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Sample records for baicalein improves histological

  1. Baicalein improves behavioral dysfunction induced by Alzheimer’s disease in rats

    PubMed Central

    Zhou, Li; Tan, Sha; Shan, Yi-long; Wang, Yu-ge; Cai, Wei; Huang, Xue-hong; Liao, Xi-yuan; Li, Hai-yan; Zhang, Lei; Zhang, Bing-jun; Lu, Zheng-qi

    2016-01-01

    E and Ach levels in the brain homogenates. The histopathology study also provides strength to the protective effect of baicalein. Conclusion The current study showed that baicalein significantly (P<0.05) improved the biochemical and histopathological condition of AD in rats. PMID:28003750

  2. An Improved Drugs Screening System Reveals that Baicalein Ameliorates the Aβ/AMPA/NMDA-Induced Depolarization of Neurons.

    PubMed

    Lin, Tian-Syuan; Tsai, Han-Jung; Lee, Chih-Han; Song, Yan-Qing; Huang, Rih-Sheng; Hsieh-Li, Hsiu-Mei; Liang, Mei-Chih; Lin, Yenshou

    2017-01-01

    The presence of amyloid-β (Aβ) plaque and tau protein hyperphosphorylation in brain tissue is the pathological hallmark of Alzheimer's disease (AD). At least some Aβ neurotoxicity is caused by the presence of excess glutamate that has been induced by Aβ accumulation. Memantine is currently the only NMDA receptor inhibitor approved for treating moderate-to-severe AD patients. We utilized primary cortical neurons and DiBAC4(3), a slow-response voltage sensitive fluorescence dye, to create a novel system for screening herbal medicines that allows the identification of pure compounds able to ameliorate Aβ-induced abnormal depolarization. The intensity of DiBAC4(3) fluorescence was increased when primary neurons were stimulated by Aβ; furthermore, pre-treatment with memantine abolished this change. Using this system, we identified six crude extracts made from herbal medicines that effectively alleviated this Aβ-induced abnormal depolarization. Among these herbal medicines, one pure compound, baicalein, which was known to be present in Scutellaria baricalensis and is known to improve memory using an AD mouse model, was identified by our assay. However, the compound's molecular mechanism remained unknown. We found that baicalein, in addition to inhibiting Aβ-induced depolarization, possibly functions as an antagonist of AMPA and NMDA receptors. Taken together, we have established a system/platform to identify herbal medicines that ameliorate Aβ-induced depolarization of neurons. Equally important, baicalein is a candidate drug with great potential for the treatment of AD patients.

  3. Pluronic P85/F68 Micelles of Baicalein Could Interfere with Mitochondria to Overcome MRP2-Mediated Efflux and Offer Improved Anti-Parkinsonian Activity.

    PubMed

    Chen, Tongkai; Li, Ye; Li, Chuwen; Yi, Xiang; Wang, Ruibing; Lee, Simon Ming-Yuen; Zheng, Ying

    2017-10-02

    Overexpression of the drug efflux transporter multidrug resistance-associated protein 2 (MRP2) in the gastrointestinal tract and blood-brain barrier compromises the oral delivery of drugs to the circulation system and brain in the treatment of Parkinson's disease (PD). In this study, we aim to develop small-sized Pluronic P85/F68 micelles loaded with baicalein (B-MCs) to overcome MRP2-mediated efflux and to investigate related mechanism, as well as the anti-Parkinsonian efficacy. Spherical and sustained-release B-MCs have a mean particle size of 40.61 nm, a low critical micelle concentration (CMC) of 5.01 × 10(-3) mg/mL with an encapsulation efficiency of 95.47% and a drug loading of 7.07%. In comparison with the free baicalein, the cellular uptake and apparent permeability coefficient (Papp) of B-MCs were significantly enhanced (p < 0.01). Fluorescence resonance energy transfer (FRET) analysis indicated that micelles carrying the hydrophobic fluorophores were internalized intact, followed by a rapid release of fluorophores inside the cells, and then the released free fluorophores were transported across the cell monolayers to the basolateral side. Further study on the MRP2 inhibitory effect showed that B-MCs could reverse the MRP2-mediated efflux of baicalein via interfering with the structure and function of mitochondria, i.e., reducing mitochondrial membrane potential and intracellular ATP level and influencing the respiration chain of mitochondria. In addition, B-MCs exerted strong neuroprotective effects on zebrafish model of PD. In summary, Pluronic P85/F68 micelles could be considered as a promising drug delivery system to reverse MRP2-mediated efflux and improve the bioactivity of this MRP2 substrate, baicalein, for the treatment of PD.

  4. Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways.

    PubMed

    Sahu, Bidya Dhar; Mahesh Kumar, Jerald; Sistla, Ramakrishna

    2015-01-01

    Acute renal failure is a serious complication of the anticancer drug cisplatin. The potential role of baicalein, a naturally occurring bioflavonoid on cisplatin-induced renal injury is unknown. Here, we assessed the effect of baicalein against a murine model of cisplatin-induced acute renal failure and investigated the underlying possible mechanisms. Renal function, kidney histology, inflammation, oxidative stress, renal mitochondrial function, proteins involved in apoptosis, nuclear translocation of Nrf2 and effects on intracellular signaling pathways such as MAPKs, and NF-κB were assessed. Pretreatment with baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and inflammation and improved kidney injury and function. Baicalein inhibited the cisplatin-induced expression of iNOS, TNF-α, IL-6 and mononuclear cell infiltration and concealed redox-sensitive transcription factor NF-κB activation via reduced DNA-binding activity, IκBα phosphorylation and p65 nuclear translocation in kidneys. Further studies demonstrated baicalein markedly attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys. Baicalein also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys. Moreover, baicalein preserved mitochondrial respiratory enzyme activities and inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2 imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP. Our findings suggest that baicalein ameliorates cisplatin-induced renal damage through up-regulation of antioxidant defense mechanisms and down regulation of the MAPKs and NF-κB signaling pathways.

  5. Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways

    PubMed Central

    Sahu, Bidya Dhar; Kumar, Jerald Mahesh; Sistla, Ramakrishna

    2015-01-01

    Acute renal failure is a serious complication of the anticancer drug cisplatin. The potential role of baicalein, a naturally occurring bioflavonoid on cisplatin-induced renal injury is unknown. Here, we assessed the effect of baicalein against a murine model of cisplatin-induced acute renal failure and investigated the underlying possible mechanisms. Renal function, kidney histology, inflammation, oxidative stress, renal mitochondrial function, proteins involved in apoptosis, nuclear translocation of Nrf2 and effects on intracellular signaling pathways such as MAPKs, and NF-κB were assessed. Pretreatment with baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and inflammation and improved kidney injury and function. Baicalein inhibited the cisplatin-induced expression of iNOS, TNF-α, IL-6 and mononuclear cell infiltration and concealed redox-sensitive transcription factor NF-κB activation via reduced DNA-binding activity, IκBα phosphorylation and p65 nuclear translocation in kidneys. Further studies demonstrated baicalein markedly attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys. Baicalein also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys. Moreover, baicalein preserved mitochondrial respiratory enzyme activities and inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2 imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP. Our findings suggest that baicalein ameliorates cisplatin-induced renal damage through up-regulation of antioxidant defense mechanisms and down regulation of the MAPKs and NF-κB signaling pathways. PMID:26222683

  6. Application of carrier and plasticizer to improve the dissolution and bioavailability of poorly water-soluble baicalein by hot melt extrusion.

    PubMed

    Zhang, Yilan; Luo, Rui; Chen, Yi; Ke, Xue; Hu, Danrong; Han, Miaomiao

    2014-06-01

    The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.

  7. Characterization and uncertainty evaluation of a new certified reference material of baicalein.

    PubMed

    Gong, Ningbo; Wang, Xiaoying; Zhang, Baoxi; Gao, Zhaolin; Du, Guanhua; Lv, Yang

    2014-02-01

    A new certified reference material (CRM) of baicalein was developed aiming to control the quality of baicalein and relative pharmaceuticals. Sample preparation, homogeneity, stability, value assignment, and uncertainty of a new certified reference material (CRM) of baicalein were presented in this paper. Characterization of the material relied on three different methods, which were differential scanning calorimetry (DSC), coulometric titration method (CT) and mass balance method. DSC and CT were used for purity determination of baicalein firstly. The certified value of baicalein CRM is 99.72% with an expanded uncertainty of 0.25% (k=2). The new CRM of baicalein can be used to validate analytical methods, improve the accuracy of measurement data as well as establish meteorological traceability of analytical results.

  8. Baicalein Promotes Neuronal and Behavioral Recovery After Intracerebral Hemorrhage Via Suppressing Apoptosis, Oxidative Stress and Neuroinflammation.

    PubMed

    Wei, Ning; Wei, Yinghai; Li, Binru; Pang, Linlin

    2017-01-21

    Intracerebral hemorrhage (ICH) is an important public health problem in neurology, which is not only associated with high mortality but also leading to disability. Yet no satisfactory treatment has been developed. The secondary injury that resulted from a number of self-destructive processes such as neuroinflammation, apoptosis and oxidative stress, is the key factor contributing to ICH-induced brain damage. Baicalein has been proved to improve neuronal functional recovery in rat model of subarachnoid hemorrhage and ischemic brain damage. To investigate the effect of baicalein on ICH and its underlying mechanism, a collagenase-induced ICH rat model was performed. Baicalein treatment significantly decreased neurological severity score at day 1 and 3 after ICH injury. Our results showed that the lesion volume, the brain water content, the expression levels of four pro-inflammatory cytokines (IL-1β, IL-4 and IL-6 and TNF-α) and the numbers of apoptotic cells were reduced significantly in ICH rats receiving baicalein treatment, especially in 50 mg/kg baicalein-treated group. Moreover, baicalein increased SOD and GSH-Px activities and down-regulated MDA level of brain tissues in rats. These results suggested that the therapeutic efficacy of baicalein on repairing brain damage is probably caused by suppressing apoptosis, oxidative stress and neuroinflammation. Baicalein could be developed into a novel drug for clinical treatment of ICH and ICH-related brain injuries.

  9. Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice.

    PubMed

    Sahu, Bidya Dhar; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Borkar, Roshan M; Srinivas, R; Sistla, Ramakrishna

    2016-01-01

    Doxorubicin is a widely used anthracycline derivative anticancer drug. Unfortunately, the clinical use of doxorubicin has the serious drawback of cardiotoxicity. In this study, we investigated whether baicalein, a bioflavonoid, can prevent doxorubicin-induced cardiotoxicity in vivo and we delineated the possible underlying mechanisms. Male BALB/c mice were treated with either intraperitoneal doxorubicin (15 mg/kg divided into three equal doses for 15 days) and/or oral baicalein (25 and 50 mg/kg for 15 days). Serum markers of cardiac injury, histology of heart, parameters related to myocardial oxidative stress, apoptosis and inflammation were investigated. Treatment with baicalein reduced doxorubicin-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and ameliorated the histopathological damage. Baicalein restored the doxorubicin-induced decrease in both enzymatic and non-enzymatic myocardial antioxidants and increased the myocardial expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Further studies showed that baicalein could inverse the Bax/Bcl-2 ratio, suppress doxorubicin-induced p53, cleaved caspase-3 and PARP expression and prevented doxorubicin-induced DNA damage. Baicalein treatment also interferes with doxorubicin-induced myocardial NF-κB signaling through inhibition of IκBα phosphorylation and nuclear translocation of p65 subunit. Doxorubicin elevated iNOS and nitrites levels were also significantly decreased in baicalein treated mice. However, we did not find any significant change (p>0.05) in the myocardial TNF-α and IL-6 levels in control and treated animals. Our finding suggests that baicalein might be a promising molecule for the prevention of doxorubicin-induced cardiotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Baicalein suppresses the SOS response system of Staphylococcus aureus induced by ciprofloxacin.

    PubMed

    Peng, Qing; Zhou, Shuqin; Yao, Fen; Hou, Bing; Huang, Yuanchun; Hua, Dexing; Zheng, Yanshan; Qian, Yuanshu

    2011-01-01

    Numerous antibiotics can induce an SOS repair system in bacteria that leads to antibiotic-resistant mutation of the bacterium. Therefore, searching for drugs that can prevent the SOS response and thus improve the long-term viability of some antibiotics is important. In this study, we aimed to detect the suppressive effects of baicalein on the SOS system and rifampin-resistant mutation in Staphylococcus aureus. We determined the reactive oxygen species (ROS) formation and intracellular ATP level in S. aureus with baicalein treatment to investigate the mechanisms involved in its effects on the SOS system. The results showed that baicalein was a potent inhibitor of the expression of the SOS genes RecA, LexA and SACOL1400. The rifampin-resistant mutation rate of S. aureus induced by ciprofloxacin was significantly reduced after treatment with baicalein. Treatment with baicalein led to a significant decrease in intracellular reactive oxygen species (ROS) formation and ATP level. Our findings indicate that baicalein may be an SOS-response inhibitor in S. aureus through inhibiting ROS formation and ATP production and may be used to prevent excessive mutation induced by antibiotics. Copyright © 2011 S. Karger AG, Basel.

  11. Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1.

    PubMed

    Kwak, Hyun Jeong; Yang, Dongki; Hwang, Yongha; Jun, Hee-Sook; Cheon, Hyae Gyeong

    2017-01-01

    β-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve β-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on β-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired β-cell function, and placed focus on the role of heme oxygenase (HO)-1. Rat pancreatic β-cell line INS-1 cells or mouse pancreatic islets were cultured with PA (500 μM) to induce lipotoxicity in the presence or absence of baicalein (50 μM), and the expressions of the ER stress markers, ATF-3, CHOP and GRP78 were detected by Western blotting and/or qPCR. The involvement of HO-1 was evaluated by HO-1 siRNA transfection and using the HO-1 inhibitor ZnPP. Baicalein reduced PA-induced ER stress and inflammation and enhanced insulin secretion, and these effects were associated with the induction of HO-1. Furthermore, these protective effects were attenuated by ZnPP and by HO-1 siRNA. Pretreatment of PD98059 (an ERK inhibitor) significantly inhibited the protective effects of baicalein and blocked HO-1 induction. On the other hand, CO production by RuCO (a CO donor) ameliorated PA-induced ER stress, suggesting that CO production followed by HO-1 induction may contribute to the protective effects of baicalein against PA-induced β-cell dysfunction. Baicalein protects pancreatic β-cells from PA-induced ER stress and inflammation via an ERK-HO-1 dependent pathway. The authors suggest HO-1 induction in pancreatic β-cells appears to be a promising therapeutic strategy for T2D.

  12. Baicalein-phospholipid complex: a novel drug delivery technology for phytotherapeutics.

    PubMed

    Rawat, Devendra Singh; Thakur, Bandana K; Semalty, Mona; Semalty, Ajay; Badoni, Prabhakar; Rawat, Mohan Singh Maniyari

    2013-09-01

    Flavonoids are a group of low-molecular-weight polyphenolic compounds of plant origin. They exhibit a variety of biological activities such as anti-inflammatory, antioxidant, antiviral, and antitumor etc. Baicalein, is a bioactive flavone constituent of Scutellariae radix with a wide range of beneficial activities. But the poor solubility and dissolution rate limit its oral intestinal absorption and bioavailability. The aim of this study was to develop an amphiphilic phytophospholipid complex in order to enhance the delivery of poorly soluble drug (baicalein). The baicalein-phospholipid complex (Ba-PLc) was prepared and evaluated for various physico-chemical parameters like drug loading, infrared absorption (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffractometry (X-RPD), scanning electron microscopy (SEM), aqueous/ n-octanol solubility and dissolution study. In the SEM, phospholipid complex (Ba-PLc) was found fluffy and porous with rough surface morphology. FT-IR, DSC and X-RPD data confirmed the formation of phospholipid complex. The water/ n-octanol solubility of baicalein was improved significantly in the complex. Improved dissolution was shown by the phospholipid complex. The results of the study concluded that the phospholipid complex may be considered as a promising drug delivery system for improving the absorption and overall bioavailability of the baicalein molecule.

  13. Modified paraffin wax for improvement of histological analysis efficiency.

    PubMed

    Lim, Jin Ik; Lim, Kook-Jin; Choi, Jin-Young; Lee, Yong-Keun

    2010-08-01

    Paraffin wax is usually used as an embedding medium for histological analysis of natural tissue. However, it is not easy to obtain enough numbers of satisfactory sectioned slices because of the difference in mechanical properties between the paraffin and embedded tissue. We describe a modified paraffin wax that can improve the histological analysis efficiency of natural tissue, composed of paraffin and ethylene vinyl acetate (EVA) resin (0, 3, 5, and 10 wt %). Softening temperature of the paraffin/EVA media was similar to that of paraffin (50-60 degrees C). The paraffin/EVA media dissolved completely in xylene after 30 min at 50 degrees C. Physical properties such as the amount of load under the same compressive displacement, elastic recovery, and crystal intensity increased with increased EVA content. EVA medium (5 wt %) was regarded as an optimal composition, based on the sectioning efficiency measured by the numbers of unimpaired sectioned slices, amount of load under the same compressive displacement, and elastic recovery test. Based on the staining test of sectioned slices embedded in a 5 wt % EVA medium by hematoxylin and eosin (H&E), Masson trichrome (MT), and other staining tests, it was concluded that the modified paraffin wax can improve the histological analysis efficiency with various natural tissues.

  14. Exploring Therapeutic Potentials of Baicalin and Its Aglycone Baicalein for Hematological Malignancies

    PubMed Central

    Chen, Haijun; Gao, Yu; Wu, Jianlei; Chen, Yingyu; Chen, Buyuan; Hu, Jianda; Zhou, Jia

    2014-01-01

    Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized. PMID:25128647

  15. Actual drawing of histological images improves knowledge retention.

    PubMed

    Balemans, Monique C M; Kooloos, Jan G M; Donders, A Rogier T; Van der Zee, Catharina E E M

    2016-01-01

    Medical students have to process a large amount of information during the first years of their study, which has to be retained over long periods of nonuse. Therefore, it would be beneficial when knowledge is gained in a way that promotes long-term retention. Paper-and-pencil drawings for the uptake of form-function relationships of basic tissues has been a teaching tool for a long time, but now seems to be redundant with virtual microscopy on computer-screens and printers everywhere. Several studies claimed that, apart from learning from pictures, actual drawing of images significantly improved knowledge retention. However, these studies applied only immediate post-tests. We investigated the effects of actual drawing of histological images, using randomized cross-over design and different retention periods. The first part of the study concerned esophageal and tracheal epithelium, with 384 medical and biomedical sciences students randomly assigned to either the drawing or the nondrawing group. For the second part of the study, concerning heart muscle cells, students from the previous drawing group were now assigned to the nondrawing group and vice versa. One, four, and six weeks after the experimental intervention, the students were given a free recall test and a questionnaire or drawing exercise, to determine the amount of knowledge retention. The data from this study showed that knowledge retention was significantly improved in the drawing groups compared with the nondrawing groups, even after four or six weeks. This suggests that actual drawing of histological images can be used as a tool to improve long-term knowledge retention.

  16. Inhibitory Effect of Baicalin and Baicalein on Ovarian Cancer Cells

    PubMed Central

    Chen, Jianchu; Li, Zhaoliang; Chen, Allen Y.; Ye, Xingqian; Luo, Haitao; Rankin, Gary O.; Chen, Yi Charlie

    2013-01-01

    Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant activity and possible anti-angiogenic, anti-cancer, anxiolytic, anti-inflammatory and neuroprotective activities. Two kinds of ovarian cancer (OVCAR-3 and CP-70) cell lines and a normal ovarian cell line (IOSE-364) were selected to be investigated in the inhibitory effect of baicalin and baicalein on cancer cells. Largely, baicalin and baicalein inhibited ovarian cancer cell viability in both ovarian cancer cell lines with LD50 values in the range of 45–55 μM for baicalin and 25–40 μM for baicalein. On the other hand, both compounds had fewer inhibitory effects on normal ovarian cells viability with LD50 values of 177 μM for baicalin and 68 μM for baicalein. Baicalin decreased expression of VEGF (20 μM), cMyc (80 μM), and NFkB (20 μM); baicalein decreased expression of VEGF (10 μM), HIF-1α (20 μM), cMyc (20 μM), and NFkB (40 μM). Therefore baicalein is more effective in inhibiting cancer cell viability and expression of VEGF, HIF-1α, cMyc, and NFκB in both ovarian cancer cell lines. It seems that baicalein inhibited cancer cell viability through the inhibition of cancer promoting genes expression including VEGF, HIF-1α, cMyc, and NFκB. Overall, this study showed that baicalein and baicalin significantly inhibited the viability of ovarian cancer cells, while generally exerting less of an effect on normal cells. They have potential for chemoprevention and treatment of ovarian cancers. PMID:23502466

  17. Inhibition of p65 Nuclear Translocation by Baicalein

    PubMed Central

    Seo, Min Bum; Lee, Seog Ki; Jeon, Young Jin

    2011-01-01

    We demonstrate that baicalein, a bioactive flavonoid originally isolated from Scutellaria baicalensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of peritoneal macrophages and RAW 264.7 cells with baicalein inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohistochemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression in RAW 264.7 cells. Immunostaining of p65, EMSA, and reporter gene assay showed that baicalein inhibited NF-κB nuclear translocation, DNA binding, and transcriptional activation, respectively. Collectively, these series of experiments indicate that baicalein inhibits iNOS gene expression by blocking NF-κB nuclear translocation. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of baicalein on iNOS suggest that baicalein may represent a useful anti-inflammatory agent. PMID:24278554

  18. Novel antiviral activity of baicalein against dengue virus

    PubMed Central

    2012-01-01

    Background Dengue is a serious arboviral disease currently with no effective antiviral therapy or approved vaccine available. Therefore, finding the effective compound against dengue virus (DENV) replication is very important. Among the natural compounds, bioflavonoids derived mainly from plants are of interest because of their biological and medicinal benefits. Methods In the present study, antiviral activity of a bioflavonoid, baicalein, was evaluated against different stages of dengue virus type 2 (DENV-2) replication in Vero cells using focus forming unit reduction assay and quantitative RT-PCR. Results Baicalein inhibited DENV-2 replication in Vero cells with IC50= 6.46 μg/mL and SI= 17.8 when added after adsorption to the cells. The IC50 against DENV-2 was 5.39 μg/mL and SI= 21.3 when cells were treated 5 hours before virus infection and continuously up to 4 days post infection. Baicalein exhibited direct virucidal effect against DENV-2 with IC 50= 1.55 μg/mL and showed anti-adsorption effect with IC50 = 7.14 μg/mL. Conclusions Findings presented here suggest that baicalein exerts potent antiviral activity against DENV. Baicalein possesses direct virucidal activity against DENV besides its effects against dengue virus adsorption and intracellular replication of DENV-2. Baicalein, hence, should be considered for in vivo evaluation in the development of an effective antiviral compound against DENV. PMID:23140177

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

    PubMed

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

    2010-02-07

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

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

    PubMed Central

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

    2010-01-01

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

  1. IVUS-based histology of atherosclerotic plaques: improving longitudinal resolution

    NASA Astrophysics Data System (ADS)

    Taki, Arash; Pauly, Olivier; Setarehdan, S. Kamaledin; Unal, Gozde; Navab, Nassir

    2010-03-01

    Although Virtual Histology (VH) is the in-vivo gold standard for atherosclerosis plaque characterization in IVUS images, it suffers from a poor longitudinal resolution due to ECG-gating. In this paper, we propose an image-based approach to overcome this limitation. Since each tissue have different echogenic characteristics, they show in IVUS images different local frequency components. By using Redundant Wavelet Packet Transform (RWPT), IVUS images are decomposed in multiple sub-band images. To encode the textural statistics of each resulting image, run-length features are extracted from the neighborhood centered on each pixel. To provide the best discrimination power according to these features, relevant sub-bands are selected by using Local Discriminant Bases (LDB) algorithm in combination with Fisher's criterion. A structure of weighted multi-class SVM permits the classification of the extracted feature vectors into three tissue classes, namely fibro-fatty, necrotic core and dense calcified tissues. Results shows the superiority of our approach with an overall accuracy of 72% in comparison to methods based on Local Binary Pattern and Co-occurrence, which respectively give accuracy rates of 70% and 71%.

  2. The Fascinating Effects of Baicalein on Cancer: A Review

    PubMed Central

    Liu, Hui; Dong, Yonghui; Gao, Yutong; Du, Zhipeng; Wang, Yuting; Cheng, Peng; Chen, Anmin; Huang, Hui

    2016-01-01

    Cancer is one of the leading causes of death worldwide and a major global health problem. In recent decades, the rates of both mortality and morbidity of cancer have rapidly increased for a variety of reasons. Despite treatment options, there are serious side effects associated with chemotherapy drugs and multiple forms of drug resistance that significantly reduce their effects. There is an accumulating amount of evidence on the pharmacological activities of baicalein (e.g., anti-inflammatory, antioxidant, antiviral, and antitumor effects). Furthermore, there has been great progress in elucidating the target mechanisms and signaling pathways of baicalein’s anti-cancer potential. The anti-tumor functions of baicalein are mainly due to its capacities to inhibit complexes of cyclins to regulate the cell cycle, to scavenge oxidative radicals, to attenuate mitogen activated protein kinase (MAPK), protein kinase B (Akt) or mammalian target of rapamycin (mTOR) activities, to induce apoptosis by activating caspase-9/-3 and to inhibit tumorinvasion and metastasis by reducing the expression of matrix metalloproteinase-2/-9 (MMP-2/-9). In this review, we focused on the relevant biological mechanisms of baicalein involved in inhibiting various cancers, such as bladder cancer, breast cancer, and ovarian cancer. Moreover, we also summarized the specific mechanisms by which baicalein inhibited the growth of various tumors in vivo. Taken together, baicalein may be developed as a potential, novel anticancer drug to treat tumors. PMID:27735841

  3. Baicalein inhibits lipid accumulation by regulating early adipogenesis and m-TOR signaling.

    PubMed

    Seo, Min-Jung; Choi, Hyeon-Son; Jeon, Hui-Jeon; Woo, Mi-Seon; Lee, Boo-Yong

    2014-05-01

    Baicalein is a type of flavonoid that originates from Scutellaria baicalensis. In this study, we examined how baicalein inhibits lipid accumulation during adipogenesis in 3T3-L1 cells. Our data show that baicalein inhibited lipid accumulation during adipogenesis in a dose-dependent manner. Baicalein inhibition was limited to the early adipogenic stage. Cell cycle analysis showed that baicalein induced cell cycle arrest in the G0/G1 phase through cyclin downregulation. In addition, baicalein suppressed the mRNA expression of early adipogenic factors leading to downregulation of late adipogenic factors at mRNA and protein levels. Inhibition of adipogenic factors by baicalein was correlated with downregulation of lipid synthetic enzymes. Additionally, baicalein negatively regulated the m-TOR signaling pathway involved in lipid accumulation during adipogenesis, thus inhibiting phosphorylation of m-TOR and p70S6K. In a zebrafish study, baicalein significantly reduced lipid accumulation in Nile Red staining. Consistent with a report using cell lines, mRNA expression of adipogenic factors was decreased in a dose-dependent manner by baicalein. This result reflects a reduction in total triglyceride levels based on a triglyceride assay. Our data suggest that baicalein inhibits lipid accumulation by controlling the cell cycle and m-TOR signaling in 3T3-L1 cells, and its anti-adipogenic effect was found in a zebrafish model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Baicalein protects mice against radiation-induced DNA damages and genotoxicity.

    PubMed

    Gandhi, Nitin Motilal

    2013-07-01

    Baicalein is the major flavonoid extracted from the root of Scutellaria baicaleins. This flavonoid is used extensively in Chinese herbal medicine. In the present study baicalein is evaluated for its radioprotective properties. Human blood cells when exposed to the γ-radiation ex vivo in presence of baicalein underwent the reduced DNA damage compared to the control. Baicalein administration prior to the whole-body γ-radiation (4 Gy) exposure of mice resulted in protecting the damage to the DNA as measured in their blood cells by alkaline comet assay. Mice when exposed to the radiation (whole body; 1.7 Gy) resulted in damage to the bone marrow as measured by micronucleated reticulocyte (MNRET) formation. Baicalein pre-treatment reduces the radiation induced damage to the bone marrow cells, as there was decrease in the percentage MNRET formation. These findings indicate radio-protecting ability of baicalein.

