclusion: The most established method for normalization of REE based on FFM and FM may lead to spurious conclusions about metabolic rate in obesity and the phenomenon of weight loss-associated adaptive thermogenesis. Using %FM-specific REE prediction from FFM and FM in kg may improve the normalization of REE when subjects with wide differences in %FM are investigated. PMID:23532370

Plasma Shh levels reduced in pancreatic cancer patients

PubMed Central

El-Zaatari, Mohamad; Daignault, Stephanie; Tessier, Art; Kelsey, Gail; Travnikar, Lisa A.; Cantu, Esperanza F.; Lee, Jamie; Plonka, Caitlyn M.; Simeone, Diane M.; Anderson, Michelle A.; Merchant, Juanita L.

2012-01-01

Objectives Normally, sonic hedgehog (Shh) is expressed in the pancreas during fetal development and transiently after tissue injury. Although pancreatic cancers express Shh, it is not known if the protein is secreted into the blood and whether its plasma levels change with pancreatic transformation. The goal of this study was to develop an ELISA to detect human Shh in blood, and determine the levels in subjects with and without pancreatic cancer. Methods A human Shh ELISA assay was developed, and plasma Shh levels were measured in blood samples from normal volunteers and subjects with pancreatitis or pancreatic cancer. The biological activity of plasma Shh was tested using NIH-3T3 cells. Results The average levels of Shh in human blood were lower in pancreatitis and pancreatic cancer patients than in normal individuals. Hematopoietic cells did not express Shh suggesting that Shh is secreted into the bloodstream. Plasma fractions enriched for Shh did not induce Gli-1 mRNA suggesting that the protein was not biologically active. Conclusions Shh is secreted from tissues and organs into the circulation but its activity is blocked by plasma proteins. Reduced plasma levels were found in pancreatic cancer patients, but alone were not sufficient to predict pancreatic cancer. PMID:22513293

Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

PubMed Central

Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

2009-01-01

Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

Monocular oral reading after treatment of dense congenital unilateral cataract

PubMed Central

Birch, Eileen E.; Cheng, Christina; Christina, V; Stager, David R.

2010-01-01

Background Good long-term visual acuity outcomes for children with dense congenital unilateral cataracts have been reported following early surgery and good compliance with postoperative amblyopia therapy. However, treated eyes rarely achieve normal visual acuity and there has been no formal evaluation of the utility of the treated eye for reading. Methods Eighteen children previously treated for dense congenital unilateral cataract were tested monocularly with the Gray Oral Reading Test, 4th edition (GORT-4) at 7 to 13 years of age using two passages for each eye, one at grade level and one at +1 above grade level. In addition, right eyes of 55 normal children age 7 to 13 served as a control group. The GORT-4 assesses reading rate, accuracy, fluency, and comprehension. Results Visual acuity of treated eyes ranged from 0.1 to 2.0 logMAR and of fellow eyes from −0.1 to 0.2 logMAR. Treated eyes scored significantly lower than fellow and normal control eyes on all scales at grade level and at +1 above grade level. Monocular reading rate, accuracy, fluency, and comprehension were correlated with visual acuity of treated eyes (rs = −0.575 to −0.875, p < 0.005). Treated eyes with 0.1-0.3 logMAR visual acuity did not differ from fellow or normal control eyes in rate, accuracy, fluency, or comprehension when reading at grade level or at +1 above grade level. Fellow eyes did not differ from normal controls on any reading scale. Conclusions Excellent visual acuity outcomes following treatment of dense congenital unilateral cataracts are associated with normal reading ability of the treated eye in school-age children. PMID:20603057

Expression of SET Protein in the Ovaries of Patients with Polycystic Ovary Syndrome

PubMed Central

Boqun, Xu; Xiaonan, Dai; YuGui, Cui; Lingling, Gao; Xue, Dai; Gao, Chao; Feiyang, Diao; Jiayin, Liu; Gao, Li; Li, Mei; Zhang, Yuan; Ma, Xiang

2013-01-01

Background. We previously found that expression of SET gene was up-regulated in polycystic ovaries by using microarray. It suggested that SET may be an attractive candidate regulator involved in the pathophysiology of polycystic ovary syndrome (PCOS). In this study, expression and cellular localization of SET protein were investigated in human polycystic and normal ovaries. Method. Ovarian tissues, six normal ovaries and six polycystic ovaries, were collected during transsexual operation and surgical treatment with the signed consent form. The cellular localization of SET protein was observed by immunohistochemistry. The expression levels of SET protein were analyzed by Western Blot. Result. SET protein was expressed predominantly in the theca cells and oocytes of human ovarian follicles in both PCOS ovarian tissues and normal ovarian tissues. The level of SET protein expression in polycystic ovaries was triple higher than that in normal ovaries (P < 0.05). Conclusion. SET was overexpressed in polycystic ovaries more than that in normal ovaries. Combined with its localization in theca cells, SET may participate in regulating ovarian androgen biosynthesis and the pathophysiology of hyperandrogenism in PCOS. PMID:23861679

Expression of SET Protein in the Ovaries of Patients with Polycystic Ovary Syndrome.

PubMed

Boqun, Xu; Xiaonan, Dai; Yugui, Cui; Lingling, Gao; Xue, Dai; Gao, Chao; Feiyang, Diao; Jiayin, Liu; Gao, Li; Li, Mei; Zhang, Yuan; Ma, Xiang

2013-01-01

Background. We previously found that expression of SET gene was up-regulated in polycystic ovaries by using microarray. It suggested that SET may be an attractive candidate regulator involved in the pathophysiology of polycystic ovary syndrome (PCOS). In this study, expression and cellular localization of SET protein were investigated in human polycystic and normal ovaries. Method. Ovarian tissues, six normal ovaries and six polycystic ovaries, were collected during transsexual operation and surgical treatment with the signed consent form. The cellular localization of SET protein was observed by immunohistochemistry. The expression levels of SET protein were analyzed by Western Blot. Result. SET protein was expressed predominantly in the theca cells and oocytes of human ovarian follicles in both PCOS ovarian tissues and normal ovarian tissues. The level of SET protein expression in polycystic ovaries was triple higher than that in normal ovaries (P < 0.05). Conclusion. SET was overexpressed in polycystic ovaries more than that in normal ovaries. Combined with its localization in theca cells, SET may participate in regulating ovarian androgen biosynthesis and the pathophysiology of hyperandrogenism in PCOS.

Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population

PubMed Central

Zhang, Jun; Zhang, Zhiwei; Ding, Yulei; Xu, Peng; Wang, Tingting; Xu, Wenjing; Lu, Huan; Li, Jun; Wang, Yan; Li, Siyuan; Liu, Zongzhi; An, Na; Yang, Li; Xie, Jianxin

2015-01-01

Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P < 0.01). The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (P < 0.01). In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue. PMID:26273678

Insulin-producing cells could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells

PubMed Central

2013-01-01

Objective The aim of this study was to compare the difference between insulin-producing cells (IPCs) and normal human pancreatic beta cells both in physiological function and morphological features in cellular level. Methods The levels of insulin secretion were measured by enzyme-linked immunosorbent assay. The insulin gene expression was determined by real-time quantitative polymerase chain reaction. The morphological features were detected by atomic force microscopy (AFM) and laser confocal scanning microscopy. Results IPCs and normal human pancreatic beta cells were similar to each other under the observation in AFM with the porous structure features in the cytoplasm. Both number of membrane particle size and average roughness of normal human beta cells were higher than those of IPCs. Conclusions Our results firstly revealed that the cellular ultrastructure of IPCs was closer to that of normal human pancreatic beta cells, but they still could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. PMID:23421382

Relationship Between 17-Hydroxyprogesterone Responses to Human Chorionic Gonadotropin and Markers of Ovarian Follicle Morphology in Women With Polycystic Ovary Syndrome

PubMed Central

Maas, Kevin H.; Chuan, Sandy S.; Cook-Andersen, Heidi; Su, H. Irene; Duleba, A.

2015-01-01

Context: Women with polycystic ovary syndrome (PCOS) have increased 17-hydroxyprogesterone (17-OHP) responses to gonadotropin stimulation although individual variability is substantial, as reflected by exaggerated as well as normal responses. The relationship between 17-OHP responses to gonadotropin stimulation and markers of ovarian function has not been assessed. Objective: To determine whether 17-OHP responses are associated with antral follicle count (AFC), anti-Mullerian hormone (AMH), or inhibin B (Inh B) levels in PCOS and normal women. Design: Prospective study. Setting: Research center at an academic medical center. Participants: Women with PCOS (n = 18) and normal controls (n = 18). Interventions: Blood samples were obtained before and 24 hours after administration of 25 μg recombinant-human chorionic gonadotropin. Ovarian imaging was conducted with three-dimensional pelvic ultrasound. Main Outcome Measures: Basal and stimulated levels of 17-OHP, androgens, estrogen, AMH, Inh B, and AFC. Results: In women with PCOS, 17-OHP responses were heterogeneous and inversely correlated with AMH and Inh B levels, but not AFC. In a subgroup of PCOS women with exaggerated 17-OHP responses, AMH levels were equivalent to that of normal women. In PCOS women with normal 17-OHP responses, AMH levels were markedly elevated. Conclusion: Based on heterogeneous 17-OHP responses to human chorionic gonadotropin in women with PCOS, AMH levels are inversely linked to ovarian androgen production while positively correlated with AFC. These findings suggest that in PCOS, AMH production may reflect redistribution of the follicle population or regulation by intraovarian mechanisms. PMID:25313914

EFFECTS OF FLUTICASONE PROPIONATE ON MYELOPEROXIDASE LEVELS IN NASAL LAVAGE FLUIDS FROM SINUSITIS, ALLERGIC RHINITIS, AND NORMAL SUBJECTS. (R825814)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Steroid Hormones in NF1 Tumorigenesis

DTIC Science & Technology

2005-08-01

Schwannomatosis , in Aspen in June this year. Table 3. Summary of current xenograft proliferation/TUNEL (apoptosis) data. Culture I sex I Outlier? I PI/Al I...Biology of NF1, NF2, and schwannomatosis . Aspen, CO, June 2005, poster. CONCLUSIONS: In vitro data indicate that steroid hormone receptor levels in normal

Valgus-varus motion of the knee in normal level walking and stair climbing.

PubMed

Yu, B; Stuart, M J; Kienbacher, T; Growney, E S; An, K-N

1997-07-01

OBJECTIVE: The knee valgus-varus moment and the knee angles were compared between normal level walking and stair climbing. DESIGN: Ten healthy subjects were tested for ascent, descent, and level walking. BACKGROUND: An understanding of the normal valgus-varus motion of the knee during stair climbing is needed to apply biomechanical analysis of stair climbing as a evaluation tool for knee osteoarthritis patients. METHODS: A motion analysis system, three force plates, and a flight of stairs were used to collect kinematic and kinetic data. The knee angles and moments were calculated from the collected kinematic and kinetic data. RESULTS: The knee varus angle for the maximum knee valgus moments in stair climbing was significantly greater than that in level walking. The knee valgus moment was significantly correlated to ground reaction forces and knee valgus-varus angle during stair climbing and level walking. CONCLUSIONS: There is a coupling between the knee valgus-varus motion and flexion-extension motion. Ground reaction forces are the major contributors to the within-subject variation in the knee valgus-varus moment during stair climbing and level walking. The knee valgus-varus angle is a major contributor to the between-subject variation in the knee valgus moment during stair climbing and level walking.

Association between folate levels and CpG island hypermethylation in normal colorectal mucosa

PubMed Central

Wallace, Kristin; Grau, Maria V.; Levine, Joan A.; Shen, Lanlan; Hamdan, Randala; Chen, Xinli; Gui, Jiang; Haile, Robert W.; Barry, Elizabeth L.; Ahnen, Dennis; McKeown-Eyssen, Gail; Baron, John A.; Issa, Jean Pierre J.

2010-01-01

Background Gene-specific promoter methylation of several genes occurs in aging normal tissues and may predispose to tumorigenesis. In the present study, we investigate the association among blood folate levels, and dietary and lifestyle factors with CpG island methylation in normal colorectal mucosa. Methods Subjects were enrolled in a multi-center chemoprevention trial of aspirin or folic acid for the prevention of large bowel adenomas. We collected 1000 biopsies from 389 patients, 501 samples from the right colon and 499 from the rectum at the follow-up colonoscopy. We measured DNA methylation of estrogen receptor alpha (ERα) and secreted frizzled related protein-1 (SFRP1) using bisulfite pyrosequencing. We used Generalized Estimating Equations regression analysis to examine the association between methylation and selected variables. Results For both ERα and SFRP1, percent methylation was significantly higher in the rectum compared to the right colon (p = 0.001). For each 10 years of age, we observed a 1.7 % increase in methylation level for ERα and a 2.9 % increase for SFRP1 (P < 0.0001). African Americans had a significantly lower level of ERα and SFRP1 methylation compared to Caucasians and Hispanics. Higher RBC folate levels were associated with higher levels of both ERα (p=0.03) and SFRP1 methylation (p=0.01). Conclusions Our results suggest that CpG island methylation in normal colorectal mucosa is related to advancing age, race, rectal location, and RBC folate levels. These data have important implications regarding the safety of supplementary folate administration in healthy adults given the hypothesis that methylation in normal mucosa may predispose to colorectal neoplasia. PMID:21149331

In vivo Investigation of Anti-diabetic Properties of Ripe Onion Juice in Normal and Streptozotocin-induced Diabetic Rats

PubMed Central

Lee, Chul-Won; Lee, Hyung-Seok; Cha, Yong-Jun; Joo, Woo-Hong; Kang, Dae-Ook; Moon, Ja-Young

2013-01-01

The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice (Commercial product name is “Black Onion Extract”) were investigated in normal and streptozotocin-induced diabetic rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyper-glycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 5 or 15 mL/kg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a relatively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glucose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypoglycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mL/kg b.w.) for a short period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced diabetic rats. In conclusion, these results suggest that the commercial product “Black Onion Extract” may possess anti-hyperglycemic potential in diabetes. PMID:24471128

Hsp27 (HSPB1) differential expression in normal salivary glands and pleomorphic adenomas and association with an increased Bcl2/Bax ratio.

PubMed

Siqueira, Elisa C de; Souza, Fabrício T A; Diniz, Marina G; Gomez, Ricardo S; Gomes, Carolina C

2015-01-01

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm. The Hsp27 (HSPB1) is an antiapoptotic protein whose synthesis follows cytotoxic stresses and result in a transient increase in tolerance to subsequent cell injury. Although Hsp27 is expressed in a range of normal tissues and neoplasms, a wide variation in its expression exists among different cells and tissues types. In certain tumours of glandular origin (such as oesophageal adenocarcinomas), the level of Hsp27 is decreased. In the present study, Hsp27 protein levels were evaluated by enzyme-linked immunosorbent assay (ELISA) in a set of 18 fresh PA and 12 normal salivary gland samples. In addition, we tested if Hsp27 protein levels correlated with p53 expression and cell proliferation index, as well as with the transcriptional levels of Bcl-2-associated X protein (BAX), B cell lymphoma 2 (BCL2) and Caspase 3 in PA. We further tested the association between Hsp27 expression and PA tumour size. While all normal salivary gland samples expressed Hsp27 protein, only half of the PA samples expressed it, resulting in a reduced expression of Hsp27 in PA when compared with normal salivary glands (P = 0.003). The expression levels of this protein correlated positively with a higher messenger ribonucleic acid (mRNA) ratio of Bcl2/Bax (R = 0.631; P = 0.01). In conclusion, a decreased Hsp27 protein expression level in PA was found. In addition, Hsp27 levels correlated positively with the Bcl2/Bax mRNA ratio, suggesting an antiapoptotic effect.

Risk of Progression to Hypertension in a Low-Income Mexican Population with Pre-hypertension and Normal Blood Pressure

PubMed Central

Jimenez-Corona, Aida; Lopez-Ridaura, Ruy; Stern, Michael P; Gonzalez-Villalpando, Clicerio

2007-01-01

BACKGROUND Blood pressure (BP) levels below the pre-hypertension category may be associated with the risk of developing hypertension. We estimated the incidence rates of hypertension in low-income Mexican population according to several subcategories of baseline BP within normal and pre-hypertension categories. METHODS A total of 1572 nonhypertensive men (n=632) and non-pregnant women (n=940), aged 35 to 64 years at baseline, were followed for a median of 5.8 years. Hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg, diastolic blood pressure (DBP) ≥90 mm Hg, or self-reported physician diagnosis with anti-hypertensive medications. RESULTS During follow-up, 267 subjects developed hypertension, of whom 83 were men and 184 were women. Age-adjusted incidence rate was higher in women (37.1 per 1000 person-years) than in men (23.7 per 1000 person-years). There was a significant association between BP levels at baseline and hypertension incidence even within the normal category. For the upper levels of normal SBP (110-119 mm Hg), the HR (95%CI) was 2.43 (1.50-3.93) in women and 2.44 (1.05-5.69) in men, compared with SBP <110 mm Hg. For the upper levels of normal DBP (70-79 mm Hg), the HR (95%CI) was 2.33 (1.65-3.31) in women and 1.80 (0.92-3.52) in men, compared with DBP <70 mm Hg, after adjustment for recognized predictors. CONCLUSIONS High risk of hypertension incidence was associated with levels of BP even within the normal category. This information could help define a population at high risk of progression to hypertension, in order to establish preventive measures. PMID:17765131

A creatinine biosensor based on admittance measurement

NASA Astrophysics Data System (ADS)

Ching, Congo Tak-Shing; Sun, Tai-Ping; Jheng, Deng-Yun; Tsai, Hou-Wei; Shieh, Hsiu-Li

2015-08-01

Regular check of blood creatinine level is very important as it is a measurement of renal function. Therefore, the objective of this study is to develop a simple and reliable creatinine biosensor based on admittance measurement for precise determination of creatinine. The creatinine biosensor was fabricated with creatinine deiminase immobilized on screen-printed carbon electrodes. Admittance measurement at a specific frequency ranges (22.80 - 84.71 Hz) showed that the biosensor has an excellent linear (r2 > 0.95) response range (50 - 250 uM), which covers the normal physiological and pathological ranges of blood creatinine levels. Intraclass correlation coefficient (ICC) showed that the biosensor has excellent reliability and validity (ICC = 0.98). In conclusion, a simple and reliable creatinine biosensor was developed and it is capable of precisely determining blood creatinine levels in both the normal physiological and pathological ranges.

[Prevalence of dyslipidemia and normal blood lipids level in Uygur population in Kashgar area of Xinjiang Uygur Autonomous Region].

PubMed

Zhang, Z B; Xue, Z X; Wu, X J; Wang, T M; Li, Y H; Song, X L; Chao, X F; Wang, G; Nazibam, Nurmamat; Ayxamgul, Bawudun; Gulbahar, Elyas; Zhou, Z Y; Sun, B S; Wang, Y Z; Wang, M

2017-06-10

Objective: To understand the prevalence of dyslipidemia and normal blood lipids level in Uygur diabetes patients in Kashgar prefecture in southern area of Xinjiang. Methods: A total of 5 078 local residents aged ≥18 years (42.56 % were men) selected through cluster random sampling in Kashgar were surveyed by means of questionnaire survey, physical examination and laboratory test, and 521 diabetes patients were screened. Results: The overall prevalence of dyslipidemia in diabetes patients was 59.50 % (310/521) with adjusted rate as 49.39 % . Age ≥65 years, overweight, obesity and abdominal obesity increased the risk for dyslipidemia by 0.771 times (95 % CI : 1.015-3.088), 1.132 times (95 % CI : 1.290-3.523), 1.688 times (95 % CI : 1.573-4.592) and 0.801 times (95 % CI : 1.028-3.155) respectively. Compared with males, female was a protective factor for dyslipidemia ( OR =0.507, 95 %CI : 0.334-0.769). The overall normal rate of blood lipids level including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) for type 2 diabetes patients was 11.13 % . Female, higher BMI and abdominal obesity were the factors influencing the overall normal blood lipids level. The normal rate of LDL-C level decreased with increase of age, BMI and waist circumferences (trend test χ (2)=18.049, P <0.001; trend test χ (2)=10.582, P =0.001; χ (2)=19.081, P <0.001), but increased with educational level (trend test χ (2)=9.764, P =0.002). Conclusion: The prevalence of dyslipidemia in Uygur diabetes patients in Kashgar was high, however, the overall normal rate of blood lipid level was relatively low. Obesity was the most important risk factor for dyslipidemia in this area. More attention should be paid to dyslipidemia prevention in women.

10 CFR Appendix A to Part 820 - General Statement of Enforcement Policy

Code of Federal Regulations, 2012 CFR

2012-01-01

... evaluated in the aggregate and a single severity level assigned for a group of violations. (c) Isolated... pre-decisional discussions regarding potential or alleged violations and will not normally be open to... forth the conclusion of the DOE Office of Nuclear Safety and Environment that one or more violations of...

10 CFR Appendix A to Part 820 - General Statement of Enforcement Policy

Code of Federal Regulations, 2014 CFR

2014-01-01

... evaluated in the aggregate and a single severity level assigned for a group of violations. (c) Isolated... pre-decisional discussions regarding potential or alleged violations and will not normally be open to... forth the conclusion of the DOE Office of Nuclear Safety and Environment that one or more violations of...

10 CFR Appendix A to Part 820 - General Statement of Enforcement Policy

Code of Federal Regulations, 2010 CFR

2010-01-01

... evaluated in the aggregate and a single severity level assigned for a group of violations. (c) Isolated... pre-decisional discussions regarding potential or alleged violations and will not normally be open to... forth the conclusion of the DOE Office of Nuclear Safety and Environment that one or more violations of...

10 CFR Appendix A to Part 820 - General Statement of Enforcement Policy

Code of Federal Regulations, 2013 CFR

2013-01-01

... evaluated in the aggregate and a single severity level assigned for a group of violations. (c) Isolated... pre-decisional discussions regarding potential or alleged violations and will not normally be open to... forth the conclusion of the DOE Office of Nuclear Safety and Environment that one or more violations of...

10 CFR Appendix A to Part 820 - General Statement of Enforcement Policy

Code of Federal Regulations, 2011 CFR

2011-01-01

... evaluated in the aggregate and a single severity level assigned for a group of violations. (c) Isolated... pre-decisional discussions regarding potential or alleged violations and will not normally be open to... forth the conclusion of the DOE Office of Nuclear Safety and Environment that one or more violations of...

SU-F-R-31: Identification of Robust Normal Lung CT Texture Features for the Prediction of Radiation-Induced Lung Disease

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

Choi, W; Riyahi, S; Lu, W

Purpose: Normal lung CT texture features have been used for the prediction of radiation-induced lung disease (radiation pneumonitis and radiation fibrosis). For these features to be clinically useful, they need to be relatively invariant (robust) to tumor size and not correlated with normal lung volume. Methods: The free-breathing CTs of 14 lung SBRT patients were studied. Different sizes of GTVs were simulated with spheres placed at the upper lobe and lower lobe respectively in the normal lung (contralateral to tumor). 27 texture features (9 from intensity histogram, 8 from grey-level co-occurrence matrix [GLCM] and 10 from grey-level run-length matrix [GLRM])more » were extracted from [normal lung-GTV]. To measure the variability of a feature F, the relative difference D=|Fref -Fsim|/Fref*100% was calculated, where Fref was for the entire normal lung and Fsim was for [normal lung-GTV]. A feature was considered as robust if the largest non-outlier (Q3+1.5*IQR) D was less than 5%, and considered as not correlated with normal lung volume when their Pearson correlation was lower than 0.50. Results: Only 11 features were robust. All first-order intensity-histogram features (mean, max, etc.) were robust, while most higher-order features (skewness, kurtosis, etc.) were unrobust. Only two of the GLCM and four of the GLRM features were robust. Larger GTV resulted greater feature variation, this was particularly true for unrobust features. All robust features were not correlated with normal lung volume while three unrobust features showed high correlation. Excessive variations were observed in two low grey-level run features and were later identified to be from one patient with local lung diseases (atelectasis) in the normal lung. There was no dependence on GTV location. Conclusion: We identified 11 robust normal lung CT texture features that can be further examined for the prediction of radiation-induced lung disease. Interestingly, low grey-level run features identified normal lung diseases. This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

Chemopreventive effect and HPTLC fingerprinting analysis of Jasminum sambac (L.) Ait. Extract against DLA-induced lymphoma in experimental animals.

PubMed

Kalaiselvi, M; Narmadha, R; Ragavendran, P; Vidya, B; Gomathi, D; Raj, C Arul; Starlinraj, T; Gopalakrishnan, V K; Uma, C; Kalaivani, K

2013-02-01

The anticancer activity of the ethanolic extract of Jasminum sambac against Dalton's lymphoma ascites-induced lymphatic cancer in Swiss albino mice was investigated. The anticancer activity of J. sambac was studied against lymphoma using lipid profiles, biochemical parameters, and membrane-bound marker enzymes by standard procedures. A high-performance thin-layer chromatography fingerprinting analysis showed the presence of terpenoids and flavonoids. The levels of cholesterol, triglyceride, VLDL cholesterol, and LDL cholesterol were significantly decreased in tumor-induced mice, while HDL cholesterol showed increased levels compared with those profiles. On treatment with J. sambac, the levels were brought back to near normal. The albumin, creatinine, total protein, urea, and uric acid contents were also approaching normal values. There was s significant increase in the levels of ATPase in group II. These levels were brought back to normal upon plant extract treatment of mice. DNA fragmentation occurred in the tumor-induced group of tissue, and treatment with ethanolic extract reduced the DNA damage caused by lymphoma. Expression of lactate dehydrogenase (LDH) isoenzymes shows an increase in the levels of LDH-4 and LDH-5 in cancer-bearing animals which is brought back to near normal. Histopathological investigation showed normal sections of liver tissues in the treatment group. The results found in mice treated with ethanolic extract 100 mg kg(-1) body weight quite promising and were comparable with the standard drug 5-fluorouracil. The statistically processed results support the conclusion that the ethanolic extract of J. sambac flower (100 mg kg(-1)) possesses a dose-dependent significant anticancer activity against lymphoma.

Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens

PubMed Central

DONG, YUCHEN; ZHENG, YAJUAN; XIAO, JUN; ZHU, CHAO; ZHAO, MEISHENG

2016-01-01

The aim of the present study was to analyze the role of Bcl-2 during the process of apoptosis in the mouse crystalline lens. In total, 12 normal mice served as the control group and 12 Bcl-2 knockout (K.O) mice served as the experimental group. The mouse crystalline lens was sampled for the detection of Bcl-2 and caspase-3 expression following exposure to ultraviolet (UV) radiation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine Bcl-2 expression in the groups of normal mice receiving UV radiation or not receiving UV radiation. Samples of the murine crystalline lens were microscopically harvested and analyzed using western blotting. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Furthermore, caspase 3 activity was examined using enzyme-linked immunosorbent assay kits, and RT-qPCR was used to analyze caspase-3 expression levels. The results of the present study demonstrated that there was no statistically significant difference in the level of Bcl-2 gene transcription between the two groups. In addition, UV radiation did not change the macrostructure of the crystalline lens in the group of normal mice or the group of Bcl-2 K.O mice. The results of the TUNEL assay indicated that the normal-UV group exhibited a more significant apoptosis level compared with the Bcl-2 K.O-UV group. Furthermore, the mRNA expression level of caspase-3 in the normal-UV group was significantly higher compared with the normal-nonUV group (P<0.05), while the levels in the Bcl-2 K.O-UV group were significantly higher compared with the Bcl-2 K.O and normal-nonUV groups (P<0.05). In addition, the mRNA expression level of caspase-3 was significantly higher in the normal-UV, as compared with the Bcl-2 K.O-UV group (P<0.05), and the variation trends in caspase-3 activity were consistent. In conclusion, the results of the present study demonstrated that Bcl-2 may have an important role in the promotion of UV-induced apoptosis in the crystalline lens. PMID:26998022

Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens.

PubMed

Dong, Yuchen; Zheng, Yajuan; Xiao, Jun; Zhu, Chao; Zhao, Meisheng

2016-03-01

The aim of the present study was to analyze the role of Bcl-2 during the process of apoptosis in the mouse crystalline lens. In total, 12 normal mice served as the control group and 12 Bcl-2 knockout (K.O) mice served as the experimental group. The mouse crystalline lens was sampled for the detection of Bcl-2 and caspase-3 expression following exposure to ultraviolet (UV) radiation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine Bcl-2 expression in the groups of normal mice receiving UV radiation or not receiving UV radiation. Samples of the murine crystalline lens were microscopically harvested and analyzed using western blotting. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Furthermore, caspase 3 activity was examined using enzyme-linked immunosorbent assay kits, and RT-qPCR was used to analyze caspase-3 expression levels. The results of the present study demonstrated that there was no statistically significant difference in the level of Bcl-2 gene transcription between the two groups. In addition, UV radiation did not change the macrostructure of the crystalline lens in the group of normal mice or the group of Bcl-2 K.O mice. The results of the TUNEL assay indicated that the normal-UV group exhibited a more significant apoptosis level compared with the Bcl-2 K.O-UV group. Furthermore, the mRNA expression level of caspase-3 in the normal-UV group was significantly higher compared with the normal-nonUV group (P<0.05), while the levels in the Bcl-2 K.O-UV group were significantly higher compared with the Bcl-2 K.O and normal-nonUV groups (P<0.05). In addition, the mRNA expression level of caspase-3 was significantly higher in the normal-UV, as compared with the Bcl-2 K.O-UV group (P<0.05), and the variation trends in caspase-3 activity were consistent. In conclusion, the results of the present study demonstrated that Bcl-2 may have an important role in the promotion of UV-induced apoptosis in the crystalline lens.

Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer

PubMed Central

2010-01-01

Background Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women. Methods A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry. Results Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer. Conclusion Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy. PMID:21162745

Is Serum Zinc Level Associated with Prediabetes and Diabetes?: A Cross-Sectional Study from Bangladesh

PubMed Central

Islam, Md. Rafiqul; Arslan, Iqbal; Attia, John; McEvoy, Mark; McElduff, Patrick; Basher, Ariful; Rahman, Waliur; Peel, Roseanne; Akhter, Ayesha; Akter, Shahnaz; Vashum, Khanrin P.; Milton, Abul Hasnat

2013-01-01

Aims To determine serum zinc level and other relevant biological markers in normal, prediabetic and diabetic individuals and their association with Homeostasis Model Assessment (HOMA) parameters. Methods This cross-sectional study was conducted between March and December 2009. Any patient aged ≥30 years attending the medicine outpatient department of a medical university hospital in Dhaka, Bangladesh and who had a blood glucose level ordered by a physician was eligible to participate. Results A total of 280 participants were analysed. On fasting blood sugar results, 51% were normal, 13% had prediabetes and 36% had diabetes. Mean serum zinc level was lowest in prediabetic compared to normal and diabetic participants (mean differences were approximately 65 ppb/L and 33 ppb/L, respectively). In multiple linear regression, serum zinc level was found to be significantly lower in prediabetes than in those with normoglycemia. Beta cell function was significantly lower in prediabetes than normal participants. Adjusted linear regression for HOMA parameters did not show a statistically significant association between serum zinc level, beta cell function (P = 0.07) and insulin resistance (P = 0.08). Low serum zinc accentuated the increase in insulin resistance seen with increasing BMI. Conclusion Participants with prediabetes have lower zinc levels than controls and zinc is significantly associated with beta cell function and insulin resistance. Further longitudinal population based studies are warranted and controlled trials would be valuable for establishing whether zinc supplementation in prediabetes could be a useful strategy in preventing progression to Type 2 diabetes. PMID:23613929

Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

PubMed

Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

2017-05-01

Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

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

Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.

Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined formore » each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.« less

Wavefront-Guided Scleral Lens Correction in Keratoconus

PubMed Central

Marsack, Jason D.; Ravikumar, Ayeswarya; Nguyen, Chi; Ticak, Anita; Koenig, Darren E.; Elswick, James D.; Applegate, Raymond A.

2014-01-01

Purpose To examine the performance of state-of-the-art wavefront-guided scleral contact lenses (wfgSCLs) on a sample of keratoconic eyes, with emphasis on performance quantified with visual quality metrics; and to provide a detailed discussion of the process used to design, manufacture and evaluate wfgSCLs. Methods Fourteen eyes of 7 subjects with keratoconus were enrolled and a wfgSCL was designed for each eye. High-contrast visual acuity and visual quality metrics were used to assess the on-eye performance of the lenses. Results The wfgSCL provided statistically lower levels of both lower-order RMS (p < 0.001) and higher-order RMS (p < 0.02) than an intermediate spherical equivalent scleral contact lens. The wfgSCL provided lower levels of lower-order RMS than a normal group of well-corrected observers (p < < 0.001). However, the wfgSCL does not provide less higher-order RMS than the normal group (p = 0.41). Of the 14 eyes studied, 10 successfully reached the exit criteria, achieving residual higher-order root mean square wavefront error (HORMS) less than or within 1 SD of the levels experienced by normal, age-matched subjects. In addition, measures of visual image quality (logVSX, logNS and logLIB) for the 10 eyes were well distributed within the range of values seen in normal eyes. However, visual performance as measured by high contrast acuity did not reach normal, age-matched levels, which is in agreement with prior results associated with the acute application of wavefront correction to KC eyes. Conclusions Wavefront-guided scleral contact lenses are capable of optically compensating for the deleterious effects of higher-order aberration concomitant with the disease, and can provide visual image quality equivalent to that seen in normal eyes. Longer duration studies are needed to assess whether the visual system of the highly aberrated eye wearing a wfgSCL is capable of producing visual performance levels typical of the normal population. PMID:24830371

Alanine transaminase level in a healthy population in Morocco.

PubMed

Laouina, A; Abouyoub, A; Soulaymani, A; Alami, R

2012-03-01

A little is known about the prevalence of elevated alanine transaminase in a Moroccan healthy population. Our aim was to search for the upper limit of normal alanine transaminase in the blood donors and then to apply the upper limit of normal alanine found in the population so as to assess the prevalence of subjects with abnormal transaminase level. We then, investigated for factors associated with increased level of transaminase in our population. This study was carried out on 14071 blood donors, (74.1% of men and 25.9% female) aged between 18 to 60 years, randomly chosen. Serum transaminase activity was measured using on IEMS Reader, Labsystems. Hepatitis B and C were performed by ELISA. The upper limit of normal transaminase found were 64 for men and 52 for women. Consequently, 2.08% blood donors had an abnormal level of transaminase. Follow up results revealed that drug was the first cause of elevated transaminase in our cohort followed by diet and alcohol consumption. One seroconversion for hepatitis C was identified. In conclusion, this study showed that even though there is an evident lack of efficiency in using alanine aminotransferase testing qualifying blood donors in our country, preventing viral potential transmission through transfusions was possible.

Evidence for insulin resistance in nonobese patients with polycystic ovarian disease.

PubMed

Jialal, I; Naiker, P; Reddi, K; Moodley, J; Joubert, S M

1987-05-01

In this study seven normal weight Indian patients with polycystic ovarian disease (PCOD) with no evidence of acanthosis nigricans and 7 age- and weight-matched normal Indian women were studied to determine whether PCOD patients were insulin-resistant. While all 14 women had normal glucose tolerance, the PCOD women had significantly higher mean plasma glucose levels at 30 and 60 min and higher mean incremental glucose areas [incremental areas: PCOD, 9.0 +/- 2.2 (+/- SEM); normal women, 4.0 +/- 0.8 mmol/L; P less than 0.05]. Insulin responses were significantly higher in the PCOD compared to normal women (incremental areas: PCOD, 623.8 +/- 78.3; normal women, 226.2 +/- 30.3 microU/mL; P less than 0.001). Both serum testosterone and androstenedione levels correlated with the insulin areas (r = 0.82; P less than 0.001 and r = 0.86; P less than 0.001, respectively). [125I] Insulin binding to erythrocytes revealed decreased maximum specific binding in the PCOD women (6.9 +/- 0.6%) compared to that in normal women (9.2 +/- 0.7%; P less than 0.02). While Scatchard analysis revealed similar receptor numbers, ID50 values demonstrated decreased receptor affinity in the women with PCOD. In conclusion, in the absence of acanthosis nigricans, nonobese patients with PCOD are insulin resistant, and this insulin resistance correlates with the hyperandrogenism.

GC-Content Normalization for RNA-Seq Data

PubMed Central

2011-01-01

Background Transcriptome sequencing (RNA-Seq) has become the assay of choice for high-throughput studies of gene expression. However, as is the case with microarrays, major technology-related artifacts and biases affect the resulting expression measures. Normalization is therefore essential to ensure accurate inference of expression levels and subsequent analyses thereof. Results We focus on biases related to GC-content and demonstrate the existence of strong sample-specific GC-content effects on RNA-Seq read counts, which can substantially bias differential expression analysis. We propose three simple within-lane gene-level GC-content normalization approaches and assess their performance on two different RNA-Seq datasets, involving different species and experimental designs. Our methods are compared to state-of-the-art normalization procedures in terms of bias and mean squared error for expression fold-change estimation and in terms of Type I error and p-value distributions for tests of differential expression. The exploratory data analysis and normalization methods proposed in this article are implemented in the open-source Bioconductor R package EDASeq. Conclusions Our within-lane normalization procedures, followed by between-lane normalization, reduce GC-content bias and lead to more accurate estimates of expression fold-changes and tests of differential expression. Such results are crucial for the biological interpretation of RNA-Seq experiments, where downstream analyses can be sensitive to the supplied lists of genes. PMID:22177264

Biomechanics of Hybrid Anterior Cervical Fusion and Artificial Disc Replacement in 3-Level Constructs: An In Vitro Investigation

PubMed Central

Liao, Zhenhua; Fogel, Guy R.; Pu, Ting; Gu, Hongsheng; Liu, Weiqiang

2015-01-01

Background The ideal surgical approach for cervical disk disease remains controversial, especially for multilevel cervical disease. The purpose of this study was to investigate the biomechanics of the cervical spine after 3-level hybrid surgery compared with 3-level anterior cervical discectomy and fusion (ACDF). Material/Methods Eighteen human cadaveric spines (C2-T1) were evaluated under displacement-input protocol. After intact testing, a simulated hybrid construct or fusion construct was created between C3 to C6 and tested in the following 3 conditions: 3-level disc plate disc (3DPD), 3-level plate disc plate (3PDP), and 3-level plate (3P). Results Compared to intact, almost 65~80% of motion was successfully restricted at C3-C6 fusion levels (p<0.05). 3DPD construct resulted in slight increase at the 3 instrumented levels (p>0.05). 3PDP construct resulted in significant decrease of ROM at C3-C6 levels less than 3P (p<0.05). Both 3DPD and 3PDP caused significant reduction of ROM at the arthrodesis level and produced motion increase at the arthroplasty level. For adjacent levels, 3P resulted in markedly increased contribution of both upper and lower adjacent levels (p<0.05). Significant motion increases lower than 3P were only noted at partly adjacent levels in some conditions for 3DPD and 3PDP (p<0.05). Conclusions ACDF eliminated motion within the construct and greatly increased adjacent motion. Artificial cervical disc replacement normalized motion of its segment and adjacent segments. While hybrid conditions failed to restore normal motion within the construct, they significantly normalized motion in adjacent segments compared with the 3-level ACDF condition. The artificial disc in 3-level constructs has biomechanical advantages compared to fusion in normalizing motion. PMID:26529430

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value

PubMed Central

Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia

2017-01-01

Background In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). Patients and methods We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Results Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Conclusions Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value. PMID:28562682

An immune reaction may be necessary for cancer development

PubMed Central

Prehn, Richmond T

2006-01-01

Background The hypothesis of immunosurveillance suggests that new neoplasms arise very frequently, but most are destroyed almost at their inception by an immune response. Its correctness has been debated for many years. In its support, it has been shown that the incidences of many tumor types, though apparently not all, tend to be increased in immunodeficient animals or humans, but this observation does not end the debate. Alternative model There is an alternative to the surveillance hypothesis; numerous studies have shown that the effect of an immune reaction on a tumor is biphasic. For each tumor, there is some quantitatively low level of immune reaction that, relative to no reaction, is facilitating, perhaps even necessary for the tumor's growth in vivo. The optimum level of this facilitating reaction may often be less than the level of immunity that the tumor might engender in a normal subject. Conclusion The failure of a tumor to grow as well in the normal as it does in the immunosuppressed host is probably not caused by a lack of tumor-cell killing in the suppressed host. Instead, the higher level of immune response in a normal animal, even if it does not rise to tumor-inhibitory levels, probably gives less positive support to tumor growth. This seems more than a semantic distinction. PMID:16457723

Levels-of-Processing Effect on Frontotemporal Function in Schizophrenia During Word Encoding and Recognition

PubMed Central

Ragland, J. Daniel; Gur, Ruben C.; Valdez, Jeffrey N.; Loughead, James; Elliott, Mark; Kohler, Christian; Kanes, Stephen; Siegel, Steven J.; Moelter, Stephen T.; Gur, Raquel E.

2015-01-01

Objective Patients with schizophrenia improve episodic memory accuracy when given organizational strategies through levels-of-processing paradigms. This study tested if improvement is accompanied by normalized frontotemporal function. Method Event-related blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) was used to measure activation during shallow (perceptual) and deep (semantic) word encoding and recognition in 14 patients with schizophrenia and 14 healthy comparison subjects. Results Despite slower and less accurate overall word classification, the patients showed normal levels-of-processing effects, with faster and more accurate recognition of deeply processed words. These effects were accompanied by left ventrolateral prefrontal activation during encoding in both groups, although the thalamus, hippocampus, and lingual gyrus were overactivated in the patients. During word recognition, the patients showed overactivation in the left frontal pole and had a less robust right prefrontal response. Conclusions Evidence of normal levels-of-processing effects and left prefrontal activation suggests that patients with schizophrenia can form and maintain semantic representations when they are provided with organizational cues and can improve their word encoding and retrieval. Areas of overactivation suggest residual inefficiencies. Nevertheless, the effect of teaching organizational strategies on episodic memory and brain function is a worthwhile topic for future interventional studies. PMID:16199830

BMI-1 Autoantibody as a New Potential Biomarker for Cervical Carcinoma

PubMed Central

Tong, Yong-Qing; Liu, Bei; Zheng, Hong-Yun; He, Yu-Juan; Gu, Jian; Li, Feng; Li, Yan

2011-01-01

BMI-1 is overexpressed in a variety of cancers, which can elicit an immune response leading to the induction of autoantibodies. However, BMI-1 autoantibody as a biomarker has seldom been studied with the exception of nasopharyngeal carcinoma. Whether BMI-1 autoantibodies can be used as a biomarker for cervical carcinoma is unclear. In this study,BMI-1 proteins were isolated by screening of a T7 phage cDNA library from mixed cervical carcinoma tissues. We analyzed BMI-1 autoantibody levels in serum samples from 67 patients with cervical carcinoma and 65 controls using ELISA and immunoblot. BMI-1 mRNA or protein levels were over-expressed in cervical carcinoma cell lines. Immunoblot results exhibited increased BMI-1 autoantibody levels in patient sera compared to normal sera. Additionally, the results for antibody affinity assay showed that there was no difference between cervical polyps and normal sera of BMI-1 autoantibody levels, but it was significantly greater in patient sera than that in normal controls (patient 0.827±0.043 and normal 0.445±0.023; P<0.001). What's more, the levels of BMI-1 autoantibody increased significantly at stage I (0.672±0.019) compared to normal sera (P<0.001), and levels of BMI-1 autoantibodies were increased gradually during the tumor progression (stage I 0.672±0.019; stage II 0.775 ±0.019; stage III 0.890 ±0.027; stage IV 1.043±0.041), which were significantly correlated with disease progression of cervical carcer (P<0.001). Statistical analyses using logistic regression and receiver operating characteristics (ROC) curves indicated that the BMI-1 autoantibody level can be used as a biomarker for cervical carcinoma (sensitivity 0.78 and specificity 0.76; AUC = 0.922). In conclusion, measuring BMI-1 autoantibody levels of patients with cervical cancer could have clinical prognostic value as well as a non-tissue specific biomarker for neoplasms expressing BMI-1. PMID:22132147

Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

PubMed Central

Qinna, Nidal A; Badwan, Adnan A

2015-01-01

Streptozotocin (STZ) is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL), noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents and insulin delivery systems. PMID:26005328

Hypertrophic Pachymeningitis and the Syndrome of Inappropriate Antidiuretic Hormone Secretion: Coincidence or Cause?

PubMed Central

Harsch, Igor Alexander; Schiffer, Anne; Konturek, Peter C.

2017-01-01

Objective To investigate a potential cause of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Clinical Presentation and Intervention A 70-year-old female patient had nausea and collapsed. Although euvolemic, pathological laboratory findings showed hyponatremia and hypoosmolality, and cerebral magnetic resonance imaging showed hypertrophic pachymeningitis. Secondary hypertrophic pachymeningitis was excluded. Other nonneurological reasons for SIADH were also excluded. Moderate fluid restriction restored an almost normal serum osmolality and sodium. Conclusion This case of SIADH was conservatively treated with moderate fluid restriction that almost restored normal serum osmolality and sodium levels. PMID:28245481

[Oxyhemoglobin dissociation curve and 2,3-diphosphoglycerate in chronic hypoxemia].

PubMed

Koizumi, M

1991-05-01

The measurement of the oxyhemoglobin dissociation curve (ODC) and 2,3-diphosphoglycerate (2,3-DPG) in patients with chronic hypoxemia is important from the view point of tissue oxygenation. However, there have been no consistent results that explain the relation among chronic hypoxemia, 2,3-DPG and P50, which is oxygen pressure at an oxygen saturation of 50 percent. The aim of this study is to clarify what factors affect P50 and 2,3-DPG. 1) Patients with chronic hypoxemia, who showed PaO2 less than 60 Torr, had significantly higher P50 than normal subjects. 2) The concentration of Hb showed significant negative correlation with both P50 and 2,3-DPG. 3) Arterial blood pH showed significant positive correlation with both P50 and 2,3-DPG. 4) In a group with normal levels of Hb and pH, there was significant negative relationship between PaO2 and P50. 5) In a group with normal levels of Hb and pH, there was significant positive relationship between PaCO2 and P50. 6) In a group with normal levels of Hb, pH and PaCO2, there was significant negative relationship between PaO2 and 2,3-DPG. In conclusion, P50 and 2,3-DPG are affected largely by Hb concentration or blood pH, with or without hypoxemia. However there is a mechanism by which P50 and 2,3-DPG are increased by hypoxemia itself in a group with normal levels of Hb, pH and PaCO2.

Raised D-dimer levels in acute sickle cell crisis and their correlation with chest X-ray abnormalities

PubMed Central

Dar, Javeed; Mughal, Inam; Hassan, Hilali; Al Mekki, Taj E.; Chapunduka, Zivani; Hassan, Imad S. A.

2010-01-01

Objective: Quantitation of D-dimer level during a sickling crisis and its correlation with other clinical abnormalities. Design: Prospective longitudinal study. Setting: Armed Forces Hospital, Southern Region, Kingdom of Saudi Arabia. Patients: Adult patients (12 years and older) admitted acutely with a sickle cell crisis who consent to taking part in the study. Candidates may re-participate if they are readmitted with a further acute painful crisis. Results: 36 patients with homozygous sickle cell disease consented to take part in the study. D-dimer levels were raised in 31 (68.9%) of 45 episodes of painful crisis of whom 13 had an abnormal chest X-ray. Of those with a normal chest X-ray only one patient had a raised D-dimer level: sensitivity of 92.3%, specificity 40.6%, positive predictive value 38.7% and negative predictive value of 92.9% for an abnormal chest X-ray. Conclusion: D-dimer levels are frequently raised during an acute painful crisis. A normal level has a high negative predictive value for an abnormal chest X-ray. PMID:21063468

Normal Morning Melanin-Concentrating Hormone Levels and No Association with Rapid Eye Movement or Non-Rapid Eye Movement Sleep Parameters in Narcolepsy Type 1 and Type 2

PubMed Central

Schrölkamp, Maren; Jennum, Poul J.; Gammeltoft, Steen; Holm, Anja; Kornum, Birgitte R.; Knudsen, Stine

2017-01-01

Study Objectives: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid (CSF) MCH levels, in contrast to previously reported normal evening/afternoon levels. Methods: Lumbar CSF and plasma were collected from 07:00 to 10:00 from 57 patients with narcolepsy (subtypes: 47 NT1; 10 NT2) diagnosed according to International Classification of Sleep Disorders, Third Edition (ICSD-3) and 20 healthy controls. HCRT-1 and MCH levels were quantified by radioimmunoassay and correlated with clinical symptoms, polysomnography (PSG), and Multiple Sleep Latency Test (MSLT) parameters. Results: CSF and plasma MCH levels were not significantly different between narcolepsy patients regardless of ICSD-3 subtype, HCRT-1 levels, or compared to controls. CSF MCH and HCRT-1 levels were not significantly correlated. Multivariate regression models of CSF MCH levels, age, sex, and body mass index predicting clinical, PSG, and MSLT parameters did not reveal any significant associations to CSF MCH levels. Conclusions: Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH measurement is not an informative diagnostic marker for narcolepsy. Citation: Schrölkamp M, Jennum PJ, Gammeltoft S, Holm A, Kornum BR, Knudsen S. Normal morning melanin-concentrating hormone levels and no association with rapid eye movement or non-rapid eye movement sleep parameters in narcolepsy type 1 and type 2. J Clin Sleep Med. 2017;13(2):235–243. PMID:27855741

Association of maternal weight with FADS and ELOVL genetic variants and fatty acid levels- The PREOBE follow-up

PubMed Central

de la Garza Puentes, Andrea; Montes Goyanes, Rosa; Chisaguano Tonato, Aida Maribel; Torres-Espínola, Francisco José; Arias García, Miriam; de Almeida, Leonor; Bonilla Aguirre, María; Guerendiain, Marcela; Castellote Bargalló, Ana Isabel; Segura Moreno, Maite; García-Valdés, Luz; Campoy, Cristina; Lopez-Sabater, M. Carmen

2017-01-01

Single nucleotide polymorphisms (SNPs) in the genes encoding the fatty acid desaturase (FADS) and elongase (ELOVL) enzymes affect long-chain polyunsaturated fatty acid (LC-PUFA) production. We aimed to determine if these SNPs are associated with body mass index (BMI) or affect fatty acids (FAs) in pregnant women. Participants (n = 180) from the PREOBE cohort were grouped according to pre-pregnancy BMI: normal-weight (BMI = 18.5–24.9, n = 88) and overweight/obese (BMI≥25, n = 92). Plasma samples were analyzed at 24 weeks of gestation to measure FA levels in the phospholipid fraction. Selected SNPs were genotyped (7 in FADS1, 5 in FADS2, 3 in ELOVL2 and 2 in ELOVL5). Minor allele carriers of rs174545, rs174546, rs174548 and rs174553 (FADS1), and rs1535 and rs174583 (FADS2) were nominally associated with an increased risk of having a BMI≥25. Only for the normal-weight group, minor allele carriers of rs174537, rs174545, rs174546, and rs174553 (FADS1) were negatively associated with AA:DGLA index. Normal-weight women who were minor allele carriers of FADS SNPs had lower levels of AA, AA:DGLA and AA:LA indexes, and higher levels of DGLA, compared to major homozygotes. Among minor allele carriers of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher DHA:EPA index than the normal-weight group; however, they did not present higher DHA concentrations than the normal-weight women. In conclusion, minor allele carriers of FADS SNPs have an increased risk of obesity. Maternal weight changes the effect of genotype on FA levels. Only in the normal-weight group, minor allele carriers of FADS SNPs displayed reduced enzymatic activity and FA levels. This suggests that women with a BMI≥25 are less affected by FADS genetic variants in this regard. In the presence of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher n-3 LC-PUFA production indexes than women with normal weight, but this was not enough to obtain a higher n-3 LC-PUFA concentration. PMID:28598979

High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

PubMed Central

2013-01-01

Background Metabolic acidosis leads to chronic kidney disease (CKD) progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression. Methods One hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR) or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome. Results Female patients were 36.3%: average age (SD), 70.4 (6.6) years; eGFR, 25.7 (13.6) ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2) mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8) mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3) mEq/l]: adjusted hazard ratio (HR), 3.511 (95% CI, 1.342-9.186). A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI), 0.684-0.914]. Conclusions In elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression. PMID:23298330

Predicting normal tissue radiosensitivity

NASA Astrophysics Data System (ADS)

Dickson, Jeanette

Two methods of predicting normal cell radiosensitivity were investigated in different patient groups. Plasma transforming growth factor beta one (TGFbeta1) levels were measured by ELISA, using a commercially available kit. Residual DNA double strand breaks were measured in normal epidermal fibroblasts following 150 Gy. After allowing 24 hours for repair, the DNA damage was assayed using pulsed field gel electrophoresis (PFGE). Pretreatment plasma TGFbeta1 levels were investigated retrospectively in patients with carcinoma of the cervix in relation to tumour control and late morbidity following radiotherapy. Plasma TGFbeta1 levels increased with increasing disease stage. They also correlated with two other known measures of tumour burden i.e. plasma levels of carcinoma antigen 125 (CA125) and tissue polypeptide antigen (TPA). Elevated pretreatment plasma TGFbeta1 levels predicted for a poor outcome both in terms of local control and overall survival. Plasma TGF?l levels did not predict for the development of radiotherapy morbidity of any grade. In conclusion pre-treatment plasma TGFbeta1 levels predict for tumour burden and tumour outcome in patients with carcinoma of the cervix. Changes in plasma TGFbeta1 levels measured prospectively may predict for radiation morbidity and should be investigated. A prospective study was undertaken in patients with carcinoma of the head and neck region. Changes in plasma TGFbeta1 levels between the start and the end of a course of radical radiotherapy were investigated in relation to the development of acute radiation toxicity. Patients were categorised according to the pattern of response of their TGFbeta1 levels over the course of their treatment. Those patients whose TGFbeta1 levels decreased, but did not normalise during radiotherapy were assigned to category 2. Category 2 predicted for a severe acute reaction, as measured using the LENT SOMA score, with a sensitivity of 33% and a specificity of 100%. The positive predictive value of was 100%. As part of the validation of the commercially available TGFbeta1 kit, samples were obtained from sixty-six normal volunteers with a wide age distribution. This large series demonstrated an unexpected age-related rise in TGFbeta1 levels that had not been previously demonstrated in the literature. In breast carcinoma patients, two assays were performed retrospectively. Both pre-treatment plasma TGFbeta1 levels and residual DNA double strand breaks (measured using PFGE) were correlated with clinical outcome. Outcome was in the form of a total LENT SOMA score and late radiation fibrosis score, as measured by clinical palpation. No relationship was demonstrated between either pretreatment TGFbeta1 levels or residual DNA double strand breaks and late radiotherapy outcome. This failed to validate a similar series of patients investigated in the same department using the same technique. This work has shown that measurement of residual DNA double strand breaks using PFGE is not sufficiently robust to be used clinically as a predictor of normal tissue radioresponse. In conclusion, changes in TGFbeta1 plasma levels occurring over time during a course of radical radiotherapy, hold promise for the development of a rapid test of intrinsic radiosensitivity.

SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

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

Zhang, Q; Lei, Y; Zheng, D

Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness weremore » created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing.« less

Repetition priming of words and nonwords in Alzheimer's disease and normal aging

PubMed Central

Ober, Beth A.; Shenaut, Gregory K.

2014-01-01

Objective This study examines the magnitude and direction of nonword and word lexical decision repetition priming effects in Alzheimer’s disease (AD) and normal aging, focusing specifically on the negative priming effect sometimes observed with repeated nonwords. Method Probable Alzheimer's disease (AD) patients (30), elderly normal controls (34), and young normal controls (49) participated in a repetition priming experiment using low-frequency words and word-like nonwords with a letter-level orthographic orienting task at study followed by a lexical decision test phase. Results Although participants' reaction times were longer in AD compared to elderly normal, and elderly normal compared to young normal, the repetition priming effect and the degree to which the repetition priming effect was reversed for nonwords compared to words was unaffected by AD or normal aging. Conclusion AD patients, like young and elderly normal participants, are able to modify (in the case of words) and create (in the case of nonwords) long-term memory traces for lexical stimuli, based on a single orthographic processing trial. The nonword repetition results are discussed from the perspective of new vocabulary learning commencing with a provisional lexical memory trace created after orthographic encoding of a novel word-like letter string. PMID:25000325

MicroRNA-300 inhibited glioblastoma progression through ROCK1.

PubMed

Zhou, Fucheng; Li, Yang; Hao, Zhen; Liu, Xuanxi; Chen, Liang; Cao, Yu; Liang, Zuobin; Yuan, Fei; Liu, Jie; Wang, Jianjiao; Zheng, Yongri; Dong, Deli; Bian, Shan; Yang, Baofeng; Jiang, Chuanlu; Li, Qingsong

2016-06-14

Glioblastoma is a common type of brain aggressive tumors and has a poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous and non-coding RNAs that play crucial roles in cell proliferation, survival and invasion. Deregulated expression of miR-300 has been studied in a lot of cancers. However, the role of miR-300 in glioblastoma is still unknown. In this study, we demonstrated that miR-300 expression was downregulated in glioblastoma tissues compared with the normal tissues. Lower expression level of miR-300 was observed in thirty cases (75 %, 30/40) of glioblastoma samples compared with the normal samples. Moreover, the overall survival of glioblastoma patients with lower miR-300 expression level was shorter than those with higher miR-300 expression level. In addition, miR-300 expression was also downregulated in glioblastoma cell lines. Overexpression of miR-300 inhibited cell proliferation, cell cycle and invasion in glioblastoma cell line U87 and U251. Moreover, we identified ROCK1 as a direct target of miR-300 in U87 and U251 cells. Overexpression of ROCK1 partially rescued the miR-300-mediated cell growth. ROCK1 expression levels in glioblastoma tissues were higher than that in normal tissues. ROCK1 expression levels were higher in thirty-one cases of glioblastoma samples than their normal samples. Furthermore, the expression level ROCK1 was inversely correlated with the expression level of miR-300. Importantly, overexpression of miR-300 suppressed glioblastoma progression in an established xenograft model. In conclusion, we revealed that miR-300 might act as a tumor suppressor gene through inhibiting ROCK1 in glioblastoma.

MicroRNA-300 inhibited glioblastoma progression through ROCK1

PubMed Central

Hao, Zhen; Liu, Xuanxi; Chen, Liang; Cao, Yu; Liang, Zuobin; Yuan, Fei; Liu, Jie; Wang, Jianjiao; Zheng, Yongri; Dong, Deli; Bian, Shan; Yang, Baofeng; Jiang, Chuanlu; Li, Qingsong

2016-01-01

Glioblastoma is a common type of brain aggressive tumors and has a poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous and non-coding RNAs that play crucial roles in cell proliferation, survival and invasion. Deregulated expression of miR-300 has been studied in a lot of cancers. However, the role of miR-300 in glioblastoma is still unknown. In this study, we demonstrated that miR-300 expression was downregulated in glioblastoma tissues compared with the normal tissues. Lower expression level of miR-300 was observed in thirty cases (75 %, 30/40) of glioblastoma samples compared with the normal samples. Moreover, the overall survival of glioblastoma patients with lower miR-300 expression level was shorter than those with higher miR-300 expression level. In addition, miR-300 expression was also downregulated in glioblastoma cell lines. Overexpression of miR-300 inhibited cell proliferation, cell cycle and invasion in glioblastoma cell line U87 and U251. Moreover, we identified ROCK1 as a direct target of miR-300 in U87 and U251 cells. Overexpression of ROCK1 partially rescued the miR-300-mediated cell growth. ROCK1 expression levels in glioblastoma tissues were higher than that in normal tissues. ROCK1 expression levels were higher in thirty-one cases of glioblastoma samples than their normal samples. Furthermore, the expression level ROCK1 was inversely correlated with the expression level of miR-300. Importantly, overexpression of miR-300 suppressed glioblastoma progression in an established xenograft model. In conclusion, we revealed that miR-300 might act as a tumor suppressor gene through inhibiting ROCK1 in glioblastoma. PMID:27145462

Circulating anti-filamin C autoantibody as a potential serum biomarker for low-grade gliomas

PubMed Central

2014-01-01

Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable due to its invasive nature. Establishment of serum biomarkers for glioma would be beneficial both for early diagnosis and adequate therapeutic intervention. Filamins are an actin cross-linker and filamin C (FLNC), normally restricted in muscle tissues, offers many signaling molecules an essential communication fields. Recently, filamins have been considered important for tumorigenesis in cancers. Methods We searched for novel glioma-associated antigens by serological identification of antigens utilizing recombinant cDNA expression cloning (SEREX), and found FLNC as a candidate protein. Tissue expressions of FLNC (both in normal and tumor tissues) were examined by immunohistochemistry and quantitative RT-PCR analyses. Serum anti-FLNC autoantibody level was measured by ELISA in normal volunteers and in the patients with various grade gliomas. Results FLNC was expressed in glioma tissues and its level got higher as tumor grade advanced. Anti-FLNC autoantibody was also detected in the serum of glioma patients, but its levels were inversely correlated with the tissue expression. Serum anti-FLNC autoantibody level was significantly higher in low-grade glioma patients than in high-grade glioma patients or in normal volunteers, which was confirmed in an independent validation set of patients’ sera. The autoantibody levels in the patients with meningioma or cerebral infarction were at the same level of normal volunteers, and they were significantly lower than that of low-grade gliomas. Total IgG and anti-glutatione S-transferase (GST) antibody level were not altered among the patient groups, which suggest that the autoantibody response was specific for FLNC. Conclusions The present results suggest that serum anti-FLNC autoantibody can be a potential serum biomarker for early diagnosis of low-grade gliomas while it needs a large-scale clinical study. PMID:24946857

Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

PubMed

Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

2016-03-01

Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.

Matrix Metalloproteinase-20 Over-Expression Is Detrimental to Enamel Development: A Mus musculus Model

PubMed Central

Shin, Masashi; Hu, Yuanyuan; Tye, Coralee E.; Guan, Xiaomu; Deagle, Craig C.; Antone, Jerry V.; Smith, Charles E.; Simmer, James P.; Bartlett, John D.

2014-01-01

Background Matrix metalloproteinase-20 (Mmp20) ablated mice have enamel that is thin and soft with an abnormal rod pattern that abrades from the underlying dentin. We asked if introduction of transgenes expressing Mmp20 would revert this Mmp20 null phenotype back to normal. Unexpectedly, for transgenes expressing medium or high levels of Mmp20, we found opposite enamel phenotypes depending on the genetic background (Mmp20−/− or Mmp20+/+) in which the transgenes were expressed. Methodology/Principal Findings Amelx-promoter-Mmp20 transgenic founder mouse lines were assessed for transgene expression and those expressing low, medium or high levels of Mmp20 were selected for breeding into the Mmp20 null background. Regardless of expression level, each transgene brought the null enamel back to full thickness. However, the high and medium expressing Mmp20 transgenes in the Mmp20 null background had significantly harder more mineralized enamel than did the low transgene expresser. Strikingly, when the high and medium expressing Mmp20 transgenes were present in the wild-type background, the enamel was significantly less well mineralized than normal. Protein gel analysis of enamel matrix proteins from the high and medium expressing transgenes present in the wild-type background demonstrated that greater than normal amounts of cleavage products and smaller quantities of higher molecular weight proteins were present within their enamel matrices. Conclusions/Significance Mmp20 expression levels must be within a specific range for normal enamel development to occur. Creation of a normally thick enamel layer may occur over a wider range of Mmp20 expression levels, but acquisition of normal enamel hardness has a narrower range. Since over-expression of Mmp20 results in decreased enamel hardness, this suggests that a balance exists between cleaved and full-length enamel matrix proteins that are essential for formation of a properly hardened enamel layer. It also suggests that few feedback controls are present in the enamel matrix to prevent excessive MMP20 activity. PMID:24466234

Androgens in Women with Anorexia Nervosa and Normal-Weight Women with Hypothalamic Amenorrhea

PubMed Central

Miller, K. K.; Lawson, E. A.; Mathur, V.; Wexler, T. L.; Meenaghan, E.; Misra, M.; Herzog, D. B.; Klibanski, A.

2011-01-01

Context Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Objective Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. Design and Setting We conducted a cross-sectional study at a general clinical research center. Study Participants A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Main Outcome Measures Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Results Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Conclusions Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women. PMID:17284620

Challenges in the association of human single nucleotide polymorphism mentions with unique database identifiers

PubMed Central

2011-01-01

Background Most information on genomic variations and their associations with phenotypes are covered exclusively in scientific publications rather than in structured databases. These texts commonly describe variations using natural language; database identifiers are seldom mentioned. This complicates the retrieval of variations, associated articles, as well as information extraction, e. g. the search for biological implications. To overcome these challenges, procedures to map textual mentions of variations to database identifiers need to be developed. Results This article describes a workflow for normalization of variation mentions, i.e. the association of them to unique database identifiers. Common pitfalls in the interpretation of single nucleotide polymorphism (SNP) mentions are highlighted and discussed. The developed normalization procedure achieves a precision of 98.1 % and a recall of 67.5% for unambiguous association of variation mentions with dbSNP identifiers on a text corpus based on 296 MEDLINE abstracts containing 527 mentions of SNPs. The annotated corpus is freely available at http://www.scai.fraunhofer.de/snp-normalization-corpus.html. Conclusions Comparable approaches usually focus on variations mentioned on the protein sequence and neglect problems for other SNP mentions. The results presented here indicate that normalizing SNPs described on DNA level is more difficult than the normalization of SNPs described on protein level. The challenges associated with normalization are exemplified with ambiguities and errors, which occur in this corpus. PMID:21992066

Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer

PubMed Central

Aldakkak, Mohammed; Christians, Kathleen K; Krepline, Ashley N; George, Ben; Ritch, Paul S; Erickson, Beth A; Johnston, Fabian M; Evans, Douglas B; Tsai, Susan

2015-01-01

Background The prognostic value of CA19-9 in patients with pancreatic cancer (PC) treated with neoadjuvant therapy has not been well described. Methods Pre-treatment CA19-9 levels (with concomitant normal bilirubin level) in patients with localized PC were categorized as normal (≤35), low (36–200), moderate (201–1000), or high (>1000). Post-treatment CA19-9 was measured after neoadjuvant therapy, prior to surgery. Results Pre-treatment CA19-9 levels were evaluable in 235 patients, levels were normal in 60 (25%) patients, low in 78 (33%) patients, moderate in 69 (29%) and high in 28 (12%). After neoadjuvant therapy, post-treatment CA19-9 normalized (≤ 35) in 40 (51%) of the patients in the low group, 14 (21%) of the moderate and 5 (19%) of the high group (P < 0.001). Of the 235 patients, 168 (71%) completed all intended therapy including a pancreatectomy; 44 (73%), 62 (79%), 46 (67%) and 16 (57%) of the normal, low, moderate and high groups (P = 0.10). Among these 168 patients, the median overall survival was 38.4, 43.6, 44.7, 27.2 and 26.4 months for normal, low, moderate and high CA19-9 groups (log rank P = 0.72). Among resected patients, an elevated pre-treatment CA19-9 was of little prognostic value; instead, it was the CA19-9 response to neoadjuvant therapy that was prognostic [hazard ratio (HR): 1.80, P = 0.02]. Conclusions Among patients who completed neoadjuvant therapy and surgery, pre-treatment CA19-9 obtained at the time of diagnosis was not predictive of overall survival, but normalization of post-treatment CA19-9 in response to neoadjuvant therapy was highly prognostic. PMID:26255895

Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients

PubMed Central

Monsanto, Stephany P.; Edwards, Andrew K.; Zhou, Juhua; Nagarkatti, Prakash; Nagarkatti, Mitzi; Young, Steven L.; Lessey, Bruce A.; Tayade, Chandrakant

2016-01-01

Objective To determine the impact of endometriotic lesion removal on local and systemic inflammation. Design Multiplex cytokine analysis on samples from endometriosis patients before surgery, 2 weeks after surgery, and 3 months after surgery. Setting Academic teaching hospital and university. Patient(s) A total of 43 endometriosis patients before and after excision of lesions by means of laparoscopic surgery, and 25 normal women. Intervention(s) None. Main Outcome Measure(s) Plasma, eutopic and ectopic tissue, and peritoneal fluid cytokine levels. Result(s) Compared with presurgery plasma samples, levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL) 2, IL-8, and IL-10 decreased significantly by 2 weeks after surgery in endometriosis patients. Interestingly, levels began to rise at 3 months after surgery in most cases. In tissue, levels of GM-CSF and IL-15 were lower in eutopic tissue, while levels of basic fibroblast growth factor, interferon-inducible protein 10, IL-1 receptor antagonist, granulocyte colony–stimulating factor, macrophage inflammatory protein 1β, IL-7, and IL-5 were higher in eutopic than in ectopic tissue. In peritoneal fluid, levels of IL-5 and IL-12 were higher in early versus advanced stages of endometriosis. Compared with normal women, plasma from endometriosis patients had higher levels of inflammatory cytokines. Conclusion(s) Endometriotic lesion removal significantly alters the inflammatory profile both locally and systemically in women with endometriosis. Our findings indicate that ectopic lesions are the major drivers of systemic inflammation in endometriosis. The transitory nature of the change may reflect the recurrence of the condition and the influence of systemic factors in its onset. PMID:26698677

System performance conclusions

NASA Technical Reports Server (NTRS)

Arndt, G. D.

1980-01-01

The advantages and disadvantages of reducing power levels and using antennas with diameters smaller than 1 Km were evaluated if rectenna costs and land usage requirements become major factors, operating at 5800 megahertz should be considered. Three sequences (random, incoherent phasing, and concentric rings - center to edge) provided satisfactory performance in that the resultant sidelobe levels during startup/ shutdown were lower than the steady-state levels present during normal operations. Grating lobe peaks and scattered power levels were used to determine the array/subarray mechanical alignment requirements. The antenna alignment requirement is 1 min or 3 min depending on phase control configuration. System error parameters were defined to minimize scattered microwave power.

Relationship of serum CEA levels to tumour size and CEA content in nude mice bearing colonic-tumour xenografts.

PubMed Central

Lewis, J. C.; Keep, P. A.

1981-01-01

The relationship of serum carcinoembryonic antigen (CEA) levels to tumour size and antigen content was studied in nude mice bearing well differentiated, mucinous human colonic-tumour xenografts. Blood samples were taken from normal nude mice and others bearing xenografts, whose size had been calculated from in vivo measurements; saline and KCl extracts were made of a proportion of these tumours. Sera and tissue extracts were assayed for CEA activity by double-antibody radioimmunoassay. Extracts were also made from the livers and spleens of tumour-bearing and normal nude mice. All normal sera and 78% of sera from tumour-bearing animals had CEA values less than 11.4 ng/ml. No clear correlation was found between serum CEA levels greater than 11.4 ng/ml and tumour size or weight, or between serum CEA and tumour CEA concentrations or total CEA burden. The concentration of CEA in those tumours tested varied from 1 to 22 microgram/g. Our results confirm and extend the conclusions reached by others (Stragand et al., 1980) studying the significance of serum CEA levels with xenograft model systems. The complexity of factors contributing to circulating CEA is discussed in the light of our findings. Images Fig. 1 PMID:7284235

Morphology of ovaries in laron dwarf mice, with low circulating plasma levels of insulin-like growth factor-1 (IGF-1), and in bovine GH-transgenic mice, with high circulating plasma levels of IGF-1

PubMed Central

2012-01-01

Background It is well known that somatotrophic/insulin signaling affects lifespan in experimental animals, and one of the signs of aging is progressive gonadal dysfunction. Methods To study the effects of insulin-like growth factor-1 (IGF-1) plasma level on ovaries, we analyzed ovaries isolated from 2-year-old growth hormone receptor knockout (GHR-KO) Laron dwarf mice, with low circulating plasma levels of IGF-1, and 6-month-old bovine growth hormone transgenic (bGHTg) mice, with high circulating plasma levels of IGF-1. The ages of the Laron dwarf mutants employed in our studies were selected based on their overall survival (up to ~ 4 years for Laron dwarf mice and ~ 1 year for bGHTg mice). Results Morphological analysis of the ovaries of mice that reached ~50% of their maximal life span revealed a lower biological age for the ovaries isolated from 2-year-old Laron dwarf mice than their normal-lifespan wild type littermates. By contrast, the ovarian morphology of increased in size 6 month old bGHTg mice was generally normal. Conclusion Ovaries isolated from 2-year-old Laron dwarf mice exhibit a lower biological age compared with ovaries from normal WT littermates at the same age. At the same time, no morphological features of accelerated aging were found in 0.5-year-old bGHTg mice compared with ovaries from normal the same age-matched WT littermates. PMID:22747742

Preventive fraction of physical fitness on risk factors in cardiac patients: Retrospective epidemiological study

PubMed Central

Caru, Maxime; Kern, Laurence; Bousquet, Marc; Curnier, Daniel

2018-01-01

AIM To quantify the preventive fraction of physical fitness on the risk factors in patients with cardiovascular diseases (CVDs). METHODS A total of 249 subjects (205 men and 44 women) suffering from CVD were categorized into four groups, according to their percentage of physical fitness. We calculated the odds ratio to obtain the preventive fraction in order to evaluate the impact of the physical fitness level on the risk factors (i.e., abdominal obesity, depression, diabetes, dyslipidemia, hypertension, obesity, overweight and smoking). RESULTS It is observed that a normal physical fitness level is sufficient to induce a preventive action on abdominal obesity (38%), diabetes (12%), hypertension (33%), obesity (12%) and overweight (11%). Also, the preventive fraction increases with the level of physical fitness, in particular for hypertension (36%) and overweight (16%). A high physical fitness level does not necessarily induce a preventive action in most risk factors, excluding depression. CONCLUSION This is the first study which demonstrates that reaching a normal physical fitness level is enough to induce a protection for some risk factors, despite having a CVD. PMID:29707165

Comparative expression analysis of Septin 14 in testes of infertile men with normal spermatogenesis and spermatogenic failure

PubMed Central

Shafipour, Maryam; Sabbaghian, Marjan; Shahhoseini, Maryam; Sadighi Gilani, Mohammad Ali

2014-01-01

Background: Septins are an evolutionary conserved group of GTP-binding and filament-forming proteins that have diverse cellular roles. An increasing body of data implicates the septin family in the pathogenesis of diverse states including cancers, neurodegeneration, and male infertility. Objective: The objective of the study was to evaluate the expression pattern of Septin14 in testis tissue of men with and without spermatogenic failure. Materials and Methods: The samples retrieved accessible random between infertile men who underwent diagnostic testicular biopsy in Royan institute. 10 infertile men with obstructive azoospermia and normal spermatogenesis and 20 infertile men with non-obstructive azoospermia were recruited for real-time reverse transcription (RT)-PCR analysis of the testicular tissue. Total RNA was extracted with trizol reagent. Results: Comparison of the mRNA level of septin14 revealed that in tissues with partial (n=10) or complete spermatogenesis (n=10), the expression of septin 14 was significantly higher than sertoli cell only tissues. Conclusion: The testicular tissues of men with hypospermatogenesis, maturation arrest and sertoli cell only had lower levels of septin 14 transcripts than normal men. These data indicates that Septin 14 expression level is critical for human spermatogenesis. PMID:24799881

Early Choline Levels From 3-Tesla MR Spectroscopy After Exclusive Radiation Therapy in Patients With Clinically Localized Prostate Cancer are Predictive of Plasmatic Levels of PSA at 1 Year

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

Crehange, Gilles, E-mail: gcrehange@cgfl.fr; Maingon, Philippe; Gauthier, Melanie

2011-11-15

Purpose: To investigate the time course response of prostate metabolism to irradiation using magnetic resonance spectroscopy (MRS) at 3-month intervals and its impact on biochemical control. Methods and Materials: Between January 2008 and April 2010, 24 patients with localized prostate cancer were prospectively enrolled in the Evaluation of the Response to Irradiation with MR Spectroscopy (ERIS) trial. All the patients had been treated with intensity-modulated radiation therapy with or without long-term adjuvant hormonal therapy (LTHT) and underwent 3-T MRS and prostate-specific antigen (PSA) assays at baseline and every 3 months thereafter up to 12 months. Results: After radiation, the meanmore » normalized citrate level (citrate/water) decreased significantly over time, both in the peripheral zone (PZ) (p = 0.0034) and in the entire prostate (p = 0.0008), whereas no significant change was observed in mean normalized choline levels (choline/water) in the PZ (p = 0.84) and in the entire prostate (p = 0.95). At 6 months after radiation, the mean choline level was significantly lower in the PZ for patients with a PSA value of {<=}0.5 ng/mL at 12 months (4.9 {+-} 1.7 vs. 7.1 {+-} 1.5, p = 0.0378). Similar results were observed at 12 months in the PZ (6.2 {+-} 2.3 vs. 11.4 {+-} 4.1, p = 0.0117 for choline level and 3.4 {+-} 0.7 vs. 16.1 {+-} 6.1, p = 0.0054 for citrate level) and also in the entire prostate (6.2 {+-} 1.9 vs. 10.4 {+-} 3.2, p = 0.014 for choline level and 3.0 {+-} 0.8 vs. 13.3 {+-} 4.7, p = 0.0054 for citrate level). For patients receiving LTHT, there was no correlation between choline or citrate levels and PSA value, either at baseline or at follow-up. Conclusions: Low normalized choline in the PZ, 6 months after radiation, predicts which patients attained a PSA {<=}0.5 ng/mL at 1 year. Further analyses with longer follow-up times are warranted to determine whether or not these new biomarkers can conclusively predict the early radiation response and the clinical outcome for patients with or without LTHT.« less

High-fat diet with stress impaired islets' insulin secretion by reducing plasma estradiol and pancreatic GLUT2 protein levels in rats' proestrus phase.

PubMed

Salimi, M; Zardooz, H; Khodagholi, F; Rostamkhani, F; Shaerzadeh, F

2016-10-01

This study was conducted to determine whether two estrus phases (proestrus and diestrus) in female rats may influence the metabolic response to a high-fat diet and/or stress, focusing on pancreatic insulin secretion and content. Animals were divided into high-fat and normal diet groups, then each group was subdivided into stress and non-stress groups, and finally, each one of these was divided into proestrus and diestrus subgroups. At the end of high-fat diet treatment, foot-shock stress was applied to the animals. Then, blood samples were taken to measure plasma factors. Finally, the pancreas was removed for determination of glucose transporter 2 (GLUT2) protein levels and assessment of insulin content and secretion of the isolated islets. In the normal and high-fat diet groups, stress increased plasma corticosterone concentration in both phases. In both study phases, high-fat diet consumption decreased estradiol and increased leptin plasma levels. In the high-fat diet group in response to high glucose concentration, a reduction in insulin secretion was observed in the proestrus phase compared with the same phase in the normal diet group in the presence and absence of stress. Also, high-fat diet decreased the insulin content of islets in the proestrus phase compared with the normal diet. High-fat diet and/or stress caused a reduction in islet GLUT2 protein levels in both phases. In conclusion, it seems possible that high-fat diet alone or combined with foot-shock, predispose female rats to impaired insulin secretion, at least in part, by interfering with estradiol levels in the proestrus phase and decreasing pancreatic GLUT2 protein levels.

Effects of hydrogen sulfide on high glucose-induced glomerular podocyte injury in mice

PubMed Central

Liu, Ye; Zhao, Huichen; Qiang, Ye; Qian, Guanfang; Lu, Shengxia; Chen, Jicui; Wang, Xiangdong; Guan, Qingbo; Liu, Yuantao; Fu, Yuqin

2015-01-01

The aim of this study was to assess the effects of hydrogen sulfide on high glucose-induced mouse podocyte (MPC) injury and the underlying mechanisms. Mouse podocytes were randomly divided into 4 groups, including high glucose (HG), normal glucose (NG), normal glucose + DL-propargylglycine (PPG), and high glucose + NaHS (HG + NaHS) groups for treatment. Then, ZO-2, nephrin, β-catenin, and cystathionine γ-lyase (CSE) protein expression levels were determined by western blot. We found that high glucose significantly reduced nephrin, ZO-2, and CSE expression levels (P<0.05), and overtly elevated β-catenin amounts (P<0.05), in a time-dependent manner. Likewise, PPG at different concentrations in normal glucose resulted in significantly lower CSE, ZO-2, and nephrin levels (P<0.05), and increased β-catenin amounts (P<0.05). Interestingly, significantly increased ZO-2 and nephrin levels, and overtly reduced β-catenin amounts were observed in the HG + NaHS group compared with HG treated cells (P<0.01). Compared with NG treated cells, decreased ZO-2 and nephrin levels and higher β-catenin amounts were obtained in the HG + NaHS group. In conclusion,CSE downregulation contributes to hyperglycemia induced podocyte injury, which is alleviated by exogenous H2S possibly through ZO-2 upregulation and the subsequent suppression of Wnt/β-catenin pathway. PMID:26261567

Effect of Alpinia calcarata on glucose uptake in diabetic rats-an in vitro and in vivo model

PubMed Central

2014-01-01

Background Diabetes mellitus is a heterogeneous metabolic disorders characterized by abnormally high levels of blood glucose The main objective of the present work is to study the effect of Alpinia calcarata on glucose uptake in streptozotocin (STZ) induced diabetic rats. Methods The diabetes was induced by single dose of STZ (45 mg/kg) in citrate buffer, while the normal control group was given the vehicle (citrate buffer) only. After induction of diabetes, the diabetic animals were treated with ethanolic extract of Alpinia calcarata (200 mg/kg) and glibenclamide (2 mg/kg) for 30 days. Blood glucose estimation was performed every week of the study. At the end of study period, animals were sacrificed for biochemical studies. Results Streptozotocin induced diabetic rats shows the altered levels of various biochemical profiles. Those levels were brought back to near normal upon treatment with ethanolic extract of Alpinia calcarata and standard drug glibanclamide. No significant changes were observed on treatment with plant extract alone group indicated that there are no toxic substances present in Alpinia calcarata. The antidiabetic activity of plant extract was also further confirmed by histopathological studies. The ethanolic extract of Alpinia calcarata shows significant inhibition of alpha glucosidase activity and also enhancing the glucose uptake in rat hemidiaphragm. Conclusions In conclusion, the ethanolic extract of Alpinia calcarata ameliorates the condition associated with diabetes. PMID:24502532

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

PubMed

Hay, Cathy J; Brady, Brian M; Zitzmann, Michael; Osmanagaoglu, Kaan; Pollanen, Pasi; Apter, Dan; Wu, Frederick C W; Anderson, Richard A; Nieschlag, Eberhard; Devroey, Paul; Huhtaniemi, Ilpo; Kersemaekers, Wendy M

2005-04-01

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women

PubMed Central

Akopians, Alin L.; Madrigal, Vanessa K.; Ramirez, Emmanuel; Margolis, Daniel J.; Sarma, Manoj K.; Thomas, Albert M.; Grogan, Tristan R.; Haykal, Rasha; Schooler, Tery A.; Okeya, Bette L.; Abbott, David H.; Chazenbalk, Gregorio D.

2016-01-01

Context: Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction. Objective: This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia. Design: This is a prospective cohort study. Setting: The setting was an academic medical center. Patients: Six normal weight PCOS women and 14 age- and body mass index-matched normoandrogenic ovulatory (NL) women were included. Intervention(s): All women underwent circulating hormone and metabolic measurements; frequently sampled intravenous glucose tolerance testing; total body dual-energy x-ray absorptiometry; abdominal magnetic resonance imaging; and SC abdominal fat biopsy. Main Outcome Measure(s): Circulating hormones and metabolites, body fat and its distribution, and adipocyte size were compared between PCOS and NL women, and were correlated with each other in all women. Results: Circulating LH and androgen levels were significantly greater in PCOS than NL women, as were fasting insulin levels, pancreatic β-cell responsiveness to glucose, and total abdominal fat mass. Intra-abdominal fat mass also was significantly increased in PCOS women and was positively correlated with circulating androgen, fasting insulin, triglyceride, and non-high-density lipoprotein cholesterol levels in all women. SC abdominal fat mass was not significantly increased in PCOS women, but contained a greater proportion of small SC abdominal adipocytes that positively correlated with serum androgen levels in all women. Conclusion: Hyperandrogenism in normal weight PCOS women is associated with preferential intra-abdominal fat deposition and an increased population of small SC abdominal adipocytes that could constrain SC adipose storage and promote metabolic dysfunction. PMID:27571186

Beneficial effect of tagatose consumption on postprandial hyperglycemia in Koreans: a double-blind crossover designed study.

PubMed

Kwak, Jung Hyun; Kim, Min Sun; Lee, Jin Hee; Yang, Yoon Jung; Lee, Ki Ho; Kim, Oh Yoen; Lee, Jong Ho

2013-08-01

The present study determined the effect of tagatose supplementation on postprandial hyperglycemia in normal (n = 54) and hyperglycemic subjects [n = 40, impaired fasting glucose (IFG) and newly diagnosed type 2 diabetes]. In a double-blind crossover designed study, study subjects were randomly assigned to consume a sucralose-erythritol drink (the placebo) or a tagatose-containing drink (the test) with a seven-day interval. Finally, 85 subjects completed the study (normal, n = 52; hyperglycemic, n = 33). Blood samples were collected at 0, 30, 60 and 120 min after ingestion and analyzed for fasting and postprandial levels of glucose, insulin and C-peptide. Basic anthropometric parameters and lipid files were also measured. Hyperglycemic subjects were basically older and heavier, and showed higher levels of triglyceride, total- and LDL-cholesterols and apolipoprotein AI and B compared with normal subjects. After consuming the tagatose (5 g)-containing drink, hyperglycemic subjects had a significant reduction in serum levels of glucose at 120 min (p = 0.019) and glucose area under the curve (AUC) (p = 0.017), however these were not observed in normal subjects. When ages were matched between the two groups, the glucose response patterns were shown to be similar. Additionally, normal subjects who received a high-dose of tagatose-containing drinks (10 g) showed significantly lower levels of insulin at 30 min (p = 0.004) and 60 min (p = 0.011), insulin AUC (p = 0.009), and C-peptide at 30 min (p = 0.004), 60 min (p = 0.011) and C-peptide AUC (p = 0.023). In conclusion, a single dietary supplement in the form of a tagatose-containing drink may be beneficial for controlling postprandial glycemic response in Koreans.

Dietary phosphate restriction normalizes biochemical and skeletal abnormalities in a murine model of tumoral calcinosis.

PubMed

Ichikawa, Shoji; Austin, Anthony M; Gray, Amie K; Allen, Matthew R; Econs, Michael J

2011-12-01

Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis.

Dietary Phosphate Restriction Normalizes Biochemical and Skeletal Abnormalities in a Murine Model of Tumoral Calcinosis

PubMed Central

Austin, Anthony M.; Gray, Amie K.; Allen, Matthew R.; Econs, Michael J.

2011-01-01

Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis. PMID:22009723

Pharmacokinetics and ovarian suppression during use of a contraceptive vaginal ring in normal-weight and obese women

PubMed Central

WESTHOFF, Carolyn L.; TORGAL, Anupama H.; MAYEDA, Elizabeth Rose; PETRIE, Kelsey; THOMAS, Tiffany; DRAGOMAN, Monica; CREMERS, Serge

2012-01-01

BACKGROUND Many observational studies indicate higher oral contraceptive failure among obese women, but most clinical trials and physiological studies do not support these differences. Limited data indicate higher failure rates among obese contraceptive patch users. Data regarding contraceptive vaginal ring (CVR) performance in obese women are needed. METHODS 20 normal weight (BMI 19.0–24.9, median 21.65) and 20 obese (BMI 30.0–39.9, median 33.7) women enrolled in a prospective study of ethinyl estradiol (EE) and etonorgestrel (ENG) pharmacokinetics and of ovarian follicle development, endometrial thickness, and bleeding patterns, all measured biweekly during the second cycle of CVR use. RESULTS Thirty-seven women completed follow-up. Mean day 0–21 EE concentrations were lower among obese versus normal weight women (15.0 versus 22.0 pg/mL, respectively. p = 0.004), while ENG concentrations were similar (1138 versus 1256 pg/mL, respectively. p = 0.39). Follicular development was minimal in both groups, with only five women achieving a maximum follicle diameter > 13mm at any time during 3 weeks follow-up (3 normal weight and 2 obese women); these women had serum progesterone levels < 1.0. Obese women reported more bleeding or spotting than normal weight women (3.6 versus 1.4 days, respectively. p = 0.01). CONCLUSIONS While obese women had lower EE levels during CVR use, they had excellent suppression of ovarian follicle development, similar to normal weight women. This predicts that CVR effectiveness will be similar in women with a BMI up to 39.9. The lower serum EE levels in the obese women may explain the greater reported bleeding or spotting days. PMID:22727346

Reference Levels for Patient Radiation Doses in Interventional Radiology: Proposed Initial Values for U.S. Practice1

PubMed Central

Miller, Donald L.; Kwon, Deukwoo; Bonavia, Grant H.

2009-01-01

Purpose: To propose initial values for patient reference levels for fluoroscopically guided procedures in the United States. Materials and Methods: This secondary analysis of data from the Radiation Doses in Interventional Radiology Procedures (RAD-IR) study was conducted under a protocol approved by the institutional review board and was HIPAA compliant. Dose distributions (percentiles) were calculated for each type of procedure in the RAD-IR study where there were data from at least 30 cases. Confidence intervals for the dose distributions were determined by using bootstrap resampling. Weight banding and size correction methods for normalizing dose to patient body habitus were tested. Results: The different methods for normalizing patient radiation dose according to patient weight gave results that were not significantly different (P > .05). The 75th percentile patient radiation doses normalized with weight banding were not significantly different from those that were uncorrected for body habitus. Proposed initial reference levels for various interventional procedures are provided for reference air kerma, kerma-area product, fluoroscopy time, and number of images. Conclusion: Sufficient data exist to permit an initial proposal of values for reference levels for interventional radiologic procedures in the United States. For ease of use, reference levels without correction for body habitus are recommended. A national registry of radiation-dose data for interventional radiologic procedures is a necessary next step to refine these reference levels. © RSNA, 2009 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2533090354/-/DC1 PMID:19789226

Impact of Body Mass Index on Plasma N-Terminal ProB-Type Natriuretic Peptides in Chinese Atrial Fibrillation Patients without Heart Failure

PubMed Central

Zheng, Li-hui; Wu, Ling-min; Yao, Yan; Chen, Wen-sheng; Bao, Jing-ru; Huang, Wen; Shi, Rui; Zhang, Kui-jun; Zhang, Shu

2014-01-01

Background An inverse relationship between body mass index (BMI) and circulating levels of N-terminal proB-type natriuretic peptide (NT-proBNP) has been demonstrated in subjects with and without heart failure. Obesity also has been linked with increased incidence of atrial fibrillation (AF), but its influence on NT-proBNP concentrations in AF patients remains unclear. This study aimed to investigate the effect of BMI on NT-proBNP levels in AF patients without heart failure. Methods A total of 239 consecutive patients with AF undergoing catheter ablation were evaluated. Levels of NT-proBNP and clinical characteristics were compared in overweight or obese (BMI≥25 kg/m2) and normal weight (BMI<25 kg/m2) patients. Results Of 239 patients, 129 (54%) were overweight or obese. Overweight or obese patients were younger, more likely to have a history of nonparoxysmal AF, hypertension, and diabetes mellitus. Levels of NT-proBNP were significantly lower in overweight or obese than in normal weight subjects (P<0.05). The relationship of obesity and decreased NT-proBNP levels persisted in subgroup of hypertension, both gender and both age levels (≥65 yrs and <65 yrs).Multivariate linear regression identified BMI as an independent negative correlate of LogNT-proBNP level. Conclusions An inverse relationship between BMI and plasma NT-proBNP concentrations have been demonstrated in AF patients without heart failure. Overweight or obese patients with AF appear to have lower NT-proBNP levels than normal weight patients. PMID:25144363

Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: A review of four cases and the literature

PubMed Central

Witte, Todd N; Ginsberg, Allen L

2008-01-01

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8×108 red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised. PMID:18299738

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

PubMed Central

Wirth, Eva K.; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-01-01

Background The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. PMID:26601078

Elevated glucose levels in early puerperium, and association with high cortisol levels during parturition.

PubMed

Risberg, Anitha; Sjöquist, Mats; Wedenberg, Kaj; Larsson, Anders

2016-07-01

Background Gestational diabetes is one of the commonest metabolic problems associated with pregnancy and an accurate diagnosis is critical for the care. Research has shown that pregnant women have high levels of cortisol during the last stage of parturition. As cortisol is a diabetogenic hormone causing increased glucose levels, we wanted to study the association between cortisol and glucose levels during parturition. Materials and methods Glucose and cortisol were analyzed during parturition in 50 females divided according to slow (n = 11) and normal labors (n = 39). Blood samples were analyzed three times during the parturition and four times in the first day after delivery. Glucose levels were also measured once in each trimester. Results In the normal group, the glucose concentration increased from 6.2 (IQR 5.6-8.0) mmol/L in the latency phase to 11.6 (10.0-13.3) mmol/L at aftercare (p < 0.05). After parturition the glucose concentrations decreased gradually. There were significant Spearman rank correlations between glucose and cortisol values. Conclusions The changes associated with birth cause significant elevations of cortisol and glucose around parturition.

C-reactive protein levels: a prognostic marker for patients with head and neck cancer?

PubMed Central

2010-01-01

Background Recent advances in understanding complex tumor interactions have led to the discovery of an association between inflammation and cancer, in particular for colon and lung cancer, but only a very few have dealt with oral cancer. Therefore, the aim of the current study was to investigate the significance of preoperative C-reactive protein (CRP) levels as a parameter for development of lymph node metastases or recurrence. Materials and methods In 278 patients with oral cancer, preoperative CRP levels were compared with development of recurrence and metastasis. Results In 27 patients from the normal CRP group, and in 21 patients from the elevated CRP group, local recurrence was observed. Concerning lymph node metastases, 37 patients were in the normal group and 9 patients in the elevated CRP group. No significant correlation could be found between elevated CRP levels and metastasis (p = 0.468) or recurrence (p = 0.137). Conclusion Our findings do not appear to support a correlation between preoperative CRP levels and development of recurrence or metastases. In further studies, CRP levels in precancerous lesions and in Human Papilloma Virus (HPV) positive patients with oral squamous cell carcinoma (SCC) should be studied. PMID:20673375

Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.

PubMed

Tietze, Julia K; Angelova, Daniela; Heppt, Markus V; Ruzicka, Thomas; Berking, Carola

2017-07-01

The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56 dim and CD56 bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56 dim NK cells, whereas the baseline levels of CD56 bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56 dim and CD56 bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56 dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56 bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56 dim NK cells as well as normal baseline levels of CD56 bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56 dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56 bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56 dim and CD56 bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A replacement for islet equivalents with improved reliability and validity.

PubMed

Huang, Han-Hung; Ramachandran, Karthik; Stehno-Bittel, Lisa

2013-10-01

Islet equivalent (IE), the standard estimate of isolated islet volume, is an essential measure to determine the amount of transplanted islet tissue in the clinic and is used in research laboratories to normalize results, yet it is based on the false assumption that all islets are spherical. Here, we developed and tested a new easy-to-use method to quantify islet volume with greater accuracy. Isolated rat islets were dissociated into single cells, and the total cell number per islet was determined by using computer-assisted cytometry. Based on the cell number per islet, we created a regression model to convert islet diameter to cell number with a high R2 value (0.8) and good validity and reliability with the same model applicable to young and old rats and males or females. Conventional IE measurements overestimated the tissue volume of islets. To compare results obtained using IE or our new method, we compared Glut2 protein levels determined by Western Blot and proinsulin content via ELISA between small (diameter≤100 μm) and large (diameter≥200 μm) islets. When normalized by IE, large islets showed significantly lower Glut2 level and proinsulin content. However, when normalized by cell number, large and small islets had no difference in Glut2 levels, but large islets contained more proinsulin. In conclusion, normalizing islet volume by IE overestimated the tissue volume, which may lead to erroneous results. Normalizing by cell number is a more accurate method to quantify tissue amounts used in islet transplantation and research.

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease

PubMed Central

2014-01-01

Aims/hypothesis Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Methods Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Results Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Conclusions/interpretations Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that Cyclophilin A is an inflammatory mediator in atherogenesis, the mechanistic role of cyclophilin A in diabetic vascular disease progression deserves detailed investigation. PMID:24502618

Insulin secretion enhancing activity of roselle calyx extract in normal and streptozotocin-induced diabetic rats

PubMed Central

Wisetmuen, Eamruthai; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Yutanawiboonchai, Wiboonchai; Itharat, Arunporn

2013-01-01

Background and Objective: Our recent study revealed the antihyperglycemic activity of an ethanolic extract of roselle calyxes (Hibiscus sabdariffa) in diabetic rats. The present study had, therefore, an objective to investigate the mechanism underlying this activity. Materials and Methods: Male Sprague Dawley rats were induced to be diabetes by intraperitoneal injection of 45 mg/kg streptozotocin (STZ). Normal rats as well as diabetic rats were administered with the ethanolic extract of H. sabdariffa calyxes (HS-EE) at 0.1 and 1.0 g/kg/day, respectively, for 6 weeks. Then, blood glucose and insulin levels, at basal and glucose-stimulated secretions, were measured. The pancreas was dissected to examine histologically. Results: HS-EE 1.0 g/kg/day significantly decreased the blood glucose level by 38 ± 12% in diabetic rats but not in normal rats. In normal rats, treatment with 1.0 g/kg HS-EE increased the basal insulin level significantly as compared with control normal rats (1.28 ± 0.25 and 0.55 ± 0.05 ng/ml, respectively). Interestingly, diabetic rats treated with 1.0 g/kg HS-EE also showed a significant increase in basal insulin level as compared with the control diabetic rats (0.30 ± 0.05 and 0.15 ± 0.01 ng/ml, respectively). Concerning microscopic histological examination, HS-EE 1.0 g/kg significantly increased the number of islets of Langerhans in both normal rats (1.2 ± 0.1 and 2.0 ± 0.1 islet number/10 low-power fields (LPF) for control and HS-EE treated group, respectively) and diabetic rats (1.0 ± 0.3 and 3.9 ± 0.6 islet number/10 LPF for control and HS-EE treated group, respectively). Conclusion: The antidiabetic activity of HS-EE may be partially mediated via the stimulating effect on insulin secretion. PMID:23798879

Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting

PubMed Central

Marui, Akira; Okabayashi, Hitoshi; Komiya, Tatsuhiko; Tanaka, Shiro; Furukawa, Yutaka; Kita, Toru; Kimura, Takeshi; Sakata, Ryuzo

2013-01-01

OBJECTIVES High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG. METHODS Among patients undergoing their first percutaneous coronary intervention (PCI) or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 1842 patients with normal SCr levels undergoing CABG were enrolled in the study. Patients were divided into two groups based on preoperative estimated GFR calculated by the Cockcroft–Gault equation: 1339 patients with estimated GFR of ≥60 ml/min/1.73 m2 (normal group) and 503 with estimated GFR of <60 ml/min/1.73 m2 (ORI group). RESULTS Preoperative estimated GFR differed between the groups (51.3 ± 6.6 vs 85.8 ± 23.0 ml/min/1.73 m2, P < 0.01). ORI was associated with high in-hospital mortality (3.2 vs 1.0%, P < 0.01) and need for dialysis (2.0 vs 0.2%, P < 0.01). In terms of long-term outcomes, ORI was associated with high mortality compared with the normal (hazard ratio [95% confidence interval]: 1.72 [1.16–2.54], P < 0.01) and high incidence of composite cardiovascular events (death, stroke or myocardial infarction: 1.53 [1.16–2.02], P < 0.01). CONCLUSIONS ORI was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal SCr levels. A more accurate evaluation of renal function through a combination of SCr and estimated GFR is needed in patients with normal SCr levels. PMID:23793709

Comparison of T1 and T2 metabolite relaxation times in glioma and normal brain at 3 T

PubMed Central

Li, Yan; Srinivasan, Radhika; Ratiney, Helene; Lu, Ying; Chang, Susan M.; Nelson, Sarah J.

2011-01-01

Purpose To measure T1 and T2 relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels. Materials and Methods Twenty-three patients with gliomas and ten volunteers were studied with single voxel 2D J-resolved PRESS using a 3T MR scanner. Voxels were chosen in normal appearing white matter and in regions of tumor. The T1 and T2 of choline containing compounds (Cho), creatine (Cr) and N-acetyl aspartate (NAA) were estimated. Results Metabolite T1 relaxation values in gliomas were not significantly different from values in normal white matter. The T2 of Cho and Cr were statistically significantly longer for Grade 4 gliomas than for normal white matter but the T2 of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P<0.001). Conclusion The differential increase in T2 for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/NAA are higher in tumor at longer echo times relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MRSI data, where limited time is available and only one echo time can be used. PMID:18666155

Living healthier for longer: Comparative effects of three heart-healthy behaviors on life expectancy with and without cardiovascular disease

PubMed Central

2009-01-01

Background Non-smoking, having a normal weight and increased levels of physical activity are perhaps the three key factors for preventing cardiovascular disease (CVD). However, the relative effects of these factors on healthy longevity have not been well described. We aimed to calculate and compare the effects of non-smoking, normal weight and physical activity in middle-aged populations on life expectancy with and without cardiovascular disease. Methods Using multi-state life tables and data from the Framingham Heart Study (n = 4634) we calculated the effects of three heart healthy behaviours among populations aged 50 years and over on life expectancy with and without cardiovascular disease. For the life table calculations, we used hazard ratios for 3 transitions (No CVD to CVD, no CVD to death, and CVD to death) by health behaviour category, and adjusted for age, sex, and potential confounders. Results High levels of physical activity, never smoking (men), and normal weight were each associated with 20-40% lower risks of developing CVD as compared to low physical activity, current smoking and obesity, respectively. Never smoking and high levels of physical activity reduced the risks of dying in those with and without a history of CVD, but normal weight did not. Never-smoking was associated with the largest gains in total life expectancy (4.3 years, men, 4.1 years, women) and CVD-free life expectancy (3.8 and 3.4 years, respectively). High levels of physical activity and normal weight were associated with lesser gains in total life expectancy (3.5 years, men and 3.4 years, women, and 1.3 years, men and 1.0 year women, respectively), and slightly lesser gains in CVD-free life expectancy (3.0 years, men and 3.1 years, women, and 3.1 years men and 2.9 years women, respectively). Normal weight was the only behaviour associated with a reduction in the number of years lived with CVD (1.8 years, men and 1.9 years, women). Conclusions Achieving high levels of physical activity, normal weight, and never smoking, are effective ways to prevent cardiovascular disease and to extend total life expectancy and the number of years lived free of CVD. Increasing the prevalence of normal weight could further reduce the time spent with CVD in the population. PMID:20034381

Deaf individuals who work with computers present a high level of visual attention

PubMed Central

Ribeiro, Paula Vieira; Ribas, Valdenilson Ribeiro; Ribas, Renata de Melo Guerra; de Melo, Teresinha de Jesus Oliveira Guimarães; Marinho, Carlos Antonio de Sá; Silva, Kátia Karina do Monte; de Albuquerque, Elizabete Elias; Ribas, Valéria Ribeiro; de Lima, Renata Mirelly Silva; Santos, Tuthcha Sandrelle Botelho Tavares

2011-01-01

Some studies in the literature indicate that deaf individuals seem to develop a higher level of attention and concentration during the process of constructing of different ways of communicating. Objective The aim of this study was to evaluate the level of attention in individuals deaf from birth that worked with computers. Methods A total of 161 individuals in the 18-25 age group were assessed. Of these, 40 were congenitally deaf individuals that worked with computers, 42 were deaf individuals that did not work, did not know how to use nor used computers (Control 1), 39 individuals with normal hearing that did not work, did not know how to use computers nor used them (Control 2), and 40 individuals with normal hearing that worked with computers (Control 3). Results The group of subjects deaf from birth that worked with computers (IDWC) presented a higher level of focused attention, sustained attention, mental manipulation capacity and resistance to interference compared to the control groups. Conclusion This study highlights the relevance sensory to cognitive processing. PMID:29213734

Extensions, Validation, and Clinical Applications of a Feedback Control System Simulator of the Hypothalamo-Pituitary-Thyroid Axis

PubMed Central

Samuels, Mary; DiStefano, Joseph J.

2008-01-01

Background We upgraded our recent feedback control system (FBCS) simulation model of human thyroid hormone (TH) regulation to include explicit representation of hypothalamic and pituitary dynamics, and updated TH distribution and elimination (D&E) parameters. This new model greatly expands the range of clinical and basic science scenarios explorable by computer simulation. Methods We quantified the model from pharmacokinetic (PK) and physiological human data and validated it comparatively against several independent clinical data sets. We then explored three contemporary clinical issues with the new model: combined triiodothyronine (T3)/thyroxine (T4) versus T4-only treatment, parenteral levothyroxine (L-T4) administration, and central hypothyroidism. Results Combined T3/T4 therapy—In thyroidectomized patients, the L-T4–only replacement doses needed to normalize plasma T3 or average tissue T3 were 145 μg L-T4/day or 165 μgL-T4/day, respectively. The combined T4 + T3 dosing needed to normalize both plasma and tissue T3 levels was 105 μg L-T4 + 9 μgT3 per day. For all three regimens, simulated mean steady-state plasma thyroid-stimulating hormone (TSH), T3, and T4 was within normal ranges (TSH: 0.5–5 mU/L; T4: 5–12 μg/dL; T3: 0.8–1.9 ng/mL). Parenteral T4 administration—800 μg weekly or 400 μg twice weekly normalized average tissue T3 levels both for subcutaneous (SC) and intramuscular (IM) routes of administration. TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM). Central hypothyroidism—We simulated steady-state plasma T3,T4, and TSH concentrations in response to varying degrees of central hypothyroidism, reducing TSH secretion from 50% down to 0.1% of normal. Surprisingly, TSH, T3, and T4 plasma concentrations remained within normal ranges for TSH secretion as low as 25% of normal. Conclusions Combined T3/T4 treatment—Simulated standard L-T4–only therapy was sufficient to renormalize average tissue T3 levels and maintain normal TSH, T3, and T4 plasma levels, supporting adequacy of standard L-T4–only treatment. Parenteral T4 administration—TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM), supporting these therapeutic alternatives for patients with compromised L-T4 gut absorption. Central hypothyroidism—These results highlight how highly nonlinear feedback in the hypothalamic-pituitary-thyroid axis acts to maintain normal hormone levels, even with severely reduced TSH secretion. PMID:18844475

Butyrylcholinesterase Levels on Admission Predict Severity and 12-Month Mortality in Hospitalized AIDS Patients

PubMed Central

Xu, Lijun; Huang, Ying; Yang, Zongxing; Sun, Jia; Xu, Yan; Zheng, Jinlei; Kinloch, Sabine; Yin, Michael T.; Weng, Honglei

2018-01-01

Background Butyrylcholinesterase (BChE) is synthesized mainly in the liver and an important marker in many infectious/inflammatory diseases, but its role in acquired immunodeficiency syndrome (AIDS) patients is not clear. We wished to ascertain if BChE level is associated with the progression/prognosis of AIDS patients. Methods BChE levels (in U/L) were measured in 505 patients; <4500 was defined as “low” and ≥4500 as “normal.” Associations between BChE level and CD4 count, WHO stage, body mass index (BMI), C-reactive protein (CRP) level, and duration of hospitalization were assessed. Kaplan–Meier curves and Cox proportional hazards model were used to assess associations between low BChE levels and mortality, after adjustment for age, CD4 count, WHO stage, and laboratory parameters. Results A total of 129 patients (25.5%) had a lower BChE level. BChE was closely associated with CD4 count, WHO stage, CRP level, and BMI (all P < 0.001). Eighty-four patients (16.6%) died in the first year of follow-up. One-year survival was 64.5 ± 4.5% for patients with low BChE and 87.6 ± 1.8% for those with normal BChE (log-rank, P < 0.001). After adjustment for sex, age, BMI, WHO stage, and CD4 count, as well as serum levels of hemoglobin, sodium, and albumin, the hazard ratio was 1.8 (95% confidence interval, 1.0–3.2) for patients with a low BChE compared with those with a normal BChE (P = 0.035). Conclusion BChE level is associated with HIV/AIDS severity and is an independent risk factor for increased mortality in AIDS patients. PMID:29736152

Stability of the Medial Olivocochlear Reflex as Measured by Distortion Product Otoacoustic Emissions

PubMed Central

Abdala, Carolina

2015-01-01

Purpose The purpose of this study was to assess the repeatability of a fine-resolution, distortion product otoacoustic emission (DPOAE)–based assay of the medial olivocochlear (MOC) reflex in normal-hearing adults. Method Data were collected during 36 test sessions from 4 normal-hearing adults to assess short-term stability and 5 normal-hearing adults to assess long-term stability. DPOAE level and phase measurements were recorded with and without contralateral acoustic stimulation. MOC reflex indices were computed by (a) noting contralateral acoustic stimulation-induced changes in DPOAE level (both absolute and normalized) at fine-structure peaks, (b) recording the effect as a vector difference, and (c) separating DPOAE components and considering a component-specific metric. Results Analyses indicated good repeatability of all indices of the MOC reflex in most frequency ranges. Short- and long-term repeatability were generally comparable. Indices normalized to a subject's own baseline fared best, showing strong short- and long-term stability across all frequency intervals. Conclusions These results suggest that fine-resolution DPOAE-based measures of the MOC reflex measured at strategic frequencies are stable, and natural variance from day-to-day or week-to-week durations is small enough to detect between-group differences and possibly to monitor intervention-related success. However, this is an empirical question that must be directly tested to confirm its utility. PMID:25320951

Clear cell variant of follicular thyroid carcinoma with normal thyroid-stimulating hormone value: a case report

PubMed Central

2014-01-01

Introduction Clear cell carcinomas of the thyroid gland with normal thyroid-stimulating hormone value are very rare, but clear cell changes are described in most reported cases of thyroidal lesions. Case presentation In this report, we describe the case of a 50-year-old Caucasian woman with a normal thyroid-stimulating hormone level who underwent surgery to treat a multi-nodular goiter. The pathology was a clear cell variant of follicular thyroid carcinoma. The tumor was 1cm in diameter and consisted of pure clear cells. Conclusion Clear cell variants of follicular thyroid carcinoma are rarely seen, especially it is misdiagnosed with metastatic renal cell carcinoma. In this report, we describe the case of a patient with a clear cell variant of follicular thyroid carcinoma with an interesting pathology. PMID:24884725

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS

PubMed Central

Cardoso, Rodolfo C.; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C.

2016-01-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype. PMID:27792406

Developmental Programming: Insulin Sensitizer Prevents the GnRH-Stimulated LH Hypersecretion in a Sheep Model of PCOS.

PubMed

Cardoso, Rodolfo C; Burns, Ashleigh; Moeller, Jacob; Skinner, Donal C; Padmanabhan, Vasantha

2016-12-01

Prenatal testosterone (T) treatment recapitulates the reproductive and metabolic phenotypes of polycystic ovary syndrome in female sheep. At the neuroendocrine level, prenatal T treatment results in disrupted steroid feedback on gonadotropin release, increased pituitary sensitivity to GnRH, and subsequent LH hypersecretion. Because prenatal T-treated sheep manifest functional hyperandrogenism and hyperinsulinemia, gonadal steroids and/or insulin may play a role in programming and/or maintaining these neuroendocrine defects. Here, we investigated the effects of prenatal and postnatal treatments with an androgen antagonist (flutamide [F]) or an insulin sensitizer (rosiglitazone [R]) on GnRH-stimulated LH secretion in prenatal T-treated sheep. As expected, prenatal T treatment increased the pituitary responsiveness to GnRH leading to LH hypersecretion. Neither prenatal interventions nor postnatal F treatment normalized the GnRH-stimulated LH secretion. Conversely, postnatal R treatment completely normalized the GnRH-stimulated LH secretion. At the tissue level, gestational T increased pituitary LHβ, androgen receptor, and insulin receptor-β, whereas it reduced estrogen receptor (ER)α protein levels. Although postnatal F normalized pituitary androgen receptor and insulin receptor-β, it failed to prevent an increase in LHβ expression. Contrarily, postnatal R treatment restored ERα and partially normalized LHβ pituitary levels. Immunohistochemical findings confirmed changes in pituitary ERα expression to be specific to gonadotropes. In conclusion, these findings indicate that increased pituitary responsiveness to GnRH in prenatal T-treated sheep is likely a function of reduced peripheral insulin sensitivity. Moreover, results suggest that restoration of ERα levels in the pituitary may be one mechanism by which R prevents GnRH-stimulated LH hypersecretion in this sheep model of polycystic ovary syndrome-like phenotype.

Serum urea and uric acid concentration in pregnant women in sub-urban commercial community in Africa.

PubMed

Ahaneku, J E; Adinma, J I; Ahaneku, G I; Nwosu, B O; Nwofor, P C; Okoli, C C

2009-06-01

Serum uric acid and urea levels were determined in 27 pregnant and 17 non-pregnant black African women. Uric acid levels for the pregnant women were significantly raised, and the relationship between uric acid elevation and gestational proteinuric hypertension was discussed. In conclusion, we recommend that uric acid estimation should be included during routine antenatal clinics in normal pregnancy. That the use of uric acid levels should be encouraged for the diagnosis and management of gestational proteinuric hypertension in African pregnant women. The above recommendation will help to reduce prenatal morbidity and mortality in African pregnant women.

Drinking water and sanitation: progress in 73 countries in relation to socioeconomic indicators

PubMed Central

Bartram, Jamie

2016-01-01

Abstract Objective To assess progress in the provision of drinking water and sanitation in relation to national socioeconomic indicators. Methods We used household survey data for 73 countries – collected between 2000 and 2012 – to calculate linear rates of change in population access to improved drinking water (n = 67) and/or sanitation (n = 61). To enable comparison of progress between countries with different initial levels of access, the calculated rates of change were normalized to fall between –1 and 1. In regression analyses, we investigated associations between the normalized rates of change in population access and national socioeconomic indicators: gross national income per capita, government effectiveness, official development assistance, freshwater resources, education, poverty, Gini coefficient, child mortality and the human development index. Findings The normalized rates of change indicated that most of the investigated countries were making progress towards achieving universal access to improved drinking water and sanitation. However, only about a third showed a level of progress that was at least half the maximum achievable level. The normalized rates of change did not appear to be correlated with any of the national indicators that we investigated. Conclusion In many countries, the progress being made towards universal access to improved drinking water and sanitation is falling well short of the maximum achievable level. Progress does not appear to be correlated with a country’s social and economic characteristics. The between-country variations observed in such progress may be linked to variations in government policies and in the institutional commitment and capacity needed to execute such policies effectively. PMID:26957676

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma.

PubMed

Maheshwari, H G; Prezant, T R; Herman-Bonert, V; Shahinian, H; Kovacs, K; Melmed, S

2000-09-01

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

Nitrogen dioxide exposures inside ice skating rinks.

PubMed Central

Brauer, M; Spengler, J D

1994-01-01

OBJECTIVES. The common operation of fuel-powered resurfacing equipment in enclosed ice skating rinks has the potential for producing high concentrations of carbon monoxide and nitrogen dioxide. Exposures to these gaseous combustion products may adversely affect the health of those inside the rink. Little information is available on pollutant concentrations under normal operating conditions. METHODS. One-week average nitrogen dioxide concentrations in 70 northeastern US rinks were measured with passive samplers during normal winter season conditions. RESULTS. The median nitrogen dioxide level inside rinks was 180 ppb, more than 10 times higher than the median outdoor concentration. One-week average nitrogen dioxide concentrations above 1000 ppb were measured in 10% of the rinks. CONCLUSIONS. Considering that short-term peak concentrations were likely to have reached two to five times the measured 1-week averages, our results suggest that nitrogen dioxide levels were well above short-term air quality guidelines and constitute a public health concern of considerable magnitude. PMID:8129060

Empirical evaluation of data normalization methods for molecular classification

PubMed Central

Huang, Huei-Chung

2018-01-01

Background Data artifacts due to variations in experimental handling are ubiquitous in microarray studies, and they can lead to biased and irreproducible findings. A popular approach to correct for such artifacts is through post hoc data adjustment such as data normalization. Statistical methods for data normalization have been developed and evaluated primarily for the discovery of individual molecular biomarkers. Their performance has rarely been studied for the development of multi-marker molecular classifiers—an increasingly important application of microarrays in the era of personalized medicine. Methods In this study, we set out to evaluate the performance of three commonly used methods for data normalization in the context of molecular classification, using extensive simulations based on re-sampling from a unique pair of microRNA microarray datasets for the same set of samples. The data and code for our simulations are freely available as R packages at GitHub. Results In the presence of confounding handling effects, all three normalization methods tended to improve the accuracy of the classifier when evaluated in an independent test data. The level of improvement and the relative performance among the normalization methods depended on the relative level of molecular signal, the distributional pattern of handling effects (e.g., location shift vs scale change), and the statistical method used for building the classifier. In addition, cross-validation was associated with biased estimation of classification accuracy in the over-optimistic direction for all three normalization methods. Conclusion Normalization may improve the accuracy of molecular classification for data with confounding handling effects; however, it cannot circumvent the over-optimistic findings associated with cross-validation for assessing classification accuracy. PMID:29666754

Associations between dietary acrylamide intake and plasma sex hormone levels

PubMed Central

Hogervorst, Janneke G.; Fortner, Renee T.; Mucci, Lorelei A.; Tworoger, Shelley S.; Eliassen, A. Heather; Hankinson, Susan E.; Wilson, Kathryn M.

2013-01-01

Background The rodent carcinogen acrylamide was discovered in 2002 in commonly consumed foods. Epidemiological studies have observed positive associations between acrylamide intake and endometrial, ovarian and breast cancer risks, which suggests that acrylamide may have sex-hormonal effects. Methods We cross-sectionally investigated the relationship between acrylamide intake and plasma levels of sex hormones and SHBG among 687 postmenopausal and 1300 premenopausal controls from nested case-control studies within the Nurses’ Health Studies. Results There were no associations between acrylamide and sex hormones or SHBG among premenopausal women overall or among never-smokers. Among normal-weight premenopausal women, acrylamide intake was statistically significantly positively associated with luteal total and free estradiol levels. Among postmenopausal women overall and among never-smokers, acrylamide was borderline statistically significantly associated with lower estrone sulfate levels but not with other estrogens, androgens, prolactin or SHBG. Among normal weight women, (borderline) statistically significant inverse associations were noted for estrone, free estradiol, estrone sulfate, DHEA, and prolactin, while statistically significant positive associations for testosterone and androstenedione were observed among overweight women. Conclusions Overall, this study did not show conclusive associations between acrylamide intake and sex hormones that would lend unequivocal biological plausibility to the observed increased risks of endometrial, ovarian and breast cancer. The association between acrylamide and sex hormones may differ by menopausal and overweight status. We recommend other studies investigate the relationship between acrylamide and sex hormones in women, specifically using acrylamide biomarkers. Impact The present study showed some interesting associations between acrylamide intake and sex hormones that urgently need confirmation. PMID:23983241

Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes.

PubMed

Pelle, Edward; Huang, Xi; Zhang, Qi; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna

2014-01-01

The endogenous oxidative state of normal human epidermal melanocytes was investigated and compared to normal human epidermal keratinocytes (NHEKs) in order to gain new insight into melanocyte biology. Previously, we showed that NHEKs contain higher levels of hydrogen peroxide (H2O2) than melanocytes and that it can migrate from NHEKs to melanocytes by passive permeation. Nevertheless, despite lower concentrations of H2O2, we now report higher levels of oxidative DNA in melanocytes as indicated by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG): 4.49 (±0.55 SEM) 8-oxo-dG/10(6) dG compared to 1.49 (±0.11 SEM) 8-oxo-dG/10(6) dG for NHEKs. An antioxidant biomarker, glutathione (GSH), was also lower in melanocytes (3.14 nmoles (±0.15 SEM)/cell) in comparison to NHEKs (5.98 nmoles (±0.33 SEM)/cell). Intriguingly, cellular bioavailable iron as measured in ferritin was found to be nearly fourfold higher in melanocytes than in NHEKs. Further, ferritin levels in melanocytes were also higher than in hepatocarcinoma cells, an iron-rich cell, and it indicates that higher relative iron levels may be characteristic of melanocytes. To account for the increased oxidative DNA and lower GSH and H2O2 levels that we observe, we propose that iron may contribute to higher levels of oxidation by reacting with H2O2 through a Fenton reaction leading to the generation of DNA-reactive hydroxyl radicals. In conclusion, our data support the concept of elevated oxidation and high iron levels as normal parameters of melanocytic activity. We present new evidence that may contribute to our understanding of the melanogenic process and lead to the development of new skin care products.

Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.

PubMed

Valcheva-Kuzmanova, S; Kuzmanov, K; Tancheva, S; Belcheva, A

2007-03-01

Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications. Copyright 2007 Prous Science.

Tinnitus and other auditory problems - occupational noise exposure below risk limits may cause inner ear dysfunction.

PubMed

Lindblad, Ann-Cathrine; Rosenhall, Ulf; Olofsson, Åke; Hagerman, Björn

2014-01-01

The aim of the investigation was to study if dysfunctions associated to the cochlea or its regulatory system can be found, and possibly explain hearing problems in subjects with normal or near-normal audiograms. The design was a prospective study of subjects recruited from the general population. The included subjects were persons with auditory problems who had normal, or near-normal, pure tone hearing thresholds, who could be included in one of three subgroups: teachers, Education; people working with music, Music; and people with moderate or negligible noise exposure, Other. A fourth group included people with poorer pure tone hearing thresholds and a history of severe occupational noise, Industry. Ntotal = 193. The following hearing tests were used: - pure tone audiometry with Békésy technique, - transient evoked otoacoustic emissions and distortion product otoacoustic emissions, without and with contralateral noise; - psychoacoustical modulation transfer function, - forward masking, - speech recognition in noise, - tinnitus matching. A questionnaire about occupations, noise exposure, stress/anxiety, muscular problems, medication, and heredity, was addressed to the participants. Forward masking results were significantly worse for Education and Industry than for the other groups, possibly associated to the inner hair cell area. Forward masking results were significantly correlated to louder matched tinnitus. For many subjects speech recognition in noise, left ear, did not increase in a normal way when the listening level was increased. Subjects hypersensitive to loud sound had significantly better speech recognition in noise at the lower test level than subjects not hypersensitive. Self-reported stress/anxiety was similar for all groups. In conclusion, hearing dysfunctions were found in subjects with tinnitus and other auditory problems, combined with normal or near-normal pure tone thresholds. The teachers, mostly regarded as a group exposed to noise below risk levels, had dysfunctions almost identical to those of the more exposed Industry group.

Tinnitus and Other Auditory Problems – Occupational Noise Exposure below Risk Limits May Cause Inner Ear Dysfunction

PubMed Central

Lindblad, Ann-Cathrine; Rosenhall, Ulf; Olofsson, Åke; Hagerman, Björn

2014-01-01

The aim of the investigation was to study if dysfunctions associated to the cochlea or its regulatory system can be found, and possibly explain hearing problems in subjects with normal or near-normal audiograms. The design was a prospective study of subjects recruited from the general population. The included subjects were persons with auditory problems who had normal, or near-normal, pure tone hearing thresholds, who could be included in one of three subgroups: teachers, Education; people working with music, Music; and people with moderate or negligible noise exposure, Other. A fourth group included people with poorer pure tone hearing thresholds and a history of severe occupational noise, Industry. Ntotal = 193. The following hearing tests were used: − pure tone audiometry with Békésy technique, − transient evoked otoacoustic emissions and distortion product otoacoustic emissions, without and with contralateral noise; − psychoacoustical modulation transfer function, − forward masking, − speech recognition in noise, − tinnitus matching. A questionnaire about occupations, noise exposure, stress/anxiety, muscular problems, medication, and heredity, was addressed to the participants. Forward masking results were significantly worse for Education and Industry than for the other groups, possibly associated to the inner hair cell area. Forward masking results were significantly correlated to louder matched tinnitus. For many subjects speech recognition in noise, left ear, did not increase in a normal way when the listening level was increased. Subjects hypersensitive to loud sound had significantly better speech recognition in noise at the lower test level than subjects not hypersensitive. Self-reported stress/anxiety was similar for all groups. In conclusion, hearing dysfunctions were found in subjects with tinnitus and other auditory problems, combined with normal or near-normal pure tone thresholds. The teachers, mostly regarded as a group exposed to noise below risk levels, had dysfunctions almost identical to those of the more exposed Industry group. PMID:24827149

Comparisons of auditory brainstem response and sound level tolerance in tinnitus ears and non-tinnitus ears in unilateral tinnitus patients with normal audiograms

PubMed Central

An, Yong-Hwi; Kim, Dong Hyun; Yoon, Ji Eun; Yoon, Ji Hyang

2017-01-01

Objective Recently, “hidden hearing loss” with cochlear synaptopathy has been suggested as a potential pathophysiology of tinnitus in individuals with a normal hearing threshold. Several studies have demonstrated that subjects with tinnitus and normal audiograms show significantly reduced auditory brainstem response (ABR) wave I amplitudes compared with control subjects, but normal wave V amplitudes, suggesting increased central auditory gain. We aimed to reconfirm the “hidden hearing loss” theory through a within-subject comparison of wave I and wave V amplitudes and uncomfortable loudness level (UCL), which might be decreased with increased central gain, in tinnitus ears (TEs) and non-tinnitus ears (NTEs). Subjects and methods Human subjects included 43 unilateral tinnitus patients (19 males, 24 females) with normal and symmetric hearing thresholds and 18 control subjects with normal audiograms. The amplitudes of wave I and V from the peak to the following trough were measured twice at 90 dB nHL and we separately assessed UCLs at 500 Hz and 3000 Hz pure tones in each TE and NTE. Results The within-subject comparison between TEs and NTEs showed no significant differences in wave I and wave V amplitude, or wave V/I ratio in both the male and female groups. Individual data revealed increased V/I amplitude ratios > mean + 2 SD in 3 TEs, but not in any control ears. We found no significant differences in UCL at 500 Hz or 3000 Hz between the TEs and NTEs, but the UCLs of both TEs and NTEs were lower than those of the control ears. Conclusions Our ABR data do not represent meaningful evidence supporting the hypothesis of cochlear synaptopathy with increased central gain in tinnitus subjects with normal audiograms. However, reduced sound level tolerance in both TEs and NTEs might reflect increased central gain consequent on hidden synaptopathy that was subsequently balanced between the ears by lateral olivocochlear efferents. PMID:29253030

Prevalence of oral health status in visually impaired children.

PubMed

Reddy, Kvkk; Sharma, A

2011-01-01

The epidemiological investigation was carried out among 228 children selected from two schools of similar socioeconomic strata in and around Chennai city. The study population consisted of 128 visually impaired and 100 normal school going children in the age group of 6-15 years. The examination procedure and criteria were those recommended by W.H.O. in 1997. The mean DMFT/deft was 1.1 and 0.17,0.87 and 0.47 in visually impaired and normal children, respectively. Oral hygiene levels in both groups were: mean value in good category was 0.19 and 0.67, in fair category was 0.22 and 0.1, and in poor category 0.40 and 0.23 in visually impaired children and normal children, respectively. Trauma experienced children were 0.29 and 0.13 in visually impaired children and normal children, respectively. The conclusions drawn from this study were that there was a greater prevalence of dental caries, poorer oral hygiene, and higher incidence of trauma in visually impaired children.

Inflammation-related microRNA expression level in the bovine milk is affected by mastitis.

PubMed

Lai, Yu-Chang; Fujikawa, Takuro; Maemura, Tadashi; Ando, Takaaki; Kitahara, Go; Endo, Yasuyuki; Yamato, Osamu; Koiwa, Masateru; Kubota, Chikara; Miura, Naoki

2017-01-01

MicroRNA (miRNA) in tissue and liquid samples have been shown to be associated with many diseases including inflammation. We aimed to identify inflammation-related miRNA expression level in the bovine mastitis milk. Expression level of inflammation-related miRNA in milk from mastitis-affected and normal cows was analyzed using qPCR. We found that expression level of miR-21, miR-146a, miR-155, miR-222, and miR-383 was significantly upregulated in California mastitis test positive (CMT+) milk. We further analyzed these miRNA using a chip-based QuantStudio Digital PCR System. The digital PCR results correlated with those of qPCR, demonstrating upregulation of miR-21, miR-146a, miR-155, miR-222, and miR-383 in CMT+ milk. In conclusion, we identified miRNA that are upregulated in CMT+ milk. These miRNA exhibited sensitivity and specificity greater than 80% for differentiating between CMT+ milk and normal milk. Our findings suggest that inflammation-related miRNA expression level in the bovine milk was affected by mastitis, and miRNA in milk have potential for use as biomarkers of bovine mastitis.

Supplementation of α-Tocopherol Attenuates Minerals Disturbance, Oxidative Stress and Apoptosis Occurring in Favism.

PubMed

Koriem, Khaled M M; Arbid, Mahmoud S; Gomaa, Nawal E

2017-10-01

The favism is a metabolic disease that characterized with an acute hemolytic anemia where α-tocopherol is a type of tocopherol accumulated inside the human body. The objective of such a study was established to evaluate the effect of α-tocopherol in favism disorders. A total of 75 human cases were divided into 5 groups as follow; group 1 normal cases without any treatment and group 2 normal cases orally administrated α-tocopherol (200 mg/kg) once a day over 30 days period. Group 3 favism patients without any treatment. Groups 4 and 5 favism patients orally administrated 100 and 200 mg α-tocopherol/kg, respectively once a day over 30 days period. The results obtained revealed that oral administration of α-tocopherol into normal cases over 30 days period did not induce any biological change. In favism, hemoglobin, hematocrit, red and white blood cells, serum glucose, glucose-6-phosphate dehydrogenase, total protein, albumin, globulin, aspartate and alanine aminotransferases, blood glutathione, superoxide dismutase, glutathione peroxidase and serum calcium, phosphorous, sodium, potassium and chloride levels were significantly decreased. On the other hand, serum alkaline phosphatase, bilirubin, selenium, zinc, manganese, copper and iron, malondialdehyde levels showed significant increase in favism. Supplementation with α-tocopherol into favism restores all the above mentioned parameters to approach the normal levels. Also, α-tocopherol has anti-apoptotic effect in favism. In conclusion, α-tocopherol attenuates minerals disturbance, oxidative stress and apoptosis occurring in favism.

Experimental murine myopia induces collagen type Iα1 (COL1A1) DNA methylation and altered COL1A1 messenger RNA expression in sclera

PubMed Central

Zhou, Xiangtian; Ji, Fengtao; An, Jianhong; Zhao, Fuxin; Shi, Fanjun; Huang, Furong; Li, Yuan; Jiao, Shiming; Yan, Dongsheng; Chen, Xiaoyan; Chen, JiangFan

2012-01-01

Purpose To investigate whether myopia development is associated with changes of scleral DNA methylation in cytosine-phosphate-guanine (CpG) sites in the collagen 1A1 (COL1A1) promoter and messenger RNA (mRNA) levels following murine form deprivation myopia. Methods Fifty-seven C57BL/6 mice (postnatal day 23) were randomly assigned to four groups: (1) monocular form deprivation (MD) in which a diffuser lens was placed over one eye for 28 days; (2) normal controls without MD; (3) MD recovery in which the diffuser lens was removed for seven days; and (4) MD recovery normal controls. The DNA methylation pattern in COL1A1 promoter and exon 1 was determined by bisulfite DNA sequencing, and the COL1A1 mRNA level in sclera was determined by quantitative PCR. Results MD was found to induce myopia in the treated eyes. Six CpG sites in the promoter and exon 1 region of COL1A1 were methylated with significantly higher frequency in the treated eyes than normal control eyes (p<0.05), with CpG island methylation in MD-contralateral eyes being intermediate. Consistent with the CpG methylation, scleral COL1A1 mRNA was reduced by 57% in the MD-treated eyes compared to normal controls (p<0.05). After seven days of MD recovery, CpG methylation was significantly reduced (p=0.01). The methylation patterns returned to near normal level in five CpG sites, but the sixth was hypomethylated compared to normal controls. Conclusions In parallel with the development of myopia and the reduced COL1A1 mRNA, the frequency of methylation in CpG sites of the COL1A1 promoter/exon 1 increased during MD and returned to near normal during recovery. Thus, hypermethylation of CpG sites in the promoter/exon 1 of COL1A1 may underlie reduced collagen synthesis at the transcriptional level in myopic scleras. PMID:22690110

Daytime decrease of prolactin levels is associated with PCOS regardless to nutritional status and other hormones levels.

PubMed

Franik, Grzegorz; Madej, Paweł; Guz-Lem, Magdalena; Owczarek, Aleksander; Chudek, Jerzy; Olszanecka-Glinianowicz, Magdalena

2017-05-01

The aim of the study is to analyze daytime changes of prolactin level depending on nutritional status and polycystic ovary syndrome (PCOS). One hundred and fifteen (69 normal weight, 21 overweight and 25 obese) diagnosed with PCOS and 77 (37 normal weight, 18 overweight and 22 obese) women - Non-PCOS without concomitant diseases were enrolled. Body mass and height were measured and BMI was calculated. Serum concentrations of FSH, LH, E2, testosterone, TSH and PRL were determined morning 6.00 a.m. after wake. Second measurement of PRL was performed at 4 p.m. The daytime decrease of prolactin level was higher in PCOS than in Non-PCOS group regardless of nutritional status (normal weight 35.8 ± 26.0 vs. 24.3 ± 15.3 ng/mL; overweight 28.5 ± 25.4 vs. 17.5 ± 8.8 ng/mL and obese 23.2 ± 21.1 vs. 18.4 ± 11.6 ng/ml, respectively). However, in both PCOS and Non-PCOS daytime changes of prolactin level were higher in normal weight than overweight and obese women (35.8 ± 26.0 vs. 28.5 ± 25.4 vs. 23.2 ± 21.1 ng/mL and 24.3 ± 15.3 vs. 17.5 ± 8.8 vs. 18.4 ± 11.6 ng/mL, respectively). The multivariate regression analysis revealed that the daytime changes of prolactin level are proportional to TSH concentration and coexistence of PCOS as well as inversely relative to BMI. In conclusions, our results suggest that overweight and obesity decreased morning PRL level and impaired its daytime decrease, but coexistence of PCOS enlarged its.

Epigallocatechin-3-Gallate Prevents Autoimmune-Associated Down-Regulation of p21 in Salivary Gland Cells Through a p53-Independent Pathway

PubMed Central

Dickinson, Douglas; Yu, Hongfang; Ohno, Seiji; Thomas, Cristina; DeRossi, Scott; Ma, Yat-Ho; Yates, Nicole; Hahn, Emily; Bisch, Frederick; Yamamoto, Tetsuya; Hsu, Stephen

2015-01-01

The submandibular salivary glands of non-obese diabetic (NOD) mice, a model for Sjogren’s syndrome and type-1 diabetes, show an elevated level of proliferating cell nuclear antigen (PCNA), a protein involved in cell proliferation and repair of DNA damage. We reported previously that epigallocatechin-3-gallate (EGCG), the most abundant green tea catechin, normalizes the PCNA level. PCNA’s activity can be regulated by the cyclin-dependent kinase inhibitor p21, which is also important for epithelial cell differentiation. In turn, expression of p21 and PCNA are partially regulated by Rb phosphorylation levels. EGCG was found to modulate p21 expression in epithelial cells, suggesting that EGCG-induced p21 could be associated with down-regulation of PCNA in vivo. The current study examined the protein levels of p21 and p53 (which can up-regulate p21) in NOD mice fed with either water or EGCG, and the effect of EGCG on p21 and p53 in cell line models with either normal or defective Rb. In NOD mice, the p21 level was low, and EGCG normalized it. In contrast to HSG cells with functional Rb, negligible expression of p21 in NS-SV-AC cells that lack Rb was not altered by EGCG treatment. Inhibition of p53 by siRNA demonstrated that p21 and p53 were induced independently in HSG cells by a physiological concentration range of EGCG, suggesting p53 could be an important but not conditional factor associated with p21 expression. In conclusion, PCNA and p21 levels are altered inversely in the NOD model for SS and in HSG cells, and warrant further study as candidate new markers for salivary dysfunction associated with xerostomia. Induction of p21 by EGCG could provide clinically useful normalization of salivary glands by promoting differentiation and reducing PCNA levels. PMID:24329914

Evaluation of reactive oxygen metabolites in patients with non-small cell lung cancer after chemotherapy

PubMed Central

2014-01-01

Background The aim of this study was to evaluate the level of reactive oxygen metabolites (ROMs) after chemotherapy in patients with non-small cell lung cancer (NSCLC) and its association with response to treatment. Methods Fifty-eight untreated NSCLC patients and twenty-three healthy subjects were selected for the study. Patients received two courses of platinum-based chemotherapy and were evaluated for oxidative stress and treatment response. As a marker of reactive oxygen species, ROMs levels were measured using the d-ROMs test. Results ROMs level (mean ± standard deviation) before chemotherapy in NSCLC patients (416 ± 135 U.CARR) was significantly elevated (p = 0.016) compared to normal healthy subjects (320 ± 59 U.CARR). Patients who responded to chemotherapy showed significantly decreased (p = 0.014) ROMs levels after chemotherapy, whereas patients who had stable disease or progressive disease showed no change in ROMs level (p = 0.387). Conclusions NSCLC patients had significantly elevated ROMs levels before chemotherapy compared with normal healthy subjects. Chemotherapy may suppress ROMs production in responders but not in non-responders. ROMs level may be a predictor of clinical outcome in patients receiving chemotherapy for NSCLC. PMID:25180083

The effect of ILLLI on peripheral blood SOD, MDA in psoriasis treatment

NASA Astrophysics Data System (ADS)

Zhu, Jing; Nie, Fan

2005-07-01

Objective: To research the effect of Intravascular low level laser irradiation (ILLLI) on the SOD,MDA in the treatment of psoriasis. Method :47 patients suffering from psoriasis from five groups were treated by Intravascular low level laser irradiation (power:4-5mw,1h per day, period of treatment: 10 days) .We checked the change of SOD,MDA peripheral blood in 10 normal people between pre and post treatment. Group A were treated by He-Ne laser combined with drug, group B were treated by semi-conductor laser combined with drug, group C were treated only by He-Ne laser, group D were treated only by semiconductor laser, group E were treated only by drug . Results: The levels of SOD in red cell of psoriatic patients from five groups after treatment were significantly lower than that of controlled group. The levels of SOD of them were significantly increased and nearly closed to that of controlled group; the levels of MDA in red cell of psoriatic patients from five groups after treatment were significantly higher than that of controlled group; the levels of MDA of them are decreased ,however, they were still not recovered to normal levels. Conclusions: ILLLI, both He-Ne laser and semiconductor laser, can activate SOD in psoriasis patients and enhance their ability of anti-oxidation.

CNS germinoma with elevated serum human chorionic gonadotropin level: Clinical characteristics and treatment outcome

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

Ogino, Hiroyuki; Shibamoto, Yuta; Takanaka, Tsuyoshi

2005-07-01

Purpose: The prognostic significance of human chorionic gonadotropin (HCG) level in central nervous system germinoma remains controversial. The purpose of this study was to compare clinical characteristics and prognosis of germinoma patients with normal and high HCG titers in the serum. Methods and Materials: We undertook a multi-institutional retrospective analysis of 103 patients with central nervous system germinoma whose serum HCG and/or {beta}-HCG level had been measured before treatment between 1984 and 2002. All patients had been treated with radiation therapy either alone (n = 66) or in combination with chemotherapy (n = 37) with a median dose of 47.8more » Gy. Results: HCG and/or {beta}-HCG level in the serum was high in 39% of all patients. The proportion of HCG-producing tumors was higher in the lesions at the basal ganglia than in the lesions at the other sites. No correlation was found between tumor size and HCG level, but there seemed to be a weak correlation between size and {beta}-HCG. The 5- and 10-year survival rates were 96% and 94%, respectively, in both patient groups with normal and high HCG (p = 0.99). The 5- and 10-year relapse-free survival rates were 87% and 82%, respectively, in patients with normal HCG level and were both 87% in patients with high HCG (p = 0.74). Also, no other patient-, tumor-, or treatment-related factors seemed to influence the prognosis of the patients. Conclusion: Serum HCG level does not seem to influence patient prognosis when treated with sufficient doses of radiation. Relationship between tumor size and site and HCG level should be investigated further.« less

Differential roles of polar orbital prefrontal cortex and parietal lobes in logical reasoning with neutral and negative emotional content.

PubMed

Eimontaite, Iveta; Goel, Vinod; Raymont, Vanessa; Krueger, Frank; Schindler, Igor; Grafman, Jordan

2018-05-14

To answer the question of how brain pathology affects reasoning about negative emotional content, we administered a disjunctive logical reasoning task involving arguments with neutral content (e.g. Either there are tigers or women in NYC, but not both; There are no tigers in NYC; There are women in NYC) and emotionally laden content (e.g. Either there are pedophiles or politicians in Texas, but not both; There are politicians in Texas; There are no pedophiles in Texas) to 92 neurological patients with focal lesions to various parts of the brain. A Voxel Lesion Symptom Mapping (VLSM) analysis identified 16 patients, all with lesions to the orbital polar prefrontal cortex (BA 10 & 11), as being selectively impaired in the emotional reasoning condition. Another 17 patients, all with lesions to the parietal cortex, were identified as being impaired in the neutral content condition. The reasoning scores of these two patient groups, along with 23 matched normal controls, underwent additional analysis to explore the effect of belief bias. This analysis revealed that the differences identified above were largely driven by trials where there was an incongruency between the believability of the conclusion and the validity of the argument (i.e. valid argument /false conclusion or invalid argument /true conclusion). Patients with lesions to polar orbital prefrontal cortex underperformed in incongruent emotional content trials and over performed in incongruent neutral content trials (compared to both normal controls and patients with parietal lobe lesions). Patients with lesions to parietal lobes underperformed normal controls (at a trend level) in neutral trials where there was a congruency between the believability of the conclusion and the validity of the argument (i.e. valid argument/true conclusion or invalid argument/false conclusion). We conclude that lesions to the polar orbital prefrontal cortex (i) prevent these patients from enjoying any emotionally induced cognitive boost, and (ii) block the belief bias processing route in the neutral condition. Lesions to parietal lobes result in a generalized impairment in logical reasoning with neutral content. Copyright © 2018. Published by Elsevier Ltd.

Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats

PubMed Central

Radhika, P.; Annapurna, A.; Rao, S. Nageswara

2012-01-01

Background & objectives: A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Methods: Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. Results: A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. Interpretation & conclusions: The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats. PMID:22771592

Hypobaric Control of Ethylene-Induced Leaf Senescence in Intact Plants of Phaseolus vulgaris L. 1

PubMed Central

Nilsen, Karl N.; Hodges, Clinton F.

1983-01-01

A controlled atmospheric-environment system (CAES) designed to sustain normal or hypobaric ambient growing conditions was developed, described, and evaluated for its effectiveness as a research tool capable of controlling ethylene-induced leaf senescence in intact plants of Phaseolus vulgaris L. Senescence was prematurely-induced in primary leaves by treatment with 30 parts per million ethephon. Ethephon-derived endogenous ethylene reached peak levels within 6 hours at 26°C. Total endogenous ethylene levels then temporarily stabilized at approximately 1.75 microliters per liter from 6 to 24 hours. Thereafter, a progressive rise in ethylene resulted from leaf tissue metabolism and release. Throughout the study, the endogenous ethylene content of ethephon-treated leaves was greater than that of nontreated leaves. Subjecting ethephon-treated leaves to atmospheres of 200 millibars, with O2 and CO2 compositions set to approximate normal atmospheric partial pressures, prevented chlorophyll loss. Alternately, subjecting ethephon-treated plants to 200 millibars of air only partially prevented chlorophyll loss. Hypobaric conditions (200 millibars), with O2 and CO2 at normal atmospheric availability, could be delayed until 48 hours after ethephon treatment and still prevent most leaf senescence. In conclusion, hypobaric conditions established and maintained within the CAES prevented ethylene-induced senescence (chlorosis) in intact plants, provided O2 and CO2 partial pressures were maintained at levels approximating normal ambient availability. An unexpected increase in endogenous ethylene was detected within nontreated control leaves 48 hours subsequent to relocation from winter greenhouse conditions (latitude, 42°00″ N) to the CAES operating at normal ambient pressure. The longer photoperiod and/or higher temperature utilized within the CAES are hypothesized to influence ethylene metabolism directly and growth-promotive processes (e.g. response thresholds) indirectly. PMID:16662806

Intraoperative hypertensive crisis due to a catecholamine-secreting esthesioneuroblastoma

PubMed Central

Salmasi, Vafi; Schiavi, Adam; Binder, Zev A.; Ruzevick, Jacob; Orr, Brent A.; Burger, Peter C.; Ball, Douglas W.; Blitz, Ari M.; Koch, Wayne M.; Ishii, Masaru; Gallia, Gary L.