  5. Baicalein Protects Human Skin Cells against Ultraviolet B-Induced Oxidative Stress

    PubMed Central

    Oh, Min Chang; Piao, Mei Jing; Fernando, Pattage Madushan Dilhara Jayatissa; Han, Xia; Hewage, Susara Ruwan Kumara Madduma; Park, Jeong Eon; Ko, Mi Sung; Jung, Uhee; Kim, In Gyu; Hyun, Jin Won

    2016-01-01

    Baicalein (5,6,7-trihydroxy-2-phenyl-chromen-4-one) is a flavone, a type of flavonoid, originally isolated from the roots of Scutellaria baicalensis. This study evaluated the protective effects of baicalein against oxidative damage-mediated apoptosis induced by ultraviolet B (UVB) radiation in a human keratinocyte cell line (HaCaT). Baicalein absorbed light within the wavelength range of UVB. In addition, baicalein decreased the level of intracellular reactive oxygen species (ROS) in response to UVB radiation. Baicalein protected cells against UVB radiation-induced DNA breaks, 8-isoprostane generation and protein modification in HaCaT cells. Furthermore, baicalein suppressed the apoptotic cell death by UVB radiation. These findings suggest that baicalein protected HaCaT cells against UVB radiation-induced cell damage and apoptosis by absorbing UVB radiation and scavenging ROS. PMID:27257012

  6. Identification of baicalein as a ferroptosis inhibitor by natural product library screening.

    PubMed

    Xie, Yangchun; Song, Xinxin; Sun, Xiaofang; Huang, Jin; Zhong, Meizuo; Lotze, Michael T; Zeh, Herbert J; Kang, Rui; Tang, Daolin

    2016-05-13

    Ferroptosis, a novel form of regulated cell death, is characterized by oxidative injury from iron accumulation and lipid peroxidation. In a natural product library screening for ferroptosis inhibitor, we found that baicalein is a potent inhibitor of erastin-induced ferroptosis in pancreatic cancer cells. Baicalein (also termed 5,6,7-trihydroxyflavone) is a flavonoid originally obtained from the roots of Scutellaria baicalensis and Scutellaria lateriflora. We showed that baicalein exhibits remarkable anti-ferroptosis activity compared with well-known ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, deferoxamine mesylate, and β-mercaptoethanol. At the biochemistry level, baicalein limits erastin-induced ferrous iron production, glutathione depletion, and lipid peroxidation. At the protein level, baicalein suppresses erastin-mediated degradation of glutathione peroxidase 4, a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation. Thus, baicalein enhances cellular anti-ferroptosis capacity and could be a potential therapeutic agent for ferroptosis-associated tissue injury.

  7. Baicalein inhibits the migration and invasive properties of human hepatoma cells

    SciTech Connect

    Chiu, Yung-Wei; Lin, Tseng-Hsi; Huang, Wen-Shih; Teng, Chun-Yuh; Liou, Yi-Sheng; Kuo, Wu-Hsien; Lin, Wea-Lung; Huang, Hai-I; Tung, Jai-Nien; Huang, Chih-Yang; Liu, Jer-Yuh; Wang, Wen-Hung; Hwang, Jin-Ming

    2011-09-15

    Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24 h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-{beta}. In addition, baicalein reduced the phosphorylation levels of PKC{alpha} and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo. - Highlight: > Baicalein inhibits several essential steps in the onset of metastasis.

  8. Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis.

    PubMed

    Leung, Henry W C; Yang, W H; Lai, M Y; Lin, C J; Lee, H Z

    2007-03-01

    Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor. The 12-LOX is found to be involved in the progression of human cancers and the inhibitor of 12-LOX offers a target for the prevention cancer. We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. Treatment of baicalein inhibited the growth of H460 cells in a dose-dependent manner. Following 24h exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Furthermore, baicalein induced the most of H460 cell apoptosis after treatment for 48h. H460 cells formed vesicles and apoptotic body, and then floated after treatment with baicalein. Baicalein-induced H460 cell apoptosis was confirmed by DNA condensation and fragmentation. Baicalein-induced apoptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels. Pretreatment with a specific caspase-3 inhibitor, Ac-DEVD-CHO, partially reduced baicalein-induced cell death, indicating baicalein induces apoptosis is partially dependent on caspase-3 pathway in H460 cells. These data suggest that baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.

  9. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders.

    PubMed

    Dinda, Biswanath; Dinda, Subhajit; DasSharma, Saikat; Banik, Rajarshi; Chakraborty, Ankita; Dinda, Manikarna

    2017-05-05

    The flavonoids, baicalin (5,6-dihydroxy-2-phenyl-4H-1-benzopyran-4-one-7-O-d-β-glucuronic acid) 1 and its aglycone, baicalein 2 are found in edible medicinal plants, Scutellaria baicalensis Georgi and Oroxylum indicum (L.) Kurz in abundant quantities. The antioxidant and anti-inflammatory effects of these flavonoids have been demonstrated in various disease models, including diabetes, cardiovascular diseases, inflammatory bowel diseases, gout and rheumatoid arthritis, asthma, neurodegenerative-, liver- and kidney diseases, encephalomyelitis, and carcinogenesis. These flavonoids have almost no toxicity to human normal epithelial, peripheral and myeloid cells. Their antioxidant and anti-inflammatory activities are largely due to their abilities to scavenge the reactive oxygen species (ROS) and improvement of antioxidant status by attenuating the activity of NF-κB and suppressing the expression of several inflammatory cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1), nitric oxide synthase, cyclooxygenases, lipoxygenases, cellular adhesion molecules, tumor necrosis factor and interleukins. In this review, we summarize the antioxidant and anti-inflammatory effects of baicalin and baicalein with molecular mechanisms for their chemopreventive and chemotherapeutic applications in the treatment of inflammatory-related diseases.

  10. In vitro evidence of baicalein's inhibition of the metabolism of zidovudine (AZT).

    PubMed

    Wang, Yu-Cun; Yang, Hai-Yan; Kong, Ling-Ting; Yu, Feng-Xia

    2014-03-01

    Herb-drug interaction (HDI) has been regarded as a key factor limiting the clinical application of herbs and drugs. Potential baicalein-zidovudine (AZT) interaction was predicted in the present study. In vitro evaluation of baicalein's inhibition towards human liver microsomes (HLMs)-catalyzed metabolism of zidovudine (AZT) was performed. Dixon and Lineweaver-Burk plots were used to determine the inhibition kinetic type, and second plot with the slopes from Lineweaver-Burk plot versus the concentrations of baicalein was employed to calculate the inhibition parameter (Ki). In combination with the in vivo concentration of baicalein, in vitro-in vivo extrapolation (IVIVE) was carried out to predict in vivo baicalein-AZT interaction. Competitive inhibition of baicalein towards AZT metabolism was demonstrated, and the Ki value was calculated to be 101.2 µM. The value of AUCi/AUC was calculated to be 2. Potential baicalein-AZT interaction was indicated in the present study, indicating the need for monitoring when AZT is co-administrated with baicalein or baicalein-containing herbs.

  11. Enhanced delivery of baicalein using cinnamaldehyde cross-linked chitosan nanoparticle inducing apoptosis.

    PubMed

    Nipun Babu, Varukattu; Kannan, Soundarapandian

    2012-12-01

    The chitosan (CS) nanoparticles, baicalein loaded chitosan nanoparticles were prepared by crosslinking method in a W/O emulsion system, using cinnamaldehyde as crosslinking agent. The FT-IR result showed the binding of anticancer compound baicalein to the nanoparticles. The TEM analysis revealed that the particles are spherical in nature. Zeta potential revealed negative charge of the particles. Ultraviolet spectrum analysis described that higher loading efficiency and encapsulation efficiency as 9.1% and 97.2%, respectively. In vitro baicalein release profile demonstrated the delivery of baicalein from the CS nanoparticles is a two stage process. RT-PCR and cell culture was carried out accordingly.

  12. Baicalein induces cell death in murine T cell lymphoma via inhibition of thioredoxin system.

    PubMed

    Patwardhan, Raghavendra S; Pal, Debojyoti; Checker, Rahul; Sharma, Deepak; Sandur, Santosh K

    2017-08-31

    We have earlier demonstrated the radioprotective potential of baicalein using murine splenic lymphocytes. Here, we have studied the effect of baicalein on murine T cell lymphoma EL4 cells and investigated the underlying mechanism of action. We observed that baicalein induced a dose dependent cell death in EL4 cells in vitro and significantly reduced the frequency of cancer stem cells. Previously, we have reported that murine and human T cell lymphoma cells have increased oxidative stress tolerance capacity due to active thioredoxin system. Hence, we monitored the effect of baicalein on thioredoxin system in EL4 cells. Docking studies revealed that baicalein could bind to the active site of thioredoxin reductase. Baicalein treatment led to significant reduction in the activity of thioredoxin reductase and nuclear levels of thioredoxin-1 thereby increasing ASK1 levels and caspase-3 activity. Interestingly, CRISPR-Cas9 based knock-out of ASK1 or over-expression of thioredoxin-1 abolished anti-tumor effects of baicalein in EL4 cells. Further, baicalein administration significantly reduced intra-peritoneal tumor burden of EL4 cells in C57BL/6 mice. Thus, our study describes anti-tumor effects of baicalein in EL4 cells via inhibition of thioredoxin system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Inclusion complexation between baicalein and β-cyclodextrin and the influence of β-cyclodextrin on the binding of baicalein with DNA: a spectroscopic approach.

    PubMed

    Sameena, Yousuf; Chandrasekaran, Sowrirajan; Israel V M V, Enoch

    2016-07-01

    This work deals with the commonly studied cyclic oligosaccharide and gains importance as it is entered on a drug delivering carbohydrate and provides insight into the oligosaccharide complex-biomolecular interaction. The binding of a flavone, baicalein, to β-cyclodextrin and calf thymus DNA is studied. The binding of baicalein to calf thymus DNA in the presence of β-cyclodextrin is analysed using the UV-vis absorption and fluorescence spectroscopy. The mode of binding and structure of the baicalein-β-cyclodextrin complex are reported. The role of the structure and the stoichiometry of the inclusion complex of baicalein-β-cyclodextrin in its influence on DNA binding are analysed. Highlights • This paper deals with the binding of a flavone, baicalein to β-cyclodextrin and/or DNA. • The inclusion complexation between baicalein and β-cyclodextrin is analysed. • The stoichiometry and the binding strength of the inclusion complex is reported. • The role of β-cyclodextrin in tuning the binding of baicalein to DNA is emphasized. • Spectroscopic and docking analysis are used to articulate the results.

  14. Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women.

    PubMed

    Al-Saqi, Shahla Hamza; Jonasson, Aino Fianu; Naessén, Tord; Uvnäs-Moberg, Kerstin

    2016-03-01

    To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo. Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks. The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04). Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells. © The Author(s) 2016.

  15. The "flipped classroom" approach: Stimulating positive learning attitudes and improving mastery of histology among medical students.

    PubMed

    Cheng, Xin; Ka Ho Lee, Kenneth; Chang, Eric Y; Yang, Xuesong

    2017-07-01

    Traditional medical education methodologies have been dramatically impacted by the introduction of new teaching approaches over the past few decades. In particular, the "flipped classroom" format has drawn a great deal of attention. However, evidence regarding the effectiveness of the flipped model remains limited due to a lack of outcome-based studies. In the present study, a pilot histology curriculum of the organ systems was implemented among 24 Traditional Chinese Medicine (TCM) students in a flipped classroom format at Jinan University. As a control, another 87 TCM students followed a conventional histology curriculum. The academic performance of the two groups was compared. In addition, a questionnaire was administered to the flipped classroom group. The test scores for the flipped classroom participants were found to be significantly higher compared to non-participants in the control group. These results suggest that students may benefit from using the flipped classroom format. Follow-up questionnaires also revealed that most of the flipped classroom participants undertook relatively more earnest preparations before class and were actively involved in classroom learning activities. The teachers were also found to have more class time for leading discussions and delivering quizzes rather than repeating rote didactics. Consequently, the increased teaching and learning activities contributed to a better performance among the flipped classroom group. This pilot study suggests that a flipped classroom approach can be used to improve histology education among medical students. However, future studies employing randomization, larger numbers of students, and more precise tracking methods are needed before definitive conclusions can be drawn. Anat Sci Educ 10: 317-327. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

  16. Effect of the Lipoxygenase Inhibitor Baicalein on Muscles in Ovariectomized Rats

    PubMed Central

    Kling, J. H.; Kosinsky, R. L.; Hoffmann, D. B.; Komrakova, M.; Wicke, M.; Menger, B.; Sehmisch, S.

    2016-01-01

    Sarcopenia, a loss of muscle mass accompanying osteoporosis, leads to falls and fall-related injuries. Baicalein, as a phytochemical agent, has an antioxidative and anti-inflammatory effect in muscle. In this study, sixty-one female Sprague Dawley rats were divided into five groups: four groups were ovariectomized (OVX) and one control group was nonovariectomized (NON-OVX). Eight weeks after ovariectomy, three disparate concentrations (1 mg/kg body weight (BW), 10 mg/kg BW, and 100 mg/kg BW) of baicalein were applied subcutaneously daily in three OVX groups. Mm. soleus, gastrocnemius, and longissimus were extracted; their diameter, area, relation to body, and muscle weights as well as number of capillaries per fibre were recorded. In Mm. soleus and gastrocnemius, the baicalein effect (increasing number of capillaries per fibre) was proportional to the dose applied. The fibre diameters and area under baicalein treatment were significantly greater compared to OVX and NON-OVX groups. In M. longissimus, we observed a shift to type IIa fibres. Serum creatine kinase levels were significantly lower in highest baicalein concentration group. We conclude that baicalein can stimulate angiogenesis, though not fibre type-specific, in skeletal muscle and reduce the estrogen-related loss of fibre diameter and area in the skeletal muscle in rats. Therefore, a protective effect of baicalein on muscle cells can be assumed. PMID:28050282

  17. Inhibitory Effects of Multiple-Dose Treatment with Baicalein on the Pharmacokinetics of Ciprofloxacin in Rats.

    PubMed

    Hwang, Youn-Hwan; Yang, Hye Jin; Kim, Dong-Gun; Ma, Jin Yeul

    2017-01-01

    Ciprofloxacin is used as a treatment for urinary and respiratory tract infections in clinical practice. Baicalein, a major flavonoid present in Scutellaria baicalensis, is a well-known and potent antibacterial compound used in complementary and alternative medicine practices. The present study aimed to clarify the effects of multiple-dose treatment with baicalein on the pharmacokinetics of ciprofloxacin in rats. Following the oral administration of baicalein (20, 40, or 80 mg/kg) for five consecutive days, the rats received an oral administration of ciprofloxacin (20 mg/kg). Blood samples were collected at specific time points, and the plasma concentrations of ciprofloxacin were determined by using high-performance liquid chromatography. To evaluate the mechanisms underlying the interaction between baicalein and ciprofloxacin, a rhodamine 123 accumulation assay was performed in LS-180 cells. A pharmacokinetic study revealed that multiple-dose treatment with baicalein significantly decreased the peak serum concentration (Cmax ), area under the curve (AUC0 → 480 min ), and relative bioavailability (Frel ) of ciprofloxacin (p < 0.05). The rhodamine 123 accumulation assay revealed that treatment with baicalein for 48 h markedly reduced the intracellular accumulation of rhodamine 123. Taken together, these findings suggest that baicalein may result in the therapeutic failure of ciprofloxacin or other quinolone-based antibiotics used for chemotherapy in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells

    PubMed Central

    Jiang, Chunping; Luo, Dongjun; Cao, Yin; Liu, Baorui

    2014-01-01

    Background. Hepatocellular carcinoma (HCC) remains a disastrous disease and the treatment for HCC is rather limited. Separation and identification of active compounds from traditionally used herbs in HCC treatment may shed light on novel therapeutic drugs for HCC. Methods. Cell viability and colony forming assay were conducted to determine anti-HCC activity. Morphology of cells and activity of caspases were analyzed. Antiapoptotic Bcl-2 family proteins and JNK were also examined. Levels of unfolded protein response (UPR) markers were determined and intracellular calcium was assayed. Small interfering RNAs (siRNAs) were used to investigate the role of UPR and autophagy in baicalein-induced cell death. Results. Among four studied flavonoids, only baicalein exhibited satisfactory inhibition of viability and colony formation of HCC cells within water-soluble concentration. Baicalein induced apoptosis via endoplasmic reticulum (ER) stress, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK. CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles. Protective autophagy was also triggered by baicalein in HCC cells. Conclusion. Baicalein exhibits prominent anti-HCC activity. This flavonoid induces apoptosis and protective autophagy via ER stress. Combination of baicalein and autophagy inhibitors may represent a promising therapy against HCC. PMID:24995326

  19. Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin.

    PubMed

    Wang, Chong-Zhi; Zhang, Chun-Feng; Chen, Lina; Anderson, Samantha; Lu, Fang; Yuan, Chun-Su

    2015-11-01

    Baicalin is a major constituent of Scutellaria baicalensis, which is a commonly used herbal medicine in many Asian countries. After oral ingestion, intestinal microbiota metabolism may change parent compound's structure and its biological activities. However, whether baicalin can be metabolized by enteric microbiota and the related anticancer activity is not clear. In this study, using human enteric microbiome incubation and HPLC analysis, we observed that baicalin can be quickly converted to baicalein. We compared the antiproliferative effects of baicalin and baicalein using a panel of human cancer cell lines, including three human colorectal cancer (CRC) cell lines. In vitro antiproliferative effects on CRC cells were verified using an in vivo xenograft nude mouse model. Baicalin showed limited antiproliferative effects on some of these cancer cell lines. Baicalein, however, showed significant antiproliferative effects in all the tested cancer cell lines, especially on HCT-116 human colorectal cancer cells. In vivo antitumor results supported our in vitro data. We demonstrated that baicalein exerts potent S phase cell cycle arrest and pro-apoptotic effects in HCT-116 cells. Baicalein induced the activation of caspase 3 and 9. The in silico modeling suggested that baicalein forms hydrogen bonds with residues Ser251 and Asp253 at the active site of caspase 3, while interactions with residues Leu227 and Asp228 in caspase 9 through its hydroxyl groups. Data from this study suggested that baicalein is a potent anticancer metabolite derived from S. baicalensis. Enteric microbiota play a key role in the colon cancer chemoprevention of S. baicalensis.

  20. Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: A cohort study.

    PubMed

    Borssén, Åsa D; Palmqvist, Richard; Kechagias, Stergios; Marschall, Hanns-Ulrich; Bergquist, Annika; Rorsman, Fredrik; Weiland, Ola; Verbaan, Hans; Nyhlin, Nils; Nilsson, Emma; Werner, Mårten

    2017-08-01

    Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis.A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared.Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy.Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

  1. Using LEAN principles to improve quality, patient safety, and workflow in histology and anatomic pathology.

    PubMed

    Serrano, Leo; Hegge, Pamela; Sato, Brendon; Richmond, Barbara; Stahnke, Lennis

    2010-05-01

    Histology and anatomic pathology have historically been slow to accept many of the process changes that have been widely accepted in the clinical laboratory. In this article, we describe the application of the Toyota Production System (LEAN) to histology and anatomic pathology as implemented at the Avera McKennan Hospital laboratory. Avera McKennan is the flagship hospital of the Avera Health System, a faith based, not for profit healthcare system based in South Dakota. Comprised of 235 hospitals, clinics, and physicians, with over 12,000 employees, Avera Health is one of the largest healthcare systems in the region. Beginning in 2004, Avera McKennan's laboratory began its "LEAN journey" and in the intervening years has expanded it throughout all areas of the laboratory. Following the example set by the laboratory, many other areas of the hospital have joined in the LEAN Process Improvement journey. In January 2009, the Avera McKennan Laboratory became the first hospital laboratory in the US to achieve the CAP ISO-15189 accreditation in both clinical and anatomic pathology.

  2. Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro.

    PubMed

    Chen, Yan; Liu, Tangjuan; Wang, Ke; Hou, Changchun; Cai, Shuangqi; Huang, Yingying; Du, Zhongye; Huang, Hong; Kong, Jinliang; Chen, Yiqiang

    2016-01-01

    Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections.

  3. Baicalein reduces angiogenesis in the inflammatory microenvironment via inhibiting the expression of AP-1

    PubMed Central

    Huang, Yujie; Miao, Zhaorui; Hu, Yang; Yuan, Yang; Zhou, Yuxin; Wei, Libin; Zhao, Kai; Guo, Qinglong; Lu, Na

    2017-01-01

    Increasing clinical and experimental studies have demonstrated that refractory chronic inflammation will result in malignant tumor and anti-angiogenic therapy may be an effective way to thwart the progression. Baicalein, one of the major active flavanoids found in Scutellaria baicalensis Georgi, has been exhibited potent anti-inflammation and anti-tumor effects by reducing angiogenesis. However, the exact mechanism of baicalein on endothelial cells in inflammatory microenvironment was not clear yet. Here, we investigated the anti-angiogenic effect of baicalein by incubating human umbilical vein endothelial cells (HUVECs) with THP-1 conditioned medium in vitro. The tube formation of HUVECs and microvessel outgrowth of rat aorta were attenuated, as well as the number of newly formed blood vessels in chicken chorioallantoic membrane (CAM) was reduced by baicalein. This anti-angiogenic effect was mainly on account of the inhibited motility, migration and invasion of HUVECs. In addition, mechanistic studies showed that baicalein could bind to AP-1 directly and the expression of c-Jun and c-Fos in HUVECs was reduced, accompanied by their increased proteasomal degradation. Besides, baicalein suppressed the nuclear translation, heterodimer formation and DNA binding affinity of c-Jun and c-Fos. What's more, the anti-angiogenic effect of baicalein was further confirmed by matrigel plug assay in vivo. Taken together, our study demonstrated that baicalein could exert its anti-angiogenic effect in the inflammation microenvironment via inhibiting the transcriptional activity of AP-1, which suggested that baicalein might be an alternative treatment against refractory chronic inflammation. PMID:27903990

  4. Synergy between baicalein and penicillins against penicillinase-producing Staphylococcus aureus.

    PubMed

    Qian, Minyi; Tang, Shusheng; Wu, Congming; Wang, Yang; He, Tao; Chen, Tingting; Xiao, Xilong

    2015-09-01

    The combination of baicalein (the active constituent of Scutellaria baicalensis) with penicillin G/amoxicillin showed potent synergy against 20 clinical penicillinase-producing Staphylococcus aureus strains including 10 isolates that were additionally methicillin-resistant (MRSA). The fractional inhibitory concentration (FIC) indices of penicillins+baiclein ranged from 0.14 to 0.38. Baicalein protected penicillins (penicillin G and amoxicillin) from penicillinase and increased the susceptibility of penicillinase-supplemented S. aureus ATCC 29213 in a dose-dependent manner. The inhibition of penicillinase activity by baicalein should be responsible for the synergism and protective effect. These findings offer us good evidence that the penicillins combined with baicalein showed potent synergistic activity against penicillinase-producing S. aureus and penicillinase-producing MRSA in vitro and might provide promising implications for clinical treatment of these bacterial infections. Copyright © 2015 Elsevier GmbH. All rights reserved.

  5. Effectiveness of an electronic histology tutorial for first-year dental students and improvement in "normalized" test scores.

    PubMed

    Rosenberg, Harold; Kermalli, Jaffer; Freeman, Eric; Tenenbaum, Howard; Locker, David; Cohen, Howard

    2006-12-01

    The effectiveness of an electronic histology tutorial (EHT) as a mode of learning was assessed by comparing performance on two term tests for an EHT class of sixty-nine students and five prior classes (n=347) who learned by traditional methods. The aims of this study were to 1) develop and introduce a self-instructional, computer-aided approach to guide student learning in the first-year histology course at the University of Toronto Faculty of Dentistry; 2) evaluate the effectiveness of the self-study electronic histology tutorial by comparing students' test scores for the EHT group to students' scores in previous years; and 3) evaluate students' acceptance of this novel mode of learning by means of a satisfaction questionnaire. The EHT group performed significantly better on both the general histology and oral histology term tests than the five prior control years (p<0.001), yet there were no significant differences in overall GPA between the groups, suggesting that the improvement was specific to the EHT/histology course grades (p=0.1 to 0.47). A statistically significant improvement in performance per unit overall GPA was noted in the test group, which demonstrated an increase in this test score normalized ratio (TSNR) of 3-18 percent in the general histology term test and 7-21 percent in the oral histology term test over the control groups. In addition to determining the effects of the EHT on grade performance, this study sought to evaluate students' acceptance of this alternative mode of learning in comparison to the standard teaching model by means of a satisfaction questionnaire. Overall, students' responses to the questionnaire were positive with an overall mean level of agreement for all ten responses of 4.5 out of 5 (90 percent).

  6. Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway Inflammation

    PubMed Central

    Mabalirajan, Ulaganathan; Ahmad, Tanveer; Rehman, Rakhshinda; Leishangthem, Geeta Devi; Dinda, Amit Kumar; Agrawal, Anurag; Ghosh, Balaram; Sharma, Surendra Kumar

    2013-01-01

    Background Baicalein, a bioflavone present in the dry roots of Scutellaria baicalensis Georgi, is known to reduce eotaxin production in human fibroblasts. However, there are no reports of its anti-asthma activity or its effect on airway injury. Methodology/Principal Findings In a standard experimental asthma model, male Balb/c mice that were sensitized with ovalbumin (OVA), treated with baicalein (10 mg/kg, ip) or a vehicle control, either during (preventive use) or after OVA challenge (therapeutic use). In an alternate model, baicalein was administered to male Balb/c mice which were given either IL-4 or IL-13 intranasally. Features of asthma were determined by estimating airway hyperresponsiveness (AHR), histopathological changes and biochemical assays of key inflammatory molecules. Airway injury was determined with apoptotic assays, transmission electron microscopy and assessing key mitochondrial functions. Baicalein treatment reduced AHR and inflammation in both experimental models. TGF-β1, sub-epithelial fibrosis and goblet cell metaplasia, were also reduced. Furthermore, baicalein treatment significantly reduced 12/15-LOX activity, features of mitochondrial dysfunctions, and apoptosis of bronchial epithelia. Conclusion/Significance Our findings demonstrate that baicalein can attenuate important features of asthma, possibly through the reduction of airway injury and restoration of mitochondrial function. PMID:23646158

  7. Erythropoietin improves functional and histological recovery of traumatized skeletal muscle tissue.

    PubMed

    Rotter, Robert; Menshykova, Marija; Winkler, Tobias; Matziolis, Georg; Stratos, Ioannis; Schoen, Matthias; Bittorf, Thomas; Mittlmeier, Thomas; Vollmar, Brigitte

    2008-12-01

    Apart from its hematopoietic effect, erythropoietin (EPO) is known as pleiotropic cytokine with anti-inflammatory and anti-apoptotic properties. Here, we evaluated for the first time the EPO-dependent regeneration capacity in an in vivo rat model of skeletal muscle trauma. A myoblast cell line was used to study the effect of EPO on serum deprivation-induced cell apoptosis in vitro. A crush injury was performed to the left soleus muscle in 80 rats treated with either EPO or saline. Muscle recovery was assessed by analysis of contraction capacities. Intravital microscopy, BrdU/laminin double immunohistochemistry and cleaved caspase-3 immunohistochemistry of muscle tissue on days 1, 7, 14, and 42 posttrauma served for assessment of local microcirculation, tissue integrity, and cell proliferation. Serum deprivation-induced myoblast apoptosis of 23.9 +/- 1.5% was reduced by EPO to 17.2 +/- 0.8%. Contraction force analysis in the EPO-treated animals revealed significantly improved muscle strength with 10-20% higher values of twitch and tetanic forces over the 42-day observation period. EPO-treated muscle tissue displayed improved functional capillary density as well as reduced leukocytic response and consecutively macromolecular leakage over day 14. Concomitantly, muscle histology showed significantly increased numbers of BrdU-positive satellite cells and interstitial cells as well as slightly lower counts of cleaved caspase-3-positive interstitial cells. EPO results in faster and better regeneration of skeletal muscle tissue after severe trauma and goes along with improved microcirculation. Thus, EPO, a compound established as clinically safe, may represent a promising therapeutic option to optimize the posttraumatic course of muscle tissue healing.

  8. Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats.