2015-01-01

Background Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. Methods We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed intraoperative hypertensive crisis. Results A patient with history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Work-up revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade prior to the second stage. Serum catecholamine levels following this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in cathecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. Conclusion Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma. PMID:25352487

Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats

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

Faid, Iman; Al-Hussaini, Heba; Kilarkaje, Narayana, E-mail: knarayana@hsc.edu.kw

Diabetes adversely affects reproductive functions in humans and animals. The present study investigated the effects of Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling and apoptosis in the testis. Adult male Wistar rats (13–15 weeks; n = 6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5 mg/kg; ip; given during last 3 weeks), 3) Streptozotocin-induced diabetic and, 4) Resveratrol-treated diabetic groups, and euthanized on day 42 after the confirmation of diabetes. Resveratrol did not normalize blood glucose levels in diabetic rats. Resveratrol supplementation recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicularmore » levels of superoxide dismutase, catalase, and glutathione peroxidase and an increase in 4-hydroxynonenal activities (P < 0.05). Resveratrol also recovered diabetes-induced increases in JNK signaling pathway proteins, namely, ASK1 (apoptosis signal-regulating kinase 1), JNKs (46 and 54 kDa isoforms) and p-JNK to normal control levels (P < 0.05). Interestingly, the expression of a down-stream target of ASK1, MKK4 (mitogen-activated protein kinase kinase 4) and its phosphorylated form (p-MKK4) did not change in experimental groups. Resveratrol inhibited diabetes-induced increases in AP-1 (activator protein-1) components, c-Jun and ATF2 (activating transcription factor 2), but not their phosphorylated forms, to normal control levels (P < 0.05). Further, Resveratrol inhibited diabetes-induced increase in cleaved-caspase-3 to normal control levels. In conclusion, Resveratrol alleviates diabetes-induced apoptosis in testis by modulating oxidative stress, JNK signaling pathway and caspase-3 activities, but not by inhibiting hyperglycemia, in rats. These results suggest that Resveratrol supplementation may be a useful strategy to treat diabetes-induced testicular dysfunction. - Highlights: • Resveratrol up-regulates glutathione peroxidase and catalase levels in the testis. • Diabetes up-regulates oxidative stress and JNK pathway in the testis. • Resveratrol inhibits diabetes-induced oxidative stress and JNK pathway. • Resveratrol mitigates diabetes-induced apoptosis of testicular cells. • Resveratrol treatment alleviates diabetes-induced testicular dysfunction.« less

Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy.

PubMed Central

Beisswenger, P J; Moore, L L; Brinck-Johnsen, T; Curphey, T J

1993-01-01

RATIONALE: Advanced glycosylation end products (AGEs) may play an important role in the development of diabetic vascular sequelae. An AGE cross-link, pentosidine, is a sensitive and specific marker for tissue levels of AGEs. OBJECTIVES: To evaluate the role of AGEs in the development of diabetic nephropathy and retinopathy, we studied pentosidine levels and the clinical characteristics of 48 subjects with insulin-dependent diabetes mellitus. Diabetic nephropathy was classified as normal, microalbuminuria, or gross proteinuria, and retinopathy was graded as none, background, or proliferative. NEWLY OBSERVED FINDINGS: Significant elevation of pentosidine (P = 0.025) was found in subjects with microalbuminuria or gross proteinuria (73.03 +/- 9.47 vs 76.46 +/- 6.37 pmol/mg col) when compared with normal (56.96 +/- 3.26 pmol/mg col). Multivariate analysis to correct for age, duration of diabetes, and gender did not modify the results. Elevated pentosidine levels were also found in those with proliferative when compared with those with background retinopathy (75.86 +/- 5.66 vs 60.42 +/- 5.98 pmol/mg col) (P < 0.05). CONCLUSIONS: Microalbuminuria is associated with elevated levels of pentosidine similar to those found in overt diabetic nephropathy suggesting that elevated AGE levels are already present during the earliest detectable phase of diabetic nephropathy. Images PMID:8325987

The Relationship between the Behavioral Hearing Thresholds and Maximum Bilirubin Levels at Birth in Children with a History of Neonatal Hyperbilirubinemia

PubMed Central

Panahi, Rasool; Jafari, Zahra; Sheibanizade, Abdoreza; Salehi, Masoud; Esteghamati, Abdoreza; Hasani, Sara

2013-01-01

Introduction: Neonatal hyperbilirubinemia is one of the most important factors affecting the auditory system and can cause sensorineural hearing loss. This study investigated the relationship between behavioral hearing thresholds in children with a history of jaundice and the maximum level of bilirubin concentration in the blood. Materials and Methods: This study was performed on 18 children with a mean age of 5.6 years and with a history of neonatal hyperbilirubinemia. Behavioral hearing thresholds, transient evoked emissions and brainstem evoked responses were evaluated in all children. Results: Six children (33.3%) had normal hearing thresholds and the remaining (66.7%) had some degree of hearing loss. There was no significant relationship (r=-0.28, P=0.09) between the mean total bilirubin levels and behavioral hearing thresholds in all samples. A transient evoked emission was seen only in children with normal hearing thresholds however in eight cases brainstem evoked responses had not detected. Conclusion: Increased blood levels of bilirubin at the neonatal period were potentially one of the causes of hearing loss. There was a lack of a direct relationship between neonatal bilirubin levels and the average hearing thresholds which emphasizes on the necessity of monitoring the various amounts of bilirubin levels. PMID:24303432

Rapidly progressing malignant insulinoma presented with multiple liver metastases: a case report.

PubMed

Erdogan, Askin; Askin, Erdogan; Kose, Fatih; Fatih, Kose; Akkaya, Hampar; Hampar, Akkaya; Bascil Tutuncu, Neslihan; Tutuncu, Neslihan Bascil; Ozyilkan, Ozgur; Ozgur, Ozyilkan

2010-12-01

A 51-year-old female was admitted to emergency unit with sudden loss of consciousness. Her blood glucose level from fingertip was 33 mg/dl, and insulin level was 55 (normal range, 4-17 IU). Abdominal ultrasonography revealed pancreatic mass with diffuse liver metastases. Biopsy of liver metastases showed differentiated neuroendocrine carcinoma. Diazoxide and chemotherapy stabilized her glucose level for more than 4 months. However, the disease showed progression, and death occurred 8 months later. In conclusion, this case may suggest that biologic behavior may differ from histological behavior in insulinoma and platin-based systemic chemotherapy may provide some benefit in patients those who had diazoxide- and octreotide-resistant tumors.

Prevalence of dental fluorosis & dental caries in association with high levels of drinking water fluoride content in a district of Gujarat, India

PubMed Central

Kotecha, P.V.; Patel, S.V.; Bhalani, K.D.; Shah, D.; Shah, V.S.; Mehta, K.G.

2012-01-01

Background & objectives: Endemic fluorosis resulting from high fluoride concentration in groundwater is a major public health problem in India. This study was carried out to measure and compare the prevalence of dental fluorosis and dental caries in the population residing in high and normal level of fluoride in their drinking water in Vadodara district, Gujarat, India. Methods: A cross-sectional study was conducted in Vadodara district, six of the 261 villages with high fluoride level and five of 1490 with normal fluoride level in drinking water were selected. The data collection was made by house-to-house visits twice during the study period. Results: The dental fluorosis prevalence in high fluoride area was 59.31 per cent while in normal fluoride area it was 39.21 per cent. The prevalence of dental caries in high fluoride area was 39.53 per cent and in normal fluoride area was 48.21 per cent with CI 6.16 to 11.18. Dental fluorosis prevalence was more among males as compared to females. Highest prevalence of dental fluorosis was seen in 12-24 yr age group. Interpretation & conclusions: The risk of dental fluorosis was higher in the areas showing more fluoride content in drinking water and to a lesser degree of dental caries in the same area. High fluoride content is a risk factor for dental fluorosis and problem of dental fluorosis increased with passage of time suggesting that the fluoride content in the water has perhaps increased over time. Longitudinal studies should be conducted to confirm the findings. PMID:22825606

Reference interval for thyrotropin in a ultrasonography screened Korean population

PubMed Central

Kim, Mijin; Kim, Soo Han; Lee, Yunkyoung; Park, Su-yeon; Kim, Hyung-don; Kwon, Hyemi; Choi, Yun Mi; Jang, Eun Kyung; Jeon, Min Ji; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

2015-01-01

Background/Aims The diagnostic accuracy of thyroid dysfunctions is primarily affected by the validity of the reference interval for serum thyroid-stimulating hormone (TSH). Thus, the present study aimed to establish a reference interval for TSH using a normal Korean population. Methods This study included 19,465 subjects who were recruited after undergoing routine health check-ups. Subjects with overt thyroid disease, a prior history of thyroid disease, or a family history of thyroid cancer were excluded from the present analyses. The reference range for serum TSH was evaluated in a normal Korean reference population which was defined according to criteria based on the guidelines of the National Academy of Clinical Biochemistry, ultrasound (US) findings, and smoking status. Sex and age were also taken into consideration when evaluating the distribution of serum TSH levels in different groups. Results In the presence of positive anti-thyroid peroxidase antibodies or abnormal US findings, the central 95 percentile interval of the serum TSH levels was widened. Additionally, the distribution of serum TSH levels shifted toward lower values in the current smokers group. The reference interval for TSH obtained using a normal Korean reference population was 0.73 to 7.06 mIU/L. The serum TSH levels were higher in females than in males in all groups, and there were no age-dependent shifts. Conclusions The present findings demonstrate that the serum TSH reference interval in a normal Korean reference population was higher than that in other countries. This result suggests that the upper and lower limits of the TSH reference interval, which was previously defined by studies from Western countries, should be raised for Korean populations. PMID:25995664

Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B

PubMed Central

Nathwani, Amit C.; Tuddenham, Edward G.D.; Rangarajan, Savita; Rosales, Cecilia; McIntosh, Jenny; Linch, David C.; Chowdary, Pratima; Riddell, Anne; Pie, Arnulfo Jaquilmac; Harrington, Chris; O’Beirne, James; Smith, Keith; Pasi, John; Glader, Bertil; Rustagi, Pradip; Ng, Catherine Y.C.; Kay, Mark A.; Zhou, Junfang; Spence, Yunyu; Morton, Christopher L.; Allay, James; Coleman, John; Sleep, Susan; Cunningham, John M.; Srivastava, Deokumar; Basner-Tschakarjan, Etiena; Mingozzi, Federico; High, Katherine A.; Gray, John T.; Reiss, Ulrike M.; Nienhuis, Arthur W.; Davidoff, Andrew M.

2012-01-01

BACKGROUND Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. METHODS We infused a single dose of a serotype-8–pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity, <1% of normal values). Study participants were enrolled sequentially in one of three cohorts (given a high, intermediate, or low dose of vector), with two participants in each group. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. RESULTS AAV-mediated expression of FIX at 2 to 11% of normal levels was observed in all participants. Four of the six discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in the other two, the interval between prophylactic injections was increased. Of the two participants who received the high dose of vector, one had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid–specific T cells in the peripheral blood; the other had a slight increase in liver-enzyme levels, the cause of which was less clear. Each of these two participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained FIX levels in the range of 3 to 11% of normal values. CONCLUSIONS Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects. Although immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this process may be controlled with a short course of glucocorticoids without loss of transgene expression. (Funded by the Medical Research Council and others; ClinicalTrials.gov number, NCT00979238.) PMID:22149959

Iron Deficiency in Patients with Nonalcoholic Fatty Liver Disease is Associated with Obesity, Female Sex, and Low Serum Hepcidin

PubMed Central

Siddique, Asma; Nelson, James E.; Aouizerat, Bradley; Yeh, Matthew M.; Kowdley, Kris V.

2014-01-01

Background & Aims Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines IL6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin and IL6 and IL1β, and other risk factors in patients with non-alcoholic fatty liver disease (NAFLD) with iron deficiency. Methods We collected data on 675 adult subjects (>18 y old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, as well as serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency. Results One third of patients (231/675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P<.01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61±45 vs 81±51 ng/mL; P<.0001). Iron deficiency was significantly associated with female sex, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, Black or American Indian/Alaska Native race (P≤.018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal; P≤.0001 and 0.45 vs 0.32 for iron normal; P≤.005). Conclusion Iron deficiency is prevalent in patients with NAFLD and associated with female sex, increased body mass index, and non-white race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiological response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD. PMID:24269922

Soluble Klotho and Autosomal Dominant Polycystic Kidney Disease

PubMed Central

Pavik, Ivana; Jaeger, Philippe; Ebner, Lena; Poster, Diane; Krauer, Fabienne; Kistler, Andreas D.; Rentsch, Katharina; Andreisek, Gustav; Wagner, Carsten A.; Devuyst, Olivier; Wüthrich, Rudolf P.; Schmid, Christoph; Serra, Andreas L.

2012-01-01

Summary Background and objectives Fibroblast growth factor 23 (FGF23) levels are elevated in patients with autosomal dominant polycystic kidney disease (ADPKD) and X-linked hypophosphatemia (XLH), but only the latter is characterized by a renal phosphate wasting phenotype. This study explored potential mechanisms underlying resistance to FGF23 in ADPKD. Design, setting, participants, & measurements FGF23 and Klotho levels were measured, and renal phosphate transport was evaluated by calculating the ratio of the maximum rate of tubular phosphate reabsorption to GFR (TmP/GFR) in 99 ADPKD patients, 32 CKD patients, 12 XLH patients, and 20 healthy volunteers. ADPKD and CKD patients were classified by estimated GFR (CKD stage 1, ≥90 ml/min per 1.73 m2; CKD stage 2, 60–89 ml/min per 1.73 m2). Results ADPKD patients had 50% higher FGF23 levels than did XLH patients; TmP/GFR was near normal in most ADPKD patients and very low in XLH patients. Serum Klotho levels were lowest in the ADPKD group, whereas the CKD and XLH groups and volunteers had similar levels. ADPKD patients with an apparent renal phosphate leak had two-fold higher Klotho levels than those without. Serum Klotho values correlated inversely with cyst volume and kidney growth. Conclusions Loss of Klotho might be a consequence of cyst growth and constrain the phosphaturic effect of FGF23 in most patients with ADPKD. Normal serum Klotho levels were associated with normal FGF23 biologic activity in all XLH patients and a minority of ADPKD patients. Loss of Klotho and FGF23 increase appear to exceed and precede the changes that can be explained by loss of GFR in patients with ADPKD. PMID:22193235

Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

PubMed Central

Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

2014-01-01

Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

Protein Degradation in Normal and Beige (Chediak-Higashi) Mice

PubMed Central

Lyons, Robert T.; Pitot, Henry C.

1978-01-01

The beige mouse, C57BL/6 (bg/bg), is an animal model for the Chediak-Higashi syndrome in man, a disease characterized morphologically by giant lysosomes in most cell types. Half-lives for the turnover of [14C]bicarbonate-labeled total soluble liver protein were determined in normal and beige mice. No significant differences were observed between the normal and mutant strain for both rapidly and slowly turning-over classes of proteins. Glucagon treatment during the time-course of protein degradation had similar effects on both normal and mutant strains and led to the conclusion that the rate of turnover of endogenous intracellular protein in the beige mouse liver does not differ from normal. The rates of uptake and degradation of an exogenous protein were determined in normal and beige mice by intravenously injecting 125I-bovine serum albumin and following, in peripheral blood, the loss with time of phosphotungstic acid-insoluble bovine serum albumin and the parallel appearance of phosphotungstic acid-soluble (degraded) material. No significant differences were observed between beige and normal mice in the uptake by liver lysosomes of 125I-bovine serum albumin (t½ = 3.9 and 2.8 h, respectively). However, it was found that lysosomes from livers of beige mice released phosphotungstic acid-soluble radioactivity at a rate significantly slower than normal (t½ = 6.8 and 3.1 h, respectively). This defect in beige mice could be corrected by chronic administration of carbamyl choline (t½ = 3.5 h), a cholinergic agonist which raises intracellular cyclic GMP levels. However, no significant differences between normal and beige mice were observed either in the ability of soluble extracts of liver and kidney to bind [3H]cyclic GMP in vitro or in the basal levels of cyclic AMP in both tissues. The relevance of these observations to the presumed biochemical defect underlying the Chediak-Higashi syndrome is discussed. PMID:202611

Plasma kisspeptin levels in male cases with hypogonadism.

PubMed

Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro

2014-01-01

The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann's syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

Problems with Using the Normal Distribution – and Ways to Improve Quality and Efficiency of Data Analysis

PubMed Central

Limpert, Eckhard; Stahel, Werner A.

2011-01-01

Background The Gaussian or normal distribution is the most established model to characterize quantitative variation of original data. Accordingly, data are summarized using the arithmetic mean and the standard deviation, by ± SD, or with the standard error of the mean, ± SEM. This, together with corresponding bars in graphical displays has become the standard to characterize variation. Methodology/Principal Findings Here we question the adequacy of this characterization, and of the model. The published literature provides numerous examples for which such descriptions appear inappropriate because, based on the “95% range check”, their distributions are obviously skewed. In these cases, the symmetric characterization is a poor description and may trigger wrong conclusions. To solve the problem, it is enlightening to regard causes of variation. Multiplicative causes are by far more important than additive ones, in general, and benefit from a multiplicative (or log-) normal approach. Fortunately, quite similar to the normal, the log-normal distribution can now be handled easily and characterized at the level of the original data with the help of both, a new sign, x/, times-divide, and notation. Analogous to ± SD, it connects the multiplicative (or geometric) mean * and the multiplicative standard deviation s* in the form * x/s*, that is advantageous and recommended. Conclusions/Significance The corresponding shift from the symmetric to the asymmetric view will substantially increase both, recognition of data distributions, and interpretation quality. It will allow for savings in sample size that can be considerable. Moreover, this is in line with ethical responsibility. Adequate models will improve concepts and theories, and provide deeper insight into science and life. PMID:21779325

Skeletal muscle mass and exercise performance in stable ambulatory patients with heart failure.

PubMed

Lang, C C; Chomsky, D B; Rayos, G; Yeoh, T K; Wilson, J R

1997-01-01

The purpose of this study was to determine whether skeletal muscle atrophy limits the maximal exercise capacity of stable ambulatory patients with heart failure. Body composition and maximal exercise capacity were measured in 100 stable ambulatory patients with heart failure. Body composition was assessed by using dual-energy X-ray absorption. Peak exercise oxygen consumption (VO2peak) and the anaerobic threshold were measured by using a Naughton treadmill protocol and a Medical Graphics CardioO2 System. VO2peak averaged 13.4 +/- 3.3 ml.min-1.kg-1 or 43 +/- 12% of normal. Lean body mass averaged 52.9 +/- 10.5 kg and leg lean mass 16.5 +/- 3.6 kg. Leg lean mass correlated linearly with VO2peak (r = 0.68, P < 0.01), suggesting that exercise performance is influences by skeletal muscle mass. However, lean body mass was comparable to levels noted in 1,584 normal control subjects, suggesting no decrease in muscle mass. Leg muscle mass was comparable to levels noted in 34 normal control subjects, further supporting this conclusion. These findings suggest that exercise intolerance in stable ambulatory patients with heart failure is not due to skeletal muscle atrophy.

Antioxidant and hypolipidemic activity of Kumbhajatu in hypercholesterolemic rats

PubMed Central

Ghosh, Rumi; Kadam, Parag P.; Kadam, Vilasrao J.

2010-01-01

Objective: To study the efficacy of Kumbhajatu in reducing the cholesterol levels and as an antioxidant in hypercholesterolemic rats. Materials and Methods: Hypercholesterolemia was induced in normal rats by including 2% w/w cholesterol, 1% w/w sodium cholate and 2.5% w/w coconut oil in the normal diet. Powdered form of Kumbhajatu was administered as feed supplement at 250 and 500 mg/kg dose levels to the hypercholesterolemic rats. Plasma lipid profile, hepatic superoxide dismutase (SOD) activity, catalase activity, reduced glutathione and extent of lipid peroxidation in the form of malondialdehyde were estimated using standard methods. Results: Feed supplementation with 250 and 500 mg/kg of Kumbhajatu resulted in a significant decline in plasma lipid profiles. The feed supplementation increased the concentration of catalase, SOD, glutathione and HDL-c significantly in both the experimental groups (250 and 500 mg/kg). On the other hand, the concentration of malondialdehyde, cholesterol, triglycerides, LDL-c and VLDL in these groups (250 and 500 mg/kg) were decreased significantly. Conclusion: The present study demonstrates that addition of Kumbhajatu powder at 250 and 500 mg/kg level as a feed supplement reduces the plasma lipid levels and also decreases lipid peroxidation. PMID:21170207

Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes

PubMed Central

Zheng, Rendong; Cao, Lin; Cao, Wen; Chu, Xiaoqiu; Hu, Yongxin; Zhang, Huifeng; Xu, Juan; Sun, Hongping; Bao, Weiping; Liu, Kemian; Liu, Chao

2016-01-01

Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). Conclusions. Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID:27006953

Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum

PubMed Central

Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J.; Ingrand, Pierre; Hankard, Régis

2016-01-01

Introduction Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. Objective To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. Materials and Methods This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Results Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, p<0.001). No difference was observed between obese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Conclusion Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period. PMID:28005966

Eldecalcitol normalizes bone turnover markers regardless of their pre-treatment levels.

PubMed

Shiraki, Masataka; Saito, Hitoshi; Matsumoto, Toshio

2012-09-01

Three-year treatment with eldecalcitol has been shown to improve lumbar and total hip bone mineral density (BMD), decrease bone turnover markers, and lower the incidences of vertebral and wrist fractures in patients with osteoporosis more than with treatment with alfacalcidol under vitamin D repletion. The purpose of this study was to determine whether there was a risk of eldecalcitol causing severely suppressed bone turnover in osteoporosis patients with low pre-treatment levels of bone turnover markers. Post-hoc analysis was conducted on the data from a 3-year, randomized, double-blind, active-comparator, clinical trial of eldecalcitol versus alfacalcidol under vitamin D repletion conducted in Japan. Enrolled patients with baseline measurements of bone turnover markers were stratified into tertiles according to their pre-treatment levels of serum bone-specific alkaline phosphatase, serum procollagen type I N-terminal propeptide, or urinary collagen-N-telopeptide. Eldecalcitol treatment rapidly reduced bone turnover markers, and kept them within the normal range. However, in the patients whose baseline values for bone turnover were low, eldecalcitol treatment did not further reduce bone turnover markers during the 3-year treatment period. Further long-term observation may be required to reach the conclusion. CLINICALTRIALS.GOV NUMBER: NCT00144456. Eldecalcitol normalizes, but does not overly suppress, bone turnover regardless of baseline levels of bone turnover markers. Thus, it is unlikely that eldecalcitol treatment will increase the risk of severely suppressed bone turnover and therefore deterioration of bone quality, at least for a treatment duration of 3 years.

Prevalence of sarcopenia among older community-dwelling people with normal health and nutritional state.

PubMed

Hedayati, Kerstin Khalaj; Dittmar, Manuela

2010-01-01

This study analyzed whether sarcopenia, a risk factor for disability in the aged, also occurs in healthy community-dwelling elders with normal nutritional state. As indicators, body cell mass (BCM) and lean body mass (LBM) were determined in 110 Germans (ages 60-83) using bioimpedance analysis. Nutritional status, muscle function, anthropometry, and physical activity level were investigated. Sarcopenia was already present in well nourished healthy elders. Its prevalence depended on the measure of muscle mass used (BCM percent, 22 percent males, 20 percent females; LBM percent, 4 percent males, 11 percent females). In conclusion, screening for presence of sarcopenia is needed in healthy, well-nourished elderly populations requiring an international standardization. Copyright © Taylor & Francis Group, LLC

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats

PubMed Central

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D.; Planer, David; Ben-Dov, Iddo Z.; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-01-01

Aims Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Methods and results Sprague–Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks (‘diet group’). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet (‘low-phosphate group’, n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor κB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. Conclusion We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies. PMID:18390899

Posterior Cingulate Glucose Metabolism, Hippocampal Glucose Metabolism, and Hippocampal Volume in Cognitively Normal, Late-Middle-Aged Persons at 3 Levels of Genetic Risk for Alzheimer Disease

PubMed Central

Protas, Hillary D.; Chen, Kewei; Langbaum, Jessica B. S.; Fleisher, Adam S.; Alexander, Gene E.; Lee, Wendy; Bandy, Daniel; de Leon, Mony J.; Mosconi, Lisa; Buckley, Shannon; Truran-Sacrey, Diana; Schuff, Norbert; Weiner, Michael W.; Caselli, Richard J.; Reiman, Eric M.

2013-01-01

Objective To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. Design Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxy-glucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. Setting Academic medical center. Participants A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. Main Outcome Measures The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. Results Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P=.60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P=.001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r=0.29, P=.0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P<.05, determined by use of pairwise Fisher z tests). Conclusions Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease. PMID:23599929

Serum Potassium Levels and Outcome in Acute Heart Failure (Data from the PROTECT and COACH Trials).

PubMed

Tromp, Jasper; Ter Maaten, Jozine M; Damman, Kevin; O'Connor, Christopher M; Metra, Marco; Dittrich, Howard C; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G F; Givertz, Michael M; Bloomfield, Daniel M; van der Wal, Martje H L; Jaarsma, Tiny; van Veldhuisen, Dirk J; Hillege, Hans L; Voors, Adriaan A; van der Meer, Peter

2017-01-15

Serum potassium is routinely measured at admission for acute heart failure (AHF), but information on association with clinical variables and prognosis is limited. Potassium measurements at admission were available in 1,867 patients with AHF in the original cohort of 2,033 patients included in the Patients Hospitalized with acute heart failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion trial. Patients were grouped according to low potassium (<3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (>5.0 mEq/l) levels. Results were verified in a validation cohort of 1,023 patients. Mean age of patients was 71 ± 11 years, and 66% were men. Low potassium was present in 115 patients (6%), normal potassium in 1,576 (84%), and high potassium in 176 (9%). Potassium levels increased during hospitalization (0.18 ± 0.69 mEq/l). Patients with high potassium more often used angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists before admission, had impaired baseline renal function and a better diuretic response (p = 0.005), independent of mineralocorticoid receptor antagonist usage. During 180-day follow-up, a total of 330 patients (18%) died. Potassium levels at admission showed a univariate linear association with mortality (hazard ratio [log] 2.36, 95% confidence interval 1.07 to 5.23; p = 0.034) but not after multivariate adjustment. Changes of potassium levels during hospitalization or potassium levels at discharge were not associated with outcome after multivariate analysis. Results in the validation cohort were similar to the index cohort. In conclusion, high potassium levels at admission are associated with an impaired renal function but a better diuretic response. Changes in potassium levels are common, and overall levels increase during hospitalization. In conclusion, potassium levels at admission or its change during hospitalization are not associated with mortality after multivariate adjustment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis.

PubMed

Vallota, E H; Forristal, J; Spitzer, R E; Davis, N C; West, C D

1971-03-01

Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.

Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance.

PubMed

Li, Weiping; Li, Qifu

2012-01-01

To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, P<0.05), lower M value but similar HOMA-βad index, while overweight/obese PCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, P<0.05) and PPG (6.15±0.84 vs. 5.44±0.97 mmol/L, P<0.05), and lower levels of both M value and HOMA-βad index. Linear regression and ROC analysis found BMI was independently associated with M value and HOMA-βad index in PCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m². In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m² indicated impaired β cell function in PCOS women with normal glucose tolerance.

CSF biomarkers of Alzheimer disease

PubMed Central

Fagan, Anne M.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.

2013-01-01

Objectives: To test whether CSF Alzheimer disease biomarkers (β-amyloid 42 [Aβ42], tau, phosphorylated tau at threonine 181 [ptau181], tau/Aβ42, and ptau181/Aβ42) predict future decline in noncognitive outcomes among individuals cognitively normal at baseline. Methods: Longitudinal data from participants (N = 430) who donated CSF within 1 year of a clinical assessment indicating normal cognition and were aged 50 years or older were analyzed. Mixed linear models were used to test whether baseline biomarker values predicted future decline in function (instrumental activities of daily living), weight, behavior, and mood. Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination scores were also examined. Results: Abnormal levels of each biomarker were related to greater impairment with time in behavior (p < 0.035) and mood (p < 0.012) symptoms, and more difficulties with independent activities of daily living (p < 0.012). However, biomarker levels were unrelated to weight change with time (p > 0.115). As expected, abnormal biomarker values also predicted more rapidly changing Mini-Mental State Examination (p < 0.041) and Clinical Dementia Rating Sum of Boxes (p < 0.001) scores compared with normal values. Conclusions: CSF biomarkers among cognitively normal individuals are associated with future decline in some, but not all, noncognitive Alzheimer disease symptoms studied. Additional work is needed to determine the extent to which these findings generalize to other samples. PMID:24212387

Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels

PubMed Central

Lv, Guo-Cai; Ma, Wen-Jiang; Ying, Lin-Jung; Jin, Xi; Zheng, Lin; Yang, Yi-Da

2010-01-01

AIM: To evaluate the efficacy and safety of telbivudine (LDT) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who have high baseline alanine aminotransferase (ALT) levels between 10 and 20 times the upper limit of normal. METHODS: Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 wk. Another forty patients with baseline ALT levels between 2 and 10 times the upper limit of normal were included as controls. We compared the virological, biochemical, serological and side effect profiles between the two groups at 52 wk. RESULTS: By week 52, the mean decrease in hepatitis B virus (HBV) DNA level compared with baseline was 7.03 log10 copies/mL in the high baseline ALT group and 6.17 log10 copies/mL in the control group, respectively (P < 0.05). The proportion of patients in whom serum HBV DNA levels were undetectable by polymerase chain reaction assay was 72.5% in the high baseline ALT group and 60% in the control group, respectively (P < 0.05). In addition, 45.0% of patients in the high baseline ALT group and 27.5% of controls became HBeAg-negative, and 37.5% of those in the high baseline group and 22.5% of controls, respectively, had HBeAg seroconversion (P < 0.05) at week 52. Moreover, in the high baseline group, 4 out of 40 patients (10%) became hepatitis B surface antigen (HBsAg)-negative and 3 (7.5%) of them seroconverted (became HBsAg-positive). Only 1 patient in the control group became HBsAg-negative, but had no seroconversion. The ALT normalization rate, viral breakthrough, genotypic resistance to LDT, and elevations in creatine kinase levels were similar in the two groups over the 52 wk. CONCLUSION: High baseline ALT level is a strong predictor for optimal results during LDT treatment. PMID:20731026

Effects of 60-Hz electric fields on serotonin metabolism in the rat pineal gland

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

Anderson, L.E.; Hilton, D.I.; Phillips, R.D.

Serotonin and two of its metabolites, melatonin and 5-methoxytryptophol, exhibit circadian rhythmicity in the pineal gland. We recently reported a marked reduction in the normal night-time increase in melatonin concentration in the pineal glands of rats exposed to 60-Hz electric fields. Concomitant with the apparent abolition of melatonin rhythmicity, serotonin-N-acetyl transferase (SNAT) activity was suppressed. We have now conducted studies to determine if abolition of the rhythm in melatonin production in electric-field-exposed rats arises solely from interference in SNAT activity, or if the availability of pineal serotonin is a factor that is affected by exposure. Pineal serotonin concentrations were comparedmore » in rats that were either exposed or sham exposed to 65 kV/m for 30 days. Sham-exposed animals exhibited normal diurnal rhythmicity for pineal concentrations of both melatonin and serotonin; melatonin levels increased markedly during the dark phase with a concurrent decrease in serotonin levels. In the exposed animals, however, normal serotonin rhythmicity was abolished; serotonin levels in these animals did not increase during the light period. The conclusion that electric field exposure results in a biochemical alteration in SNAT enzyme activity can be inferred from the loss of both serotonin and melatonin rhythmicity, as well as by direct measurement of SNAT activity itself. 35 references, 3 figures, 1 table.« less

Role of Dicer1 in thyroid cell proliferation and differentiation.

PubMed

Penha, Ricardo Cortez Cardoso; Sepe, Romina; De Martino, Marco; Esposito, Francesco; Pellecchia, Simona; Raia, Maddalena; Del Vecchio, Luigi; Decaussin-Petrucci, Myriam; De Vita, Gabriella; Pinto, Luis Felipe Ribeiro; Fusco, Alfredo

2017-01-01

DICER1 plays a central role in the biogenesis of microRNAs and it is important for normal development. Altered microRNA expression and DICER1 dysregulation have been described in several types of tumors, including thyroid carcinomas. Recently, our group identified a new somatic mutation (c.5438A>G; E1813G) within DICER1 gene of an unknown function. Herein, we show that DICER1 is overexpressed, at mRNA level, in a significant-relative number of papillary (70%) and anaplastic (42%) thyroid carcinoma samples, whereas is drastically downregulated in all the analyzed human thyroid carcinoma cell lines (TPC-1, BCPAP, FRO and 8505c) in comparison with normal thyroid tissue samples. Conversely, DICER1 is downregulated, at protein level, in PTC in comparison with normal thyroid tissues. Our data also reveals that DICER1 overexpression positively regulates thyroid cell proliferation, whereas its silencing impairs thyroid cell differentiation. The expression of DICER1 gene mutation (c.5438A>G; E1813G) negatively affects the microRNA machinery and cell proliferation as well as upregulates DICER1 protein levels of thyroid cells but has no impact on thyroid differentiation. In conclusion, DICER1 protein is downregulated in papillary thyroid carcinomas and affects thyroid proliferation and differentiation, while DICER1 gene mutation (c.5438A>G; E1813G) compromises the DICER1 wild-type-mediated microRNA processing and cell proliferation.

Plasma galanin concentrations in obese, normal weight and anorectic women.

PubMed

Invitti, C; Brunani, A; Pasqualinotto, L; Dubini, A; Bendinelli, P; Maroni, P; Cavagnini, F

1995-05-01

Galanin is believed to play a role in the control of eating behavior. No information is available on its concentrations in the biological fluids in human obesity, and this study aimed to clarify this. We measured plasma galanin and serum insulin levels in 30 obese, 35 normal weight and 11 anorectic women. Mean galanin values were quite similar in obese and control subjects (76.8 +/- 3.20 vs 76.1 +/- 2.33 pg/ml) and only slightly reduced in anorectic patients (67.9 +/- 2.30 pg/ml). Insulin levels were significantly increased and decreased in obese and anorectic patients, respectively, compared to controls. Insulin correlated positively with BMI in the whole group of subjects studied (r = 0.72, P < 0.0001) and in the obese subgroup (r = 0.56, P < 0.02). No correlations could be detected between WH ratio, insulin and galanin concentrations and between galanin and BMI. In conclusion, plasma galanin concentrations appear to be comparable in obese, normal weight and anorectic subjects. This does not exclude a role of galanin in the regulation of eating behavior since variations of the peptide in discrete brain areas may not be detectable in general circulation and peripheral sources of the peptide may contribute to its plasma levels. Also, our data suggest that galanin does not play a major role in the regulation of insulin secretion in humans.

Relationship between hamstring length and gluteus maximus strength with and without normalization.

PubMed

Lee, Dong-Kyu; Oh, Jae-Seop

2018-01-01

[Purpose] This study assessed the relationship between hamstring length and gluteus maximus (GM) strength with and without normalization by body weight and height. [Subjects and Methods] In total, 34 healthy male subjects volunteered for this study. To measure GM strength, subjects performed maximal hip joint extension with the knee joints flexed to 90° in the prone position. GM strength was normalized for body weight and height. [Results] GM strength with normalization was positively correlated with hamstring length, whereas GM strength without normalization was negatively correlated with hamstring length. [Conclusion] The normalization of GM strength by body weight and height has the potential to lead to more appropriate conclusions and interpretations about its correlation with hamstring length. Hamstring length may be related to GM strength.

The Investigation of Serum Vaspin Level in Atherosclerotic Coronary Artery Disease

PubMed Central

Kobat, Mehmet Ali; Celik, Ahmet; Balin, Mehmet; Altas, Yakup; Baydas, Adil; Bulut, Musa; Aydin, Suleyman; Dagli, Necati; Yavuzkir, Mustafa Ferzeyn; Ilhan, Selcuk

2012-01-01

Background It was speculated that fatty tissue originated adipocytokines may play role in pathogenesis of atherosclerosis. These adipocytokines may alter vascular homeostasis by effecting endothelial cells, arterial smooth muscle cells and macrophages. Vaspin is a newly described member of adipocytokines family. We aimed to investigate whether plasma vaspin level has any predictive value in coronary artery disease (CAD). Methods Forty patients who have at least single vessel ≥ 70 % stenosis demostrated angiographically and 40 subjects with normal coronary anatomy were included to the study. The vaspin levels were measured from serum that is obtained by centrifigation of blood and stored at -20 oC by ELISA method. The length, weight and body mass index of patients were measured. Biochemical parameters including total cholesterol, low density lipoprotein, high density lipoprotein, creatinine, sodium, potassium, hemoglobine, uric acid and fasting glucose were also measured. Results Biochemical markers levels were similar in both groups. Serum vaspin levels were significantly lower in CAD patients than control group (respectively; 256 ± 219 pg/ml vs. 472 ( 564 pg/ml, P < 0.02). Beside this serum vaspin level was lower in control group with high systolic blood pressure. Conclusion Serum vaspin levels were found significantly lower in patients with CAD than age-matched subjects with normal coronary anatomy. Vaspin may be used as a predictor of CAD. Keywords Coronary artery disease; Vaspin; Adipokine PMID:22505983

Effect of Powder Leaf Breadfruit Disposals (Arthocarpus Altilis) in Oil Mandar District and Polman Against Cholesterol and Glucose Mice (Mus Musculus)

NASA Astrophysics Data System (ADS)

Mu'nisa, A.; Asmawati, A.; Farida, A.; FA, Fressy; Erni

2018-01-01

The purpose of this study was to determine the effect of powdered leaves of breadfruit (Arthocarpus altilis) on oil is mandated origin of the Polman glucose and cholesterol levels in mice (Mus musculus). This study comprised 4 treatments and each treatment consisted of 5 replicates, ie groups of mice were fed a standard (negative control); 2 groups: group of mice fed with standard and cholesterol feed (positive control); Group 3 that mice fed with standard and Selayar oil; and group 4: group of mice fed with standard and Mandar oil that has been given powdered leaves of breadfruit. Measurement of glucose and blood cholesterol levels in mice done 3 times ie 2 weeks after the adaptation period (phase 1), 2 weeks after administration of the oil (phase 2) and 2 weeks after feeding cholesterol (stage 3). Based on the analysis of data both cholesterol and glucose levels showed that in a group of 4 decreased glucose and cholesterol levels in stage 2 but at stage 3 an increase in the group of mice given only the oil while in the group of mice given the oil and powdered leaves of breadfruit indicate glucose levels and normal cholesterol. The conclusion of this study show that the addition of powdered leaves of breadfruit into cooking oil Mandar influential in glucose levels and normalize blood cholesterol levels in mice.

WE-H-207A-03: The Universality of the Lognormal Behavior of [F-18]FLT PET SUV Measurements

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

Scarpelli, M; Eickhoff, J; Perlman, S

Purpose: Log transforming [F-18]FDG PET standardized uptake values (SUVs) has been shown to lead to normal SUV distributions, which allows utilization of powerful parametric statistical models. This study identified the optimal transformation leading to normally distributed [F-18]FLT PET SUVs from solid tumors and offers an example of how normal distributions permits analysis of non-independent/correlated measurements. Methods: Forty patients with various metastatic diseases underwent up to six FLT PET/CT scans during treatment. Tumors were identified by nuclear medicine physician and manually segmented. Average uptake was extracted for each patient giving a global SUVmean (gSUVmean) for each scan. The Shapiro-Wilk test wasmore » used to test distribution normality. One parameter Box-Cox transformations were applied to each of the six gSUVmean distributions and the optimal transformation was found by selecting the parameter that maximized the Shapiro-Wilk test statistic. The relationship between gSUVmean and a serum biomarker (VEGF) collected at imaging timepoints was determined using a linear mixed effects model (LMEM), which accounted for correlated/non-independent measurements from the same individual. Results: Untransformed gSUVmean distributions were found to be significantly non-normal (p<0.05). The optimal transformation parameter had a value of 0.3 (95%CI: −0.4 to 1.6). Given the optimal parameter was close to zero (which corresponds to log transformation), the data were subsequently log transformed. All log transformed gSUVmean distributions were normally distributed (p>0.10 for all timepoints). Log transformed data were incorporated into the LMEM. VEGF serum levels significantly correlated with gSUVmean (p<0.001), revealing log-linear relationship between SUVs and underlying biology. Conclusion: Failure to account for correlated/non-independent measurements can lead to invalid conclusions and motivated transformation to normally distributed SUVs. The log transformation was found to be close to optimal and sufficient for obtaining normally distributed FLT PET SUVs. These transformations allow utilization of powerful LMEMs when analyzing quantitative imaging metrics.« less

Study of Plasma Adrenomedullin Level In Normal Pregnancy and Preclampsia

PubMed Central

Senna, Azza Abo; Zedan, Magda; Abd El Salam, Gamal E.; El Mashad, Ashraf I.

2008-01-01

Aim The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. Subjects and Methods In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Results Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Conclusion Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy. PMID:18382699

Albumin as a prognostic marker for ulcerative colitis

PubMed Central

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Trivedi, Chinmay; Yang, Yu-Xiao

2017-01-01

AIM To evaluate the role of albumin at the time of ulcerative colitis (UC) diagnosis in predicting the clinical course of disease. METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia (i.e., ≤ 3.5 gm/dL) or normal albumin levels (i.e., > 3.5 gm/dL) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined as albumin level ≤ 3.5 g/dL at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids (CS), thiopurines, anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients, but 92 (11.4%) patients did not have their albumin levels checked at the time of UC diagnosis, and they were excluded. A total of 710 patients, who had albumin levels checked at time of UC diagnosis, were included in our study. Amongst them, 536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use (adjusted HR = 1.7, 95%CI: 1.3-2.3), higher likelihood of thiopurine or anti- TNF use (adjusted HR = 1.72, 95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients, but it was not statistically significant (Adjusted HR = 1.7, 95%CI: 0.90-3.25). CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis. PMID:29259376

Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event

PubMed Central

2011-01-01

Background Imatinib mesylate has been the standard therapeutic treatment for chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor (GIST). It is well tolerated with mild adverse effects. Gynecomastia development during the course of treatment has been rarely reported. Methods Ninety-eight patients with advanced or recurrent GIST were treated with imatinib mesylate. Among the fifty-seven male patients six developed gynecomastia during the treatment. The lesions were confirmed by sonography. Sex hormone levels were determined in six patients with and without the presence of gynecomastia respectively. The patients with gynecomatia were treated with tamoxifene and the sex hormones were assayed before and after tamoxifene treatment. Results In patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5 centimeters in diameter. Their serum free testosterone levels ranged between 356.61 and 574.60 ng/dl with a mean ± SD of 408.64 ± 82.06 ng/dl (95% CI 343.03~474.25 ng/dl), which is within the normal range. The level of serum estradiol was 42.89 ± 16.54 pg/ml (95% CI 29.66~56.12 pg/ml). Three patients had higher levels (43.79~71.21 pg/ml) and the others' were within normal range of 27.00~34.91 pg/ml. Six patients without the development of gynecomastia had normal free testosterone. One patient died because of large tumor burden. The sex hormones had no significant changes before and after tamoxifene treatment.(P > 0.05) Conclusions Testosterone levels were not decreased in the six GIST patients with gynecomastia. Three patients had increased serum estradiol level which suggests that imbalance of sex hormones may be the cause of gynecomastia during treatment with imatinib mesylate. PMID:22047550

HYPERHOMOCYSTEINEMIA AND ITS TREATMENT IN PATIENTS WITH PARKINSON’S DISEASE

PubMed Central

Ibrahimagic, Omer C.; Smajlovic, Dzevdet; Dostovic, Zikrija; Pasic, Zejneba; Kunic, Suljo; Iljazovic, Amra; Hajdarevic, Denisa Salihovic

2016-01-01

Introduction: Homocysteine is process-product of methionine demethylation. It has proatherogenic, prothrombotic, prooxidative, proapoptotic, osteoporotic, neurotoxic, neuroinflamatory, and neurodegenerative effects. Hyperhomocysteinemia correlates with C667T MTHFR mutation, decrease of folic acid and vitamin B, as well as prolonged use of certain medications. Materials and Methods: We measured levels of homocysteine in thirty patients (15::15) with “de novo” Parkinson’s disease, with average age 64.17 ± 13.19 (28-82) years (Department of Neurology, University Clinical Center Tuzla). Normal level of homocysteine for women was 3.36-20.44 micromole/l and 5.9-16 micromole/l for men. We followed the effects of medicament approach (folic acid) every six months for next five years. Results: 20% of patients with “de novo” Parkinson’s disease exhibited hyperhomocysteinemia. An average level of homocysteine was 13.85 ± 5.82 micromole/l. Differences due to age and homocysteine levels, regardless of sex, were not concluded. For the next five years intake of folic acid (periodically, 1-2 months, 5 mg per day, orally) was effective to normalized levels of homocysteine in all. Conclusion: Hyperhomocysteinemia is present in every fifth patient with “de novo” Parkinson’s disease. Folic acid is medication of choice in treatment of hyperhomocysteinemia coexisting with Parkinson’s disease. PMID:27698607

Withdrawal From Chronic Nicotine Reduces Thyroid Hormone Levels and Levothyroxine Treatment Ameliorates Nicotine Withdrawal-Induced Deficits in Hippocampus-Dependent Learning in C57BL/6J Mice

PubMed Central

Leach, Prescott T.; Holliday, Erica; Kutlu, Munir G.

2015-01-01

Introduction: Cigarette smoking alters a variety of endocrine systems including thyroid hormones. Altered thyroid hormone signaling may lead to a subclinical or overt hypothyroid condition that could contribute to nicotine withdrawal-related symptoms, such as cognitive deficits. Thus, normalizing thyroid hormone levels may represent a novel therapeutic target for ameliorating nicotine withdrawal-associated cognitive deficits. Methods: The current studies conducted an analysis of serum thyroid hormone levels after chronic and withdrawal from chronic nicotine treatment in C57BL/6J mice using an enzyme-linked immunosorbent assay. The present studies also evaluated the effect of synthetic thyroid hormone (levothyroxine) on contextual and cued memory. Results: The current studies found that nicotine withdrawal reduces secreted thyroid hormone levels by 9% in C57BL/6J mice. Further, supplemental thyroid hormone not only enhanced memory in naïve animals, but also ameliorated deficits in hippocampus-dependent learning associated with nicotine withdrawal. Conclusions: These results suggest that smokers attempting to quit should be monitored closely for changes in thyroid function. If successfully treated, normalization of thyroid hormone levels may ameliorate some deficits associated with nicotine withdrawal and this may lead to higher rates of successful abstinence. PMID:25358661

Serum HSP70

PubMed Central

Dutta, Sudhir K.; Girotra, Mohit; Singla, Montish; Dutta, Anand; Stephen, F. Otis; Nair, Padmanabhan P.; Merchant, Nipun B.

2014-01-01

Objectives Heat shock protein 70 (HSP70) is overexpressed in human pancreatic cancer cell lines. To determine if serum HSP70 levels are elevated in patients with pancreatic cancer and can function as a biomarker for early detection of pancreatic cancer. Methods Study subjects were divided into 3 groups: histologically proven pancreatic cancer (PC; n = 23), chronic pancreatitis (CP; n = 12), and matched normal control subjects (C; n = 10). Serum HSP70 levels were determined using a novel immunoelectrophoresis method developed and validated by the authors. Significance of difference between the groups was analyzed with analysis of variance (ANOVA). Receiver operating characteristic (ROC) curve analysis was performed to discriminate patients with pancreatic cancer from normal controls. Results The mean ± SE serum HSP70 levels in the PC, CP, and C groups were 1.68 ± 0.083 ng/mL, 0.40 ± 0.057 ng/mL, and 0.04 ng/mL, respectively. Serum HSP70 levels in the PC group were significantly higher compared with either the CP or C groups (P < 0.01). The sensitivity and specificity of elevated serum HSP70 in the PC group was 74% and 90%, respectively. Conclusions Serum HSP70 levels are significantly increased in patients with pancreatic cancer and may be useful as an additional biomarker for the detection of pancreatic cancer. PMID:22158074

Association of Low Levels of Vitamin D with Chronic Stable Angina: A Prospective Case-Control Study

PubMed Central

Raina, Ab Hameed; Allai, Mohammad Sultan; Shah, Zafar Amin; Changal, Khalid Hamid; Raina, Manzoor Ahmad; Bhat, Fayaz Ahmad

2016-01-01

Background: Coronary artery disease (CAD) is a major cause of death and disability in developed countries. Chronic stable angina is the initial manifestation of CAD in approximately 50% of the patients. Recent evidence suggests that vitamin D is crucial for cardiovascular health. The prevalence of vitamin D deficiency in our region is 83%. A low level of vitamin D is associated with chronic stable angina. Aim: This study was aimed at supporting or refuting this hypothesis in our population. Materials and Methods: The study was a prospective case-control study. We studied 100 cases of chronic stable angina and compared them with 100 matched controls. Vitamin D deficiency was defined as <20 ng/mL, vitamin D insufficiency as 20-30 ng/mL and normal vitamin D level as 31-150 ng/mL. Results: The prevalence of vitamin D deficiency among cases and controls was 75% and 10%, respectively. 75% of the cases were vitamin D-deficient (<20 ng/mL); 12% were vitamin D-insufficient (20-30 ng/mL), and 13% had normal vitamin D levels (31-150 ng/mL). None had a toxic level of vitamin D. Among the controls, 10% were vitamin D-deficient, 33% were vitamin D-insufficient, and 57% had normal vitamin D levels. The mean vitamin level among cases and controls was 15.53 ng/mL and 40.95 ng/mL, respectively, with the difference being statistically significant (P ≤ 0.0001). There was no statistically significant relation between the disease severities, i.e., on coronary angiography (CAG) with vitamin D level. Among the cases, we found that an increasing age was inversely related to vitamin D levels (P = 0.027). Conclusion: Our study indicates a correlation between vitamin D deficiency and chronic stable angina. Low levels may be an independent, potentially modifiable cardiovascular risk factor. PMID:27114971

Normal weight adiposity in a Swedish population: how well is cardiovascular risk associated with excess body fat captured by BMI?

PubMed Central

Strandhagen, Elisabeth; Mehlig, Kirsten; Subramoney, Sreevidya; Lissner, Lauren; Björck, Lena

2015-01-01

Summary Objective The aim of this study was to examine how well body mass index (BMI) reflects cardiovascular risk associated with excess adiposity in a Swedish population by examining the association between body fat, BMI and cardiovascular risk factors. Methods A total of 3,010 adults participated. Normal weight adiposity was defined as the combination of BMI < 25 kg/m2 and percentage body fat ≥35% for women and ≥25% for men. Associations with blood pressure, blood lipids, apolipoproteins and C‐reactive protein were analysed in age‐adjusted regression models. Results The majority of the individuals with overweight and obesity were correctly classified to adiposity, while a wide range of body fat was observed among the normal weight subjects. In total, 9% of the participants were categorised as normal weight with adiposity. Compared with the normal weight leanness group, participants with normal weight adiposity had higher levels of serum triglycerides, low‐density lipoprotein cholesterol, C‐reactive protein, apolipoptotein B and the apolipoprotein B/A‐I ratio. In normal weight men, adiposity was also associated with higher blood pressure and lower high‐density lipoprotein cholesterol. Conclusions Higher percentage of body fat was associated with less favourable risk factor profile even in subjects who were normal weight. Thus, it might be relevant to screen for metabolic risk factors in the upper end of the normal weight category. PMID:27721982

Effects of endurance and high intensity training on ICAM-1 and VCAM-1 levels and arterial pressure in obese and normal weight adolescents.

PubMed

Kargarfard, Mehdi; Lam, Eddie T C; Shariat, Ardalan; Asle Mohammadi, Mahmoud; Afrasiabi, Saleh; Shaw, Ina; Shaw, Brandon S

2016-09-01

Obesity prevalence has increased in Iranian adolescents in recent years. However, few studies have examined the impact of intervention programs on this health issue. The main objective of this study was to evaluate the effects of 8-week endurance training (ET) and high intensity interval training (HIIT) on intercellular adhesion molecule-1(ICAM-1) and vascular adhesion molecule-1(VCAM-1) levels among obese and normal-weight male adolescents. Thirty obese and 30 normal-weight subjects were assigned to the ET, HIIT, or control group for eight weeks. Before and after the intervention, ICAM-1, VCAM-1, body weight, BMI, VO2max, and blood pressures were measured. SPSS (Version 21) was used for data analysis, and the significance level was set at p < 0.05. Mixed design ANOVAs indicated that the obese participants had significantly (p < 0.05) lower ICAM-1 levels in the ET (from 509 ± 61 ng/ml to 387 ± 43 ng/ml) and HIIT (from 517 ± 72 ng/ml to 374 ± 50 ng/ml), but their VCAM-1 level was significantly (p < 0.05) reduced only after the HIIT (from 1689 ± 119 ng/ml to 1282 ± 63 ng/ml). Similarly, normal weight participants significantly (p < 0.05) lowered their ICAM-1 levels in the ET (from 296 ± 18 ng/ml to 216 ± 14 ng/ml) and HIIT (from 289 ± 22 ng/ml to 202 ± 12 ng/ml), but their VCAM-1 level was significantly (p < 0.05) reduced only after the HIIT (from 895 ± 50 ng/ml to 673 ± 142 ng/ml). Systolic blood pressure and diastolic blood pressures of all the participants were significantly (p < 0.01) decreased at the conclusion of the ET and HIIT. While both the ET and HIIT were useful in lowering the SBP and DBP of the participants, HIIT was more effective than ET in reducing ICAM-1 and VCAM-1 content in normal and obese adolescents.

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

PubMed Central

Eizayaga, Francisco; Scorticati, Camila; Prestifilippo, Juan P; Romay, Salvador; Fernandez, Maria A; Castro, José L; Lemberg, Abraham; Perazzo, Juan C

2006-01-01

AIM: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized. METHODS: Adult male Wistar rats were divided into four groups: Group I: Sham14d , sham operated; Group II: PH14d , portal vein stenosis; (both groups were used 14 days after surgery); Group III: Sham40d, Sham operated and Group IV: PH40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment. PMID:16552803

Familial Dysalbuminemic Hyperthyroxinemia in a Japanese Man Caused by a Point Albumin Gene Mutation (R218P)

PubMed Central

Osaki, Yoshinori; Hayashi, Yoshitaka; Nakagawa, Yoshinori; Yoshida, Katsumi; Ozaki, Hiroshi; Fukazawa, Hiroshi

2016-01-01

Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant disease caused by mutation in the albumin gene that produces a condition of euthyroid hyperthyroxinemia. In patients with FDH, serum-free thyroxine (FT4) and free triiodothyronine (FT3) concentrations as measured by several commercial methods are often falsely increased with normal thyrotropin (TSH). Therefore, several diagnostic steps are needed to differentiate TSH-secreting tumor or generalized resistance to thyroid hormone from FDH. We herein report a case of a Japanese man born in Aomori prefecture, with FDH caused by a mutant albumin gene (R218P). We found that a large number of FDH patients reported in Japan to date might have been born in Aomori prefecture and have shown the R218P mutation. In conclusion, FDH needs to be considered among the differential diagnoses in Japanese patients born in Aomori prefecture and showing normal TSH levels and elevated FT4 levels. PMID:27081329

Possible stressors in a neonatal intensive care unit at a university hospital

PubMed Central

Jordão, Kamila Reis; Pinto, Lauriane de Assis Proença; Machado, Lucimer Rocha; Costa, Laetitia Braga Vasconcellos de Lima; Trajano, Eduardo Tavares Lima

2016-01-01

Objective To investigate possible stressors to which newborns are exposed in the neonatal intensive care unit. Methods The levels of continuous noise were checked by a decibel meter positioned near the ear of the newborn, brightness was observed by a light meter positioned in the incubator in front of the newborn's eyes, and temperature was checked through the incubator display. The evaluations were performed in three periods of the day, with ten measurements taken at one-minute intervals during each shift for the subsequent statistical analysis. Results All shifts showed noise above acceptable levels. Morning (p < 0.001), afternoon (p < 0.05) and night (p < 0.001) showed a significant increase compared to the control. The brightness significantly exceeded the normal range (p < 0.01) in the morning. We observed that only one of the incubators was within the normal temperature limits. Conclusion The noise, brightness and temperature intensities were not in accordance with regulatory standards and thus might be possible stressors to newborns. PMID:27626948

Evaluation of safety profile of black shilajit after 91 days repeated administration in rats

PubMed Central

Velmurugan, C; Vivek, B; Wilson, E; Bharathi, T; Sundaram, T

2012-01-01

Objective To evaluate the safety of shilajit by 91 days repeated administration in different dose levels in rats. Methods In this study the albino rats were divided into four groups. Group I received vehicle and group II, III and IV received 500, 2 500 and 5 000 mg/kg of shilajit, respectively. Finally animals were sacrificed and subjected to histopathology and iron was estimated by flame atomic absorption spectroscopy and graphite furnace. Results The result showed that there were no significant changes in iron level of treated groups when compared with control except liver (5 000 mg/kg) and histological slides of all organs revealed normal except negligible changes in liver and intestine with the highest dose of shilajit. The weight of all organs was normal when compared with control. Conclusions The result suggests that black shilajit, an Ayurvedic formulation, is safe for long term use as a dietary supplement for a number of disorders like iron deficiency anaemia. PMID:23569899

Gestational Gigantomastia Complicating Pregnancy: A Case Report and Review of the Literature

PubMed Central

Rezai, Shadi; Nakagawa, Jenna T.; Tedesco, John; Chadee, Annika; Gottimukkala, Sri; Mercado, Ray; Henderson, Cassandra E.

2015-01-01

Background. Gestational gigantomastia is a rare disorder without clear etiology or well-established risk factors. Several pathogenic mechanisms contributing to the disease process have been proposed, all of which can lead to a similar phenotype of breast hypertrophy. Case. A 28-year-old Guinean woman presented at 37 weeks of gestation with bilateral gigantomastia, mastalgia, peau d'orange, and back pain. Prolactin levels were 103.3 μg/L (with a normal reference value for prolactin in pregnancy being 36–372 μg/L). The patient was treated with bromocriptine (2.5 mg twice daily), scheduled for a repeat cesarean, and referred to surgery for bilateral mammoplasty. Conclusion. Gestational gigantomastia is a rare disorder, characterized by enlargement and hypertrophy of breast tissue. Our patient presented with no endocrine or hematological abnormalities, adding to a review of the literature for differential diagnoses, workup, and management of cases of gestational gigantomastia with normal hormone levels. PMID:26713166

Androgen Responses to ACTH Infusion among Individual Women with Polycystic Ovary Syndrome

PubMed Central

Maas, Kevin H.; Chuan, Sandy; Harrison, Evan; Cook-Andersen, Heidi; Duleba, Antoni J; Chang, R. Jeffrey

2016-01-01

Objective To compare androgen responses during ACTH infusion among women with PCOS and normal women. Design Cross-sectional study. Setting Research center at an academic medical center. Participants Women with PCOS (n=13) and normal controls (n=15). Interventions Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. Main Outcome Measures Comparison of basal and stimulated levels of 17-OHP, androgens, and cortisol during ACTH infusion with those following hCG injection within individual subjects. Results In women with PCOS increased 17-OHP, A4, and DHEA responses during ACTH infusion were comparable to those observed in normal controls. The magnitude of responses was highly variable among PCOS women. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in PCOS and normal controls. Conclusion Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues. PMID:27473350

Comparing the Social Skills of Students Addicted to Computer Games with Normal Students

PubMed Central

Zamani, Eshrat; Kheradmand, Ali; Cheshmi, Maliheh; Abedi, Ahmad; Hedayati, Nasim

2010-01-01

Background This study aimed to investigate and compare the social skills of studentsaddicted to computer games with normal students. The dependentvariable in the present study is the social skills. Methods The study population included all the students in the second grade ofpublic secondary school in the city of Isfahan at the educational year of2009-2010. The sample size included 564 students selected using thecluster random sampling method. Data collection was conducted usingQuestionnaire of Addiction to Computer Games and Social SkillsQuestionnaire (The Teenage Inventory of Social Skill or TISS). Findings The results of the study showed that generally, there was a significantdifference between the social skills of students addicted to computer gamesand normal students. In addition, the results indicated that normal studentshad a higher level of social skills in comparison with students addicted tocomputer games. Conclusion As the study results showed, addiction to computer games may affectthe quality and quantity of social skills. In other words, the higher theaddiction to computer games, the less the social skills. The individualsaddicted to computer games have less social skills.). PMID:24494102

Probable levetiracetam-related serum alkaline phosphatase elevation

PubMed Central

2012-01-01

Background Levetiracetam (LEV) is an antiepileptic drug with a favorable tolerability and safety profile with little or no effect on liver function. Case presentation Here, we reported an epileptic pediatric patient who developed a significant elevation in serum alkaline phosphatase level (ALP) during LEV monotherapy. Moreover, the serum ALP level was surprisingly decreased to normal after LEV discontinuation. The Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating firstly LEV was a probable cause for the increased serum ALP. Conclusions Cautious usage and concerns of the LEV-associated potential ALP elevation should be considered when levetiracetam is prescribed to epilepsy patients, especially pediatric patients. PMID:22994584

Unique spatial and cellular expression patterns of Hoxa5, Hoxb4 and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia

PubMed Central

Volpe, MaryAnn Vitoria; Wang, Karen Ting Wai; Nielsen, Heber Carl; Chinoy, Mala Romeshchandra

2009-01-01

Background Hox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern-specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 proteins compared to normal lung development. Methods Temporal, spatial and cellular Hoxa5, Hoxb4 and Hoxb6 expression was studied in normal (untreated) and nitrofen-induced hypoplastic (NT-PH) lungs from gestational day 13.5, 16, 19 fetuses and neonates using western blot and immunohistochemistry. Results Modification of protein levels and spatial and cellular Hox expression patterns in NT-PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 isoforms changed with development and further in NT-PH lungs. Compared to normal lungs, Gd19 and neonatal NT-PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways. Conclusions Unique spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 participates in branching morphogenesis and terminal sac formation. Altered Hox protein temporal and cellular balance of expression either contributes to pulmonary hypoplasia or functions as a compensatory mechanism attempting to correct abnormal lung development and maturation in this condition. PMID:18553509

Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis.

PubMed

Mori, T; Ishida, K; Mukumoto, S; Yamada, Y; Imokawa, G; Kabashima, K; Kobayashi, M; Bito, T; Nakamura, M; Ogasawara, K; Tokura, Y

2010-01-01

Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.

Decision strategies of hearing-impaired listeners in spectral shape discrimination

NASA Astrophysics Data System (ADS)

Lentz, Jennifer J.; Leek, Marjorie R.

2002-03-01

The ability to discriminate between sounds with different spectral shapes was evaluated for normal-hearing and hearing-impaired listeners. Listeners detected a 920-Hz tone added in phase to a single component of a standard consisting of the sum of five tones spaced equally on a logarithmic frequency scale ranging from 200 to 4200 Hz. An overall level randomization of 10 dB was either present or absent. In one subset of conditions, the no-perturbation conditions, the standard stimulus was the sum of equal-amplitude tones. In the perturbation conditions, the amplitudes of the components within a stimulus were randomly altered on every presentation. For both perturbation and no-perturbation conditions, thresholds for the detection of the 920-Hz tone were measured to compare sensitivity to changes in spectral shape between normal-hearing and hearing-impaired listeners. To assess whether hearing-impaired listeners relied on different regions of the spectrum to discriminate between sounds, spectral weights were estimated from the perturbed standards by correlating the listener's responses with the level differences per component across two intervals of a two-alternative forced-choice task. Results showed that hearing-impaired and normal-hearing listeners had similar sensitivity to changes in spectral shape. On average, across-frequency correlation functions also were similar for both groups of listeners, suggesting that as long as all components are audible and well separated in frequency, hearing-impaired listeners can use information across frequency as well as normal-hearing listeners. Analysis of the individual data revealed, however, that normal-hearing listeners may be better able to adopt optimal weighting schemes. This conclusion is only tentative, as differences in internal noise may need to be considered to interpret the results obtained from weighting studies between normal-hearing and hearing-impaired listeners.

Cumulative lactate and hospital mortality in ICU patients

PubMed Central

2013-01-01

Background Both hyperlactatemia and persistence of hyperlactatemia have been associated with bad outcome. We compared lactate and lactate-derived variables in outcome prediction. Methods Retrospective observational study. Case records from 2,251 consecutive intensive care unit (ICU) patients admitted between 2001 and 2007 were analyzed. Baseline characteristics, all lactate measurements, and in-hospital mortality were recorded. The time integral of arterial blood lactate levels above the upper normal threshold of 2.2 mmol/L (lactate-time-integral), maximum lactate (max-lactate), and time-to-first-normalization were calculated. Survivors and nonsurvivors were compared and receiver operating characteristic (ROC) analysis were applied. Results A total of 20,755 lactate measurements were analyzed. Data are srpehown as median [interquartile range]. In nonsurvivors (n = 405) lactate-time-integral (192 [0–1881] min·mmol/L) and time-to-first normalization (44.0 [0–427] min) were higher than in hospital survivors (n = 1846; 0 [0–134] min·mmol/L and 0 [0–75] min, respectively; all p < 0.001). Normalization of lactate <6 hours after ICU admission revealed better survival compared with normalization of lactate >6 hours (mortality 16.6% vs. 24.4%; p < 0.001). AUC of ROC curves to predict in-hospital mortality was the largest for max-lactate, whereas it was not different among all other lactate derived variables (all p > 0.05). The area under the ROC curves for admission lactate and lactate-time-integral was not different (p = 0.36). Conclusions Hyperlactatemia is associated with in-hospital mortality in a heterogeneous ICU population. In our patients, lactate peak values predicted in-hospital mortality equally well as lactate-time-integral of arterial blood lactate levels above the upper normal threshold. PMID:23446002

Non-Gaussian Distributions Affect Identification of Expression Patterns, Functional Annotation, and Prospective Classification in Human Cancer Genomes

PubMed Central

Marko, Nicholas F.; Weil, Robert J.

2012-01-01

Introduction Gene expression data is often assumed to be normally-distributed, but this assumption has not been tested rigorously. We investigate the distribution of expression data in human cancer genomes and study the implications of deviations from the normal distribution for translational molecular oncology research. Methods We conducted a central moments analysis of five cancer genomes and performed empiric distribution fitting to examine the true distribution of expression data both on the complete-experiment and on the individual-gene levels. We used a variety of parametric and nonparametric methods to test the effects of deviations from normality on gene calling, functional annotation, and prospective molecular classification using a sixth cancer genome. Results Central moments analyses reveal statistically-significant deviations from normality in all of the analyzed cancer genomes. We observe as much as 37% variability in gene calling, 39% variability in functional annotation, and 30% variability in prospective, molecular tumor subclassification associated with this effect. Conclusions Cancer gene expression profiles are not normally-distributed, either on the complete-experiment or on the individual-gene level. Instead, they exhibit complex, heavy-tailed distributions characterized by statistically-significant skewness and kurtosis. The non-Gaussian distribution of this data affects identification of differentially-expressed genes, functional annotation, and prospective molecular classification. These effects may be reduced in some circumstances, although not completely eliminated, by using nonparametric analytics. This analysis highlights two unreliable assumptions of translational cancer gene expression analysis: that “small” departures from normality in the expression data distributions are analytically-insignificant and that “robust” gene-calling algorithms can fully compensate for these effects. PMID:23118863

Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques

PubMed Central

2011-01-01

Background Mature carotid plaques are complex structures, and their histological classification is challenging. The carotid plaques of asymptomatic and symptomatic patients could exhibit identical histological components. Objectives To investigate whether matrix metalloproteinase 9 (MMP-9), tissue inhibitor of MMP (TIMP), and cyclooxygenase-2 (COX-2) have different expression levels in advanced symptomatic carotid plaques, asymptomatic carotid plaques, and normal tissue. Methods Thirty patients admitted for carotid endarterectomy were selected. Each patient was assigned preoperatively to one of two groups: group I consisted of symptomatic patients (n = 16, 12 males, mean age 66.7 ± 6.8 years), and group II consisted of asymptomatic patients (n = 14, 8 males, mean age 67.6 ± 6.81 years). Nine normal carotid arteries were used as control. Tissue specimens were analyzed for fibromuscular, lipid and calcium contents. The expressions of MMP-9, TIMP-1 and COX-2 in each plaque were quantified. Results Fifty-eight percent of all carotid plaques were classified as Type VI according to the American Heart Association Committee on Vascular Lesions. The control carotid arteries all were classified as Type III. The median percentage of fibromuscular tissue was significantly greater in group II compared to group I (p < 0.05). The median percentage of lipid tissue had a tendency to be greater in group I than in group II (p = 0.057). The percentages of calcification were similar among the two groups. MMP-9 protein expression levels were significantly higher in group II and in the control group when compared with group I (p < 0.001). TIMP-1 expression levels were significantly higher in the control group and in group II when compared to group I, with statistical difference between control group and group I (p = 0.010). COX-2 expression levels did not differ among groups. There was no statistical correlation between MMP-9, COX-2, and TIMP-1 levels and fibrous tissue. Conclusions MMP-9 and TIMP-1 are present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. When sections of a plaque are analyzed without preselection, MMP-9 concentration is higher in normal tissues and asymptomatic surgical specimens than in symptomatic specimens, and TIMP-1 concentration is higher in normal tissue than in symptomatic specimens. PMID:21457581

Effect of Hypertonic Saline Infusion versus Normal Saline on Serum NGAL and Cystatin C Levels in Patients Undergoing Coronary Artery Bypass Graft

PubMed Central

Yousefshahi, Fardin; Bashirzadeh, Mona; Abdollahi, Mohammad; Mojtahedzadeh, Mojtaba; Salehiomran, Abbass; Jalali, Arash; Mazandarani, Mahnaz; Zaare, Elmira; Ahadi, Mehdi

2013-01-01

Background: Acute kidney injury (AKI) is a common and life-threatening complication following coronary artery bypass graft (CABG). Neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin C have shown to be good predictive factors for AKI. Recently, there has been a growing interest in the use of hypertonic saline in cardiac operations. The purpose of this study was to evaluate the prophylactic anti-inflammatory effect of hypertonic saline (Group A) infusion versus normal saline (Group B) on serum NGAL and Cystatin C levels as the two biomarkers of AKI in CABG patients. Methods: This randomized double-blinded clinical trial recruited 40 patients undergoing CABG in Tehran Heart Center, Tehran, Iran. After applying exclusion criteria, the effects of preoperative hypertonic saline (294 meq Na) versus normal saline (154 meq Na) infusion on serum NGAL and Cystatin C levels were investigated in three intervals: before surgery and 24 and 48 hours postoperatively. The probable intraoperative or postoperative confounders, including pump time, cross-clamp time, heart rate, systolic and diastolic blood pressures, central venous pressure, arterial pH, partial pressure of arterial oxygen, fraction of inspired oxygen, blood sugar, Na, K, Mg, hemoglobins, white blood cells, hematocrits, and platelets, were recorded and compared between the two groups of study. Results: The study population comprised 40 patients, including 25 (62.5%) males, at a, mean age ± SD of 61.75 ± 8.13 years. There were no statistically significant differences between the patients’ basic, intraoperative, and postoperative characteristics, including intraoperative and postoperative hemodynamic variables and supports such as inotropic use. Intra-aortic balloon pump use and mortality were not seen in our cases. Three patients in the normal saline group and one patient in the hypertonic saline group had serum NGAL levels greater than 400 ng/ml. Moreover, 10 patients in Group A and 17 patients in group B showed a rise in serum Cystatin C levels above 1.16 mg/dl. Patients with AKI had significantly elevated NGAL and Cystatin C levels (p value < 0.001), but there were no significant differences in the decrease in the NGAL level in the hypertonic saline group versus the normal saline group (230.91 ± 92.68 vs. 239.74 ± 116.58 ng/ml, respectively; p value = 0.792), or in the decrease in the Cystatin C level in the hypertonic saline group versus the normal saline group (1.05 ± 0.26 vs. 1.06 ± 0.31, respectively; p value = 0.874). Conclusion: Pre-treatment of CABG patients with hypertonic saline had no significant effect on serum NGAL and Cystatin C levels compared to the normal saline-receiving group. Our present data, albeit promising, have yet to fully document outcome differences. PMID:23646044

Influence of Blood Lipids on Global Coagulation Test Results

PubMed Central

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon

2015-01-01

Background High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). Methods PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). Results The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. Conclusion High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels. PMID:25553275

Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

PubMed Central

Hämäläinen, Anssi; Sipponen, Taina; Kolho, Kaija-Leena

2011-01-01

AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn’s disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the patient was doing well. RESULTS: At introduction of infliximab, median fecal calprotectin level was 1150 μg/g (range 54-6032 μg/g). By week 2, the fecal calprotectin level had declined to a median 261 μg/g (P < 0.001). In 37% of the patients, fecal calprotectin was normal (< 100 μg/g) at 2 wk. By week 6, there was no additional improvement in the fecal calprotectin level (median 345 μg/g). In 22% of the patients, fecal calprotectin levels increased by week 6 to pretreatment levels or above, suggesting no response (or a loss of early response). Thus, in CD, the proportion of non-responsive patients by week 6 seemed lower, because only 9% showed no improvement in their fecal calprotectin level when compared to the respective figure of 46% of the UC patients (P < 0.05). CONCLUSION: When treated with infliximab, fecal calprotectin levels reflecting intestinal inflammation normalized rapidly in one third of pediatric patients suggesting complete mucosal healing. PMID:22215940

Effect of Bizhongxiao decoction and its dismantled formulae on IL-1 and TNF levels in collagen-induced arthritis in rat synovial joints

PubMed Central

2012-01-01

Background Rheumatoid arthritis (RA), a chronic autoimmune disease, affects sufferers in many different ways. Treatment of this chronic condition is particularly challenging. Traditional Chinese Medicine (TCM) provides alternatives. Bizhongxiao decoction (BZX) is a TCM complex, which has been used clinically for many years to treat RA. The purpose of this study is to compare the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels in rats with RA, and to elucidate its mechanism of action. Methods Ninety healthy normal female SD rats were randomly divided into six groups: normal (control), model, BZX decoction, and the three dismantled formulae (I: heat-clearing and detoxication, II: dissipating dampness, and III: blood circulation promotion). Apart from the normal (control) group, the rats in each group were injected subcutaneously with bovine type II collagen and complete Freund adjuvant to establish a collagen-induced arthritis model, so that inhibition of foot swelling in the rats by BZX decoction and its dismantled formulae could be observed. Immunohistochemistry was used to assess the levels of the inflammatory cytokines IL-1 and TNF in synovial joints at various time points. Results Twenty-one days after the model was established, the levels of TNF and IL-1 were significantly higher in the model group, BZX decoction group and dismantled formula groups I, II and III than in the normal controls (P < 0.05). The levels of these cytokines were significantly higher in the model group than the BZX decoction or the three dismantled formula groups (P <0.01). At longer times, the TNF and IL-1 levels in model group rose gradually; those in the BZX decoction and dismantled formula groups were gradually reduced. The cytokine levels in the BZX decoction group were lower than in the three dismantled formula groups and continued to decline. Conclusions BZX decoction and the three dismantled formulae examined down-regulated the inflammatory factors IL-1 and TNF in collagen-induced arthritis rat models, but BZX exerted the strongest effect. PMID:23163934

[Study on relationship between prevalence or co-prevalence of risk factors for cardiovascular disease and blood pressure level in adults in China].

PubMed

Chen, Z H; Zhang, M; Li, Y C; Zhao, Z P; Zhang, X; Huang, Z J; Li, C; Wang, L M

2018-05-10

Objective: To study the relationship between blood pressure level and major risk factors for cardiovascular diseases in adults in China. Methods: A total of 179 347 adults aged ≥18 years were recruited from 298 surveillance points in 31 provinces in China in 2013 through complex multistage stratified sampling. The survey included face to face interview and physical examination to collect information about risk factors, such as smoking, drinking, diet pattern, physical activity, overweight or obesity, and the prevalence of hypertension. The blood pressure was classified into 6 levels (ideal blood pressure, normal blood pressure, normal high blood pressure and hypertension phase Ⅰ, Ⅱ and Ⅲ). The relationship between the prevalence or co-prevalence of risk factors for cardiovascular disease and blood pressure was analyzed. Results: The adults with ideal blood pressure, normal blood pressure, normal high pressure, hypertension phase Ⅰ, Ⅱ and Ⅲ accounted for 36.14 % , 22.77 % , 16.22 % , 16.43 % , 5.97 % and 2.48 % , respectively. Among them, the blood pressure was higher in men, people in Han ethnic group and those married, and the blood pressure was higher in those with older age, lower income level and lower education level, the differences were all significant ( P <0.05). Whether taking antihypertensive drug or not, co-prevalence of risk factors influenced the blood pressure levels of both sexes ( P <0.05), and the blood pressure levels of those taking no antihypertensive drug was influenced more by the co-prevalence of risk factors. Finally, multiple logistic analysis showed that the risks for high blood pressure in adults with 1, 2 and ≥3 risk factors were 1.36, 1.79 and 2.38 times higher, respectively, than that of the adults without risk factor. Conclusion: The more the risk factors for cardiovascular disease in adults, the higher their blood pressure were. It is necessary to conduct comprehensive behavior intervention targeting ≥ 2 risk factors for the better control of blood pressure in general population.

Matrix metalloproteinase-7 expression in gastric carcinoma.

PubMed Central

Honda, M; Mori, M; Ueo, H; Sugimachi, K; Akiyoshi, T

1996-01-01

BACKGROUND/AIMS: Matrix metalloproteinase-7 (MMP-7) belongs to the same family as matrix degrading metalloproteinase (MMPs) that may play an important part in cancer cell invasion and metastasis. This study reports on the MMP-7 mRNA expression level both in human gastric carcinomas and the normal gastric mucosa. METHODS: From fresh specimens of 47 surgical pairs of primary gastric carcinomas and corresponding normal tissue specimens, cDNA was obtained by reverse transcription (RT) and thereafter MMP-7 mRNAs were detected by means of a polymerase chain reaction. The tumour/normal (T/N) ratio of MMP-7 expression was calculated after correcting for glyceraldehyde-3-phosphate dehydrogenase as an internal control. RESULTS: The expression corrected levels of MMP-7 mRNA of the tumour was greater than that of the normal mucosa in 41 of 47 cases (87%). The 13 cases whose T/N ratio was more than 2.1 showed a deeper invasion of the gastric wall, and more frequent lymphatic or vascular permeations than the 34 cases whose T/N ratio was less than 2.0. An immunohistochemical study showed that MMP-7 was predominantly expressed in the cancer cells, weakly expressed in normal epithelial cells, and not expressed in the surrounding stromal cells. CONCLUSIONS: These findings suggest that the overexpression of MMP-7 may thus play an important part in tumour invasion in gastric carcinomas while, in addition, MMP-7 may also prove to be a useful marker for determining the biological aggressiveness of gastric carcinoma. Images Figure 1 Figure 2 Figure 3 PMID:8949652

Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease

PubMed Central

Kester, Maartje I.; Teunissen, Charlotte E.; Crimmins, Daniel L.; Herries, Elizabeth M.; Ladenson, Jack. H.; Scheltens, Philip; van der Flier, Wiesje M.; Morris, John C.; Holtzman, David M.; Fagan, Anne M.

2015-01-01

IMPORTANCE Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. OBJECTIVE To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS Longitudinal study of consecutive patients who underwent 2 lumbar punctures between the beginning of 1995 and the end of 2010 within the memory clinic–based Amsterdam Dementia Cohort. The study included 163 patients: 37 cognitively normal participants (mean [SE] age, 64 [2] years; 38% female; and mean [SE] Mini-Mental State Examination [MMSE] score, 28 [0.3]), 61 patients with mild cognitive impairment (MCI) (mean [SE] age, 68 [1] years; 38% female; and mean [SE] MMSE score, 27 [0.3]), and 65 patients with AD (mean [SE] age, 65 [1] years; 45% female; and mean [SE] MMSE score, 22 [0.7]). The mean (SE) interval between lumbar punctures was 2.0 (0.1) years, and the mean (SE) duration of cognitive follow-up was 3.8 (0.2) years. Measurements of CSF NGRN levels were obtained in January and February 2014. MAIN OUTCOME AND MEASURE Levels of NGRN in CSF samples. RESULTS Baseline CSF levels of NGRN in patients with AD (median level, 2381 pg/mL [interquartile range, 1651-3416 pg/mL]) were higher than in cognitively normal participants (median level, 1712 pg/mL [interquartile range, 1206-2724 pg/mL]) (P = .04). Baseline NGRN levels were highly correlated with total tau and tau phosphorylated at threonine 181 in all patient groups (all P < .001), but not with Aβ42. Baseline CSF levels of NGRN were also higher in patients with MCI who progressed to AD (median level, 2842 pg/mL [interquartile range, 1882-3950 pg/mL]) compared with those with stable MCI (median level, 1752 pg/mL [interquartile range, 1024-2438 pg/mL]) (P = .004), and they were predictive of progression from MCI to AD (hazard ratio, 1.8 [95% CI, 1.1-2.9]; stratified by tertiles). Linear mixed-model analyses demonstrated that within-person levels of NGRN increased over time in cognitively normal participants (mean [SE] level, 90 [45] pg/mL per year; P < .05) but not in patients with MCI or AD. CONCLUSIONS AND RELEVANCE Neurogranin is a promising biomarker for AD because levels were elevated in patients with AD compared with cognitively normal participants and predicted progression from MCI to AD. Within-person levels of NGRN increased in cognitively normal participants but not in patients with later stage MCI or AD, which suggests that NGRN may reflect presymptomatic synaptic dysfunction or loss. PMID:26366630

Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

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

Zois, Christos E.; Giatromanolaki, Alexandra; Kainulainen, Heikki

2011-01-07

Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response ofmore » normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 mRNA levels significantly declined following irradiation (p < 0.01), whereas Bnip3 levels increased. Conclusions: It is suggested that irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. Whether this is due to defective maturation or to aberrant degradation of the autophagosomes requires further investigation.« less

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

PubMed

Oktar, Süleyman; Ilhan, Selçuk; Meydan, Sedat; Aydin, Mehmet; Yönden, Zafer; Gökçe, Ahmet

2010-01-01

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.

[Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level].

PubMed

Yan, Ling; Ye, Lu; Wang, Kun; Zhou, Jie; Zhu, Chunjia

2016-05-25

Objective: To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels. Methods: One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed. Results: Serum uric acid levels were decreased after treatment in both groups (all P <0.05), and patients with hyperuricemia showed more significant decrease in serum uric acid level ( P <0.05). Compared with the routine dose group, serum uric acid level in patients with hyperuricemia decreased more significantly in the high dose group ( P <0.05), but no significant difference was observed between patients with normal serum uric acid levels in two groups ( P >0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels ( P <0.01). In the high dose group, there were 7 patients without reflow, in which 2 had normal uric acid and 5 had high uric acid ( P <0.05). Logistic regression analysis showed that hyperuricemia was one of independent risk factors for no-reflow after PCI ( OR =1.01, 95% CI :1.01-1.11, P <0.01). The incidence of no-flow after PCI in the routine dose group was 21.8% (12/55), and that in the high dose group was 11.9% (7/59) ( P <0.01). Conclusion: High dose atorvastatin can decrease serum uric acid levels and improve reflow after PCI in patients with STEMI.

Cushing’s Disease

PubMed Central

ElShafie, Omayma; Osman, Anjum; Aamer, Fatima; Al-Mamari, Ali; Woodhouse, NJY

2012-01-01

We report five cases of Cushing’s disease where the patients were given a therapeutic trial of cabergoline. Morning serum cortisol, adrenocorticotrophic hormone (ACTH), and sleeping cortisol concentrations were significantly raised. Magnetic resonance imaging (MRI) scans revealed pituitary microadenomas in 3 patients but were normal in the others. Ectopic ACTH production was excluded in the 2 patients with normal MRI scans. All were given a therapeutic trial of cabergoline (1 mg daily). Four patients responded with a prompt fall in serum cortisol levels and had a sustained clinical and biochemical remission for 378, 44, 28 and 14 days, respectively. One patient failed to respond. In conclusion, we suggest that all patients with Cushing’s disease should undergo a therapeutic trial of cabergoline. Responders can then be prepared for surgery or, if needed, treated medically in the long term. PMID:23275847

Decorin and biglycan of normal and pathologic human corneas

NASA Technical Reports Server (NTRS)

Funderburgh, J. L.; Hevelone, N. D.; Roth, M. R.; Funderburgh, M. L.; Rodrigues, M. R.; Nirankari, V. S.; Conrad, G. W.

1998-01-01

PURPOSE: Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the core proteins that carry these atypical glycosaminoglycans. In this study the proteoglycan proteins attached to dermatan sulfate in normal and pathologic human corneas were examined to identify primary genes involved in the pathobiology of corneal scarring. METHODS: Proteoglycans from human corneas with chronic edema, bullous keratopathy, and keratoconus and from normal corneas were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunoblotting, and immunohistology with peptide antibodies to decorin and biglycan. RESULTS: Proteoglycans from pathologic corneas exhibit increased size heterogeneity and binding of the cationic dye alcian blue compared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribution patterns. In approximately half of the pathologic corneas, the level of biglycan was elevated an average of seven times above normal, and decorin was elevated approximately three times above normal. The increases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan sulfate chains of increased sulfation. Immunostaining of corneal sections showed an abnormal stromal localization of biglycan in pathologic corneas. CONCLUSIONS: The increased dermatan sulfate associated with chronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compared with normal stromal proteoglycans.

Age-related accumulation of the advanced glycation endproduct pentosidine in human articular cartilage aggrecan: the use of pentosidine levels as a quantitative measure of protein turnover.

PubMed

Verzijl, N; DeGroot, J; Bank, R A; Bayliss, M T; Bijlsma, J W; Lafeber, F P; Maroudas, A; TeKoppele, J M

2001-11-01

During aging, non-enzymatic glycation results in the formation and accumulation of the advanced glycation endproduct pentosidine in long-lived proteins, such as articular cartilage collagen. In the present study, we investigated whether pentosidine accumulation also occurs in cartilage aggrecan. Furthermore, pentosidine levels in aggrecan subfractions of different residence time were used to explore pentosidine levels as a quantitative measure of aggrecan turnover. In order to compare protein turnover rates, protein residence time was measured as racemization of aspartic acid. As has previously been shown for collagen, pentosidine levels increase with age in cartilage aggrecan. Consistent with the faster turnover of aggrecan compared to collagen, the rate of pentosidine accumulation was threefold lower in aggrecan than in collagen. In the subfractions of aggrecan, pentosidine levels increased with protein residence time. These pentosidine levels were used to estimate the half-life of the globular hyaluronan-binding domain of aggrecan to be 19.5 years. This value is in good agreement with the half-life of 23.5 years that was estimated based on aspartic acid racemization. In aggrecan from osteoarthritic (OA) cartilage, decreased pentosidine levels were found compared with normal cartilage, which reflects increased aggrecan turnover during the OA disease process. In conclusion, we showed that pentosidine accumulates with age in aggrecan and that pentosidine levels can be used as a measure of turnover of long-lived proteins, both during normal aging and during disease.

Retinal degeneration increases susceptibility to myopia in mice

PubMed Central

Park, Hanna; Tan, Christopher C.; Faulkner, Amanda; Jabbar, Seema B.; Schmid, Gregor; Abey, Jane; Iuvone, P. Michael

2013-01-01

Purpose Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associated with myopia; however, the underlying link between these conditions is not known. This study examines the influence of photoreceptor degeneration on refractive development by testing two mouse models of retinitis pigmentosa under normal and form deprivation visual conditions. Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism. Methods Refractive eye growth in mice that were homozygous for a mutation in Pde6b, Pde6brd1/rd1 (rd1), or Pde6brd10/rd10 (rd10) was measured weekly from 4 to 12 weeks of age and compared to age-matched wild-type (WT) mice. Refractive error was measured using an eccentric infrared photorefractor, and axial length was measured with partial coherence interferometry or spectral domain ocular coherence tomography. A cohort of mice received head-mounted diffuser goggles to induce form deprivation from 4 to 6 weeks of age. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured with high-performance liquid chromatography in each strain after exposure to normal or form deprivation conditions. Results The rd1 and rd10 mice had significantly greater hyperopia relative to the WT controls throughout normal development; however, axial length became significantly longer only in WT mice starting at 7 weeks of age. After 2 weeks of form deprivation, the rd1 and rd10 mice demonstrated a faster and larger myopic shift (−6.14±0.62 and −7.38±1.46 diopter, respectively) compared to the WT mice (−2.41±0.47 diopter). Under normal visual conditions, the DOPAC levels and DOPAC/dopamine ratios, a measure of dopamine turnover, were significantly lower in the rd1 and rd10 mice compared to the WT mice, while the dopamine levels were similar or higher than WT in the rd10 mice. Lower basal levels of DOPAC were highly correlated with increasing myopic shifts. Conclusions Refractive development under normal visual conditions was disrupted toward greater hyperopia from 4 to 12 weeks of age in these photoreceptor degeneration models, despite significantly lower DOPAC levels. However, the retinal degeneration models with low basal levels of DOPAC had increased susceptibility to form deprivation myopia. These results indicate that photoreceptor degeneration may alter dopamine metabolism, leading to increased susceptibility to myopia with an environmental visual challenge. PMID:24146540

Performance of coagulation tests in patients on therapeutic doses of rivaroxaban. A cross-sectional pharmacodynamic study based on peak and trough plasma levels.

PubMed

Francart, Suzanne J; Hawes, Emily M; Deal, Allison M; Adcock, Dorothy M; Gosselin, Robert; Jeanneret, Cheryl; Friedman, Kenneth D; Moll, Stephan

2014-06-01

Knowledge of anticoagulation status during rivaroxaban therapy is desirable in certain clinical situations. It was the study objective to determine coagulation tests most useful for assessing rivaroxaban's anticoagulant effect. Peak and trough blood samples from 29 patients taking rivaroxaban 20 mg daily were collected. Mass spectrometry and various coagulation assays were performed. "On-therapy range" was defined as the rivaroxaban concentrations determined by LC-MS/MS. A "misprediction percentage" was calculated based on how often results of each coagulation assay were in the normal reference range, while the rivaroxaban concentration was in the "on-therapy" range. The on-therapy range was 8.9-660 ng/ml. The misprediction percentages for prothrombin time (PT) and activated partial thromboplastin time (aPTT), using multiple reagents and coagulometers, ranged from 10%-52% and 31%-59%, respectively. PT, aPTT and activated clotting time (ACT) were insensitive to trough rivaroxaban: 59%, 62%, and 80% of samples had a normal result, respectively. Over 95% of PT and ACT values were elevated at peak. Four different rivaroxaban calibrated anti-Xa assays had R² values >0.98, demonstrating strong correlations with rivaroxaban drug levels. In conclusion, PT, aPTT and ACT are often normal in patients on therapeutic doses of rivaroxaban. However, PT and ACT may have clinical utility at higher drug plasma levels. Rivaroxaban calibrated anti-factor Xa assays can accurately identify low and high on-therapy rivaroxaban drug levels and, therefore, have superior utility in all clinical situations where assessment of anticoagulation status may be beneficial.

Impaired thrombin generation and fibrin clot formation in patients with dilutional coagulopathy during major surgery.

PubMed

Schols, S E M; Lancé, M D; Feijge, M A H; Damoiseaux, J; Marcus, M A; Hamulyák, K; Ten Cate, H; Heemskerk, J W M; van Pampus, E C M

2010-02-01

Patients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53-60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38-41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88-93% of the patients with (persistent) bleeding, but only in 40-53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.

Early pregnancy assessment with transvaginal ultrasound scanning.

PubMed Central

Daya, S; Woods, S; Ward, S; Lappalainen, R; Caco, C

1991-01-01

OBJECTIVE: To establish normal parameters in early pregnancy through transvaginal ultrasonography so that gestational age can be determined and to correlate the sonographic findings with serum human chorionic gonadotropin (hCG) levels calibrated against the first international reference preparation standard. SETTING: Infertility clinic. PATIENTS: Thirty-five women with normal intrauterine pregnancy. INTERVENTIONS: Serial measurement of the serum hCG level and the diameter of the gestational sac through transvaginal ultrasonography. MAIN RESULTS: The gestational sac could not be visualized when the hCG level was less than 1100 IU/L. The average growth rate of the sac was 0.9 mm/d. The threshold values for sac diameter, serum hCG level and gestational age below which the yolk sac was not visible were 3.7 mm, 1900 IU/L and 36 days respectively; the corresponding values above which the yolk sac was always visible were 6.7 mm, 5800 IU/L and 40 days. The threshold values below which cardiac activity was not visible were 8.3 mm, 9200 IU/L and 41 days respectively, and the corresponding values above which cardiac activity was always visible were 14.0 mm, 24,000 IU/L and 46 days. The mean gestational ages and the 95% confidence and prediction intervals were tabulated so that measurement of the gestational sac diameter could be used to estimate gestational age early in normal pregnancy. CONCLUSIONS: Transvaginal ultrasonography enables detection of an intrauterine sac and reliable estimation of gestational age on the basis of sac dimensions before an embryo can be seen. PMID:1993291

Physiological Ranges of Matrix Rigidity Modulate Primary Mouse Hepatocyte Function In Part Through Hepatocyte Nuclear Factor 4 Alpha

PubMed Central

Desai, Seema S.; Tung, Jason C.; Zhou, Vivian X.; Grenert, James P.; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M.; Chang, Tammy T.

2016-01-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of hepatic-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150Pa and increased to 1–6kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α) whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase (FAK). In addition, blockade of the Rho/Rho-associated protein kinase (ROCK) pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Conclusion Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/ROCK pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. PMID:26755329

Inulin-type fructan improves diabetic phenotype and gut microbiota profiles in rats

PubMed Central

Xin, Fengjiao; Yu, Xiaobing

2018-01-01

Background & Aims Accumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats. Methods A diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed. Results We found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck, G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3–V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Phascolarctobacterium, and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio, which produce lipopolysaccharide (LPS). The abundance of Lachnospiraceae was negatively correlated with the blood glucose response after a glucose load. Conclusion In summary, diabetic rats have different gut microbiota from control rats. Inulin treatment can alleviate gut microbiota dysbiosis in T2D model rats. Moreover, inulin treatment enhanced serum GLP-1 level to suppress IL-6 secretion and production and hepatic gluconeogenesis, resulted in moderation of insulin tolerance. PMID:29507837

Treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection.

PubMed

Larijani, Bagher; Pajouhi, Mohammad; Ghanaati, Hossein; Bastanhagh, Mohammad-Hassan; Abbasvandi, Fereshteh; Firooznia, Kazem; Shirzad, Mahmood; Amini, Mohammad-Reza; Sarai, Maryam; Abbasvandi, Nasreen; Baradar-Jalili, Reza

2002-12-06

BACKGROUND: Autonomous thyroid nodules can be treated by a variety of methods. We assessed the efficacy of percutaneous ethanol injection in treating autonomous thyroid nodules. METHODS: 35 patients diagnosed by technetium-99 scanning with hyperfunctioning nodules and suppressed sensitive TSH (sTSH) were given sterile ethanol injections under ultrasound guidance. 29 patients had clinical and biochemical hyperthyroidism. The other 6 had sub-clinical hyperthyroidism with suppressed sTSH levels (<0.24 &mgr;IU/ml) and normal thyroid hormone levels. Ethanol injections were performed once every 1-4 weeks. Ethanol injections were stopped when serum T3, T4 and sTSH levels had returned to normal, or else injections could no longer be performed because significant side effects. Patients were followed up at 3, 6 and, in 15 patients, 24 months after the last injection. RESULTS: Average pre-treatment nodule volume [18.2 PlusMinus; 12.7 ml] decreased to 5.7 PlusMinus; 4.6 ml at 6 months follow-up [P < 0.001]. All patients had normal thyroid hormone levels at 3 and 6 months follow-up [P < 0.001 relative to baseline]. sTSH levels increased from 0.09 PlusMinus; 0.02 &mgr;IU/ml to 0.65 PlusMinus; 0.8 &mgr;IU/ml at the end of therapy [P < 0.05]. Only 3 patients had persistent sTSH suppression at 6 months post-therapy. T4 and sTSH did not change significantly between 6 months and 2 years [P > 0.05]. Ethanol injections were well tolerated by the patients, with only 2 cases of transient dysphonia. CONCLUSION: Our findings indicate that ethanol injection is an alternative to surgery or radioactive iodine in the treatment of autonomous thyroid nodules.

Preventive activity of banana peel polyphenols on CCl4-induced experimental hepatic injury in Kunming mice.

PubMed

Wang, Rui; Feng, Xia; Zhu, Kai; Zhao, Xin; Suo, Huayi

2016-05-01

The aim of the present study was to evaluate the preventive effects of banana peel polyphenols (BPPs) against hepatic injury. Mice were divide into normal, control, 100 mg/kg and 200 mg/kg banana peel polyphenol and silymarin groups. All the mice except normal mice were induced with hepatic damage using CCl 4 . The serum and tissue levels of mice were determined by a kit and the tissues were further examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. BPPs reduced the serum levels of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase in a CCl 4 -induced mouse model of hepatic injury. Furthermore, BPPs reduced the levels of malondialdehyde and triglyceride, while increasing glutathione levels in the serum and liver tissues of mice. In addition, the effects of 200 mg/kg treatment were more evident, and these effects were comparable to those of the drug silymarin. Serum levels of the cytokines, interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-α and interferon-γ, were reduced in the mice treated with BPPs compared with injury control group mice, and these levels were comparable to those of the normal and silymarin-treated groups. Histopathological examination indicated that BPPs were able to reduce the extent of CCl 4 -induced liver tissue injury and protect the liver cells. Furthermore, the mRNA and protein expression levels of the inflammation-associated factors cyclooxygenase-2, nitric oxide synthase, TNF-α and IL-1β were reduced in mice treated with BPPs compared with the control group mice. Mice that received 200 mg/kg BPP exhibited reduced expression levels of these factors compared with mice that received 100 mg/kg BPP. In conclusion, the results of the present study suggested that BPPs exert a good preventive effect against hepatic injury.

Assessment of the Rotation Motion at the Papillary Muscle Short-Axis Plane with Normal Subjects by Two-Dimensional Speckle Tracking Imaging: A Basic Clinical Study

PubMed Central

Ni, Xian-Da; Huang, Jun; Hu, Yuan-Ping; Xu, Rui; Yang, Wei-Yu; Zhou, Li-Ming

2013-01-01

Background The aim of this study was to observe the rotation patterns at the papillary muscle plane in the Left Ventricle(LV) with normal subjects using two-dimensional speckle tracking imaging(2D-STI). Methods We acquired standard of the basal, the papillary muscle and the apical short-axis images of the LV in 64 subjects to estimate the LV rotation motion by 2D-STI. The rotational degrees at the papillary muscle short-axis plane were measured at 15 different time points in the analysis of two heart cycles. Results There were counterclockwise rotation, clockwise rotation, and counterclockwise to clockwise rotation at the papillary muscle plane in the LV with normal subjects, respectively. The ROC analysis of the rotational degrees was performed at the papillary muscle short-axis plane at the peak LV torsion for predicting whether the turnaround point of twist to untwist motion pattern was located at the papillary muscle level. Sensitivity and specificity were 97% and 67%, respectively, with a cut-off value of 0.34°, and an area under the ROC curve of 0.8. At the peak LV torsion, there was no correlation between the rotational degrees at the papillary muscle short-axis plane and the LVEF in the normal subjects(r = 0.000, p = 0.998). Conclusions In the study, we conclude that there were three rotation patterns at the papillary muscle short-axis levels, and the transition from basal clockwise rotation to apical counterclockwise rotation is located at the papillary muscle level. PMID:24376634

Food Choices and Consequences for the Nutritional Status: Insights into Nutrition Transition in an Hospital Community

PubMed Central

Piple, Jitendra; Gora, Ranjeet; Purbiya, Pragati; Puliyel, Ashish; Chugh, Parul; Bahl, Pinky; Puliyel, Jacob

2015-01-01

Introduction Although economic development is generally accompanied by improvements in the overall nutritional status of the country’s population the ‘nutritional transition’ often involves a shift to high energy diets and less exercise with negative consequences. This pilot study was done to examine if education of parents operates at the household level to influence dietary choices and the nutritional status of children in a small community of hospital workers. Material and Methods 3 groups of persons with varying skill and education levels participated. Weighed food logs were used in all households to calculate ‘adult equivalent’ per-capita-consumption. Nutrients were calculated using nutrients calculator software. BMI was used to classify children as underweight, normal weight and overweight. Results 128 individuals participated from 30 families included 47 children. 10 children (21%) were underweight, 29 (62%) were normal and 8 (17%) were overweight. Energy consumption was highest in families with overweight children 2692 +/-502 compared to 2259 +/-359 in families with normal weight and 2031+/-354 in the family of underweight children. These differences were statistically significant. 42% underweight children belonged to Class 1 at the lowest skill level and there were no overweight children in this group. Most of the overweight children belonged to Class 2. In Class 3 there were no underweight children and the majority was normal weight children. Conclusion Underweight children came from the poorer households. Per capita intake of the family as a whole correlated well with BMI in the children. There was increased obesity in middle income families belonging to Class 2—probably in families who move up the scale from deprivation. Nutritional status in children correlated mostly with maternal education status. PMID:26559817

Objective Evaluation of Vergence Disorders and a Research-Based Novel Method for Vergence Rehabilitation

PubMed Central

Kapoula, Zoï; Morize, Aurélien; Daniel, François; Jonqua, Fabienne; Orssaud, Christophe; Brémond-Gignac, Dominique

2016-01-01

Purpose We performed video-oculography to evaluate vergence eye movement abnormalities in students diagnosed clinically with vergence disorders. We tested the efficiency of a novel rehabilitation method and evaluated its benefits with video-oculography cross-correlated with clinical tests and symptomatology. Methods A total of 19 students (20–27 years old) underwent ophthalmologic, orthoptic examination, and a vergence test coupled with video-oculography. Eight patients were diagnosed with vergence disorders with a high symptomatology score (CISS) and performed a 5-week session of vergence rehabilitation. Vergence and rehabilitation tasks were performed with a trapezoid surface of light emitting diodes (LEDs) and adjacent buzzers (US 8851669). We used a novel Vergence double-step (Vd-s) protocol: the target stepped to a second position before the vergence movement completion. Afterward the vergence test was repeated 1 week and 1 month later. Results Abnormally increased intertrial variability was observed for many vergence parameters (gain, duration, and speed) for the subjects with vergence disorders. High CISS scores were correlated with variability and increased latency. After the Vd-s, variability of all parameters dropped to normal or better levels. Moreover, the convergence and divergence latency diminished significantly to levels better than normal; benefits were maintained 1 month after completion of Vd-s. CISS scores dropped to normal level, which was maintained up to 1 year. Conclusions and Translational Relevance: Intertrial variability is the major marker of vergence disorders. The Vd-s research-based method leads to normalization of vergence properties and lasting removal of symptoms. The efficiency of the method is due to the spatiotemporal parameters of repetitive trials that stimulate neural plasticity. PMID:26981330

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs

PubMed Central

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

Objective To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. Methods In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. Results 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average −4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = −19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Conclusion Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. PMID:27454447

Vitamin D deficiency and insufficiency among patients with prostate cancer

PubMed Central

Trump, Donald L.; Chadha, Manpreet K.; Sunga, Annette Y.; Fakih, Marwan G.; Ashraf, Umeer; Silliman, Carrie G.; Hollis, Bruce W.; Nesline, Mary K.; Tian, Lili; Tan, Wei; Johnson, Candace S.

2009-01-01

Objective To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. Patients, subjects and methods The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. Results The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (< 20 ng/mL) and insufficiency (20–31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32–100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Conclusions Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region. PMID:19426195

Insulin resistance and associated factors: a cross-sectional study of bank employees

PubMed Central

Salaroli, Luciane Bresciani; Cattafesta, Monica; Molina, Maria del Carmen Bisi; Zandonade, Eliana; Bissoli, Nazaré Souza

2017-01-01

OBJECTIVE: Insulin resistance is characterized by the failure of target cells to respond to normal levels of circulating insulin, and this condition is related to cardiovascular disease. This study sought to evaluate the prevalence of insulin resistance and its association with markers of metabolic abnormalities and metabolic syndrome in bank employees. METHODS: A cross-sectional study was performed on 498 working men and women aged ≥20 years old. The Homeostasis Model Assessment (HOMA-IR) was used to determine the presence of insulin resistance based on cut-off values of ≤2.71 for normal insulin levels and >2.71 for insulin resistance, as established for the adult Brazilian population. RESULTS: It was observed that the 52 (10.4%) overweight individuals with insulin resistance were 4.97 times (95%CI 1.31-18.83) more likely to have high HOMA-IR values than the normal-weight participants; among those who were obese, the likelihood increased to 17.87 (95%CI 4.36-73.21). Individuals with large waist circumferences were 3.27 times (95%CI 1.03-10.38) more likely to develop insulin resistance than those who were within normal parameters. The HOMA-IR values differed between subjects with and without metabolic syndrome, with values of 2.83±2.5 and 1.10±0.81 (p=0.001), respectively. The levels of insulin, ultrasensitive C-reactive protein and uric acid were also associated with insulin resistance. CONCLUSION: The prevalence of insulin resistance among bank employees is high, and insulin resistance is associated with and serves as a marker of metabolic syndrome. Cardiovascular disease and metabolic syndrome-associated metabolic abnormalities were observed, and insulin resistance may be a risk factor in this group of professionals. PMID:28492722

Small airway dysfunction in smokers with stable ischemic heart disease

PubMed Central

Llontop, Claudia; Garcia-Quero, Cristina; Castro, Almudena; Dalmau, Regina; Casitas, Raquel; Galera, Raúl; Iglesias, Alberto; Martinez-Ceron, Elisabet; Soriano, Joan B.; García-Río, Francisco

2017-01-01

Background A higher prevalence of airflow limitation (AL) has been described in patients with ischemic heart disease (IHD). Although small airway dysfunction (SAD) is an early feature of AL, there is little information about its occurrence in IHD patients. Our objective was to describe the prevalence of SAD in IHD patients, while comparing patient-related outcomes and future health risk among IHD patients with AL, SAD and normal lung function. Methods In 118 consecutive smoking patients with stable IHD, comorbidities, utilization of healthcare resources, current treatment, blood biochemistry and health status were recorded. SAD was evaluated by impulse oscillometry, and pre- and post-bronchodilator spirometry was performed. Results The prevalence of AL and SAD were 20.3 (95% CI, 13.1–27.6%) and 26.3% (95% CI, 18.3–34.2%), respectively. Compared to the normal lung function group, patients with SAD and without AL had lower spirometric values, poorer quality of life and higher levels of C-reactive protein (CRP), as well as increased cardiovascular risk and more vascular age. In patients with normal spirometry, the presence of SAD was independently associated with pack-years, HDL-cholesterol and CRP levels. Conclusion In patients with IHD, the presence of SAD is common and that it is associated with reduced health status and increased future cardiac risk. PMID:28846677

The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective Study

PubMed Central

Vilar, Lucio; Albuquerque, José Luciano; Lyra, Ruy; Trovão Diniz, Erik; Rangel Filho, Frederico; Gadelha, Patrícia; Thé, Ana Carolina; Ibiapina, George Robson; Gomes, Barbara Sales; Santos, Vera; Melo da Fonseca, Maíra; Frasão Viana, Karoline; Lopes, Isis Gabriella; Araújo, Douglas; Naves, Luciana

2016-01-01

Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6–12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6–12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism. PMID:27034666

Perceived health status and cardiometabolic risk among a sample of youth in Mexico

PubMed Central

Flores, Yvonne N.; Shaibi, Gabriel Q.; Morales, Leo S.; Salmerón, Jorge; Skalicky, Anne M.; Edwards, Todd C.; Gallegos-Carrillo, Katia; Patrick, Donald L.

2015-01-01

Purpose To examine differences in self-reported perceived mental and physical health status (PHS), as well as known cardiometabolic risk factors in a sample of normal weight, overweight, and obese Mexican youths. Methods Cross-sectional analysis of 164 youths aged 11-18 years recruited in Cuernavaca, Mexico. Participants completed a self-administered questionnaire that included measures of generic and weight-specific quality of life (QoL), perceived health, physical function, depressive symptoms, and body shape satisfaction. Height, weight and waist circumference were measured and body mass index (BMI) was determined. Fasting blood samples from participants yielded levels of glucose, triglycerides, and cholesterol (total, HDL and LDL). Results Nearly 50% of participants were female, 21% had a normal BMI, 39% were overweight, and 40% were obese. Obese youths reported significantly lower measures of PHS and showed an increase in cardiometabolic risk, compared to normal weight youths. Physical functioning, generic and weight-specific QoL were inversely associated with BMI, waist circumference and glucose. Depressive symptoms were positively correlated with BMI, waist circumference, glucose levels and HDL cholesterol. No correlation was found between PHS and cardiometabolic risk measures after controlling for BMI. Conclusions In this sample of Mexican youths, obesity was associated with a significantly lower PHS and increased cardiometabolic risk. PMID:25648756

Fibrinogen gamma-A chain precursor in CSF: a candidate biomarker for Alzheimer's disease

PubMed Central

Lee, Joung Wook; Namkoong, Hong; Kim, Hyun Kee; Kim, Sanghee; Hwang, Dong Whi; Na, Hae Ri; Ha, Seon-Ah; Kim, Jae-Ryong; Kim, Jin Woo

2007-01-01

Background Cerebrospinal fluid (CSF) may be valuable for exploring protein markers for the diagnosis of Alzheimer's disease (AD). The prospect of early detection and treatment, to slow progression, holds hope for aging populations with increased average lifespan. The aim of the present study was to investigate candidate CSF biological markers in patients with mild cognitive impairment (MCI) and AD and compare them with age-matched normal control subjects. Methods We applied proteomics approaches to analyze CSF samples derived from 27 patients with AD, 3 subjects with MCI and 30 controls. The AD group was subdivided into three groups by clinical severity according to clinical dementia rating (CDR), a well known clinical scale for dementia. Results We demonstrated an elevated level of fibrinogen gamma-A chain precursor protein in CSF from patients with mild cognitive impairment and AD compared to the age-matched normal subjects. Moreover, its expression was more prominent in the AD group than in the MCI and correlated with disease severity and progression. In contrast, fibrinogen gamma-A chain precursor protein was detected very low in the age-matched normal group. Conclusion These findings suggest that the CSF level of fibrinogen gamma-A chain precursor may be a candidate biomarker for AD. PMID:17565664

GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in Obese Patients with Fibromyalgia Syndrome.

PubMed

Rigamonti, Antonello E; Grugni, Graziano; Arreghini, Marco; Capodaglio, Paolo; De Col, Alessandra; Agosti, Fiorenza; Sartorio, Alessandro

2017-01-01

Reportedly, fibromyalgia (FM) is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or <-2 SDS), underwent the combined GHRH plus arginine test. Four out of 16 obese women with FM (25%) had low IGF-1 SDS values, 2 cases of this subgroup (12.5%) failing also to normally respond to the test. Among patients with normal GH responses, 4 showed a delayed GH peak. The subgroup with low IGF-1 SDS values had higher BMI than that with normal IGF-1 SDS. GH peak and area under the curve were not correlated with CRP, ESR, or tender point score, while significant correlations were found with fat-free mass and fat mass. In conclusion, this study shows the existence of a high prevalence of GH-IGF-1 dysfunction in patients with both FM and obesity, presumably as a consequence of the obese rather than fibromyalgic condition.

Placental release of distinct DNA-associated microparticles into maternal circulation: reflective of gestation time and preeclampsia

PubMed Central

Orozco, Aaron F.; Jorgez, Carolina J.; Ramos-Perez, William D.; Popek, Edwina J.; Yu, Xiaoying; Kozinetz, Claudia A.; Bischoff, Farideh Z.; Lewis, Dorothy E.

2009-01-01

Background The aim of this study was to determine whether DNA-associated micro-particles (MPs) in maternal plasma express fetal-derived human leukocyte antigen-G (HLA-G) or placental alkaline phosphatase (PLAP) and whether the levels differ between women with normotensive pregnancies and preeclampsia. Methods DNA-associated MPs expressing HLA-G or PLAP were examined in the plasma of normal pregnant women and preeclamptic patients using flow cytometric analysis. Results DNA-associated HLA-G+ MPs were significantly increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.005), with highest levels found in first and second trimesters. DNA-associated PLAP+ MPs were also increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.006), with highest levels in second and third trimesters. Term preeclamptic women had higher levels of DNA-associated MPs than control pregnant women. HLA-G+ MPs from the plasma of preeclamptic women had more DNA per MP than HLA-G+ MPs from the plasma of normal pregnant women (p < 0.03). Conclusions HLA-G and PLAP MPs increase in maternal circulation at different times during gestation. DNA amounts per HLA-G+ MP increase in preeclamptic women which might indicate dysfunctional extravillous cytotrophoblasts. PMID:19692120

Global manipulation of digital images can lead to variation in cytological diagnosis

PubMed Central

Prasad, H; Wanjari, Sangeeta; Parwani, Rajkumar

2011-01-01

Background: With the adoption of a completely electronic workflow by several journals and the advent of telepathology, digital imaging has become an integral part of every scientific research. However, manipulating digital images is very easy, and it can lead to misinterpretations. Aim: To analyse the impact of manipulating digital images on their diagnosis. Design: Digital images were obtained from Papanicolaou-stained smears of dysplastic and normal oral epithelium. They were manipulated using GNU Image Manipulation Program (GIMP) to alter their brightness and contrast and color levels. A Power Point presentation composed of slides of these manipulated images along with the unaltered originals arranged randomly was created. The presentation was shown to five observers individually who rated the images as normal, mild, moderate or severe dysplasia. Weighted κ statistics was used to measure and assess the levels of agreement between observers. Results: Levels of agreement between manipulated images and original images varied greatly among observers. Variation in diagnosis was in the form of overdiagnosis or under-diagnosis, usually by one grade. Conclusion: Global manipulations of digital images of cytological slides can significantly affect their interpretation. Such manipulations should therefore be kept to a minimum, and avoided wherever possible. PMID:21572507

Ocimum gratissmum aqueous extract reduces plasma lipid in hypercholesterol-fed hamsters

PubMed Central

Chao, Pei-Yu; Lin, James A.; Ting, Wei-Jen; Lee, Hsueh-Hui; Hsieh, Kuanghui; Chiu, Yung-Wei; Lai, Te-Jen; Hwang, Jin-Ming; Liu, Je-rYuh; Huang, Chih-Yang

2016-01-01

Objectives: Hyperlipidemia is a significant risk factor in the development of atherosclerosis and related diseases which are major health problem in many developed and developing countries that can lead to fatality due to the changes in lifestyle and dietary habits in this modern age. Methods: In the present study, the Ocimum gratissimum aqueous extract (OGE) was tested for the lowering effect on the serum lipid level of male hamsters on a high-fat (12%) and high-cholesterol (0.2%) diet (HFCD). Results: The results showed that the levels of serum high-density-lipoprotein-cholesterol (HDL-C) low-density-lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglycerols (TG) were increased in the HFCD group (113±11, 259±87, 629±175 and 625±262, respectively), as compared to the control normal diet group (51±8, 19±5, 77±16 and 101±44, respectively). When co-treated with various doses (10 and 20 mg/kg) of the OGE or rosuvastatin, the rats exhibited the restoration of normal serum LDL-C, TC, and TG levels. Conclusion: Therefore, we suggest that the Ocimum gratissimum aqueous extract may have the potential function of lowering serum lipid in rats. PMID:27877073

Androgens as double-edged swords: Induction and suppression of follicular development.

PubMed

Pan, Jie-Xue; Zhang, Jun-Yu; Ke, Zhang-Hong; Wang, Fang-Fang; Barry, John A; Hardiman, Paul J; Qu, Fan

2015-01-01

Androgens, which are mediated via the androgen receptor (AR), play important roles in normal follicular development and female fertility. However, just like a double-edged sword, besides the positive effects of androgen on follicular development, abnormal androgen levels, especially as in hyperandrogenism, seriously suppress normal follicular development. A crucial balance exists between the importance of androgens in follicular development and their negative effects when in excess. As the first meiotic division and epigenetic reprogramming are two critical events in oogenesis, abnormal androgen levels or deficiency in androgen/AR signaling in the ovary may affect these vital events. Oocytes have a tendency to develop genomic instability, thus resulting in an increasing incidence of unpredictable adult diseases. Although many studies have explored the effects of androgens and AR on follicular development, the conclusions are controversial and there has been no thorough review of this topic. This review focuses on the roles of androgens in the physiological process of follicular development, summarizes new insights into the roles of androgens in the arrested development of follicles, and discusses the potential risk of adult diseases originating from abnormal follicular androgen levels or androgen receptor signals, which may determine areas for future studies.

Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits

PubMed Central

Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Ameyaw, Elvis Ofori; Asiamah, Emmanuel Akomanin

2016-01-01

AIM To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE) on endotoxin-induced uveitis in New Zealand white rabbits. METHODS Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS) -induced uveitic rabbits treated orally with HIE (30-300 mg/kg), prednisolone (30 mg/kg), or normal saline (10 mL/kg). The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and monocyte chemmoattrant protein-1 (MCP-1) in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed. RESULTS The extract and prednisolone-treatment significantly reduced (P≤0.001) both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits) and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001). Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells. CONCLUSION The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators. PMID:27162723

Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

PubMed Central

2011-01-01

Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile) to those of lower birth weight (5-25th centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk. PMID:21999700

A large kindred with X-linked neutropenia with an I294T mutation of the Wiskott-Aldrich syndrome gene.

PubMed

Beel, Karolien; Cotter, Melanie M; Blatny, Jan; Bond, Jonathan; Lucas, Geoff; Green, Frances; Vanduppen, Vik; Leung, Daisy W; Rooney, Sean; Smith, Owen P; Rosen, Michael K; Vandenberghe, Peter

2009-01-01

X-linked neutropenia (XLN, OMIM #300299) is a rare form of severe congenital neutropenia. It was originally described in a three-generation family with five affected members that had an L270P mutation in the GTP-ase binding domain (GBD) of the Wiskott-Aldrich syndrome protein (WASP) [Devriendt et al (2001) Nature Genetics, Vol. 27, 313-317]. Here, we report and describe a large three-generation family with XLN, with 10 affected males and eight female carriers. A c.882T>C mutation was identified in the WAS gene, resulting in an I294T mutation. The infectious course is variable and mild in view of the profound neutropenia. In addition to the original description, low-normal IgA levels, low to low-normal platelet counts and reduced natural killer (NK)-cell counts also appear as consistent XLN features. However, inverted CD4/CD8 ratios were not found in this family, nor were cases identified with myelodysplastic syndrome or acute myeloid leukaemia. Female carriers exhibited a variable attenuated phenotype. Like L270P WASP, I294T WASP is constitutively active towards actin polymerization. In conclusion, this largest XLN kindred identified to date provides new independent genetic evidence that mutations disrupting the auto-inhibitory GBD of WASP are the cause of XLN. Reduced NK cells, low to low normal platelet counts and low to low-normal IgA levels are also features of XLN.

Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis

PubMed Central

Zhang, Zhiqiang; Li, Zhennan; Zou, Chen; Zhang, Jingjing; Zhu, Yi; Miao, Yi

2015-01-01

Background/aims: Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis. Methodology: To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis). Results: The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). Conclusions: The results suggest that a liver with cirrhosis has a better ischemic tolerance than a normal liver. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. More research on the pathogenesis of IBDLs is needed for developing more specific preventive or therapeutic strategies. PMID:26550120

Do acute phase markers explain body temperature and brain temperature after ischemic stroke?

PubMed Central

Whiteley, William N.; Thomas, Ralph; Lowe, Gordon; Rumley, Ann; Karaszewski, Bartosz; Armitage, Paul; Marshall, Ian; Lymer, Katherine; Dennis, Martin

2012-01-01

Objective: Both brain and body temperature rise after stroke but the cause of each is uncertain. We investigated the relationship between circulating markers of inflammation with brain and body temperature after stroke. Methods: We recruited patients with acute ischemic stroke and measured brain temperature at hospital admission and 5 days after stroke with multivoxel magnetic resonance spectroscopic imaging in normal brain and the acute ischemic lesion (defined by diffusion-weighted imaging [DWI]). We measured body temperature with digital aural thermometers 4-hourly and drew blood daily to measure interleukin-6, C-reactive protein, and fibrinogen, for 5 days after stroke. Results: In 44 stroke patients, the mean temperature in DWI-ischemic brain soon after admission was 38.4°C (95% confidence interval [CI] 38.2–38.6), in DWI-normal brain was 37.7°C (95% CI 37.6–37.7), and mean body temperature was 36.6°C (95% CI 36.3–37.0). Higher mean levels of interleukin-6, C-reactive protein, and fibrinogen were associated with higher temperature in DWI-normal brain at admission and 5 days, and higher overall mean body temperature, but only with higher temperature in DWI-ischemic brain on admission. Conclusions: Systemic inflammation after stroke is associated with elevated temperature in normal brain and the body but not with later ischemic brain temperature. Elevated brain temperature is a potential mechanism for the poorer outcome observed in stroke patients with higher levels of circulating inflammatory markers. PMID:22744672

Relationship between inflammation, insulin resistance and type 2 diabetes: 'cause or effect'?

PubMed

Greenfield, Jerry R; Campbell, Lesley V

2006-05-01

Inflammation has been implicated as an important aetiological factor in the development of both insulin resistance and type 2 diabetes mellitus. This conclusion is predominantly drawn from studies demonstrating associations between elevated (but 'normal range') levels of circulating acute phase inflammatory markers, typified by C-reactive protein (CRP), and indices of insulin resistance and the development of type 2 diabetes. There is debate as to whether these associations are independent of body fatness or, rather, an epiphenomenon of obesity, particularly central obesity, a strong predictor of insulin resistance and type 2 diabetes and an important source of inflammatory cytokines, such as interleukin-6. Some of this controversy and the inability to draw definitive conclusions from these studies relate to the fact that most studies measure body fat and its distribution indirectly using anthropometric estimates, such as Body Mass Index and waist circumference, rather than directly by dual-energy X-ray absorptiometry, computed tomography or magnetic resonance imaging. Furthermore, use of the term inflammation may be inappropriate when describing mild elevations of CRP in the 'normal range' in the absence of the other changes that characterise classical inflammatory diseases, such as a reduction in levels (or evidence of consumption) of complement proteins. Debate as to whether obesity mediates the association between circulating levels of inflammatory markers and insulin resistance can be resolved by well-designed studies using body fat measured by gold-standard methods. In this review, we present evidence to support the suggestion that body fat is the primary determinant of circulating inflammatory marker levels in the basal state and that marginally elevated levels of circulating interleukin-6 and CRP in obesity are a consequence rather than a cause of insulin resistance. The importance of genetic influences in determining both body fatness and circulating CRP levels will also be discussed. The review will conclude with a discussion of possible mechanisms linking body fat and insulin resistance to elevated circulating levels of inflammatory markers, including the possible role of the toll-like family of immune receptors.

Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

PubMed Central

Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

2013-01-01

Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

Longitudinal Change of Biomarkers in Cognitive Decline

PubMed Central

Lo, Raymond Y.; Hubbard, Alan E.; Shaw, Leslie M.; Trojanowski, John Q.; Petersen, Ronald C.; Aisen, Paul S.; Weiner, Michael W.; Jagust, William J.

2017-01-01

Objective To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design Cohort study. Setting The 59 study sites for the Alzheimer’s Disease Neuroimaging Initiative. Participants A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease’s Assessment Scale–cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease’s Assessment Scale–cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent. PMID:21670386

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

PubMed Central

Ingber, Adam P.; Hassenstab, Jason; Fagan, Anne M.; Benzinger, Tammie L.S.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.; Roe, Catherine M.

2016-01-01

Background The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD. PMID:27104893

Impact of gastroesophageal reflux control through tailored proton pump inhibition therapy or fundoplication in patients with Barrett’s esophagus

PubMed Central

Baldaque-Silva, Francisco; Vieth, Michael; Debel, Mumen; Håkanson, Bengt; Thorell, Anders; Lunet, Nuno; Song, Huan; Mascarenhas-Saraiva, Miguel; Pereira, Gisela; Lundell, Lars; Marschall, Hanns-Ulrich

2017-01-01

AIM To determine the impact of upwards titration of proton pump inhibition (PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication. METHODS Two cohorts of long-segment Barrett’s esophagus (BE) patients were studied. In group 1 (n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. At each assessment, ambulatory 24 h pH recording, endoscopy with biopsies and symptom scoring (by a gastroesophageal reflux disease health related quality of life questionnaire, GERD/HRLQ) were performed. Group 2 (n = 30) consisted of patients with a previous fundoplication. RESULTS In group 1, acid reflux normalized in 23 of 24 patients, resulting in improved GERD/HRQL scores (P = 0.001), which were most pronounced after the starting dose of PPI (P < 0.001). PPI treatment reached the same level of GERD/HRQL scores as after a clinically successful fundoplication (P = 0.5). Normalization of acid reflux in both groups was associated with reduction in papillary length, basal cell layer thickness, intercellular space dilatation, and acute and chronic inflammation of squamous epithelium. CONCLUSION This study shows that acid reflux and symptom scores co-vary throughout PPI increments in long-segment BE patients, especially after the first dose of PPI, reaching the same level as after a successful fundoplication. Minor changes were found among GERD markers at the morphological level. PMID:28533674

Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS-mediated cardiomyocyte hypertrophy.

PubMed

Tigchelaar, Wardit; Yu, Hongjuan; de Jong, Anne Margreet; van Gilst, Wiek H; van der Harst, Pim; Westenbrink, B Daan; de Boer, Rudolf A; Silljé, Herman H W

2015-01-15

Recently, a locus at the mitochondrial exo/endonuclease EXOG gene, which has been implicated in mitochondrial DNA repair, was associated with cardiac function. The function of EXOG in cardiomyocytes is still elusive. Here we investigated the role of EXOG in mitochondrial function and hypertrophy in cardiomyocytes. Depletion of EXOG in primary neonatal rat ventricular cardiomyocytes (NRVCs) induced a marked increase in cardiomyocyte hypertrophy. Depletion of EXOG, however, did not result in loss of mitochondrial DNA integrity. Although EXOG depletion did not induce fetal gene expression and common hypertrophy pathways were not activated, a clear increase in ribosomal S6 phosphorylation was observed, which readily explains increased protein synthesis. With the use of a Seahorse flux analyzer, it was shown that the mitochondrial oxidative consumption rate (OCR) was increased 2.4-fold in EXOG-depleted NRVCs. Moreover, ATP-linked OCR was 5.2-fold higher. This increase was not explained by mitochondrial biogenesis or alterations in mitochondrial membrane potential. Western blotting confirmed normal levels of the oxidative phosphorylation (OXPHOS) complexes. The increased OCR was accompanied by a 5.4-fold increase in mitochondrial ROS levels. These increased ROS levels could be normalized with specific mitochondrial ROS scavengers (MitoTEMPO, mnSOD). Remarkably, scavenging of excess ROS strongly attenuated the hypertrophic response. In conclusion, loss of EXOG affects normal mitochondrial function resulting in increased mitochondrial respiration, excess ROS production, and cardiomyocyte hypertrophy. Copyright © 2015 the American Physiological Society.

Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery

PubMed Central

Vidal Fortuny, J.; Belfontali, V.; Sadowski, S. M.; Karenovics, W.; Guigard, S.

2016-01-01

Background Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. Methods Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. Results Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. Conclusion PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. PMID:26864909

Changes in the predominant human Lactobacillus flora during in vitro fertilisation

PubMed Central

Jakobsson, Tell; Forsum, Urban

2008-01-01

Background Signature matching of nucleotide sequences in the V1 and V3 regions 16S rRNA genes using pyrosequencing technology is a powerful tool for typing vaginal Lactobacilli to the species level and has been used for investigating the vaginal microbial niche. Methods This study has characterized the normal cultivable vaginal Lactobacillus flora at varying estradiol levels in plasma; the study comprised 17 patients undergoing ovarian stimulation for In Vitro Fertilization (IVF) treatment. The vaginal status of each participant was initially assessed as normal according to Amsel and Nugent criteria. Results L. crispatus, L. gasseri and/or L. jensenii were present in 10 of the patients throughout the study period, and little variation among these three species was encountered in individual patients. The flora of three women was dominated by L. delbrüeckii, L. rhamnosus or L. vaginalis. One woman exhibited a dominance of L. iners. The flora of the remaining three women were initially dominated by L. rhamnosus or L. reuteri, but as their estrogen levels rose, their flora composition altered, to become dominated by one of the three species most common in a normal, healthy vagina. Conclusion Signature matching of nucleotide sequences in the V1 and V3 regions of 16S rRNA genes is a discriminative tool for the study of vaginal Lactobacilli and can be used to track the Lactobacillus flora under a variety of physiological conditions. PMID:18590533

The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

PubMed

Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

2016-01-01

Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

PubMed Central

2013-01-01

Background Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. Methods A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. Results The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Conclusions Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next logical step is the assessment of whether the aluminum concentration is related to the key genomic abnormalities associated with breast carcinogenesis. PMID:23496847

The quantitative insulin sensitivity check index is not able to detect early metabolic alterations in young patients with polycystic ovarian syndrome.

PubMed

Angioni, Stefano; Sanna, Stefania; Magnini, Roberta; Melis, Gian Benedetto; Fulghesu, Anna Maria

2011-07-01

To verify whether QUICKY is a suitable method for the identification of metabolic deterioration in normal weight patients affected by polycystic ovarian syndrome (PCOS). Prospective clinical study. Seventy-nine PCOS normal weight adolescent subjects, 50 eumenorrheic, normal weight, non-hirsute controls matched for age and BMI. Quantitative insulin sensitivity check index (QUICKY) and integrated secretory area under the curve of insulin values (I-AUC) during oral glucose tolerance test were calculated. Seventy-nine PCOS and 50 controls were studied. Normal insulin sensitivity was defined as upper control 95th percentile by QUICKY values <0.31, I-AUC at 180 min < 16,645. When applying the calculated I-AUC cut-off, 41 PCOS were classified as normoinsulinemic and 38 as hyperinsulinemic, whereas using the calculated QUICKY cut-off, only 19 PCOS could be classified as insulin resistant (IR). Fifteen out of the 60 non-IR PCOS presented hyperinsulinemia; fasting glucose and insulin levels and QUICKY were not sufficient to identify these subjects. Thus, QUICKY displayed a low sensitivity (44%) and specificity (91%) in the diagnosis of the metabolic disorder disclosed by I-AUC. CONCLUSIONS.: In young normal weight patients with PCOS the prevalence of early alterations of insulin metabolism are not detectable by QUICKY studies.

Exaggerated Liver Injury Induced by Renal Ischemia Reperfusion in Diabetes: Effect of Exenatide

PubMed Central

Vaghasiya, Jitendra D.; Sheth, Navin R.; Bhalodia, Yagnik S.; Jivani, Nurudin P.

2010-01-01

Background/Aim: This study was designed to investigate the possible effect of exenatide (Glucagon like Peptide-1 receptor agonist) on liver injury (distant organ) induced by renal ischemia reperfusion (IR) in diabetic rats. Materials and Methods: In vivo renal IR was performed in both type 2 diabetic and normal rats. Each protocol comprised ischemia for 30 minutes followed by reperfusion for 24 hours and a treatment period of 14 days before induction of ischemia. Results: Lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity and nitric oxide level in liver tissue were significantly increased (P < 0.01, P < 0.001, P < 0.001, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Antioxidant enzymes like glutathione, superoxide dismutase, catalase and glutathione peroxidase were significantly reduced (P < 0.05, P < 0.05, P < 0.01, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Exenatide treatment significantly normalized (P < 0.01), these biochemical parameters in treated rats compared to diabetic IR rats. Serum creatinine phosphokinase activity and liver function enzymes were also significantly normalized (P < 0.001, P < 0.001, respectively), after administration of exenatide. Conclusion: Exenatide exerted protective effect on exaggerated remote organ (liver) injury induced by renal IR in diabetes. PMID:20616412

Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice

PubMed Central

Islam, Farhadul; Ali, Shaikh Mohummad Mohsin; Khanam, Jahan Ara

2013-01-01

Objective To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice. Methods Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed. Results The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC. Conclusions ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice. PMID:23593588

Association of Lead Levels and Cerebral Palsy

PubMed Central

Bansal, Neha; Aggarwal, Anju; Faridi, M. M. A.; Sharma, Tusha; Baneerjee, B. D.

2017-01-01

Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods: Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer). Data were analyzed using SPSS version 17. P < .05 was taken as significant. Results: Mean blood lead levels were 9.20 ± 8.31 µg/dL in cerebral palsy cases and 2.89 ± 3.04 µg/dL in their controls (P < .001). Among children with cerebral palsy, 19 (55.88%) children had blood lead levels ≥5 µg/dL. Lead levels in children with pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029). No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children. PMID:28491920

ERP C250 Shows the Elderly (Cognitively Normal, Alzheimer’s Disease) Store More Stimuli in Short-Term Memory than Young Adults Do

PubMed Central

Chapman, Robert M.; Gardner, Margaret N.; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P.; Dupree, Haley M.; Antonsdottir, Inga M.; Kamalyan, Lily

2016-01-01

Objective To determine how aging and dementia affect the brain’s initial storing of task-relevant and irrelevant information in short-term memory. Methods We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. Results In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in intratrial parts 1–3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Conclusions Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. Significance C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. PMID:27178862

Joint feedback analysis modeling of nonesterified fatty acids in obese Zucker rats and normal Sprague-Dawley rats after different routes of administration of nicotinic acid.

PubMed

Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

2014-08-01

Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague-Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague-Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration-response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the "degree of disease" can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

PubMed

Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

2003-09-01

Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.

Concentrations of cadmium and selected essential elements in malignant large intestine tissue

PubMed Central

Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

2015-01-01

Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

Levels of Antibodies against Human Heat Shock Protein (HSP) 60 in Patients with Glaucoma in Poland

PubMed Central

Grabska-Liberek, Iwona; Skonieczna, Katarzyna; Olesińska, Marzena; Terelak-Borys, Barbara; Kocięcki, Jarosandlstrokaw; Sikora, Mariusz; Jamrozy-Witkowska, Agnieszka; Tesla, Piotr; Czarnocka, Barbara

2015-01-01

Background Although elevated intraocular pressure is a major risk factor for the development of glaucoma, there is increasing evidence that the immune system may be involved in the development of normal-tension glaucoma (NTG). The aim of this study was to determine if NTG is associated with elevated levels of antibodies against human heat shock protein (HSP) 60. Material/Methods The study was conducted in 139 subjects (35 subjects with NTG [Group 1], 34 subjects with primary open-angle glaucoma/POAG/[Group 2], 24 subjects with autoimmune rheumatic diseases [Group 3], and 36 healthy controls [Group 4]). All subjects had complete ophthalmologic examination (visual acuity, slit-lamp examination, tonometry, gonioscopy; visual-field examination, and optical coherence tomography/OCT/of the optic nerve head and the macula). Blood samples were collected for the measurements of serum levels of antibodies against human HSP60. Results The subjects with rheumatic diseases had the highest median serum level of antibodies against HSP60 – 20.49 ng/mL. The values in the subjects with NTG, POAG, and in controls were 18.79 ng/mL, 18.61 ng/mL and 17.61 ng/mL, respectively (p=0.96). Conclusions This study does not confirm the hypothesis that normal-tension glaucoma is associated with elevated blood levels of antibodies against human heat shock protein (HSP) 60. PMID:25786333

Hydrostatic pressure as epigenetic modulator in chondrocyte cultures: A study on miRNA-155, miRNA-181a and miRNA-223 expression levels.

PubMed

De Palma, Anna; Cheleschi, Sara; Pascarelli, Nicola Antonio; Giannotti, Stefano; Galeazzi, Mauro; Fioravanti, Antonella

2018-01-03

Mechanical stimuli and hydrostatic pressure (HP) play an important role in the regulation of chondrocytes metabolism. Growing evidence demonstrated the ability of mechanical loading to modulate the expression of microRNA (miRNA) involved in chondrocytes homeostasis and in the pathogenesis of osteoarthritis (OA). The expression of miR-155, miR-181a and miR-223 in normal and OA chondrocyte cultures, and their potential modifications following exposure to three hours of a cyclic HP (1-5 MPa, frequency 0.25 Hz) were investigated. Also evaluated the expression of Chuk, regulator of the NF-kB pathway activation, which is a target gene of miR-223, was evaluated. Chondrocytes were collected immediately after pressurization (T0), and following 12, 24, and 48 h. Total RNA was extracted, reverse transcribed and used for real-time PCR. At basal condition, a significant increase of miR-155 and miR-181a was observed in OA in comparison to normal cells; on the contrary, no differences in miR-223 and Chuk expression levels were detected between normal and OA chondrocytes. miR-155 and miR-181a resulted significantly downregulated immediately after pressurization (T0) in OA cells. The pressure effect on miR-155 and miR-181a levels was maintained over time. No modifications of miR-223 were observed in response to HP, while Chuk levels resulted significantly reduced at T0 and after 12 h. Pressurization did not cause any modifications in normal cells. In conclusion, HP was able to modulate the expression of miRNA associated to OA pathogenesis. The preliminary results about Chuk response to pressure raised interest in its involvement in the possible HP induced NF-kB pathway modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease

PubMed Central

Sundgren, Pia C.; Strandberg, Olof; Zetterberg, Henrik; Minthon, Lennart; Blennow, Kaj; Wahlund, Lars-Olof; Westman, Eric

2016-01-01

Objective: We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity. Methods: In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF β-amyloid 42 (Aβ42), (2) cognitively healthy elderly with abnormal CSF Aβ42, (3) patients with subjective cognitive decline and abnormal CSF Aβ42, (4) patients with mild cognitive decline and abnormal CSF Aβ42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aβ42, phosphorylated tau, total tau, [18F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE. Results: Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p < 0.05). In amyloid-positive healthy elderly, mI/creatine and mI/NAA correlated with cortical retention of [18F] flutemetamol tracer ( = 0.44, p = 0.02 and = 0.51, p = 0.01, respectively). Healthy elderly APOE ε4 carriers with normal CSF Aβ42 levels had significantly higher mI/creatine levels (p < 0.001) than ε4 noncarriers. Finally, elevated mI/creatine was associated with decreased functional connectivity within the default mode network (rpearson = −0.16, p = 0.02), independently of amyloid pathology. Conclusions: mI levels are elevated already at asymptomatic stages of AD. Moreover, mI/creatine concentrations were increased in healthy APOE ε4 carriers with normal CSF Aβ42 levels, suggesting that mI levels may reveal regional brain consequences of APOE ε4 before detectable amyloid pathology. PMID:27164711

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

Altazi, B; Fernandez, D; Zhang, G

Purpose: Site-specific investigations of the role of Radiomics in cancer diagnosis and therapy are needed. We report of the reproducibility of quantitative image features over different discrete voxel levels in PET/CT images of cervical cancer. Methods: Our dataset consisted of the pretreatment PET/CT scans from a cohort of 76 patients diagnosed with cervical cancer, FIGO stage IB-IVA, age range 31–76 years, treated with external beam radiation therapy to a dose range between 45–50.4 Gy (median dose: 45 Gy), concurrent cisplatin chemotherapy and MRI-based Brachytherapy to a dose of 20–30 Gy (median total dose: 28 Gy). Two board certified radiation oncologistsmore » delineated Metabolic Tumor volume (MTV) for each patient. Radiomics features were extracted based on 32, 64, 128 and 256 discretization levels (DL). The 64 level was chosen to be the reference DL. Features were calculated based on Co-occurrence (COM), Gray Level Size Zone (GLSZM) and Run-Length (RLM) matrices. Mean Percentage Differences (Δ) of features for discrete levels were determined. Normality distribution of Δ was tested using Kolomogorov - Smirnov test. Bland-Altman test was used to investigate differences between feature values measured on different DL. The mean, standard deviation and upper/lower value limits for each pair of DL were calculated. Interclass Correlation Coefficient (ICC) analysis was performed to examine the reliability of repeated measures within the context of the test re-test format. Results: 3 global and 5 regional features out of 48 features showed distribution not significantly different from a normal one. The reproducible features passed the normality test. Only 5 reproducible results were reliable, ICC range 0.7 – 0.99. Conclusion: Most of the radiomics features tested showed sensitivity to voxel level discretization between (32 – 256). Only 4 GLSZM, 3 COM and 1 RLM showed insensitivity towards mentioned discrete levels.« less

Comparison of serum Concentration of Se, Pb, Mg, Cu, Zn, between MS patients and healthy controls

PubMed Central

Alizadeh, Anahita; Mehrpour, Omid; Nikkhah, Karim; Bayat, Golnaz; Espandani, Mahsa; Golzari, Alireza; Jarahi, Lida; Foroughipour, Mohsen

2016-01-01

Introduction Multiple Sclerosis (MS) is defined as one of the inflammatory autoimmune disorders and is common. Its exact etiology is unclear. There are some evidences on the role of environmental factors in susceptible genetics. The aim of this study is to evaluate the possible role of Selenium, Zinc, Copper, Lead and Magnesium metals in Multiple Sclerosis patients. Methods In the present analytical cross-sectional study, 56 individuals including 26 patients and 30 healthy controls were enrolled in the evaluation. The serum level of Se, Zn, Cu, Pb were quantified in graphite furnace conditions and flame conditions by utilizing an atomic absorption Perkin Elmer spectrophotometer 3030. The serum levels of Mg were measured by auto analyzer 1500 BT. The mean level of minerals (Zn, Pb, Cu, Mg, Se) in serum samples were compared in both cases and controls. The mean level of minerals (Zn, Pb, Cu, Mg, Se) in serum samples were compared in both cases and controls by using independent-samples t-test for normal distribution and Mann-Whitney U test as a non-parametric test. All statistical analyses were carried out using SPSS 11.0. Results As well as the Zn, Cu, and Se, there was no significant difference between MS patients and healthy individuals in Pb concentrations (p-value = 0.11, 0.14, 0.32, 0.20 respectively) but the level of Mg was significantly different (p= 0.001). Conclusion All serum concentrations of Zn, Pb, Se, Cu in both groups were in normal ranges and there was no difference in MS patients compared with the healthy group who were matched in genetics. Blood level of Mg was significantly lower in MS patients. But it should be noted that even with the low level of serum magnesium in MS patients, this value is still in the normal range. PMID:27757186

Hormonal Treatment of Transgender Women with Oral Estradiol.

PubMed

Leinung, Matthew C; Feustel, Paul J; Joseph, Jalaja

2018-01-01

Purpose: Maintaining cross-sex hormone levels in the normal physiologic range for the desired gender is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve this. We investigated the effectiveness of oral estradiol therapy in achieving this goal. Methods: We analyzed data on all transgender females seen in our clinic since 2008 treated with oral estradiol. We looked at the success of achieving serum levels of testosterone and 17-β estradiol in the normal range on various doses of estradiol (with and without antiandrogens spironolactone and finasteride). Results: There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more. Nearly a third of patients did not achieve adequate treatment goals on 6 or even 8 mg daily of estradiol. Spironolactone, but not finasteride, use was associated with impairment of obtaining desired 17-β estradiol levels. Spironolactone did not enhance testosterone suppression, and finasteride was associated with higher testosterone levels. Conclusions: Oral estradiol was effective in achieving desired serum levels of 17-β estradiol, but there was wide individual variability in the amount required. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression. Spironolactone did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels. Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized.

Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats

PubMed Central

Chaturvedi, Padmaja; Kwape, Tebogo Elvis

2015-01-01

Objectives: This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. Methods: SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). Results: OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. Conclusion: The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes. PMID:26998385

Internal associations and dynamic expression of c-kit and nanog genes in ventricular remodelling induced by adriamycin.

PubMed

Liu, Zhen; Li, Shuo; Liu, Lingling; Guo, Zhikun; Wang, Pengfei

2016-09-01

The present study aimed to investigate the dynamic expression of the c-kit and nanog genes in rats with left ventricular remodelling induced by adriamycin (ADR), and explore its internal association and mechanism of action. Sprague-Dawley male rats were randomly divided into a normal control group and a heart failure model group. Heart failure was induced by a single intraperitoneal injection of ADR (4 mg/kg) weekly for six weeks. The normal control group was given the same amount of saline. At the eighth week, rat cardiac function was examined to demonstrate the formation of heart failure. The rat hearts were harvested frozen and sectioned, and the expression levels of the nanog and c-kit genes in the myocardial tissue samples were detected using immunohistochemistry, immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). Hematoxylin and eosin staining demonstrated various pathological changes in the myocardial cells in the heart failure model group, whereas myocardial infarction was not observed in the normal control group. Immunohistochemistry and immunofluorescence demonstrated that nanog-positive cells were predominantly expressed in the vascular endothelium, with a few myocardial cells and stem cells in normal myocardium. The expression levels of c-kit and nanog in the myocardium of the rats with heart failure decreased significantly. c-kit-positive cells clustered together in the epicardium and its vicinity, and c-kit expression significantly decreased in the myocardium of rats with heart failure, as compared with normal rats. In both groups, some cells co-expressed both the c-kit and nanog genes. The RT-PCR results demonstrated that the expression levels of the two genes in the heart failure model group were significantly lower compared with those in the normal control group (P<0.05). In conclusion, the c-kit- and nanog-positive stem cells decreased in the myocardium of the rats with left ventricular remodelling induced by ADR. Their abnormal expression was significantly correlated with left ventricular remodelling, thereby indicating an internal association (influences of two indexes in the experimental group and control group) between them.

Expression of HSP27, HSP72 and MRP proteins in in vitro co-culture of colon tumour cell spheroids with normal cells after incubation with rhTGF- beta1 and/or CPT-11.