    PubMed

    Lo, Thomas Pang; Cho, Kyoung-Suok; Garg, Maneesh Sen; Lynch, Michael Patrick; Marcillo, Alexander Eduardo; Koivisto, Denise Leigh; Stagg, Monica; Abril, Rosa Marie; Patel, Samik; Dietrich, W Dalton; Pearse, Damien Daniel

    2009-06-10

    Hypothermia has been employed during the past 30 years as a therapeutic modality for spinal cord injury (SCI) in animal models and in humans. With our newly developed rat cervical model of contusive SCI, we investigated the therapeutic efficacy of transient systemic hypothermia (beginning 5 minutes post-injury for 4 hours, 33 degrees C) with gradual rewarming (1 degrees C per hour) for the preservation of tissue and the prevention of injury-induced functional loss. A moderate cervical displacement SCI was performed in female Fischer rats, and behavior was assessed for 8 weeks. Histologically, the application of hypothermia after SCI resulted in significant increases in normal-appearing white matter (31% increase) and gray matter (38% increase) volumes, greater preservation (four-fold) of neurons immediately rostral and caudal to the injury epicenter, and enhanced sparing of axonal connections from retrogradely traced reticulospinal neurons (127% increase) compared with normothermic controls. Functionally, a faster rate of recovery in open field locomotor ability (BBB score, weeks 1-3) and improved forelimb strength, as measured by both weight-supported hanging (43% increase) and grip strength (25% increase), were obtained after hypothermia. The current study demonstrates that mild systemic hypothermia is effective for retarding tissue damage and reducing neurological deficits following a clinically relevant contusive cervical SCI.

  9. Histology-based classification predicts pattern of recurrence and improves risk stratification in primary retroperitoneal sarcoma

    PubMed Central

    Tan, Marcus C.B.; Brennan, Murray F.; Kuk, Deborah; Agaram, Narasimhan P.; Antonescu, Cristina; Qin, Li-Xuan; Moraco, Nicole; Crago, Aimee M.; Singer, Samuel

    2015-01-01

    Objective To determine the prognostic significance of histologic type/subtype in a large series of patients with primary resected retroperitoneal sarcoma. Summary Background Data The histologic diversity and rarity of retroperitoneal sarcoma has hampered the ability to predict patient outcome. Methods From a single-institution, prospective database, 675 patients treated surgically for primary, non-metastatic retroperitoneal sarcoma during 1982–2010 were identified and histologic type/subtype was reviewed. Clinicopathologic variables were analyzed for association with disease-specific death (DSD), local recurrence (LR), and distant recurrence (DR). Results Median follow-up for survivors was 7.5 years. The predominant histologies were well-differentiated liposarcoma, dedifferentiated liposarcoma, and leiomyosarcoma. Five-year cumulative incidence of DSD was 31%, and factors independently associated with DSD were R2 resection, resection of ≥3 contiguous organs, and histologic type. Five-year cumulative incidence for LR was 39% and for DR was 24%. R1 resection, age, tumor size, and histologic type were independently associated with LR; size, resection of ≥3 organs, and histologic type were independently associated with DR. Liposarcoma and leiomyosarcoma were associated with late recurrence and DSD (as long as 15 years from diagnosis). For solitary fibrous tumor, local recurrence was uncommon (<10%), but early distant recurrence was common (36% at 5 years). Nomograms were developed to predict DSD, LR, and DR. Conclusions Histologic type/subtype is the most important independent predictor of DSD, LR, and DR in primary retroperitoneal sarcoma. Histology predicts the pattern and incidence of LR and DR and will aid in more accurate patient counseling and selection of patients for adjuvant therapy trials. PMID:25915910

  10. Baicalein mediates inhibition of migration and invasiveness of skin carcinoma through Ezrin in A431 cells

    PubMed Central

    2011-01-01

    Background Ezrin is highly expressed in skin cancer and promotes tumor metastasis. Ezrin serves as a promising target for anti-metastasis therapy. The aim of this study is to determine if the flavonoid bacailein inhibits the metastasis of skin cancer cells through Ezrin. Methods Cells from a cutaneous squamous carcinoma cell line, A431, were treated with baicalein at 0-60 μM to establish the non-cytotoxic concentration (NCC) range for baicalein. Following treatment with baicalein within this range, total Ezrin protein (both phosphorylated and unphosphorylated forms) and phosphorylated-Ezrin (phos-Ezrin) were detected by western blotting, and Ezrin RNA was detected in A431 cells using reverse transcription-polymerase chain reaction (RT-PCR). Thereafter, the motility and invasiveness of A431 cells following baicalein treatment were determined using wound-healing and Boyden chamber invasion assays. Short-interfering RNA (si-RNA) specifically targeting Ezrin was transfected into A431 cells, and a si-RNA Ezrin-A431 cell line was established by G418 selection. This stable cell line was transiently transfected with Ezrin and mutant Ezrin plasmids, and its motilityand invasiveness was subsequently determined to clarify whether bacailein inhibits these processes through Ezrin. Results We determined the range of NCCs for baicalein to be 2.5-40 μM in A431 cells. Baicalein displayed a dose- and time-dependent inhibition of expressions of total Ezrin and phos-Ezrin within this range NCCs. In addition, it exerted this inhibitory effect through the reduction of Ezrin RNA transcript. Baicalein also inhibited the motility and invasiveness of A431 skin carcinoma cells within the range of NCCs, in a dose- and time-dependent manner. A431 cell motility and invasiveness were inhibited by 73% and 80% respectively when cells were treated with 20 μM baicalein. However, the motility and invasiveness of A431 cells containing the Ezrin mutant were not effectively inhibited by baicalein

  11. Heme oxygenase 1 improves glucoses metabolism and kidney histological alterations in diabetic rats.

    PubMed

    Ptilovanciv, Ellen On; Fernandes, Gabryelle S; Teixeira, Luciana C; Reis, Luciana A; Pessoa, Edson A; Convento, Marcia B; Simões, Manuel J; Albertoni, Guilherme A; Schor, Nestor; Borges, Fernanda T

    2013-01-16

    One important concern in the treatment of diabetes is the maintenance of glycemic levels and the prevention of diabetic nephropathy. Inducible heme oxygenase 1 (HO-1) is a rate-limiting enzyme thought to have antioxidant and cytoprotective roles. The goal of the present study was to analyze the effect of HO-1 induction in chronically hyperglycemic rats. The hyperglycemic rats were divided into two groups: one group, called STZ, was given a single injection of streptozotocin; and the other group was given a single streptozotocin injection as well as daily injections of hemin, an HO-1 inducer, over 60 days (STZ + HEME). A group of normoglycemic, untreated rats was used as the control (CTL).Body weight, diuresis, serum glucose levels, microalbuminuria, creatinine clearance rate, urea levels, sodium excretion, and lipid peroxidation were analyzed. Histological alterations and immunohistochemistry for HO-1 and inducible nitric oxide synthase (iNOS) were assessed. After 60 days, the STZ group exhibited an increase in blood glucose, diuresis, urea, microalbuminuria, and sodium excretion. There was no weight gain, and there was a decrease in creatinine clearance in comparison to the CTL group. In the STZ + HEME group there was an improvement in the metabolic parameters and kidney function, a decrease in blood glucose, serum urea, and microalbuminuria, and an increase of creatinine clearance, in comparison to the STZ group.There was glomerulosclerosis, collagen deposition in the STZ rats and increase in iNOS and HO-1 expression. In the STZ + HEME group, the glomerulosclerosis and fibrosis was prevented and there was an increase in the expression of HO-1, but decrease in iNOS expression and lipid peroxidation. In conclusion, our data suggest that chronic induction of HO-1 reduces hyperglycemia, improves glucose metabolism and, at least in part, protects the renal tissue from hyperglycemic injury, possibly through the antioxidant activity of HO-1.

  12. γ-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein

    SciTech Connect

    Yamashita, Shuya; Baba, Kiwako; Makio, Akiko; Kumazoe, Motofumi; Huang, Yuhui; Lin, I-Chian; Bae, Jaehoon; Murata, Motoki; Yamada, Shuhei; Tachibana, Hirofumi

    2016-05-13

    Previous studies have identified biomolecules that mediate the physiological actions of food factors, such as amino acids, vitamins, fatty acids, minerals, plant polyphenols, and lactobacilli, suggesting that our bodies are equipped with an innate system that senses which food factors are required to maintain our health. However, the effects of environmental factors on food factor sensing (FFS) remains largely unknown. Tocotorienols (T3s), which belongs to the vitamin E family, possess several physiological functions, including cholesterol lowering and neuroprotective effects. Here, we investigated the effects of naturally abundant γ-T3 on FFS-related gene expressions in melanoma using a DNA chip. Our results showed that γ-T3 increased the expression level of aryl hydrocarbon receptor (AhR), a sensing molecule to plant polyphenol baicalein. The co-treatment with γ-T3 and baicalein enhanced the anti-proliferative activity of baicalein, accompanied by the downstream events of AhR-activation induced by baicalein. These data suggest that γ-T3 upregulates AhR expression and enhances its sensitivity to baicalein. - Highlights: • γ-T3 upregulated the expression of AhR in mouse melanoma. • Promotion of the binding activity of Sp1 is associated with the increasing effect of γ-T3 on AhR expression. • γ-T3 enhanced the anti-proliferative activity of baicalein that has an AhR ligand activity. • γ-T3 enhanced the inducing activity of baicalein on the expression of AhR target genes.

  13. Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin

    PubMed Central

    WANG, CHONG-ZHI; ZHANG, CHUN-FENG; CHEN, LINA; ANDERSON, SAMANTHA; LU, FANG; YUAN, CHUN-SU

    2015-01-01

    Baicalin is a major constituent of Scutellaria baicalensis, which is a commonly used herbal medicine in many Asian countries. After oral ingestion, intestinal micro-biota metabolism may change parent compound's structure and its biological activities. However, whether baicalin can be metabolized by enteric microbiota and the related anti-cancer activity is not clear. In this study, using human enteric microbiome incubation and HPLC analysis, we observed that baicalin can be quickly converted to baicalein. We compared the antiproliferative effects of baicalin and baicalein using a panel of human cancer cell lines, including three human colorectal cancer (CRC) cell lines. In vitro antiproliferative effects on CRC cells were verified using an in vivo xenograft nude mouse model. Baicalin showed limited antiproliferative effects on some of these cancer cell lines. Baicalein, however, showed significant antiproliferative effects in all the tested cancer cell lines, especially on HCT-116 human colorectal cancer cells. In vivo antitumor results supported our in vitro data. We demonstrated that baicalein exerts potent S phase cell cycle arrest and pro-apoptotic effects in HCT-116 cells. Baicalein induced the activation of caspase 3 and 9. The in silico modeling suggested that baicalein forms hydrogen bonds with residues Ser251 and Asp253 at the active site of caspase 3, while interactions with residues Leu227 and Asp228 in caspase 9 through its hydroxyl groups. Data from this study suggested that baicalein is a potent anticancer metabolite derived from S. baicalensis. Enteric microbiota play a key role in the colon cancer chemoprevention of S. baicalensis. PMID:26398706

  14. Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice

    PubMed Central

    Trinh, Hien-trung; Joh, Eun-ha; Kwak, Ho-young; Baek, Nam-in; Kim, Dong-hyun

    2010-01-01

    Aim: To explore whether intestinal microflora plays a role in anti-pruritic activity of baicalin, a main constituent of the rhizome of Scutellaria baicalensis (SB). Methods: Baicalin was anaerobically incubated with human fecal microflora, and its metabolites, baicalein and oroxylin A, were isolated. The inhibitory effect of baicalin and its metabolites was accessed in histamine- or compound 48/80-induced scratching behavior in mice. Results: Baicalin was metabolized to baicalein and oroxylin A, with metabolic activities of 40.2±26.2 and 1.2±1.1 nmol·h−1·mg−1 wet weight of human fecal microflora, respectively. Baicalin (20, 50 mg/kg) showed more potent inhibitory effect on histamine-induced scratching behavior when orally administered than intraperitoneally. In contrast, baicalein and oroxylin A had more potent inhibitory effect when the intraperitoneally administered. The anti-scratching behavior activity of oral baicalin and its metabolites was in proportion to their inhibition on histamine-induced increase of vascular permeability with oroxylin A more potent than baicalein and baicalin. In Magnus test using guinea pig ileum, oroxylin A is more potent than baicalein and baicalin in inhibition of histamine-induced contraction. The anti-scratching behavioral effect of oral baicalin was significantly reduced when oral antibiotics were simultaneously administered, whereas the effect of baicalein and oroxylin A were not affected. Conclusion: Oral baicalin may be metabolized by intestinal microflora into baicalein and oroxylin A, which ameliorate pruritic reactions through anti-histamine action. PMID:20453872

  15. Gene expression profiling and pathway network analysis of hepatic metabolic enzymes targeted by baicalein.

    PubMed

    Qin, Si; Chen, Jihua; Tanigawa, Shunsuke; Hou, De-Xing

    2012-03-06

    Baicalein is a flavone originally isolated from the roots of traditional Chinese medicinal herb, Scutellaria baicalensis, which has been proved as a promising chemopreventive compound for many chronic human diseases. The present study aimed to clarify the molecular mechanism targeted by baicalein. Gene expression profiling of HepG2 cells treated with baicalein was carried out, using the Affymetrix 42K oligonucleotide microarray in the present study. Microarray data analyzed by Ingenuity Pathway Analysis (IPA), further study performed by real time PCR, reporter gene assay, and Western blot. Among total 42K gene probes, baicalein treatment up-regulated the signals of 440 gene probes (1.04% of total gene probes) and down-regulated signals of 254 gene probes (0.6% of total gene probes) by ≥2-fold. These genes were categorized into 35 groups and hit for biological processes, molecular functions, and signaling pathways. The network and pathway analyses of these data further revealed that an Nrf2 (nuclear factor-erythroid 2 p45-related factor 2)-mediated ARE (antioxidant response element) pathway is involved in baicalein-induced gene expression of hepatic metabolic enzymes. The representative enzymes involved in Nrf2/ARE pathway were further confirmed at mRNA level by real time PCR and at protein level by Western blot analysis. Moreover, the ARE-reporter gene assay demonstrated that baicalein stimulated Nrf2-mediated ARE transactivation. Our results provide a comprehensive data for understanding the hepatic metabolism, bioactive role and the molecular mechanisms of baicalein. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Structural Characteristics of the Alpha-Synuclein Oligomers Stabilized By the Flavonoid Baicalein

    SciTech Connect

    Hong, D.-P.; Fink, A.L.; Uversky, V.N.

    2009-05-18

    The flavonoid baicalein inhibits fibrillation of alpha-synuclein, which is a major component of Lewy bodies in Parkinson's disease. It has been known that baicalein induces the formation of alpha-synuclein oligomers and consequently prevents their fibrillation. In order to evaluate the structural properties of baicalein-stabilized oligomers, we purified oligomer species by HPLC and examined their stability and structure by CD, Fourier transform infrared spectroscopy, size exclusion chromatography HPLC, small-angle X-ray scattering, and atomic force microscopy. Baicalein-stabilized oligomers are beta-sheet-enriched according to CD and Fourier transform infrared spectroscopy analyses. They did not form fibrils even after very prolonged incubation. From small-angle X-ray scattering data and atomic force microscopy images, the oligomers were characterized as quite compact globular species. Oligomers were extremely stable, with a GdmCl C(m)=3.3 M. This high stability explains the previously observed inhibition properties of baicalein against alpha-synuclein fibrillation. These baicalein-stabilized oligomers, added to the solution of aggregating alpha-synuclein, were able to noticeably inhibit its fibrillation. After prolonged coincubation, short fibrils were formed, suggesting an effective interaction of oligomers with monomeric alpha-synuclein. Membrane permeability tests suggested that the baicalein-stabilized oligomers had a mild effect on the integrity of the membrane surface. This effect was rather similar to that of the monomeric protein, suggesting that targeted stabilization of certain alpha-synuclein oligomers might offer a potential strategy for the development of novel Parkinson's disease therapies.

  17. Baicalein induces CD4+Foxp3+ T cells and enhances intestinal barrier function in a mouse model of food allergy

    PubMed Central

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Kwon, Da-Ae; Shon, Dong-Hwa

    2016-01-01

    The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy. PMID:27561877

  18. [Baicalein promotes the apoptosis of HeLa cells by inhibiting ERK1/2 expression].

    PubMed

    Wang, Yongzhou; Xia, Jiyi; Tang, Xiaoping; Tang, Li; Mao, Xiguang; Zhang, Yujiao; Yu, Xiaolan

    2016-11-01

    Objective To investigate the effects of baicalein and U0126 treatment on the apoptosis of human cervical carcinoma HeLa cells and the potential mechanism. Methods HeLa cells were subjected to (1, 2, 5, 10, 20, 50, 100, 200, 300) μmol/L baicalein or (1, 2, 5, 10, 20, 30) μmol/L U0126 treatment for 24 hours. The optimal concentrations of baicalein and U0126 for HeLa inhibition was determined by a cell counting Kit-8 assay. HeLa cells were then treated with these inhibitory concentrations for 24 hours separately or in combination. The cell cycle and the degree of apoptosis were analyzed by flow cytometry. The cell apoptosis index was evaluated by the TUNEL assay. The expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), Bax, and Bcl-2 at the mRNA and protein levels were examined by real-time PCR and Western blotting, respectively. Results Optimal inhibitory concentrations of baicalein and U0126 for HeLa cells were 200 μmol/L and 10 μmol/L, respectively. Compared with the control group, baicalein treatment increased the growth rate of cells in the G0/G1 phase but decreased the S phase. Combination treatment of 200 μmol/L baicalein and 10 μmol/L U0126 for 24 hours further reduced the S phase growth rate. Treatment with 10 μmol/L U0126 or 200 μmol/L baicalein for 24 hours induced cell apoptosis, and the combination treatment induced more apoptosis. Treatment by baicalein alone or in combination with U0126 for 24 hours significantly decreased ERK1/2 and Bcl-2 mRNA expressions, and upregulated Bax mRNA expression. It also downregulated ERK1/2 phosphorylation and Bcl-2 protein expression, while increasing Bax protein expression. Conclusion Both baicalein and U012 appear to inhibit proliferation, induce apoptosis, and increase the growth rate in the G0/G1 phase but reduce the S phase of HeLa cells. This effect is enhanced when they are used synergistically.

  19. Baicalein-nicotinamide cocrystal with enhanced solubility, dissolution, and oral bioavailability.

    PubMed

    Huang, Yanting; Zhang, Bowen; Gao, Yuan; Zhang, Jianjun; Shi, Limin

    2014-08-01

    The purpose of this study was to investigate the effect of preparation methods on cocrystallization between baicalein (BE) and nicotinamide (NCT), their intermolecular interaction, and to demonstrate that BE-NCT cocrystal can achieve the simultaneous enhancement in solubility, dissolution, and oral bioavailability of BE. The cocrystals from three preparation methods have the similar differential scanning calorimetry thermograms and X-ray powder diffraction patterns. Compared with crystalline BE, BE-NCT cocrystal has significantly improved the solubility and dissolution of BE. In addition, the cocrystal exhibits a 2.49-fold higher peak plasma concentration (Cmax) and 2.80-fold higher area under the curve (AUC) in rats. This prominent improvement in oral bioavailability is even greater than the previously reported BE nanocrystal. This investigation enriched the present understanding of cocrystals on their behavior in vitro and in vivo, and built the groundwork for future development of BE as a promising compound into efficacious drug products. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Scutellaria baicalensis and a constituent flavonoid, baicalein, attenuate ritonavir-induced gastrointestinal side-effects

    PubMed Central

    Mehendale, Sangeeta; Aung, Han; Wang, Chong-Zhi; Tong, Robin; Foo, Adela; Xie, Jing-Tian; Yuan, Chun-Su

    2009-01-01

    Ritonavir, a protease inhibitor drug, is commonly used in AIDS therapy. As with other chemotherapeutic drugs that cause gastrointestinal adverse effects, ritonavir treatment is associated with significant nausea and vomiting. This study investigated whether Scutellaria baicalensis, and its active flavonoid constituent, baicalein, attenuate the gastrointestinal effects of ritonavir. The effects of herb administration were evaluated in ritonavir-treated rats using a rat pica model, which simulates nausea and vomiting in humans. The effects of herb administration on gastric emptying in rats were also measured. Ritonavir treatment resulted in increased kaolin intake or severe pica, the intensity of which was reduced significantly with S. baicalensis administration (1 mg kg−1; P < 0.05). High-performance liquid chromatography analysis of S. baicalensis showed the presence of an extremely potent flavonoid constituent, baicalein. The study aimed to determine if baicalein contributed to the anti-pica effect of the extract. It was observed that baicalein dose-dependently decreased pica in ritonavir-treated rats (P < 0.001). In addition to inducing pica, ritonavir also significantly delayed gastric emptying, which could contribute to ritonavir-induced gastrointestinal dysfunction. When S. baicalensis extract was administered to ritonavir-treated rats the delayed gastric emptying was significantly attenuated (P < 0.05). The results suggest that S. baicalensis and the constituent baicalein reduce the gastrointestinal dysfunction caused by ritonavir. It is concluded that S. baicalensis may potentially have a role to play in reducing drug-induced adverse effects. PMID:17976269

  1. In Vitro Sensitization of Erythrocytes to Programmed Cell Death Following Baicalein Treatment

    PubMed Central

    Bissinger, Rosi; Malik, Abaid; Honisch, Sabina; Warsi, Jamshed; Jilani, Kashif; Lang, Florian

    2014-01-01

    The polyphenolic flavonoid Baicalein has been shown to trigger suicidal death or apoptosis of tumor cells and is thus considered for the prevention and treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide. The present study explored whether Baicalein stimulates eryptosis. To this end, forward scatter was taken for measurement of cell volume, annexin-V-binding for phosphatidylserine-exposure, Fluo3 fluorescence for [Ca2+]i and fluorescent antibodies for ceramide abundance. As a result, a 48 h exposure of human erythrocytes to Baicalein was followed by significant decrease of forward scatter (≥10 µM), significant increase of the percentage of annexin-V-binding cells (≥25 µM), significant increase of [Ca2+]i (50 µM) and significant increase of ceramide abundance (50 µM). The effect of Baicalein (50 µM) on annexin-V-binding was significantly blunted but not abrogated by removal of extracellular Ca2+. In conclusion, at the concentrations employed, Baicalein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to the combined effects of Ca2+ entry and ceramide formation. PMID:25238045

  2. Baicalein induces apoptosis of human cervical cancer HeLa cells in vitro.

    PubMed

    Peng, Yong; Guo, Congshan; Yang, Yanhong; Li, Fenglin; Zhang, Yanxia; Jiang, Bin; Li, Qingwang

    2015-03-01

    A number of studies have shown that baicalein shows high antitumor activity in vitro and in vivo. In this study, the inhibitory effect of baicalein on human cervical cancer HeLa cells was studied in vitro. HeLa cells were treated with high (100 µg/ml) and low (50 µg/ml) doses of baicalein, and cell growth inhibition rates were examined by the MTT assay. The morphological changes of apoptotic cells were observed under the light and electron microscope, while the rate of cell apoptosis was examined by flow cytometry. The expression of apoptosis-related proteins was analyzed by western blot, and caspase-3 activation was examined by a caspase-3 activity assay and spectrophotometry. The results demonstrated that baicalein inhibits the proliferation of HeLa cells and induces apoptosis in a caspase-3-dependent pathway, through downregulation of the B-cell lymphoma 2 (Bcl-2) protein and upregulation of the Bcl-2-associated X protein (Bax), Fas, Fas ligand (FasL) and caspase-8. Thus, we conclude that baicalein induces apoptosis of HeLa cells via the mitochondrial and the death receptor pathways. Cell apoptosis in HeLa cells was most likely promoted by the activation of the proteolytic enzyme caspase-3 in both pathways.

  3. Vascular barrier protective effects of baicalin, baicalein and wogonin in vitro and in vivo

    SciTech Connect

    Kwak, Soyoung; Ku, Sae-Kwang; Han, Min-Su; Bae, Jong-Sup

    2014-11-15

    Inhibition of high mobility group box 1 (HMGB1) protein and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of sepsis. Here, three structurally related polyphenols found in the Chinese herb Huang Qui, baicalin (BCL), baicalein (BCN), and wogonin (WGN), were examined for their effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. According to our data, BCL, BCN, and WGN inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. BCL, BCN, and WGN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with BCL, BCN, and WGN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that BCL, BCN, and WGN could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway. - Highlights: • HMGB1 is an inflammatory mediator for vascular inflammation. • Baicalin, baicalein and wogonin inhibited HMGB1-induced hyperpermeability in vitro and in vivo. • Baicalin, baicalein and wogonin inhibited HMGB1-mediated inflammatory responses. • Baicalin, baicalein and wogonin suppressed the activation of NF-κB and ERK1/2 and production of TNF-α and IL-6. • Baicalin, baicalein and wogonin prevent CLP-induced septic mortality.

  4. An Agent-Based Approach to Dynamically Represent the Pharmacokinetic Properties of Baicalein.

    PubMed

    Zhu, Xiao; Deng, Jianyuan; Zuo, Zhong; Lam, Tai Ning

    2016-11-01

    Baicalein, a typical flavonoid presented in Scutellariae radix, exhibits a unique metabolic profile during first-pass metabolism: parallel glucuronidation and sulfation pathways, with possible substrate inhibition in both pathways. In this project, we aimed to construct an agent-based model to dynamically represent baicalein pharmacokinetics and to verify the substrate inhibition hypothesis. The model consisted of three 3D spaces and two membranes: apical space (S1), intracellular space (S2), basolateral space (S3), apical membrane (M1), and basolateral membrane (M2). In silico enzymes (UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs)) and binder components were placed in S2. The model was then executed to simulate one-pass metabolism experiments of baicalein. With the implementation of a two-site enzyme design, the simulated results captured the preset qualitative and quantitative features of the wet-lab observations. The feasible parameter set showed that substrate inhibition happened in both conjugation pathways of baicalein. The simulation results suggested that the sulfation pathway was dominant at low concentrations and that SULT was more inclined to substrate inhibition than UGT. Cross-model validation was satisfactory. Our findings were consistent with a previously reported catenary model. We conclude that the mechanisms represented by our model are plausible. Our novel modeling approach could dynamically represent the metabolic pathways of baicalein in a Caco-2 system.

  5. Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis.

    PubMed

    Alexander, Jeffrey A; Jung, Kee Wook; Arora, Amindra S; Enders, Felicity; Katzka, David A; Kephardt, Gail M; Kita, Hirohito; Kryzer, Lori A; Romero, Yvonne; Smyrk, Thomas C; Talley, Nicholas J

    2012-07-01

    We evaluated the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults with eosinophilic esophagitis (EoE). We performed a double-blind, randomized, placebo-controlled trial of fluticasone in 42 adult patients with a new diagnosis of EoE (30 men; mean age, 37.5 y). Participants were assigned randomly to groups that swallowed 880 μg of aerosolized fluticasone twice daily (n = 21), or took a placebo inhaler twice daily (n = 15) for 6 weeks. End points of the study were symptomatic and histologic response. A complete histologic response (>90% decrease in mean eosinophil count) was observed in 11 of 15 subjects who received 6 weeks of fluticasone (62%), compared with none of the 15 subjects who received placebo (P < .001), based on intention-to-treat analysis; histologic responses were observed in 68% of subjects who received fluticasone (13 of 19) compared with none of those who received placebo (0 of 15) by per-protocol analysis (P < .001). Intracellular staining for eosinophil-derived neurotoxin was reduced in 81% of subjects who received fluticasone (13 of 16) compared with 8% who received placebo (1 of 13) (P < .001). Dysphagia was reduced in 57% of subjects who received fluticasone (12 of 21) compared with 33% who received placebo (7 of 21) (P = .22) by intention-to-treat analysis; dysphagia was reduced in 63% of patients who received fluticasone (12 of 19) and 47% of those who received placebo (7 of 15) (P = .49) based on per-protocol analysis. Esophageal candidiasis developed in 26% of subjects who received fluticasone (5 of 19), but in none of the subjects in the placebo group (P = .05). Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Microradiography of Microcalcifications in Breast Specimen: A New Histological Correlation Procedure and the Effect of Improved Resolution on Diagnostic Validity

    PubMed Central

    Langen, H.-J.; Koehler, S.; Bielmeier, J.; Jocher, R.; Kranzfelder, D.; Jagusch, N.; Treutlein, G.; Wetzler, Th.; Müller, J.; Ott, G.