PubMed

Paduch, Roman; Jakubowicz-Gil, Joanna; Kandefer-Szerszen, Martyna

2009-12-01

We studied the expression of inducible heat shock protein (HSP27, HSP72) and multidrug-resistance protein (MRP) in co-cultures of human colon carcinoma cell spheroids obtained from different grades of tumour with normal human colon epithelium, myofibroblast and endothelial cell monolayers. We also measured the influence of recombinant human transforming growth factor beta1 (rhTGF-beta1) and camptothecin (CPT-11), added as single agents or in combination, on the levels of the HSPs, MRP, interleukin (IL)-6 and nitric oxide (NO). An immunoblotting analysis with densitometry showed that rhTGF-beta1 and/or CPT-11 increased HSP27, HSP72 and MRP expression in tumour cells and myofibroblasts, as well as in co-cultures compared with appropriate controls. By contrast, in colonic epithelium, inhibition of HSPs and MRP was comparable with that of the control. In endothelial cells, HSP72 was undetectable. Direct interaction of colon tumour spheroids with normal myofibroblasts caused a significant, tumour-grade dependent increase in IL-6 production. Production of IL-6 was significantly lowered by rhTGF-beta1 and/or CPT-11. Tumour cell spheroids cultivated alone produced larger amounts of NO than normal cells. In co-culture, the level of the radical decreased compared with the sum of NO produced by the monocultures of the two types of cells. rhTGF-beta1 and/or CPT-11 decreased NO production both in tumour and normal cell monocultures and their co-cultures. In conclusion, direct interactions between tumour and normal cells influence the expression of HSP27, HSP72 and MRP, and alter IL-6 and NO production. rhTGF-beta1 and/or CPT-11 may potentate resistance to chemotherapy by increasing HSP and MRP expression but, on the other hand, they may limit tumour cell spread by decreasing the level of some soluble mediators of inflammation (IL-6 and NO).

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

PubMed Central

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A.; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A.; Sachdev, Perminder S.

2012-01-01

Objectives Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. Methods 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. Results At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Conclusions Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals. PMID:22701550

Transcriptional expression of type-I interferon response genes and stability of housekeeping genes in the human endometrium and endometriosis.

PubMed

Vestergaard, Anna L; Knudsen, Ulla B; Munk, Torben; Rosbach, Hanne; Martensen, Pia M

2011-04-01

Endometriosis is a painful chronic female disease defined by the presence of endometrial tissue implants in ectopic (Ec) locations. The pathogenesis is much debated, and type-I interferons (IFNs) could be involved. The expression of genes of the type-I IFN response were profiled by a specific PCR array of RNA obtained from Ec and eutopic (Eu) endometrium collected from nine endometriosis patients and nine healthy control women. Transcriptional expression levels of selected IFN-regulated and housekeeping genes (HKGs) were investigated by real-time quantitative reverse transcriptase PCR (qRT-PCR). Stably expressed HKGs for valid normalization of transcriptional studies of endometrium and endometriosis have not yet been published. Here, seven HKGs were evaluated for stability using the GeNorm and NormFinder software. A normalization factor based on HMBS, TBP and YWHAZ expression was suitable for normalization of qRT-PCR studies of Eu versus Ec endometrium. In the endometrial cell lines HEC1A, HEC1B, Ishikawa and RL95-2, HMBS and HPRT1 were the most stably expressed. The IFN-specific PCR array indicated significantly different expression of the genes BST2, COL16A1, HOXB2 and ISG20 between the endometrial tissue types. However, by correctly normalized qRT-PCR, levels of BST2, COL16A1 and the highly type-I IFN-stimulated genes ISG12A and 6-16 displayed insignificant variations. Conversely, HOXB2 and ISG20 transcriptions were significantly reduced in endometriosis lesions compared with endometrium from endometriosis patients and healthy controls. In conclusion, appropriate HKGs for normalization of qRT-PCR studies of endometrium and endometriosis have been identified here. Abolished expression of ISG20 and HOX genes could be important in endometriosis.

Akt1/NFκB signaling pathway activation by a small molecule DMA confers radioprotection to intestinal epithelium in xenograft model.

PubMed

Tiwari, Vinod; Kamran, Mohammad Zahid; Ranjan, Atul; Nimesh, Hemlata; Singh, Manish; Tandon, Vibha

2017-07-01

Normal tissue protection and recovery of radiation-induced damage are of paramount importance for development of radioprotector. Radioprotector which selectively protects normal tissues over cancerous tissues improves the therapeutic window of radiation therapy. In the present study, small bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo radioprotective effects to selectively protect normal tissue over tumor with underlying molecular mechanism. Administration of single DMA dose prior to radiation has enhanced survival of Balb/c mice against sublethal and supralethal total body irradiation. DMA ameliorated radiation-induced damage of normal tissues such as hematopoietic (HP) and gastrointestinal tract (GI) system. Oxidative stress marker Malondialdehyde level was decreased by DMA whereas it maintained endogenous antioxidant status by increasing the level of reduced glutathione, glutathione reductase, glutathione-s-transferase, superoxide dismutase and total thiol content in hepatic tissue of irradiated mice. Mechanistic studies revealed that DMA treatment prior to radiation leads to Akt1/NFκB signaling which reduced radiation-induced genomic instability in normal cells. However, these pathways were not activated in tumor tissues when subjected to DMA treatment in similar conditions. Abrogation of Akt1 and NFκB genes resulted in no radioprotection by DMA and enhanced apoptosis against radiation. Plasma half-life of DMA was 3.5h and 2.65h at oral and intravenous dose respectively and 90% clearance was observed in 16h. In conclusion, these data suggests that DMA has potential to be developed as a safe radioprotective agent for radiation countermeasures and an adjuvant in cancer therapy. Copyright © 2017. Published by Elsevier Inc.

Investigation into the distinct subcellular effects of docosahexaenoic acid loaded low-density lipoprotein nanoparticles in normal and malignant murine liver cells

PubMed Central

Moss, Lacy R.; Mulik, Rohit S.; Van Treuren, Tim; Kim, Soo Young; Corbin, Ian R.

2016-01-01

Background Recent studies have shown that low density lipoproteins reconstituted with the natural omega 3 fatty acid docosahexaenoic acid (LDL-DHA) is selectively cytotoxic to liver cancer cells over normal hepatocytes. To date, little is known about the subcellular events which transpire following LDL-DHA treatment. Methods Herein, murine noncancer and cancer liver cells, TIB-73 and TIB-75 respectively, were investigated utilizing confocal microscopy, flow cytometry and viability assays to demonstrate differential actions of LDL-DHA nanoparticles in normal versus malignant cells. Results Our studies first showed that basal levels of oxidative stress are significantly higher in the malignant TIB-75 cells compared to the normal TIB-73 cells. As such, upon entry of LDL-DHA into the malignant TIB-75 cells, DHA is rapidly oxidized precipitating global and lysosomal lipid peroxidation along with increased lysosomal permeability. This leakage of lysosomal contents and lipid peroxidation products trigger subsequent mitochondrial dysfunction and nuclear injury. The cascade of LDL-DHA mediated lipid peroxidation and organelle damage was partially reversed by the administration of the antioxidant, N-acetylcysteine, or the iron-chelator, deferoxamine. LDL-DHA treatment in the normal TIB-73 cells was well tolerated and did not elicit any cell or organelle injury. Conclusion These studies have shown that LDL-DHA is selectively cytotoxic to liver cancer cells and that increased levels of ROS and iron catalyzed reactions promote the peroxidation of DHA which lead to organelle dysfunction and ultimately the demise of the cancer cell. General significance LDL-DHA selectively disrupts lysosomal, mitochondrial and nuclear function in cancer cells as a novel pathway for eliminating cancer cells. PMID:27418237

Radioprotective effects of delphinidin on normal human lung cells against proton beam exposure

PubMed Central

Kim, Hyun Mi; Kim, Suk Hee

2018-01-01

BACKGROUND/OBJECTIVES Exposure of the normal lung tissue around the cancerous tumor during radiotherapy causes serious side effects such as pneumonitis and pulmonary fibrosis. Radioprotectors used during cancer radiotherapy could protect the patient from side effects induced by radiation injury of the normal tissue. Delphinidin has strong antioxidant properties, and it works as the driving force of a radioprotective effect by scavenging radiation-induced reactive oxygen species (ROS). However, no studies have been conducted on the radioprotective effect of delphinidin against high linear energy transfer radiation. Therefore, this study was undertaken to evaluate the radioprotective effects of delphinidin on human lung cells against a proton beam. MATERIALS/METHODS Normal human lung cells (HEL 299 cells) were used for in vitro experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay assessed the cytotoxicity of delphinidin and cell viability. The expression of radiation induced cellular ROS was measured by the 2′-7′-dicholordihydrofluorescein diacetate assay. Superoxide dismutase activity assay and catalase activity assay were used for evaluating the activity of corresponding enzymes. In addition, radioprotective effects on DNA damage-induced cellular apoptosis were evaluated by Western blot assay. RESULTS Experimental analysis, including cell survival assay, MTT assay, and Western blot assay, revealed the radioprotective effects of delphinidin. These include restoring the activities of antioxidant enzymes of damaged cells, increase in the levels of pro-survival protein, and decrease of pro-apoptosis proteins. The results from different experiments were compatible with each to provide a substantial conclusion. CONCLUSION Low concentration (2.5 µM/mL) of delphinidin administration prior to radiation exposure was radioprotective against a low dose of proton beam exposure. Hence, delphinidin is a promising shielding agent against radiation, protecting the normal tissues around a cancerous tumor, which are unintentionally exposed to low doses of radiation during proton therapy. PMID:29399295

The Relationship Between Serum Endocan Levels With the Presence of Slow Coronary Flow: A Cross-Sectional Study.

PubMed

Kundi, Harun; Gok, Murat; Kiziltunc, Emrullah; Topcuoglu, Canan; Cetin, Mustafa; Cicekcioglu, Hulya; Ugurlu, Burcu; Ulusoy, Feridun Vasfi

2017-07-01

The aim of this study was to investigate the relationship between endocan levels with the presence of slow coronary flow (SCF). In this cross-sectional study, a total of 88 patients, who admitted to our hospital, were included in this study. Of these, 53 patients with SCF and 35 patients with normal coronary flow were included in the final analysis. Coronary flow rates of all patients were determined by the Timi Frame Count (TFC) method. In correlation analysis, endocan levels revealed a significantly positive correlation with high sensitive C-reactive protein and corrected TFC. In multivariate logistic regression analysis, the endocan levels were found as independently associated with the presence of SCF. Finally, using a cutoff level of 2.3, endocan level predicted the presence of SCF with a sensitivity of 77.2% and specificity of 75.2%. In conclusion, our study showed that higher endocan levels were significantly and independently related to the presence of SCF.

Auditory Brainstem Response Altered in Humans With Noise Exposure Despite Normal Outer Hair Cell Function

PubMed Central

Bramhall, Naomi F.; Konrad-Martin, Dawn; McMillan, Garnett P.; Griest, Susan E.

2017-01-01

Objectives Recent animal studies demonstrated that cochlear synaptopathy, a partial loss of inner hair cell-auditory nerve fiber synapses, can occur in response to noise exposure without any permanent auditory threshold shift. In animal models, this synaptopathy is associated with a reduction in the amplitude of wave I of the auditory brainstem response (ABR). The goal of this study was to determine whether higher lifetime noise exposure histories in young people with clinically normal pure-tone thresholds are associated with lower ABR wave I amplitudes. Design Twenty-nine young military Veterans and 35 non Veterans (19 to 35 years of age) with normal pure-tone thresholds were assigned to 1 of 4 groups based on their self-reported lifetime noise exposure history and Veteran status. Suprathreshold ABR measurements in response to alternating polarity tone bursts were obtained at 1, 3, 4, and 6 kHz with gold foil tiptrode electrodes placed in the ear canal. Wave I amplitude was calculated from the difference in voltage at the positive peak and the voltage at the following negative trough. Distortion product otoacoustic emission input/output functions were collected in each participant at the same four frequencies to assess outer hair cell function. Results After controlling for individual differences in sex and distortion product otoacoustic emission amplitude, the groups containing participants with higher reported histories of noise exposure had smaller ABR wave I amplitudes at suprathreshold levels across all four frequencies compared with the groups with less history of noise exposure. Conclusions Suprathreshold ABR wave I amplitudes were reduced in Veterans reporting high levels of military noise exposure and in non Veterans reporting any history of firearm use as compared with Veterans and non Veterans with lower levels of reported noise exposure history. The reduction in ABR wave I amplitude in the groups with higher levels of noise exposure cannot be accounted for by sex or variability in outer hair cell function. This change is similar to the decreased ABR wave I amplitudes observed in animal models of noise-induced cochlear synaptopathy. However, without post mortem examination of the temporal bone, no direct conclusions can be drawn concerning the presence of synaptopathy in the study groups with higher noise exposure histories. PMID:27992391

Avascular Necrosis in the Contralateral Hip in Patients With Congenital Femoral Deficiency: A Report of 3 Cases.

PubMed

Brown, Timothy S; Wimberly, Robert L; Birch, John G

2017-01-01

Congenital femoral deficiency is an uncommon clinical entity. We report 3 patients who developed avascular necrosis of the hip in the long (normal) leg during longitudinal observation and/or treatment of congenital femoral deficiency. Patients were identified in limb length discrepancy clinic and their charts were retrospectively reviewed for clinical and radiographic data collection. We describe the occurrence of idiopathic avascular necrosis in the normal limb in patients being followed for limb length discrepancy. Although no conclusion could be drawn about the etiology of the avascular necrosis, we describe a previously undocumented relationship between congenital femoral deficiency and avascular necrosis in the contralateral hip. This occurred in our congenital femoral deficiency population at a rate higher than expected compared with published incidences of avascular necrosis of the hip in children. Level IV-case series.

Colon Cancer Associated Transcript-1 (CCAT1) Expression in Adenocarcinoma of the Stomach

PubMed Central

Mizrahi, Ido; Mazeh, Haggi; Grinbaum, Ronit; Beglaibter, Nahum; Wilschanski, Michael; Pavlov, Vera; Adileh, Muchamad; Stojadinovic, Alexander; Avital, Itzhak; Gure, Ali Osmay; Halle, David; Nissan, Aviram

2015-01-01

Background: Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC). Methods: Tissue samples were obtained from patients undergoing resection for gastric carcinoma (n=19). For each patient, tumor tissue and normal appearing gastric mucosa were taken. Normal gastric tissues obtained from morbidly obese patients, undergoing laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric carcinoma cell line (AGS) served as positive control. RNA was extracted from all tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR). Results: Low expression of CCAT1 was identified in normal gastric mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ) = 1.95±0.4]. AGS human gastric carcinoma cell line showed an elevated level of CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8 fold higher in GC samples than in samples taken from the negative control group (RQ=21.1±5 vs. RQ=1.95±0.4, respectively, p<0.001). Interestingly, CCAT1 expression was significantly overexpressed in adjacent normal tissues when compared to the negative control group (RQ = 15.25±2 vs. RQ=1.95±0.4, respectively, p<0.001). Tissues obtained from recurrent GC cases showed the highest expression levels (RQ = 88.8±31; p<0.001). Expression levels increased with tumor stage (T4- 36.4±15, T3- 16.1±6, T2- 4.7±1), however this did not reach statistical significance (p=0.2). There was no difference in CCAT1 expression between intestinal and diffuse type GC (RQ=22.4±7 vs. 22.4±16, respectively, p=0.9). Within the normal gastric tissue samples, no significant difference in CCAT1 expression was observed in helicobacter pylori negative and positive patients (RQ= 2.4±0.9 vs. 0.93±0.2, respectively, p=0.13). Conclusion: CCAT1 is up-regulated in gastric cancer, and may serve as a potential bio-marker for early detection and surveillance. PMID:25561974

The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas

PubMed Central

Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

2016-01-01

Introduction Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. Aim The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. Materials and Methods This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn’t warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Results Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple’s procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Conclusion Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn’t predict vascular involvement and liver metastasis. PMID:27134925

Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults

PubMed Central

2012-01-01

Background The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging. Methods We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31). Results We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions. Conclusion Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging. PMID:22537877

Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer's Disease.

PubMed

Jiang, Jing; Liu, Gang; Shi, Suhua; Li, Zhigang

2016-01-01

Objectives . To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer's disease. Methods . In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer's disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer's disease (AD), and normal (N) groups were assessed. Results . The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and A β amyloid content in the frontal lobe, compared with the AD group ( P < 0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD. Conclusion . MEA therapy may be superior to EA in treating Alzheimer's disease as demonstrated in SAMP8 mice.

Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer's Disease

PubMed Central

Jiang, Jing; Liu, Gang

2016-01-01

Objectives. To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer's disease. Methods. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer's disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer's disease (AD), and normal (N) groups were assessed. Results. The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and Aβ amyloid content in the frontal lobe, compared with the AD group (P < 0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD. Conclusion. MEA therapy may be superior to EA in treating Alzheimer's disease as demonstrated in SAMP8 mice. PMID:27974974

On a Heat Exchange Problem under Sharply Changing External Conditions

NASA Astrophysics Data System (ADS)

Khishchenko, K. V.; Charakhch'yan, A. A.; Shurshalov, L. V.

2018-02-01

The heat exchange problem between carbon particles and an external environment (water) is stated and investigated based on the equations of heat conducting compressible fluid. The environment parameters are supposed to undergo large and fast variations. In the time of about 100 μs, the temperature of the environment first increases from the normal one to 2400 K, is preserved at this level for about 60 μs, and then decreases to 300 K during approximately 50 μs. At the same periods of time, the pressure of the external environment increases from the normal one to 67 GPa, is preserved at this level, and then decreases to zero. Under such external conditions, the heating of graphite particles of various sizes, their phase transition to the diamond phase, and the subsequent unloading and cooling almost to the initial values of the pressure and temperature without the reverse transition from the diamond to the graphite phase are investigated. Conclusions about the maximal size of diamond particles that can be obtained in experiments on the shock compression of the mixture of graphite with water are drawn.

Comparative analysis of salivary zinc level in recurrent herpes labialis

PubMed Central

Khozeimeh, Faezeh; Jafari, Nasim; Attar, Ahmad Movahedian; Jafari, Shahram; Ataie, Masoud

2012-01-01

Background: Recurrent Herpes Labialis (RHL) is one of most common infective vesiculoulcerative lesions. According to some studies administration of topical and/or systemic zinc compositions has been effective in treatment and prevention. This article aims to comparison of zinc level in healthy subjects and RHL patients in acute and convalescent phases. Materials and Methods: This was a retrospective case – control study, carried on 80 individuals (40 normal and 40 RHL patients) mean age=34.5 and 34.4, respectively. Saliva samples were taken in patients in acute phase once and after healing of lesions in convalescent phase (averagely 21 days later) and in normal individuals. Salivary zinc level concentration was measured by flame atomic absorption spectrophotometer by dry digestion method. The results were statistically analyzed with SPSS software by t-test (α=0.05). Results: Results showed that salivary zinc level in case group in acute and convalescent phases were 160.8 ngr/mland 205.7 ngr/ml respectivly and significant differences between them were existed (P <0.05). Also significant differences were existed between zinc concentration in healthy subjects and patient groups (in both phases) (P=.001 and .002 for acute and convalescent phases respectively). Conclusion: According to the results, zinc level is significantly lower in acute phase than in convalescent phase and significantly lower in both phases compared to healthy individuals,so determination of serum zinc level and prescribing zinc complement in low serum status has both treatmental and preventive effects in RHL patients. PMID:22363358

Ovarian Cancer-Related Hypophosphatemic Osteomalacia—A Case Report

PubMed Central

Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao

2014-01-01

Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. Objective: We investigated a 57-year-old woman with progressive low back pain. Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia. PMID:25181387

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

Budker, D.; Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720; Rochester, S.M.

Recent work on {lambda} resonances in alkali-metal vapors (E. Mikhailov, I. Novikova, Yu. V. Rostovtsev, and G. R. Welch, e-print quant-ph/0309171, and references therein) investigated a type of electromagnetically induced absorption resonance that occurs in three-level systems under specific conditions normally associated with electromagnetically induced transparency. In this note, we show that these resonances have a direct analog in nonlinear magneto-optics, and support this conclusion with a calculation for a J=1{yields}J{sup '}=0 system interacting with a single, nearly circularly polarized light field in the presence of a weak longitudinal magnetic field.

Effect of a prenatal lifestyle intervention on physical activity level in late pregnancy and the first year postpartum

PubMed Central

Sagedal, Linda Reme; Haakstad, Lene Annette Hagen; Lohne-Seiler, Hilde

2017-01-01

Background Despite documented health benefits for mother and baby, physical activity (PA)-level tends to decline in pregnancy. Overweight/obese and physically inactive women are two selected groups at increased risk of pregnancy complications. Thus, efficient strategies to maintain or increase PA-level in pregnancy and the postpartum period, especially among these women, are warranted. This secondary analysis examined the effect of a prenatal lifestyle-intervention on PA-level in late pregnancy and the first year postpartum, with subanalysis on initially physically active versus inactive and normal-weight versus overweight/obese women. Method The Norwegian Fit for Delivery (NFFD) randomized controlled trial included healthy primiparous women with singleton pregnancies and body mass index (BMI) ≥19 kg/m2 assigned to an intervention group, n = 303 (twice weekly group-exercises and dietary counseling) or a control group, n = 303 (standard prenatal care). The International Physical Activity Questionnaire short-form was used to assess PA-levels at inclusion (mean gestational week (GW) 16), GW 36, and six and 12 months postpartum. Results At GW 36, a positive intervention-effect with a significant between-group difference in total PA-level compared to time of inclusion was found for the total group (530 MET-min/week, p = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and initially active women (717 MET-min/week, p<0.001). Intervention-effect was dependent on exercise-adherence among overweight/obese and inactive women. Compared to time of inclusion, the intervention groups maintained total PA-level at GW 36, while total PA-level decreased in the control groups. The PA-levels increased postpartum, but with no significant differences between the randomization groups. Conclusion The NFFD prenatal combined lifestyle intervention had a significant effect on TPA-level in late pregnancy among women entering pregnancy normal-weight or physically active, thereby preventing the downward trend typically seen during pregnancy. Intervention-effect among overweight/obese and physically inactive women was, however, dependent on exercise-adherence. Long-term intervention-effect was not observed in the postpartum period. PMID:29176762

Consequences of phosphorus interactions with calcium, phytase, and cholecalciferol on zootechnical performance and mineral retention in broiler chickens.

PubMed

Delezie, E; Maertens, L; Huyghebaert, G

2012-10-01

The objective was to determine the effect of calcium (Ca), total phosphorus (Ptot), cholecalciferol, and phytase level in the diet on the performance, tibia ash percentage, and Ca and P retention in broilers until slaughter age. Broilers were randomly assigned to 12 treatments, each with 6 replicates, comprising 3 diets differing in Ca and P level: 1) normal Ca and Ptot level (NN); 2) normal Ca and low Ptot level (NL), 3) low Ca and Ptot level (LL). Broilers were also given 2 levels of cholecalciferol and 2 levels of phytase. The normal levels of Ca and Ptot for the starter, grower, and finisher phases were 0.90, 0.82, 0.74% and 0.67, 0.62, 0.57%, respectively. The low Ca and Ptot levels for the 3 phases were 0.67, 0.60, 0.52% and 0.57, 0.51, 0.46%, respectively. Broilers of the NL treatment obtained the lowest BW, whereas BW of the NN and LL groups were comparable. Cholecalciferol significantly affected the BW, with differences up to 2.6 and 1.2% for the starter and grower phases, respectively. The highest cholecalciferol effect was found in combination with the NN treatment. The percentage of retained Ca increased from 33% to 41% and 48% when the imbalanced diet was replaced by the NN and LL balanced diets, respectively. P release from phytate was 64 and 67% for the NL and LL diets, respectively. Phytase and cholecalciferol had significantly favorable effects on retention values but these effects were dependent on Ca and Ptot levels and their ratio. In conclusion, both diets with the balanced Ca/Ptot ratio resulted in the best performance, highest tibia ash percentage and P release from phytate. A reduction of the Aviagen (2009) recommended P requirements by 25 to 30% and Ca by 15 to 20% over the various phases did not negatively affect performance, bone development, and improved Ca and Ptot retention. The effects of supplementing cholecalciferol and phytase were additive but not significant and no synergism between both was present.

Influence of mental stress on the plasma homocysteine level and blood pressure change in young men.

PubMed

Sawai, Asuka; Ohshige, Kenji; Kura, Naoki; Tochikubo, Osamu

2008-04-01

Objective. This study aimed to determine whether mental stress influences the plasma total homocysteine level or blood pressure in young men. Method. Twenty-seven male university students were assigned to a normal blood pressure group (24-h systolic blood pressure <125 mmHg and diastolic blood pressure <75 mmHg; 13 subjects) or a high blood pressure group (24-h systolic blood pressure > or =125 mmHg, or 24-h diastolic blood pressure > or =75 mmHg; 14 subjects). Wearing an ambulatory blood pressure monitoring device, subjects rested for 30 minutes, underwent an arithmetic test for 15 minutes, and rested again for 15 minutes. Blood samples were taken before and after the test. Plasma total homocysteine levels were measured. Heart rate, blood pressure, and sympathovagal balance were determined during the test. Results. The mean total homocysteine level at rest in the high blood pressure group was slightly, but not significantly, higher than that in the normal blood pressure group. The resting total homocysteine level was significantly higher in subjects with parental history of hypertension than in those without (p < 0.01). Blood pressure, heart rate, and the plasma total homocysteine level were increased significantly by mental stress (p < 0.05). The change in total homocysteine correlated significantly with the changes in systolic blood pressure and sympathovagal balance (p < 0.05). Conclusion. Resting total homocysteine level was significantly higher in male students with a parental history of hypertension than in those without. It was shown that mental stress elevates heart rate, blood pressure, sympathovagal activity, and the plasma total homocysteine level in young men.

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms.

PubMed

Zhang, Hong-Feng; Dai, Yu-Chuan; Wu, Jing; Jia, Mei-Xiang; Zhang, Ji-Shui; Shou, Xiao-Jing; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

2016-10-01

Autism spectrum disorder (ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The "twin" nonapeptides oxytocin (OXT) and arginine-vasopressin (AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children. As expected, children with ASD had lower plasma OXT levels than gender-matched controls (P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication (Rho = -0.22, P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects (Rho = -0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children (P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

2011-01-01

BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

Outcome after Discontinuing Long-Term Benzimidazole Treatment in 11 Patients with Non-resectable Alveolar Echinococcosis with Negative FDG-PET/CT and Anti-EmII/3-10 Serology

PubMed Central

Stumpe, Katrin D. M.; Grimm, Felix; Deplazes, Peter; Huber, Sabine; Bertogg, Kaja; Fischer, Dorothee R.; Müllhaupt, Beat

2015-01-01

Background/Aims Benzimidazoles are efficacious for treating non-resectable alveolar echinococcosis (AE), but their long-term parasitocidal (curative) effect is disputed. In this study, we prospectively analyzed the potential parasitocidal effect of benzimidazoles and whether normalization of FDG-PET/CT scans and anti-Emll/3-10-antibody levels could act as reliable "in vivo" parameters of AE-inactivation permitting to abrogate chemotherapy with a low risk for AE-recurrence. Method This prospective study included 34 patients with non-resectable AE subdivided into group A (n = 11), followed-up after diagnosis and begin of chemotherapy at months 6, 12 and 24, and group B (n = 23) with a medium duration of chemotherapy of 10 (range 2–25) years. All patients were assessed by FDG-PET/CT examinations and anti-EmII/3-10 serology. Chemotherapy was abrogated in patients with normalization of FDG-PET/CT and serum anti-EmII/3-10 levels. These patients were closely followed-up for AE recurrence. Endpoint (parasitocidal efficacy) was defined by the absence of AE-recurrence >24 months after stopping treatment. Results Normalization of FDG-PET/CT scan and anti-EmII/3-10 levels occurred in 11 of 34 patients (32%). After abrogation of chemotherapy in these 11 patients, there was no evidence of AE-recurrence within a median of 70.5 (range 16–82) months. However, the patients’ immunocompetence appears pivotal for the described long-term parasitocidal effect of benzimidazoles. Conclusions The combination of negative FDG-PET/CT-scans and anti-EmII/3-10 antibody levels seem to be reliable parameters for assessing in vivo AE-larval inactivity after long-term benzimidazole chemotherapy. Trial Registration clinicaltrials.gov: NCT00658294 PMID:26389799

Gut Microbiota and Metabolic Endotoxemia in Young Obese Mexican Subjects

PubMed Central

Radilla-Vázquez, Romina Belén; Parra-Rojas, Isela; Martínez-Hernández, Norma Edith; Márquez-Sandoval, Yolanda Fabiola; Illades-Aguiar, Berenice; Castro-Alarcón, Natividad

2016-01-01

Background The gut microbiota plays an important role in human metabolism; previous studies suggest that the imbalance can cause a metabolic endotoxemia that may be linked to weight gain and insulin resistance. The purpose of this study was to investigate the relationship between the gut microbiota composition, the lipopolysaccharide levels and the metabolic profile in obese and normal-weight young subjects. Methods We studied 32 obese (BMI ≥ 30 kg/m2) and 32 normal-weight subjects (BMI = 18.5-24.9 kg/m2), aged 18-25 years. Quantification of intestinal bacteria was performed by real-time PCR. Endotoxin units were determined with the test QCL-1000, and biochemical profile was performed under a standard protocol of Spinreact. Results Obese individuals had a BMI of 34.5 (32.9-36.45) kg/m2, increased triglycerides (123 vs. 70 mg/dl), total cholesterol (168 vs. 142 mg/dl), and LDL-cholesterol (114 vs. 96.5 mg/dl). In obese subjects body temperature was higher than in normal-weight subjects. We found a greater number of Clostridum leptum and Lactobacillus (p < 0.001) and lower numbers of Prevotella and Escherichia coli (p < 0.001) in the obese group. A decrease of E. coli was associated with an increased risk of lipopolysaccharide levels ranging from 1 to 1.3 EU/ml. A positive correlation was found between serum lipopolysaccharides and BMI (r = 0.46, p = 0.008), triglyceride levels (r = 0.44, p = 0.011) as well as waist circumference (r = 0.34, p = 0.040), being more evident in young obese females. Conclusion Subclinical metabolic endotoxemia determined by serum concentration of lipopolysaccharides was related to the smallest amount of E. coli, high triglyceride levels, and central adiposity in obese young persons. PMID:26745497

Normalization of Patient-Identified Plasma Biomarkers in SMNΔ7 Mice following Postnatal SMN Restoration

PubMed Central

Arnold, W. David; Duque, Sandra; Iyer, Chitra C.; Zaworski, Phillip; McGovern, Vicki L.; Taylor, Shannon J.; von Herrmann, Katharine M.; Kobayashi, Dione T.; Chen, Karen S.; Kolb, Stephen J.; Paushkin, Sergey V.; Burghes, Arthur H. M.

2016-01-01

Introduction and Objective Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function. The goal was to determine whether levels of plasma markers were altered in the SMNΔ7 mouse model of SMA and whether postnatal SMN restoration resulted in normalization of the biomarkers. Methods SMNΔ7 and control mice were treated with antisense oligonucleotides (ASO) targeting ISS-N1 to increase SMN protein from SMN2 or scramble ASO (sham treatment) via intracerebroventricular injection on postnatal day 1 (P1). Brain, spinal cord, quadriceps muscle, and liver were analyzed for SMN protein levels at P12 and P90. Ten plasma biomarkers (a subset of biomarkers in the SMA-MAP panel available for analysis in mice) were analyzed in plasma obtained at P12, P30, and P90. Results Of the eight plasma biomarkers assessed, 5 were significantly changed in sham treated SMNΔ7 mice compared to control mice and were normalized in SMNΔ7 mice treated with ASO. Conclusion This study defines a subset of the SMA-MAP plasma biomarker panel that is abnormal in the most commonly used mouse model of SMA. Furthermore, some of these markers are responsive to postnatal SMN restoration. These findings support continued clinical development of these potential prognostic and pharmacodynamic biomarkers. PMID:27907033

Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase

PubMed Central

Park, Joong-Won

2016-01-01

Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p< 0.001). Multivariate analysis showed that an AFP ratio > 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT. PMID:27304617

Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation

PubMed Central

Ren, Xingxing; Han, Tingting; Chen, Yawen; Qiu, Huiying; Wu, Peihong; Zheng, Jun; Wang, Lihua; Liu, Wei; Hu, Yaomin

2017-01-01

Aims To investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR). Methods 544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function. Results Among subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters. Conclusions Dyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals. PMID:28199386

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects

PubMed Central

2013-01-01

Background This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. Methods The sample consisted of 103 men (18–66 y) and 26 women (18–65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. Results Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (−11%, p <0.001), LDL-cholesterol (−18%, p < 0.001), apolipoprotein B (apo B) (−12%, p < 0.01) and LDL/HDL ratio (−12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (−5%, p <0.02), LDL-cholesterol (−12%, p <0.03), apolipoprotein B (−12%, p <0.01) and LDL/HDL ratio (−16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. Conclusion Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet. PMID:23919812

Differential expression of cytokeratin mRNA and protein in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma.

PubMed Central

Yang, Y.; Hao, J.; Liu, X.; Dalkin, B.; Nagle, R. B.

1997-01-01

The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was investigated in normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and invasive carcinoma using in situ hybridization. Protein localization was carried out in adjacent sections using immunohistochemistry and correlated with mRNA expression. Snap-frozen human prostate samples including 22 examples of normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were examined. CK5 and -14 mRNA and protein were prominently expressed only in the basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal cells of the most of the PIN lesions but was seen at a low level in some PIN lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the cell that makes up the PIN lesions is derived from a basal cell, CK14 translation is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein were constitutively expressed in all epithelia of normal and abnormal prostate tissues. CK19 mRNA and protein were persistently expressed in both basal and luminal cells of the tubular portion of normal glands as well as PIN lesions, but were expressed heterogeneously in both basal and luminal cells of normal alveoli. CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not detected either in normal or in abnormal prostate tissues. In conclusion, the expression of CK19 in PIN lesions is similar to its tubular expression and would support an origin of PIN lesions from this structure rather than the alveolar portion of the glands. The similar cytokeratin expression between PIN lesions and invasive carcinoma further supports the concept that PIN is a precursor lesion of invasive carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9033282

Antimüllerian hormone levels are independently related to ovarian hyperandrogenism and polycystic ovaries

PubMed Central

Rosenfield, Robert L.; Wroblewski, Kristen; Padmanabhan, Vasantha; Littlejohn, Elizabeth; Mortensen, Monica; Ehrmann, David A.

2013-01-01

Objective To determine the relationship of antimüllerian hormone (AMH) levels to polycystic ovaries and ovarian androgenic function. Design Prospective case-control study. Setting General clinical research center. Participant(s) Eumenorrheic asymptomatic volunteers without (V-NO; n = 19; reference population) or with (V-PCO; n = 28) a polycystic ovary and hyperandrogenemic anovulatory subjects grouped according to ovarian function into typical PCOS (PCOS-T; n = 37) and atypical PCOS (PCOS-A; n = 18). Intervention(s) Pelvic ultrasonography, short dexamethasone androgen-suppression test (SDAST), and GnRH agonist (GnRHag) test. Main Outcome Measure(s) Baseline AMH levels were related to polycystic ovary status, testosterone response to SDAST, and 17-hydroxyprogesterone response to GnRHag test. Result(s) AMH levels correlated with SDAST and GnRHag test outcomes. AMH was elevated (>6.2 ng/mL) in 32% of V-PCO versus 5% V-NO. The 21% of V-PCO who met Rotterdam PCOS criteria all had functional ovarian hyperandrogenism, but AMH levels were similar to nonhyperandrogenic V-PCO. AMH >10.7 ng/mL discriminated V-PCO from PCOS with 96% specificity and 41% sensitivity for PCOS-T, and insignificantly for PCOS-A. Conclusion(s) AMH levels are independently related to ovarian androgenic function and polycystic ovaries. Very high AMH levels are specific but insensitive for PCOS. In the absence of hyperandrogenism, moderate AMH elevation in women with normal-variant polycystic ovaries seems to indicate an enlarged oocyte pool. PMID:22541936

The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study

PubMed Central

Kwon, Yu Hyun; Kim, Seul-Ki; Cho, Jung Hwan; Kwon, Hyemi; Park, Se Eun; Oh, Hyung-Geun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo

2018-01-01

Background Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time. Methods A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal (<150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014. Results Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80). Conclusion In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI. PMID:29388400

Normal Postprandial Nonesterified Fatty Acid Uptake in Muscles Despite Increased Circulating Fatty Acids in Type 2 Diabetes

PubMed Central

Labbé, Sébastien M.; Croteau, Etienne; Grenier-Larouche, Thomas; Frisch, Frédérique; Ouellet, René; Langlois, Réjean; Guérin, Brigitte; Turcotte, Eric E.; Carpentier, André C.

2011-01-01

OBJECTIVE Postprandial plasma nonesterified fatty acid (NEFA) appearance is increased in type 2 diabetes. Our objective was to determine whether skeletal muscle uptake of plasma NEFA is abnormal during the postprandial state in type 2 diabetes. RESEARCH DESIGN AND METHODS Thigh muscle blood flow and oxidative metabolism indexes and NEFA uptake were determined using positron emission tomography coupled with computed tomography (PET/CT) with [11C]acetate and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (18FTHA) in seven healthy control subjects (CON) and seven subjects with type 2 diabetes during continuous oral intake of a liquid meal to achieve steady postprandial NEFA levels with insulin infusion to maintain similar plasma glucose levels in both groups. RESULTS In the postprandial state, plasma NEFA level was higher in type 2 diabetic subjects versus CON (P < 0.01), whereas plasma glucose was at the same level in both groups. Muscle NEFA fractional extraction and blood flow index levels were 56% (P < 0.05) and 24% (P = 0.27) lower in type 2 diabetes, respectively. However, muscle NEFA uptake was similar to that of CON (quadriceps femoris [QF] 1.47 ± 0.23 vs. 1.37 ± 0.24 nmol ⋅ g−1 ⋅ min−1, P = 0.77; biceps femoris [BF] 1.54 ± 0.26 vs. 1.46 ± 0.28 nmol ⋅ g−1 ⋅ min−1, P = 0.85). Muscle oxidative metabolism was similar in both groups. Muscle NEFA fractional extraction and blood flow index were strongly and positively correlated (r = 0.79, P < 0.005). CONCLUSIONS Postprandial muscle NEFA uptake is normal despite elevated systemic NEFA levels and acute normalization of plasma glucose in type 2 diabetes. Lower postprandial muscle blood flow with resulting reduction in muscle NEFA fractional extraction may explain this phenomenon. PMID:21228312

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

PubMed

Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C

2003-10-01

The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Exertional Rhabdomyolysis in a Collegiate American Football Player After Preventive Cold-Water Immersion: A Case Report

PubMed Central

Kahanov, Leamor; Eberman, Lindsey E.; Wasik, Mitchell; Alvey, Thurman

2012-01-01

Objective: To describe a case of exertional rhabdomyolysis in a collegiate American football player after preventive cold-water immersion. Background: A healthy man (19 years old) participated in full-contact football practice followed by conditioning (2.5 hours). After practice, he entered a coach-mandated post-practice cold-water immersion and had no signs of heat illness before developing leg cramps, for which he presented to the athletic training staff. After 10 minutes of repeated stretching, massage, and replacement of electrolyte-filled fluids, he was transported to the emergency room. Laboratory tests indicated a creatine kinase (CK) level of 2545 IU/L (normal range, 45–260 IU/L), CK-myoglobin fraction of 8.5 ng/mL (normal < 6.7 ng/mL), and CK-myoglobin relative index of 30% (normal range, 25%– 30%). Myoglobin was measured at 499 ng/mL (normal = 80 ng/mL). The attending physician treated the athlete with intravenous fluids. Differential Diagnosis: Exercise-associated muscle cramps, dehydration, exertional rhabdomyolysis. Treatment: The patient was treated with rest and rehydration. One week after the incident, he began biking and swimming. Eighteen days later, the patient continued to demonstrate elevated CK levels (527 IU/L) but described no other symptoms and was allowed to return to football practice as tolerated. Two months after the incident, his CK level remained high (1900 IU/L). Uniqueness: The athlete demonstrated no signs of heat illness upon entering the cold-water immersion but experienced severe leg cramping after immersion, resulting in a diagnosis of exertional rhabdomyolysis. Previously described cases have not linked cold-water immersion with the pathogenesis of rhabdomyolysis. Conclusions: In this football player, CK levels appeared to be a poor indicator of rhabdomyolysis. Our patient demonstrated no other signs of the illness weeks after the incident, yet his elevated CK levels persisted. Cold-water immersion immediately after exercise should be monitored by the athletic training staff and may not be appropriate to prevent muscle damage, given the lack of supporting evidence. PMID:22488291

Are Plasma Thyroid-Stimulating Hormone Levels Associated with Degree of Obesity and Metabolic Syndrome in Euthyroid Obese Patients? A Turkish Cohort Study

PubMed Central

Bakiner, Okan; Bozkirli, Emre; Cavlak, Gulhan; Ozsahin, Kursad; Ertorer, Eda

2014-01-01

We aimed to observe the association between degree of obesity and metabolic syndrome and plasma thyrotropin levels in obese, euthyroid Turkish patients. 947 obese and overweight patients who admitted to our outpatient clinic were assessed retrospectively. 150 healthy euthyroid cases were also recruited as the control group. Cases with metabolic syndrome were determined. Patients were divided into various subgroups as overweight, obese, morbid obese, men, and women. No statistical significance was determined when all the patients' and subgroups' plasma thyrotropin levels were compared to normal weight control group. No association was shown between the presence of metabolic syndrome and plasma thyrotropin levels for both all patients and subgroups. Also there was not any association between each component of metabolic syndrome and plasma thyrotropin levels. In conclusion, we did not found any significant association between plasma thyrotropin levels and obesity and metabolic syndrome in our euthyroid subjects. PMID:24527220

3D modeling of effects of increased oxygenation and activity concentration in tumors treated with radionuclides and antiangiogenic drugs

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

Lagerloef, Jakob H.; Kindblom, Jon; Bernhardt, Peter

Purpose: Formation of new blood vessels (angiogenesis) in response to hypoxia is a fundamental event in the process of tumor growth and metastatic dissemination. However, abnormalities in tumor neovasculature often induce increased interstitial pressure (IP) and further reduce oxygenation (pO{sub 2}) of tumor cells. In radiotherapy, well-oxygenated tumors favor treatment. Antiangiogenic drugs may lower IP in the tumor, improving perfusion, pO{sub 2} and drug uptake, by reducing the number of malfunctioning vessels in the tissue. This study aims to create a model for quantifying the effects of altered pO{sub 2}-distribution due to antiangiogenic treatment in combination with radionuclide therapy. Methods:more » Based on experimental data, describing the effects of antiangiogenic agents on oxygenation of GlioblastomaMultiforme (GBM), a single cell based 3D model, including 10{sup 10} tumor cells, was developed, showing how radionuclide therapy response improves as tumor oxygenation approaches normal tissue levels. The nuclides studied were {sup 90}Y, {sup 131}I, {sup 177}Lu, and {sup 211}At. The absorbed dose levels required for a tumor control probability (TCP) of 0.990 are compared for three different log-normal pO{sub 2}-distributions: {mu}{sub 1} = 2.483, {sigma}{sub 1} = 0.711; {mu}{sub 2} = 2.946, {sigma}{sub 2} = 0.689; {mu}{sub 3} = 3.689, and {sigma}{sub 3} = 0.330. The normal tissue absorbed doses will, in turn, depend on this. These distributions were chosen to represent the expected oxygen levels in an untreated hypoxic tumor, a hypoxic tumor treated with an anti-VEGF agent, and in normal, fully-oxygenated tissue, respectively. The former two are fitted to experimental data. The geometric oxygen distributions are simulated using two different patterns: one Monte Carlo based and one radially increasing, while keeping the log-normal volumetric distributions intact. Oxygen and activity are distributed, according to the same pattern. Results: As tumor pO{sub 2} approaches normal tissue levels, the therapeutic effect is improved so that the normal tissue absorbed doses can be decreased by more than 95%, while retaining TCP, in the most favorable scenario and by up to about 80% with oxygen levels previously achieved in vivo, when the least favourable oxygenation case is used as starting point. The major difference occurs in poorly oxygenated cells. This is also where the pO{sub 2}-dependence of the oxygen enhancement ratio is maximal. Conclusions: Improved tumor oxygenation together with increased radionuclide uptake show great potential for optimising treatment strategies, leaving room for successive treatments, or lowering absorbed dose to normal tissues, due to increased tumor response. Further studies of the concomitant use of antiangiogenic drugs and radionuclide therapy therefore appear merited.« less

Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

PubMed Central

2012-01-01

Background Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB), normal differentiated squamous epithelium (ND), and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA) were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and molecular pathways mediating ESCC development and provide information potentially useful in designing novel therapeutic interventions for this tumor type. PMID:22280838

Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men

PubMed Central

Yao, Qi; Fan, Kai; Wang, Guo-Hong; Feng, Rui-Xiang; Liang, Yuan-Jiao; Chen, Li; Ge, Yi-Feng; Yao, Bing

2016-01-01

Objective This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters. Methods 631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT), estradiol (E2) and SHBG levels were detected. Results Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P < 0.001), while only seminal plasma TG was positively related to them (P < 0.05). For lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042). There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV), sperm concentration (SC), total sperm count (TSC), sperm motility, progressive motility (PR) and total normal-progressively motile sperm counts (TNPMS). Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012), both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002), and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051). Conclusion The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility. PMID:26726884

The sleep of elite athletes at sea level and high altitude: a comparison of sea-level natives and high-altitude natives (ISA3600)

PubMed Central

Roach, Gregory D; Schmidt, Walter F; Aughey, Robert J; Bourdon, Pitre C; Soria, Rudy; Claros, Jesus C Jimenez; Garvican-Lewis, Laura A; Buchheit, Martin; Simpson, Ben M; Hammond, Kristal; Kley, Marlen; Wachsmuth, Nadine; Gore, Christopher J; Sargent, Charli

2013-01-01

Background Altitude exposure causes acute sleep disruption in non-athletes, but little is known about its effects in elite athletes. The aim of this study was to examine the effects of altitude on two groups of elite athletes, that is, sea-level natives and high-altitude natives. Methods Sea-level natives were members of the Australian under-17 soccer team (n=14). High-altitude natives were members of a Bolivian under-20 club team (n=12). Teams participated in an 18-day (19 nights) training camp in Bolivia, with 6 nights at near sea level in Santa Cruz (430 m) and 13 nights at high altitude in La Paz (3600 m). Sleep was assessed on every day/night using activity monitors. Results The Australians’ sleep was shorter, and of poorer quality, on the first night at altitude compared with sea level. Sleep quality returned to normal by the end of the first week at altitude, but sleep quantity had still not stabilised at its normal level after 2 weeks. The quantity and quality of sleep obtained by the Bolivians was similar, or greater, on all nights at altitude compared with sea level. The Australians tended to obtain more sleep than the Bolivians at sea level and altitude, but the quality of the Bolivians’ sleep tended to be better than that of the Australians at altitude. Conclusions Exposure to high altitude causes acute and chronic disruption to the sleep of elite athletes who are sea-level natives, but it does not affect the sleep of elite athletes who are high-altitude natives. PMID:24282197

Cardiac Uptake of Minocycline and Mechanisms for In Vivo Cardioprotection

PubMed Central

Romero-Perez, Diego; Fricovsky, Eduardo; Yamasaki, Katrina Go; Griffin, Michael; Barraza-Hidalgo, Maraliz; Dillmann, Wolfgang; Villarreal, Francisco

2008-01-01

Objectives The ability of minocycline to be transported into cardiac cells, concentrate in normal and ischemic myocardium and act as in vivo cardioprotector was examined. We also determined minocycline's capacity to act as a reducer of myocardial oxidative stress and matrix metalloproteinase (MMP) activity. Background The identification of compounds with the potential to reduce myocardial ischemic injury is of great interest. Tetracyclines (TTCs) are antibiotics with pleiotropic cytoprotective properties that accumulate in normal and diseased tissues. Minocycline is highly lipophilic and has shown promise as a possible cardioprotector. However, minocycline's potential as an in vivo cardioprotector as well as the means by which this action is attained are not well understood. Methods Rats were subjected to 45 min of ischemia and 48 h of reperfusion. Animals were treated 48 h before and 48 h after thoracotomy with either vehicle or 50 mg/kg/day minocycline. Tissue samples were used for biochemical assays and cultured cardiac cells for minocycline uptake experiments. Results Minocycline significantly reduced infarct size (∼33%), tissue MMP-9 activity and oxidative stress. Minocycline was concentrated ∼24-fold in normal (0.5 mM) and ∼50-fold in ischemic regions (1.1 mM) vs. blood. Neonatal rat cardiac fibroblasts, myocytes and adult fibroblasts demonstrate a time- and temperature-dependent uptake of minocycline to levels that approximate those of normal myocardium. Conclusions Given the high intracellular levels observed and results from the assessment of in vitro antioxidant and MMP inhibitor capacities, it is likely that minocycline acts to limit myocardial ischemic injury via mass action effects. PMID:18848143

ANG-1 TIE-2 and BMPR Signalling Defects Are Not Seen in the Nitrofen Model of Pulmonary Hypertension and Congenital Diaphragmatic Hernia

PubMed Central

Corbett, Harriet Jane; Connell, Marilyn Gwen; Fernig, David Garth

2012-01-01

Background Pulmonary hypertension (PH) is a lethal disease that is associated with characteristic histological abnormalities of the lung vasculature and defects of angiopoetin-1 (ANG-1), TIE-2 and bone morphogenetic protein receptor (BMPR)-related signalling. We hypothesized that if these signalling defects cause PH generically, they will be readily identifiable perinatally in congenital diaphragmatic hernia (CDH), where the typical pulmonary vascular changes are present before birth and are accompanied by PH after birth. Methods CDH (predominantly left-sided, LCDH) was created in Sprague-Dawley rat pups by e9.5 maternal nitrofen administration. Left lungs from normal and LCDH pups were compared at fetal and postnatal time points for ANG-1, TIE-2, phosphorylated-TIE-2, phosphorylated-SMAD1/5/8 and phosphorylated-ERK1/2 by immunoprecipitation and Western blotting of lung protein extracts and by immunohistochemistry on lung sections. Results In normal lung, pulmonary ANG-1 protein levels fall between fetal and postnatal life, while TIE-2 levels increase. Over the corresponding time period, LCDH lung retained normal expression of ANG-1, TIE-2, phosphorylated-TIE-2 and, downstream of BMPR, phosphorylated-SMAD1/5/8 and phosphorylated-p44/42. Conclusion In PH and CDH defects of ANG-1/TIE-2/BMPR-related signalling are not essential for the lethal vasculopathy. PMID:22539968

Analysis of alternative splicing associated with aging and neurodegeneration in the human brain

PubMed Central

Tollervey, James R.; Wang, Zhen; Hortobágyi, Tibor; Witten, Joshua T.; Zarnack, Kathi; Kayikci, Melis; Clark, Tyson A.; Schweitzer, Anthony C.; Rot, Gregor; Curk, Tomaž; Zupan, Blaž; Rogelj, Boris; Shaw, Christopher E.; Ule, Jernej

2011-01-01

Age is the most important risk factor for neurodegeneration; however, the effects of aging and neurodegeneration on gene expression in the human brain have most often been studied separately. Here, we analyzed changes in transcript levels and alternative splicing in the temporal cortex of individuals of different ages who were cognitively normal, affected by frontotemporal lobar degeneration (FTLD), or affected by Alzheimer's disease (AD). We identified age-related splicing changes in cognitively normal individuals and found that these were present also in 95% of individuals with FTLD or AD, independent of their age. These changes were consistent with increased polypyrimidine tract binding protein (PTB)–dependent splicing activity. We also identified disease-specific splicing changes that were present in individuals with FTLD or AD, but not in cognitively normal individuals. These changes were consistent with the decreased neuro-oncological ventral antigen (NOVA)–dependent splicing regulation, and the decreased nuclear abundance of NOVA proteins. As expected, a dramatic down-regulation of neuronal genes was associated with disease, whereas a modest down-regulation of glial and neuronal genes was associated with aging. Whereas our data indicated that the age-related splicing changes are regulated independently of transcript-level changes, these two regulatory mechanisms affected expression of genes with similar functions, including metabolism and DNA repair. In conclusion, the alternative splicing changes identified in this study provide a new link between aging and neurodegeneration. PMID:21846794

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties

PubMed Central

Godlewska, Marlena; Arczewska, Katarzyna D.; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław

2017-01-01

Background Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. Methods In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. Results We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Conclusions Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism. PMID:28575127

Effect of maternal hypothyroidism during pregnancy on insulin resistance, lipid accumulation and mitochondrial dysfunction in skeletal muscle of fetal rats.

PubMed

Xia, Tongjia; Zhang, Xue; Wang, Youmin; Deng, Datong

2018-05-21

This study aimed to investigate the effect of maternal hypothyroidism during pregnancy on thyroid function of the fetal rat. Female Sprague-Dawley rats were randomized into two groups. PTU group received propylthiouracil (PTU) in drinking water for 6 weeks (n = 90), normal group received drinking normal water (n = 50). The pregnant rats were obtained and had a cesarean-section to get at gestational age of 8.5 d, 13d and 21 d, following blood samples and skeletal muscle were obtained from fetal rats. Levels of thyroid hormone, insulin, mitochondrial protein and adipokines were detected using ELISA. Western blotting was performed to analyze mitochondria and insulin signal transduction-related protein in fetal rat skeletal muscle. Immunostaining of periodic acid-Schiff (PAS) and Oil Red O was used to observe accumulation of muscle glycogen and lipid in the fetal rat. The results showed that levels of thyroid hormone, insulin, insulin signal transduction-related protein, mitochondrial protein and adipokines increased with the fetus developed, but had no statistical differences in PTU the group compared to the normal group. In conclusion, pregnant rats with hypothyroidism have not an influence on insulin resistance, lipid accumulation and mitochondrial dysfunction in skeletal muscle of fetal rats. ©2018 The Author(s).

Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation

PubMed Central

Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

2015-01-01

Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Material/Methods Eighteen human cadaveric spines (C2–T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3–4 ACDR+C4–6 ACDF+C6–7ACDR; hybrid C3–5ACDF+C5–6ACDR+C6–7ACDR; hybrid C3–4ACDR+C4–5ACDR+C5–7ACDF); and 4-level fusion. Results Four-level fusion resulted in significant decrease in the C3–C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. Conclusions Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation.

PubMed

Liao, Zhenhua; Fogel, Guy R; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

2015-12-23

BACKGROUND The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. MATERIAL AND METHODS Eighteen human cadaveric spines (C2-T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3-4 ACDR+C4-6 ACDF+C6-7ACDR; hybrid C3-5ACDF+C5-6ACDR+C6-7ACDR; hybrid C3-4ACDR+C4-5ACDR+C5-7ACDF); and 4-level fusion. RESULTS Four-level fusion resulted in significant decrease in the C3-C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. CONCLUSIONS Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion.

The correlation between urinary 5-hydroxyindoleacetic acid and sperm quality in infertile men and rotating shift workers

PubMed Central

2010-01-01

Background Serotonin is a neurotransmitter that modulates a wide range of neuroendocrine functions. However, excessive circulating serotonin levels may induce harmful effects in the male reproductive system. The objective of this study was to evaluate whether the levels of urinary 5-hydroxyindoleacetic acid (5-HIIA), a major serotonin metabolite, correlate with different classical seminal parameters. Methods Human ejaculates were obtained from 40 men attending infertility counselling and rotating shift workers by masturbation after 4-5 days of abstinence. Urinary 5- HIIA concentration was quantified by using a commercial ELISA kit. Forward motility was assessed by a computer-aided semen analysis (CASA) system. Sperm concentration was determined using the haemocytometer method. Sperm morphology was evaluated after Diff-Quik staining, while sperm vitality was estimated after Eosin-Nigrosin vital staining. Results Our results show that urinary 5-HIIA levels obtained from a set of 20 volunteers negatively correlated with sperm concentration, forward motility, morphology normal range and sperm vitality. On the other hand, we checked the relationship between male infertility and urinary 5-HIIA levels in 20 night shift workers. Thus, urinary 5-HIIA levels obtained from 10 recently-proven fathers were significantly lower than those found in 10 infertile males. Additionally, samples from recent fathers exhibited higher sperm concentration, as well as better forward motility and normal morphology rate. Conclusions In the light of our findings, we concluded that high serotonin levels, indirectly measured as urinary 5-HIIA levels, appear to play a role as an infertility determinant in male subjects. PMID:21059225

Diet enriched with fresh coconut decreases blood glucose levels and body weight in normal adults.

PubMed

Vijayakumar, Venugopal; Shankar, Nagashree R; Mavathur, Ramesh; Mooventhan, A; Anju, Sood; Manjunath, N K

2018-02-20

Background There exist controversies about the health effects of coconut. Fresh coconut consumption on human health has not been studied substantially. Fresh coconut consumption is a regular part of the diet for many people in tropical countries like India, and thus there is an increasing need to understand the effects of fresh coconut on various aspects of health. Aim To compare the effects of increased saturated fatty acid (SFA) and fiber intake, provided by fresh coconut, versus monounsaturated fatty acid (MUFA) and fiber intake, provided by a combination of groundnut oil and groundnuts, on anthropometry, serum insulin, glucose levels and blood pressure in healthy adults. Materials Eighty healthy volunteers, randomized into two groups, were provided with a standardized diet along with either 100 g fresh coconut or an equivalent amount of groundnuts and groundnut oil for a period of 90 days. Assessments such as anthropometric measurements, blood pressure, blood sugar and insulin levels were performed before and after the supplementation period. Results Results of this study showed a significant reduction in fasting blood sugar (FBS) in both the groups. However, a significant reduction in body weight was observed in the coconut group, while a significant increase in diastolic pressure was observed in the groundnut group. Conclusions Results of this study suggest that fresh coconut-added diet helps reduce blood glucose levels and body weight in normal healthy individuals.

Rosa canina L. Fruit Hydro-Alcoholic Extract Effects on Some Immunological and Biochemical Parameters in Rats

PubMed Central

Sadigh-Eteghad, Saeed; Tayefi-Nasrabadi, Hossein; Aghdam, Zahra; Zarredar, Habib; Shanehbandi, Dariush; Khayyat, Leila; Seyyed-Piran, Seyyed-Hamed

2011-01-01

Introduction This research investigates the possible potential of Rosa canina (RC) as an immunomodulator in rats and its effects on some biochemical parameters. Methods In this experiment, 45 male Wistar rats were obtained and divided into three groups (n = 15). These groups received normal saline (10 mg/kg), RC fruit extract (250 mg/kg) and RC fruit extract (500 mg/kg) as oral gavages every day for a period of four weeks, respective-ly. After obtaining blood samples (at the end of each week), differential white blood cell (WBC) counts, phagocyte activity (number), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP) albumin and globulins levels of sam-ples were obtained. The malondialdehyde (MDA) and glutathione (GSH) levels in the se-rum were determined only in day 28 of study. The radical scavenger activity (RSA) of the RC extract was measured spectrophotometrically. Results the gamma globulin level, neu-trophil and monocyte counts and phagocyte activity increased significantly in comparison with the normal saline group. ALT, AST and ALP had not significantly differences in compared to control group. RC extract significantly increased thiobarbituric acid reactive substances (TBARS) and also decreased GSH levels in comparing to control group in day 28. Conclusion the data suggest that the RC extract has been used in traditional medicine might have immunomodulatory effects. PMID:23678431

Overweight and Obesity in Portuguese Children: Prevalence and Correlates

PubMed Central

Gomes, Thayse Natacha; Katzmarzyk, Peter T.; dos Santos, Fernanda K.; Souza, Michele; Pereira, Sara; Maia, José A. R.

2014-01-01

There are widespread differences in overweight/obesity prevalence in children, and understanding the reasons for this is very important. The present study aims: (I) to conduct a meta-analysis on overweight/obesity prevalence in Portuguese children; (II) to identify differences in biological and behavioural characteristics between normal-weight and overweight/obese children; and (III) to investigate the importance of individual- and school-level correlates of variation in children’s BMI using multilevel modelling. A search was done for all published papers including Portuguese children during the last decade; further, 686 Portuguese children (9–11 years old) were sampled and their BMI, family income, maturity offset, nutritional habits, physical activity, sedentariness, sleep time, and school environment information were collected. Results showed a stabilization of overweight/obesity during the last decade, 30.6% (95%CI: 0.287–0.34) for boys, 28.4% (95%CI: 0.23–0.35) for girls, and 30.3% (95%CI: 0.27–0.34) for boys and girls together. Differences between weight groups were only found in individual-level biological traits. The multilevel analysis did not identify significant contributions of school-level variables to children’s BMI variation. In conclusion, no increase was found in the prevalence of overweight/obesity among Portuguese children since 2000. Normal-weight and overweight/obese children only differ in individual-level characteristics, and school context variables were not related to variation in BMI. PMID:25372884

State-dependent alterations of lipid profiles in patients with bipolar disorder.

PubMed

Huang, Yu-Jui; Tsai, Shang-Ying; Chung, Kuo-Hsuan; Chen, Pao-Huan; Huang, Shou-Hung; Kuo, Chian-Jue

2018-07-01

Objective Serum lipid levels may be associated with the affective severity of bipolar disorder, but data on lipid profiles in Asian patients with bipolar disorder and the lipid alterations in different states of opposite polarities are scant. We investigated the lipid profiles of patients in the acute affective, partial, and full remission state in bipolar mania and depression. Methods The physically healthy patients aged between 18 and 45 years with bipolar I disorder, as well as age-matched healthy normal controls were enrolled. We compared the fasting blood levels of glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein of manic or depressed patients in the acute phase and subsequent partial and full remission with those of their normal controls. Results A total of 32 bipolar manic patients (12 women and 20 men), 32 bipolar depressed participants (18 women and 14 men), and 64 healthy control participants took part in this study. The mean cholesterol level in acute mania was significantly lower than that in acute depression (p < 0.025). The lowest rate of dyslipidemia (hypertriglyceridemia or low high-density lipoprotein cholesterol) was observed in acute bipolar mania. Conclusion Circulating lipid profiles may be easily affected by affective states. The acute manic state may be accompanied by state-dependent lower cholesterol and triglyceride levels relative to that in other mood states.

Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study

PubMed Central

Zhang, Ying; Lee, Elisa T.; Cowan, Linda D.; Fabsitz, Richard R.; Howard, Barbara V.

2009-01-01

Background and aims It was reported that high coffee consumption was related to decreased diabetes risk. The aim of this study is to examine the association between coffee consumption and the incidence of type 2 diabetes in persons with normal glucose tolerance in a population with a high incidence and prevalence of diabetes. Methods and results In a prospective cohort study, information about daily coffee consumption was collected at the baseline examination (1989-1992) in a population-based sample of American Indian men and women 45-74 years of age. Participants with normal glucose tolerance (N=1141) at the baseline examination were followed for an average of 7.6 years. The incidence of diabetes was compared across the categories of daily coffee consumption. The hazard ratios of diabetes related to coffee consumption were calculated using Cox proportional hazards models, adjusted for potential confounders. Levels of coffee consumption were positively related to levels of current smoking and inversely related to body mass index, waist circumference, female gender, and hypertension. Compared to those who did not drink coffee, participants who drank 12 or more cups of coffee daily had 67% less risk of developing diabetes during the follow-up (hazard ratio: 0.33, 95% confidence interval: 0.13, 0.81). Conclusion In this population, a high level of coffee consumption was associated with a reduced risk of deterioration of glucose metabolism over an average 7.6 years of follow-up. More work is needed to understand whether there is a plausible biological mechanism for this observation. PMID:20171062

A molecular analysis by gene expression profiling reveals Bik/NBK overexpression in sporadic breast tumor samples of Mexican females

PubMed Central

García, Normand; Salamanca, Fabio; Astudillo-de la Vega, Horacio; Curiel-Quesada, Everardo; Alvarado, Isabel; Peñaloza, Rosenda; Arenas, Diego

2005-01-01

Background Breast cancer is one of the most frequent causes of death in Mexican women over 35 years of age. At molecular level, changes in many genetic networks have been reported as associated with this neoplasia. To analyze these changes, we determined gene expression profiles of tumors from Mexican women with breast cancer at different stages and compared these with those of normal breast tissue samples. Methods 32P-radiolabeled cDNA was synthesized by reverse transcription of mRNA from fresh sporadic breast tumor biopsies, as well as normal breast tissue. cDNA probes were hybridized to microarrays and expression levels registered using a phosphorimager. Expression levels of some genes were validated by real time RT-PCR and immunohistochemical assays. Results We identified two subgroups of tumors according to their expression profiles, probably related with cancer progression. Ten genes, unexpressed in normal tissue, were turned on in some tumors. We found consistent high expression of Bik gene in 14/15 tumors with predominant cytoplasmic distribution. Conclusion Recently, the product of the Bik gene has been associated with tumoral reversion in different neoplasic cell lines, and was proposed as therapy to induce apoptosis in cancers, including breast tumors. Even though a relationship among genes, for example those from a particular pathway, can be observed through microarrays, this relationship might not be sufficient to assign a definitive role to Bik in development and progression of the neoplasia. The findings herein reported deserve further investigation. PMID:16060964

Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus

PubMed Central

2014-01-01

Objective: This article discusses why CSF biomarkers found in normal-pressure hydrocephalus (NPH) can be misleading when distinguishing NPH from comorbid NPH with Alzheimer disease (AD). Methods: We describe NPH CSF biomarkers and how shunt surgery can change them. We hypothesize the effects that hydrocephalus may play on interstitial fluid space and amyloid precursor protein (APP) fragment drainage into the CSF based on a recent report and how this may explain the misleading CSF NPH biomarker findings. Results: In NPH, β-amyloid protein 42 (Aβ42) is low (as in AD), but total tau (t-tau) and phospho-tau (p-tau) levels are normal, providing conflicting biomarker findings. Low Aβ42 supports an AD diagnosis but tau findings do not. Importantly, not only Aβ42, but all APP fragments and tau proteins are low in NPH CSF. Further, these proteins increase after shunting. An increase in interstitial space and APP fragment drainage into the CSF during sleep was reported recently. Conclusions: In the setting of hydrocephalus when the brain is compressed, a decrease in interstitial space and APP protein fragment drainage into the CSF may be impeded, resulting in low levels of all APP fragments and tau proteins, which has been reported. Shunting, which decompresses the brain, would create more room for the interstitial space to increase and protein waste fragments to drain into the CSF. In fact, CSF proteins increase after shunting. CSF biomarkers in pre-shunt NPH have low Aβ42 and tau protein levels, providing misleading information to distinguish NPH from comorbid NPH plus AD. PMID:25332445

Living Donor Liver Transplantation Using a Liver Graft With Congenital Intrahepatic Portosystemic Shunt

PubMed Central

Kamei, Hideya; Imai, Hisashi; Onishi, Yasuharu; Sugimoto, Hiroyuki; Suzuki, Kojiro; Ogura, Yasuhiro

2016-01-01

Background Despite of recent development of imaging modalities, congenital intrahepatic portosystemic shunt (IPSS) is rarely diagnosed. Therefore, living donor liver transplantation using a liver graft with IPSS has not been previously published. Materials and Methods We report a 28-year-old male patient with end-stage liver disease secondary to Wilson disease. His 26-year-old brother was a potential living donor, who had an IPSS of 25 mm in diameter at segment 6 as shown by computed tomography. Liver function tests were normal, and blood ammonia concentration was in the upper limit of normal. Results Living donor liver transplantation was uneventfully performed. After surgery, a recipient liver function tests showed a quick recovery, and serum ammonia levels were consistently normal. Although thrombosis inside the IPSS was confirmed by computed tomography on postoperative day 21, this thrombosis disappeared at 3 months posttransplant with anticoagulants. Currently (12 months posttransplant), the patient has fully recovered, and the IPSS is still the same size. Conclusions Based on our experience, liver allografts with IPSS can be accepted as potential liver allografts. PMID:27500240

Increased expression of stathmin and elongation factor 1α in precancerous nodules with telomere dysfunction in hepatitis B viral cirrhotic patients

PubMed Central

2014-01-01

Background Telomere dysfunction is important in carcinogenesis, and recently, stathmin and elongation factor 1α (EF1α) were reported to be up-regulated in telomere dysfunctional mice. Methods In the present study, the expression levels of stathmin and EF1α in relation to telomere length, telomere dysfunction-induced foci (TIF), γ-H2AX, and p21WAF1/CIP1 expression were assessed in specimens of hepatitis B virus (HBV)-related multistep hepatocarcinogenesis, including 13 liver cirrhosis specimens, 14 low-grade dysplastic nodules (DN), 17 high-grade DNs, and 14 hepatocellular carcinomas (HCC). Five normal liver specimens were used as controls. TIF were analyzed by telomere fluorescent in situ hybridization (FISH) combined with immunostaining, while the protein expressions of stathmin, EF1α, γ-H2AX, and p21WAF1/CIP1 were detected by immunohistochemistry. Result The expressions of stathmin and EF1α gradually increased as multistep hepatocarcinogenesis progressed, showing the highest levels in HCC. Stathmin mRNA levels were higher in high-grade DNs than normal liver and liver cirrhosis, whereas EF1α mRNA expression did not show such a difference. The protein expressions of stathmin and EF1α were found in DNs of precancerous lesions, whereas they were absent or present at very low levels in normal liver and liver cirrhosis. Stathmin histoscores were higher in high-grade DNs and low-grade DNs than in normal liver (all, P < 0.05). EF1α histoscores were higher in high-grade DNs than in normal liver and liver cirrhosis (all, P < 0.05). Stathmin mRNA levels and histoscores, as well as EF1α histoscores (but not mRNA levels), were positively correlated with telomere shortening and γ-H2AX labeling index (all, P < 0.05). EF1α histoscores were also positively correlated with TIF (P < 0.001). Significantly greater inactivation of p21WAF1/CIP1 was observed in low-grade DNs, high-grade DNs, and HCC, compared to liver cirrhosis (all, P < 0.05). p21WAF1/CIP1 labeling index was inversely correlated with TIF, stathmin mRNA level, and EF1α histoscore (all, P < 0.05). Conclusion Stathmin and EF1α are suggested to be closely related to telomere dysfunction, DNA damage, and inactivation of p21WAF1/CIP1 in HBV-related multistep hepatocarcinogenesis. Accordingly, assessment of stathmin and EF1α levels as a reflection of telomere dysfunction may be helpful in evaluating the biological characteristics of precancerous hepatic nodules in hepatitis B viral cirrhotic patients. PMID:24885363

Joint Feedback Analysis Modeling of Nonesterified Fatty Acids in Obese Zucker Rats and Normal Sprague–Dawley Rats after Different Routes of Administration of Nicotinic Acid

PubMed Central

Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

2014-01-01

Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague–Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague–Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration–response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the “degree of disease” can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2571–2584, 2014 PMID:24986056

Frequency and Pathophysiology of Acute Liver Failure in Ornithine Transcarbamylase Deficiency (OTCD)

PubMed Central

Laemmle, Alexander; Gallagher, Renata C.; Keogh, Adrian; Stricker, Tamar; Gautschi, Matthias; Nuoffer, Jean-Marc; Baumgartner, Matthias R.; Häberle, Johannes

2016-01-01

Background Acute liver failure (ALF) has been reported in ornithine transcarbamylase deficiency (OTCD) and other urea cycle disorders (UCD). The frequency of ALF in OTCD is not well-defined and the pathogenesis is not known. Aim To evaluate the prevalence of ALF in OTCD, we analyzed the Swiss patient cohort. Laboratory data from 37 individuals, 27 females and 10 males, diagnosed between 12/1991 and 03/2015, were reviewed for evidence of ALF. In parallel, we performed cell culture studies using human primary hepatocytes from a single patient treated with ammonium chloride in order to investigate the inhibitory potential of ammonia on hepatic protein synthesis. Results More than 50% of Swiss patients with OTCD had liver involvement with ALF at least once in the course of disease. Elevated levels of ammonia often correlated with (laboratory) coagulopathy as reflected by increased values for international normalized ratio (INR) and low levels of hepatic coagulation factors which did not respond to vitamin K. In contrast, liver transaminases remained normal in several cases despite massive hyperammonemia and liver involvement as assessed by pathological INR values. In our in vitro studies, treatment of human primary hepatocytes with ammonium chloride for 48 hours resulted in a reduction of albumin synthesis and secretion by approximately 40%. Conclusion In conclusion, ALF is a common complication of OTCD, which may not always lead to severe symptoms and may therefore be underdiagnosed. Cell culture experiments suggest an ammonia-induced inhibition of hepatic protein synthesis, thus providing a possible pathophysiological explanation for hyperammonemia-associated ALF. PMID:27070778

Impaired glucose tolerance in patients with amyotrophic lateral sclerosis.

PubMed

Pradat, Pierre-Francois; Bruneteau, Gaelle; Gordon, Paul H; Dupuis, Luc; Bonnefont-Rousselot, Dominique; Simon, Dominique; Salachas, Francois; Corcia, Philippe; Frochot, Vincent; Lacorte, Jean-Marc; Jardel, Claude; Coussieu, Christiane; Le Forestier, Nadine; Lacomblez, Lucette; Loeffler, Jean-Philippe; Meininger, Vincent

2010-01-01

Our objectives were to analyse carbohydrate metabolism in a series of ALS patients and to examine potential association with parameters of lipid metabolism and clinical features. Glucose tolerance was assessed by the oral glucose tolerance test in 21 non-diabetic ALS patients and compared with 21 age- and sex-matched normal subjects. Lipids and lactate/pyruvate ratio, levels of pro-inflammatory cytokines (tumour necrosis factor-alpha and interleukin-6) and adipocytokines (leptin and adiponectin) were also measured in ALS patients. Mann-Whitney U-tests analysed continuous data and Fisher's exact tests assessed categorical data. Blood glucose determined 120 min after the glucose bolus was significantly higher in patients with ALS (7.41 mmol/l+/-1.68) compared to controls (6.05+/-1.44, p=0.006). ALS patients with impaired glucose tolerance (IGT) according to WHO criteria (n=7, 33%) were more likely to have elevated free fatty acids (FFA) levels compared to patients with normal glucose tolerance (0.77 nmol/l+/-0.30 vs. 0.57+/-0.19, p=0.04). IGT was not associated with disease duration or severity. In conclusion, patients with ALS show abnormal glucose tolerance that could be associated with increased FFA levels, a key determinant of insulin resistance. The origin of glucose homeostasis abnormalities in ALS may be multifactorial and deserves further investigation.

Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence

PubMed Central

Irwin, Michael R.; Olmstead, Richard; Valladares, Edwin M.; Breen, Elizabeth Crabb; Ehlers, Cindy L.

2009-01-01

Background In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-α (TNF-α) normalizes REM sleep in alcohol-dependent adults. Methods In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order. Polysomnographic sleep was measured at baseline and for 3 nights after the acute dose of etanercept or placebo. Results Compared with placebo, administration of etanercept produced significant decreases in the amount and percentage of REM sleep. Decreases in REM sleep were robust and approached low levels typically found in age-comparable control subjects. Individual differences in biologically active drug as indexed by circulating levels of soluble tumor necrosis factor receptor II negatively correlated with the percentage of REM sleep. Conclusions Pharmacologic neutralization of TNF-α activity is associated with significant reductions in REM sleep in abstinent alcohol-dependent patients. These data suggest that circulating levels of TNF-α may have a physiologic role in the regulation of REM sleep in humans. PMID:19185287

Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

PubMed Central

Adeyemi, O. S.; Elebiyo, T. C.

2014-01-01

Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4) in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity. PMID:25295181

Estrogen receptor β regulates endometriotic cell survival through SGK1 activation

PubMed Central

Monsivais, Diana; Dyson, Matthew T.; Yin, Ping; Navarro, Antonia; Coon, John S; Pavone, Mary Ellen; Bulun, Serdar E.

2016-01-01

OBJECTIVE To determine the expression and biological roles of SGK1 in tissues and cells from patients with endometriosis and from healthy controls. DESIGN Case-control. SETTING University research setting. PATIENTS Premenopausal women. INTERVENTIONS Endometriotic tissues (E-Osis) were obtained from women with ovarian endometriosis and normal endometrial tissues (NoEM) were obtained from women undergoing hysterectomy for benign conditions. MAIN OUTCOMES MEASURES Expression levels of serum and glucocorticoid regulated kinase (SGK1), the role of SGK1 in E-Osis pathology, and the regulation of SGK1 by ERβ. RESULTS Transcript and protein levels of SGK1 were significantly higher in endometriotic tissues and cells compared to normal endometrium. SGK1 mRNA and protein levels were stimulated by estradiol, by the ERβ-selective agonist, diarylpropionitrile, and by prostaglandin E2. SGK1 was transcriptionally regulated by ERβ based on siRNA knockdown and chromatin immunoprecipitation of ERβ followed by quantitative PCR (ChIP-qPCR). SGK1 knockdown led to increased cleavage of PARP, and SGK1 activation was correlated with the phosphorylation of FOXO3a, a pro-apoptotic factor. CONCLUSIONS ERβ leads to SGK1 overexpression in endometriosis, which contributes to the survival of endometriotic lesions through inhibition of apoptosis. PMID:26827666

Effect of sulfite treatment on total antioxidant capacity, total oxidant status, lipid hydroperoxide, and total free sulfydryl groups contents in normal and sulfite oxidase-deficient rat plasma.

PubMed

Herken, Emine Nur; Kocamaz, Erdogan; Erel, Ozcan; Celik, Hakim; Kucukatay, Vural

2009-08-01

Sulfites, which are commonly used as preservatives, are continuously formed in the body during the metabolism of sulfur-containing amino acids. Sulfite oxidase (SOX) is an essential enzyme in the pathway of the oxidative degradation of sulfite to sulfate protecting cells from sulfite toxicity. This article investigated the effect of sulfite on total antioxidant capacity (TAC), total oxidant status, lipid hydroperoxide (LOOH), and total free sulfydryl groups (-SH) levels in normal and SOX-deficient male albino rat plasma. For this purpose, rats were divided into four groups: control, sulfite-treated, SOX-deficient, and sulfite-treated SOX-deficient groups. SOX deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten. Sulfite (70 mg/kg) was administered to the animals via their drinking water. SOX deficiency together with sulfite treatment caused a significant increase in the plasma LOOH and total oxidant status levels. -SH content of rat plasma significantly decreased by both sulfite treatment and SOX deficiency compared to the control. There was also a significant decrease in plasma TAC level by sulfite treatment. In conclusion, sulfite treatment affects the antioxidant/oxidant balance of the plasma cells of the rats toward oxidants in SOX-deficient groups.

Maternal psychological responses during pregnancy after ultrasonographic detection of structural fetal anomalies: A prospective longitudinal observational study

PubMed Central

Kaasen, Anne; Helbig, Anne; Malt, Ulrik F.; Næs, Tormod; Skari, Hans; Haugen, Guttorm

2017-01-01

In this longitudinal prospective observational study performed at a tertiary perinatal referral centre, we aimed to assess maternal distress in pregnancy in women with ultrasound findings of fetal anomaly and compare this with distress in pregnant women with normal ultrasound findings. Pregnant women with a structural fetal anomaly (n = 48) and normal ultrasound (n = 105) were included. We administered self-report questionnaires (General Health Questionnaire-28, Impact of Event Scale-22 [IES], and Edinburgh Postnatal Depression Scale) a few days following ultrasound detection of a fetal anomaly or a normal ultrasound (T1), 3 weeks post-ultrasound (T2), and at 30 (T3) and 36 weeks gestation (T4). Social dysfunction, health perception, and psychological distress (intrusion, avoidance, arousal, anxiety, and depression) were the main outcome measures. The median gestational age at T1 was 20 and 19 weeks in the group with and without fetal anomaly, respectively. In the fetal anomaly group, all psychological distress scores were highest at T1. In the group with a normal scan, distress scores were stable throughout pregnancy. At all assessments, the fetal anomaly group scored significantly higher (especially on depression-related questions) compared to the normal scan group, except on the IES Intrusion and Arousal subscales at T4, although with large individual differences. In conclusion, women with a known fetal anomaly initially had high stress scores, which gradually decreased, resembling those in women with a normal pregnancy. Psychological stress levels were stable and low during the latter half of gestation in women with a normal pregnancy. PMID:28350879

Neither Hematocrit Normalization nor Exercise Training Restores Oxygen Consumption to Normal Levels in Hemodialysis Patients

PubMed Central

Stray-Gundersen, James; Parsons, Dora Beth; Thompson, Jeffrey R.

2016-01-01

Patients treated with hemodialysis develop severely reduced functional capacity, which can be partially ameliorated by correcting anemia and through exercise training. In this study, we determined perturbations of an erythroid-stimulating agent and exercise training to examine if and where limitation to oxygen transport exists in patients on hemodialysis. Twenty-seven patients on hemodialysis completed a crossover study consisting of two exercise training phases at two hematocrit (Hct) values: 30% (anemic) and 42% (physiologic; normalized by treatment with erythroid-stimulating agent). To determine primary outcome measures of peak power and oxygen consumption (VO2) and secondary measures related to components of oxygen transport and utilization, all patients underwent numerous tests at five time points: baseline, untrained at Hct of 30%, after training at Hct of 30%, untrained at Hct of 42%, and after training at Hct of 42%. Hct normalization, exercise training, or the combination thereof significantly improved peak power and VO2 relative to values in the untrained anemic phase. Hct normalization increased peak arterial oxygen and arteriovenous oxygen difference, whereas exercise training improved cardiac output, citrate synthase activity, and peak tissue diffusing capacity. However, although the increase in arterial oxygen observed in the combination phase reached a value similar to that in healthy sedentary controls, the increase in peak arteriovenous oxygen difference did not. Muscle biopsy specimens showed markedly thickened endothelium and electron–dense interstitial deposits. In conclusion, exercise and Hct normalization had positive effects but failed to normalize exercise capacity in patients on hemodialysis. This effect may be caused by abnormalities identified within skeletal muscle. PMID:27153927

Being Normal Weight but Feeling Overweight in Adolescence May Affect Weight Development into Young Adulthood-An 11-Year Followup: The HUNT Study, Norway.

PubMed

Cuypers, Koenraad; Kvaløy, Kirsti; Bratberg, Grete; Midthjell, Kristian; Holmen, Jostein; Holmen, Turid Lingaas

2012-01-01

Objectives. To explore if self-perceived overweight in normal weight adolescents influence their weight development into young adulthood and if so, whether physical activity moderates this association. Methods. A longitudinal study of 1196 normal weight adolescents (13-19 yrs) who were followed up as young adults (24-30 yrs) in the HUNT study. Lifestyle and health issues were assessed employing questionnaires, and standardized anthropometric measurements were taken. Chi square calculations and regression analyses were performed to investigate the associations between self-perceived overweight and change in BMI or waist circumference (WC) adjusted for age, age squared, sex, and other relevant cofactors. Results. Adolescents, defined as being normal weight, but who perceived themselves as overweight had a larger weight gain into young adulthood than adolescents who perceived themselves as normal weight (difference in BMI: 0.66 units [CI95%: 0.1, 1.2] and in WC: 3.46 cm [CI95%: 1.8, 5.1]). Level of physical activity was not found to moderate this association. Conclusions. This study reveals that self-perceived overweight during adolescence may affect development of weight from adolescence into young adulthood. This highlights the importance of also focusing on body image in public health interventions against obesity, favouring a "healthy" body weight taking into account natural differences in body shapes.

Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues.

PubMed

Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

2008-10-01

Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and breast cancer tissue. Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed Western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Applying the four IDE-directed antibodies, we demonstrated IDE expression at the protein level, by means of immunoblotting and immunocytochemistry, in each of the tumor cell lines analyzed. Insulin-degrading enzyme protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in each of the cell lines and tissues assessed. In conclusion, we performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells thus extending our knowledge on the cellular and tissue distribution of IDE, an enzyme which to date has mainly been studied in connection with Alzheimer's disease and diabetes but not in cancer.

Changes in Fasting Plasma Glucose Levels with Ribavirin and Pegylated Interferon Treatment in Normal and Impaired Glucose Tolerant Patients with Chronic Hepatitis C

PubMed Central

Sarasombath, Ongkarn; Suwantarat, Nuntra; Tice, Alan D

2012-01-01

Background Patients with Hepatitis C Virus (HCV) infection have increased rates of glucose intolerance, and studies have shown the improvement of fasting plasma glucose (FPG) levels after clearance of HCV infection with standard ribavirin plus pegylated interferon treatment. The purpose of this study was to examine glycemic changes with standard HCV treatment in patients with impaired fasting glucose (IFG) and normal fasting glucose (NFG). Methods A retrospective study of FPG changes in HCV patients with IFG and NFG treated with standard HCV therapy was conducted. Baseline characteristics and viral responses were assessed; FPG levels before treatment, at the end of treatment, and more than one-month post treatment were compared. Results The mean FPG levels increased by 8.68 mg/dl at the end of treatment in the NFG group but decreased by 9.0 mg/dl in the IFG group, a statistically significant difference (P=0.019). The change in FPG levels remained significantly different after adjusting for weight change (P=0.009) and weight changes and initial weight (P=0.039). FPG change from baseline at more than one month after treatment were similar in both groups (P=0.145). The change in FPG levels was not associated with sustained viral response. Conclusions In HCV-infected patients, standard ribavirin plus pegylated interferon treatment reduced FPG levels in patients with IFG and increased FPG levels in NFG individuals; independent of initial weight, weight change, or viral response. Standard HCV treatment modulates fasting plasma glucose levels which supports the need for a prospective study to determine the clinical significance of this finding. PMID:22737650

Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations

PubMed Central

Hsiao, Edward C.; O'Donnell, Betsy; Salmeen, Kirsten; Nussbaum, Robert; Krebs, Michael; Baumgartner-Parzer, Sabina; Kaufmann, Martin; Jones, Glenville; Bikle, Daniel D.; Wang, YongMei; Mathew, Allen S.; Shoback, Dolores; Block-Kurbisch, Ingrid

2015-01-01

Context: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. Case: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. Conclusions: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated. PMID:26097993

Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue

PubMed Central

2012-01-01

Background Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. Methods Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. Results Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. Conclusions Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue. PMID:22974251

Influence of antigenic competition on the development of antibody-forming cell clones.

PubMed Central

Pritchard-Briscoe, H; McDougall, C; Inchley, C J

1977-01-01

Isoelectric focusing in polyacrylamide gels was used to investigate the anti-sheep red blood cell antibody responses of mice subjected to antigenic competition. A reduction in the number and intensity of antibody bands was found, even in situations where the suppression of IgG antibody titres was minimal, while with large reductions in titre, antibody bands were rarely seen. It thus appeared that the output of individual B-cell clones was severely depressed during competition. It was concluded that inhibition of clonal expansion is an important feature of competition, and that this may reflect a normal regulatory activity which acts to limit cellular proliferation during immune responses. This conclusion was supported by observations on the level of DNA synthesis, following immunization with sheep red cells, in the spleens of normal and suppressed mice. Images Fig. 2 Fig. 3 Fig. 4 PMID:300313

Pilot Metabolome-Wide Association Study of Benzo(a)pyrene in Serum from Military Personnel

PubMed Central

Walker, Douglas I.; Pennell, Kurt D.; Uppal, Karan; Xia, Xiaoyan; Hopke, Philip K.; Utell, Mark J.; Phipps, Richard P.; Sime, Patricia J.; Rohrbeck, Patricia; Mallon, COL Timothy M.; Jones, Dean P.

2016-01-01

Objective A pilot study was conducted to test the feasibility of using Department of Defense Serum Repository (DoDSR) samples to study health and exposure-related effects. Methods Thirty unidentified human serum samples were obtained from the DoDSR and analyzed for normal serum metabolites with high-resolution mass spectrometry and serum levels of free benzo(a)pyrene (BaP) by gas chromatography-mass spectrometry. Metabolic associations with BaP were determined using a metabolome wide association study (MWAS) and metabolic pathway enrichment. Results The serum analysis detected normal ranges of glucose, selected amino acids, fatty acids, and creatinine. Free BaP was detected in a broad concentration range. MWAS of BaP showed associations with lipids, fatty acids, and sulfur amino acid metabolic pathways. Conclusion The results show the DoDSR samples are of sufficient quality for chemical profiling of DoD personnel. PMID:27501104

Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction

PubMed Central

García Robles, Reggie; Rojas, Juan Diego; Bermúdez, Martha; Bernal, Jaime

2012-01-01

Objective: to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. Methods: 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase. Results: plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL gene (p= 0.5785) between cases and controls. Conclusion: messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy. PMID:24893189

Identification and Comparison of the Polar Phospholipids in Normal and Dry Eye Rabbit Tears by MALDI-TOF Mass Spectrometry

PubMed Central

Ham, Bryan M.; Cole, Richard B.; Jacob, Jean T.

2008-01-01

Purpose To identify and compare the phosphorylated lipids in normal and dry eye rabbit tears using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Methods MALDI-TOF MS studies were performed on tear samples from normal and dry eyes of female New Zealand White rabbits. Experimental dry eye was induced by complete removal of the main and accessory lacrimal glands and nictitating membranes. A solid ionic crystal MALDI matrix of paranitroaniline and butyric acid was used to enhance the mass spectral responses of the phospholipids. In addition, a novel lipid isolation, preconcentration, and clean-up method using pipettes containing immobilized metal ion affinity chromatography (IMAC) medium was used. Results The polar phospholipids present in the normal and dry eye rabbit tears showed both similarities and differences. Species related to platelet-activating factor (PAF) and/or lysophosphatidylcholine (lyso-PC), phosphatidylcholine (PC), and sphingomyelin (SM) were found in both the normal and dry eye rabbit tears. However, the number of types and the concentrations of SM molecules were markedly greater in the dry eye tears than in the normal tears. In addition, phosphatidylserine (PS) species that were readily detectable in dry eye tears were not found in normal tears. Conclusions The combination of immobilized metal ion affinity chromatography and the solid ionic crystal matrix for MALDI enabled the detection and study of phosphorylated lipids in the tears. Specific differences between phospholipid levels in normal and dry eye tears were observable with this methodology. The appearance of various SM species only in the dry eye tears may provide markers for this disease state in the future. PMID:16877399

Airborne asbestos in public buildings

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

Chesson, J.; Hatfield, J.; Schultz, B.

The U.S. Environmental Protection Agency sampled air in 49 government-owned buildings (six buildings with no asbestos-containing material, six buildings with asbestos-containing material in generally good condition, and 37 buildings with damaged asbestos-containing material). This is the most comprehensive study to date of airborne asbestos levels in U.S. public buildings during normal building activities. The air outside each building was also sampled. Air samples were analyzed by transmission electron microscopy using a direct transfer preparation technique. The results show an increasing trend in average airborne asbestos levels; outdoor levels are lowest and levels in buildings with damaged asbestos-containing material are highest.more » However, the measured levels and the differences between indoors and outdoors and between building categories are small in absolute magnitude. Comparable studies from Canada and the UK, although differing in their estimated concentrations, also conclude that while airborne asbestos levels may be elevated in buildings that contain asbestos, levels are generally low. This conclusion does not eliminate the possibility of higher airborne asbestos levels during maintenance or renovation that disturbs the asbestos-containing material.« less

Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors.

PubMed

Giraudier, Stéphane; Chagraoui, Hédia; Komura, Emiko; Barnache, Stéphane; Blanchet, Benoit; LeCouedic, Jean Pierre; Smith, David F; Larbret, Frédéric; Taksin, Anne-Laure; Moreau-Gachelin, Françoise; Casadevall, Nicole; Tulliez, Michel; Hulin, Anne; Debili, Najet; Vainchenker, William

2002-10-15

Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by megakaryocyte hyperplasia and bone marrow fibrosis. Biologically, an autonomous megakaryocyte growth and differentiation is noticed, which contributes to the megakaryocyte accumulation. To better understand the molecular mechanisms involved in this spontaneous growth, we searched for genes differentially expressed between normal megakaryocytes requiring cytokines to grow and IMF spontaneously proliferating megakaryocytes. Using a differential display technique, we found that the immunophilin FKBP51 was 2 to 8 times overexpressed in megakaryocytes derived from patients' CD34(+) cells in comparison to normal megakaryocytes. Overexpression was moderate and confirmed in 8 of 10 patients, both at the mRNA and protein levels. Overexpression of FKBP51 in a UT-7/Mpl cell line and in normal CD34(+) cells induced a resistance to apoptosis mediated by cytokine deprivation with no effect on proliferation. FKBP51 interacts with both calcineurin and heat shock protein (HSP)70/HSP90. However, a mutant FKBP51 deleted in the HSP70/HSP90 binding site kept the antiapoptotic effect, suggesting that the calcineurin pathway was responsible for the FKBP51 effect. Overexpression of FKBP51 in UT-7/Mpl cells induced a marked inhibition of calcineurin activity. Pharmacologic inhibition of calcineurin by cyclosporin A mimicked the effect of FKBP51. The data support the conclusion that FKBP51 inhibits apoptosis through a calcineurin-dependent pathway. In conclusion, FKBP51 is overexpressed in IMF megakaryocytes and this overexpression could be, in part, responsible for the megakaryocytic accumulation observed in this disorder by regulating their apoptotic program.

The slippery slope: prediction of successful weight maintenance in anorexia nervosa

PubMed Central

Kaplan, A. S.; Walsh, B. T.; Olmsted, M.; Attia, E.; Carter, J. C.; Devlin, M. J.; Pike, K. M.; Woodside, B.; Rockert, W.; Roberto, C. A.; Parides, M.

2015-01-01

Background Previous research has found that many patients with anorexia nervosa (AN) are unable to maintain normal weight after weight restoration. The objective of this study was to identify variables that predicted successful weight maintenance among weight-restored AN patients. Method Ninety-three patients with AN treated at two sites (Toronto and New York) through in-patient or partial hospitalization achieved a minimally normal weight and were then randomly assigned to receive fluoxetine or placebo along with cognitive behavioral therapy (CBT) for 1 year. Clinical, demographic and psychometric variables were assessed after weight restoration prior to randomization and putative predictors of successful weight maintenance at 6 and 12 months were examined. Results The most powerful predictors of weight maintenance at 6 and 12 months following weight restoration were pre-randomization body mass index (BMI) and the rate of weight loss in the first 28 days following randomization. Higher BMI and lower rate of weight loss were associated with greater likelihood of maintaining a normal BMI at 6 and 12 months. An additional predictor of weight maintenance was site; patients in Toronto fared better than those in New York. Conclusions This study found that the best predictors of weight maintenance in weight-restored AN patients over 6 and 12 months were the level of weight restoration at the conclusion of acute treatment and the avoidance of weight loss immediately following intensive treatment. These results suggest that outcome might be improved by achieving a higher BMI during structured treatment programs and on preventing weight loss immediately following discharge from such programs. PMID:18845008

Glycerol Phenylbutyrate Treatment in Children with Urea Cycle Disorders: Pooled Analysis of Short and Long-term Ammonia Control and Outcomes

PubMed Central

Berry, Susan A.; Lichter-Konecki, Uta; Diaz, George A.; McCandless, Shawn E.; Rhead, William; Smith, Wendy; LeMons, Cynthia; Nagamani, Sandesh C.S.; Coakley, Dion F.; Mokhtarani, Masoud; Scharschmidt, Bruce F.; Lee, Brendan

2015-01-01

Objective To evaluate glycerol phenylbutyrate (GPB) in the treatment of pediatric patients with urea cycle disorders (UCDs). Study Design UCD patients (n=26) ages 2 months through 17 years were treated with GPB and sodium phenylbutyrate (NaPBA) in two short-term, open-label crossover studies, which compared 24-hour ammonia exposure (AUC0–24) and glutamine levels during equivalent steady-state dosing of GPB and sodium phenylbutyrate (NaPBA). These 26 patients plus an additional 23 patients also received GPB in one of three 12-month, open label extension studies, which assessed long-term ammonia control, hyperammonemic (HA) crises, amino acids levels, and patient growth. Results Mean ammonia exposure on GPB was non-inferior to NaPBA in each of the individual crossover studies. In the pooled analyses, it was significantly lower on GPB vs. NaPBA (mean [SD] AUC0–24: 627 [302] vs. 872 [516] µmol/L; p=0.008) with significantly fewer abnormal values (15% on GPB vs. 35% on NaPBA; p = 0.02). Mean ammonia levels remained within the normal range during 12 months of GPB dosing and, when compared with the 12 months preceding enrollment, a smaller percentage of patients (24.5% vs. 42.9%) experienced fewer (17 vs. 38) HA crises. Glutamine levels tended to be lower with GPB than with NaPBA during short-term dosing (mean [SD]: 660.8 [164.4] vs. 710.0 [158.7] µmol/L; p=0.114) and mean glutamine and branched chain amino acids levels, as well as other essential amino acids, remained within the normal range during 12 months of GPB dosing. Mean height and weight Z-scores were within normal range at baseline and did not change significantly during 12 months of GPB treatment. Conclusions Dosing with GPB was associated with 24-hour ammonia exposure that was non-inferior to that during dosing with NaPBA in individual studies and significantly lower in the pooled analysis. Long-term GPB dosing was associated with normal levels of glutamine and essential amino acids, including branched chain amino acids, age-appropriate growth and fewer HA crises as compared with the 12 month period preceding enrollment. PMID:24630270

Vestibular Evoked Myogenic Potentials in Normal Mice and Phex Mice With Spontaneous Endolymphatic Hydrops

PubMed Central

Sheykholeslami, Kianoush; Megerian, Cliff A.; Zheng, Qing Y.

2010-01-01

Objective and Background Vestibular evoked myogenic potentials (VEMPs) have been recorded from the neck musculature and the cervical spinal cord in humans and a limited number of laboratory animals in response to loud sound. However, the mouse VEMP has yet to be described. Evaluation of the sacculocollic pathway via VEMPs in mice can set the stage for future evaluations of mutant mice that now play an important role in research regarding human auditory and vestibular dysfunction. Materials and Methods Sound-evoked potentials were recorded from the neck extensor muscles and the cervical spinal cord in normal adult mice and in circling PhexHyp-Duk/y mice with known vestibular abnormalities, including endolymphatic hydrops (ELH). Results Biphasic potentials were recorded from all normal animals. The mean threshold of the VEMP response in normal adult mice was 60 dB normal hearing level with a mean peak latency of 6.25 ± 0.46 and 7.95 ± 0.42 milliseconds for p1 and n1 peaks, respectively. At the maximum sound intensity used (100 dB normal hearing level), 4 of 5 Phex mice did not exhibit VEMP responses, and 1 showed an elevated threshold, but normal response, with regard to peak latency and amplitude. The histologic findings in all of these Phex mice were consistent with distended membranous labyrinth, displaced Reissner membrane, ganglion cell loss, and ELH. Conclusion This is the first report of VEMP recordings in mice and the first report of abnormal VEMPs in a mouse model with ELH. The characteristics of these potentials such as higher response threshold in comparison to auditory brainstem response, myogenic nature of the response, and latency correlation with the cervical recording (accessory nerve nucleus) were similar to those of VEMPs in humans, guinea pigs, cats, and rats, suggesting that the mouse may be used as an animal model in the study of VEMPs. The simplicity and reliability of these recordings make the VEMP a uniquely informative test for assessing vestibular function, and these results suggest that they may be informative in mice with various mutations. However, further investigation is necessary. PMID:19300299

A comparative study of functional properties of normal and wooden breast broiler chicken meat with NaCl addition.

PubMed

Xing, Tong; Zhao, Xue; Han, Minyi; Cai, Linlin; Deng, Shaolin; Zhou, Guanghong; Xu, Xinglian

2017-09-01

The selection of broilers for augmented growth rate and breast has brought about wooden-breast (WB) muscle abnormalities, which caused substantial economic losses. The objective of this study was to compare water holding capacity, water mobility and distribution, salt-soluble protein (SSP) content, and protein profiles of normal and WB chicken meat with different additions of NaCl. Thirty WB and 30 normal chicken breasts were selected from a deboning line of a major Chinese processing plant at 2 to 3 h post mortem. Two different meat batters were formulated to 150 mg/g meat protein and different NaCl contents (0%, 1%, 2%, 3%, and 4%). Results indicated that as NaCl contents increased, the cooking loss of meat batters decreased (P < 0.05). Increasing the NaCl content to 3% or more increased the solubility of myofibrillar protein and the extraction of SSPs, which resulted in the improving of cooking yield. Over a range of salt concentrations, normal and WB meat showed different protein profiles, with myosin heavy chain exhibiting a higher intensity at ≥3% salt level. Low-field nuclear magnetic resonance (LF-NMR)revealed an increased T22 and higher P22 in raw WB meat compared to normal meat (P < 0.05). Regarding the meat batters, WB meat batters had reduced T21 and lower immobilized water proportions at low NaCl contents (<2%). After heating, T2 shifted towards higher relaxation times with increasing NaCl contents in meat gels. Meat gels prepared from WB had a lower proportion of water within the myofibrillar protein matrix and a greater proportion of exuded bulk water at NaCl contents <3% (P < 0.05), while at higher NaCl contents the difference was eliminated, thus improving water retention capacity. In conclusion, for raw meat, meat batters and gels, water distribution and mobility of WB exhibited significant differences compared to normal meat. The addition of NaCl affected water mobility and distributions in meat batters, with a level of 3% NaCl eliminating the differences between processed normal and WB meat products. © 2017 Poultry Science Association Inc.

Artifacts associated with the measurement of oxidized DNA bases.

PubMed Central

Cadet, J; Douki, T; Ravanat, J L

1997-01-01

In this paper we review recent aspects of the measurement of oxidized DNA bases, currently a matter of debate. There has long been an interest in the determination of the level of oxidized bases in cellular DNA under both normal and oxidative stress conditions. In this respect, the situation is confusing because variations that may be as large as two orders of magnitude have been reported for the yield of the formation of 8-oxo-7,8-dihydroguanine (8-oxoGua) in similar DNA samples. However, recent findings clearly show that application of several assays like gas chromatography-mass spectrometry (GC-MS) and -32P--postlabeling may lead to a significant overestimation of the level of oxidized bases in cellular DNA. In particular, the silylation step, which is required to make the samples volatile for the GC-MS analysis, has been shown to induce oxidation of normal bases at the level of about one oxidized base per 10(4) normal bases. This has been found to be a general process that applies in particular to 8-oxoGua, 8-oxo-7, 8-dihydroadenine,5-hydroxycytosine, 5-(hydroxymethyl)uracil, and 5-formyluracil. Interestingly, prepurification of the oxidized bases from DNA hydrolysate prior to the derivatization reaction prevents artefactual oxidation. Under these conditions, the level of oxidized bases measured by GC-MS is similar to that obtained by HPLC associated with electrochemical detection (HPLC-EC). It should be added that the level of 8-oxo-7,8-dihydro-2;-deoxyguanosine in control cellular DNA has been found to be about fivefold lower than in earlier HPLC-EC measurements by using appropriate conditions of extraction and enzymatic digestion of DNA. Similar conclusions were reached by measuring formamidopyrimidine-DNA glycosylase sensitive sites as revealed by the single cell gel electrophoresis (comet) assay. Images Figure 1. PMID:9349826

Evaluation of the Hepato and Nephron-Protective Effect of a Polyherbal Mixture using Wistar Albino Rats

PubMed Central

Adebesin, Olumide Adedapo; Okpuzor, Joy

2014-01-01

Aim: A polyherbal formulation prepared from a mixture of leaves of Gongronema latifolia, Ocimum gratissimum and Vernonia amygdalina (GOV) was evaluated for hepato-nephro protective properties against acetaminophen-induced toxicity in Wistar albino rats. Materials and Methods: Normal Wistar albino rats were orally treated with different doses of GOV extract (2, 4 and 8 g/kg b. wt), distilled water and some standard hepatoprotective drugs such as Liv 52 and silymarin for 14 days. However, a day prior to the 14th day, 3 g/kg body weight dose of Acetaminophen (APAP) was administered p.o. 1h before GOV and the standard drugs to induce hepatic and renal damage. The normal control was setup which received only distilled water. The serum levels of liver marker enzymes, biochemical analytes, antioxidant enzymes and hematological parameters were monitored. Results: The results showed that pretreatment of experimental animals with a different doses of the polyherbal formulation dose dependently caused a significant (p≤0.05) increase in the levels of most of the measured hematological parameters but significantly (p≤0.05) reduced the levels of MCV and monocytes when compared to the APAP induced toxin control group. Rats pretreated with GOV exhibited significant (p < 0.05) increase in serum levels of ALP, ALT, AST, GGT, LDH, Cholesterol, Triglycerides, Urea and a subsequent decrease in Albumin, Creatine and Total protein when compared to the normal rats. This trend in enzyme and biochemical analytes levels were significantly (p < 0.05) reversed when compared to toxin control group. GOV significantly (p < 0.05) and dose dependently increased the serum, kidney and hepatic CAT, GPx, GSH, GST, SOD and total protein activity in APAP induced damage in rats compared to the toxin control groups. Conclusion: The data from this study suggest that the polyherbal formulation possess hepato and nephron-protective potential against acetaminophen induced hepatotoxicity in rats, thus providing scientific rationale for its use in traditional medicine for the treatment of liver diseases. PMID:25121002

Developing a Signature Based Safeguards Approach for the Electrorefiner and Salt Cleanup Unit Operations in Pyroprocessing Facilities

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

Murphy, Chantell Lynne-Marie

Traditional nuclear materials accounting does not work well for safeguards when applied to pyroprocessing. Alternate methods such as Signature Based Safeguards (SBS) are being investigated. The goal of SBS is real-time/near-real-time detection of anomalous events in the pyroprocessing facility as they could indicate loss of special nuclear material. In high-throughput reprocessing facilities, metric tons of separated material are processed that must be accounted for. Even with very low uncertainties of accountancy measurements (<0.1%) the uncertainty of the material balances is still greater than the desired level. Novel contributions of this work are as follows: (1) significant enhancement of SBS developmentmore » for the salt cleanup process by creating a new gas sparging process model, selecting sensors to monitor normal operation, identifying safeguards-significant off-normal scenarios, and simulating those off-normal events and generating sensor output; (2) further enhancement of SBS development for the electrorefiner by simulating off-normal events caused by changes in salt concentration and identifying which conditions lead to Pu and Cm not tracking throughout the rest of the system; and (3) new contribution in applying statistical techniques to analyze the signatures gained from these two models to help draw real-time conclusions on anomalous events.« less

Treatment with PPARδ agonist alleviates non-alcoholic fatty liver disease by modulating glucose and fatty acid metabolic enzymes in a rat model.

PubMed

Li, Xiuli; Li, Jin; Lu, Xiaolan; Ma, Huihui; Shi, Haitao; Li, Hong; Xie, Danhong; Dong, Lei; Liang, Chunlian

2015-09-01

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition which is associated with certain features of metabolic syndrome and insulin resistance. Peroxisome proliferator‑activated receptor (PPAR)δ is an important regulator of energy metabolism and insulin resistance in diabetes. However, the function of PPARδ in NAFLD has not yet been fully elucidated. In the present study, in order to explore the function of PPARδ in NAFLD, we created a rat model of NALFD induced by a high-fat diet (HFD) and treated the rats with GW501516, a PPARδ agonist. We found that the lipid levels decreased, and hepatocellular ballooning and inflammatory cell infiltration were also significantly decreased following treatment of the rats with GW501516 compared to the untreated rats. Treatment with GW501516 also significantly decreased the homeostasis model assessment of insulin resistance (HOMA-IR) index, as well as the low‑density lipoprotein (LDL) levels. In addition, treatment with GW501516 increased the levels of insulin‑like growth factor‑1 (IGF-1) and high‑density lipoprotein (HDL) compared to the HFD group. Furthermore, the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‑glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) in the HFD group were all restored to the normal control levels following treatment with GW501516. RT‑qPCR and immunohistochemical staining revealed that the expression levels of sterol regulatory element binding protein‑1c (SREBP‑1c) and glucose transporter 2 (GLUT‑2) were both restored to normal control levels following treatment with GW501516. Also, the levels of enzymes related to lipid metabolism were increased following treatment with GW501516. In conclusion, our findings demonstrate that treatment with GW501516 alleviates NAFLD by modulating glucose and fatty acid metabolism.

Association between cardiorespiratory fitness and body fat in girls

PubMed Central

Minatto, Giseli; de Sousa, Thiago Ferreira; de Carvalho, Wellington Roberto Gomes; Ribeiro, Roberto Régis; Santos, Keila Donassolo; Petroski, Edio Luiz

2016-01-01

Abstract Objective: To estimate the prevalence of low cardiorespiratory fitness and its association with excess body fat, considering the sexual maturation and economic level in female adolescents. Methods: Cross-sectional, epidemiological study of 1223 adolescents (10-17 years) from the public school system of Cascavel, PR, Brazil, in 2006. We analyzed the self-assessed sexual maturation level (prepubertal, pubertal and post-pubertal), the economic level (high and low) through a questionnaire and body fat (normal and high) through triceps and subscapular skinfolds. The 20-meter back-and-forth test was applied to estimate maximum oxygen consumption. Cardiorespiratory fitness was assessed according to reference criteria and considered low when the minimum health criterion for age and sex was not met. Chi-square test and logistic regression were applied, with a significance level of 5%. Results: The prevalence of low cardiorespiratory fitness was 51.3%, being associated with all study variables (p<0.001). At the crude analysis, adolescents with high body fat were associated with low cardiorespiratory fitness, when compared to those with normal body fat (OR=2.76; 95%CI: 2.17-3.52). After adjustment by sexual maturation, this association remained valid and showed an effect that was 1.8-fold higher (95%CI: 1.39-2.46) and after adjusting by economic level, the effect was 1.9-fold higher (95%CI: 1.45-2.61). Conclusions: Approximately half of the assessed girls showed unsatisfactory levels of cardiorespiratory fitness for health, which was associated with high body fat, regardless of sexual maturation level and economic level. Effective public health measures are needed, with particular attention to high-risk groups. PMID:27131896

Comparison of Mucin Levels at the Ocular Surface of Postmenopausal Women With and Without a History of Dry Eye

PubMed Central

Gipson, Ilene K.; Spurr-Michaud, Sandra J.; Senchyna, Michelle; Ritter, Robert; Schaumberg, Debra

2011-01-01

Purpose Determine 1) if levels of the glycocalyx membrane mucins, MUC1 and MUC16, and the secreted goblet cell mucin MUC5AC are altered in conjunctival cells and tears of postmenopausal women presenting with a history of non-Sjögren's dry eye, and 2) if mucin levels correlate with dry eye clinical diagnostic data. Methods Eighty-four postmenopausal women with a history of non-Sjögren's dry eye and 30 normal subjects were recruited for this study. Impression cytology samples were collected for mucin mRNA and protein analysis. Tears were collected for mucin protein assay. qPCR, western blot, and ELISA assays were used to quantitate MUC1, MUC16 and MUC5AC levels. Results Postmenopausal women with a history of dry eye displayed significantly increased MUC1 mRNA expression and cellular protein compared to normal subjects (P<0.001 and P<0.0l, respectively). Similarly, cellular MUC16 protein levels were significantly higher (P<0.001). Mucin levels were found to be correlated with the clinical characterization of the subjects, including staining and symptoms. Although cellular MUC5AC protein levels were increased in symptomatic subjects, the increase did not reach statistical significance. Conclusion Elevation in MUC1 and MUC16 mRNA and/or protein levels in postmenopausal non-Sjögren's dry eye patients with a history of dry eye may be a compensatory response to irritation and inflammation associated with the disease. Understanding the pattern of mucin expression associated with dry eye pathology may clarify factors involved in the progression of the disease and enhance the development of targeted therapies. PMID:22089171

The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model

PubMed Central

Lindqvist, Andreas; Ekelund, Mikael; Garcia-Vaz, Eliana; Ståhlman, Marcus; Pierzynowski, Stefan; Gomez, Maria F.; Rehfeld, Jens F.; Groop, Leif; Hedenbro, Jan

2017-01-01

Background A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood. Methods In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder. Results A similar weight development in both groups of pigs validated our experimental model. Despite similar changes in fasting insulin, RYGB-pigs had lower fasting glucose levels. During an IVGTT RYGB-pigs had higher insulin and lower glucose levels. VLDL and IDL were lower in RYGB- than in sham-pigs. RYGB-pigs had increased levels of most amino acids, including branched-chain amino acids, but these were more efficiently suppressed by glucose. Levels of bile acids in the gallbladder were higher, whereas plasma and faecal bile acid levels were lower in RYGB- than in sham-pigs. Conclusion In a lean model RYGB caused lower plasma lipid and bile acid levels, which were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period. PMID:28257455

Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing

PubMed Central

Edelman, Alison B; Cherala, Ganesh; Blue, Steven W; Erikson, David W; Jensen, Jeffrey T

2016-01-01

Objective To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations. Study design Healthy, reproductive-age women with obese and normal BMIs received 1.5 mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5 hours. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group. Results A total of 10 women enrolled and completed the study (normal BMI = 5, median 22.8 kg/m2, range 20.8–23.7; obese BMI = 5, 39.5 kg/m2, range 35.9–46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48 ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=0.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=0.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern. Conclusion Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women. Implications This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women. PMID:27000996

Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

NASA Astrophysics Data System (ADS)

Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

2007-02-01

Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time course of BBB dysfunction thus allowing the use of fewer animals.

Non-Essential Role for TLR2 and Its Signaling Adaptor Mal/TIRAP in Preserving Normal Lung Architecture in Mice

PubMed Central

Ruwanpura, Saleela M.; McLeod, Louise; Lilja, Andrew R.; Brooks, Gavin; Dousha, Lovisa F.; Seow, Huei J.; Bozinovski, Steven; Vlahos, Ross; Hertzog, Paul J.; Anderson, Gary P.; Jenkins, Brendan J.

2013-01-01

Myeloid differentiation factor 88 (MyD88) and MyD88-adaptor like (Mal)/Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) play a critical role in transducing signals downstream of the Toll-like receptor (TLR) family. While genetic ablation of the TLR4/MyD88 signaling axis in mice leads to pulmonary cell death and oxidative stress culminating in emphysema, the involvement of Mal, as well as TLR2 which like TLR4 also signals via MyD88 and Mal, in the pathogenesis of emphysema has not been studied. By employing an in vivo genetic approach, we reveal here that unlike the spontaneous pulmonary emphysema which developed in Tlr4−/− mice by 6 months of age, the lungs of Tlr2−/− mice showed no physiological or morphological signs of emphysema. A more detailed comparative analysis of the lungs from these mice confirmed that elevated oxidative protein carbonylation levels and increased numbers of alveolar cell apoptosis were only detected in Tlr4−/− mice, along with up-regulation of NADPH oxidase 3 (Nox3) mRNA expression. With respect to Mal, the architecture of the lungs of Mal−/− mice was normal. However, despite normal oxidative protein carbonylation levels in the lungs of emphysema-free Mal−/− mice, these mice displayed increased levels of apoptosis comparable to those observed in emphysematous Tlr4−/− mice. In conclusion, our data provide in vivo evidence for the non-essential role for TLR2, unlike the related TLR4, in maintaining the normal architecture of the lung. In addition, we reveal that Mal differentially facilitates the anti-apoptotic, but not oxidant suppressive, activities of TLR4 in the lung, both of which appear to be essential for TLR4 to prevent the onset of emphysema. PMID:24205107

The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

PubMed Central

Ryan, James; Curran, Catherine E.; Hennessy, Emer; Newell, John; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M.

2011-01-01

Introduction The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Methods Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. Results The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, p<0.005) and malignant breast tissue (1.18(0.07) Log10RQ, p<0.05). Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05) and RARα (r = 0.29, p<0.005), with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001). An inverse relationship between NIS and PI3K expression was also observed (r = −0.21, p<0.05). In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6–16 fold), while ATRA and Thyroxine combined caused the greatest increase (range 16–26 fold). Conclusion Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones. PMID:21283523

[Revelation of a polymicrocystic ovary syndrome after one month's treatment by pulsatile GnRH in a patient presenting with functional hypothalamic amenorrhea].

PubMed

Reyss, A C; Merlen, E; Demerle, C; Dewailly, D

2003-12-01

Polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA) are the most frequent causes of endocrine infertility, but their association is an uncommon occurrence. We report the case of a 28-year old woman suffering from infertility and amenorrhea. Her weight was normal (BMI = 19) and she had no hirsutism. She self-reported food restriction and a 10 kg weight loss 5 years ago, concomitant with the onset of amenorrhea. At the initial evaluation, the patient was considered as having HA due to food restriction. At ultrasonography, ovaries were small and multifollicular (right and left area: 2.2 and 2.5 cm(2), respectively; number of cysts 2-9 mm in diameter: 15 and 12, respectively), and no stromal hypertrophy was noted. She has been treated for 1 month by intravenous pulsatile GnRH administration. Although the doses were increased from 5 to 15 microg/pulse every 90 min, no E2 response and no follicular development were observed. Hormonal re-evaluation revealed normal levels of serum LH, FSH and androgens, and a normal LH/FSH ratio. However, a typical aspect of PCO was found at ultrasound (right and left area: 6.5 and 5.5 cm(2), respectively, and more than 15 small cysts arranged peripherally around an increased central stroma in each ovary). The treatment has been then switched to hMG, using the low dose step-up regimen and starting with 75 U/day. In the absence of response after 2 weeks, the dose was increased to 112.5 U/day and a multifollicular reaction occurred, leading to cancellation. In conclusion, we hypothesize that this patient had a "hidden" PCOS when she was hypogonadotrophic and that it developed very rapidly after restitution of a normal gonadotropin level under exogenous GnRH. This occurred despite a low insulin level, showing that hyperinsulinism is not a prerequisite for the development of PCOS in every case.

Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity

PubMed Central

Edelman, Alison B; Carlson, Nichole E; Cherala, Ganesh; Munar, Myrna Y.; Stouffer, Richard L; Cameron, Judy L; Stanczyk, Frank Z.; Jensen, Jeffrey T

2009-01-01

Objective This study was conducted to determine whether increased body mass index (BMI) affects oral contraceptive (OC) pharmacokinetics and suppression of hypothalamic-pituitary-ovarian (HPO) axis activity. Study design Ovulatory reproductive-age women of normal (< 25 kg/m2; n = 10) and obese (> 30 kg/m2; n = 10) BMI received OCs for two cycles (prospective cohort). Subjects were admitted for two 48-h inpatient stays at the beginning and end of the hormone-free interval. Ethinyl estradiol (EE) and levonorgestrel (LNG) levels were evaluated during both inpatient stays. Gonadotropin pulsatility (FSH and LH) was measured during the second inpatient stay. Estradiol (E2) and progesterone (P) were measured daily during inpatient stays and twice per week in Cycle 2. Results BMI was greater in the obese, compared to the normal BMI group [37.3 kg/m2 (SD 6.0) versus 21.9 kg/m2 (SD 1.6); p < 0.05]. The LNG half-life was significantly longer in the obese group (52.1 ± 29.4 h versus 25.6 ± 9.3 h, p < 0.05) which correlated with a lower maximum LNG concentration on Cycle 2, Day 1 [1.9 ng/mL (SD 0.5) versus 2.5 ng/mL (SD 0.7)] and a longer time to reach steady-state (10 versus 5 days), in obese women. There were no significant differences in volume of distribution between groups. LH pulse parameters did not differ statistically between groups but trended towards greater HPO activity in the obese group. Additionally, more obese (6/10 versus 3/10 normal BMI, p > 0.05) women exhibited E2 levels consistent with development of a dominant follicle, and P levels consistent with ovulation (2/10 versus 1/10) during Cycle 2. Conclusions Compared to women of normal BMI, obese women exhibit differences in OC pharmacokinetics that are associated with greater HPO activity. PMID:19631786

A comparison of four different blood gas analysers.

PubMed

Kofstad, J

1981-06-01

Four automatic blood gas analysers from four different manufactures were evaluated and compared. The measurements were performed on blood representing respiratory acidosis and hypoxemia, normal conditions, and respiratory alkalosis and hyperoxemia. On each level nine complete runs were carried out, each run consisting of six replicates of each parameter (pH, Pco2 and Po2) on each instrument (six rounds). Only the directly measured parameters (pH, Pco2, Po2) were compared. The main conclusion is that the four instruments can be used alternatively, and that the differences between the values measured by the four instruments are of little clinical significance.

Percutaneous release of the plantar fascia. New surgical procedure

PubMed Central

Oliva, Francesco; Piccirilli, Eleonora; Tarantino, Umberto; Maffulli, Nicola

2017-01-01

Summary Background Plantar fasciopathy presents with pain at the plantar and medial aspect of the heel. If chronic, it can negatively impact on quality of life. Plantar fasciopathy is not always self-limiting, and can be debilitating. Methods Surgical management involves different procedures. We describe a percutaneous plantar fascia release. A minimally invasive access to the plantar tuberosity of the calcaneus is performed, and a small scalpel blade is used to release the fascia. Conclusion With this procedure, skin healing problems, nerve injuries, infection and prolonged recovery time are minimised, allowing early return to normal activities. Level of Evidence V. PMID:29264346

A decreased soluble Klotho level with normal eGFR, FGF23, serum phosphate, and FEP in an ADPKD patient with enlarged kidneys due to multiple cysts.

PubMed

Kanai, Takahiro; Shiizaki, Kazuhiro; Betsui, Hiroyuki; Aoyagi, Jun; Yamagata, Takanori

2018-05-16

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. ADPKD is characterized clinically by the presence of multiple bilateral renal cysts that lead to chronic renal failure. The cysts evolve from renal tubular epithelial cells that express the Klotho gene. Notably, Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23); in this context, it induces phosphaturia and maintains serum phosphate at a normal level. Many reports have shown that decreases in the soluble Klotho level and increases in the FGF23 level are associated with glomerular filtration rate (GFR) decline, but a recent study observed these changes in patient with normal eGFR. It remains unclear whether the decrease in the Klotho level precedes the increase in FGF23. Here, we present an ADPKD patient with enlarged kidneys due to multiple cysts who had a decreased soluble Klotho level but a normal eGFR and a normal FGF23 level. The patient's serum phosphate level was normal, as was the fractional excretion of phosphate (FEP). This appears to be the first reported case to show a decreased soluble Klotho level plus normal eGFR, FGF23, and FEP. These results suggest that Klotho decreases before FGF23 increases and further suggest that Klotho is not required to maintain normal serum phosphate levels in ADPKD if the FEP and serum phosphate levels are normal.

Normal and pathological serum levels of alpha2-macroglobulins in men and mice.

PubMed Central

Tunstall, A M; Merriman, J M; Milne, I; James, K

1975-01-01

The serum levels of alpha2-macroglobulin have been measured in normal men and mice and in a number of immunopathological conditions. Normal human concentrations are high in youth, reach their minimum in middle age, and gradually increase with old age. In all age groups the mean is higher in the female than in the male. Conversely, in normal mice the alpha2M level is low in youth, maximum in middle age, and shows a slight depression with old age, and the levels are frequently higher in males than in females; there are also strain variations. In human immunopathological conditions, there are some deviations from the normal alpha2M level but these are seen to be changes from the normal distribution of values around the mean, rather than significant elevation or depression of mean values. In some disease states studied there are differences between the sexes in the deviation from normal. "Abnormal" strains of mice had alpha2M levels within the range exhibited by "normal" mice but changes in the levels are seen in mice with various myelomas. Images PMID:47865

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

Sanders, J.E.; Buckner, C.D.; Leonard, J.M.

One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30more » had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.« less

Nitrates in drinking water and methemoglobin levels in pregnancy: a longitudinal study

PubMed Central

2010-01-01

Background Private water systems are more likely to have nitrate levels above the maximum contaminant level (MCL). Pregnant women are considered vulnerable to the effects of exposure to high levels of nitrates in drinking water due to their altered physiological states. The level of methemoglobin in the blood is the biomarker often used in research for assessing exposure to nitrates. The objective of this study was to assess methemoglobin levels and examine how various factors affected methemoglobin levels during pregnancy. We also examined whether differences in water use practices existed among pregnant women based on household drinking water source of private vs. public supply. Methods A longitudinal study of 357 pregnant women was conducted. Longitudinal regression models were used to examine changes and predictors of the change in methemoglobin levels over the period of gestation. Results Pregnant women showed a decrease in methemoglobin levels with increasing gestation although <1% had levels above the physiologic normal of 2% methemoglobin, regardless of the source of their drinking water. The multivariable analyses did not show a statistically significant association between methemoglobin levels and the estimated nitrate intake from tap water among pregnant women around 36 weeks gestation (β = 0.046, p = 0.986). Four women had tap water nitrate levels above the MCL of 10 mg/L. At enrollment, a greater proportion of women who reported using water treatment devices were private wells users (66%) compared to public system users (46%) (p < 0.0001). Also, a greater proportion of private well users (27%) compared to public system users (13%) were using devices capable of removing nitrate from water (p < 0.0001). Conclusion Pregnant women potentially exposed to nitrate levels primarily below the MCL for drinking water were unlikely to show methemoglobin levels above the physiologic normal. Water use practices such as the use of treatment devices to remove nitrates varied according to water source and should be considered in the assessment of exposure to nitrates in future studies. PMID:20946657

Mangifera indica L. leaf extract alleviates doxorubicin induced cardiac stress

PubMed Central

Bhatt, Laxit; Joshi, Viraj

2017-01-01

Aim: The study was undertaken to evaluate the cardioprotective effect of the alcoholic leaf extract of Mangifera indica L. against cardiac stress caused by doxorubicin (DOX). Materials and Methods: Rats were treated with 100 mg/kg of M. indica leaf extract (MILE) in alone and interactive groups for 21 days. Apart from the normal and MILE control groups, all the groups were subjected to DOX (15 mg/kg, i.p.) toxicity for 21 days and effects of different treatments were analyzed by changes in serum biomarkers, tissue antioxidant levels, electrocardiographic parameters, lipid profile, and histopathological evaluation. Results: The MILE treated group showed decrease in serum biomarker enzyme levels and increase in tissue antioxidants levels. Compared to DOX control group, MILE treated animals showed improvement in lipid profile, electrocardiographic parameters, histological score, and mortality. Conclusion: These findings clearly suggest the protective role of alcoholic leaf extract of M. indica against oxidative stress induced by DOX. PMID:28894627

GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance.

PubMed

Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

2016-01-01

Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice.

Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients

PubMed Central

Habib, Samy L

2009-01-01

Background The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. Loss of heterozygosity at the 8-oxoG-DNA glycosylase (OGG1) allele is found in human kidney clear cell carcinoma identifying loss of OGG1 function as a possible contributor to tumorigenesis in the kidney. Tuberin regulates OGG1 through the transcription factor NF-YA in cultured cells. The purpose of this study is to determine the effect of tuberin-deficiency on OGG1 protein and mRNA levels as well as on 8-oxodG levels in kidney tumors from patients with TSC. In addition we evaluated the phophorylation level of downstream targets of mTOR, phospho-S70K, in kidney tumor tissue from TSC patients. Results Kidney angiomyolipoma tissue from TSC patients expresses significant levels of phopho-tuberin and low levels of tuberin compared to control kidney tissue. The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. The decrease OGG1 expression is also associated with significant decrease in the transcription factor, NF-YA, expression in tumor samples compared to normal tissues. In addition, the levels of 8-oxodG are 4-fold higher in tumors compared to control samples. The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. Cyclin D1 expression is also 3-fold higher in increase in the tumor tissues compared to normal kidney tissues. Conclusion These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. These data suggest that tuberin and OGG1 are important proteins in the pathogenesis of angiomyolipoma in TSC patients. PMID:19265534

Relation of N-Terminal Pro-B-Type Natriuretic Peptide and Left Ventricular Diastolic Function to Exercise Tolerance in Patients With Significant Valvular Heart Disease and Normal Left Ventricular Systolic Function.

PubMed

Hwang, Ji-Won; Park, Sung-Ji; Cho, Eun Jeong; Kim, Eun Kyoung; Lee, Ga Yeon; Chang, Sung-A; Choi, Jin-Oh; Lee, Sang-Chol; Park, Seung Woo

2017-06-01

An association between N-terminal prohormone brain natriuretic peptide (NT-proBNP) and exercise tolerance in patients with valvular heart disease (VHD) has been suggested; however, there are few data available regarding this relation. The aim of this study is to evaluate the correlation between exercise tolerance and NT-proBNP in patients with asymptomatic or mildly symptomatic significant VHD and normal left ventricular ejection fraction (LV EF). A total of 96 patients with asymptomatic or mildly symptomatic VHD and normal LV EF (≥50%) underwent cardiopulmonary exercise echocardiography. NT-proBNP levels were determined at baseline and after exercise in 3 hours. Patients were divided in 2 groups based on lower (<26 ml/kg/min, n = 47) or higher (≥26 ml/kg/min, n = 49) peak oxygen consumption (VO 2 ) as a representation of exercise tolerance. In the 2 groups, after adjusting for age and gender, the NT-proBNP level after exercise in 3 hours, left atrial volume index before exercise, right ventricular systolic pressure before exercise, E velocity after exercise, and E/e' ratio after exercise varied significantly. In addition, peak VO 2 was inversely related to NT-proBNP before (r = -0.352, p <0.001) and after exercise (r = -0.351, p <0.001). The NT-proBNP level before exercise was directly related to the left atrial volume index, E/e' ratio, and right ventricular systolic pressure before and after exercise. NT-proBNP after exercise was also directly related to the same parameters. NT-proBNP levels both before and after exercise were higher in the group with lower exercise tolerance. In conclusion, through the correlation among exercise tolerance, NT-proBNP, and parameters of diastolic dysfunction, we demonstrated that diastolic dysfunction and NT-proBNP could predict exercise tolerance in patients with significant VHD and normal LV EF. Copyright © 2017 Elsevier Inc. All rights reserved.

Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus

PubMed Central

Limbrick, David D.; Baksh, Brandon; Morgan, Clinton D.; Habiyaremye, Gakwaya; McAllister, James P.; Inder, Terrie E.; Mercer, Deanna; Holtzman, David M.; Strahle, Jennifer; Wallendorf, Michael J.; Morales, Diego M.

2017-01-01

Introduction Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value. Methods CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC. Results CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC. Conclusions CSF proteins such as sAPPα and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment. PMID:28212403

High normal fasting blood glucose is associated with dementia in Chinese elders

PubMed Central

Mortimer, J.A.; Borenstein, A.R.; Ding, D.; DeCarli, C.; Zhao, Q.; Copenhaver, C.; Guo, Q.; Chu, S.; Galasko, D.; Salmon, D.P.; Dai, Q.; Wu, Y.; Petersen, R.; Hong, Z.

2010-01-01

Background Diabetes is a risk factor for MCI and dementia. However, the association between high normal fasting blood glucose (FBG) and dementia has not been studied. Methods Polytomous logistic regression was used to assess the association of dementia and MCI with FBG in an age- and sex-matched sample of 32 dementia patients, 27 amnestic MCI (aMCI) patients and 31 normal controls (NC). Analyses were repeated for those with normal FBG. Correlations between FBG and cognitive test scores were obtained. Results Controlling for age, sex, education, body mass index, Hachinski Ischemic Score, MRI stroke, and normalized brain, hippocampal and white matter hyperintensity MRI volumes; higher FBG was associated with dementia vs. aMCI status (OR= 3.13; 95% CI:1.28–7.69). This association remained (OR= 7.75; 95% CI:1.10–55.56) when analyses were restricted to subjects with normal FBG. When dementia patients were compared with NC adjusting for age, sex and education a significant association with FBG also was seen (OR=1.83; 95%CI:1.09–3.08), but the association was lost when vascular covariates were added to the model. FBG was not associated with aMCI status vs. NC. Higher FBG was correlated with poorer performance on the Trailmaking Test Part B (p=0.003). The percentage of dementia patients with high normal FBG (90%) was significantly higher than that of aMCI patients with high normal FBG (32.9%) (χ2=13.9, p<0.001). Conclusions Higher FBG was associated with dementia (vs. aMCI) independent of vascular risk factors and MRI indicators of vascular disease, and remained a significant risk factor when analyses were restricted to subjects with normal FBG. The results of this cross-sectional study suggest that a high normal level of FBG may be a risk factor for dementia. PMID:21044774

A Patient with Cystinosis Presenting Like Bartter Syndrome and Review of Literature

PubMed Central

Ertan, Pelin; Evrengul, Havva; Ozen, Serkan; Emre, Sinan

2012-01-01

Background Nephropathic cystinosis is an autosomal recessively inherited metabolic disorder presenting with metabolic acidosis, Fanconi syndrome and renal failure. Case Presentation We present a 6-year-old girl with severe growth failure, hyponatremia and hypokalemia. Her parents were 4th degree relatives. Two relatives were diagnosed as end stage renal failure. She also had persistant hypokalemic hypochloremic metabolic alkalosis. Her renal function was normal at presentation. She was thought to have Bartter syndrome with supporting findings of elevated levels of renin and aldosterone with normal blood pressure, and hyperplasia of juxtaglomerular apparatus. Her metabolic alkalosis did not resolve despite supportive treatment. At 6th month of follow-up proteinuria, glucosuria and deterioration of renal function developed. Diagnosis of cystinosis was made with slit lamp examination and leukocyte cystine levels. At 12th month of follow-up her metabolic alkalosis has converted to metabolic acidosis. Conclusion In children presenting with persistant metabolic alkalosis, with family history of renal failure, and parental consanguinity, cystinosis should always be kept in mind as this disease is an important cause of end stage renal failure which may have features mimmicking Bartter syndrome. PMID:23431081

Apigenin exhibits protective effects in a mouse model of d-galactose-induced aging via activating the Nrf2 pathway.

PubMed

Sang, Ying; Zhang, Fan; Wang, Heng; Yao, Jianqiao; Chen, Ruichuan; Zhou, Zhengdao; Yang, Kun; Xie, Yan; Wan, Tianfeng; Ding, Hong

2017-06-21

The aim of the present research was to study the protective effects and underlying mechanisms of apigenin on d-galactose-induced aging mice. Firstly, apigenin exhibited a potent antioxidant activity in vitro. Secondly, d-galactose was administered by subcutaneous injection once daily for 8 weeks to establish an aging mouse model to investigate the protective effect of apigenin. We found that apigenin supplementation significantly ameliorated aging-related changes such as behavioral impairment, decreased organic index, histopathological injury, increased senescence-associated β-galactosidase (SAβ-gal) activity and advanced glycation end product (AGE) level. Further data showed that apigenin facilitated Nrf2 nuclear translocation both in aging mice and normal young mice, and the Nrf2 expression of normal young mice was higher than that of natural senile mice. In addition, the expressions of Nrf2 downstream gene targets, including HO-1 and NQO1, were also promoted by apigenin administration. Moreover, apigenin also decreased the MDA level and elevated SOD and CAT activities. In conclusion, focusing on the Nrf2 pathway is a suitable strategy to delay the aging process, and apigenin may exert an anti-senescent effect process via activating the Nrf2 pathway.

Delay and trace fear conditioning in C57BL/6 and DBA/2 mice: issues of measurement and performance.

PubMed

Tipps, Megan E; Raybuck, Jonathan D; Buck, Kari J; Lattal, K Matthew

2014-08-01

Strain comparison studies have been critical to the identification of novel genetic and molecular mechanisms in learning and memory. However, even within a single learning paradigm, the behavioral data for the same strain can vary greatly, making it difficult to form meaningful conclusions at both the behavioral and cellular level. In fear conditioning, there is a high level of variability across reports, especially regarding responses to the conditioned stimulus (CS). Here, we compare C57BL/6 and DBA/2 mice using delay fear conditioning, trace fear conditioning, and a nonassociative condition. Our data highlight both the significant strain differences apparent in these fear conditioning paradigms and the significant differences in conditioning type within each strain. We then compare our data to an extensive literature review of delay and trace fear conditioning in these two strains. Finally, we apply a number of commonly used baseline normalization approaches to compare how they alter the reported differences. Our findings highlight three major sources of variability in the fear conditioning literature: CS duration, number of CS presentations, and data normalization to baseline measures. © 2014 Tipps et al.; Published by Cold Spring Harbor Laboratory Press.

The Impact of Rate Reduction and Increased Loudness on Fundamental Frequency Characteristics in Dysarthria

PubMed Central

Tjaden, Kris; Wilding, Greg

2011-01-01

Objective This study examined the extent to which articulatory rate reduction and increased loudness were associated with adjustments in utterance-level measures of fundamental frequency (F0) variability for speakers with dysarthria and healthy controls that have been shown to impact on intelligibility in previously published studies. More generally, the current study sought to compare and contrast how a slower-than-normal rate and increased vocal loudness impact on a variety of utterance-level F0 characteristics for speakers with dysarthria and healthy controls. Patients and Methods Eleven speakers with Parkinson's disease, 15 speakers with multiple sclerosis, and 14 healthy control speakers were audio recorded while reading a passage in habitual, loud, and slow conditions. Magnitude production was used to elicit variations in rate and loudness. Acoustic measures of duration, intensity and F0 were obtained. Results and Conclusions For all speaker groups, a slower-than-normal articulatory rate and increased vocal loudness had distinct effects on F0 relative to the habitual condition, including a tendency for measures of F0 variation to be greater in the loud condition and reduced in the slow condition. These results suggest implications for the treatment of dysarthria. PMID:20938199

EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis

PubMed Central

Li, Youe; Manaligod, Jose M.; Weeks, Daniel L.

2009-01-01

Background information. The BOR (branchio-oto-renal) syndrome is a dominant disorder most commonly caused by mutations in the EYA1 (Eyes Absent 1) gene. Symptoms commonly include deafness and renal anomalies. Results. We have used the embryos of the frog Xenopus laevis as an animal model for early ear development to examine the effects of different EYA1 mutations. Four eya1 mRNAs encoding proteins correlated with congenital anomalies in human were injected into early stage embryos. We show that the expression of mutations associated with BOR, even in the presence of normal levels of endogenous eya1 mRNA, leads to morphologically abnormal ear development as measured by overall otic vesicle size, establishment of sensory tissue and otic innervation. The molecular consequences of mutant eya1 expression were assessed by QPCR (quantitative PCR) analysis and in situ hybridization. Embryos expressing mutant eya1 showed altered levels of multiple genes (six1, dach, neuroD, ngnr-1 and nt3) important for normal ear development. Conclusions. These studies lend support to the hypothesis that dominant-negative effects of EYA1 mutations may have a role in the pathogenesis of BOR. PMID:19951260

The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction

PubMed Central

Michalakis, Konstantinos G.; Segars, James H.

2011-01-01

Objective To summarize the effects of the adipokine adiponectin on the reproductive endocrine system, from the hypothalamic-pituitary axis to the gonads and target tissues of the reproductive system. Design A Medline computer search was performed to identify relevant articles. Setting Research institution. Intervention(s) None. Result(s) Adiponectin is a hormone secreted by adipose tissue that acts to reduce insulin resistance and atherogenic damage, but it also exerts actions in other tissues. Adiponectin mediates its actions in the periphery mainly via two receptors, AdipoR1 and AdipoR2. Adiponectin receptors are present in many reproductive tissues, including the central nervous system, ovaries, oviduct, endometrium, and testes. Adiponectin influences gonadotropin release, normal pregnancy, and assisted reproduction outcomes. Conclusion(s) Adiponectin, a beneficial adipokine, represents a major link between obesity and reproduction. Higher levels of adiponectin are associated with improved menstrual function and better outcomes in assisted reproductive cycles. PMID:20561616

Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia

PubMed Central

Li, Sheng-Mian; Yao, Shu-Kun; Yamamura, Nobuyoshi; Nakamura, Toshitsugu

2003-01-01

AIM: To compare the difference of expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia, and to analyze the role of Bcl-2 and Bax proteins in the progression from dysplasia to carcinoma and to evaluate the correlation of Bcl-2/Bax protein expression with the biological behaviors. METHODS: Expressions of Bcl-2 and Bax were examined immunohistochemically in 27 cases of extrahepatic biliary tract carcinomas (bile duct carcinoma: n = 21, carcinoma of ampulla of Vater: n = 6), and 10 cases of atypical dysplasia. Five cases of normal biliary epithelial tissues were used as controls. A semiquantitative scoring system was used to assess the Bcl-2 and Bax reactivity. RESULTS: The expression of Bcl-2 was observed in 10 out of 27 (37.0%) invasive carcinomas, 1 out of 10 dysplasias, none out of 5 normal epithelial tissues. Bax expression rate was 74.1% (20/27) in invasive carcinoma, 30% (3/10) in dysplasia, and 40% (2/5) in normal biliary epithelium. Bcl-2 and Bax activities were more intense in carcinoma than in dysplasia, with no significant difference in Bcl-2 expression (P = 0.110), and significant difference in Bax expression (P = 0.038). Level of Bax expression was higher in invasive carcinoma than in dysplasia and normal tissue (P = 0.012). Bcl-2 expression was correlated to Bax expression (P = 0.0059). However, Bcl-2/Bax expression had no correlation with histological subtype, grade of differentiation, or level of invasion. CONCLUSION: Increased Bcl-2/Bax expression from dysplasia to invasive tumors supports the view that this is the usual route for the development of extrahepatic biliary tract carcinoma. Bcl-2/Bax may be involved, at least in part, in the apoptotic activity in extrahepatic biliary carcinoma. PMID:14606101

Neutraceutical approaches to control diabetes: A natural requisite approach

PubMed Central

Srivastava, N.; Tiwari, G.; Tiwari, R.; Bhati, L. K.; Rai, Awani K

2012-01-01

Objective: The aim of this study is to screen the polyherbal preparation for antidiabetic activity in rats. Materials and Methods: The blood glucose lowering activity of the polyherbal preparation-I (1:1:1 of wheat germ oil, Coraidrum sativum, and Aloe vera) was studied in normal rats after oral administration at doses of 1.0 ml/kg and 2.0 ml/kg and polyherbal preparation-I, II (wheat germ oil, fresh juice of C. sativum, and A. vera in the ratio of 2:2:1), and III (wheat germ oil, fresh juice of C. sativum and A. vera in the ratio of 1:2:2) on alloxan-induced diabetic rats, after oral administration at doses of 1.0 ml/kg and 2.0 ml/kg. Blood samples were collected from the tail vein method at 0, 0.5, 1, 2, 4, 8, 12, and 24 h in normal rats and in diabetic rats at 0, 1, 3, 7, 15, and 30 days. Blood plasma glucose was estimated by the GOD/POD (glucose oxidase and peroxidase) method. The data were compared statistically by using the one-way ANOVA method followed by the Dunnett multiple component test. Statistical significance was set at P < 0.05. Results: The polyherbal preparation-I produced significant (P < 0.05) reduction in the blood glucose level of normal rats and polyherbal preparation-I, II, and III produced significant (P < 0.01) reduction in the blood glucose level of diabetic rats during 30-day study and compared with that of control and glibenclamide. Conclusion: The polyherbal preparation-I showed a significant glucose lowering effect in normal rats and polyherbal preparation-I, II, and III in diabetic rats. This preparation is going to be promising antidiabetic preparation for masses; however, it requires further extensive studies in human beings. PMID:23225980

Computerized scheme for detection of diffuse lung diseases on CR chest images

NASA Astrophysics Data System (ADS)

Pereira, Roberto R., Jr.; Shiraishi, Junji; Li, Feng; Li, Qiang; Doi, Kunio

2008-03-01

We have developed a new computer-aided diagnostic (CAD) scheme for detection of diffuse lung disease in computed radiographic (CR) chest images. One hundred ninety-four chest images (56 normals and 138 abnormals with diffuse lung diseases) were used. The 138 abnormal cases were classified into three levels of severity (34 mild, 60 moderate, and 44 severe) by an experienced chest radiologist with use of five different patterns, i.e., reticular, reticulonodular, nodular, air-space opacity, and emphysema. In our computerized scheme, the first moment of the power spectrum, the root-mean-square variation, and the average pixel value were determined for each region of interest (ROI), which was selected automatically in the lung fields. The average pixel value and its dependence on the location of the ROI were employed for identifying abnormal patterns due to air-space opacity or emphysema. A rule-based method was used for determining three levels of abnormality for each ROI (0: normal, 1: mild, 2: moderate, and 3: severe). The distinction between normal lungs and abnormal lungs with diffuse lung disease was determined based on the fractional number of abnormal ROIs by taking into account the severity of abnormalities. Preliminary results indicated that the area under the ROC curve was 0.889 for the 44 severe cases, 0.825 for the 104 severe and moderate cases, and 0.794 for all cases. We have identified a number of problems and reasons causing false positives on normal cases, and also false negatives on abnormal cases. In addition, we have discussed potential approaches for improvement of our CAD scheme. In conclusion, the CAD scheme for detection of diffuse lung diseases based on texture features extracted from CR chest images has the potential to assist radiologists in their interpretation of diffuse lung diseases.