    2012-01-01

    Introduction. Does high-resolution visualization of microcalcifications improve diagnostic reliability? Method. X-rays were taken of mamma specimens with microcalcifications in 32 patients (10 malignant; 22 benign) using conventional radiography (12 Lp/mm) and high-resolution radiography (2000 Lp/mm). Histological sections were subsequently prepared and correlated to the microradiographic image and every calcification was assigned an exact malignant or benign histological diagnosis. Five radiologists classified single groups of calcifications in both methods according to the BIRADS classification system. Results. Using microradiography microcalcifications can be shown in high resolution at the cell level including histological correlation. In some cases, the diagnostic validity was improved by the high resolution in microradiography. In other cases, the high resolution resulted in more visible calcifications, thus giving benign calcifications a malignant appearance. In the BIRADS 2 and 3 group, the probability of malignancy was 28.6% in the conventional radiography evaluation and 37.8% in the microradiography evaluation. In the BIRADS 4 and 5 group, the probability of malignancy was 34.2% in the conventional radiography evaluation and 24.4% in the microradiography evaluation. The differences were not significant. Summary. Overall, the improved resolution in microradiography did not show an improvement in diagnostic accuracy compared to conventional radiography. PMID:23097699

  7. Microradiography of microcalcifications in breast specimen: a new histological correlation procedure and the effect of improved resolution on diagnostic validity.

    PubMed

    Langen, H-J; Koehler, S; Bielmeier, J; Jocher, R; Kranzfelder, D; Jagusch, N; Treutlein, G; Wetzler, Th; Müller, J; Ott, G

    2012-01-01

    Introduction. Does high-resolution visualization of microcalcifications improve diagnostic reliability? Method. X-rays were taken of mamma specimens with microcalcifications in 32 patients (10 malignant; 22 benign) using conventional radiography (12 Lp/mm) and high-resolution radiography (2000 Lp/mm). Histological sections were subsequently prepared and correlated to the microradiographic image and every calcification was assigned an exact malignant or benign histological diagnosis. Five radiologists classified single groups of calcifications in both methods according to the BIRADS classification system. Results. Using microradiography microcalcifications can be shown in high resolution at the cell level including histological correlation. In some cases, the diagnostic validity was improved by the high resolution in microradiography. In other cases, the high resolution resulted in more visible calcifications, thus giving benign calcifications a malignant appearance. In the BIRADS 2 and 3 group, the probability of malignancy was 28.6% in the conventional radiography evaluation and 37.8% in the microradiography evaluation. In the BIRADS 4 and 5 group, the probability of malignancy was 34.2% in the conventional radiography evaluation and 24.4% in the microradiography evaluation. The differences were not significant. Summary. Overall, the improved resolution in microradiography did not show an improvement in diagnostic accuracy compared to conventional radiography.

  8. Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons.

    PubMed

    Li, F-Q; Wang, T; Pei, Z; Liu, B; Hong, J-S

    2005-03-01

    Accumulating evidence has suggested that inflammation in the brain participates in the pathogenesis of Parkinson's disease (PD). Therefore, anti-inflammatory therapy has attracted much attention as novel interference to neurodegenerative diseases. Baicalein, a major flavonoid extracted from a traditional Chinese herb Scutellaria baicalensis Georgi (Huangqin), possesses potent anti-inflammatory and antioxidant properties. To test the potential neuroprotective effect of baicalein on dopaminergic neurons, primary midbrain neuron-glia cultures from E-14 rat embryos were used. Cultures were pretreated with baicalein for 30 min prior to stimulation with lipopolysaccharide (LPS, 10 ng/ml). LPS leads to massive activation of microglial cells revealed by OX-42 immunostaining, and produced excessive quantities of NO. Excessive elevation of superoxide level was also observed in enriched-microglia after stimulating with LPS. LPS-induced damage to dopaminergic neurons was evaluated by uptake capacity for [3H]dopamine and tyrosine hydroxylase (TH)-immunocytochemistry. Pretreatment with baicalein concentration-dependently attenuated LPS-induced decrease in [3H]dopamine uptake and loss of TH-immunoreactive (TH-ir) neurons, which the maximum protective effect was observed at the concentration of 5 microM. Post-treatment with baicalein (5 microM) was also shown to be effective even if baicalein administered up to 2 h later than LPS application. Morphological study shows that baicalein (5 microM) almost completely blocked LPS-induced activation of microglia. Excessive production of TNF(alpha) and free radicals such as NO and superoxide by LPS stimulation were also attenuated by baicalein at a concentration-dependent pattern. The present study indicates that baicalein exerts potent neuroprotective effect on LPS-induced injury of dopaminergic neurons. We hypothesize that the inhibition of LPS-induced production of NO and free radicals from microglia may underlie the mechanism of

  9. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer.

    PubMed Central

    Ikeda, Y.; Mori, M.; Kamakura, T.; Haraguchi, Y.; Saku, M.; Sugimachi, K.

    1995-01-01

    The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types. PMID:7640228

  10. Improved differential diagnosis of breast masses on ultrasonographic images with a computer-aided diagnosis scheme for determining histological classifications.

    PubMed

    Kashikura, Yumi; Nakayama, Ryohei; Hizukuri, Akiyoshi; Noro, Aya; Nohara, Yuki; Nakamura, Takashi; Ito, Minori; Kimura, Hiroko; Yamashita, Masako; Hanamura, Noriko; Ogawa, Tomoko

    2013-04-01

    A computer-aided diagnosis (CAD) scheme for determining histological classifications of breast masses is expected to be useful for clinicians in making a differential diagnosis. The purpose of this study was to evaluate the usefulness of using the CAD scheme on ultrasonographic images. The database consisted of 390 breast ultrasonographic images with masses. Three experienced clinicians independently provided subjective ratings on the likelihood of malignancy for each of the 390 masses. Fifty benign masses (25 cysts and 25 fibroadenomas) and 50 malignant masses (25 noninvasive ductal carcinomas and 25 invasive ductal carcinomas) were selected as unknown cases for an observer study based on a stratified randomization method with the ratings. The likelihood of the histological classification in each unknown case was evaluated by the CAD scheme with image features that clinicians commonly use for describing masses. In the observer study, seven observers provided their confidence levels regarding the malignancy of the unknown case before and after viewing the likelihood of the histological classification. The usefulness of the CAD scheme was evaluated with a multireader multicase receiver operating characteristic (ROC) analysis. The areas under the ROC curves (AUCs) for all observers were improved by use of the CAD scheme. The average AUC increased from 0.716 without to 0.864 with the CAD scheme (P = .006). The presentation of the likelihood of the histological classification evaluated by the CAD scheme improved the clinicians' performance and therefore would be useful in making a differential diagnosis of masses on ultrasonographic images. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

  11. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial.

    PubMed

    Rautiainen, Henna; Kärkkäinen, Päivi; Karvonen, A-L; Nurmi, Heimo; Pikkarainen, Pekka; Nuutinen, Hannu; Färkkilä, Martti

    2005-04-01

    Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to III, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15 mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22% in group A but deteriorated 20% in group B (P = .009). Fibrosis decreased 25% in group A but increased 70% in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P = .02), but only 10% in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.

  12. The submucosal cushion does not improve the histologic evaluation of adenomatous colon polyps resected by snare polypectomy.

    PubMed

    Jovanovic, Ivan; Caro, Carlos; Neumann, Helmut; Lux, Anke; Kuester, Doerthe; Fry, Lucia C; Malfertheiner, Peter; Mönkemüller, Klaus

    2011-10-01

    Although the "submucosal cushion" technique or injection-assisted polypectomy (IAP) is often used to resect colon polyps, little is known on the influence of this technique on histologic interpretation. We aimed to evaluate whether the use of a submucosal cushion improves the histologic and margin evaluation of colon polyps. Consecutive patients undergoing polypectomy with and without IAP were included. An experienced blinded gastrointestinal pathologist evaluated the specimens using standardized criteria. One hundred eleven sessile colon adenomas were analyzed (IAP, n = 65, standard, n = 46). Two-thirds of polyps ranged in size from 10 to 20 mm; the average polyp size was 13.2 mm for IAP and 9.9 mm for standard snare polypectomy (P = .001). The cautery degree, cautery amount, and margin evaluability, did not differ substantially with regard to the resection technique. For polyps ≥10-20 mm, the overall architecture quality was better in polyps resected with standard technique as compared with IAP. The utilization of IAP did not result in a better margin evaluability of the resected polyp. Overall, IAP does not result in a better histologic polyp evaluability. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Proposal of an improved histological sub-typing system for lung adenocarcinoma – significant prognostic values for stage I disease

    PubMed Central

    Okudela, Koji; Woo, Tetsukan; Mitsui, Hideaki; Yazawa, Takuya; Shimoyamada, Hiroaki; Tajiri, Michihiko; Ogawa, Nobuo; Masuda, Munetaka; Kitamura, Hitoshi

    2010-01-01

    We have established a concise sub-typing system suitable for predicting the postoperative outcome in cases of stage I lung adenocarcinoma (ADC), using morphometric profiling. The association between postoperative disease recurrence and a variety of morphological features including histological architecture, cell type, cytoplasmic color/internal structure, nuclear shape/size, chromatin pattern, and nucleoli count/remarkableness, was analyzed. Histological architecture had the most prognostic value and could be subdivided into low-grade (bronchioloalveolar, papillary and tubular: “tubular” in this paper is defined as a tubular or glandular structure lined with single-layered neoplastic cells) and high-grade (acinar and solid: “acinar” is defined as a tubular or glandular structure lined with poly-layered neoplastic cells or as a fused glandular structure such as the cribriform pattern) components. The subgroups separated based on a cut-off value, 71.5% of the high-grade component comprised by a tumor, which was calculated according to a relative operating characteristic curve, exhibited a significant difference in disease recurrence [estimated 5-year disease-free survival rate, 95.3% in the low-grade group versus 66.7% in the high-grade group, hazard ratio 7.35, Log-rank test p = 0.002]. The sub-grouping system is concise and suitable for practical use. It will improve the histological classification of ADC. PMID:20490327

  14. Amylin Amyloid Inhibition by Flavonoid Baicalein: Key Roles of Its Vicinal Dihydroxyl Groups of the Catechol Moiety.

    PubMed

    Velander, Paul; Wu, Ling; Ray, W Keith; Helm, Richard F; Xu, Bin

    2016-08-09

    Amyloid formation of the 37-residue amylin is involved in the pathogenesis of type 2 diabetes and, potentially, diabetes-induced neurological deficits. Numerous flavonoids exhibit inhibitory effects against amylin amyloidosis, but the mechanisms of inhibition remain unclear. Screening a library of natural compounds uncovered a potent lead compound, the flavone baicalein. Baicalein inhibits amylin amyloid formation and reduces amylin-induced cytotoxicity. Analogue analyses demonstrated, for the first time, key roles of the vicinal hydroxyl groups on the A-ring. We provided mass spectrometric evidence that incubating baicalein and amylin leads to their conjugation, consistent with a Schiff base mechanism.

  15. A Combination Therapy with Baicalein and Taxol Promotes Mitochondria-Mediated Cell Apoptosis: Involving in Akt/β-Catenin Signaling Pathway.

    PubMed

    Pan, Qiong; Xue, Min; Xiao, Song-Shu; Wan, Ya-Jun; Xu, Da-Bao

    2016-11-01

    Baicalein, a major flavonoid, possesses anticancer and anti-inflammatory activity. The aim of the study is to explore the efficiency of combination therapy with baicalein and taxol, as well as the molecular mechanism on antitumor activity. Human ovarian cancer cells were treated with different concentration of baicalein for 48 h, and cell viability was determined by MTT assay. Baicalein inhibited cell proliferation of ovarian cancer cells, and IC50 value of baicalein in A2780 cells, SKOV3 cells, and OVCAR cells was 46.23, 60.68, and 38.03 μM, respectively. The ovarian cancer cells were treated with 10 μM of baicalein combined with increasing concentration of taxol for 48 h, and the results demonstrated that combination therapy with baicalein and taxol had much higher antitumor effects compared with the monotherapy. The molecular mechanisms involving in combination therapy promoted the caspase-3 activity then leading to cleavage of poly-ADP-ribose polymerase, which increased the cell apoptosis of ovarian cancer cells. Moreover, Z-VAD-FMK treatment partially decreased the baicalein-induced proliferation inhibition in human ovarian cancer cells. Furthermore, baicalein induced apoptosis through activation of the activities of caspase-3,-9, and increased cytoplasmic cytochrome C release. Importantly, baicalein inhibited the growth of A2780 cells by inhibiting Akt/β-catenin signaling pathway. In conclusion, our result revealed that baicalein combinated with taxol at low concentrations could exert synergistic antitumor effects in ovarian cancer cells through mitochondria-mediated cell apoptosis and Akt/β-catenin signaling pathway. Baicalein has a promising potential to be developed as an antitumor compound, and combination therapy of baicalein and taxol exhibits an antitumor potential in clinical therapy for human ovarian cancers.

  16. Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR).

    PubMed

    Carazo Fernández, Alejandro; Smutny, Tomas; Hyrsová, Lucie; Berka, Karel; Pavek, Petr

    2015-03-04

    The constitutive androstane receptor (CAR) is a crucial transcriptional regulator of key xenobiotic-metabolizing enzymes such as cytochrome P450 CYP3A4, CYP2C9 and CYP2B6. The flavonoids chrysin, baicalein and galangin have been reported to activate CAR and interfere with EGFR signaling. Nevertheless, it is not known if these flavonoids are direct CAR ligands or indirect phenobarbital-like CAR activators via the inhibition of epidermal growth factor receptor (EGFR) signaling. We analyze the interactions of chrysin, galangin and baicalein and its glycoside baicalin with human CAR. We have employed and validated methods that can study direct interaction with the CAR ligand binding pocket. Secondly, we determined if the compounds affect human EGFR signaling and interact with EGFR. Employing a TR-FRET coactivator assay with recombinant CAR or CAR assembly assay, a consistent activation of CAR with flavonoids and phenobarbital was not observed. It was determined, however, that galangin, chrysin, and baicalein may slightly repress EGFR-Tyr1068 autophosphorylation after EGF treatment, phosphorylation of downstream transcription factor ELK1 and stimulate EGFP-CAR nuclear translocation in primary human hepatocytes. These data suggest that flavonoids chrysin, galangin and baicalein are indirect human CAR activators. This study also demonstrates new approach how to test the direct CAR interaction with its ligands.

  17. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus

    PubMed Central

    Moghaddam, Ehsan; Teoh, Boon-Teong; Sam, Sing-Sin; Lani, Rafidah; Hassandarvish, Pouya; Chik, Zamri; Yueh, Andrew; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    Baicalin, a flavonoid derived from Scutellaria baicalensis, is the main metabolite of baicalein released following administration in different animal models and human. We previously reported the antiviral activity of baicalein against dengue virus (DENV). Here, we examined the anti-DENV properties of baicalin in vitro, and described the inhibitory potentials of baicalin at different steps of DENV-2 (NGC strain) replication. Our in vitro antiviral experiments showed that baicalin inhibited virus replication at IC50 = 13.5 ± 0.08 μg/ml with SI = 21.5 following virus internalization by Vero cells. Baicalin exhibited virucidal activity against DENV-2 extracellular particles at IC50 = 8.74 ± 0.08 μg/ml and showed anti-adsorption effect with IC50 = 18.07 ± 0.2 μg/ml. Our findings showed that baicalin as the main metabolite of baicalein exerting in vitro anti-DENV activity. Further investigations on baicalein and baicalin to deduce its antiviral therapeutic effects are warranted. PMID:24965553

  18. Antiviral Activity of Baicalein and Quercetin against the Japanese Encephalitis Virus

    PubMed Central

    Johari, Jefree; Kianmehr, Aynaz; Mustafa, Mohd Rais; Abubakar, Sazaly; Zandi, Keivan

    2012-01-01

    Japanese encephalitis (JE), a mosquito-borne viral disease, is endemic to the entire east and southeast Asia, and some other parts of the world. Currently, there is no effective therapeutic available for JE; therefore, finding the effective antiviral agent against JEV replication is crucial. In the present study, the in vitro antiviral activity of baicalein and quercetin, two purportedly antiviral bioflavonoids, was evaluated against Japanese encephalitis virus (JEV) replication in Vero cells. Anti-JEV activities of these compounds were examined on different stages of JEV replication cycle. The effects of the compounds on virus replication were determined by foci forming unit reduction assay (FFURA) and quantitative RT-PCR. Baicalein showed potent antiviral activity with IC50 = 14.28 μg/mL when it was introduced to the Vero cells after adsorption of JEV. Quercetin exhibited weak anti-JEV effects with IC50 = 212.1 μg/mL when the JEV infected cells were treated with the compound after virus adsorption. However, baicalein exhibited significant effect against JEV adsorption with IC50 = 7.27 μg/mL while quercetin did not show any anti-adsorption activity. Baicalein also exhibited direct extracellular virucidal activity on JEV with IC50 = 3.44 μg/mL. However, results of quantitative RT-PCR experiments confirmed the findings from FFURA. This study demonstrated that baicalein should be considered as an appropriate candidate for further investigations, such as the study of molecular and cellular mechanism(s) of action and in vivo evaluation for the development of an effective antiviral compound against Japanese encephalitis virus. PMID:23222683

  19. Luna stain, an improved selective stain for detection of microsporidian spores in histologic sections.

    PubMed

    Peterson, Tracy S; Spitsbergen, Jan M; Feist, Stephen W; Kent, Michael L

    2011-06-16

    Microsporidia in histologic sections are most often diagnosed by observing spores in host tissues. Spores are easy to identify if they occur in large aggregates or xenomas when sections are stained with hematoxylin and eosin (H&E). However, individual spores are not frequently detected in host tissues with conventional H&E staining, particularly if spores are scattered within the tissues, areas of inflammation, or small spores in nuclei (i.e. Nucleospora salmonis). Hence, a variety of selective stains that enhance visualization of spores is recommended. We discovered that the Luna stain, used to highlight eosinophils, red blood cells, and chitin in arthropods and other invertebrates, also stains spores of Pseudoloma neurophilia. We compared this stain to the Gram, Fite's acid fast, Giemsa, and H&E stains on 8 aquatic microsporidian organisms that were readily available in our 2 laboratories: Loma salmonae, Glugea anomala, Pseudoloma neurophilia, Pleistophora hyphessobryconis, Pleistophora vermiformis, Glugea sp., Steinhausia mytilovum, and an unidentified microsporidian from UK mitten crabs Eriocheir sinensis. Based on tinctorial properties and background staining, the Luna stain performed better for detection of 6 of the 8 microsporidia. Gram stain was superior for the 2 microsporidia from invertebrates: S. mytilovum and the unidentified microsporidian from E. sinensis.

  20. The Luna stain, an improved selective stain for detection of microsporidian spores in histologic sections

    PubMed Central

    Peterson, Tracy S.; Spitsbergen, Jan M.; Feist, Stephen W.; Kent, Michael L.

    2014-01-01

    Microsporidia in histologic sections are most often diagnosed by observing spores in host tissues. Spores are easy to identify if they occur in large aggregates or xenomas when sections are stained with hematoxylin and eosin (H&E). However, individual spores are not frequently detected in host tissues with conventional H&E staining, particularly if spores are scattered within the tissues, areas of inflammation or small spores in nuclei (i.e., Nucleospora salmonis). Hence, a variety of selective stains that enhance visualization of spores are recommended. We discovered that the Luna stain, used to highlight eosinophils, red blood cells and chitin in arthropods and other invertebrates, also stains spores of Pseudoloma neurophilia. We compared this stain to the Gram, Fite’s acid fast, Giemsa, and H&E stains on eight aquatic microsporidian organisms that were readily available in our two laboratories: Loma salmonae, Glugea anomala, Pseudoloma neurophilia, Pleistophora hyphessobryconis, Pleistophora vermiformis, Glugea sp., Steinhausia mytilovum and an unidentified microsporidian from E. sinensis, UK. Based on tinctorial properties and background staining, the Luna stain performed better for detection of 6 of the 8 microsporidia. Gram stain was superior for the two microsporidia from invertebrates, Steinhausia mytilovum and the unidentified microsporidian from E. sinensis. PMID:21848126

  1. Weigners fixative-an alternative to formalin fixation for histology with improved preservation of nucleic acids.

    PubMed

    Klopfleisch, R; von Deetzen, M; Weiss, A Th; Weigner, J; Weigner, F; Plendl, J; Gruber, A D

    2013-01-01

    Formalin fixation and paraffin embedding (FFPE) is the standard method for tissue storage in histopathology. However, FFPE has disadvantages in terms of user health, environment, and nucleic acid integrity. Weigners fixative has been suggested as an alternative for embalming cadavers in human and veterinary anatomy. The present study tested the applicability of Weigners for histology and immunohistochemistry and the preservation of nucleic acids. To this end, a set of organs was fixed for 2 days and up to 6 months in Weigners (WFPE) or formalin. WFPE tissues from the skin, brain, lymphatic tissues, liver, and muscle had good morphologic preservation, comparable to formalin fixation. The quality of kidney and lung samples was inferior to FFPE material due to less accentuated nuclear staining and retention of proteinaceous interstitial fluids. Azan, Turnbull blue, toluidin, and immunohistochemical stainings for CD79a, cytokeratin, vimentin, and von Willebrand factor led to comparable results with both fixates. Of note, immunohistochemical detection of CD3 was possible after 6 months in WFPE but not in FFPE tissues. mRNA, miRNA, and DNA from WFPE tissues had superior quality and allowed for amplification of miRNA, 400-bp-long mRNA, and 1000-bp-long DNA fragments after 6 months of fixation in WFPE. In summary, Weigners fixative is a nonhazardous alternative to formalin, which provides a good morphologic preservation of most organs, a similar sensitivity for protein detection, and a superior preservation of nucleic acids. Weigners may therefore be a promising alternative to cryopreservation and may be embraced by people affected by formalin allergies.

  2. Nanoparticle-encapsulated baicalein markedly modulates pro-inflammatory response in gingival epithelial cells.

    PubMed

    Li, Xuan; Luo, Wei; Ng, Tsz Wing; Leung, Ping Chung; Zhang, Chengfei; Leung, Ken Cham-Fai; Jin, Lijian

    2017-09-14

    Severe gum disease (periodontitis), which is one of the major global oral diseases, results from microbe-host dysbiosis and dysregulated immuno-inflammatory responses. It seriously affects oral health and general wellbeing with significant socio-economic implications. It has been well documented that natural flavonoids such as baicalin (BA) and baicalein (BE) possess potent anti-inflammatory effects. However, their intrinsic poor solubility and low bioavailability severely limit their biomedical applications. In the present study, BA and BE were encapsulated in our synthesized and amine-modified mesoporous silica nanoparticles (MSNs) (Nano-BA and Nano-BE, respectively), and their loading efficiencies and releasing profiles were investigated. Their cytotoxicity was examined on primary human gingival epithelial cells (hGECs), and the cellular uptake of Nano-BA or Nano-BE was visualized via a transmission electron microscope. Their anti-inflammatory effects were evaluated in IL-1β-treated hGECs using the cytokine array and enzyme-linked immunosorbent assay. The present study shows that the amine-modified MSNs could encapsulate BA and BE, and nano-encapsulation greatly enhances the drug delivery rate and prolongs the release of BA and BE up to 216 h. Moreover, both Nano-BA and Nano-BE could be internalized by hGECs and retained intracellularly in nanoparticle-free media for at least 24 h. Note that Nano-BE pre-treatment effectively down-regulates the IL-1β-induced expression of IL-6 and IL-8 in hGECs. In conclusion, nanoparticle-encapsulated BE exhibits notable anti-inflammatory effects through effective release and cellular internalization approaches. This study may facilitate the development of novel drug delivery systems for improving oral care.

  3. Baicalein Decreases Hydrogen Peroxide-Induced Damage to NG108-15 Cells via Upregulation of Nrf2.

    PubMed

    Yeh, Chao-Hung; Ma, Kuo-Hsing; Liu, Pei-Shan; Kuo, Jung-Kuei; Chueh, Sheau-Huei

    2015-08-01

    Baicalein is a flavonoid inhibitor of 12-lipoxygenase. Here, we investigated its effect on hydrogen peroxide-induced damage to NG108-15 cells. Hydrogen peroxide activated the mitochondrial apoptotic pathway, decreased Nrf2 expression, increased reactive oxygen species (ROS) levels, reduced viability, and increased cell death after 2-24 h treatment of NG108-15 cells. Co-treatment with hydrogen peroxide and baicalein completely suppressed the activation of mitochondrial apoptotic pathway by upregulating Nrf2 expression and reducing ROS stress and partially inhibited the effects on cell viability and cell death. Silencing of 12-lipoxygenase had a similar protective effect to baicalein on hydrogen peroxide-induced damage by blocking the hydrogen peroxide-induced decrease in Nrf2 expression and increase in ROS levels. Neither protective effect was altered by addition of 12-hydroxyeicosatetraenoic acid, the product of 12-lipoxygenase, suggesting that hydrogen peroxide induced damage via 12-lipoxygenase by another, as yet unknown, mechanism, rather than activating it. Co-treatment of cells with hydrogen peroxide and N-acetylcysteine or the Nrf2 inducer sulforaphane reduced hydrogen peroxide-induced damage in a similar fashion to baicalein, while the Nrf2 inhibitor retinoic acid blocked the protective effect of baicalein. Silencing Nrf2 also inhibited the protective effects of baicalein, sulforaphane, and N-acetylcysteine and resulted in high ROS levels, suggesting ROS elimination was mediated by Nrf2. Taken together our results suggest that baicalein protects cells from hydrogen peroxide-induced activation of the mitochondrial apoptotic pathway by upregulating Nrf2 and inhibiting 12-lipoxygenase to block the increase in ROS levels. Hydrogen peroxide also activates a second mitochondrial dysfunction independent death pathway which is resistant to baicalein. © 2015 Wiley Periodicals, Inc.

  4. Improved droplet-vitrification and histological studies of cryopreserved shoot tips of cultivated Jerusalem artichoke genotypes

    USDA-ARS?s Scientific Manuscript database

    Germplasm conservation of Jerusalem artichoke (Helianthus tuberosus L.) is crucial to preserve genetic diversity and to secure materials for genetic improvement. Long-term conservation is accomplished through cryopreservation, storing cells or tissues at an ultralow temperature in liquid nitrogen (-...

  5. Baicalin and baicalein attenuate renal fibrosis in vitro via inhibition of the TGF-β1 signaling pathway.

    PubMed

    Hu, Qin; Gao, Lina; Peng, Bo; Liu, Xinmin

    2017-10-01

    Baicalin and baicalein are flavonoid compounds derived from Scutellaria baicalensis Georgi. These compounds have been used in the treatment of numerous diseases, including fibrotic diseases. However, research regarding their antifibrotic effects and mechanism of action in renal fibrosis is limited. In the present study, normal rat kidney interstitial fibroblast (NRK-49F) cells were stimulated with transforming growth factor (TGF)-β1, with or without baicalin/baicalein, and assessed for proliferation, apoptosis, extracellular matrix (ECM) accumulation, collagen expression, TGF-β1 expression and mothers against decapentaplegic homolog 3 (SMAD3) protein activation. The results revealed that baicalin and baicalein exhibited antifibrotic effects in vitro, whereas baicalein had a stronger inhibitory action compared with baicalin on TGF-β1-induced NRK-49F cell proliferation, deposition of ECM, collagen synthesis, endogenous TGF-β1 expression and phosphorylation of SMAD3. In conclusion, the findings of the present study indicate that baicalin and baicalein, particularly baicalein, exhibit antifibrotic effects in vitro by inhibiting the TGF-β1 pathway. Therefore, these compounds have the potential to be developed as novel agents to treat renal fibrosis.

  6. Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage

    PubMed Central

    Lei, Beilei; James, Michael L.; Liu, Ji; Zhou, Guanen; Venkatraman, Talaignair N.; Lascola, Christopher D.; Acheson, Shawn K.; Dubois, Laura G.; Laskowitz, Daniel T.; Wang, Haichen

    2016-01-01

    Presently, no pharmacological treatments have been demonstrated to improve long-term functional outcomes following intracerebral hemorrhage (ICH). Clinical evidence associates apolipoprotein E (apoE) genotype with ICH incidence and outcome. While apoE modifies neuroinflammatory responses through its adaptive role in glial downregulation, intact apoE holoprotein is too large to cross the blood-brain barrier (BBB). Therefore, we developed a 5-amino acid peptide – CN-105 – that mimics the polar face of the apoE helical domain involved in receptor interactions. In the current study, we investigated the therapeutic potential of CN-105 in a mouse model of ICH. Three doses of CN-105 (0.05 mg/kg) was administered by tail vein injection within 24 hours after ICH induction. Functional assessment showed durable improvement in vestibulomotor performance after CN-105 treatment, as quantified by increased Rotarod latencies on Days 1–5 post-ICH, and long-term improvement in neurocognitive performance, as quantified by reduced Morris water maze latencies on Days 29–32 post-ICH. Further, brain water content was significantly reduced, neuroinflammation was decreased and hippocampal CA3 neuronal survival was increased, although hemorrhage volume was not affected by CN-105. We concluded, therefore, that pentapeptide CN-105 improved short- and long-term neurobehavioral outcomes in a murine model of ICH, suggesting therapeutic potential for patients with acute ICH. PMID:27713572

  7. Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.

    PubMed

    Lei, Beilei; James, Michael L; Liu, Ji; Zhou, Guanen; Venkatraman, Talaignair N; Lascola, Christopher D; Acheson, Shawn K; Dubois, Laura G; Laskowitz, Daniel T; Wang, Haichen

    2016-10-07

    Presently, no pharmacological treatments have been demonstrated to improve long-term functional outcomes following intracerebral hemorrhage (ICH). Clinical evidence associates apolipoprotein E (apoE) genotype with ICH incidence and outcome. While apoE modifies neuroinflammatory responses through its adaptive role in glial downregulation, intact apoE holoprotein is too large to cross the blood-brain barrier (BBB). Therefore, we developed a 5-amino acid peptide - CN-105 - that mimics the polar face of the apoE helical domain involved in receptor interactions. In the current study, we investigated the therapeutic potential of CN-105 in a mouse model of ICH. Three doses of CN-105 (0.05 mg/kg) was administered by tail vein injection within 24 hours after ICH induction. Functional assessment showed durable improvement in vestibulomotor performance after CN-105 treatment, as quantified by increased Rotarod latencies on Days 1-5 post-ICH, and long-term improvement in neurocognitive performance, as quantified by reduced Morris water maze latencies on Days 29-32 post-ICH. Further, brain water content was significantly reduced, neuroinflammation was decreased and hippocampal CA3 neuronal survival was increased, although hemorrhage volume was not affected by CN-105. We concluded, therefore, that pentapeptide CN-105 improved short- and long-term neurobehavioral outcomes in a murine model of ICH, suggesting therapeutic potential for patients with acute ICH.

  8. Histological Mohs Maps Improve the Accuracy of Dermatology Residents' Interpretations of Mohs Slides: A Pilot Study.

    PubMed

    Tiger, Jeffrey B; Ganesh, Zai; Mouzakis, John; Iwamoto, Satori

    2017-08-01

    Effective Mohs surgery depends on accurate histopathological identification and mapping of tumor burden to ensure complete removal of tumor. The purpose of this study is to evaluate whether using a photograph of the histopathological slide as the Mohs map improves mapping accuracy. Single-blinded pilot study. Five dermatology residents at one academic institution mapped 11 cases of basal cell carcinoma using both traditional hand-drawn maps and color photographic maps. Residents' marked maps were assessed for global diagnostic accuracy, sensitivity, and specificity compared with the Mohs map verified by the attending surgeon on the day of surgery. Diagnostic accuracy, sensitivity, and specificity were higher using the photographic Mohs maps compared with using the traditional hand-drawn maps (58.2% vs 29.1%, 84.5% vs 76.4%, and 87.1% vs 70.8%, respectively). These results were statistically significant for accuracy and specificity, but not for sensitivity. Using histopathological photographs as the Mohs map significantly improved accuracy and specificity within a small group of residents with limited Mohs experience. More research is warranted to evaluate whether using histopathological photographs improves accuracy of Mohs mapping for experienced Mohs surgeons in a real-world setting, and whether this translates to improved clinical outcomes.

  9. Life style modification improves insulin resistance and liver histology in patients with non-alcoholic fatty liver disease

    PubMed Central

    Bhat, Ganesh; Baba, Chalamalasetty Sreenivasa; Pandey, Amaresh; Kumari, Neeraj; Choudhuri, Gourdas

    2012-01-01

    AIM: To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m2). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6 mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo. RESULTS: Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m2 to 25.0 ± 3.3 kg/m2, WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient’s insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, rs = 0.90) and liver histology (P = 0.03, rs = 0.73). CONCLUSION: Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients

  10. Life style modification improves insulin resistance and liver histology in patients with non-alcoholic fatty liver disease.

    PubMed

    Bhat, Ganesh; Baba, Chalamalasetty Sreenivasa; Pandey, Amaresh; Kumari, Neeraj; Choudhuri, Gourdas

    2012-07-27

    To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m(2)). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6 mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo. Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m(2) to 25.0 ± 3.3 kg/m(2), WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient's insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, r(s) = 0.90) and liver histology (P = 0.03, r(s) = 0.73). Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients.

  11. [Application of diversified teaching methods to improve the teaching effects in the course of oral histology and pathology].

    PubMed

    Tian, Zhen; Li, Lei; Wang, Li-zhen; Hu, Yu-hua; Zhang, Chun-ye; Li, Jiang

    2016-02-01

    Oral histology and pathology is one of the most important courses in stomatological education which works as a bridge between basic medical courses and clinical courses of oral science. The knowledge of oral histopathology may help the students to correctly understand the histogenesis and development of oral diseases and provide the information for correct treatment and prevention. In order to make the students grasp the necessary basic theories, increase the interest in learning, and improve the teaching effect, we explored a diversified teaching system which included diverse teaching modes, online courses and courseware construction. The application of this system offered the interaction between students and teachers and combination of classes with the internet, and made the boring pathological knowledge be associated with clinical practice. These diversified teaching methods had been used in practice and obtained good teaching results.

  12. Functional and histological outcome after focal traumatic brain injury is not improved in conditional EphA4 knockout mice.

    PubMed

    Hånell, Anders; Clausen, Fredrik; Djupsjö, Anders; Vallstedt, Anna; Patra, Kalicharan; Israelsson, Charlotte; Larhammar, Martin; Björk, Maria; Paixão, Sónia; Kullander, Klas; Marklund, Niklas

    2012-11-20

    We investigated the role of the axon guidance molecule EphA4 following traumatic brain injury (TBI) in mice. Neutralization of EphA4 improved motor function and axonal regeneration following experimental spinal cord injury (SCI). We hypothesized that genetic absence of EphA4 could improve functional and histological outcome following TBI. Using qRT-PCR in wild-type (WT) mice, we evaluated the EphA4 mRNA levels following controlled cortical impact (CCI) TBI or sham injury and found it to be downregulated in the hippocampus (p<0.05) but not the cortex ipsilateral to the injury at 24 h post-injury. Next, we evaluated the behavioral and histological outcome following CCI using WT mice and Emx1-Cre-driven conditional knockout (cKO) mice. In cKO mice, EphA4 was completely absent in the hippocampus and markedly reduced in the cortical regions from embryonic day 16, which was confirmed using Western blot analysis. EphA4 cKO mice had similar learning and memory abilities at 3 weeks post-TBI compared to WT controls, although brain-injured animals performed worse than sham-injured controls (p<0.05). EphA4 cKO mice performed similarly to WT mice in the rotarod and cylinder tests of motor function up to 29 days post-injury. TBI increased cortical and hippocampal astrocytosis (GFAP immunohistochemistry, p<0.05) and hippocampal sprouting (Timm stain, p<0.05) and induced a marked loss of hemispheric tissue (p<0.05). EphA4 cKO did not alter the histological outcome. Although our results may argue against a beneficial role for EphA4 in the recovery process following TBI, further studies including post-injury pharmacological neutralization of EphA4 are needed to define the role for EphA4 following TBI.

  13. Progesterone improves long-term functional and histological outcomes after permanent stroke in older rats.

    PubMed

    Wali, Bushra; Ishrat, Tauheed; Stein, Donald G; Sayeed, Iqbal

    2016-05-15

    Previous studies have shown progesterone to be beneficial in animal models of central nervous system injury, but less is known about its longer-term sustained effects on recovery of function following stroke. We evaluated progesterone's effects on a panel of behavioral tests up to 8 weeks after permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats 12m.o. were subjected to pMCAO and, beginning 3h post-pMCAO, given intraperitoneal injections of progesterone (8mg/kg) or vehicle, followed by subcutaneous injections at 8h and then every 24h for 7 days, with tapering of the last 2 treatments. The rats were then tested on functional recovery at 3, 6 and 8 weeks post-stroke. We observed that progesterone-treated animals showed attenuation of infarct volume and improved functional outcomes at 8 weeks after stroke on grip strength, sensory neglect, motor coordination and spatial navigation tests. Progesterone treatments significantly improved motor deficits in the affected limb on a number of gait parameters. Glial fibrillary acidic protein expression was increased in the vehicle group and considerably lowered in the progesterone group at 8 weeks post-stroke. With repeated post-stroke testing, sensory neglect and some aspects of spatial learning performance showed spontaneous recovery, but on gait and grip-strength measres progesterone given only in the acute stage of stroke (first 7 days) showed sustained beneficial effects on all other measures of functional recovery up to 8 weeks post-stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway

    PubMed Central

    Ma, Xingcong; Yan, Wanjun; Dai, Zhijun; Gao, Xiaoyan; Ma, Yinan; Xu, Quntao; Jiang, Jiantao; Zhang, Shuqun

    2016-01-01

    Background The flavonoid baicalein, a historically used Chinese herbal medicine, shows a wide range of biological and pharmaceutical effects, among which its potent antitumor activity has raised great interest in recent years. However, the molecular mechanism involved in the antimetastatic effect of baicalein remains poorly understood. This study aimed to verify the inhibitory effects of baicalein on metastasis of MDA-MB-231 human breast cancer cells both in vitro and in vivo, as well as to investigate the related mechanisms. Methods MTT assay was used to examine the inhibition of baicalein on proliferation of MDA-MB-231 cells. Wound healing assay and the in vitro invasion assay was carried out to investigate the effects of baicalein on migration and invasion of MDA-MB-231 cells, respectively. In order to explore the effects of baicalein on tumor metastasis in vivo, xenograft nude mouse model of MDA-MB-231 cells was established. Animals were randomly divided into four groups (control, therapy group, and low-dose and high-dose prevention group, n=6), and treated with baicalein as designed. Following sacrifice, their lungs and livers were collected to examine the presence of metastases. qRT-PCR and Western blot were performed to study the effects of baicalein on expression of SATB1, EMT-related molecules, and Wnt/β-catenin signaling components of MDA-MB-231 cells as well as the metastatic tissue. Effects of baicalein on the expression of target proteins in vivo were also analyzed by immunohistochemistry. Results Our results indicated that baicalein suppressed proliferation, migration, and invasion of MDA-MB-231 cells in a time- and dose-dependent manner. Based on assays carried out in xenograft nude mouse model, we found that baicalein inhibited tumor metastasis in vivo. Furthermore, baicalein significantly decreased the expression of SATB1 in MDA-MB-231 cells. It suppressed the expression of vimentin and SNAIL while enhancing the expression of E-cadherin. Baicalein

  15. Correlation of breast tissue histology and optical signatures to improve margin assessment techniques

    NASA Astrophysics Data System (ADS)

    Kennedy, Stephanie; Caldwell, Matthew; Bydlon, Torre; Mulvey, Christine; Mueller, Jenna; Wilke, Lee; Barry, William; Ramanujam, Nimmi; Geradts, Joseph

    2016-06-01

    Optical spectroscopy is sensitive to morphological composition and has potential applications in intraoperative margin assessment. Here, we evaluate ex vivo breast tissue and corresponding quantified hematoxylin & eosin images to correlate optical scattering signatures to tissue composition stratified by patient characteristics. Adipose sites (213) were characterized by their cell area and density. All other benign and malignant sites (181) were quantified using a grid method to determine composition. The relationships between mean reduced scattering coefficient (<μs‧>), and % adipose, % collagen, % glands, adipocyte cell area, and adipocyte density were investigated. These relationships were further stratified by age, menopausal status, body mass index (BMI), and breast density. We identified a positive correlation between <μs‧> and % collagen and a negative correlation between <μs‧> and age and BMI. Increased collagen corresponded to increased <μs‧> variability. In postmenopausal women, <μs‧> was similar regardless of fibroglandular content. Contributions from collagen and glands to <μs‧> were independent and equivalent in benign sites; glands showed a stronger positive correlation than collagen to <μs‧> in malignant sites. Our data suggest that scattering could differentiate highly scattering malignant from benign tissues in postmenopausal women. The relationship between scattering and tissue composition will support improved scattering models and technologies to enhance intraoperative optical margin assessment.

  16. Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase.

    PubMed

    Chan, Ben C L; Ip, Margaret; Lau, Clara B S; Lui, S L; Jolivalt, Claude; Ganem-Elbaz, Carine; Litaudon, Marc; Reiner, Neil E; Gong, Huansheng; See, Raymond H; Fung, K P; Leung, P C

    2011-09-01

    Baicalein, the active constituent derived from Scutellaria baicalensis Georgi., has previously been shown to significantly restore the effectiveness of β-lactam antibiotics and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA). With multiple therapeutic benefits, the antibacterial actions of baicalein may also be involved in overcoming other bacterial resistance mechanisms. The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms. A panel of clinical MRSA strains was used for further confirmation of the antibacterial activities of baicalein. The effect of baicalein on inhibiting the enzymatic activity of a newly discovered MRSA-specific pyruvate kinase (PK), which is essential for Staphylococcus aureus growth and survival was also examined. In the checkerboard dilution test and time-kill assay, baicalein at 16 μg/ml could synergistically restore the antibacterial actions of ciprofloxacin against the NorA efflux pump overexpressed SA-1199B, but not with the poor NorA substrate, pefloxacin. Moreover, synergistic effects were observed when baicalein was combined with ciprofloxacin against 12 out of 20 clinical ciprofloxacin resistant strains. For MRSA PK studies, baicalein alone could inhibit the enzymatic activity of MRSA PK in a dose-dependent manner. Our results demonstrated that baicalein could significantly reverse the ciprofloxacin resistance of MRSA possibly by inhibiting the NorA efflux pump in vitro. The inhibition of MRSA PK by baicalein could lead to a deficiency of ATP which might further contribute to the antibacterial actions of baicalein against MRSA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

    PubMed

    Sun, Yu-Yo; Lin, Shang-Hsuan; Lin, Hung-Cheng; Hung, Chia-Chi; Wang, Chen-Yu; Lin, Yen-Chu; Hung, Kuo-Sheng; Lien, Cheng-Chang; Kuan, Chia-Yi; Lee, Yi-Hsuan

    2013-01-01

    The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.

  18. Cell Type-Specific Dependency on the PI3K/Akt Signaling Pathway for the Endogenous Epo and VEGF Induction by Baicalein in Neurons versus Astrocytes

    PubMed Central

    Sun, Yu-Yo; Lin, Shang-Hsuan; Lin, Hung-Cheng; Hung, Chia-Chi; Wang, Chen-Yu; Lin, Yen-Chu; Hung, Kuo-Sheng; Lien, Cheng-Chang; Kuan, Chia-Yi; Lee, Yi-Hsuan

    2013-01-01

    The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo. PMID:23904909

  19. Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury

    PubMed Central

    Galvan, Manuel D.; Luchetti, Sabina; Burgos, Adrian M.; Nguyen, Hal X.; Hooshmand, Mitra J.; Anderson, Aileen J.; Hamers, Frank P.T.

    2009-01-01

    Although studies have suggested a role for the complement system in the pathophysiology of spinal cord injury (SCI), that role remains poorly defined. Additionally, the relative contribution of individual complement pathways in SCI is unknown. Our initial studies revealed that systemic complement activation was strongly influenced by genetic background and gender. Thus, to investigate the role of the classical complement pathway in contusion-induced SCI, male C1q knockout (KO) and wildtype (WT) mice on a complement sufficient background (BUB) received a mild-moderate T9 contusion injury with the Infinite Horizon (IH) impactor. BUB C1q KO mice exhibited greater locomotor recovery in comparison to BUB WT mice (p < 0.05). Improved recovery observed in BUB C1q KO mice was also associated with decreased threshold for withdrawal from a mild stimulus using von Frey filament testing. Surprisingly, quantification of microglia/macrophages (F4/80) by FACS analysis showed that BUB C1q KO mice exhibited a significantly greater percentage of macrophages in the spinal cord compared to BUB WT mice 3 days post injury (p < 0.05). However, this increased macrophage response appeared to be transient as stereological assessment of spinal cord tissue obtained 28 days post injury revealed no difference in F4/80 positive cells between groups. Stereological assessment of spinal cord tissue showed that BUB C1q KO mice had reduced lesion volume and an increase in tissue sparing in comparison to BUB WT mice (p < 0.05). Taken together, these data suggest that initiation of the classical complement pathway via C1q is detrimental to recovery after SCI. PMID:19091977

  20. Biotransformation of baicalin to baicalein significantly strengthens the inhibition potential towards UDP-glucuronosyltransferases (UGTs) isoforms.

    PubMed

    Teng, Yanjie; Nian, Hong; Zhao, Hongtao; Chen, Pei; Wang, Guan

    2013-09-01

    The aim of the present study was to investigate the influence of biotransformation of baicalin into baicalein towards the inhibition potential towards one of the most important drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferases (UGTs). in vitro incubation method using recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used to evaluate the inhibition towards important UGT isoforms in the liver, including UGT1A1, 1A3, 1A6, 1A9, and 2B7. At the same concentration (100 microM), baicalein showed stronger inhibition potential than baicalin towards all the tested UGT isoforms. Data fitting using Dixon plot and Lineweaver-Burk plot was carried out to determine the inhibition type, and the second plot with the slopes from Lineweaver-Burk plot towards baicalein's concentrations was used to calculate the inhibition kinetic parameters (K(i)). Competitive inhibition type was observed for UGT1A1, 1A6, 1A9 and 2B7, and noncompetitive inhibition was detected for UGT1A3. The inhibition kinetic parameters (K(i)) were calculated to be 1.2, 5.1, 15.3, 26.3, and 48.9 microM for UGT1A1, 1A3, 1A6, 1A9, and 2B7, respectively. All these information reminds us of the necessary monitoring when oral administration of baicalin or baicalin-containing herbs.

  1. Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF-κB and MAPK signaling pathways in LPS-induced mastitis in mice.

    PubMed

    He, Xuexiu; Wei, Zhengkai; Zhou, Ershun; Chen, Libin; Kou, Jinhua; Wang, Jingjing; Yang, Zhengtao

    2015-09-01

    Baicalein is a phenolic flavonoid presented in the dry roots of Scutellaria baicalensis Georgi. It has been reported that baicalein possesses a number of biological properties, such as antiviral, antioxidative, anti-inflammatory, antithrombotic, and anticancer properties. However, the effect of baicalein on mastitis has not yet been reported. This research aims to detect the effect of baicalein on lipopolysaccharide (LPS)-induced mastitis in mice and to investigate the molecular mechanisms. Baicalein was administered intraperitoneally 1h before and 12h after LPS treatment. The results indicated that baicalein treatment markedly attenuated the damage of the mammary gland induced by LPS, suppressed the activity of myeloperoxidase (MPO) and the levels of tumor necrosis factor (TNF-α) and interleukin (IL-1β) in mice with LPS-induced mastitis. Besides, baicalein blocked the expression of Toll-like receptor 4 (TLR4) and then suppressed the phosphorylation of nuclear transcription factor-kappaB (NF-κB) p65 and degradation inhibitor of NF-κBα (IκBα) and, and inhibited the phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) in mitogen-activated protein kinase (MAPK) signal pathway. These findings suggested that baicalein may have a potential prospect against mastitis.

  2. Interactions of the baicalin and baicalein with bilayer lipid membranes investigated by cyclic voltammetry and UV-Vis spectroscopy.

    PubMed

    Zhang, Ying; Wang, Xuejing; Wang, Lei; Yu, Miao; Han, Xiaojun

    2014-02-01

    The baicalin and baicalein are the major flavonoids found in Radix Scutellariae, an essential herb in traditional Chinese medicine for thousands of years. The interactions of the baicalin and baicalein with lipid bilayer membranes were studied using cyclic voltammetry and UV-Vis spectroscopy. The thickness d of supported bilayer lipid membranes was calculated as d=4.59(±0.36) nm using AC impedance spectroscopy. The baicalein interacted with egg PC bilayer membranes in a dose-dependent manner. The responses of K3Fe(CN)6 on lipid bilayer membrane modified Pt electrode linearly increased in a concentration range of baicalein from 6.25μM to 25μM with a detection limit of 0.1μM and current-concentration sensitivity of 0.11(±0.01) μA/μM, and then reached a plateau from 25μM to 50μM. However the baicalin showed much weaker interactions with egg PC bilayer membranes. UV-Vis spectroscopy also confirmed that the baicalein could interact with egg PC membranes noticeably, but the interaction of baicalin with membranes was hard to be detected. The results provide useful information on understanding the mechanism of action of Radix Scutellariae in vivo.

  3. Treatment with nasal neuro-EPO improves the neurological, cognitive, and histological state in a gerbil model of focal ischemia.

    PubMed

    Rodríguez Cruz, Yamila; Mengana Támos, Yuneidys; Muñoz Cernuda, Adriana; Subirós Martines, Nelvis; González-Quevedo, Alina; Sosa Testé, Iliana; García Rodríguez, Julio César

    2010-11-16

    Vascular illness of the brain constitutes the third cause of death and the first cause of disability in Cuba and many other countries. Presently, no medication has been registered as a neuroprotector. Neuroprotection with intranasal Neuro-EPO (EPO, erythropoietin) has emerged as a multifunctional therapy that plays a significant role in neural survival and functional recovery in an animal model of stroke. On the other hand, there is limited access to the brain through the blood brain barrier (BBB) for intravenously applied EPO, and the high EPO dosages needed to obtain a protective effect increase the danger of elevated hematocrit levels and practically exclude chronic or subchronic treatment with EPO. A promising approach has been recently developed with a nonerythropoietic variant of EPO, Neuro-EPO, with low sialic acid content, a very short plasma half-life, and without erythropoietic activity, probably similar to endogenous brain EPO. The objective of this work was to determine the neuroprotective effect of intranasal Neuro-EPO in comparison with the human recombinant EPO injected intraperitoneally in the acute phase of cerebral ischemia, employing the common carotid artery occlusion model in gerbils. Neuro-EPO has demonstrated a better neuroprotective effect, evidenced through increased viability, improvements of the neurological state and cognitive functions, as well as protection of the CA3 region of the hippocampus, temporal cortex, and the thalamus. In conclusion, the intranasal application of Neuro-EPO has a better neuroprotective effect than intraperitoneal EPO, evidenced by the significant improvement of neurological, cognitive, and histological status in the animal model of stroke employed.

  4. Synergistic effects of baicalein with cefotaxime against Klebsiella pneumoniae through inhibiting CTX-M-1 gene expression.

    PubMed

    Cai, Wenhui; Fu, Yingmei; Zhang, Wenli; Chen, Xiaobei; Zhao, Jizi; Song, Wuqi; Li, Yujun; Huang, Ying; Wu, Zheng; Sun, Rui; Dong, Chunping; Zhang, Fengmin

    2016-08-08

    Generation of extended- spectrum β- lactamases is one of the major mechanisms by which clinical Klebsiella pneumoniae develop resistance to antibiotics. Combined antibiotics prove to be a relatively effective method of controlling such resistant strains. Some of Chinese herbal active ingredients are known to have synergistic antibacterial effects. This study is aimed to investigate synergistic effects of Chinese herbal active ingredients with cefotaxime on the extended- spectrum β- lactamase positive strains of Klebsiella pneumoniae, and to analyze mechanism of synergistic action, providing experimental evidence for clinical application of antimicrobial drugs. For total sixteen strains including fifteen strains of cefotaxime resistant K. pneumoniae and one extended- spectrum β- lactamase positive standard strain, the synergy rates of cefotaxime with baicalein, matrine, and clavulanic acid were 56.3 %, 0 %, and 100 %, respectively. The fractional inhibitory concentration index of combined baicalein and cefotaxime was correlated with the percentage decrease of cefotaxime MIC of all the strains (r = -0.78, p <0.01). In the group of synergy baicalein and cefotaxime, the transcribed mRNA level of CTX-M-1 after treatment of baicalein was decreased significantly (p <0.05). Moreover, the CTX-M-1 mRNA expression percentage inhibition (100 %, 5/5) was significantly higher than non- synergy group (25 %, 1/4) (p <0.05). Our study demonstrated that baicalein exhibited synergistic activity when combined with cefotaxime against some of extended- spectrum β- lactamases positive K. pneumoniae strains by inhibiting CTX-M-1 mRNA expression. However, no direct bactericidal or bacteriostatic activity was involved in the synergistic action. Baicalein seems to be a promising novel effective synergistic antimicrobial agent.

  5. Development and extraction optimization of baicalein and pinostrobin from Scutellaria violacea through response surface methodology

    PubMed Central

    Subramaniam, Shankar; Raju, Ravikumar; Palanisamy, Anbumathi; Sivasubramanian, Aravind

    2015-01-01

    Objective: To develop a process that involves optimization of the amount of baicalein and pinostrobin from the hydro-methanolic extract of the leaves of Scutellaria violacea by response surface methodology (RSM). Materials and Methods: The combinatorial influence of various extraction parameters on the extraction yield was investigated by adopting Box–Behnken experimental design. Preliminary experiments carried out based on the traditional one variable at a time optimization revealed four such operational parameters to play a crucial role by influencing the yield. These four process parameters at three levels were considered to obtain the Box–Behnken experimental design. Results: RSM based model fitted to the resulting experimental data suggested that 52.3% methanol/water, 12.46:1 solvent-solid ratio, 285 rpm agitation and 6.07 h of extraction time are the optimal conditions which yielded a maximized amount of baicalein and pinostrobin of 2.9 and 4.05 mg/g DM. Analysis of variance revealed a high correlation coefficient (R2 = 0.999 for baicalein and 0.994 for pinostrobin), signifying a good fit between the regression model (second order) and the experimental observations. Conclusion: The present study signifies that both the metabolites have been extracted from S. violacea for the first time. Further, this study developed an optimized extraction procedure to obtain maximum yield of the metabolites, which is unique and better than conventional extraction methodology. The operational parameters under optimized conditions accounts for the lowest cost in extraction process thus, providing an efficient, rapid and cost-effective method for isolation and scale up of these commercially vital flavonoids. PMID:26109758

  6. Baicalein Inhibits the Migration and Invasion of B16F10 Mouse Melanoma Cells through Inactivation of the PI3K/Akt Signaling Pathway

    PubMed Central

    Choi, Eun-Ok; Cho, Eun-Ju; Jeong, Jin-Woo; Park, Cheol; Hong, Su-Hyun; Hwang, Hye-Jin; Moon, Sung-Kwon; Son, Chang Gue; Kim, Wun-Jae; Choi, Yung Hyun

    2017-01-01

    Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway. PMID:27530117

  7. Baicalein protects C6 glial cells against hydrogen peroxide-induced oxidative stress and apoptosis through regulation of the Nrf2 signaling pathway.