Analysis of proteomic differences between liquefied after-cataracts and normal lenses using two-dimensional gel electrophoresis and mass spectrometry

PubMed Central

Ge, Jia-Jia; Huang, Yu-Sen

2017-01-01

AIM To analyze and identify the proteomic differences between liquefied after-cataracts and normal lenses by means of liquefied chromatography-tandem mass spectrometry (LC-MS/MS). METHODS Three normal lenses and three liquefied after-cataracts were exposed to depolymerizing reagents to extract the total proteins. Protein concentrations were separated using two-dimensional gel electrophoresis (2-DE). The digitized images obtained with a GS-800 scanner were then analyzed with PDQuest7.0 software to detect the differentially-expressed protein spots. These protein spots were cut from the gel using a proteome work spot cutter and subjected to in-gel digestion with trypsin. The digested peptide separation was conducted by LC-MS/MS. RESULTS The 2-DE maps showed that lens proteins were in a pH range of 3-10 with a relative molecular weight of 21-70 kD. The relative molecular weight of the more abundant proteins was localized at 25-50 kD, and the isoelectric points were found to lie between PI 4-9. The maps also showed that the protein level within the liquefied after-cataracts was at 29 points and significantly lower than in normal lenses. The 29 points were identified by LC-MS/MS, and ten of these proteins were identified by mass spectrometry and database queries: beta-crystallin B1, glyceraldehyde-3-phosphate dehydrogenase, carbonyl reductase (NADPH) 1, cDNA FLJ55253, gamma-crystallin D, GAS2-like protein 3, sorbitol dehydrogenase, DNA FLJ60282, phosphoglycerate kinase, and filensin. CONCLUSION The level of the ten proteins may play an important role in the development of liquefied after-cataracts. PMID:28944190

Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

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

Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng

2013-11-01

Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays,more » were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.« less

Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats.

PubMed

Cuenca, Nicolás; Pinilla, Isabel; Sauvé, Yves; Lund, Raymond

2005-09-01

The Royal College of Surgeons (RCS) rat has a retinal pigment epithelial cell defect that causes progressive loss of photoreceptors. Although it is extensively used in retinal degeneration and repair studies, how photoreceptor degeneration affects retinal circuitry has not been fully explored. This study examined the changes in synaptic connectivity between photoreceptors and their target cells using immunocytochemistry and correlated these changes with retinal function using the electroretinogram (ERG). Immunostaining with bassoon and synaptophysin (as presynaptic markers) and metabotropic glutamate receptor (mGluR6, a postsynaptic marker for ON-bipolar dendrites) was already impaired at postnatal day (P) 21 and progressively lost with infrequent pairing of presynaptic and postsynaptic elements at P60. By P90 to P120, staining became increasingly patchy and was eventually restricted to sparsely and irregularly distributed foci in which the normal pairing of presynaptic and postsynaptic markers was lost. ERG results showed that mixed scotopic a-waves and b-waves were already reduced by P21 but not oscillatory potentials. While cone-driven responses (photopic b-wave) reached normal levels at P30, they were impaired by P60 but could still be recorded at P120, although with reduced amplitude; rod responses never reached normal amplitudes. Thus, only cone-driven activity attained normal levels, but declined rapidly thereafter. In conclusion, the synaptic markers associated with photoreceptors and processes of bipolar and horizontal cells show abnormalities prior to significant photoreceptor loss. These changes are paralleled with the deterioration of specific aspects of ERG responsiveness with age. Besides providing information on the effects of photoreceptor dysfunction and loss on connection patterns in the retina, the work addresses the more general issue of how disorder of input neurons affects downstream circuitry.

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.

PubMed

Sathya, S; Kokilavani, R; Gurusamy, K

2008-10-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level.

Comparison of ambulatory blood pressure reference standards in children evaluated for hypertension

PubMed Central

Jones, Deborah P.; Richey, Phyllis A.; Alpert, Bruce S.

2009-01-01

Objective The purpose of this study was to systematically compare methods for standardization of blood pressure levels obtained by ambulatory blood pressure monitoring (ABPM) in a group of 111 children studied at our institution. Methods Blood pressure indices, blood pressure loads and standard deviation scores were calculated using he original ABPM and the modified reference standards. Bland—Altman plots and kappa statistics for the level of agreement were generated. Results Overall, the agreement between the two methods was excellent; however, approximately 5% of children were classified differently by one as compared with the other method. Conclusion Depending on which version of the German Working Group’s reference standards is used for interpretation of ABPM data, the classification of the individual as having hypertension or normal blood pressure may vary. PMID:19433980

Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects

PubMed Central

Onishi, Airin; Fujiwara, Yoshinori; Ishiwata, Kiichi; Ishii, Kenji

2017-01-01

Background Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. Methods Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. Results Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05), and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4–5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). Conclusion This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images. PMID:28715453

Blood cadmium levels are associated with a decline in lung function in males

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

Oh, Chang-Mo; The Korea Central Cancer Registry, National Cancer Center, Goyang; Oh, In-Hwan

Background: Cadmium exposure was found to cause a decline in lung function among the general population, but these findings were limited to smokers and gender differences were not explored. Objectives: To examine the relationship between cadmium and chronic obstructive pulmonary disease (COPD) according to gender and smoking status in Korea. Methods: Cross-sectional data from the Korean National Health and Nutrition Examination Survey from 2008 to 2011 were analyzed. COPD was defined by a pre-bronchodilator forced expiratory volume in 1 s divided by forced vital capacity of <0.70. A logistic regression model was used to elucidate the association between blood cadmiummore » levels and COPD according to gender and smoking status. Results: Among 3861 eligible participants, 3622 were included in the analysis. The prevalence of COPD demonstrated an increasing trend in males (P for trend<0.001), but not in females (P for trend=0.67). After adjusting for covariates, a higher blood cadmium level, but within the normal range, was associated with COPD in males, including those who had never-smoked (P for trend <0.001 and P for trend=0.008). However, a higher blood cadmium level was not significantly associated with COPD in females, including those who had never smoked (P for trend=0.39 and P for trend=0.43). Conclusions: A higher blood cadmium level, within the normal range, was associated with COPD in males, including those who had never smoked. However, there was no significant association between blood cadmium levels and COPD in females. - Highlights: • Elevated blood cadmium level is associated with chronic obstructive pulmonary disease in male. • This association can be seen even in never smoked male. • However, this association is present only in male, but not in female.« less

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

PubMed Central

2013-01-01

Background Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation. PMID:23664008

Hemoglobin level in older persons and incident Alzheimer disease

PubMed Central

Buchman, A.S.; Wilson, R.S.; Leurgans, S.E.; Bennett, D.A.

2011-01-01

Objective: To test the hypothesis that level of hemoglobin is associated with incident Alzheimer disease (AD). Methods: A total of 881 community-dwelling older persons participating in the Rush Memory and Aging Project without dementia and a measure of hemoglobin level underwent annual cognitive assessments and clinical evaluations for AD. Results: During an average of 3.3 years of follow-up, 113 persons developed AD. In a Cox proportional hazards model adjusted for age, sex, and education, there was a nonlinear relationship between baseline level of hemoglobin such that higher and lower levels of hemoglobin were associated with AD risk (hazard ratio [HR] for the quadratic of hemoglobin 1.06, 95% confidence interval [CI] 1.01–1.11). Findings were unchanged after controlling for multiple covariates. When compared to participants with clinically normal hemoglobin (n = 717), participants with anemia (n = 154) had a 60% increased hazard for developing AD (95% CI 1.02–2.52), as did participants with clinically high hemoglobin (n = 10, HR 3.39, 95% CI 1.25–9.20). Linear mixed-effects models showed that lower and higher hemoglobin levels were associated with a greater rate of global cognitive decline (parameter estimate for quadratic of hemoglobin = −0.008, SE −0.002, p < 0.001). Compared to participants with clinically normal hemoglobin, participants with anemia had a −0.061 z score unit annual decline in global cognitive function (SE 0.012, p < 0.001), as did participants with clinically high hemoglobin (−0.090 unit/year, SE 0.038, p = 0.018). Conclusions: In older persons without dementia, both lower and higher hemoglobin levels are associated with an increased hazard for developing AD and more rapid cognitive decline. PMID:21753176

[Establishment of the mathematic model of total quantum statistical moment standard similarity for application to medical theoretical research].

PubMed

He, Fu-yuan; Deng, Kai-wen; Huang, Sheng; Liu, Wen-long; Shi, Ji-lian

2013-09-01

The paper aims to elucidate and establish a new mathematic model: the total quantum statistical moment standard similarity (TQSMSS) on the base of the original total quantum statistical moment model and to illustrate the application of the model to medical theoretical research. The model was established combined with the statistical moment principle and the normal distribution probability density function properties, then validated and illustrated by the pharmacokinetics of three ingredients in Buyanghuanwu decoction and of three data analytical method for them, and by analysis of chromatographic fingerprint for various extracts with different solubility parameter solvents dissolving the Buyanghanwu-decoction extract. The established model consists of four mainly parameters: (1) total quantum statistical moment similarity as ST, an overlapped area by two normal distribution probability density curves in conversion of the two TQSM parameters; (2) total variability as DT, a confidence limit of standard normal accumulation probability which is equal to the absolute difference value between the two normal accumulation probabilities within integration of their curve nodical; (3) total variable probability as 1-Ss, standard normal distribution probability within interval of D(T); (4) total variable probability (1-beta)alpha and (5) stable confident probability beta(1-alpha): the correct probability to make positive and negative conclusions under confident coefficient alpha. With the model, we had analyzed the TQSMS similarities of pharmacokinetics of three ingredients in Buyanghuanwu decoction and of three data analytical methods for them were at range of 0.3852-0.9875 that illuminated different pharmacokinetic behaviors of each other; and the TQSMS similarities (ST) of chromatographic fingerprint for various extracts with different solubility parameter solvents dissolving Buyanghuanwu-decoction-extract were at range of 0.6842-0.999 2 that showed different constituents with various solvent extracts. The TQSMSS can characterize the sample similarity, by which we can quantitate the correct probability with the test of power under to make positive and negative conclusions no matter the samples come from same population under confident coefficient a or not, by which we can realize an analysis at both macroscopic and microcosmic levels, as an important similar analytical method for medical theoretical research.

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets

PubMed Central

Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

Introduction During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). Materials and Methods To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Results Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. Conclusions In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI. PMID:26474181

Combined Therapy with Renin-Angiotensin System and Calcium Channel Blockers in Type 2 Diabetic Hypertensive Patients with Proteinuria: Effects on Soluble TWEAK, PTX3, and Flow-Mediated Dilation

PubMed Central

Yilmaz, Mahmut Ilker; Carrero, Juan Jesús; Martín-Ventura, Jose Luis; Sonmez, Alper; Saglam, Mutlu; Celik, Turgay; Yaman, Halil; Yenicesu, Mujdat; Eyileten, Tayfun; Moreno, Juan Antonio; Egido, Jesús

2010-01-01

Background and objectives: Soluble TNF-like weak inducer of apoptosis (sTWEAK) and long pentraxin-3 (PTX3) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). This study tested the hypothesis that the improvement in endothelial function after initiation of angiotensin II receptor blocker (valsartan), calcium channel blocker (amlodipine) therapy, or a combination of both is directly linked to the normalization of sTWEAK and PTX3. Design, setting, participants, & measurements: One-hundred-eight diabetic CKD stage I patients with hypertension (56% men, 46.7 ± 5.3 years) were allocated to a 12-week intervention with amlodipine (10 mg/d), valsartan (160 mg/d), or their combination. Plasma levels of sTWEAK, PTX3, and flow-mediated dilation (FMD) were studied during the interventions. Results: All treatment strategies effectively increased FMD and reduced proteinuria, confirming a more prone reduction with the combined therapy. These improvements were followed by significant PTX3 reductions. Valsartan alone and in combination with amlodipine achieved significant incremental raises in sTWEAK plasma levels. More importantly, the changes observed in sTWEAK (β = 0.25, P = 0.006) or PTX3 (β = −0.24, P = 0.007) plasma levels were independently associated with the improvement in ultrasonographically measured FMD. Conclusions: This study shows that treatment with antihypertensive drugs improves FMD and normalizes proteinuria, PTX3, and sTWEAK in diabetic CKD stage I patients with hypertension. The improvement in FMD was independently associated with PTX3 and sTWEAK normalization. Two surrogate biomarkers of endothelial function are therefore identified with potential as therapeutic targets. The study was registered in clinicaltrials.gov as NCT00921570. PMID:20430947

Proteomics detection of S100A6 in tumor tissue interstitial fluid and evaluation of its potential as a biomarker of cholangiocarcinoma.

PubMed

Onsurathum, Sudarat; Haonon, Ornuma; Pinlaor, Porntip; Pairojkul, Chawalit; Khuntikeo, Narong; Thanan, Raynoo; Roytrakul, Sittiruk; Pinlaor, Somchai

2018-04-01

Tumor interstitial fluid contains tumor-specific proteins that may be useful biomarkers for cancers. In this study, we identified proteins present in cholangiocarcinoma interstitial fluid. Proteins derived from three samples of tumor interstitial fluid and paired samples of adjacent normal interstitial fluid from cholangiocarcinoma patients were subjected to two-dimensional liquid chromatography with tandem mass spectrometry. Candidate proteins were selected based on a greater than twofold change in expression levels between tumor interstitial fluid and normal interstitial fluid. Upregulation of six proteins in tumor interstitial fluid, including S100 calcium binding protein A6 (S100A6), S100 calcium binding protein A9, aldo-keto reductase family 1 member C4, neuropilin-1, 14-3-3 zeta/delta, and triosephosphate isomerase was assessed by western blot and immunohistochemistry. Their potential as markers was evaluated in human cholangiocarcinoma tissue arrays, and in serum using enzyme-linked immunosorbent assay. Expression of S100A6 was higher in tumor interstitial fluid than in normal interstitial fluid and showed the highest positive rate (98.96%) in cholangiocarcinoma tissues. Serum levels of S100A6 did not differ between cholangitis and cholangiocarcinoma patients, but were significantly higher than in healthy individuals ( p < 0.0001). In cholangiocarcinoma cases, S100A6 level was associated with vascular invasion ( p = 0.007) and could distinguish cholangiocarcinoma patients from healthy individuals as effectively as the carbohydrate antigen 19-9. In addition, potential for drug treatment targeting S100A6 and other candidate proteins was also demonstrated using STITCH analysis. In conclusion, proteomics analysis of tumor interstitial fluid could be a new approach for biomarker discovery, and S100A6 is a potential risk marker for screening of cholangiocarcinoma.

Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors

PubMed Central

Barollo, Susi; Bertazza, Loris; Watutantrige-Fernando, Sara; Censi, Simona; Cavedon, Elisabetta; Galuppini, Francesca; Pennelli, Gianmaria; Fassina, Ambrogio; Citton, Marilisa; Rubin, Beatrice; Pezzani, Raffaele; Benna, Clara; Opocher, Giuseppe; Iacobone, Maurizio; Mian, Caterina

2016-01-01

Background 6-18F-fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET is a useful tool in the clinical management of pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC). 18F-FDOPA is a large neutral amino acid biochemically resembling endogenous L-DOPA and taken up by the L-type amino acid transporters (LAT1 and LAT2). This study was conducted to examine the expression of the LAT system in PHEO and MTC. Methods Real-time PCR and Western blot analyses were used to assess LAT1 and LAT2 gene and protein expression in 32 PHEO, 38 MTC, 16 normal adrenal medulla and 15 normal thyroid tissue samples. Immunohistochemistry method was applied to identify the proteins’ subcellular localization. Results LAT1 and LAT2 were overexpressed in both PHEO and MTC by comparison with normal tissues. LAT1 presented a stronger induction than LAT2, and their greater expression was more evident in PHEO (15.1- and 4.1-fold increases, respectively) than in MTC (9.9- and 4.1-fold increases, respectively). Furthermore we found a good correlation between LAT1/2 and GLUT1 expression levels. A positive correlation was also found between urinary noradrenaline and adrenaline levels and LAT1 gene expression in PHEO. The increased expression of LAT1 is also confirmed at the protein level, in both PHEO and MTC, with a strong cytoplasmic localization. Conclusions The present study is the first to provide experimental evidence of the overexpression in some NET cancers (such as PHEO or MTC) of L-type amino acid transporters, and the LAT1 isoform in particular, giving the molecular basis to explain the increase of the DOPA uptake seen in such tumor cells. PMID:27224648

High dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis

PubMed Central

Imam, Mohamad H.; Sinakos, Emmanouil; Gossard, Andrea A.; Kowdley, Kris V.; Luketic, Velimir A. C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Keach, Jill; DeCook, Alisha C.; Enders, Felicity; Lindor, Keith D.

2013-01-01

Background Ursodeoxycholic acid (UDCA) in a dose of 28–30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. Aim Our aim was to compare the risk of adverse clinical endpoints in patients with varying disease status. Methods We reviewed records from patients previously enrolled in a study evaluating the effects of high-dose (28–30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histologic stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, esophageal varices and cholangiocarcinoma was sought. Results One hundred fifty patients were included of which 49 patients developed endpoints. There was an increased development of endpoints amongst patients using UDCA vs. placebo (14 vs. 4, p = 0.0151) with early histologic disease (stage 1–2, n = 88) but not with late stage (stage 3–4, n = 62) disease (17 vs. 14, p = 0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, p = 0.0008) with normal bilirubin levels (total bilirubin ≤ 1.0 mg/dl) but not in patients with elevated bilirubin levels (15 vs. 16, p = 0.6018). Among patients not reaching endpoints 31.68% had normalization of their alkaline phosphatase levels as compared to 14.29% in patients who reached endpoints (p = 0.073). Conclusion The increased risk of adverse events with UDCA treatment as compared to placebo is only apparent in patients with early histologic stage disease or normal total bilirubin. PMID:21957881

The large-conductance calcium-activated potassium channel holds the key to the conundrum of familial hypokalemic periodic paralysis

PubMed Central

Kim, Sung-Jo; Kang, Sun-Yang; Yi, Jin Woong; Kim, Seung-Min

2014-01-01

Purpose Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium (KCa) channel genes in HOKPP patients. Methods We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. Results Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the KCa channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes KCa1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. Conclusion These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels. PMID:25379045

The effects of Momordica charantia on obesity and lipid profiles of mice fed a high-fat diet

PubMed Central

Wang, Jun

2015-01-01

BACKGROUND/OBJECTIVES The present study was conducted to investigate the effects of dried Momordica charantia aqueous extracts (MCA) and ethanol extracts (MCE) on obesity and lipid profiles in mice fed a high-fat diet. MATERIALS/METHODS Forty two ICR mice were randomly divided into six groups. The normal group was fed a basal diet, and other groups were fed a 45% high-fat diet (HFD) for 7 weeks. The normal and HFD groups were also orally administered distilled water each day for 7 weeks. The remaining groups received Momordica charantia extract (0.5 or 1.0 g/kg/day MCA, and 0.5 or 1.0 g/kg/day MCE). In order to measure the anti-obesity and lipid profile improvement effects, body and visceral tissue weight, lipid profiles, plasma insulin levels, hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. RESULTS Both MCA and MCE significantly decreased body and visceral tissue weight relative to those of the HFD group (P < 0.05). Additionally high doses of MCE and MCA significantly reduced the plasmatic insulin levels compared to the HFD groups (P < 0.05) to concentrations comparable to those found in the normal group. MCA and MCE supplementation also significantly modulated the lipid profiles in plasma, liver, and feces compared to mice fed the HFD (P < 0.05). Furthermore MCA and MCE significantly increased hepatic SOD activity, and reduced MDA generation in the liver of the HFD mice (P < 0.05). CONCLUSIONS Results from the present study suggest that Momordica charantia extracts have anti-obesity effects and the ability to modulate lipid prolife of mice fed a HFD by suppressing body weight gain, visceral tissue weight, plasma and hepatic lipid concentrations, and lipid peroxidation along with increasing lipid metabolism. PMID:26425278

Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer

PubMed Central

2012-01-01

Background G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E2), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. Methods The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed. Results Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. Conclusion The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression. PMID:23273253

Adjunctive Aripiprazole Versus Placebo for Antipsychotic-Induced Hyperprolactinemia: Meta-Analysis of Randomized Controlled Trials

PubMed Central

Li, Xianbin; Tang, Yilang; Wang, Chuanyue

2013-01-01

Objective To compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia. Methods Population: adult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms. Interventions: adjunctive aripiprazole vs. adjunctive placebo. Outcome measures: adverse events and efficacy of treatment. Studies: randomized controlled trials. Results Five randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo) met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158) prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed) −0.05 to 0.04 (95% confidence interval −0.13 to 0.16); I2 = 0% to 68%, P = 0.20 to 0.70). However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random) 0.76 (95% confidence interval 0.67 to 0.85); I2 = 43%, P<0.00001). The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms. Conclusion Adjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day. PMID:23936389

Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

PubMed Central

Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

2015-01-01

Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

PubMed Central

Engert, Veronika; Efanov, Simona I.; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C.

2010-01-01

Background In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic–pituitary–adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group. PMID:20964960

Antihypertensive and cardioprotective effects of pumpkin seed oil.

PubMed

El-Mosallamy, Aliaa E M K; Sleem, Amany A; Abdel-Salam, Omar M E; Shaffie, Nermeen; Kenawy, Sanaa A

2012-02-01

Pumpkin seed oil is a natural product commonly used in folk medicine for treatment of prostatic hypertrophy. In the present study, the effects of treatment with pumpkin seed oil on hypertension induced by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg /kg/day) in rats were studied and compared with those of the calcium channel blocker amlodipine. Pumpkin seed oil (40 or 100 mg/kg), amlodipine (0.9 mg/kg), or vehicle (control) was given once daily orally for 6 weeks. Arterial blood pressure (BP), heart rate, electrocardiogram (ECG) changes, levels of serum nitric oxide (NO) (the concentrations of nitrite/nitrate), plasma malondialdehyde (MDA), blood glutathione, and erythrocytic superoxide dismutase activity were measured. Histopathological examination of heart and aorta was conducted as well. L-NAME administration resulted in a significant increase in BP starting from the second week. Pumpkin seed oil or amlodipine treatment significantly reduced the elevation in BP by L-NAME and normalized the L-NAME-induced ECG changes-namely, prolongation of the RR interval, increased P wave duration, and ST elevation. Both treatments significantly decreased the elevated levels of MDA and reversed the decreased levels of NO metabolites to near normal values compared with the L-NAME-treated group. Amlodipine also significantly increased blood glutathione content compared with normal (but not L-NAME-treated) rats. Pumpkin seed oil as well as amlodipine treatment protected against pathological alterations in heart and aorta induced by L-NAME. In conclusion, this study has shown that pumpkin seed oil exhibits an antihypertensive and cardioprotective effects through a mechanism that may involve generation of NO.

Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine

PubMed Central

Faller, Kiterie M E; Atzler, Dorothee; McAndrew, Debra J; Zervou, Sevasti; Whittington, Hannah J; Simon, Jillian N; Aksentijevic, Dunja; ten Hove, Michiel; Choe, Chi-un; Isbrandt, Dirk; Casadei, Barbara; Schneider, Jurgen E; Neubauer, Stefan; Lygate, Craig A

2018-01-01

Abstract Aims Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality. Methods and results Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function. Conclusions Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases. PMID:29236952

Treatment of severe neutropenia with high-dose pyridoxine in a patient with chronic graft versus host disease and squamous cell carcinoma: a case report

PubMed Central

2011-01-01

Introduction The differential diagnosis of neutropenia includes medications, infections, autoimmune diseases, and deficiencies of Vitamin B12 and folate. The association of Vitamin B6 deficiency with severe neutropenia is a rare finding. Case presentation A 51-year-old Caucasian woman presented with fever and profound neutropenia (48 neutrophils/uL). Her clinical history included non-Hodgkin lymphoma, in remission following treatment with allogeneic bone marrow transplantation, quiescent chronic graft-versus-host disease, and squamous cell carcinoma of the skin metastatic to cervical lymph nodes. Medications included atenolol, topical clobetasol, Ditropan (oxybutynin), prophylactic voriconazole, prophylactic valganciclovir, Soriatane (acitretin), and Carac (fluorouracil) cream. The bone marrow was hypocellular without metastatic cancer or myelodysplasia. Neutropenia did not respond to stopping medications that have been associated with neutropenia (valganciclovir, voriconazole and Soriatane) or treatment with antibiotics or granulocyte colony stimulating factor. Blood tests revealed absence of antineutrophil antibodies, normal folate and B12 levels, moderate zinc deficiency and severe Vitamin B6 deficiency. Replacement therapy with oral Vitamin B6 restored blood vitamin levels to the normal range and corrected the neutropenia. Her cervical adenopathy regressed clinically and became negative on scintography following Vitamin B6 therapy and normalization of the blood neutrophil count. Conclusion Severe pyridoxine deficiency can lead to neutropenia. Screening for Vitamin B6 deficiency, along with folate and Vitamin B12 levels, is recommended in patients with refractory neutropenia, especially those with possible malabsorption syndromes, or a history of chronic-graft-versus host disease. Severe neutropenia may facilitate progression of squamous cell carcinoma. PMID:21838907

An automated normative-based fluorodeoxyglucose positron emission tomography image-analysis procedure to aid Alzheimer disease diagnosis using statistical parametric mapping and interactive image display

NASA Astrophysics Data System (ADS)

Chen, Kewei; Ge, Xiaolin; Yao, Li; Bandy, Dan; Alexander, Gene E.; Prouty, Anita; Burns, Christine; Zhao, Xiaojie; Wen, Xiaotong; Korn, Ronald; Lawson, Michael; Reiman, Eric M.

2006-03-01

Having approved fluorodeoxyglucose positron emission tomography (FDG PET) for the diagnosis of Alzheimer's disease (AD) in some patients, the Centers for Medicare and Medicaid Services suggested the need to develop and test analysis techniques to optimize diagnostic accuracy. We developed an automated computer package comparing an individual's FDG PET image to those of a group of normal volunteers. The normal control group includes FDG-PET images from 82 cognitively normal subjects, 61.89+/-5.67 years of age, who were characterized demographically, clinically, neuropsychologically, and by their apolipoprotein E genotype (known to be associated with a differential risk for AD). In addition, AD-affected brain regions functionally defined as based on a previous study (Alexander, et al, Am J Psychiatr, 2002) were also incorporated. Our computer package permits the user to optionally select control subjects, matching the individual patient for gender, age, and educational level. It is fully streamlined to require minimal user intervention. With one mouse click, the program runs automatically, normalizing the individual patient image, setting up a design matrix for comparing the single subject to a group of normal controls, performing the statistics, calculating the glucose reduction overlap index of the patient with the AD-affected brain regions, and displaying the findings in reference to the AD regions. In conclusion, the package automatically contrasts a single patient to a normal subject database using sound statistical procedures. With further validation, this computer package could be a valuable tool to assist physicians in decision making and communicating findings with patients and patient families.

Maternal OGTT Glucose Levels at 26–30 Gestational Weeks with Offspring Growth and Development in Early Infancy

PubMed Central

Liu, Gongshu; Li, Nan; Sun, Shurong; Wen, Jing; Lyu, Fengjun; Gao, Wen; Li, Lili; Chen, Fang; Baccarelli, Andrea A.; Hou, Lifang

2014-01-01

Aims. We aim to evaluate the association of maternal gestational oral glucose tolerance test (OGTT) glucose concentrations with anthropometry in the offspring from birth to 12 months in Tianjin, China. Methods. A total of 27,157 pregnant women underwent OGTT during 26–30 weeks gestation, and their children had body weight/length measured from birth to 12 months old. Results. Maternal OGTT glucose concentrations at 26–30 gestational weeks were positively associated with Z-scores for birth length-for-gestational age and birth weight-for-length. Compared with infants born to mothers with normal glucose tolerance, infants born to mothers with gestational diabetes mellitus (impaired glucose tolerance/new diabetes) had higher mean values of Z-scores for birth length-for-gestational age (0.07/0.23; normal group −0.08) and birth weight-for-length (0.27/0.57; normal group −0.001), smaller changes in mean values of Z-scores for length-for-age (0.75/0.62; normal group 0.94) and weight-for-length (0.18/−0.17; normal group 0.37) from birth to month 3, and bigger changes in mean values in Z-scores for weight-for-length (0.07/0.12; normal group 0.02) from month 9 to 12. Conclusions. Abnormal maternal glucose tolerance during pregnancy was associated with higher birth weight and birth length, less weight and length gain in the first 3 months of life, and more weight gain in the months 9–12 of life. PMID:24689042

Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010

PubMed Central

Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K.; Kramer, Holly; Rosas, Sylvia E.; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L.

2016-01-01

Objective Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. Methods We analyzed data from the NHANES 1999–2010 for 6918 young adults ages 20–40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Results Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6–12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Conclusion Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease. PMID:27224643

Comparison of the Effects of Lidocaine Prilocaine Cream (EMLA) and Lidocaine Injection on Reduction of Perineal Pain During Perineum Repair in Normal Vaginal Delivery

PubMed Central

Kargar, Roxana; Aghazadeh-Nainie, Afsaneh; Khoddami-Vishteh, Hamid Reza

2016-01-01

Objective: To compare the efficacy of EMLA cream and lidocaine injection to reduce pain during episiotomy repair. Materials and methods: A total of 46 primiparous women with normal pregnancy who referred for normal vaginal delivery and needed episiotomy repair were selected and randomly divided into two groups. For EMLA group, one hour before the estimated time of delivery, 5g of EMLA cream was applied to perinealmediolateral incision, and after the delivery of the fetus and placenta, again 5g of EMLA cream was applied to healthy skin around the episiotomy for repair. In the other group, lidocaine 2% was used before episiotomy and for its repair, too. Results: Only 8 people (19%) were in need of further analgesia. The mean ± SD of pain during repair of episiotomy on the VAS scale in all cases was 4.2 ± 2.3 cm. Most people (97%) were satisfied with their episiotomy repair. Comparing the two groups of EMLA and lidocaine, there was no difference between the two groups in terms of the duration of episiotomy repair, need for further analgesia, pain on the VAS scale, and satisfaction with the repair method. Conclusion: The findings of this study showed that the use of EMLA cream in the site of episiotomy incision in primiparous women can induce a level of analgesia equal to that of lidocaine, and cause a similar level of satisfaction. PMID:27385970

Interaural time discrimination of envelopes carried on high-frequency tones as a function of level and interaural carrier mismatch

PubMed Central

Blanks, Deidra A.; Buss, Emily; Grose, John H.; Fitzpatrick, Douglas C.; Hall, Joseph W.

2009-01-01

Objectives The present study investigated interaural time discrimination for binaurally mismatched carrier frequencies in listeners with normal hearing. One goal of the investigation was to gain insights into binaural hearing in patients with bilateral cochlear implants, where the coding of interaural time differences may be limited by mismatches in the neural populations receiving stimulation on each side. Design Temporal envelopes were manipulated to present low frequency timing cues to high frequency auditory channels. Carrier frequencies near 4 kHz were amplitude modulated at 128 Hz via multiplication with a half-wave rectified sinusoid, and that modulation was either in-phase across ears or delayed to one ear. Detection thresholds for non-zero interaural time differences were measured for a range of stimulus levels and a range of carrier frequency mismatches. Data were also collected under conditions designed to limit cues based on stimulus spectral spread, including masking and truncation of sidebands associated with modulation. Results Listeners with normal hearing can detect interaural time differences in the face of substantial mismatches in carrier frequency across ears. Conclusions The processing of interaural time differences in listeners with normal hearing is likely based on spread of excitation into binaurally matched auditory channels. Sensitivity to interaural time differences in listeners with cochlear implants may depend upon spread of current that results in the stimulation of neural populations that share common tonotopic space bilaterally. PMID:18596646

Expression of the serine/threonine kinase hSGK1 in chronic viral hepatitis.

PubMed

Fillon, Sophie; Klingel, Karin; Wärntges, Simone; Sauter, Martina; Gabrysch, Sabine; Pestel, Sabine; Tanneur, Valerie; Waldegger, Siegfried; Zipfel, Annette; Viebahn, Richard; Häussinger, Dieter; Bröer, Stefan; Kandolf, Reinhard; Lang, Florian

2002-01-01

The human serine/threonine kinase hSGK1 is expressed ubiquitously with highest transcript levels in pancreas and liver. This study has been performed to determine the hSGK1 distribution in normal liver and its putative role in fibrosing liver disease. HSGK1-localization was determined by in situ hybridization, regulation of hSGK1-transcription by Northern blotting, fibronectin synthesis and hSGK1 phosphorylation by Western blotting. In normal liver hSGK1 was mainly transcribed by Kupffer cells. In liver tissue from patients with chronic viral hepatitis, hSGK1 transcript levels were excessively high in numerous activated Kupffer cells and inflammatory cells localized within fibrous septum formations. HSGK1 transcripts were also detected in activated hepatic stellate cells. Accordingly, Western blotting revealed that tissue from fibrotic liver expresses excessive hSGK1 protein as compared to normal liver. TGF-beta1 (2 ng/ml) increases hSGK1 transcription in both human U937 macro-phages and HepG2 hepatoma cells. H(2)O(2) (0.3 mM) activated hSGK1 and increased fibronectin formation in HepG2 cells overexpressing hSGK1 but not in HepG2 cells expressing the inactive mutant hSGK1(K127R). In conclusion hSGK1 is upregulated by TGF-beta1 during hepatitis and may contribute to enhanced matrix formation during fibrosing liver disease. Copyright 2002 S. Karger AG, Basel

Comparison of Gated Audiovisual Speech Identification in Elderly Hearing Aid Users and Elderly Normal-Hearing Individuals

PubMed Central

Lidestam, Björn; Rönnberg, Jerker

2016-01-01

The present study compared elderly hearing aid (EHA) users (n = 20) with elderly normal-hearing (ENH) listeners (n = 20) in terms of isolation points (IPs, the shortest time required for correct identification of a speech stimulus) and accuracy of audiovisual gated speech stimuli (consonants, words, and final words in highly and less predictable sentences) presented in silence. In addition, we compared the IPs of audiovisual speech stimuli from the present study with auditory ones extracted from a previous study, to determine the impact of the addition of visual cues. Both participant groups achieved ceiling levels in terms of accuracy in the audiovisual identification of gated speech stimuli; however, the EHA group needed longer IPs for the audiovisual identification of consonants and words. The benefit of adding visual cues to auditory speech stimuli was more evident in the EHA group, as audiovisual presentation significantly shortened the IPs for consonants, words, and final words in less predictable sentences; in the ENH group, audiovisual presentation only shortened the IPs for consonants and words. In conclusion, although the audiovisual benefit was greater for EHA group, this group had inferior performance compared with the ENH group in terms of IPs when supportive semantic context was lacking. Consequently, EHA users needed the initial part of the audiovisual speech signal to be longer than did their counterparts with normal hearing to reach the same level of accuracy in the absence of a semantic context. PMID:27317667

Chromium picolinate inhibits resistin secretion in insulin-resistant 3T3-L1 adipocytes via activation of amp-activated protein kinase.

PubMed

Wang, Yi-Qun; Dong, Yi; Yao, Ming-Hui

2009-08-01

1. Chromium picolinate (CrPic) has been recommended as an alternative therapeutic regimen for Type 2 diabetes mellitus (T2DM). However, the molecular mechanism underlying the action of CrPic is poorly understood. 2. Using normal and insulin-resistant 3T3-L1 adipocytes, we examined the effects of CrPic on the gene transcription and secretion of adiponectin and resistin. In addition, using immunoblotting, ELISA and real-time reverse transcription-polymerase chain reaction (RT-PCR), we investigated the effects of 10 nmol/L CrPic for 24 h on AMP-activated protein kinase (AMPK) to determine whether this pathway contributed to the regulation of adiponectin and resistin expression and secretion. 3. Chromium picolinate did not modulate the expression of adiponectin and resistin; however, it did significantly inhibit the secretion of resistin, but not adiponectin, by normal and insulin-resistant 3T3-L1 adipocytes in vitro. Furthermore, although CrPic markedly elevated levels of phosphorylated AMPK and acetyl CoA carboxylase in 3T3-L1 adipocytes, it had no effect on the levels of AMPK alpha-1 and alpha-2 mRNA transcripts. Importantly, inhibition of AMPK by 2 h pretreatment of cells with 20 micromol/L compound C completely abolished the CrPic-induced suppression of resistin secretion. 4. In conclusion, the data suggest that CrPic inhibits resistin secretion via activation of AMPK in normal and insulin-resistant 3T3-L1 adipocytes.

Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later

PubMed Central

Fagan, Anne M.; Grant, Elizabeth A.; Hassenstab, Jason; Moulder, Krista L.; Maue Dreyfus, Denise; Sutphen, Courtney L.; Benzinger, Tammie L.S.; Mintun, Mark A.; Holtzman, David M.; Morris, John C.

2013-01-01

Objectives: We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (Aβ42, tau, ptau181, tau/Aβ42, ptau181/Aβ42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years. Methods: Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants with amyloid imaging and CSF collection within 1 year of a clinical assessment indicating normal cognition were eligible. Cox proportional hazards models tested whether the individual biomarkers were related to time to incident cognitive impairment. “Expanded” models were developed using the biomarkers and participant demographic variables. The predictive values of the models were compared. Results: Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years. No differences in predictive value were found between the individual biomarkers (p > 0.074), nor did we find differences between the expanded biomarker models (p > 0.312). Each expanded model better predicted incident cognitive impairment than the model containing the biomarker alone (p < 0.005). Conclusions: Our results indicate that all AD biomarkers studied here predicted incident cognitive impairment, and support the hypothesis that biomarkers signal underlying AD pathology at least several years before the appearance of dementia symptoms. PMID:23576620

Impact of taurine depletion on glucose control and insulin secretion in mice.

PubMed

Ito, Takashi; Yoshikawa, Natsumi; Ito, Hiromi; Schaffer, Stephen W

2015-09-01

Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Effects of Aqueous Extract of Three Cultivars of Banana (Musa acuminata) Fruit Peel on Kidney and Liver Function Indices in Wistar Rats.

PubMed

Edenta, Chidi; Okoduwa, Stanley I R; Okpe, Oche

2017-10-23

Background: Musa acuminata fruit peels are used in the northern part of Nigeria for the treatment of hypertension and other cardiovascular related diseases. The effects of aqueous extracts of ripped fruit peel of three cultivars of Musa acuminata ( Saro, Ominni and Oranta ) on the hepatic and renal parameters of normal rats were examined. Methods: Fruit peel aqueous extracts (FPAE) of the 3 cultivars of Bananas (100 mg/kg b.w.) were administered by oral intubation (that is through esophageal cannula) to normal rats (140-180 g) for a period of 28 days. Blood samples were collected for determination of plasma aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase ALK-P), total protein, albumin, creatinine as well as urea. Results: From the results obtained, there were no significant ( p < 0.05) changes in the ALK-P, AST, ALT, total protein and albumin among the experimental rats administered FPAE of the 3 cultivars of Musa acuminata when compared with the normal control group. There was a significant ( p < 0.05) increase in the level of serum creatinine (in mg/dL) (1.53 ± 0.23) when compared to the normal control (0.72 ± 0.15), Ominni (0.92 ± 0.39) and Oranta (0.74 ± 0.22). Similarly, there was a significant ( p < 0.05) increase in the level of serum urea (in mg/dL) of Saro (41.56 ± 4.68) when compared to the normal control (26.05 ± 0.73), Ommini (28.44 ± 2.43) and Oranta (26.10 ± 2.94). Conclusion: The findings reveal the Saro cultivar of Musa acuminata to be nephrotoxic and not a good potential drug candidate among the cultivars studied hence should be discouraged in the treatment of hypertension and other cardiovascular related diseases.

Effects of Aqueous Extract of Three Cultivars of Banana (Musa acuminata) Fruit Peel on Kidney and Liver Function Indices in Wistar Rats

PubMed Central

Edenta, Chidi; Okpe, Oche

2017-01-01

Background: Musa acuminata fruit peels are used in the northern part of Nigeria for the treatment of hypertension and other cardiovascular related diseases. The effects of aqueous extracts of ripped fruit peel of three cultivars of Musa acuminata (Saro, Ominni and Oranta) on the hepatic and renal parameters of normal rats were examined. Methods: Fruit peel aqueous extracts (FPAE) of the 3 cultivars of Bananas (100 mg/kg b.w.) were administered by oral intubation (that is through esophageal cannula) to normal rats (140–180 g) for a period of 28 days. Blood samples were collected for determination of plasma aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase ALK-P), total protein, albumin, creatinine as well as urea. Results: From the results obtained, there were no significant (p < 0.05) changes in the ALK-P, AST, ALT, total protein and albumin among the experimental rats administered FPAE of the 3 cultivars of Musa acuminata when compared with the normal control group. There was a significant (p < 0.05) increase in the level of serum creatinine (in mg/dL) (1.53 ± 0.23) when compared to the normal control (0.72 ± 0.15), Ominni (0.92 ± 0.39) and Oranta (0.74 ± 0.22). Similarly, there was a significant (p < 0.05) increase in the level of serum urea (in mg/dL) of Saro (41.56 ± 4.68) when compared to the normal control (26.05 ± 0.73), Ommini (28.44 ± 2.43) and Oranta (26.10 ± 2.94). Conclusion: The findings reveal the Saro cultivar of Musa acuminata to be nephrotoxic and not a good potential drug candidate among the cultivars studied hence should be discouraged in the treatment of hypertension and other cardiovascular related diseases. PMID:29065553

Use of alternative and complementary therapies in labor and delivery care: a cross-sectional study of midwives’ training in Catalan hospitals accredited as centers for normal birth

PubMed Central

2013-01-01

Background The use of complementary and alternative medicine (CAM) and complementary and alternative therapies (CAT) during pregnancy is increasing. Scientific evidence for CAM and CAT in the field of obstetrics mainly covers pain relief in labor. Midwives are responsible for labor and delivery care: hence, their knowledge of CAM and CAT is important. The aims of this study are to describe the professional profile of midwives who provide care for natural childbirth in Catalan hospitals accredited as centers for normal birth, to assess midwives’ level of training in CAT and their use of these therapies, and to identify specific resources for CAT in labor wards. Methods A descriptive, cross-sectional, quantitative method was used to assess the level of training and use of CAT by midwives working at 28 hospitals in Catalonia, Spain, accredited as public normal birth centers. Results Just under a third of midwives (30.4%) trained in CAT after completion of basic training. They trained in an average of 5.97 therapies (SD 3.56). The number of CAT in which the midwives were trained correlated negatively with age (r = - 0.284; p < 0.001) and with their time working at the hospital in years (r = - 0.136; p = 0.036). Midwives trained in CAT considered that the following therapies were useful or very useful for pain relief during labor and delivery: relaxation techniques (64.3%), hydrotherapy (84.8%) and the application of compresses to the perineum (75.9%). The availability of resources for providing CAT during normal birth care varied widely from center to center. Conclusions Age may influence attitudes towards training. It is important to increase the number of midwives trained in CAM for pain relief during childbirth, in order to promote the use of CAT and ensure efficiency and safety. CAT resources at accredited hospitals providing normal childbirth care should also be standardized. PMID:24238197

Aberrant Expression of the Cell Polarity Regulator aPKCλ/ι is Associated With Disease Progression in Cervical Intraepithelial Neoplasia (CIN): A Possible Marker for Predicting CIN Prognosis.

PubMed

Mizushima, Taichi; Asai-Sato, Mikiko; Akimoto, Kazunori; Nagashima, Yoji; Taguri, Masataka; Sasaki, Kazunori; Nakaya, Masa-aki; Asano, Ryoko; Tokinaga, Aya; Kiyono, Tohru; Hirahara, Fumiki; Ohno, Shigeo; Miyagi, Etsuko

2016-03-01

Atypical protein kinase C λ/ι (aPKCλ/ι) is a regulator of epithelial cellular polarity. It is also overexpressed in several cancers and functions in cell proliferation and invasion. Therefore, we hypothesized that aPKCλ/ι may be involved in development and progression of cervical intraepithelial neoplasia (CIN), the precancerous disease of cervical cancer induced by human papillomavirus. To do this, we investigated the relationship between aPKCλ/ι expression and CIN. aPKCλ/ι expression level and subcellular localization were assessed in 192 CIN biopsy samples and 13 normal epithelial samples using immunohistochemistry. aPKCλ/ι overexpression (normal epithelium, 7.7%; CIN1, 41.7%; CIN2/3, 76.4%) and aPKCλ/ι nuclear localization (normal epithelium, 0.0%; CIN1, 36.9%; CIN2/3, 78.7%) were higher in CIN samples than normal samples (P<0.05), suggesting that CIN grade is related to aPKCλ/ι overexpression and nuclear localization. Then, 140 CIN cases were retrospectively analyzed for 4-yr cumulative disease progression and regression rates using the Cox proportional hazards model. CIN1 cases with aPKCλ/ι overexpression or aPKCλ/ι nuclear localization had a higher progression rate than CIN1 cases with normal aPKCλ/ι expression levels or cytoplasmic localization (62.5% vs. 9.7% and 63.1% vs. 9.4%, respectively; P<0.001). Multivariate analysis indicated that human papillomavirus types 16 and 18, aPKCλ/ι overexpression (hazard ratio=4.26; 95% confidence interval, 1.50-12.1; P=0.007), and aPKCλ/ι nuclear localization (hazard ratio=3.59; 95% confidence interval, 1.24-10.4; P=0.019) were independent risk factors for CIN1 progression. In conclusion, aPKCλ/ι could be useful for the therapeutic management of patients with CIN, particularly those with non-human papillomavirus 16/18 types.

Effect of high pressurization versus normal pressurization on changes in intraocular pressure immediately after clear corneal cataract surgery.

PubMed

Hayashi, Ken; Yoshida, Motoaki; Manabe, Shin-Ichi; Yoshimura, Koichi

2014-01-01

To compare changes in intraocular pressure (IOP) immediately after clear corneal incision (CCI) cataract surgery between eyes in which IOP was adjusted to a high or normal range at the conclusion of surgery. Hayashi Eye Hospital, Fukuoka, Japan. Comparative case series. Either eye of patients scheduled for phacoemulsification was randomized to 1 of 2 groups as follows: eyes that were to be adjusted to (1) high IOP (22 to 40 mm Hg) or (2) normal IOP (10 to 21 mm Hg). The IOP was measured using a rebound tonometer preoperatively; at the conclusion of surgery; and 15, 30, 60, 120, and 180 minutes and 24 hours postoperatively. The Seidel test and anterior segment optical coherence tomography (AS-OCT) were performed. The mean IOP at the conclusion of surgery was 31.3 mm Hg in the high IOP group and 17.1 mm Hg in the normal IOP group. The IOP decreased to approximately 15 mm Hg by 15 minutes and did not change until 60 minutes in either group. The mean IOP did not differ significantly between groups throughout the observation period (P ≥.0634). Hypotony of 5 mm Hg or less was not detected in any eye. The Seidel test was negative and based on AS-OCT, the wound was closed at 60 minutes in all eyes. After adjusting IOP to a high or normal range, the IOP normalized within 15 minutes postoperatively and was stable for 24 hours. The wound was closed within 60 minutes postoperatively. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

CXCR6 promotes tumor cell proliferation and metastasis in osteosarcoma through the Akt pathway.

PubMed

Ma, Yunsheng; Xu, Xin; Luo, Mei

2017-01-01

Chemokine (C-X-C motif) receptor 6 (CXCR6) is up-regulated in many malignancies, indicating that CXCR6 plays an important role in tumor progression. However, the expression and function of CXCR6 in osteosarcoma (OS) remains unclear. This study aimed to explore the expression levels and function of CXCR6 in OS tissues and osteosarcoma cell lines MG-63, HOS and U2OS. The protein expression levels of CXCR6 in OS patient tissues and three osteosarcoma cell lines MG-63, HOS and U2OS were assessed. CXCR6-overexpression MG-63 cell lines were established and then the proliferation, invasion and the epithelial-mesenchymal transition (EMT) in those cells were assessed. CXCR6 mRNA levels in OS tissues were significantly higher than those in normal bone tissues. Consistently, both of the mRNA and protein levels of CXCR6 in OS cell lines MG-63, HOS and U2OS were higher than those in normal bone cells hFOB1.19. CXCR6 overexpression not only promoted cell proliferation, invasion and EMT, but also enhanced the phosphorylation of Akt in MG-63 cells. After inhibition of Akt-phosphorylation by Akt inhibitor, LY2940023, CXCR6-induced cell proliferation and invasion were dramatically attenuated. In conclusion, the present study demonstrated that CXCR6 enhances OS cell proliferation and invasion through the Akt pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

A rabbit vocal fold laser scarring model for testing lamina propria tissue engineering therapies

PubMed Central

Mau, Ted; Du, Mindy; Xu, Chet C.

2015-01-01

Objectives/Hypothesis To develop a vocal fold scarring model using an ablative laser in the rabbit as a platform for testing bioengineered therapies for missing or damaged lamina propria. Study Design Prospective controlled animal study. Methods An optimal laser energy level was first determined by assessing the depths of vocal fold injury created by a Holmium:YAG laser at various energy levels on fresh cadaveric rabbit larynges. The selected energy level was then used to create controlled unilateral injuries in vocal folds of New Zealand white rabbits, with the contralateral folds serving as uninjured controls. After 4 weeks, the larynges were harvested and subjected to excised-larynx phonation with high-speed imaging and immunohistochemical staining for collagen types I and III, elastin, and hyaluronic acid (HA) with quantitative histological analysis. Results 1.8 joules produced full-thickness injury of the lamina propria without extensive muscle injury. After 4 weeks, the injured vocal folds vibrated with reduced amplitude (P = 0.036) in excised-larynx phonation compared to normal vocal folds. The injured vocal folds contained a higher relative density of collagen type I (P = 0.004), higher elastin (P = 0.022), and lower HA (P = 0.030) compared to normal controls. Collagen type III was unchanged. Conclusions With its potential for higher precision of injury, this laser vocal fold scarring model may serve as an alternative to scarring produced by cold instruments for studying the effects of vocal fold lamina propria bioengineered therapies. Level of Evidence N/A. PMID:24715695

Restricted cell elongation in Arabidopsis hypocotyls is associated with a reduced average pectin esterification level

PubMed Central

Derbyshire, Paul; McCann, Maureen C; Roberts, Keith

2007-01-01

Background Cell elongation is mainly limited by the extensibility of the cell wall. Dicotyledonous primary (growing) cell walls contain cellulose, xyloglucan, pectin and proteins, but little is known about how each polymer class contributes to the cell wall mechanical properties that control extensibility. Results We present evidence that the degree of pectin methyl-esterification (DE%) limits cell growth, and that a minimum level of about 60% DE is required for normal cell elongation in Arabidopsis hypocotyls. When the average DE% falls below this level, as in two gibberellic acid (GA) mutants ga1-3 and gai, and plants expressing pectin methyl-esterase (PME1) from Aspergillus aculeatus, then hypocotyl elongation is reduced. Conclusion Low average levels of pectin DE% are associated with reduced cell elongation, implicating PMEs, the enzymes that regulate DE%, in the cell elongation process and in responses to GA. At high average DE% other components of the cell wall limit GA-induced growth. PMID:17572910

pH and salivary sodium bicarbonate during the administration protocol for methotrexate in children with leukemia.

PubMed

Rojas de Morales, Thais; Navas, Rita; Viera, Ninoska; Alvarez, Carmen Julia; Chaparro, Neira; Griman, Dariana

2007-10-01

To analyze the behavior of pH and sodium bicarbonate (NAHCO3) in the saliva of patients with leukemia during the administration protocol for Methotrexate (Mtx). A controlled clinical essay was carried out on 23 patients between 4 and 18 years of age with high-risk Acute Lymphoblastic Leukemia. Sampling was carried out at To: basal condition; T1: 12 hours after intravenous administration of sodium bicarbonate, before administering Mtx and T2: 3 hours after administering Mtx, the time of maximum concentration. Chiron-Diagnostic 378 equipment was used to determine pH and sodium bicarbonate. The data was interpreted using Analysis of Variance at the 5% significance level. The highest values of sodium bicarbonate were observed at T2, with salivary pH levels remaining within neutrality ranges, diminishing slightly in T1. CONCLUSION. In this study, the dose of sodium bicarbonate considered in the administration protocol of 3 g /m2 Mtx, kept sodium bicarbonate levels in saliva at normal levels and pH neutral.

Targeted delivery of HGF to the skeletal muscle improves glucose homeostasis in diet-induced obese mice.

PubMed

Sanchez-Encinales, Viviana; Cozar-Castellano, Irene; Garcia-Ocaña, Adolfo; Perdomo, Germán

2015-12-01

Hepatocyte growth factor (HGF) is a cytokine that increases glucose transport ex vivo in skeletal muscle. The aim of this work was to decipher the impact of whether conditional overexpression of HGF in vivo could improve glucose homeostasis and insulin sensitivity in mouse skeletal muscle. Following tetracyclin administration, muscle HGF levels were augmented threefold in transgenic mice (SK-HGF) compared to control mice without altering plasma HGF levels. In conditions of normal diet, SK-HGF mice showed no differences in body weight, plasma triglycerides, blood glucose, plasma insulin and glucose tolerance compared to control mice. Importantly, obese SK-HGF mice exhibited improved whole-body glucose tolerance independently of changes in body weight or plasma triglyceride levels compared to control mice. This effect on glucose homeostasis was associated with significantly higher (∼80%) levels of phosphorylated protein kinase B in muscles from SK-HGF mice compared to control mice. In conclusion, muscle expression of HGF counteracts obesity-mediated muscle insulin resistance and improves glucose tolerance in mice.

GESTATIONAL DIABETES MELLITUS SEEMS TO BE ASSOCIATED WITH INFLAMMATION.

PubMed

Aktulay, Ayla; Engin-Ustun, Yaprak; Ozkan, Mehmet Sahin; Erkaya, Salim; Kara, Mustafa; Kaymak, Oktay; Danisman, Nuri

2015-12-01

The aim of this study was to investigate whether gestational diabetes mellitus (GDM) is associated with inflammation by comparing serum levels of human chitinase-3-like pro- tein 1 (YKL-40), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). This case control study included 29 pregnant women with GDM and 29 pregnant women with normal glucose tolerance matched for age (± 2 years) and pre-pregnancy body mass index (± 2 kg/m²). The YKL-40/CHI3L1 levels were measured, and NLR and PLR investigated. There were no statisti- cally significant differences in maternal age, gestational age, gravidity and parity. Higher YKL-40 levels were recorded in pregnant women with GDM compared to control subjects (203 (65-300) ng/ mL vs. 159.2 (14-290) ng/mL, p = 0.007). NLR and PLR were significantly higher in GDM com- pared with control group. In conclusion, GDM is associated with high levels of YKL-40, NLR and PLR, which indicate inflammatory status.

Alterations in Protein Expression in Tree Shrew Sclera during Development of Lens-Induced Myopia and Recovery

PubMed Central

Norton, Thomas T.

2012-01-01

Purpose. During the development of, and recovery from, negative lens-induced myopia there is regulated remodeling of the scleral extracellular matrix (ECM) that controls the extensibility of the sclera. Difference gel electrophoresis (DIGE) was used to identify and categorize proteins whose levels are altered in this process. Methods. Two groups of five tree shrews started monocular lens wear 24 days after eye opening (days of visual experience [VE]). The lens-induced myopia (LIM) group wore a −5 D lens for 4 days. The recovery (REC) group wore a −5 D lens for 11 days and then recovered for 4 days. Two normal groups (28 and 39 days of VE; n = 5 each) were also examined, age-matched to each of the treatment groups. Refractive and A-scan measures confirmed the effect of the treatments. Scleral proteins were isolated and resolved by DIGE. Proteins that differed in abundance were identified by mass spectrometry. Ingenuity pathway analysis was used to investigate potential biological pathway interactions. Results. During normal development (28–39 days of VE), eight proteins decreased and one protein increased in relative abundance. LIM-treated eyes were myopic and longer than control eyes; LIM-control eyes were slightly myopic compared with 28N eyes, indicating a yoking effect. In both the LIM-treated and the LIM-control eyes, there was a general downregulation from normal of proteins involved in transcription, cell adhesion, and protein synthesis. Additional proteins involved in cell adhesion, actin cytoskeleton, transcriptional regulation, and ECM structural proteins differed in the LIM-treated eyes versus normal but did not differ in the control eyes versus normal. REC-treated eyes were recovering from the induced myopia. REC-control eye refractions were not significantly different from the 39N eyes, and few proteins differed from age-matched normal eyes. The balance of protein expression in the REC-treated eyes, compared with normal eyes and REC-control eyes, shifted toward upregulation or a return to normal levels of proteins involved in cell adhesion, cell division, cytoskeleton, and ECM structural proteins, including upregulation of several cytoskeleton-related proteins not affected during myopia development. Conclusions. The DIGE procedure revealed new proteins whose abundance is altered during myopia development and recovery. Many of these are involved in cell-matrix adhesions, cytoskeleton, and transcriptional regulation and extend our understanding of the remodeling that controls the extensibility of the sclera. Reductions in these proteins during minus lens wear may produce the increased scleral viscoelasticity that results in faster axial elongation. Recovery is not a mirror image of lens-induced myopia—many protein levels, decreased during LIM, returned to normal, or slightly above normal, and additional cytoskeleton proteins were upregulated. However, no single protein or pathway appeared to be responsible for the scleral changes during myopia development or recovery. PMID:22039233

Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

PubMed

Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

2018-01-01

Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P < 0.05). Genes co-expressed with ANGPTL3 and CFHR5 were significantly enriched in metabolism pathways characterizing liver tissues, including "starch and sucrose metabolism" and "drug metabolism-cytochrome P450". Conclusions: For primary CRC with liver metastasis, both the liver metastases and corresponding primary colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

Visualization of CD44 and CD133 in Normal Pancreas and Pancreatic Ductal Adenocarcinomas

PubMed Central

Immervoll, Heike; Hoem, Dag; Steffensen, Ole Johnny; Miletic, Hrvoje; Molven, Anders

2011-01-01

Tumor-initiating cells of pancreatic ductal adenocarcinoma (PDAC) have been isolated based on expression of either CD133 or CD44. The authors aimed to visualize pancreatic cells simultaneously expressing both these cell surface markers by employing the same antibodies commonly used in cell-sorting studies. Normal and diseased pancreatic tissue, including 51 PDAC cases, were analyzed. CD44 and CD133 expression was determined by immunohistochemical double staining on formalin-fixed material and subcellular protein distribution evaluated by immunofluorescence/confocal microscopy. In the normal pancreas, CD44 and CD133 were coexpressed in the centroacinar regions but in non-overlapping subcellular compartments. As expected, CD44 was found mainly basolaterally, whereas CD133 was present on the apical/endoluminal membrane. This was also the case in chronically inflamed/atrophic pancreatic tissue and in PDAC. In some malignant ducts, CD44 was found at the apical cell membrane adjacent to but never overlapping with CD133 expression. CD44 level was significantly associated with the patient’s lymph node status. In conclusion, a CD44+/CD133+ cell population does exist in the normal and neoplastic pancreas. The preferentially centroacinar localization of the doubly positive cells in the normal parenchyma suggests that this population could be of particular interest in attempts to identify tumor-initiating cells in PDAC. This article contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. PMID:21411814

Expression of metalloprotease insulin-degrading enzyme (insulysin) in normal and malignant human tissues

PubMed Central

Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

2013-01-01

Background Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and in breast cancer tissue (Radulescu et al., Int J Oncol 30:73; 2007). Materials and Methods Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Results Applying the four IDE-directed antibodies, we demonstrate IDE expression at the protein level, both by means of immunoblotting and immunocytochemistry, in all of the tumor cell lines analyzed. Besides, IDE protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in all of the cell lines and tissues assessed. Conclusions We performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells and thus extend knowledge about cellular and tissue distribution of IDE, an enzyme which so far has mainly been studied in connection with Alzheimer’s disease and diabetes but not in cancer. PMID:18813847

Serum Antioxidant Status in Patients with Systemic Sclerosis

PubMed Central

Hassan, Iffat; Sajad, Peerzada; Majid, Sabiya; Hassan, Tehseen

2013-01-01

Background: Vascular endothelial dysfunction is a central event in pathogenesis of a variety of human diseases. Systemic sclerosis is one of such diseases. The oxidative stress and depletion of antioxidants in the serum is believed to be one of the factors in causing this dysfunction. Aims: The aim of this case control study was to compare the levels of antioxidants in the serum of patients with systemic sclerosis and the normal age and sex matched controls. Materials and Methods: Our study consisted of 16 successively admitted patients with systemic sclerosis and 16 healthy, age and sex matched controls. The age group of patient's ranged between 25 and 55 years. The duration of the disease in patients ranged from 1 to 8 years. The serum of patients and controls were assayed for the levels of antioxidants (GSH, NO, MDA, SOD and GPX) by spectrophotometry. The statistical method of analysis used was the one sample t-test. Results: The median levels of antioxidants in the control patients were: SOD-4.14 units/ml; GSH-4.76 units/ml; NO-5.58 nmol/l; MDA-0.53 nmol/l and GPX-49 μmol/l. The levels of NO, GSH and SOD were decreased in these patients with a significant P value (<0.001) whereas the levels of GPX and MDA were normal to increased with a significant P value. Conclusion: The depletion of antioxidants and oxidative stress in serum might be responsible for the vascular dysfunction and other hallmark manifestations of systemic sclerosis. Therefore micronutrient antioxidant supplements may be of therapeutic value. PMID:23723482

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature.

PubMed

Hu, Fang-Ke; Yuan, Fang; Jiang, Cheng-Ying; Lv, Da-Wei; Mao, Bei-Bei; Zhang, Qiang; Yuan, Zeng-Qiang; Wang, Yan

2011-11-01

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Usefulness of Serum Triiodothyronine (T3) to Predict Outcomes in Patients Hospitalized With Acute Heart Failure.

PubMed

Rothberger, Gary D; Gadhvi, Sonya; Michelakis, Nickolaos; Kumar, Amit; Calixte, Rose; Shapiro, Lawrence E

2017-02-15

Thyroid hormone plays an important role in cardiac function. Low levels of serum triiodothyronine (T 3 ) due to nonthyroidal illness syndrome may have adverse effects in heart failure (HF). This study was designed to assess the ability of T 3 to predict in-hospital outcomes in patients with acute HF. In total, 137 patients without thyroid disease or treatment with drugs which affect TH levels, who were hospitalized with acute HF were prospectively enrolled and studied. TH levels were tested upon hospital admission, and outcomes were compared between patients with low (<2.3 pg/ml) and normal (≥2.3 pg/ml) free T 3 levels as well as between those with low (<0.6 ng/ml) and normal (≥0.6 ng/ml) total T 3 levels. Low free T 3 correlated with an increased length of stay in the hospital (median 11 vs 7 days, p <0.001) and higher rates of intensive care unit admission (31.8% vs 16.9%, p = 0.047), with a trend toward increased need for invasive mechanical ventilation (9.0% vs 1.4%, p = 0.056). Low total T3 correlated with an increased length of stay in the hospital (median 11 vs 7 days, p <0.001) and increased need for invasive mechanical ventilation (9.8% vs 1.3%, p = 0.045). In conclusion, low T 3 predicts worse hospital outcomes in patients with acute HF and can be useful in the risk stratification of these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

The Prognostic Value of Epithelial Membrane Protein 1 (EMP-1) in Patients with Laryngeal Carcinoma

PubMed Central

Liu, Chang; Wei, Xiaojun; Li, Feng; Wang, Li; Ruan, Xinjian; Jia, Jia; Zhang, Xia

2017-01-01

Background In the present study, we aimed to investigate the prognostic value of epithelial membrane protein 1 (EMP-1) gene in patients diagnosed with laryngeal carcinoma (LC). Material/Methods Patients who were pathologically diagnosed with LC were enrolled in the present study. The expression levels of EMP-1 in tumor tissues and corresponding normal tissues collected from the LC patients were detected by semi-reverse transcriptase polymerase chain reaction (semi-RT-PCR). Chi-square analysis was used to evaluate the relationship between EMP-1 expression level and clinical characteristics. Survival analysis for the study population was analyzed by Kaplan-Meier method with log rank test. Additionally, Cox regression model was applied to evaluate the prognostic value of EMP-1 in LC patients. Results 106 LC patients, including 55 men and 51 women, were enrolled in the present study. Semi-RT-PCR demonstrated that the expression level of EMP-1 was decreased in tumor tissues, compared with adjacent normal tissues (p<0.001). Moreover, the level was significantly associated with lymph node metastasis, histological grade, and clinical stage (p<0.05 for all). In addition, low levels of EMP-1 was significantly correlated with poor survival rate (log rank test, p=0.020). Cox regression analysis indicated that EMP-1 was an independent marker for LC prognosis (HR=2.755, 95% CI=1.123–6.760, p=0.027). Conclusions The abnormal expression of EMP-1 may be associated with progression of LC and the gene may act as a prognostic marker for LC. PMID:28779068

The Prognostic Value of Epithelial Membrane Protein 1 (EMP-1) in Patients with Laryngeal Carcinoma.

PubMed

Liu, Chang; Wei, Xiaojun; Li, Feng; Wang, Li; Ruan, Xinjian; Jia, Jia; Zhang, Xia

2017-08-05

BACKGROUND In the present study, we aimed to investigate the prognostic value of epithelial membrane protein 1 (EMP-1) gene in patients diagnosed with laryngeal carcinoma (LC). MATERIAL AND METHODS Patients who were pathologically diagnosed with LC were enrolled in the present study. The expression levels of EMP-1 in tumor tissues and corresponding normal tissues collected from the LC patients were detected by semi-reverse transcriptase polymerase chain reaction (semi-RT-PCR). Chi-square analysis was used to evaluate the relationship between EMP-1 expression level and clinical characteristics. Survival analysis for the study population was analyzed by Kaplan-Meier method with log rank test. Additionally, Cox regression model was applied to evaluate the prognostic value of EMP-1 in LC patients. RESULTS 106 LC patients, including 55 men and 51 women, were enrolled in the present study. Semi-RT-PCR demonstrated that the expression level of EMP-1 was decreased in tumor tissues, compared with adjacent normal tissues (p<0.001). Moreover, the level was significantly associated with lymph node metastasis, histological grade, and clinical stage (p<0.05 for all). In addition, low levels of EMP-1 was significantly correlated with poor survival rate (log rank test, p=0.020). Cox regression analysis indicated that EMP-1 was an independent marker for LC prognosis (HR=2.755, 95% CI=1.123-6.760, p=0.027). CONCLUSIONS The abnormal expression of EMP-1 may be associated with progression of LC and the gene may act as a prognostic marker for LC.

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats

PubMed Central

Sathya, S.; Kokilavani, R.; Gurusamy, K.

2008-01-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level. PMID:22557305

Short children with familial short stature show enhancement of somatotroph secretion but normal IGF-I levels.

PubMed

Bellone, S; Corneli, G; Bellone, J; Baffoni, C; Rovere, S; de Sanctis, C; Bona, G; Ghigo, E; Aimaretti, G

2002-05-01

The aim of the present study was to evaluate the GH status in children with familial, idiopathic short stature (FSS). To this goal we evaluated the GH response to GHRH (1 microg/kg iv) + arginine (ARG) (0.5 g/kg iv) test which is one of the most potent and reproducible provocative tests of somatotroph secretion, in 67 children with FSS [50 boys and 17 girls, age 10.8+/-0.4 yr, pubertal stages I-III, height between -3.6 and -1.6 standard deviation score (SDS), target height <10 degrees centile, normality of both spontaneous and stimulated GH secretion as well as of IGF-I levels]. The results in FSS were compared with those in groups of children of normal height (NHC) (42 NHC, 35 boys and 7 girls, age 12.0+/-0.5 yr, pubertal stages I-III, height between -1.3 and 1.4 SDS, height velocity standard deviation score (HVSDS)>25 degrees centile, GH peak >20 microg/l after GHRH+ARG test, mean GH concentration [mGHc]>3 microg/l) and children with organic GH deficiency (GHD) (38 GHD, 29 boys and 9 girls, age 11.2+/-3.7 yr, pubertal stages I-III, height between -5.7 and -1.3 SDS, GH peak <20 microg/l after GHRH +ARG test, mGHc <3 mg/l). Basal IGF-I levels and mGHc were also evaluated in each group over 8 nocturnal hours. IGF-I levels in FSS (209.2+/-15.6 microg/l) were similar to those in NHC (237.2+/-17.2 microg/l) and both were higher (p<0.0001) than those in GHD (72.0+/-4.0 microg/l). The GH response to GHRH +ARG test in FSS (peak: 66.4+/-5.6 microg/l) was very marked and higher (p<0.01) than that in NHC (53.3+/-4.5 microg/l) which, in turn, was higher (p<0.01) than in GHD (8.2+/-0.8 microg/l). Similarly, the mGHc in FSS was higher than in NHC (6.7+/-0.5 microg/l vs 5.1+/-0.7 microg/l, p<0.05) which, in turn, was higher than in GHD (1.5+/-0.2 microg/l, p<0.0001). In conclusion, our present study demonstrates that short children with FSS show enhancement of both basal and stimulated GH secretion but normal IGF-I levels. These findings suggest that increased somatotroph function would be devoted to maintain normal IGF-I levels thus reflecting a slight impairment of peripheral GH sensitivity in FSS.

An Evaluation of Deficits in Semantic Cuing, Proactive and Retroactive Interference as Early Features of Alzheimer’s disease

PubMed Central

Crocco, Elizabeth; Curiel, Rosie E.; Acevedo, Amarilis; Czaja, Sara J.; Loewenstein, David A.

2015-01-01

OBJECTIVE To determine the degree to which susceptibility to different types of semantic interference may reflect the earliest manifestations of early Alzheimer disease (AD) beyond the effects of global memory impairment. METHODS Normal elderly (NE) subjects (n= 47), subjects with amnestic mild cognitive impairment (aMCI: n=34) and 40 subjects with probable AD were evaluated using a unique cued recall paradigm that allowed for an evaluation of both proactive and retroactive interference effects while controlling for global memory impairment (LASSI-L procedure). RESULTS Controlling for overall memory impairment, aMCI subjects had much greater proactive and retroactive interference effects than NE subjects. LASSI-L indices of learning using cued recall evidenced high levels of sensitivity and specificity with an overall correct classification rate of 90%. These provided better discrimination than traditional neuropsychological measures of memory function. CONCLUSION The LASSI-L paradigm is unique and unlike other assessments of memory in that items presented for cued recall are explicitly presented, and semantic interference and cuing effects can be assessed while controlling for initial level of memory impairment. This represents a powerful procedure allowing the participant to serve as his or her own control. The high levels of discrimination between subjects with aMCI and normal cognition that exceeded traditional neuropsychological measures makes the LASSI-L worthy of further research in the detection of early AD. PMID:23768680

The role of urotensin II and atherosclerotic risk factors in patients with slow coronary flow

PubMed Central

Şatıroğlu, Ömer; Emre Durakoğlugil, Murtaza; Çetin, Mustafa; Çiçek, Yüksel; Erdoğan, Turan; Duman, Hakan

2016-01-01

Background Slow coronary flow (SCF) is an angiographic finding characterized with delayed opacification of epicardial coronary arteries without obstructive coronary disease. Urotensin II (UII) is an important vascular peptide, which has an important role in hypertension, coronary artery disease, and vascular remodeling in addition to potent vasoconstrictor effect. Objectives We investigated UII levels, hypertension, and other atherosclerotic risk factors in patients with SCF, a variety of coronary artery disease. Methods We enrolled 14 patients with SCF and 29 subjects with normal coronary arteries without SCF. We compared the UII levels and the atherosclerotic risk factors between patients with SCF and control subjects with normal coronary flow. Results UII concentrations were significantly higher in patients with SCF compared to controls (711.0 ± 19.4 vs. 701.5 ± 27.2 ng/mL, p = 0.006). We detected a positive correlation between SCF and age (r = 0.476, p = 0.001), BMI (r = 0.404, p = .002), UII concentrations (r = 0.422, p = 0.006), and hypertension (r = 0.594, p = 0.001). Conclusion We identified increased UII levels in patients with SCF. We think that UII concentrations may be informative on SCF pathogenesis due to relationship with inflammation, atherosclerosis, and vascular remodeling. PMID:28180005

Effect of Hemoconcentration on Dural Sinus Computed Tomography Density in a Pediatric Population.

PubMed

Yurttutan, Nursel; Kizildag, Betul; Sarica, Mehmet Akif; Baykara, Murat

2016-10-01

Unenhanced brain computed tomography (CT) is inexpensive, easily available, and the first-choice imaging modality for patients presenting with various neurologic symptoms. Venous thrombosis is not rare in childhood, but diagnosis can be difficult. In some cases, only denser vessels can be used to highlight an issue. The aim of this study was to retrospectively evaluate the relationship between X-ray attenuation and hemoconcentration in a pediatric population. This study enrolled 99 pediatric patients who had been referred radiology department for unenhanced brain CT. Images were retrospectively evaluated for measurement of dural sinus densities from four distinct dural sinus locations. Correlation between mean Hounsfield unit (HU) values and hemoglobin/hematocrit (Hb/Htc) levels, as well as age and gender were further analyzed. There was a strong correlation between mean HU and Hb levels (r = 0.411; standard deviation: 0.001) and also between mean HU and Htc levels (r = 0.393; p < 0.001). According to the results of this study, the mean sinus density and H:H (HU:Htc) values were 44.06 HU and 1.19, respectively, in a normal pediatric group. In conclusion, before deciding between a diagnosis of thrombosis and a determination of normal findings during an evaluation of unenhanced CT in a pediatric population, radiologists should consider complete blood count results as well as H:H ratios. Georg Thieme Verlag KG Stuttgart · New York.

Redox environment in stem and differentiated cells: A quantitative approach.