    PubMed

    Choi, Eun-Ok; Jeong, Jin-Woo; Park, Cheol; Hong, Su Hyun; Kim, Gi-Young; Hwang, Hye-Jin; Cho, Eun-Ju; Choi, Yung Hyun

    2016-03-01

    Baicalein, a flavonoid originally obtained from the roots of Scutellaria baicalensis Georgi, has been reported to possess various biological properties. Although several studies have demonstrated the anti-oxidative activity of baicalein, its neuroprotective mechanisms have not been clearly established. The present study aimed to detect the effects of baicalein against hydrogen peroxide (H2O2)-induced neuronal damage in C6 glial cells and to investigate the molecular mechanisms involved in this process. The results demonstrated that baicalein effectively inhibited H2O2-induced growth and reactive oxygen species (ROS) generation. We noted that Baicalein also attenuated the H2O2‑induced formation of comet tail, phosphorylation of p-γH2A.X, loss of mitochondrial membrane potential (MMP or ΔΨm), and changes to apoptosis‑related protein expression, which suggests that it can prevent H2O2‑induced cellular DNA damage and apoptotic cell death. Furthermore, treatment with baicalein effectively induced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as heme oxygenase-1 (HO-1) and thioredoxin reductase 1 (TrxR1) in a concentration and time-dependent manner. Moreover, the protective effects of baicalein against H2O2‑induced DNA damage and apoptosis were abolished by zinc protoporphyrin (ZnPP) IX, a HO-1 inhibitor, and auranofin, a TrxR inhibitor. In addition, we noted that the cytoprotective effects of baicalein were attenuated by transient transfection with Nrf2-specific small interfering RNA (siRNA). The findings of our present study suggest that baicalein enhances cellular antioxidant defense capacity through the inhibition of ROS generation and the activation of the Nrf2 signaling pathway, thus protecting C6 cells from H2O2-induced neuronal damage.

  8. Interactive Atlas of Histology

    PubMed Central

    Goubran, Emile Z.; Vinjamury, Sivarama P.

    2007-01-01

    Purpose: An interactive atlas of histology was developed for online use by chiropractic students to enable them to practice and self-assess their ability to identify various histological structures. This article discusses the steps in the development, implementation, and usefulness of an interactive atlas of histology for students who take histology examinations. Methods: The atlas was developed by digitizing images imported through a video-microscope using actual microscope slides. Leica EWS 2100 and PowerPoint software were used to construct the atlas. The usefulness of the atlas was assessed through a comparison of histology exam scores between four classes before and four classes after the use of the atlas. Analysis of admissions data, including overall grade point average (GPA), science and nonscience GPA, and a number of course units, was done initially to avoid any identifiable differences in the academic competency between the two being compared. A survey of the students was also done to assess atlas usefulness and students' satisfaction with the atlas. Results: Analysis of histology exam scores showed that the average scores in the lab exam were significantly higher for the classes that used the atlas. Survey results showed a high level of student satisfaction with the atlas. Conclusion: The development and use of an online interactive atlas of histology for chiropractic students helped to improve lab exams scores. In addition, students were satisfied with the features and usefulness of this atlas. PMID:18483638

  9. Rapid determination of baicalin and total baicalein content in Scutellariae radix by ATR-IR and NIR spectroscopy.

    PubMed

    Navarro Escamilla, M; Rodenas Sanz, F; Li, H; Schönbichler, S A; Yang, B; Bonn, G K; Huck, C W

    2013-09-30

    In this study methods for the quantification of baicalin and total baicalein in Scutellariae radix with near infrared (NIR) spectroscopy and attenuated-total-reflectance mid-infrared (ATR-IR) spectroscopy in hyphenation with multivariate analysis were developed and compared. The reference analysis was performed by high performance liquid chromatography coupled to diode array detection (HPLC-DAD). Different pretreatments like standard normal variate (SNV), multiplicative scatter correction (MSC), first and second derivative Savitzky-Golay were applied on the spectra to optimize the calibrations. A principal component analysis was performed with both spectroscopic methods to distinguish wild and cultivated samples. Quality parameters obtained for test-set calibration models of ATR-IR spectroscopy (baicalin: standard error of prediction (SEP)=1.31, ratio performance to deviation (RPD)=2.91 and R(2)=0.88; total baicalein: SEP=1.02, RPD=3.24 and R(2)=0.89) and NIR spectroscopy (baicalin: SEP=1.50, RPD=2.54 and R(2)=0.88; total baicalein: SEP=1.19, RPD=2.76 and R(2)=0.84) demonstrate that both spectroscopic techniques in combination with multivariate analysis are successful tools for the quantification of baicalin and total baicalein in Scutellariae radix, but it was found that ATR-IR spectroscopy provides higher accuracy in the given application. Furthermore it was proved that wild and cultivated samples can be distinguished by ATR-IR.

  10. [Preparation of baicalein using thermophilic and sugar-tolerant beta-glucosidase].

    PubMed

    Li, Shi-ping; Wen, Jian-hui; Zhao, Yi-wu; Huang, Wen-zhe; Pei, Jian-jun; Wang, Zhen-zhong; Zhao, Lin-guo; Xiao, Wei

    2015-12-01

    The reaction conditions of baicalin hydrolyzed into baicalein by a kind of thermophilic and sugar-tolerant beta-glucosidase were studied in this paper. The beta-glucosidase could catalyze baicalin into baicalein well in the acetic acid-sodium acetate buffer. The optimal enzyme activity was at 85 degrees C and pH 5.5. The enzyme was stable at the temperature less than 85 degrees C and pH range of 5-7.5. The maximum reaction rate V. and michaelis constant K. were 0.41 mmol x L(-1) x min(-1) and 3.31 mmol x L(-1) respectively. Different metal ions had different effects on the activity of enzyme. Na+ existing in acetic acid-sodium acetate buffer had an activation effect on enzyme. The enzyme activity was enhanced by the concentrations of glucose below 0.6 mol x L(-1), and was gradually inhibited when monosaccharide concentration was over 0.6 mol x L(-1). When the monosaccharide concentration reached 1.2 mol x L(-1), the inhibition rate of enzyme activity was about 50%, which showed good glucose tolerance. The good reaction conditions through the experiment have been determined as follows, the substrate: enzyme dose was 1 g: 0.2 mL, acetic acid-sodium acetate buffer pH 5.5, reaction temperature 85 degrees C, reaction time 10 h, and the enzymatic hydrolyzation ratio could reach 97%.

  11. Brain histology.

    PubMed

    Jeans, Alexander; Esiri, Margaret

    2008-10-01

    In this article we summarise nervous system histology in health and disease and acquaint the reader with developments in the staining techniques that are in current use, particularly immunostains. Although clinicians do not need to know the details of stain appearances, some familiarity with these aspects of neuropathology is invaluable in interpreting the reports they receive from the laboratory, as well as reminding them of the amazing beauty of the central nervous system's microscopic structure.

  12. Simultaneous Determination of Baicalein and Baicalin in Human Plasma by High Performance Liquid Chromatograph-Tandem Spectrometry and its Application in a Food-Effect Pharmacokinetic Study.

    PubMed

    Pang, H; Shi, A; Li, M; Xue, W; Li, Y; Cao, G; Yan, B; Dong, F; Xiao, W; He, G; Du, G; Hu, X; Cheng, G

    2016-08-01

    Baicalein is a flavonoid isolated from skullcap and it is likely to exist in plasma at a low concentration because of the extensive first-pass metabolism in vivo. The aim of our study was to develop and fully validate a sensitive and selective HPLC-MS/MS method for simultaneous determination of baicalein and its main metabolite baicalin (baicalein-7-O-β-glucopyranuronoside) in human plasma. Liquid-liquid extraction was used for pretreatment of plasma samples. The mobile phase consisted of aqueous phase A (0.5% formic acid in 3 mM ammonium acetate solution) and organic phase B (methanol-acetonitrile-formic acid, 50:50:0.5, v:v:v). Detection was performed on a triple-quadrupole tandem mass spectrometer using positive electrospray ionization. Quantification was performed by multiple reaction monitoring mode at m/z transitions of 271.1→123.1 for baicalein and 447.1→271.0 for baicalin, respectively. The calibration curve was linear over the range of 1~400 ng/mL (r(2)>0.99) for both baicalein and baicalin. The intra-day and inter-day precision values were below 6.84% for baicalein and 8.56% for baicalin at 3 quality control levels. The mean accuracy was 95.27 ~ 110.56%, 91.82 ~ 105.01% for baicalein and baicalin, respectively. Analytes were stable during sample storage and handling. The method was proved to be accurate and specific and was applied to a pharmacokinetic study of baicalein in healthy volunteers under both fasted and fed states. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Technical note: Improvement of cadaveric skin samples (with severe morphological alteration connected to putrefaction or injury) by an extended histological processing.

    PubMed

    Boracchi, M; Andreola, S; Gentile, G; Maghin, F; Marchesi, M; Muccino, M; Zoja, R

    2016-04-01

    The microscopic study and the interpretation of skin samples with advanced post-mortal phenomena or with particular destructive injuries is problematic for the forensic pathologist. In an attempt of restoring the histological architecture of cadaveric skin and overcoming these types of problem, the Authors performed a histological processing that was longer than the standard: it was extended until 62 days to evaluate the improvement of the microscopic morphological aspect. Cutaneous samples were taken from 25 cadavers (5 typologies of skin: charred, putrified, corifed, mummified and partially skeletonized), fixed with a 10%-buffered formalin and then processed in two different ways: one half of the samples was routinely addressed to the standard-time automatic technique, while the other half was manually processed with prolonged times. All the slides were then stained in Hematoxylin-Eosin. The standard-processed slides demonstrated marked morphological alterations and artefacts at the microscopic observation; conversely, those processed with the prolonged manual technique showed an improvement in the morphological structure, sometimes permitting the identification of the anatomical components. Though it is characterized by the inconvenience of protracted times, the application of a long-term manual histological processing to cadaveric skin samples with advanced post-mortal alteration permits to better observe the anatomical architecture of skin and it could be useful and helpful in the evaluation of such cases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Baicalein inhibits TNF-α-induced NF-κB activation and expression of NF-κB-regulated target gene products.

    PubMed

    Li, Junbo; Ma, Juan; Wang, Ke Si; Mi, Chunliu; Wang, Zhe; Piao, Lian Xun; Xu, Guang Hua; Li, Xuezheng; Lee, Jung Joon; Jin, Xuejun

    2016-11-01

    The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, apoptosis and angiogenesis. In our search for NF-κB inhibitors from natural resources, we identified baicalein from Scutellaria baicalensis as an inhibitor of NF-κB activation. As examined by the NF-κB luciferase reporter assay, we found that baicalein suppressed TNF-α-induced NF-κB activation in a dose-dependent manner. It also inhibited TNF-α-induced nuclear translocation of p65 through inhibition of phosphorylation and degradation of IκBα. Furthermore, baicalein blocked the TNF-α-induced expression of NF-κB target genes involved in anti-apoptosis (cIAP-1, cIAP-2, FLIP and BCL-2), proliferation (COX-2, cyclin D1 and c-Myc), invasion (MMP‑9), angiogenesis (VEGF) and major inflammatory cytokines (IL-8 and MCP1). The flow cytometric analysis indicated that baicalein potentiated TNF-α-induced apoptosis and induced G1 phase arrest in HeLa cells. Moreover, baicalein significantly blocked activation of p38, extracellular signal-regulated kinase 1/2 (ERK1/2). Our results imply that baicalein could be a lead compound for the modulation of inflammatory diseases as well as certain cancers in which inhibition of NF-κB activity may be desirable.

  15. Development of new and accurate measurement devices (TruSlice and TruSlice Digital) for use in histological dissection: an attempt to improve specimen dissection precision.

    PubMed

    Orchard, G E; Shams, M; Nwokie, T; Bulut, C; D'Amico, C; Gabriel, J; Ramji, Z; Georgaki, A; Neichcial, A; Shams, F; Neesam, H; Haine, N; Brewer, C

    2015-01-01

    Histological dissection of human tissue has relied on conventional procedures, which have largely remained unchanged for decades. Practices to determine measurement parameters employed in these procedures have largely relied on the use of rulers and weighing scales. It is well documented in the scientific literature that both fixation and processing of tissue can significantly affect the viability of the of tissue sections both for tinctorial and immunocytochemical investigations. Both of these factors can be compounded in their negative effects by inappropriate sampling of tissue at histological cut up. There are five key factors to ensure good surgical grossing technique, flat uniformly perpendicular specimen cutting face, appropriate immobilisation of the tissue specimen during grossing, good visualisation of the cutting tissue face, sharp cutting knives and the grossing knife action. Meeting these factors implies the devices are fit for purpose. Here we describe an innovative approach to designing cut up devices to improve accuracy and precision, which take these five key requirements into consideration. The devices showed accuracy and precision, enabling tissue slices to be produced in a uniformly perpendicular fashion to within 2 mm in thickness and to enable consistency and reproducibility of performance across a series of tissue types. The application of a digital rule on one of these devices ensures accuracy and also enables quality control issues to be clearly assessed. As cellular pathology laboratories conform to ever increasing standards of compliance and performance in practice, the advent of assured precision and accuracy at cut up is awaited. Recommendations from accreditation bodies such as the United Kingdom Accreditation Service (UKAS) continue to push for improvements in this area of histological investigation. These newly designed devices may give the answers to these requirements and provide the impetus for a new generation of innovative

  16. Dopamine treatment of brain-dead Fisher rats improves renal histology but not early renal function in Lewis recipients after prolonged static cold storage.

    PubMed

    Fontana, J; Yard, B; Stamellou, E; Wenz, H; Benck, U; Schnuelle, P; Hoeger, S

    2014-12-01

    Brain death (BD) and cold preservation are major risk factors for an unfavorable transplantation outcome. Although donor dopamine treatment in brain-dead rats improves renal function and histology in allogeneic recipients, it remains to be assessed if this also holds true for the combinations of BD and prolonged static cold preservation. BD was induced in F344 donor rats, which were subsequently treated with NaCl 1 mL/h (BD, n = 11), NaCl/hydroxy ethyl starch (BD-norm, n = 10), or 10 μg/min/kg dopamine (BD-dopa, n = 10). Renal grafts were harvested 4 h after BD and transplanted into bilateral nephrectomized Lewis recipients 6 h after cold preservation in University of Wisconsin solution. Renal function was evaluated by use of serum creatinine and urea concentrations at days 0, 1, 3, 5, and 10. Ten days after transplantation, recipients were killed and the renal allografts were processed for light microscopy and immune histology. Serum urea concentrations at days 5 and 10 were significantly lower in recipients that received a renal graft from dopamine-treated rats; for serum creatinine, only a trend was observed at day 10. Immune histology revealed a lower degree of ED1-positive cells in the donor dopamine-treated group. Under light microscopy, Banff classification revealed significantly less intimal arteritis in these grafts (P < .05). Although donor dopamine treatment clearly improves renal histology in this model, the beneficial effect on early renal function was marginal. It remains to be assessed if donor dopamine treatment has a beneficial effect on renal function in long-term follow-up. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    SciTech Connect

    Cheng, Ya-Hsin; Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan; Hung, Chein-Hui; Chang, Nai Wen; Lin, Chingju

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  18. Baicalein acts as a nephroprotectant that ameliorates colistin-induced nephrotoxicity by activating the antioxidant defence mechanism of the kidneys and down-regulating the inflammatory response.

    PubMed

    Dai, Chongshan; Tang, Shusheng; Wang, Yang; Velkov, Tony; Xiao, Xilong

    2017-09-01

    Nephrotoxicity is the major adverse effect patients experience during colistin therapy. The development of effective nephroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy. To investigate the nephroprotective effect of baicalein, a component of the root of Scutellaria baicalensis, against colistin-induced nephrotoxicity using a mouse model. C57BL/6 mice were randomly divided into the following groups: control, baicalein 100 mg/kg/day (administered orally), colistin (18 mg/kg/day administered intraperitoneally) and colistin (18 mg/kg/day) plus baicalein (25, 50 and 100 mg/kg/day). After 7 day treatments, histopathological damage, the markers of renal functions, oxidative stress and inflammation were examined. The expressions of Nrf2, HO-1 and NF-κB mRNAs were also further examined using quantitative RT-PCR examination. Baicalein co-administration markedly attenuated colistin-induced oxidative and nitrative stress, apoptosis, the infiltration of inflammatory cells, and caused decreases in IL-1β and TNF-α levels (all P < 0.05 or 0.01) in the kidney tissues. Baicalein co-administration up-regulated expression of Nrf2 and HO-1 mRNAs and down-regulated the expression of NF-κB mRNA, compared with those in the colistin alone group. To the best of our knowledge, this is the first study demonstrating the protective effect of baicalein on colistin-induced nephrotoxicity and apoptosis by activating the antioxidant defence mechanism in kidneys and down-regulating the inflammatory response. Our study highlights that oral baicalein could potentially ameliorate nephrotoxicity in patients undergoing polymyxin therapy.

  19. Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury.

    PubMed

    Chen, Szu-Fu; Tsai, Hsin-Ju; Hung, Tai-Ho; Chen, Chien-Cheng; Lee, Chao Yu; Wu, Chun-Hu; Wang, Pei-Yi; Liao, Nien-Chieh

    2012-01-01

    Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling pathway.

  20. Two-Armed Activation of Bone Mineral Deposition by the Flavones Baicalin and Baicalein, Encapsulated in Polyphosphate Microparticles.

    PubMed

    Wang, Xiao-Hong; Guo, Yue-Wei; Tolba, Emad; Kokkinopoulou, Maria; Wiens, Matthias; Schröder, Heinz C; Müller, Werner E G

    2017-04-02

    In this study, we investigated the effect of the two flavonoids, baicalin (baicalein 7-O-β-d-glucuronic acid) and its aglycone, baicalein (5,6,7-trihydroxyflavone), after encapsulation into amorphous calcium polyphosphate (Ca-polyP) microparticles on mineralization of primary human osteoblasts (phOSB). Both flavonoids, which come from root extracts of Scutellaria baicalensis Georgi, are used in Traditional Chinese Medicine, and are nontoxic in cells up to a concentration of 3[Formula: see text]μg/ml. The morphogenetically active, energy-rich Ca-polyP particles with a stoichiometric P:Ca ratio of 1:2 are degraded by cellular alkaline phosphatase (ALP) to ortho-phosphate used for bone hydroxyapatite formation. Here we show that the flavone-loaded Ca-polyP microparticles are readily taken up by phOSB, resulting in the accumulation of polyP around the nuclei and the formation of intracellular vesicles containing the ALP. In addition, we demonstrate that baicalin/baicalein causes a rise of the intracellular calcium [Ca[Formula: see text

  1. A comparative study of the anti-allergic effects of disodium baicalein 6-phosphate (BPS) and disodium cromoglycate (DSCG).

    PubMed

    Koda, A; Watanabe, S; Yanagihara, Y; Nagai, H; Sakamoto, K

    1977-02-01

    A comparative study was carried out on the effects of a soluble derivative of baicalein, disodium baicalein 6-phosphate (BPS) and disodium cromoglycate (DSCG) on the immediate type allergic reactions. BPS not only inhibited reaginic antibody-mediated reactions including antigen-induced mediator release from monkey lung, homologous PCA in rats, and reaginic antibody-mediated degranulation of mast cell, but also non-reaginic antibody-mediated reactions such as mediator release from guinea pig lung sensitized with ovalbumin and that from human lung caused by anti-IgE. The agent, however, did not affect the mediator release from lung of rats sensitized with dinitrophynylated ascaris extract plus Bordetella pertussis. On the other hand, DSCG showed characteristic properties as an inhibitor of reaginic antibody-mediated reaction. It is thus assumed that the functional site of reaginic antibody is well fixed with DSCG at a definite distance between the two-chromone-nuclei while that of IgG is readily fixed with the two molecules of baicalein or BPS.

  2. Sensitive, simultaneous determination of chrysin and baicalein based on Ta2O5-chitosan composite modified carbon paste electrode.

    PubMed

    Xie, Zhengkun; Li, Gaiping; Fu, Yamin; Sun, Mengjiao; Ye, Baoxian

    2017-04-01

    Chrysin and baicalein are the major flavonoids found in oroxylum indicum, an essential herb in traditional Chinese medicine (TCM). Owing to their similar characteristics and physiochemical property, it is a great challenge to detect both of them simultaneously. In this work, tantalum oxide (Ta2O5) particles and chitosan modified carbon paste electrode (Ta2O5-CTS-CPE) was prepared and characterized by scanning electron microscope (SEM), X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), cyclic voltammetry (CV) and electrochemical impedance spectrum(EIS). Under the optimum conditions, the prepared Ta2O5-CTS-CPE exhibited excellent electrocatalytic activity toward the oxidation of chrysin and baicalein, and it could serve as the sensor for highly sensitive and simultaneous determination both of them. The linear range is 0.08-4.0μM for both of them, and the detection limits were determined to be 0.03 and 0.05μM (S/N=3) for chrysin and baicalein, respectively. Furthermore, the proposed electrochemical sensor displayed high sensitivity, excellent stability and got satisfactory results in oroxylum indicum samples analysis.

  3. Baicalein, a natural product, selectively activating AMPKα(2) and ameliorates metabolic disorder in diet-induced mice.

    PubMed

    Pu, Peng; Wang, Xin-An; Salim, Mohamed; Zhu, Li-Hua; Wang, Lang; Chen, Kvo-Jv; Xiao, Jin-Feng; Deng, Wei; Shi, Hong-Wei; Jiang, Hong; Li, Hong-Liang

    2012-10-15

    The aim of the present study was to determine the effect of baicalein on metabolic syndrome induced by a high-fat diet in mice. The mice developed obesity, dyslipidemia, fatty liver, diabetes and insulin resistance. These disorders were effectively normalized in baicalein-treated mice. Further investigation revealed that the inhibitory effect on inflammation and insulin resistance was mediated by inhibition of the MAPKs pathway and activation of the IRS1/PI3K/Akt pathway. The lipid-lowering effect was attributed to the blocking of synthesis way mediated by SERBP-1c, PPARγ and the increased fatty acid oxidation. All of these effects depended on AMPKα activation. These results were confirmed in the primary hepatocytes from wild type and AMPKα(2)(-/-) mice. However, the IRS-1/PI3K/AKT pathway showed no change, which may be due to the time of stimulation and concentration. Thus, these data suggested that baicalein protects mice from metabolic syndrome through an AMPKα(2)-dependent mechanism involving multiple intracellular signaling pathways.

  4. Suppression of Very Early Stage Of Adipogenesis by Baicalein, a Plant-Derived Flavonoid through Reduced Akt-C/EBPα-GLUT4 Signaling-Mediated Glucose Uptake in 3T3-L1 Adipocytes

    PubMed Central

    2016-01-01

    Baicalein has been used as a Chinese medicine, and is an abundant plant flavonoid present in fruits and vegetables. Here, we examined the effects of baicalein in adipogenesis and investigated its molecular mechanism in adipocytes. Baicalein lowered the intracellular lipid accumulation and decreased the transcription levels of the adipocyte-specific genes in mouse 3T3-L1 adipocytes. Glucose uptake mediated by glucose transporter 4 (GLUT4) was reduced, causing down-regulation of the intracellular lipid accumulation. These reductions were also observed even when baicalein was added in only early stage of adipogenesis (0–2 days) of 6-day-adipogenesis. Chromatin immunoprecipitation assay showed that baicalein decreased the binding level of C/EBPα protein to the promoter region of the GLUT4 gene. Phosphorylation of Akt at 1 h after the initiation of adipogenesis was inhibited by the treatment with baicalein. Inhibition during only the first 1.5 h after the initiation of adipogenesis by baicalein or an Akt inhibitor was enough to decrease the lipid contents in the cells undergoing adipocyte differentiation for 6 days. These results indicate that baicalein decreased the intracellular lipid accumulation by down-regulation of glucose uptake via repression of Akt-C/EBPα-GLUT4 signaling in the very early stage of adipogenesis of 3T3-L1 adipocytes. PMID:27669565

  5. Baicalein reduces endometriosis by suppressing the viability of human endometrial stromal cells through the nuclear factor-κB pathway in vitro.

    PubMed

    Jin, Zhixing; Huang, Jianqin; Zhu, Zhiling

    2017-10-01

    The aim of the present study was to evaluate the effects of baicalein on human endometrial stromal cells in vitro. Ectopic endometrium samples were obtained from 6 female patients with ovarian endometriosis who underwent laparoscopic surgical procedures from July to September 2015. After culturing the cells, immunocytochemistry was performed to verify the purity and homogeneity of the endometrial stromal cells, and a Cell Counting Kit-8 assay was used to evaluate cell viability. In addition, cell cycle progression was analyzed using flow cytometry, and the effects of baicalein on the expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cyclin D1 in endometrial stromal cells were evaluated using western blot analysis. The related signaling pathways were also investigated by incubating cells with inhibitors of signaling pathways, prior to adding 40 µM baicalein for 48 h, followed by analysis of cell viability using a Cell Counting Kit-8 assay. The results indicated that treatment with baicalein significantly induced a dose-dependent decrease (P<0.05) in the viability of human endometrial stromal cells, which was abolished by inhibition of the nuclear factor (NF)-κB signaling pathway. However, baicalein treatment did not induce a time-dependent decrease in viability, as cell viabilities between the 24, 48 and 72 h treatment groups did not differ significantly. The number of cells in the G0/G1 phase significantly increased following treatment with baicalein (P<0.05), while the number of cells in the S and G2/M phases significantly decreased (P<0.05). Baicalein-treated cells also exhibited significantly reduced expression of Bcl-2, PCNA and cyclin D1 compared with control cells (P<0.05). These results suggested that baicalein may suppress the viability of human endometrial stromal cells through the NF-κB signaling pathway in vitro, and may induce apoptosis and promote cell cycle arrest at the G0/G1

  6. Baicalein is an available anti-atherosclerotic compound through modulation of nitric oxide-related mechanism under oxLDL exposure

    PubMed Central

    Chan, Shih-Hung; Hung, Ching-Hsia; Shih, Jhih-Yuan; Chu, Pei-Ming; Cheng, Yung-Hsin; Tsai, Yi-Ju; Lin, Huei-Chen; Tsai, Kun-Ling

    2016-01-01

    OxLDL facilitate reactive oxygen species (ROS) formation and up-regulation of the executioner caspase-3 via the mitochondrial apoptotic pathway involves several critical steps in human endothelial cells. Previous studies reported that oxLDL-facilitated endothelial oxidative stress is associated with impairment of eNOS and up-regulation of inducible nitric oxide synthase (iNOS). Baicalein is the most abundant component that has anti-HIV, anti-tumor, anti-oxidant and free radical scavenging functions. In this present study, we shown that baicalein hinibits oxLDL-caused endothelial dysfunction through suppression of endothelial inflammation and oxidative stress that causes to cellular apoptosis. Specifically, baicalein reduces the elevation of ROS concentration, which subsequently inhibits the oxLDL-decreased expression of anti-oxidant enzymes, enriches the bioavailability of NO, stabilizes the mitochondrial membrane, thereby inhibiting the discharge of cytochrome c from mitochondria, a molecule required for the activation of the pro-apoptotic protein caspase 3. However, inhibition of eNOS impairs the anti-apoptotic and anti-inflammatory effects of baicalein. These results provide new insight into the possible molecular mechanisms by which baicalein protects against atherogenesis by NO-related pathways. PMID:27356749

  7. The design and synthesis of a novel compound of berberine and baicalein that inhibits the efficacy of lipid accumulation in 3T3-L1 adipocytes.

    PubMed

    Hao, Mengjiao; Li, Yan; Liu, Lixian; Yuan, Xiao; Gao, Ying; Guan, Zhuoji; Li, Weimin

    2017-08-09

    The combination of berberine and baicalein may have a better therapeutic effect against disease. To explore the combined effect of baicalein and berberine in the treatment of obesity, we designed and synthesized a hybrid compound, and its biological activities were evaluated in 3T3-L1 adipocytes. The structures of the berberine-baicalein (BBS) compounds were confirmed by (1)H NMR, (13)C NMR, ultraviolet spectroscopy and high resolution mass spectrometry (HRMS). The present study showed that the IC50 values of the inhibitory effects of baicalein, berberine and BBS against 3T3-L1 cells were 29.81±0.90, 21.84±1.67 and 9.42±0.60µM, respectively. The expression of mRNAs related to lipolysis and lipogenesis were examined by quantitative real-time PCR. The results showed that BBS could up-regulate the expression of the Atgl gene and down-regulate the mRNA expression of Srebp-1c, Fasn, Scd1, and Acc in 3T3-L1 adipocytes. These results indicate that BBS may have a stronger effect than baicalein and berberine on the viability of 3T3-L1 preadipocytes. In addition, BBS may have therapeutic effects and pharmacological activities against obesity. This "medicine couple" may be beneficial for studies of traditional Chinese medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Combinatorial treatment of acute spinal cord injury with ghrelin, ibuprofen, C16, and ketogenic diet does not result in improved histologic or functional outcome.

    PubMed

    Streijger, F; Lee, J H T; Duncan, G J; Ng, M T L; Assinck, P; Bhatnagar, T; Plunet, W T; Tetzlaff, W; Kwon, B K

    2014-07-01

    Because of the complex, multifaceted nature of spinal cord injury (SCI), it is widely believed that a combination of approaches will be superior to individual treatments. Therefore, we employed a rat model of cervical SCI to evaluate the combination of four noninvasive treatments that individually have been reported to be effective for acute SCI during clinically relevant therapeutic time windows. These treatments included ghrelin, ibuprofen, C16, and ketogenic diet (KD). These were selected not only because of their previously reported efficacy in SCI models but also for their potentially different mechanisms of action. The administration of ghrelin, ibuprofen, C16, and KD several hours to days postinjury was based on previous observations by others that each treatment had profound effects on the pathophysiology and functional outcome following SCI. Here we showed that, with the exception of a modest improvement in performance on the Montoya staircase test at 8-10 weeks postinjury, the combinatorial treatment with ghrelin, ibuprofen, C16, and KD did not result in any significant improvements in the rearing test, grooming test, or horizontal ladder. Histologic analysis of the spinal cords did not reveal any significant differences in tissue sparing between treatment and control groups. Although single approaches of ghrelin, ibuprofen, C16, and KD have been reported to be beneficial after SCI, our results show that the combination of the four interventions did not confer significant functional or histological improvements in a cervical model of SCI. Possible interactions among the treatments may have negated their beneficial effects, emphasizing the challenges that have to be addressed when considering combinatorial drug therapies for SCI. Copyright © 2014 Wiley Periodicals, Inc.

  9. Salidroside Improves Behavioral and Histological Outcomes and Reduces Apoptosis via PI3K/Akt Signaling after Experimental Traumatic Brain Injury

    PubMed Central

    Chen, Szu-Fu; Tsai, Hsin-Ju; Hung, Tai-Ho; Chen, Chien-Cheng; Lee, Chao Yu; Wu, Chun-Hu; Wang, Pei-Yi; Liao, Nien-Chieh

    2012-01-01

    Background Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Methodology/Principal Findings Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside_significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside_also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Conclusions/Significance Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis

  10. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver.

    PubMed

    El-Lakkany, Naglaa Mohamed; Seif El-Din, Sayed Hassan; Sabra, Abdel-Nasser Abdel-Aal; Hammam, Olfat Ali; Ebeid, Fatma Abdel-Latif

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05) serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1) and hepatic malondialdehyde (MDA) compared with group I. Meanwhile, hepatic superoxide dismutase (SOD), glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05). These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH).

  11. Radiation therapy for favorable histology Wilms tumor: Prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

    SciTech Connect

    Breslow, Norman E. . E-mail: norm@u.washington.edu; Beckwith, J. Bruce; Haase, Gerald M.; Kalapurakal, John A.; Ritchey, Michael L.; Shamberger, Robert C.; Thomas, Patrick; D'Angio, Giulio J.; Green, Daniel M.

    2006-05-01

    Purpose: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Methods and Materials: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Results: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Conclusions: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes.

  12. Baicalein and hydroxypropyl-γ-cyclodextrin complex in poloxamer thermal sensitive hydrogel for vaginal administration.

    PubMed

    Zhou, Qiuna; Zhong, Lin; Wei, Xiaohui; Dou, Wei; Chou, Guixin; Wang, Zhengtao

    2013-09-15

    The present study aimed to prepare a chemically and physically stable formulation of baicalein (Ba) in an in situ thermally sensitive hydrogel for vaginal administration. An inclusion complex of Ba and hydroxypropyl-γ-cyclodextrin (HP-γ-CD) was first developed to increase the stability and solubility of Ba in an aqueous solution. The formation of the Ba-HP-γ-CD complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray powder diffractometry (XRPD). Poloxamers 407, 188 (P407, P188), sodium alginate (SA), hydroxypropylmethylcellulose (HPMC), and benzalkonium bromide were mixed to obtain a hydrogel with an appropriate gelation temperature for vaginal use. Among the formulations examined, P407/Ba-HP-γ-CD/HPMC/P188/benzalkonium bromide (18/0.96/0.5/4.0/0.02%) represented the appropriate gelation temperature and acceptable drug release rate at the administration site. Release of Ba-HP-γ-CD from the poloxamer hydrogel followed Peppas equation, which suggests that it occurred through coupled corrosion-diffusion mechanism, and the corrosion-release curve showed that corrosion was the primary mode of release. In animal study, treatment by using Ba-HP-γ-CD thermosensitive hydrogel could produce a restoration of damaged tissues. Thermosensitive hydrogel formulation of the Ba-HP-γ-CD complex appears to be a promising treatment for cervicitis. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Histological Response to Fluticasone Propionate in Patients With Eosinophilic Esophagitis Is Associated With Improved Functional Esophageal Mucosal Integrity.

    PubMed

    van Rhijn, Bram D; Verheij, Joanne; van den Bergh Weerman, Marius A; Verseijden, Caroline; van den Wijngaard, René M J G J; de Jonge, Wouter J; Smout, Andreas J P M; Bredenoord, Albert J

    2015-09-01

    The esophageal mucosal integrity is impaired in patients with eosinophilic esophagitis (EoE). We aimed to evaluate the effect of fluticasone propionate on inflammation and functional and structural markers of esophageal mucosal barrier integrity in adult patients with EoE. In this prospective study, we included 15 EoE patients (median age (IQR), 43 (30-45) years). Patients underwent upper endoscopy before and after an 8-week course of swallowed fluticasone propionate 500 μg BID. Several parameters of esophageal mucosal barrier integrity were evaluated: esophageal electrical tissue impedance in vivo during endoscopy, transepithelial electrical resistance (TER) and transepithelial molecule flux in Ussing chambers using esophageal biopsy specimens, and intercellular spaces as a structural marker of permeability using electron microscopy. Esophageal eosinophils and mast cells were counted, and expression of inflammatory cytokines and barrier integrity proteins was investigated using qPCR. Esophageal symptoms and signs were also assessed. Peak eosinophil and mast cell counts decreased significantly after fluticasone propionate treatment. The esophageal mucosal integrity increased substantially during treatment, as shown by increased extracellular impedance and TER (both P<0.01) and decreased transepithelial molecule flux in Ussing chambers (P<0.05). Whereas expression of genes encoding for inflammatory cytokines (IL5, IL13, eotaxin-3, periostin, TSLP) decreased after treatment, expression of genes encoding for barrier integrity proteins (filaggrin and desmoglein-1) increased. Fluticasone propionate treatment decreases eosinophilic inflammation and improves the esophageal mucosal barrier integrity in adult EoE patients. Improvement of the mucosal barrier integrity correlates with normalization of expression of desmoglein-1 and filaggrin marker genes.

  14. In vitro potential modulation of baicalin and baicalein on P-glycoprotein activity and expression in Caco-2 cells and rat gut sacs.

    PubMed

    Miao, Qing; Wang, Zhiyong; Zhang, Yuanyuan; Miao, Peipei; Zhao, Yuanyuan; Zhang, Yujie; Ma, Shuangcheng

    2016-09-01

    Context Previous studies have shown that Scutellariae Radix, the dried root of Scutellaria baicalensis Georgi (Labiatae), has a certain inhibitory effect on P-glycoprotein (P-gp), but the effects of its main active constituents on P-gp are still ambiguous. Objectives In vitro studies were performed to investigate the effects of its main active constituents (baicalin and its aglycone, baicalein) on the activity and expression of P-gp in intestine using Caco-2 cells and rat gut sacs. Materials and methods In Caco-2 cell experiments, the effects of baicalin and baicalein on P-gp activity were investigated using a P-gp substrate, rhodamine 123 and non-substrate fluorescein Na, by determining their intracellular fluorescence accumulation, and their effects on P-gp expression were determined using flow cytometry. In addition, rat gut sac model was selected to investigate the effects of baicalin and baicalein on the transport of verapamil, a classical P-gp substrate. The gut sacs of male Sprague-Dawley rats were filled with 0.4 mL the test solution contained verapamil (0.2575 mg/mL) and the drugs [baicalin and baicalein, at concentrations of 1/8 IC50 (59.875, 41.5 μg/mL), 1/4 IC50 (119.75, 83 μg/mL) and 1/2 IC50 (239.5, 166 μg/mL)], and then incubated in Tyrode's solution for a period of time. After termination of the incubation, the incubated solution was processed for the subsequent detection. Results According to the results of MTT assay, the IC50 values of verapamil, baicalin and baicalein were 104, 479, 332 μg/mL, respectively. The obtained results from the two models were confirmed mutually. As a result, baicalin exhibited no obvious effect on intracellular accumulation of Rh-123, and almost had no effect on P-gp expression and verapamil transportation, while baicalein significantly increased intracellular accumulation of Rh-123 (p < 0.01), down-regulated P-gp expression (p < 0.01) and increased the transport of verapamil (p < 0

  15. Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells.

    PubMed

    Sithisarn, Patchima; Michaelis, Martin; Schubert-Zsilavecz, Manfred; Cinatl, Jindrich

    2013-01-01

    From a panel of 22 flavonoids, we identified six compounds (apigenin, baicalein, biochanin A, kaempferol, luteolin, naringenin) that inhibited influenza A nucleoprotein production in human lung epithelial (A549) cells infected with the highly pathogenic avian influenza H5N1 virus strain A/Thailand/Kan-1/04 in non-toxic concentrations. Baicalein (IC(50): 18.79±1.17μM, selectivity index 5.82) and biochanin A (IC(50) 8.92±1.87μM, selectivity index 5.60) were selected for further experiments. Both compounds reduced H5N1 infectious titres (baicalein 40μM: 29-fold reduction, biochanin A 40μM: 55-fold reduction after infection at MOI 0.01), virus-induced caspase 3 cleavage, nuclear export of viral RNP complexes, and enhanced the effects of the neuraminidase inhibitor zanamivir. Biochanin A and baicalein also inhibited the replication of the H5N1 strain A/Vietnam/1203/04. Time of addition experiments indicated that both compounds interfere with H5N1 replication after the adsorption period. Further mechanistic investigations revealed clear differences between these two flavonoids. Only baicalein interfered with the viral neuraminidase activity (39±7% inhibition at 100μM, the maximum concentration tested). In contrast to baicalein, biochanin A affected cellular signalling pathways resulting in reduced virus-induced activation of AKT, ERK 1/2, and NF-kB. Moreover, biochanin A inhibited the virus-induced production of IL-6, IL-8, and IP-10 while baicalein inhibited IL-6 and IL-8 production without affecting IP-10 levels. In primary human monocyte-derived macrophages, only baicalein but not biochanin A impaired H5N1 virus replication. Both flavonoids interfered with the H5N1-induced production of IL-6, IP-10, and TNF-α but not of IL-8 in macrophages. These findings indicate that closely related flavonoids can exert anti-H5N1 effects by different molecular mechanisms.

  16. An Improved Molecular Histology Method for Ion Suppression Monitoring and Quantification of Phosphatidyl Cholines During MALDI MSI Lipidomics Analyses.

    PubMed

    Jadoul, Laure; Smargiasso, Nicolas; Pamelard, Fabien; Alberts, Deborah; Noël, Agnès; De Pauw, Edwin; Longuespée, Rémi

    2016-02-01

    Tissue lipidomics is one of the latest omics approaches for biomarker discovery in pharmacology, pathology, and the life sciences at large. In this context, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is the most versatile tool to map compounds within tissue sections. However, ion suppression events occurring during MALDI MSI analyses make it impossible to use this method for quantitative investigations without additional validation steps. This is especially true for lipidomics, since different lipid classes are responsible for important ion suppression events. We propose here an improved lipidomics method to assess local ion suppression of phospatidylcholines in tissues. Serial tissue sections were spiked with different amounts of PC(16:0 d31/18:1) using a nebulization device. Settings for standard nebulization were strictly controlled for a detection similar to when using spiked tissue homogenates. The sections were simultaneously analyzed by MALDI MSI using a Fourier transform ion cyclotron resonance analyzer. Such a spray-based approach allows taking into account the biochemical heterogeneity of the tissue for the detection of PC(16:0 d31/18:1). Thus, here we present the perspective to use this method for quantification purposes. The linear regression lines are considered as calibration curves and we calculate PC(16:0/18:1) quantification values for different ROIs. Although those values need to be validated by a using a different independent approach, the workflow offers an insight into new quantitative mass spectrometry imaging (q-MSI) methods. This approach of ion suppression monitoring of phosphocholines in tissues may be highly interesting for a large range of applications in MALDI MSI, particularly for pathology using translational science workflows.

  17. Prophylactic effect of baicalein against renal dysfunction in type 2 diabetic rats.

    PubMed

    Ahad, Amjid; Mujeeb, Mohd; Ahsan, Haseeb; Siddiqui, Waseem Ahmad

    2014-11-01

    Despite a tremendous advancement in the management of diabetes mellitus, diabetic nephropathy (DN) is still a significant problem for many patients with diabetes, because of the inefficacy and associated side effects of pharmacological drugs. There is a demand for new therapeutic drugs which on one hand efficiently prevent the development of DN by targeting several metabolic and inflammatory pathways, and on the other hand, are side-effect free. In recent years, many researchers have suggested that inflammation plays an important role in the development of DN, hence, NF-κB has received much attention. We investigated the nephroptotective effects of baicalein (BAC), a flavonoid, in high fat diet/streptozotocin induced type 2 diabetic Wistar rats. BAC (10 mg/kg bw/day and 20 mg/kg bw/day) treatment was given to the diabetic rats by oral gavage for 16 weeks post induction of diabetes. The effect of BAC was compared to a commercial antidiabetic drug rosiglitazone (RZ, 3 mg/kg bw/day). BAC and RZ treatment significantly lowered food intake, body weight and levels of fasting blood glucose, HbA1c and homeostasis model assessment index (HOMA-IR) in diabetic rats. Both, BAC and RZ restored normal renal function and mitigated renal oxidative stress. BAC and RZ also suppressed the activation of NF-κB, decreased expression of iNOS and TGF-β1, and ameliorated the structural changes in renal tissues. Moreover, BAC also normalized the levels of serum pro-inflammatory cytokines and liver function enzymes. However, rosiglitazone treatment produced liver toxicity as was evident from increased serum levels of liver function enzymes; ALP, SGOT and SGPT. Taken together, BAC treatment preserved renal function by anti-hyperglycemic, antioxidant and anti-inflammatory effects. Moreover, BAC was found to be more effective as compared to RZ, suggesting the efficacy of BAC in the treatment of DN.

  18. Baicalein Inhibits Epithelial to Mesenchymal Transition via Downregulation of Cyr61 and LOXL-2 in MDA-MB231 Breast Cancer Cells

    PubMed Central

    Nguyen, Linh Thi Thao; Song, Yeon Woo; Cho, Somi Kim

    2016-01-01

    Epithelial-mesenchymal transition (EMT) is a critical step in the acquisition of the migratory and invasive capabilities associated with metastatic competence. Cysteine-rich protein 61 (CCN1/Cyr61) has been implicated as an important mediator in the proliferation and metastasis of breast cancer. Hence, Cyr61 and associated pathways are attractive targets for therapeutic interventions directed against the EMT. In the present study, we report that baicalein significantly inhibits the expression of Cyr61 and migration and invasion of MDA-MB231 human breast cancer cells. Exposure to baicalein led to increased E-cadherin expression, possibly due to the ubiquitination of Snail and Slug, which was mediated by the Cyr61/Akt/glycogen synthase kinase 3β (GSK3β) pathway. Further analysis revealed that baicalein inhibited the expression of lysyl oxidase like-2 (LOXL-2), which is a functional collaborator of Snail and Slug, and subsequently attenuated the direct interaction between LOXL-2 and Snail or Slug, thereby enhancing GSK3β-dependent Snail and Slug degradation. Our findings provide new insights into the antimetastatic mechanism of baicalein and may contribute to its beneficial use in breast cancer therapies. PMID:28008161

  19. Baicalein protects against retinal ischemia by antioxidation, antiapoptosis, downregulation of HIF-1α, VEGF, and MMP-9 and upregulation of HO-1.

    PubMed

    Chao, Hsiao-Ming; Chuang, Min-Jay; Liu, Jorn-Hon; Liu, Xiao-Qian; Ho, Li-Kang; Pan, Wynn H T; Zhang, Xiu-Mei; Liu, Chi-Ming; Tsai, Shen-Kou; Kong, Chi-Woon; Lee, Shou-Dong; Chen, Mi-Mi; Chao, Fang-Ping

    2013-01-01

    Retinal ischemia-associated ocular disorders are vision threatening. This study examined whether the flavonoid baicalein is able to protect against retinal ischemia/reperfusion. Using rats, the intraocular pressure was raised to 120 mmHg for 60 min to induce retinal ischemia. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating dissociated retinal cells with 100 μM ascorbate and 5 μM FeSO4 (iron) for 1 h. The rats or the dissociated cells had been pretreated with baicalein (in vivo: 0.05 or 0.5 nmol; in vitro: 100 μM), vehicle (1% ethanol), or trolox (in vivo: 5 nmol; in vitro: 100 μM or 1 mM). The effects of these treatments on the retina or the retinal cells were evaluated by electrophysiology, immunohistochemistry, terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) staining, Western blotting, or in vitro dichlorofluorescein assay. In addition, real-time-polymerase chain reaction was used to assess the retinal expression of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), vascular endothelium growth factor (VEGF), and heme oxygenase-1 (HO-1). The retinal changes after ischemia included a decrease in the electroretinogram b-wave amplitude, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, an increase in vimentin immunoreactivity, which is a marker for Müller cells, an increase in apoptotic cells in the retinal ganglion cell layer linked to a decrease in the Bcl-2 protein, and changes in the mRNA levels of HIF-1α, VEGF, MMP-9, and HO-1. Of clinical importance, the ischemic detrimental effects were concentration dependently and/or significantly (0.05 nmol and/or 0.5 nmol) altered when baicalein was applied 15 min before retinal ischemia. Most of all, 0.5 nmol baicalein significantly reduced the upregulation of MMP-9; in contrast, 5 nmol trolox only had a weak attenuating effect. In dissociated retinal cells subjected to ascorbate

  20. Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

    PubMed

    Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

    2014-06-01

    Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

  1. Flavonoid baicalein modulates H2O2-induced mitogen-activated protein kinases activation and cell death in SK-N-MC cells.

    PubMed

    Moslehi, Maryam; Meshkini, Azadeh; Yazdanparast, Razieh

    2012-05-01

    It is believed that ROS-induced oxidative stress triggers numerous signaling pathways which are involved in neurodegenerative diseases, including Alzheimer's disease. To find the effective drugs for neurodegenerative diseases, the deep delve into molecular mechanisms underlie these diseases is necessary. In the current study, we investigated the effects of flavonoid baicalein on H(2)O(2)-induced oxidative stress and cell death in SK-N-MC cells. Our results revealed that the treatment of SK-N-MC cells with H(2)O(2) led to a decrease in cell viability through phosphorylation and activation of extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs) pathways followed by increase in Bax/Bcl2 ratio and initiation of caspase-dependent apoptotic pathways. In addition, our results showed that the exposure of SK-N-MC cells to H(2)O(2) ended up in reduction of glutathione (GSH) levels of SK-N-MC cells via JNK/ERK-mediated down-regulation of γ-glutamyl-cysteine synthetase (γ-GCS) expression. Our results demonstrated that flavonoid baicalein protected against H(2)O(2)-induced cell death by inhibition of JNK/ERK pathways activation and other key molecules in apoptotic pathways, including blockage of Bax and caspase-9 activation, induction of Bcl-2 expression and prevention of cell death. Baicalein supported intracellular defense mechanisms through maintaining GSH levels in SK-N-MC cells by the removal of inhibition effects of JNK/ERK pathways from γ-GCS expression. In addition, baicalein attenuated lipid and protein peroxidation and intracellular reactive oxygen species in SK-N-MC cells. In accordance with these observations, baicalein can be a promising candidate in antioxidant therapy and designing of natural-based drug for ROS-induced neurodegenerative disorders.

  2. ASK1/JNK-mediated TAp63 activation controls the cell survival signal of baicalein-treated EBV-transformed B cells.

    PubMed

    Park, Ga Bin; Kim, Yeong Seok; Lee, Hyun-Kyung; Yang, Jae Wook; Kim, Daejin; Hur, Dae Young

    2016-01-01

    Transcriptionally active p63 (TAp63) promotes cell cycle arrest, senescence, and apoptosis in several cancer cells. Migration inhibitory factor (MIF)/CD74 regulates B-cell survival through nuclear factor (NF)-κB-dependent TAp63 expression. In this study, we investigated how the level of TAp63 expression influences the induction of apoptosis in baicalein-treated EBV-transformed B cells. Baicalein induced the expression of TAp63 and apoptosis signal-regulating kinase 1 (ASK1), as well as cytotoxicity, by disrupting the mitochondrial membrane and inhibiting the activation of phosphoinositide 3-kinase (PI3K)/Akt and NF-κB. Genetic knockdown of TAp63 or ASK1 by small interfering RNA resulted in protection from apoptosis accompanied by the recovery of CD74, CD44, α4 integrin, Bcl-2, and NF-κB activation. Baicalein-induced reactive oxygen species activated the ASK1/JNK pathway with subsequent expression of TAp63. Pre-engagement with MIF/CD74 maintained the expression of CD74, CD44, and α4 integrin, as well as Syk/Src-mediated PI3K/Akt activation, in baicalein-treated EBV-transformed B cells. Meanwhile, ASK1/JNK-dependent TAp63 expression was efficiently suppressed after pre-treatment with MIF. Our results suggest that baicalein-mediated ASK1/JNK activation regulates the mitochondria-dependent apoptosis pathway through the up-regulation of TAp63 and down-regulation of NF-κB and CD74/CD44 in B-cell malignancies.

  3. Clinico-histologic conferences: histology and disease.

    PubMed

    Shaw, Phyllis A; Friedman, Erica S

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical context, promote integration and application of science knowledge, and to foster peer teaching and learning: the Clinico-Histologic Conference (CHC) for the Mount Sinai School of Medicine Histology course. Teams of six students were each assigned specific disease processes and were charged with creating oral presentations and handouts that taught their classmates about the clinical manifestations, etiopathogeneses, diagnoses, and treatments of the assigned processes, along with comparisons of normal histology to the pathology of the disease. Each team also created four questions, some of which were used on Histology written examinations. The physician facilitator evaluated the presentation and handouts. About two-thirds of students agreed the CHC enhanced appreciation of the importance of histology, provided a context for integration and application of basic science to patient care and enhanced their ability to teach their peers. Student feedback demonstrated that the CHCs were successful in promoting teamwork, peer teaching, and the application of histology to diagnose diseases. The authors believe that teaching basic science content in this new format enhanced student learning and application of medical knowledge, and that this new teaching format can be adopted by other medical school courses.

  4. Synthetic polymers improve vitrification outcomes of macaque ovarian tissue as assessed by histological integrity and the in vitro development of secondary follicles.

    PubMed

    Ting, Alison Y; Yeoman, Richard R; Lawson, Maralee S; Zelinski, Mary B

    2012-08-01

    Ovarian tissue cryopreservation is the only proven option for fertility preservation in female cancer patients who are prepubertal or require immediate treatment. However it remains unclear which cryopreservation protocol is best in cases where the tissue may contain cancerous cells, as these should be matured in vitro rather than autografted. This study evaluated different cryoprotectant exposure times and whether the addition of synthetic polymers (Supercool X-1000, Z-1000 and polyvinylpyrrolidone [PVP K-12]) to the vitrification solution is beneficial to tissue morphology, cellular proliferation and subsequent in vitro function of secondary follicles. Pieces of macaque (n=4) ovarian cortex were exposed to vitrification solution containing glycerol (25%, v/v) and ethylene glycol (25%, v/v) for 3 or 8 min, without (V3, V8) or with (VP3, VP8) polymers (0.2% [v/v] X-1000, 0.4% Z-1000 and 0.2% PVP). Fresh and vitrified tissues were fixed for histology and phosphohistone H3 (PPH3) analysis, or used for secondary follicle isolation followed by encapsulated 3D culture. Five-week follicle survival and growth, as well as steroid hormones (estradiol [E(2)], progesterone, androstenedione) were measured weekly. Morphology of the stroma and preantral follicles as well as PPH3 expression, was preserved in all vitrified tissues. Vitrification with polymers and shorter incubation time (VP3) increased in vitro follicle survival and E(2) production compared to other vitrified groups. Thus, a short exposure of macaque ovarian tissue to a vitrification solution containing synthetic polymers preserves morphology and improves in vitro function of secondary follicles. Published by Elsevier Inc.

  5. Synthetic polymers improve vitrification outcomes of macaque ovarian tissue as assessed by histological integrity and the in vitro development of secondary follicles☆

    PubMed Central

    Ting, Alison Y.; Yeoman, Richard R.; Lawson, Maralee S.; Zelinski, Mary B.

    2013-01-01

    Ovarian tissue cryopreservation is the only proven option for fertility preservation in female cancer patients who are prepubertal or require immediate treatment. However it remains unclear which cryopreservation protocol is best in cases where the tissue may contain cancerous cells, as these should be matured in vitro rather than autografted. This study evaluated different cryoprotectant exposure times and whether the addition of synthetic polymers (Supercool X-1000, Z-1000 and polyvinylpyrrolidone [PVP K-12]) to the vitrification solution is beneficial to tissue morphology, cellular proliferation and subsequent in vitro function of secondary follicles. Pieces of macaque (n = 4) ovarian cortex were exposed to vitrification solution containing glycerol (25%, v/v) and ethylene glycol (25%, v/v) for 3 or 8 min, without (V3, V8) or with (VP3, VP8) polymers (0.2% [v/v] X-1000, 0.4% Z-1000 and 0.2% PVP). Fresh and vitrified tissues were fixed for histology and phosphohistone H3 (PPH3) analysis, or used for secondary follicle isolation followed by encapsulated 3D culture. Five-week follicle survival and growth, as well as steroid hormones (estradiol [E2], progesterone, androstenedione) were measured weekly. Morphology of the stroma and preantral follicles as well as PPH3 expression, was preserved in all vitrified tissues. Vitrification with polymers and shorter incubation time (VP3) increased in vitro follicle survival and E2 production compared to other vitrified groups. Thus, a short exposure of macaque ovarian tissue to a vitrification solution containing synthetic polymers preserves morphology and improves in vitro function of secondary follicles. PMID:22569078

  6. Peripheral and central administration of T3 improved the histological changes, memory and the dentate gyrus electrophysiological activity in an animal model of Alzheimer's disease.

    PubMed

    Farbood, Yaghoob; Shabani, Sahreh; Sarkaki, Alireza; Mard, Seyyed Ali; Ahangarpour, Akram; Khorsandi, Layasadat

    2017-01-26

    The amyloid beta (Aβ) induced Alzheimer's disease (AD) is associated with formation the amyloid plaques, cognitive impairments and decline in spontaneous discharge of neurons. In the current study, we evaluated the effect of subcutaneous (S. C) and intrahippocampal (I. H) administrations of triiodothyronine (T3) on the histological changes, memory and the dentate gyrus (DG) electrophysiological activity in an animal model of AD. Eighty adult male Wistar rats (250-300 g) were divided randomly into five groups: Sham-Operated (Sh-O), AD + Vehicle (S. C), AD + Vehicle (I. H), AD+ T3 (S. C) and AD + T3 (I. H). In order to induce animal model of AD, Aβ (10 ng/μl, bilaterally) were injected intrahippocampally. Rats were treated with T3 and/or normal saline for 10 days. Passive avoidance and spatial memory were evaluated in shuttle box apparatus and Morris water maze, respectively. Neuronal single unit recording was assessed from hippocampal DG. The percent of total time that animals spent in target quarter, the mean latency time (sec), the step through latency and the average number of spikes/bin were decreased significantly in AD rats compared with the Sh-O group (p < 0.001) and were increased significantly in AD groups that have received T3 (S. C and I. H) in compared with AD group (p < 0.01, p < 0.001). Also, formation of amyloid plaques was decreased in AD rats treated with T3.The results showed that T3 injection (S. C and I. H), by reduction of neural damage and increment of neuronal spontaneous activity improved the memory deficits in Aβ-induced AD rats.