PubMed

Lyublinskaya, O G; Ivanova, Ju S; Pugovkina, N A; Kozhukharova, I V; Kovaleva, Z V; Shatrova, A N; Aksenov, N D; Zenin, V V; Kaulin, Yu A; Gamaley, I A; Nikolsky, N N

2017-08-01

Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity. However, biochemical normalization of these parameters to cell volume/protein leads to matching of normalized values in stem and differentiated cells and shows that tested in the present study cells (human embryonic stem cells and their fibroblast-like progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar intracellular redox status. Based on these observations, we propose to use ROS concentration averaged over the cell volume instead of ROS level as a measure of intracellular redox balance. We show that attempts to use ROS level for comparative analysis of redox status of morphologically different cells could lead to false conclusions. Methods for the assessment of ROS concentration based on flow cytometry analysis with the use of H 2 DCFDA dye and HyPer, genetically encoded probe for hydrogen peroxide, are discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Nephroprotective Effect of the Leaves of Aloe barbadensis (Aloe Vera) against Toxicity Induced by Diclofenac Sodium in Albino Rabbits

PubMed Central

Iftikhar, A; Hasan, IJ; Sarfraz, M; Jafri, L; Ashraf, MA

2015-01-01

ABSTRACT Background: The present study was designed to evaluate the nephroprotective effect of the leaves of Aloe barbadensis against toxicity induced by diclofenac sodium in albino rabbits. Subjects and Method: Thirty-six healthy albino rabbits were randomly divided into six groups each with six animals. Group 1 served as the untreated control, group 2 was treated only with diclofenac sodium, group 3 with the nephroprotective drug silymarin and groups 4, 5, and 6 were treated with different doses of Aloe barbadensis, ie 200 mg/kg, 400 mg/kg and 600 mg/kg, respectively after being treated with diclofenac sodium. Blood samples were collected after every five days up to fifteen days. Haematological and histopathological parameters were determined by using diagnostic kits. Results: Results of haematological studies showed that use of the powder of Aloe barbadensis normalized the level of different factors eg, white blood cells (WBCs), red blood cells (RBCs), platelet count, packed cell volume (PCV), mean cell volume (MCV) and haemoglobin (Hb) values. Histopathological studies showed that Aloe barbadensis ameliorated pyknotic nuclei in the renal epithelial cells and reduced oxidative stress by increasing the level of catalase and decreasing malondialdehyde (MDA) level. Conclusion: These results have shown that Aloe barbadensis can normalize oxidative stress and can be used as an effective nephroprotective agent against drug-induced nephrotoxicity. PMID:27398602

Heterogeneous Downregulation of Angiotensin II AT1-A and AT1-B Receptors in Arterioles in STZ-Induced Diabetic Rat Kidneys

PubMed Central

Razga, Zsolt; Talapka, Petra; Nyengaard, Jens Randel

2014-01-01

Introduction. The renin granulation of kidney arterioles is enhanced in diabetes despite the fact that the level of angiotensin II in the diabetic kidney is elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in afferent and efferent arteriole's renin-positive and renin-negative smooth muscle cells (SMC) was estimated. Method. Immunohistochemistry at the electron microscopic level was combined with 3D stereological sampling techniques. Results. In diabetes the enhanced downregulation of AT1-B receptors in the renin-positive than in the renin-negative SMCs in both arterioles was resulted: the significant difference in the number of AT1 (AT1-A + AT1-B) receptors between the two types of SMCs in the normal rats was further increased in diabetes and in contrast with the significant difference observed between the afferent and efferent arterioles in the normal animals, there was no such difference in diabetes. Conclusions. The enhanced downregulation of the AT1-B receptors in the renin-negative SMCs in the efferent arterioles demonstrates that the regulation of the glomerular filtration rate by the pre- and postglomerular arterioles is changed in diabetes. The enhanced downregulation of the AT1-B receptors in the renin-positive SMCs in the arterioles may result in an enhanced level of renin granulation in the arterioles. PMID:24587998

Function of the hypothalamic-pituitary-gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases.

PubMed

Somali, Maria; Mpatakoias, Vassilios; Avramides, Avraam; Sakellari, Ioanna; Kaloyannidis, Panayotis; Smias, Christos; Anagnostopoulos, Achilleas; Kourtis, Anargyros; Rousso, David; Panidis, Dimitrios; Vagenakis, Apostolos

2005-07-01

Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic-pituitary-gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2-9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.

Antioxidant and hypolipidemic effects of soymilk fermented via Lactococcus acidophilus MF204.

PubMed

Chen, Jie; Wu, Yan; Yang, Chunmei; Xu, Xuejiao; Meng, Yuecheng

2017-12-13

Previous studies have shown that fermentations can enhance the bioactivity and absorption rate of soybean products. Fermented soybean products can alleviate hyperlipidemia and decrease risks of atherosclerosis and cardiovascular diseases. This study aimed to investigate the effects and mechanisms of soymilk fermented by Lactococcus acidophilus on blood lipids and antioxidant enzyme activities of rats fed with a high fat diet. Sixty rats were randomly assigned to six groups: normal control group (NC), high-fat control group (HFC), positive control group (cholestyramine, PC), Lactococcus acidophilus group (LA), soymilk group (SM), and fermented soymilk group (FSM), respectively. The NC group was fed with a basic diet, while the other groups were fed with a high-fat diet. After the experimental period (6 W), rats were sacrificed by decapitation. Blood and liver were collected to measure the concentrations of lipids and antioxidant enzyme activities. Results demonstrated that fermented soymilk could regulate lipid levels, restore HDL-c and TG to normal levels, and lower the concentrations of LDL-c than hypolipidemic drugs in hyperlipidemia rats. More importantly, fermented soymilk caused significant reduction in arteriosclerosis index and coronary risk index. Fermented soymilk also improved antioxidant capacities of hyperlipidemia rats. The increase of aglycone isoflavones in fermented soymilk could explain the above phenomena. In conclusion, soymilk fermented by Lactococcus acidophilus reduced risks of arteriosclerosis and coronary heart disease by regulating lipid levels and improving the antioxidant capacities of hyperlipidemia rats.

Concurrent auditory perception difficulties in older adults with right hemisphere cerebrovascular accident

PubMed Central

Talebi, Hossein; Moossavi, Abdollah; Faghihzadeh, Soghrat

2014-01-01

Background: Older adults with cerebrovascular accident (CVA) show evidence of auditory and speech perception problems. In present study, it was examined whether these problems are due to impairments of concurrent auditory segregation procedure which is the basic level of auditory scene analysis and auditory organization in auditory scenes with competing sounds. Methods: Concurrent auditory segregation using competing sentence test (CST) and dichotic digits test (DDT) was assessed and compared in 30 male older adults (15 normal and 15 cases with right hemisphere CVA) in the same age groups (60-75 years old). For the CST, participants were presented with target message in one ear and competing message in the other one. The task was to listen to target sentence and repeat back without attention to competing sentence. For the DDT, auditory stimuli were monosyllabic digits presented dichotically and the task was to repeat those. Results: Comparing mean score of CST and DDT between CVA patients with right hemisphere impairment and normal participants showed statistically significant difference (p=0.001 for CST and p<0.0001 for DDT). Conclusion: The present study revealed that abnormal CST and DDT scores of participants with right hemisphere CVA could be related to concurrent segregation difficulties. These findings suggest that low level segregation mechanisms and/or high level attention mechanisms might contribute to the problems. PMID:25679009

Relationship between zinc and the growth and development of young children.

PubMed

Gao, S; Tu, D N; Li, H; Cao, X; Jiang, J X; Shi, Y; Zhou, X Q; You, J B

2015-08-19

The purpose of this study was to evaluate the relationship between zinc and the growth and development of young children. The parents of 8102 young children were surveyed in person by a trained surveyor using structured questionnaires. The hair zinc concentration of the children was determined using an atomic absorption spectrophotometer. The height, weight, sitting height, and head circumference of the children were measured at follow-up visits. There was a positive correlation between hair zinc concentration and adaptive developmental quotient (ADQ; r = 0.3164, P = 0.0272) while no correlation was found between hair zinc concentration and body measurement Z scores or intelligence quotient (IQ). There was a strong positive correlation between hair zinc concentration and weight-for-age Z scores (r = 0.3618, P = 0.0416) and ADQ (r = 0.2761, P = 0.0387) in boys; there was no correlation between hair zinc concentration and body measurement Z scores, IQ, and ADQ in girls. In boys with normal hair zinc levels, ADQ was 9.58 (P = 0.0392), higher than in boys who had zinc-deficient hair. In girls with normal hair zinc levels, ADQ was 2.52 (P = 0.0296), lower than in girls with zinc-deficient hair. In conclusion, there is no significant correlation between hair zinc levels and IQ or Z scores for all body measurements in young children.

Role of emmprin in endometrial cancer

PubMed Central

2012-01-01

Background Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Methods Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. Results The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p < 0.05). The disease-free survival (DFS) and overall survival (OS) rates of patients with high emmprin expression were significantly higher than those of patients with low emmprin expression (DFS: p < 0.001; OS: p < 0.001). Emmprin knockdown by the siRNA led to cell proliferation, migration and invasion through TGF-β, EGF, NF-κB, VEGF, MMP-2, and MMP-9 expression, which in turn resulted in increased levels of E-cadherin and reduced levels of Vimentin and Snail in endometrial cancer. Conclusions The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer. PMID:22640183

Nature of the Renal Concentrating Defect in Sickle Cell Disease*

PubMed Central

Hatch, Fred E.; Culbertson, James W.; Diggs, Lemuel W.

1967-01-01

Free water reabsorption (TcH2O) measured during 10% mannitol diuresis and subsequently during 3% saline diuresis was compared in patients with sickle cell anemia and in normal subjects. During mannitol infusion, TcH2O progressively rose with increasing osmolar clearance (Cosm) and reached a maximal level in both groups studied. During hypertonic saline diuresis, TcH2O progressively rose in the normal subjects and exceeded the maximal levels attained during mannitol diuresis, with no evidence of a maximal TcH2O level appearing. In contrast, none of the saline curves significantly exceeded the mannitol curves in the sickle cell patients but tended to parallel the mannitol curves at comparable rates of solute clearance. Since TcH2O is an index of both solute (sodium) transport from the loop of Henle and solute accumulation in the hypertonic medullary interstitium, tubular sodium handling was examined in both sickle cell patients and control subjects alike. No difference in the tubular transport of sodium could be demonstrated either under conditions of sodium loading or under conditions in which the tubular sodium load was low (water diuresis). These data support the conclusion that the defect in urinary concentration in sickle cell patients is caused by a limitation in maintaining a high concentration of solute in the medullary interstitium, thus limiting the rate of TcH2O from the collecting duct. PMID:6023770

Average ambulatory measures of sound pressure level, fundamental frequency, and vocal dose do not differ between adult females with phonotraumatic lesions and matched control subjects

PubMed Central

Van Stan, Jarrad H.; Mehta, Daryush D.; Zeitels, Steven M.; Burns, James A.; Barbu, Anca M.; Hillman, Robert E.

2015-01-01

Objectives Clinical management of phonotraumatic vocal fold lesions (nodules, polyps) is based largely on assumptions that abnormalities in habitual levels of sound pressure level (SPL), fundamental frequency (f0), and/or amount of voice use play a major role in lesion development and chronic persistence. This study used ambulatory voice monitoring to evaluate if significant differences in voice use exist between patients with phonotraumatic lesions and normal matched controls. Methods Subjects were 70 adult females: 35 with vocal fold nodules or polyps and 35 age-, sex-, and occupation-matched normal individuals. Weeklong summary statistics of voice use were computed from anterior neck surface acceleration recorded using a smartphone-based ambulatory voice monitor. Results Paired t-tests and Kolmogorov-Smirnov tests resulted in no statistically significant differences between patients and matched controls regarding average measures of SPL, f0, vocal dose measures, and voicing/voice rest periods. Paired t-tests comparing f0 variability between the groups resulted in statistically significant differences with moderate effect sizes. Conclusions Individuals with phonotraumatic lesions did not exhibit differences in average ambulatory measures of vocal behavior when compared with matched controls. More refined characterizations of underlying phonatory mechanisms and other potentially contributing causes are warranted to better understand risk factors associated with phonotraumatic lesions. PMID:26024911

Creatine phosphokinase levels in children with severe developmental disturbances.

PubMed

Cohen, D J; Johnson, W; Caparulo, B K; Young, J G

1976-06-01

Serum creatine phosphokinase (CPK) levels were studied in individuals: 40 psychotic children suffering from childhood autism, atypical personality development, and childhood schizophrenia; five children with childhood aphasia; 22 children with severe personality disorders; 29 normal children and normal siblings of psychotic children; and 14 normal parents of psychotic children. Creatine phosphokinase levels from the entire population of adults and children were normally disturbed, and the mean CPK levels for the eight diagnostic groups were within normal limits. Those 22 children with personality disorders had significantly higher CPK levels than the other diagnostic groups. This relatively higher level of CPK may be related to vulnerability to later development of schizophrenic spectrum disorders. There was no apparent relationship between CPK levels and motor activity, nor was there any change in the level of CPK during a trial of psychoactive medication. Creatine phosphokinase levels remained relatively stable on test-retest determination.

The association between the levels of CRP, IL-10, PLA2, Fbg and prognosis in traumatic fracture of lower limb.

PubMed

Jiao, Jing; Wang, Jun-Wen; Xiao, Fei; Huang, Yu-Cheng

2016-11-01

The aim of the present study was to examine changes of sera levels of C-reactive protein (CRP), interleukin-10 (IL-10), phospholipase A2 (PLA2) and fibrinogen β polypeptide chain gene (Fbg) in patients with traumatic fracture of lower limb, and to evaluate their association with prognosis. The changes in sera levels of CRP, IL-10, PLA2 and Fbg were observed at the time of injury, 24 h, and 5 and 7 days after surgery in 90 patients with traumatic fracture of lower limb. In addition, 50 cases, who presented for health examination, were included as the normal controls. The expression of sera levels of CRP, IL-10, PLA2 and Fbg in patients with traumatic fracture of lower limb, was markedly higher than that in the normal controls prior to surgery (P<0.05). The concentration of CRP significantly increased within 24 h after emergency, but decreased gradually as the wound healed, compared to the controls. Pre- and postoperative IL-10 levels increased within 24 h and then decreased gradually. The level of PLA2 in patients before and after surgery was increased, and then decreased gradually. The level of Fbg in patients with trauma was increased after 24 h and then decreased, and increased gradually. The correlation of serum CRP and IL-10 levels (r=0.634, P<0.05), and that of PLA2 and IL-10 levels (r=0.617, P<0.05) were positive. In conclusion, the expression of CRP, IL-10, PLA2 and Fbg levels in traumatic fracture of lower limb markedly increased and was closely associated with prognosis. CRP, IL-10, PLA2 and Fbg levels may therefore serve as useful indexes in determining the progression and prognosis of patients with traumatic fracture of lower limb.

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China

PubMed Central

Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Background and Objective Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Methods Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels(≥14ng/L) and patients with normal hs-cTnT levels (<14ng/L). Results The final analysis involved 84 patients (31 males; mean age, 61.6±12.2years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Conclusion Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies. PMID:26849554

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

PubMed Central

Li, Wen; Li, Zhenshu; Li, Shou; Wang, Xinyan; Wilson, John X.; Huang, Guowei

2018-01-01

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function. PMID:29494536

[Hepatocellular carcinoma arising in the normal liver. A clinical study and long-term prognosis after surgical resection in 12 patients].

PubMed

Fekete, F; Belghiti, J; Flejou, J F; Panis, Y; Molas, G

1990-01-01

Hepatocellular carcinoma mainly affects patients with cirrhosis or with various degrees of fibrosis. From 1979 to 1990, among 87 patients who underwent hepatic resection for non fibrolamellar hepatocellular carcinoma, 12 (14%) had a non fibrolamellar hepatocellular carcinoma developed in a normal liver. There were 8 men and 4 women, aged 29 to 74 years. In 7 patients (58%) hepatocellular carcinoma was associated with clinical manifestations. Serum hepatitis B surface antigen were absent in all patients. Serum alphafetoprotein level was less than 100 ng/ml in 10 (83%), size of the tumor was greater than or equal to 5 cm in 10 (83%) and capsule was present in 10 (83%). Resections included removal of 2 segments or more in 11 (91%). One patient died postoperatively. Actuarial survival rate at 3 and 5 years were respectively 57% and 38%. Intra or extrahepatic recurrence was recognized in 8 (67%), 2 patients were alive respectively 28 and 16 months after treatment of their intrahepatic recurrence (resection in one and intraarterial embolisation in one). In conclusion, our results suggest that aggressive surgical efforts are justified in non fibrolamellar hepatocellular carcinoma arising in normal liver.

Aging enhances serum cytokine response but not task-induced grip strength declines in a rat model of work-related musculoskeletal disorders

PubMed Central

2011-01-01

Background We previously reported early tissue injury, increased serum and tissue inflammatory cytokines and decreased grip in young rats performing a moderate demand repetitive task. The tissue cytokine response was transient, the serum response and decreased grip were still evident by 8 weeks. Thus, here, we examined their levels at 12 weeks in young rats. Since aging is known to enhance serum cytokine levels, we also examined aged rats. Methods Aged and young rats, 14 mo and 2.5 mo of age at onset, respectfully, were trained 15 min/day for 4 weeks, and then performed a high repetition, low force (HRLF) reaching and grasping task for 2 hours/day, for 12 weeks. Serum was assayed for 6 cytokines: IL-1alpha, IL-6, IFN-gamma, TNF-alpha, MIP2, IL-10. Grip strength was assayed, since we have previously shown an inverse correlation between grip strength and serum inflammatory cytokines. Results were compared to naïve (grip), and normal, food-restricted and trained-only controls. Results Serum cytokines were higher overall in aged than young rats, with increases in IL-1alpha, IFN-gamma and IL-6 in aged Trained and 12-week HRLF rats, compared to young Trained and HRLF rats (p < 0.05 and p < 0.001, respectively, each). IL-6 was also increased in aged 12-week HRLF versus aged normal controls (p < 0.05). Serum IFN-gamma and MIP2 levels were also increased in young 6-week HRLF rats, but no cytokines were above baseline levels in young 12-week HRLF rats. Grip strength declined in both young and aged 12-week HRLF rats, compared to naïve and normal controls (p < 0.05 each), but these declines correlated only with IL-6 levels in aged rats (r = -0.39). Conclusion Aging enhanced a serum cytokine response in general, a response that was even greater with repetitive task performance. Grip strength was adversely affected by task performance in both age groups, but was apparently influenced by factors other than serum cytokine levels in young rats. PMID:21447183

Effect of resection depth of early glottic cancer on vocal outcome: An optimized finite element simulation

PubMed Central

Mau, Ted; Palaparthi, Anil; Riede, Tobias; Titze, Ingo R.

2015-01-01

Objectives/Hypothesis To test the hypothesis that subligamental cordectomy produces superior acoustic outcome than subepithelial cordectomy for early (T1-2) glottic cancer that requires complete removal of the superficial lamina propria but does not involve the vocal ligament. Study Design Computer simulation Methods A computational tool for vocal fold surgical planning and simulation (the National Center for Voice and Speech Phonosurgery Optimizer-Simulator) was used to evaluate the acoustic output of alternative vocal fold morphologies. Four morphologies were simulated: normal, subepithelial cordectomy, subligamental cordectomy, and transligamental cordectomy (partial ligament resection). The primary outcome measure was the range of fundamental frequency (F0) and sound pressure level (SPL). A more restricted F0-SPL range was considered less favorable because of reduced acoustic possibilities given the same range of driving subglottic pressure and identical vocal fold posturing. Results Subligamental cordectomy generated solutions covering an F0-SPL range 82% of normal for a rectangular vocal fold. In contrast, transligamental and subepithelial cordectomies produced significantly smaller F0-SPL ranges, 57% and 19% of normal, respectively. Conclusion This study illustrates the use of the Phonosurgery Optimizer-Simulator to test a specific hypothesis regarding the merits of two surgical alternatives. These simulation results provide theoretical support for vocal ligament excision with maximum muscle preservation when superficial lamina propria resection is necessary but the vocal ligament can be spared on oncological grounds. The resection of more tissue may paradoxically allow the eventual recovery of a better speaking voice, assuming glottal width is restored. Application of this conclusion to surgical practice will require confirmatory clinical data. PMID:26010240

Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis

PubMed Central

2012-01-01

Background Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level. Methods Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression. Results SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer. Conclusions The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the plasminogen activator protease cascade warrants further investigation. PMID:23236990

Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog.

PubMed

Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P

2016-10-01

The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog. © 2016 Society for Reproduction and Fertility.

Effect of heavy-ion beam irradiation on the level of serum soluble interleukin-2 receptors in hamster cheek pouch carcinoma model

PubMed Central

AN, XIAOLI; LI, MINGXIN; LI, NA; LIU, BIN; ZHANG, HONG; WANG, JIZENG

2014-01-01

Soluble interleukin-2 receptor (sIL-2R) is a glycoprotein derived from α chain of interleukin 2 receptors of mononuclear as well as T-cell membranes. The aims of this study were to detect the changes of serum soluble interleukin-2 receptor (sIL-2R) levels following heavy-ion beam irradiation in the hamster model with cheek pouch carcinoma, as well as to examine the impact of immune status of the hamster cheek pouch carcinoma model using heavy-ion beam irradiation. sIL-2R serum levels were detected by radioimmunoassay (RIA) in 40 hamsters bearing cheek pouch carcinoma prior to and following exposure to heavy-ion beam irradiation, and 8 normal animals served as the control. The sIL-2R serum level in hamster cheek pouch carcinoma model was significantly increased as compared to the normal control group (P<0.05). Results showed that an increase in the irradiation dose led to a gradual decrease in the sIL-2R serum level. Additionally, a statistical significance was observed compared to the tumor group (P<0.05). In conclusion, alterations in serum sIL-2R expression have an effect on the hamsters cheek pouch carcinoma model subsequent to heavy-ion beam irradiation. An increase in the irradiation dose indicated a decreased tendency in serum sIL-2R content. Detection of serum level changes may lead to an improved understanding of heavy-ion irradiation in vivo immune status, which is crucial for clinical diagnosis and prognosis. It can also provide a sensitive indicator to help estimate the effects of heavy-ion cancer targets. PMID:24748984

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

PubMed

Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

2000-03-01

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

PubMed

Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

2013-01-01

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

[Mild preeclampsia and serum insulin values in the third pregnancy trimester].

PubMed

Martínez-Abundis, E; González-Ortíz, M; Cardona-Muñoz, E G; Hernández-Chávez, A

1998-06-01

The purpose of this investigation was to determine the baseline insulin level in sera during fasting and after an oral glucose load in patients with mild preeclampsia and compare these values with those obtained from pregnant women with normal arterial pressure during the third trimester of their pregnancy. A cross-sectional study was realized in 38 patients with mild preeclamsia and 39 patients with normal arterial pressure values, both groups in their third trimester of pregnancy. We determined baseline arterial pressure, serum glucose and insulin, and the insulin/glucose ratio with at least 6 hours of fasting, and one hour after 50 g of glucose PO. The hypertensive group was under treatment with alfametildopa and/or hidralazine, patients with known coexistent conditions that would alter glucose or insulin levels were not included. The glucose was measured with the glucose oxidase method and the insulin levels by radioimmunoanalysis. The insulin/glucose ratio was obtained as the coefficient of insulin/glucose. Both patient groups had similar ages, number of pregnancies, gestational age and pre-pregnancy body mass index. We found no difference in glucose levels during fasting nor glucose post-load between groups. Insulin fasting levels were lower in the preeclampsia group compared with the normotensive one (7.1 +/- 3.8 vs 10.6 +/- 8.7 microU/mL, p = 0.02), however there was no difference in either group after the glucose load was administered (66.8 +/- 46.5 vs 71.0 +/- 51.9, p = N.S.). The insulin/glucose ratio had the same behavior than insulin. The hypertensive group showed a lower fasting insulin levels compared with the normotensive group. We suggest further research be done on this matter with strict selection criteria in order to emit final conclusions.

Where they live, how they play: Neighborhood greenness and outdoor physical activity among preschoolers

PubMed Central

2011-01-01

Background Emerging empirical evidence suggests exposure to "green" environments may encourage higher levels of physical activity among children. Few studies, however, have explored this association exclusively in pre-school aged children in the United States. We examined whether residing in neighborhoods with higher levels of greenness was associated with higher levels of outdoor physical activity among preschoolers. In addition, we also explored whether outdoor playing behaviors (e.g., active vs. quiet) were influenced by levels of neighborhood greenness independent of demographic and parental support factors. Results Higher levels of neighborhood greenness as measured by the Normalized Difference Vegetation Index (NDVI) was associated with higher levels of outdoor playing time among preschool-aged children in our sample. Specifically, a one unit increase in neighborhood greenness increased a child's outdoor playing time by approximately 3 minutes. A dose-response relationship was observed between increasing levels of parental support for physical activity (e.g., time spent playing with children) and child outdoor physical activity (p < 0.01). Conclusions Consistent with previous studies, neighborhood greenness influences physical activity behavior. However, for preschoolers, parental involvement may be more critical for improving physical activity levels. PMID:22165919

Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance.

PubMed

Guler, Ismail; Himmetoglu, Ozdemir; Turp, Ahmet; Erdem, Ahmet; Erdem, Mehmet; Onan, M Anıl; Taskiran, Cagatay; Taslipinar, Mine Yavuz; Guner, Haldun

2014-06-01

In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

The Relationship between Serum Zinc Level and Heart Failure: A Meta-Analysis

PubMed Central

Yu, Xuefang; Huang, Lei; Zhao, Jinyan; Wang, Zhuoqun; Yao, Wei; Wu, Xianming; Huang, Jingjing

2018-01-01

Zinc is essential for the maintenance of normal cellular structure and functions. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. However, there are conflicting reports on the relationship between serum zinc levels and heart failure (HF). The purpose of the present study is to explore the relationship between serum zinc levels and HF by using a meta-analysis approach. PubMed, Web of Science, and OVID databases were searched for reports on the association between serum zinc levels and HF until June 2016. 12 reports with 1453 subjects from 27 case-control studies were chosen for the meta-analysis. Overall, the pooled analysis indicated that patients with HF had lower zinc levels than the control subjects. Further subgroup analysis stratified by different geographic locations also showed that HF patients had lower zinc levels than the control subjects. In addition, subgroup analysis stratified by HF subgroups found that patients with idiopathic dilated cardiomyopathy (IDCM) had lower zinc levels than the control subjects, except for patients with ischemic cardiomyopathy (ICM). In conclusion, the results of the meta-analysis indicate that there is a significant association between low serum zinc levels and HF. PMID:29682528

Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats.

PubMed

Behrendt, Patrick; Buchenauer, Tobias; Horn, Rüdiger; Brabant, Georg; Jacobs, Roland; Bode, Felix; Stephan, Michael; Nave, Heike

2010-08-01

The adipocyte-derived catabolic protein leptin alters cell-mediated immunity and cytokine crosstalk. This may provide new insights into the altered immune response, seen in obese individuals. Therefore, we determined the tissue distribution of immune cells in diet-induced obese (dio) and normal weight F344 rats challenged with MADB106 tumor cells or leptin. Immune cell distribution in blood (by FACS analysis) and tissues (NK cells in spleen and liver, immunohistologically) as well as pro-inflammatory cytokines (IL-6, TNF-α; by flow cytometry) were investigated in 28 normal weight and 28 dio rats (n = 4-6/group). Pro-inflammatory cytokines were increased 3-fold for IL-6 and 7-fold for TNF-α in obese animals. Higher numbers of blood monocytes and NK cells were found in obese as compared to normal weight animals. In dio rats challenged with leptin and MADB106 tumor cells, monocyte numbers were decreased as compared to the obese control animals. Immunohistochemistry revealed an altered NK cell distribution in a compartment-, treatment-, and bodyweight-specific manner. In conclusion, our data reveal a distinct distribution pattern of monocytes and NK cells in dio rats as compared to normal weight littermates and an additional modulatory effect of a leptin- and MADB106 tumor cell challenge.

Maternal and Perinatal Outcomes in Second Hemoglobin Measurement in Nonanemic Women at First Booking: Effect of Altitude of Residence in Peru

PubMed Central

Gonzales, Gustavo F.; Tapia, Vilma; Fort, Alfredo L.

2012-01-01

Objective. To determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes. Methods. This is a secondary analysis of a large database obtained from the Perinatal Information System in Peru which includes 379,816 pregnant women and their babies from 43 maternity units in Peru. Results. Most women remained with normal hemoglobin values at second measurement (75.1%). However, 21.4% of women became anemic at the second measurement. In all, 2.8% resulted with moderate/severe anemia and 3.5% with erythrocytosis (Hb>14.5 g/dL). In all cases Hb was higher as altitude increased. Risk for moderate/severe anemia increased associated with higher gestational age at second measurement of hemoglobin, BMI <19.9 kg/m2, living without partner, <5 antenatal care visits, first parity, multiparity, and preeclampsia. Lower risk for moderate/severe anemia was observed with normal high Hb level at first booking living at moderate and high altitude, and high BMI. Conclusion. Prevalence of anemia increases as pregnancy progress, and that a normal value at first booking may not be considered sufficient as Hb values should be observed throughout pregnancy. BMI was a risk for anemia in a second measurement. PMID:22577573

Maternal and perinatal outcomes in second hemoglobin measurement in nonanemic women at first booking: effect of altitude of residence in peru.

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Fort, Alfredo L

2012-01-01

Objective. To determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes. Methods. This is a secondary analysis of a large database obtained from the Perinatal Information System in Peru which includes 379,816 pregnant women and their babies from 43 maternity units in Peru. Results. Most women remained with normal hemoglobin values at second measurement (75.1%). However, 21.4% of women became anemic at the second measurement. In all, 2.8% resulted with moderate/severe anemia and 3.5% with erythrocytosis (Hb>14.5 g/dL). In all cases Hb was higher as altitude increased. Risk for moderate/severe anemia increased associated with higher gestational age at second measurement of hemoglobin, BMI <19.9 kg/m(2), living without partner, <5 antenatal care visits, first parity, multiparity, and preeclampsia. Lower risk for moderate/severe anemia was observed with normal high Hb level at first booking living at moderate and high altitude, and high BMI. Conclusion. Prevalence of anemia increases as pregnancy progress, and that a normal value at first booking may not be considered sufficient as Hb values should be observed throughout pregnancy. BMI was a risk for anemia in a second measurement.

Improving the Identification of Neonatal Encephalopathy: Utility of a Web-Based Video Tool.

PubMed

Ivy, Autumn S; Clark, Catherine L; Bahm, Sarah M; Meurs, Krisa P Van; Wusthoff, Courtney J

2017-04-01

Objective  This study tested the effectiveness of a video teaching tool in improving identification and classification of encephalopathy in infants. Study Design  We developed an innovative video teaching tool to help clinicians improve their skills in interpreting the neonatal neurological examination for grading encephalopathy. Pediatric residents were shown 1-minute video clips demonstrating exam findings in normal neonates and neonates with various degrees of encephalopathy. Findings from five domains were demonstrated: spontaneous activity, level of alertness, posture/tone, reflexes, and autonomic responses. After each clip, subjects were asked to identify whether the exam finding was normal or consistent with mild, moderate, or severe abnormality. Subjects were then directed to a web-based teaching toolkit, containing a compilation of videos demonstrating normal and abnormal findings on the neonatal neurological examination. Immediately after training, subjects underwent posttesting, again identifying exam findings as normal, mild, moderate, or severe abnormality. Results  Residents improved in their overall ability to identify and classify neonatal encephalopathy after viewing the teaching tool. In particular, the identification of abnormal spontaneous activity, reflexes, and autonomic responses were most improved. Conclusion  This pretest/posttest evaluation of an educational tool demonstrates that after viewing our toolkit, pediatric residents were able to improve their overall ability to detect neonatal encephalopathy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Associations Between Macrolevel Economic Factors and Weight Distributions in Low- and Middle-Income Countries: A Multilevel Analysis of 200 000 Adults in 40 Countries

PubMed Central

Sweet, Elizabeth; Kawachi, Ichiro; Heymann, Jody; Galea, Sandro

2014-01-01

Objectives. We examined associations between macrolevel economic factors hypothesized to drive changes in distributions of weight and body mass index (BMI) in a representative sample of 200 796 men and women from 40 low- and middle-income countries. Methods. We used meta-regressions to describe ecological associations between macrolevel factors and mean BMIs across countries. Multilevel regression was used to assess the relation between macrolevel economic characteristics and individual odds of underweight and overweight relative to normal weight. Results. In multilevel analyses adjusting for individual-level characteristics, a 1–standard-deviation increase in trade liberalization was associated with 13% (95% confidence interval [CI] = 0.76, 0.99), 17% (95% CI = 0.71, 0.96), 13% (95% CI = 0.76, 1.00), and 14% (95% CI = 0.75, 0.99) lower odds of underweight relative to normal weight among rural men, rural women, urban men, and urban women, respectively. Economic development was consistently associated with higher odds of overweight relative to normal weight. Among rural men, a 1–standard-deviation increase in foreign direct investment was associated with 17% (95% CI = 1.02, 1.35) higher odds of overweight relative to normal weight. Conclusions. Macrolevel economic factors may be implicated in global shifts in epidemiological patterns of weight. PMID:24228649

Mechanical analysis of the roundhouse kick according to height and distance in taekwondo.

PubMed

Estevan, I; Falco, C

2013-12-01

Competition regulation in taekwondo has experienced several changes during the last few years, for example, kicks to the head score more points than kicks to the chest. In addition, some external factors such as the height of target and execution distance seem to affect the kick performance. The aim of this study was to analyse selected biomechanical parameters (impact force, reaction time, and execution time) according to the height and execution distance in two different male groups (experts (n = 12) and novices (n = 21)). Athletes kicked twice from every execution distance (short, normal and long) and towards two different heights of target (chest and head) in a random order. Novices kicked to the head with a longer reaction time than to the chest (p < 0.05) but experts were able to kick with similar performance for both heights. From short and normal distances experts kicked with similar performance; whereas from the normal distance novices had longer reaction and execution time than from the short distance (p < 0.05). In conclusion, in counterattacking situations, experts should perform the roundhouse kick to the head instead of to the chest, because it produces better scores with similar performance; whereas novice athletes should avoid kicking to the head because they are not able to kick with similar performance. Moreover, it is recommended that during counterattacks higher-level taekwondo athletes should intend to kick from normal distances.

MECHANICAL ANALYSIS OF THE ROUNDHOUSE KICK ACCORDING TO HEIGHT AND DISTANCE IN TAEKWONDO

PubMed Central

Falco, C.

2013-01-01

Competition regulation in taekwondo has experienced several changes during the last few years, for example, kicks to the head score more points than kicks to the chest. In addition, some external factors such as the height of target and execution distance seem to affect the kick performance. The aim of this study was to analyse selected biomechanical parameters (impact force, reaction time, and execution time) according to the height and execution distance in two different male groups (experts (n = 12) and novices (n = 21)). Athletes kicked twice from every execution distance (short, normal and long) and towards two different heights of target (chest and head) in a random order. Novices kicked to the head with a longer reaction time than to the chest (p < 0.05) but experts were able to kick with similar performance for both heights. From short and normal distances experts kicked with similar performance; whereas from the normal distance novices had longer reaction and execution time than from the short distance (p < 0.05). In conclusion, in counterattacking situations, experts should perform the roundhouse kick to the head instead of to the chest, because it produces better scores with similar performance; whereas novice athletes should avoid kicking to the head because they are not able to kick with similar performance. Moreover, it is recommended that during counterattacks higher-level taekwondo athletes should intend to kick from normal distances. PMID:24744499

Diagnosis of Diabetes Mellitus by Extraction of Morphological Features of Red Blood Cells Using an Artificial Neural Network.

PubMed

Palanisamy, Vinupritha; Mariamichael, Anburajan

2016-10-01

Background and Aim: Diabetes mellitus is a metabolic disorder characterized by varying hyperglycemias either due to insufficient secretion of insulin by the pancreas or improper utilization of glucose. The study was aimed to investigate the association of morphological features of erythrocytes among normal and diabetic subjects and its gender-based changes and thereby to develop a computer aided tool to diagnose diabetes using features extracted from RBC. Materials and Methods: The study involved 138 normal and 144 diabetic subjects. The blood was drawn from the subjects and the blood smear prepared was digitized using Zeiss fluorescent microscope. The digitized images were pre-processed and texture segmentation was performed to extract the various morphological features. The Pearson correlation test was performed and subsequently, classification of subjects as normal and diabetes was carried out by a neural network classifier based on the features that demonstrated significance at the level of P <0.05. Result: The proposed system demonstrated an overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 93.3, 93.71, 92.8, 93.1 and 93.5% respectively. Conclusion: The morphological features exhibited a statistically significant difference (P<0.01) between the normal and diabetic cells, suggesting that it could be helpful in the diagnosis of Diabetes mellitus using a computer aided system. © Georg Thieme Verlag KG Stuttgart · New York.

On the progenitors of Type Ia supernovae

NASA Astrophysics Data System (ADS)

Livio, Mario; Mazzali, Paolo

2018-03-01

We review all the models proposed for the progenitor systems of Type Ia supernovae and discuss the strengths and weaknesses of each scenario when confronted with observations. We show that all scenarios encounter at least a few serious difficulties, if taken to represent a comprehensive model for the progenitors of all Type Ia supernovae (SNe Ia). Consequently, we tentatively conclude that there is probably more than one channel leading SNe Ia. While the single-degenerate scenario (in which a single white dwarf accretes mass from a normal stellar companion) has been studied in some detail, the other scenarios will need a similar level of scrutiny before any firm conclusions can be drawn.

Methods to evvaluate normal rainfall for short-term wetland hydrology assessment

Treesearch

Jaclyn Sumner; Michael J. Vepraskas; Randall K. Kolka

2009-01-01

Identifying sites meeting wetland hydrology requirements is simple when long-term (>10 years) records are available. Because such data are rare, we hypothesized that a single-year of hydrology data could be used to reach the same conclusion as with long-term data, if the data were obtained during a period of normal or below normal rainfall. Long-term (40-45 years)...

Levels-Of-Processing Effect on Word Recognition in Schizophrenia

PubMed Central

Ragland, J. Daniel; Moelter, Stephen T.; McGrath, Claire; Hill, S. Kristian; Gur, Raquel E.; Bilker, Warren B.; Siegel, Steven J.; Gur, Ruben C.

2015-01-01

Background Individuals with schizophrenia have difficulty organizing words semantically to facilitate encoding. This is commonly attributed to organizational rather than semantic processing limitations. By requiring participants to classify and encode words on either a shallow (e.g., uppercase/lowercase) or deep level (e.g., concrete/abstract), the levels-of-processing paradigm eliminates the need to generate organizational strategies. Methods This paradigm was administered to 30 patients with schizophrenia and 30 healthy comparison subjects to test whether providing a strategy would improve patient performance. Results Word classification during shallow and deep encoding was slower and less accurate in patients. Patients also responded slowly during recognition testing and maintained a more conservative response bias following deep encoding; however, both groups showed a robust levels-of-processing effect on recognition accuracy, with unimpaired patient performance following both shallow and deep encoding. Conclusions This normal levels-of-processing effect in the patient sample suggests that semantic processing is sufficiently intact for patients to benefit from organizational cues. Memory remediation efforts may therefore be most successful if they focus on teaching patients to form organizational strategies during initial encoding. PMID:14643082

[Emodin alleviates pulmonary fibrosis through inactivation of TGF-β1/ADAMTS-1 signaling pathway in rats].

PubMed

Liu, Lijing; Qian, Hong; Xiao, Hua; He, Jianbin; Xie, Maofeng; Wang, Zaiyan; Long, Xingyun

2016-10-01

Objective To explore the role of transforming growth factor-β1 (TGF-β1)/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) signaling pathway in emodin's anti-pulmonary fibrosis. Methods Sixty SD rats were randomly divided into 6 groups: normal control group, sham-operated group, model group, low-dose emodin intervention group (20 mg/kg), high-dose emodin intervention group (80 mg/kg) and prednisone group (5 mg/kg). Each group included 10 animals. Rats in the latter 4 groups were intratracheally injected with bleomycin A5 to induce pulmonary fibrosis, whereas bleomycin A5 was replaced by normal saline in sham-operated group. From the second day, rats in the low- and high-dose emodin intervention groups were intragastrically treated with 2 mL of 20 and 80 mg/kg emodin, respectively. Rats in the prednisone group were intragastrically administrated with 2 mL of 5 mg/kg prednisone acetate. However, rats in the normal control and sham-operated and model groups were treated with 2 mL of normal saline. All rats were sacrificed on day 28 after modeling. Subsequently, blood and pulmonary tissue specimen were taken. The pathological changes of pulmonary tissues were observed using routine HE and Masson staining. The expressions of TGF-β1, ADAMTS-1, collagen type 1 (Col1) and Col3 in pulmonary tissues were measured by quantitative real-time PCR and Western blotting. Serum levels of procollagen type 1 carboxy terminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) were detected by ELISA. Results Compare with the model group, the alveolitis and pulmonary fibrosis extent in each drug-treated group were significantly alleviated. In comparison with normal control group or sham-operated group, the mRNA and protein levels of TGF-β1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP increased, but the mRNA and protein levels of ADAMTS-1 decreased in model group. After treatment with low- and high-dose emodin or prednisone, the mRNA and protein levels of TGF-β1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP were significantly downregulated, while the mRNA and protein levels of ADAMTS-1 in pulmonary tissues were significantly upregulated as compared with the model group. Moreover, In comparison with the low-dose emodin intervention group, the above indicators were significantly improved in the high-dose emodin intervention or prednisone group. However, the above indicators were not significantly different between the high-dose emodin intervention group and the prednisone group. Conclusion Increased degradation of Col1 and Col3 in pulmonary tissues due to the inactivation of TGF-β1/ADAMTS-1 signaling pathway may be a significant mechanism by which emodin protects rats against pulmonary fibrosis.

The Running Athlete

PubMed Central

Henning, P. Troy

2014-01-01

Context: Pelvic stress fractures, osteitis pubis, and snapping hip syndrome account for a portion of the overuse injuries that can occur in the running athlete. Evidence Acquisition: PubMed searches were performed for each entity using the following keywords: snapping hip syndrome, coxa sultans, pelvic stress fracture, and osteitis pubis from 2008 to 2013. Topic reviews, case reports, case series, and randomized trials were included for review. Study Design: Clinical review. Level of Evidence: Level 4. Results: Collectively, 188 articles were identified. Of these, 58 were included in this review. Conclusion: Based on the available evidence, the majority of these overuse injuries can be managed non-operatively. Primary treatment should include removal from offending activity, normalizing regional muscle strength/length imbalances and nutritional deficiencies, and mitigating training errors through proper education of the athlete and training staff. Strength of Recommendation Taxonomy: C PMID:24587861

A critical analysis of the cumulative rainfall departure concept.

PubMed

Weber, Kenneth; Stewart, Mark

2004-01-01

Evaluation of trends in time-series, such as precipitation or ground water levels, is an essential element in many hydrologic evaluations, including water resource studies and planning efforts. The cumulative rainfall departure (CRD) from normal rainfall is a concept sometimes utilized to evaluate the temporal correlation of rainfall with surface water or ground water levels. Permutations of the concept have been used to estimate recharge or aquifer storativity, and in attempts to explain declining ground water levels. The cumulative departure concept has hydrologic meaning in the short term, as a generalized evaluation of either meager or abundant rainfall, and when utilized in connection with a detailed water budget analysis can be used in a predictive fashion. However, the concept can be misapplied if extended over lengthy periods. Misapplication occurs because of several factors including the separation of the mean and median in nonnormal distributions, how the choice of beginning and end points of the data can affect the results, the lack of consideration that above-average rainfall can reset the hydrologic system without mathematically eliminating the accumulated deficit, and the lack of support for the necessary inference that rainfall events and hydrologic levels widely separated in time are linked. Standard statistical techniques are available to reliably determine trends and can provide rigorous statistical measures of the significance of conclusions. Misuse of the CRD concept can lead to erroneous and unsupported conclusions regarding hydrologic relationships and can potentially result in misguided water resource decision-making.

Distortion in fingerprints: a statistical investigation using shape measurement tools.

PubMed

Sheets, H David; Torres, Anne; Langenburg, Glenn; Bush, Peter J; Bush, Mary A

2014-07-01

Friction ridge impression appearance can be affected due to the type of surface touched and pressure exerted during deposition. Understanding the magnitude of alterations, regions affected, and systematic/detectable changes occurring would provide useful information. Geometric morphometric techniques were used to statistically characterize these changes. One hundred and fourteen prints were obtained from a single volunteer and impressed with heavy, normal, and light pressure on computer paper, soft gloss paper, 10-print card stock, and retabs. Six hundred prints from 10 volunteers were rolled with heavy, normal, and light pressure on soft gloss paper and 10-print card stock. Results indicate that while different substrates/pressure levels produced small systematic changes in fingerprints, the changes were small in magnitude: roughly the width of one ridge. There were no detectable changes in the degree of random variability of prints associated with either pressure or substrate. In conclusion, the prints transferred reliably regardless of pressure or substrate. © 2014 American Academy of Forensic Sciences.

Proline analogue of nitrosourea as a new cytotoxic prodrug.

PubMed

Stankiewicz-Kranc, Anna; Bielawska, Anna; Bielawski, Krzysztof; Skrzydlewska, Elzbieta

2009-11-01

Carmustine is frequently used as anticancer drug. High toxicity and low selectivity reduces the application of this drug. Though, there is a necessity to find new compounds characterized by similar therapeutic effects but a higher selectivity and safety. As a result, the proline analogue of nitrosourea, N-[N'-(2-bromophenyl)-N'-nitrosocarbamoyl]proline (AC), has been synthesized. The aim of this study was to compare the influence of carmustine and the proline analogue of nitrosourea on the antioxidant abilities of fibroblasts and leukemia cells, MOLT4. It was shown that carmustine as well as AC cause an increase in hydrogen peroxide concentration in normal and neoplastic cells. Incubation with both compounds led to a diminution of the activity of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and reductase. Changes in activity / level of antioxidant parameters were accompanied by augmentation of lipid and oxidative protein modifications. In conclusion, carmustine and AC cause changes in the antioxidative system of normal and MOLT4 cells and are a reason of oxidative stress formation.

Locally applied simvastatin improves fracture healing at late period in osteoporotic rat

NASA Astrophysics Data System (ADS)

Tian, Faming; Zhang, Liu; Kang, Yuchuan; Zhang, Junshan; Ao, Jiao; Yang, Fang

effect of simvastatin locally applied from a bioactive polymer coating of implants on osteoporotic fracture healing at late period. Methods:Femur fracture model was established on normal or osteotoporotic mature female SD rats, intramedullary stabilization was achieved with uncoated titanium Kirschnerwires in normal rats(group A),with polymer-only coated vs. polymer plus simvastatin coated titanium Kirschner wires in osteoporotic rats(group B and C, respectively).Femurs were harvested after 12 weeks, and underwent radiographic and histologic analysis, as well as immunohistochemical evaluation for BMP-2 expression. Results:Radiographic results demonstrated progressed callus in the simvastatin-treated groups compared to the uncoated group.The histologic analysis revealed a significantly processed callus with irregular-shaped newly formed bone trabeculae in simvastatin-treated group. Immunohistochemical evaluation showed markedly higher expression levels of B:MP-2 in simvastatin-treated group.Conclusions: The present study revealed a improved fracture healing under local application of simvastatin in osteoporotic rat,which might partially from upregulation of the B:MP-2 expression at fractured site.

A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. I. Serum growth hormone-binding protein.

PubMed

Martha, P M; Rogol, A D; Carlsson, L M; Gesundheit, N; Blizzard, R M

1993-08-01

Previous studies have provided compelling evidence that GH secretion increases transiently during midpuberty in normally growing children. Although it is likely that the increase in GH production serves a primary role in generating the pubertal growth spurt, such a conclusion necessarily assumes that other essential "down-stream" components of the GH axis responsible for mediating the effects of GH remain unchanged. To investigate this concept, we assessed longitudinally another important component of the endogenous GH axis, the serum GH-binding protein (GHBP)/receptor system, in a cohort of 11 normal boys as they matured through normal puberty. At 4-month intervals over 4.0-5.1 yr, 24-h serum GH concentration profiles and serum GHBP activity were evaluated. Serum GHBP levels varied over a more than 12-fold range (40-504 pmol/L) among all subjects. However, the values for individual subjects consistently varied within more narrow limits. The coefficient of variation for values from all subjects was 51% compared to the mean intrasubject coefficient of variation of only 30% (P < 0.05). Although the highest GHBP level (all subjects) was 12.6-fold greater than the lowest, the mean intrasubject range was only 3.1 +/- 0.5-fold (P < 0.05). The overall mean serum GHBP level correlated directly with the overall mean body mass index (r = 0.69; P = 0.018), but correlated inversely with the mean 24-h GH concentration (r = -0.61; P < 0.05). There was no significant increase in the GHBP level during puberty. However, because mean 24-h GH concentrations did increase during midpuberty, the data suggest that an increase in the relative amounts of free vs. bound GH develops during the period of the pubertal growth spurt. These data indicate that serum GHBP levels are regulated in individual children within much more narrow limits than those present in the larger population and do not undergo the dramatic changes during puberty typical of GH secretion and linear growth velocity. As a consequence, alterations may develop in the relative amounts of free vs. bound GH present in serum during the midpubertal years compared to those present during either the prepubertal or postpubertal periods. The majority of the known age-related increase in serum GHBP levels probably occurs before the period of active pubertal development. These findings strengthen further the concept that the midpubertal changes in GH secretion serve a primary role in generating the growth spurt.(ABSTRACT TRUNCATED AT 400 WORDS)

Housekeeping while brain's storming Validation of normalizing factors for gene expression studies in a murine model of traumatic brain injury

PubMed Central

Rhinn, Hervé; Marchand-Leroux, Catherine; Croci, Nicole; Plotkine, Michel; Scherman, Daniel; Escriou, Virginie

2008-01-01

Background Traumatic brain injury models are widely studied, especially through gene expression, either to further understand implied biological mechanisms or to assess the efficiency of potential therapies. A large number of biological pathways are affected in brain trauma models, whose elucidation might greatly benefit from transcriptomic studies. However the suitability of reference genes needed for quantitative RT-PCR experiments is missing for these models. Results We have compared five potential reference genes as well as total cDNA level monitored using Oligreen reagent in order to determine the best normalizing factors for quantitative RT-PCR expression studies in the early phase (0–48 h post-trauma (PT)) of a murine model of diffuse brain injury. The levels of 18S rRNA, and of transcripts of β-actin, glyceraldehyde-3P-dehydrogenase (GAPDH), β-microtubulin and S100β were determined in the injured brain region of traumatized mice sacrificed at 30 min, 3 h, 6 h, 12 h, 24 h and 48 h post-trauma. The stability of the reference genes candidates and of total cDNA was evaluated by three different methods, leading to the following rankings as normalization factors, from the most suitable to the less: by using geNorm VBA applet, we obtained the following sequence: cDNA(Oligreen); GAPDH > 18S rRNA > S100β > β-microtubulin > β-actin; by using NormFinder Excel Spreadsheet, we obtained the following sequence: GAPDH > cDNA(Oligreen) > S100β > 18S rRNA > β-actin > β-microtubulin; by using a Confidence-Interval calculation, we obtained the following sequence: cDNA(Oligreen) > 18S rRNA; GAPDH > S100β > β-microtubulin > β-actin. Conclusion This work suggests that Oligreen cDNA measurements, 18S rRNA and GAPDH or a combination of them may be used to efficiently normalize qRT-PCR gene expression in mouse brain trauma injury, and that β-actin and β-microtubulin should be avoided. The potential of total cDNA as measured by Oligreen as a first-intention normalizing factor with a broad field of applications is highlighted. Pros and cons of the three methods of normalization factors selection are discussed. A generic time- and cost-effective procedure for normalization factor validation is proposed. PMID:18611280

Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats

PubMed Central

Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

2015-01-01

AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15th day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group (on the 3rd and 5th days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6th day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment significantly reduced the DSS colitis-induced TNF-α increase (P < 0.01). No statistically significant differences were observed among groups for IL-10 and MDA levels. Colon tissue iNOS levels in the colitis group were significantly higher than those in the control and kefir-colitis groups (P < 0.05). CONCLUSION: Kefir reduces the clinical DAI and histologic colitis scores in a DSS-induced colitis model, possibly via reduction of MPO, TNF-α, and iNOS levels. PMID:26676086

Relationship between respiratory failure and plasma noradrenaline levels in amyotrophic lateral sclerosis.

PubMed

Yamashita, A; Koike, Y; Takahashi, A; Hirayama, M; Murakami, N; Sobue, G

1997-08-01

We evaluated plasma noradrenaline (NA) levels at test and during head-up tilt test in 20 patients with sporadic amyotrophic lateral sclerosis (ALS). Their fasting plasma NA levels ranged from 195 to 4227 pg/ml. The average plasma NA level was 483 pg/ml in five ambulatory patients, 341 in two wheelchair-bound patients, 1264 in 11 bedridden patients, and 208 in two respirator-dependent patients whose disability grading was the worst among the four groups. Arterial carbon dioxide (PCO2) was evaluated as a measure of respiratory function. The coefficient of correlation between PCO2 and plasma NA was r = 0.654 (p < 0.01). Either respiratory failure or lower motor neuron dysfunction may relate to the elevation of plasma NA levels. In the two bedridden patients, plasma NA levels and heart rate at rest increased significantly as the disease progressed. Cardiovascular responses to head-up tilting were normal. These data suggest that the elevation of plasma NA levels may be related to progression of respiratory failure and lower motor neuron dysfunction. In conclusion, sympathetic hyperactivity in ALS is considered to be not primary, but secondary to somatic motor disabilities and respiratory failure.

Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity

PubMed Central

Koo, Hyeon-Kyoung; Hong, Yoonki; Lim, Myoung Nam; Yim, Jae-Joon; Kim, Woo Jin

2016-01-01

Objective Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease–antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity. Methods Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses. Results There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant. Conclusion Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients. PMID:27313452

Differential Expression of c-fos Proto-Oncogene in Normal Oral Mucosa versus Squamous Cell Carcinoma

PubMed Central

Krishna, Akhilesh; Bhatt, Madan Lal Brahma; Singh, Vineeta; Singh, Shraddha; Gangwar, Pravin Kumar; Singh, Uma Shankar; Kumar, Vijay; Mehrotra, Divya

2018-01-01

Background: The c-Fos nuclear protein dimerizes with Jun family proteins to form the transcription factor AP-1 complex which participates in signal transduction and regulation of normal cellular processes. In tumorigenesis, c-Fos promotes invasive growth through down-regulation of tumor suppressor genes but its role in oral carcinogenesis is not clear. Objectives: This study concerned c-fos gene expression in normal and malignant tissues of the oral cavity, with attention to associations between expression status and clinico-pathological profiles of OSCC patients. Method: A total of 65 histopathologically confirmed OSCC tissue samples were included in case group along with an equal number of age and sex-matched normal tissue samples of oral cavity for the control group. c-Fos protein and m-RNA expressions were analyzed using immunohistochemistry and qRT-PCR, respectively. Results: A significant low expression of c-Fos protein was observed in OSCC cases than normal control subjects (p= <0.001). The mean percent positivity of c-Fos protein in cases vs. controls was 24.91± 2.7 vs. 49.68± 2.2 (p= <0.001). Most OSCC tissue samples showed weak or moderate c-Fos expression whereas 53.8% of normal tissue sections presented with strong immunostaining. Moreover, the relative m-RNA expression for the c-fos gene was significantly decreased in case group (0.93± 0.48) as compared to the control group (1.22± 0.87). Majority of c-Fos positive cases were diagnosed with well developed tumor. The mean percent positivity of c-Fos protein was significantly lower in higher grade tumor as compared with normal oral mucosa (p= < 0.001). Conclusion: The present study suggested that the c-fos gene is downregulated in oral carcinomas. The disparity of c-Fos protein levels in different pathological grades of tumor and normal oral tissue samples may indicate that loss of c-Fos expression is related with the progression of OSCC. PMID:29582647

Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students.

PubMed

Hinney, Anke; Hoch, Anne; Geller, Frank; Schäfer, Helmut; Siegfried, Wolfgang; Goldschmidt, Hanspeter; Remschmidt, Helmut; Hebebrand, Johannes

2002-06-01

Ghrelin induces obesity via central and peripheral mechanisms. Administration of ghrelin leads to increased food intake and decreased fat utilisation in rodents. Ghrelin levels are decreased in obese individuals. Recently, a polymorphism (Arg-51-Gln) within the ghrelin gene (GHRL) was described to be associated with obesity. We screened the GHRL coding region in 215 extremely obese German Children and adolescents (study group 1) and 93 normal weight students (study group 2) by single strand conformation polymorphism analysis (SSCP). We found the two previously described single nucleotide polymorphisms (SNP: Arg-51-Gln and Leu-72-Met) in similar frequencies in study groups 1 and 2 (allele frequencies were: 0.019 and 0.016 for the 51-Gln allele and 0.091 and 0.086 for the 72-Met allele, respectively). Hence, we could not confirm the previous finding. Additionally, two novel variants were identified within the coding region: (1) We detected one healthy normal weight individual with a frameshift mutation (2bp deletion at codon 34). This frameshift mutation affects the coding region of the mature ghrelin. Hence, it is highly likely that the normal weight student is haplo-insufficient for ghrelin. (2) An A to T transversion leads to an amino acid exchange from Gln to Leu at amino acid position 90. The frequency of the 90-Leu allele was significantly higher in the extremely obese children and adolescents (0.063) than in the normal weight students (0.016; nominal p = 0.011). Additionally, we genotyped 134 underweight students and 44 normal weight adults for this SNP. Genotype frequencies were similar in extremely obese children and adolescents, underweight students and normal weight adults (p > 0.8). In conclusion, we identified four sequence variants in the coding region of the ghrelin gene in individuals belonging to different weight extremes. A frameshift mutation was detected in a normal weight individual. None of the variants seem to influence weight regulation.

Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals

PubMed Central

Avraham, Yosefa; Saidian, Mayer; Burston, James J.; Mevorach, Raphael; Vorobiev, Lia; Magen, Iddo; Kunkes, Eithan; Borges, Beatriz; Lichtman, Aron H.; Berry, Elliot M.

2010-01-01

Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits, and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with canola oil, would ameliorate the morbidity and mortality associated with these conditions by normalizing endocannabinoid and monoaminergeric systems as well as other systems involved in satiety and cognitive function within the hypothalamus and hippocampus. Female Sabra mice restricted to 40% of their daily food intake exhibited decreased body weight, were sickly in appearance, displayed cognitive deficits, and had increased mortality rates. Strikingly, fish oil supplementation that contains high omega-3 fatty acids levels decreased mortality and morbidity, and normalized the expression of genes and neurotransmitters in the hippocampus and hypothalamus. Fish oil supplementation, but not canola oil, increased survival rates, improved general appearance, and prevented cognitive decline, despite the facts that both diets contained an equivalent number of calories and that there were no differences in weight between mice maintained on the two diets in 100% but decrease in the 40%. In the hypothalamus, the beneficial effects of fish oil supplementation were related to normalization of the endocannabinoid 2-arachidonylglycerol (2-AG), serotonin (5-HT) (p<0.056), dopamine (DA), neuropeptide Y (NPY), and Ca2+/calmodulin (CaM)-dependent protein kinase (Camkk2). In the hippocampus, fish oil supplementation normalized 5-HT, Camkk2, silent mating type information regulation 1 (SIRT-1), and brain-derived neurotrophic factor (BDNF). In conclusion, dietary supplements of fish oil, as source of omega-3 fatty acids, may alleviate cognitive impairments associated with severe diet restriction and prolong survival independently of weight gain by normalizing neurochemical systems. PMID:21109417

Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas, acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist

PubMed Central

Uchida, Masahiko; Ito, Tetsuhide; Nakamura, Taichi; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Takayanagi, Ryoichi; Jensen, Robert T.

2014-01-01

Objectives Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1) in acute/chronic pancreatitis, however the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues, and the effects of CX3CL1 on activated-PSCs. Methods CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues were evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated-PSCs were examined with realtime-PCR, BrdU assays and Western Blotting. Results In normal pancreas, acinar cells expressed CX3CR1 within granule-like-formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal and activated-PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1, did not induce inflammatory-genes expression in activated-PSCs, but induced proliferation. Conclusions CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis and the CX3CR1s are activated. CX3CL1 induces proliferation of activated-PSCs without increasing release of inflammatory-mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSCs proliferation in pancreatitis where CX3CL1 levels are elevated. PMID:24681877

Age-Related Vascular Changes Affect Turbulence in Aortic Blood Flow

PubMed Central

Ha, Hojin; Ziegler, Magnus; Welander, Martin; Bjarnegård, Niclas; Carlhäll, Carl-Johan; Lindenberger, Marcus; Länne, Toste; Ebbers, Tino; Dyverfeldt, Petter

2018-01-01

Turbulent blood flow is implicated in the pathogenesis of several aortic diseases but the extent and degree of turbulent blood flow in the normal aorta is unknown. We aimed to quantify the extent and degree of turbulece in the normal aorta and to assess whether age impacts the degree of turbulence. 22 young normal males (23.7 ± 3.0 y.o.) and 20 old normal males (70.9 ± 3.5 y.o.) were examined using four dimensional flow magnetic resonance imaging (4D Flow MRI) to quantify the turbulent kinetic energy (TKE), a measure of the intensity of turbulence, in the aorta. All healthy subjects developed turbulent flow in the aorta, with total TKE of 3–19 mJ. The overall degree of turbulence in the entire aorta was similar between the groups, although the old subjects had about 73% more total TKE in the ascending aorta compared to the young subjects (young = 3.7 ± 1.8 mJ, old = 6.4 ± 2.4 mJ, p < 0.001). This increase in ascending aorta TKE in old subjects was associated with age-related dilation of the ascending aorta which increases the volume available for turbulence development. Conversely, age-related dilation of the descending and abdominal aorta decreased the average flow velocity and suppressed the development of turbulence. In conclusion, turbulent blood flow develops in the aorta of normal subjects and is impacted by age-related geometric changes. Non-invasive assessment enables the determination of normal levels of turbulent flow in the aorta which is a prerequisite for understanding the role of turbulence in the pathophysiology of cardiovascular disease. PMID:29422871

Natural course of hypogonadism diagnosed during hospitalization in aged male patients.

PubMed

Iglesias, P; Prado, F; Muñoz, A; Guerrero, M T; Macías, M C; Ridruejo, E; Tajada, P; García-Arévalo, C; Díez, J J

2015-04-01

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7±5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4±48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5%), 20 (46.5%), and 3 (7.0%) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9±135.6 ng/dl, p<0.001). At this point, more than half of the patients (n=27, 62.8%) showed normal serum T concentrations. Both gonadotropins, FSH (p<0.001), and LH (p=0.04) also increased one month after discharge. Approximately, half of the patients (13, 48.1%) who normalized serum T concentrations also showed normal serum gonadotropin concentrations. Patients who normalized their serum T concentrations one month after discharge showed significantly higher baseline values of T (134.7±33.9 ng/dl) than those who persisted with hypogonadism (n=16, 32.7%; 82.8±51.6 ng/dl, p<0.001). Lastly, serum T was the only independent predictor for achieving eugonadal status (OR 1.030; CI 95%, 1.010-1.050; p<0.001). In conclusion, about 63% of aged patients hospitalized for acute illness with hypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Association of High Pulse Pressure With Proteinuria in Subjects With Diabetes, Prediabetes, or Normal Glucose Tolerance in a Large Japanese General Population Sample

PubMed Central

Yano, Yuichiro; Sato, Yuji; Fujimoto, Shouichi; Konta, Tsuneo; Iseki, Kunitoshi; Moriyama, Toshiki; Yamagata, Kunihiro; Tsuruya, Kazuhiko; Yoshida, Hideaki; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi

2012-01-01

OBJECTIVE To examine whether there is a difference in the association between high pulse pressure and proteinuria, independent of other blood pressure (BP) indices, such as systolic or diastolic BP, among subjects with diabetes, prediabetes, or normal glucose tolerance. RESEARCH DESIGN AND METHODS Using a nationwide health checkup database of 228,778 Japanese aged ≥20 years (mean 63.2 years; 39.3% men; none had pre-existing cardiovascular disease), we examined the association between high pulse pressure, defined as the highest quintile of pulse pressure (≥63 mmHg, n = 40,511), and proteinuria (≥1+ on dipstick, n = 12,090) separately in subjects with diabetes (n = 27,913), prediabetes (n = 100,214), and normal glucose tolerance (n = 100,651). RESULTS The prevalence of proteinuria was different among subjects with diabetes, prediabetes, and normal glucose tolerance (11.3 vs. 5.0 vs. 3.9%, respectively; P < 0.001). In subjects with diabetes, but not those with prediabetes or normal glucose tolerance, high pulse pressure was associated with proteinuria independently of significant covariates, including systolic BP (odds ratio 1.15 [95% CI 1.04–1.28]) or diastolic or mean BP (all P < 0.01). In patients with diabetes, a +1 SD increase of pulse pressure (+13 mmHg) was associated with proteinuria, even after adjustment for systolic BP (1.07 [1.00–1.13]) or diastolic or mean BP (all P < 0.05). CONCLUSIONS Among the Japanese general population, there was a significant difference in the association between high pulse pressure and proteinuria among subjects with diabetes, prediabetes, and normal glucose tolerance. Only in diabetes was high pulse pressure associated with proteinuria independent of systolic, diastolic, or mean BP levels. PMID:22474041

Prolactin as a Marker of Successful Catheterization during IPSS in Patients with ACTH-Dependent Cushing's Syndrome

PubMed Central

Sharma, S. T.; Raff, H.

2011-01-01

Context: Anomalous venous drainage can lead to false-negative inferior petrosal sinus sampling (IPSS) results. Baseline inferior petrosal sinus to peripheral (IPS/P) prolactin ratio higher than 1.8 ipsilateral to the highest ACTH ratio has been proposed to verify successful catheterization. Prolactin-normalized ACTH IPS/P ratios may differentiate Cushing's disease (CD) from ectopic ACTH syndrome (EAS). Objective: Our objective was to examine the utility of prolactin measurement during IPSS. Design, Setting, and Participants: We conducted a retrospective analysis of prolactin levels in basal and CRH-stimulated IPSS samples in ACTH-dependent Cushing's syndrome (2007–2010). Results: Twenty-five of 29 patients had a pathologically proven diagnosis (17 CD and eight EAS). IPSS results were partitioned into true positive for CD (n = 16), true negative (n = 7), false negative (n = 1), and false positive (n = 1). Prolactin IPS/P ratio suggested successful IPSS in eight of 11 with abnormal venograms. Baseline prolactin IPS/P ratio was helpful in two patients with abnormal venograms and false-negative (catheterization unsuccessful) or true-negative (catheterization successful) IPSS results; the normalized ratio correctly diagnosed their disease. Normalized ACTH IPS/P ratio was at least 1.3 in all with CD, but prolactin IPS/P ratios were misleadingly low in two. One patient with cyclic EAS had a false-positive IPSS when eucortisolemic (baseline prolactin IPS/P = 1.7; normalized ratio = 5.6). All other EAS patients had normalized ratios no higher than 0.7. Conclusion: Prolactin measurement and evaluation of the venogram can improve diagnostic accuracy when IPSS results suggest EAS but is not necessary with positive IPSS results. Confirmation of hypercortisolemia remains a prerequisite for IPSS. A normalized ratio of 0.7–1.3 was not diagnostic. PMID:22031511

Selection of housekeeping genes for gene expression studies in the adult rat submandibular gland under normal, inflamed, atrophic and regenerative states

PubMed Central

Silver, Nicholas; Cotroneo, Emanuele; Proctor, Gordon; Osailan, Samira; Paterson, Katherine L; Carpenter, Guy H

2008-01-01

Background Real-time PCR is a reliable tool with which to measure mRNA transcripts, and provides valuable information on gene expression profiles. Endogenous controls such as housekeeping genes are used to normalise mRNA levels between samples for sensitive comparisons of mRNA transcription. Selection of the most stable control gene(s) is therefore critical for the reliable interpretation of gene expression data. For the purpose of this study, 7 commonly used housekeeping genes were investigated in salivary submandibular glands under normal, inflamed, atrophic and regenerative states. Results The program NormFinder identified the suitability of HPRT to use as a single gene for normalisation within the normal, inflamed and regenerative states, and GAPDH in the atrophic state. For normalisation to multiple housekeeping genes, for each individual state, the optimal number of housekeeping genes as given by geNorm was: ACTB/UBC in the normal, ACTB/YWHAZ in the inflamed, ACTB/HPRT in the atrophic and ACTB/GAPDH in the regenerative state. The most stable housekeeping gene identified between states (compared to normal) was UBC. However, ACTB, identified as one of the most stably expressed genes within states, was found to be one of the most variable between states. Furthermore we demonstrated that normalising between states to ACTB, rather than UBC, introduced an approximately 3 fold magnitude of error. Conclusion Using NormFinder, our studies demonstrated the suitability of HPRT to use as a single gene for normalisation within the normal, inflamed and regenerative groups and GAPDH in the atrophic group. However, if normalising to multiple housekeeping genes, we recommend normalising to those identified by geNorm. For normalisation across the physiological states, we recommend the use of UBC. PMID:18637167

The Impact of Maternal Obesity and Gestational Weight Gain on Early and Mid-Pregnancy Lipid Profiles

PubMed Central

Scifres, Christina M.; Catov, Janet M.; Simhan, Hyagriv N.

2015-01-01

Objective We evaluated the impact of maternal overweight/obesity and excessive weight gain on maternal serum lipids in the first and second trimester of pregnancy. Design and Methods Prospective data were collected for 225 women. Maternal serum lipids and fatty acids were measured at <13 weeks and between 24–28 weeks. Analyses were stratified by normal weight versus overweight/obese status and excessive vs. non-excessive weight gain. Results Overweight/obese women had higher baseline cholesterol (161.3±29.6 vs 149.4±26.8 mg/dL, p<0.01), LDL (80.0±19.9 vs 72.9 ±18.8 mg/dL, p<0.01) and triglycerides ( 81.7±47.2 vs 69.7±40.3 mg/dL, p=0.05) when compared to normal weight women, while HDL (43.6 ±10.4 47.6±11.5 mg/dL, p<0.01) was lower. However, cholesterol and LDL increased at a higher weekly rate in normal weight women, resulting in higher total cholesterol in normal weight women (184.1±28.1 vs. 176.0 ±32.1 mg/dL, p=0.05) at 24–28 weeks. Excessive weight gain did not affect the rate of change in lipid profiles in either group. Overweight/obese women had higher levels of arachidonic acid at both time points. Conclusions Overweight/obese women have significantly more atherogenic lipid profiles than normal weight women during the period of early pregnancy, delineating one physiologic pathway that could explain differences in pregnancy outcomes between normal weight and overweight/obese women. PMID:23853155

Blood glucose may condition factor VII levels in diabetic and normal subjects.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Torella, R

1988-12-01

Increased factor VII levels have been reported in Type 1 (insulin-dependent) diabetic subjects. A direct correlation between fasting plasma glucose and factor VII level was found to exist in both diabetic and normal subjects. Induced-hyperglycaemia was able to increase factor VII levels in both diabetic patients and normal control subjects while, when euglycaemia was achieved in diabetic patients, factor VII values returned to normal range. This study shows that the level of factor VII may be directly conditioned by circulating blood glucose and, therefore, stresses the role of hyperglycaemia in conditioning coagulation abnormalities in diabetes mellitus.

Excitations Élémentaires au Voisinage de la Surface de Séparation d'un Métal Normal et d'un Métal Supraconducteur

NASA Astrophysics Data System (ADS)

Saint-James, Par D.

On étudie le spectre d'excitation pour une couche de métal normal déposée sur un supraconducteur. On montre que si l'interaction attractive électron-électron est négligeable dans le métal normal, il n'y a pas de gap d'énergie dans le spectre d'excitation, même si l'épaisseur de la couche normale est petite. Une étude analogue, conduisant à une conclusion similaire, est menée pour deux supraconducteurs accolés et pour des sphères de métal normal baignant dans un supraconducteur. L'effet prévu pourrait expliquer quelques résultats particuliers observés dans des mesures d'effet tunnel dans des supraconducteurs durs. The excitation spectrum of a layer of normal metal (N) deposited on a superconducting substrate (S) is discussed. It is shown that if the electron-electron attractive interaction is negligibly small in (N) there is no energy gap in the excitation spectrum even if the thickness of the layer (N) is small. A similar study, with equivalent conclusions, has been carried out for two superconductors and for normal metal spheres embedded in a superconductor. The effect may possibly explain some peculiar results of tunnelling experiments on hard superconductors.