  7. Baicalein prevents 6-hydroxydopamine-induced mitochondrial dysfunction in SH-SY5Y cells via inhibition of mitochondrial oxidation and up-regulation of DJ-1 protein expression.

    PubMed

    Wang, Yue-Hua; Yu, Hai-Tao; Pu, Xiao-Ping; Du, Guan-Hua

    2013-11-27

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons at the substantia nigra. Mitochondrial dysfunction is involved in the mechanism of cell damage in Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a dopamine analog which specifically damages dopaminergic neurons. Baicalein has been previously reported to have potential in the treatment of PD. The purpose of the present study was to investigate the mechanism of action of baicalein against 6-OHDA injury in SH-SY5Y cells. The results showed that baicalein significantly alleviated alterations of mitochondrial redox activity and mitochondrial membrane potential induced by 6-OHDA in a dose-dependent manner in SH-SY5Y cells compared with vehicle group. Futhermore, baicalein decreased the production of ROS and upregulated the DJ-1 protein expression in SH-SY5Y cells. In addition, baicalein also inhibited ROS production and lipid peroxidation (IC50 = 6.32 ± 0.03 μM) in rat brain mitochondia. In summary, the underlying mechanisms of baicalein against 6-OHDA-induced mitochondrial dysfunction may involve inhibition of mitochondrial oxidation and upregulation of DJ-1 protein expression.

  8. Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin-induced allergic airway inflammation and mast cell-mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release.

    PubMed

    Bui, Thi Tho; Piao, Chun Hua; Song, Chang Ho; Lee, Chang-Hyun; Shin, Hee Soon; Chai, Ok Hee

    2017-06-01

    Asthma is characterized by chronic inflammation, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration into the lungs. In this study, we examined the effects of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced asthma by evaluating Th1/Th2 cytokine levels, histopathologic analysis, and compound 48/80-induced systemic anaphylaxis and mast cell activation, focusing on the histamine release from rat peritoneal mast cells. Baicalein, wogonin, and S. baicalensis ethanol extract also decreased the number of inflammatory cells especially eosinophils and downregulated peribronchial and perivascular inflammation in the lungs of mice challenged by OVA. Baicalein, wogonin, and S. baicalensis ethanol extract significantly reduced the levels of tumor necrosis factor α, interleukin (IL)-1β, IL-4, IL-5 and the production of OVA-specific IgE and IgG1, and upregulated the level of interferon-γ and OVA-specific IgG2a. In addition, oral administration of baicalein, wogonin, and S. baicalensis ethanol extract inhibited compound 48/80-induced systemic anaphylaxis and plasma histamine release in mice. Moreover, baicalein, wogonin, and S. baicalensis ethanol extract suppressed compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells. Conclusively, baicalein and wogonin as major flavonoids of S. baicalensis may have therapeutic potential for allergic asthma through modulation of Th1/Th2 cytokine imbalance and histamine release from mast cells.

  9. Metabolism and pharmacokinetics of 8-hydroxypiperidinylmethyl-baicalein (BA-j) as a novel selective CDK1 inhibitor in monkey.

    PubMed

    Guo, Hong-Min; Sun, Yu-Ming; Zhang, Shi-Xuan; Ju, Xiu-Lan; Xie, Ai-Yun; Li, Jing; Zou, Liang; Sun, Xiao-Dan; Li, Hai-Liang; Zheng, Yang

    2015-12-01

    Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in the cell proliferation process and a new target in the research and development of anti-cancer drugs. 8-Hydroxypiperidinemethyl-baicalein (BA-j) is a Mannich base derivative of baicalein (BA) isolated from Scutellaria baicalensis, as a novel selective CDK1 inhibitor. 12 metabolites of BA-j in the monkey urine were identified by LC-MS-MS and (1)H NMR. The major metabolic pathways of BA-j, by capturing oxygen free radicals ((.)O2(-)) and releasing peroxides (H2O2), are degraded into active intermediate metabolite dihydroflavonol, then into main metabolite M179 by Shiff reaction, second metabolite M264 by sulfation, trace amount of metabolite M559 by glucuronidation UGT1A9, and without metabolism by CYP3A4. The metabolic process of BA-j by regulating intracellular reactive oxygen species (ROS) was related with BA-j selectively inducing apoptosis in cancer cells. Pharmacokinetics of 10mg/kg oral BA-j in monkey by HPLC-UV was best fitted to a two-compartment open model, with t1/2(β) of 4.2h, Cmax 25.4μM at 2h, and Vd 12.6L, meaning the drug distributing widely in body fluids with no special selectivity to certain tissues, and being able to permeate through the blood-brain barrier. The protein binding rate of BA-j was 91.8%. BA-j has excellent druggability for oral administration or injection, and it may be developed into a novel anti-cancer drug as a selective CDK1 inhibitor.

  10. Clinico-Histologic Conferences: Histology and Disease

    ERIC Educational Resources Information Center

    Shaw, Phyllis A.; Friedman, Erica S.

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical…

  11. Clinico-Histologic Conferences: Histology and Disease

    ERIC Educational Resources Information Center

    Shaw, Phyllis A.; Friedman, Erica S.

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical…

  12. Baicalein attenuates the quorum sensing-controlled virulence factors of Pseudomonas aeruginosa and relieves the inflammatory response in P. aeruginosa-infected macrophages by downregulating the MAPK and NFκB signal-transduction pathways

    PubMed Central

    Luo, Jing; Kong, Jin-liang; Dong, Bi-ying; Huang, Hong; Wang, Ke; Wu, Li-hong; Hou, Chang-chun; Liang, Yue; Li, Bing; Chen, Yi-qiang

    2016-01-01

    Burgeoning antibiotic resistance and unfavorable outcomes of inflammatory injury after Pseudomonas aeruginosa infection have necessitated the development of novel agents that not only target quorum sensing (QS) but also combat inflammatory injury with the least risk of resistance. This study aimed to assess the anti-QS and anti-inflammatory activities of baicalein, a traditional herbal medicine that is widely used in the People’s Republic of China, against P. aeruginosa infection. We found that subminimum inhibitory concentrations of baicalein efficiently interfered with the QS-signaling pathway of P. aeruginosa via downregulation of the transcription of QS-regulated genes and the translation of QS-signaling molecules. This interference resulted in the global attenuation of QS-controlled virulence factors, such as motility and biofilm formation, and the secretion into the culture supernatant of extracellular virulence factors, including pyocyanin, LasA protease, LasB elastase, and rhamnolipids. Moreover, we examined the anti-inflammatory activity of baicalein and its mode of action via a P. aeruginosa-infected macrophage model to address its therapeutic effect. Baicalein reduced the P. aeruginosa-induced secretion of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNFα. In addition, baicalein suppressed P. aeruginosa-induced activation of the MAPK and NFκB signal-transduction pathways in cocultured macrophages; this may be the mechanism by which baicalein inhibits the production of proinflammatory cytokines. Therefore, our study demonstrates that baicalein represents a potential treatment for P. aeruginosa infection because it clearly exhibits both antibacterial and anti-inflammatory activities. PMID:26792984

  13. Analysis of histological and immunological parameters of metastatic lymph nodes from colon cancer patients reveals that T-helper 1 type immune response is associated with improved overall survival

    PubMed Central

    Nizri, Eran; Greenman-Maaravi, Nofar; Bar-David, Shoshi; Ben-Yehuda, Amir; Weiner, Gilad; Lahat, Guy; Klausner, Joseph

    2016-01-01

    Abstract Lymph node (LN) involvement in colonic carcinoma (CC) is a grave prognostic sign and mandates the addition of adjuvant treatment. However, in light of the histological variability and outcomes observed, we hypothesized that patients with LN metastases (LNM) comprise different subgroups. We retrospectively analyzed the histological sections of 82 patients with CC and LNM. We studied various histological parameters (such as tumor grade, desmoplasia, and preservation of LN architecture) as well as the prevalence of specific peritumoral immune cells (CD8+, CD20+, T-bet+, and GATA-3+). We correlated the histological and immunological data to patient outcome. Tumor grade was a significant prognostic factor even in patients with LNM. So was the number of LN involved (N1/N2 stage). From the morphological parameters tested (LN extracapsular invasion, desmoplasia in LN, LN architecture preservation, and mode of metastases distribution), none was found to be significantly associated with overall survival (OS). The mean OS of CD8+ low patients was 66.6 ± 6.25 versus 71.4 ± 5.1 months for CD8+ high patients (P = 0.79). However, T-helper (Th) 1 immune response skewing (measured by Th1/Th2 ratio >1) was significantly associated with improved OS. For patients with low ratio, the median OS was 35.5 ± 5 versus 83.5 months for patients with high Th1/Th2 ratio (P = 0.001). The histological presentation of LNM does not entail specific prognostic information. However, the finding of Th1 immune response in LN signifies a protective immune response. Future studies should be carried to verify this marker and develop a strategy that augments this immune response during subsequent adjuvant treatment. PMID:27828856

  14. Baicalein Protects Against Retinal Ischemia by Antioxidation, Antiapoptosis, Downregulation of HIF-1α, VEGF, and MMP-9 and Upregulation of HO-1

    PubMed Central

    Chuang, Min-Jay; Liu, Xiao-Qian; Ho, Li-Kang; Pan, Wynn H.T.; Zhang, Xiu-Mei; Liu, Chi-Ming; Tsai, Shen-Kou; Kong, Chi-Woon; Lee, Shou-Dong; Chen, Mi-Mi; Chao, Fang-Ping

    2013-01-01

    Abstract Purpose Retinal ischemia-associated ocular disorders are vision threatening. This study examined whether the flavonoid baicalein is able to protect against retinal ischemia/reperfusion. Methods Using rats, the intraocular pressure was raised to 120 mmHg for 60 min to induce retinal ischemia. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating dissociated retinal cells with 100 μM ascorbate and 5 μM FeSO4 (iron) for 1 h. The rats or the dissociated cells had been pretreated with baicalein (in vivo: 0.05 or 0.5 nmol; in vitro: 100 μM), vehicle (1% ethanol), or trolox (in vivo: 5 nmol; in vitro: 100 μM or 1 mM). The effects of these treatments on the retina or the retinal cells were evaluated by electrophysiology, immunohistochemistry, terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) staining, Western blotting, or in vitro dichlorofluorescein assay. In addition, real-time-polymerase chain reaction was used to assess the retinal expression of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), vascular endothelium growth factor (VEGF), and heme oxygenase-1 (HO-1). Results The retinal changes after ischemia included a decrease in the electroretinogram b-wave amplitude, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, an increase in vimentin immunoreactivity, which is a marker for Müller cells, an increase in apoptotic cells in the retinal ganglion cell layer linked to a decrease in the Bcl-2 protein, and changes in the mRNA levels of HIF-1α, VEGF, MMP-9, and HO-1. Of clinical importance, the ischemic detrimental effects were concentration dependently and/or significantly (0.05 nmol and/or 0.5 nmol) altered when baicalein was applied 15 min before retinal ischemia. Most of all, 0.5 nmol baicalein significantly reduced the upregulation of MMP-9; in contrast, 5 nmol trolox only had a weak

  15. [DR (a-Se) versus CR (DLR)--is an improvement of the accuracy possible? A retrospective histologic analysis (n = 100)].

    PubMed

    Schulz-Wendtland, Rüdiger; Lell, Michael; Wenkel, Evelyn; Böhner, Cathrin; Dassel, Marc-Steffen; Bautz, Werner

    2007-01-01

    A retrospective clinical-histological study to determine the diagnostic accuracy using high-resolution digital phosphor storage plates (CR) (hardcopy) and full-field digital mammography (DR) (hardcopy) for microcalcifications and focal lesions (BI-RADS category 4 or 5) (n = 100). From 01/2004 to 06/2004, 100 patients underwent digital storage plate mammography (CR) and, after diagnosis and preoperative wire localization, full-field digital mammography (a-Se) (DR) with the same exposure parameters. Five investigators retrospectively determined the diagnosis after the operation from randomly distributed mediolateral views (hardcopy reading). These results were correlated with the final histology. The accuracy of digital storage plate mammography (CR) and full-field digital mammography (DR) was 73% and 76% for all findings (n = 100), 74%, 78% for microcalcifications (n = 50) and 72%, 74% for focal lesions (n = 50). The overall results showed no difference. Our findings indicate equivalence of high-resolution digital phosphor storage plate mammography (CR) and full-field digital mammography (a-Se) (DR).

  16. Renal cell carcinoma: applicability of the apparent coefficient of the diffusion-weighted estimated by MRI for improving their differential diagnosis, histologic subtyping, and differentiation grade.

    PubMed

    Mytsyk, Yulian; Dutka, Ihor; Borys, Yuriy; Komnatska, Iryna; Shatynska-Mytsyk, Iryna; Farooqi, Ammad Ahmad; Gazdikova, Katarina; Caprnda, Martin; Rodrigo, Luis; Kruzliak, Peter

    2017-02-01

    Renal cell carcinoma (RCC) represents the most common malignant epithelial neoplasm of the kidney. Accurate assessment of the renal masses, defining the histologic subtype and the grade of differentiation of the tumor, is vital to ensure an adequate case management as well as for staging and prognosis. Recently, diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) tends to be increasingly appealing for the clinicians as an imaging procedure of choice for the diagnosis and staging of the RCC, which is predetermined by several advantages over CT. The goal of the survey was to assess the applicability of the apparent diffusion coefficient (ADC) of the DWI MRI for the differential diagnostics, histologic subtyping, and defining the grade of differentiation of the RCC. The study enrolled 288 adult patients with renal lesions: 188 patients with solid RCC-126 patients with clear cell subtype (ccRCC), 32 patients with papillary RCC (pRCC), 30 patients with chromophobe RCC (chRCC); 27 patient with cystic form or RCC (Bosniak cyst, category IV); 32 patients with renal angiomyolipoma (AML); 25 patients with renal oncocytoma (OC); and 16 patients with the renal abscess (AB). In total, 245 lesions were pathologically verified. As a reference, 19 healthy volunteers were included into the study. All patients underwent MRI of the kidneys, involving DWI with subsequent evaluation of the ADC. There was a reliable difference (p < 0.05) in mean ADC values between the normal renal parenchyma (NRP), solid RCC of different histologic subtypes and grades, cystic RCC, and benign renal lesions. The mean ADC values obtained in the result of the study were (×10(-3) mm(2)/s): 2.47 ± 0.12 in NRP, 1.63 ± 0.29 in all solid RCCs, 1.82 ± 0.22 in solid ccRCC (1.92 ± 0.11-Fuhrman grade I, 1.84 ± 0.14-Fuhrman grade II, 1.79 ± 0.10-Fuhrman grade III, 1.72 ± 0.06-Fuhrman grade IV), 1.61 ± 0.07 in pRCC, 1.46 ± 0.09 in chRCC, 2.68 ± 0.11 in cystic RCC, 2.13

  17. Baicalein 5,6,7-trimethyl ether activates peroxisomal but not mitochondrial fatty acid beta-oxidation.

    PubMed

    Morita, M; Kanai, M; Mizuno, S; Iwashima, M; Hayashi, T; Shimozawa, N; Suzuki, Y; Imanaka, T

    2008-06-01

    Recently, we reported that baicalein 5,6,7-trimethyl ether (BTM), a flavonoid, is capable of activating fatty acid beta-oxidation in X-linked adrenoleukodystrophy (X-ALD) fibroblasts (FEBS Lett. 2005; 579: 409-414). The objective of this study was to clarify whether BTM activates peroxisomal and/or mitochondrial fatty acid beta-oxidation. We first analysed the effect of BTM on fatty acid beta-oxidation in fibroblasts derived from healthy controls as well as patients with X-ALD, mitochondrial carnitine-acylcarnitine translocase (CACT) deficiency, and peroxisome biogenesis disorder, Zellweger syndrome. Lignoceric acid (C(24:0)) beta-oxidation in the fibroblasts was stimulated by treatment with BTM, except for Zellweger fibroblasts. In contrasts, palmitic acid (C(16:0)) beta-oxidation was increased (2.8-fold) only in CACT-deficient fibroblasts. In U87 glioblastoma cells, C(24:0) beta-oxidation was also activated by treatment with BTM but C(16:0) beta-oxidation was not. The C(16:0) beta-oxidation was, however, significantly increased in the presence of 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA), a carnitine palmitoyltransferase I inhibitor. These results indicate that BTM activates peroxisomal but not mitochondrial fatty acid beta-oxidation. In addition, we found that BTM did not upregulate the expression of ABCD2/ALDR, ABCD3/PMP70, ACOX1 and FATP4 genes but slightly increased ACSVL1 gene expression.

  18. Biocompatible nanoemulsions based on hemp oil and less surfactants for oral delivery of baicalein with enhanced bioavailability.

    PubMed

    Yin, Juntao; Xiang, Cuiyu; Wang, Peiqing; Yin, Yuyun; Hou, Yantao

    2017-01-01

    Baicalein (BCL) possesses high pharmacological activities but low solubility and stability in the intestinal tract. This study aimed to probe the potential of nanoemulsions (NEs) consisting of hemp oil and less surfactants in ameliorating the oral bioavailability of BCL. BCL-loaded NEs (BCL-NEs) were prepared by high-pressure homogenization technique to reduce the amount of surfactants. BCL-NEs were characterized by particle size, entrapment efficiency (EE), in vitro drug release, and morphology. Bioavailability was studied in Sprague-Dawley rats following oral administration of BCL suspensions, BCL conventional emulsions, and BCL-NEs. The obtained NEs were ~90 nm in particle size with an EE of 99.31%. BCL-NEs significantly enhanced the oral bioavailability of BCL, up to 524.7% and 242.1% relative to the suspensions and conventional emulsions, respectively. BCL-NEs exhibited excellent intestinal permeability and transcellular transport ability. The cytotoxicity of BCL-NEs was documented to be low and acceptable for oral purpose. Our findings suggest that such novel NEs and preparative process provide a promising alternative to current formulation technologies and suitable for oral delivery of drugs with bioavailability issues.

  19. Molecularly imprinted polymers based on SBA-15 for selective solid-phase extraction of baicalein from plasma samples.

    PubMed

    He, Hongliang; Gu, Xiaoli; Shi, Liying; Hong, Junli; Zhang, Hongjuan; Gao, Yankun; Du, Shuhu; Chen, Lina

    2015-01-01

    Highly selective molecularly imprinted mesoporous silica polymer (SBA-15@MIP) for baicalein (BAI) extraction was synthesized using a surface molecular imprinting technique on the SBA-15 supporter. Computational simulation was used to predict the optimal functional monomer for the rational design of SBA-15@MIP. Meanwhile, high adsorption capacity was obtained when a suitable yield of molecularly imprinted polymers (MIPs) layer was grafted onto the surface of SBA-15. Characterization and performance tests of the obtained polymer revealed that SBA-15@MIP possessed a highly ordered mesoporous structure, reached saturated adsorption within 60 min, and exhibited higher sorption capacity to the target molecule BAI compared with non-imprinted mesoporous silica polymer (SBA-15@NIP) and SBA-15. Finally, SBA-15@MIP was successfully applied to solid-phase extraction (SPE) coupled with high-performance liquid chromatography and ultraviolet detection (HPLC-UV) for the determination of trace BAI in plasma samples. Mean recoveries of BAI through the molecularly imprinted solid-phase extraction (MISPE) sorbent, non-imprinted solid-phase extraction (NISPE) sorbent, and SBA-15 solid-phase extraction (SBA-15-SPE) sorbent were 94.4, 22.7, and 10.7 %, respectively, and the relative standard deviations were 2.9, 2.6, and 3.6 %, respectively. These results reveal that SBA-15@MIP as a SPE sorbent has good applicability to selectively separate and enrich trace BAI from complex samples.

  20. Salaries in histology.

    PubMed

    Buesa, René J

    2008-04-01

    An analysis of histology salaries from the last 4 national surveys conducted by the American Society of Clinical Pathologists is presented. The regional variations within and between years for histology salaries presented in the last 4 national surveys of medical laboratory specialties are not statistically significant. Local variations greater than the national variations reflect the preponderant effect of local supply and demand over regional characteristics. Salaries by hospitals are significantly different only between 2 size categories and the supervisors' salary. There is no correlation between the salary increase for any histology position in any one year and the vacancy level in the previous year. On the other hand, the correlation between histotechnicians' salaries and both the cost of living and the median income are significant, as well as between the latter and the supervisors' salary. The histotechnologists' salaries are significantly correlated with the consumer price index but not with the inflation rate. A survey of histology salaries in foreign countries was also undertaken and compared with salaries in the United States. National salaries rank close to the general average for 10 foreign countries when expressed as ratios with the personal gross domestic product or with the countries' minimum wage. For the midpoint salary ranges, the United States ranks fourth after Canada, the United Kingdom, and Australia, the latter 3 countries with structured pay rates adjusted to local costs of living in contrast with United States' salary characteristics. Histology salaries rest on negotiations within each employer's salary structure and fluctuate according to license level, documented studies, special training(s), years of experience, references, and the ability to negotiate, where each side tries to take advantage of the other. The result is a heterogeneous and chaotic salary situation driven by personal and local needs, where the histology worker usually

  1. Adapting lean to histology laboratories.

    PubMed

    Buesa, René J

    2009-10-01

    Histology laboratories (histolabs) can increase productivity and reduce turnaround time and errors by using any one of several available management tools. After a few years of operation, all histolabs develop workflow problems. Histology laboratories handling more than 20,000 cases per year benefit the most from implementing management tools, as occurred in the 25 facilities summarized in this article. Discontinuous workflow, lack of "pulling" between steps, accepting unavoidable waiting times while working with small batches within work cells, and a workflow with an uneven rate of completion, are some of the adaptations required by the Lean system when it is used in histology because 70% of the tasks are manual and the flow has to be interrupted to add value to the pieces of tissue during tissue processing, no matter how short that step is. After all these adaptations are incorporated, the histolab becomes as "Lean" as it can be, and the qualifier is also a recognition of the effort and personnel involvement in the implementation. Given its service nature, productivity increments do not expand the histolab customer base and could lead to staffing reductions. This is one of the causes of reluctance by some employees for implementing these techniques which are mostly driven by cost reductions sought by insurance companies and administrators, and not necessarily because of a real medical need to reduce the turnaround time. Finally, any histolab wanting to improve its workflow can follow some easy steps presented here as a guide to accomplish that objective. These steps stress the need for the supervisors to insure that the personnel in the histology laboratory are being paid at a comparable rate as other histolabs in the area.

  2. The Mechanism of Ca(2+) Movement in the Involvement of Baicalein-Induced Cytotoxicity in ZR-75-1 Human Breast Cancer Cells.

    PubMed

    Chang, Hong-Tai; Chou, Chiang-Ting; Kuo, Daih-Huang; Shieh, Pochuen; Jan, Chung-Ren; Liang, Wei-Zhe

    2015-07-24

    Baicalein (5,6,7-trihydroxyflavone) (1) has been found to be active against a wide variety of cancer cells. However, the molecular mechanism underlying the effects of 1 on the induction of Ca(2+) movement and cytotoxicity in human breast cancer cells is unknown. This study examined the relationship between 1-induced Ca(2+) signaling and cytotoxicity in ZR-75-1 human breast cancer cells. The in vitro investigations reported herein produced the following results: (i) Compound 1 increased intracellular Ca(2+) concentration ([Ca(2+)]i) in a concentration-dependent manner. The signal was decreased by approximately 50% by removal of extracellular Ca(2+). (ii) Compound 1-triggered [Ca(2+)]i increases were significantly suppressed by store-operated Ca(2+) channel blockers 2-aminoethoxydiphenyl borate (2-APB) and the PKC inhibitor GF109203X. (iii) In Ca(2+)-free medium, compound 1-induced [Ca(2+)]i increases were also inhibited by GF109203X. Furthermore, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-ditert-butylhydroquinone (BHQ) abolished 1-induced [Ca(2+)]i increases. Inhibition of phospholipase C (PLC) with U73122 abolished 1-induced [Ca(2+)]i increases. (iv) Compound 1 (20-40 μM) caused cytotoxicity, increased reactive oxygen species (ROS) production, and activated caspase-9/caspase-3. Furthermore, compound 1-induced apoptosis was significantly inhibited by prechelating cytosolic Ca(2+) with BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester) or by decreasing ROS with the antioxidant NAC (N-acetylcysteine). Together, baicalein (1) induced a [Ca(2+)]i increase by inducing PLC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via PKC-dependent, 2-APB-sensitive store-operated Ca(2+) channels. Moreover, baicalein (1) induced Ca(2+)-associated apoptosis involved ROS production in ZR-75-1 cells.

  3. Anti-fibrillation propensity of a flavonoid baicalein against the fibrils of hen egg white lysozyme: potential therapeutics for lysozyme amyloidosis.

    PubMed

    Fazili, Naveed Ahmad; Bhat, Imtiyaz Ahmad; Bhat, Waseem Feeroze; Naeem, Aabgeena

    2016-10-01

    More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3 M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20-fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in Congo red assay and appearance of a network of long rope-like fibrils in transmission electron microscope (TEM) analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose-dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150-μM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 and 450 nm, respectively, together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis.

  4. Gastritis: the histology report.

    PubMed

    Rugge, Massimo; Pennelli, Gianmaria; Pilozzi, Emanuela; Fassan, Matteo; Ingravallo, Giuseppe; Russo, Valentina M; Di Mario, Francesco

    2011-03-01

    Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice.

  5. Histologic classification of gliomas.

    PubMed

    Perry, Arie; Wesseling, Pieter

    2016-01-01

    Gliomas form a heterogeneous group of tumors of the central nervous system (CNS) and are traditionally classified based on histologic type and malignancy grade. Most gliomas, the diffuse gliomas, show extensive infiltration in the CNS parenchyma. Diffuse gliomas can be further typed as astrocytic, oligodendroglial, or rare mixed oligodendroglial-astrocytic of World Health Organization (WHO) grade II (low grade), III (anaplastic), or IV (glioblastoma). Other gliomas generally have a more circumscribed growth pattern, with pilocytic astrocytomas (WHO grade I) and ependymal tumors (WHO grade I, II, or III) as the most frequent representatives. This chapter provides an overview of the histology of all glial neoplasms listed in the WHO 2016 classification, including the less frequent "nondiffuse" gliomas and mixed neuronal-glial tumors. For multiple decades the histologic diagnosis of these tumors formed a useful basis for assessment of prognosis and therapeutic management. However, it is now fully clear that information on the molecular underpinnings often allows for a more robust classification of (glial) neoplasms. Indeed, in the WHO 2016 classification, histologic and molecular findings are integrated in the definition of several gliomas. As such, this chapter and Chapter 6 are highly interrelated and neither should be considered in isolation.

  6. Gastric lymphoma: the histology report.

    PubMed

    Doglioni, Claudio; Ponzoni, Maurilio; Ferreri, Andrés J M; Savio, Antonella

    2011-03-01

    The diagnosis of gastric MALT lymphoma is frequently difficult for the general histopathologist. During recent years there have been relevant changes in the therapeutic approach to gastric MALT lymphoma and our knowledge about its pathogenesis has greatly improved. The management of this disease actually requires a close cooperation between the histopathologist and the clinicians. The histology report of biopsies of a newly diagnosed or of an already treated case implies information of clinical and therapeutical relevance. This paper aims at giving the histopathologist a general knowledge about the state of art of this disease and its management. The diagnostic process leading to a complete and competent report is then described step by step.

  7. Delivery of baicalein and paclitaxel using self-assembled nanoparticles: synergistic antitumor effect in vitro and in vivo.

    PubMed

    Wang, Wei; Xi, Mei; Duan, Xuezhong; Wang, Yong; Kong, Fansheng

    2015-01-01

    Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance. The aim of the study reported here was to develop multifunctional, dual-ligand, modified, self-assembled nanoparticles (NPs) for the combination delivery of baicalein (BCL) and paclitaxel (PTX) prodrugs. Prodrug of PTX and prodrug of BCL, containing dual-targeted ligands of folate (FA) and hyaluronic acid (HA), were synthesized. Multifunctional self-assembled NPs for combination delivery of PTX prodrug and BCL prodrug (PTX-BCL) were prepared and the synergistic antitumor effect was evaluated in vitro and in vivo. The in vitro transfection efficiency of the novel modified vectors was evaluated in human lung cancer A549 cells and drug-resistant lung cancer A549/PTX cells. The in vivo antitumor efficiency and systemic toxicity of different formulations were further investigated in mice bearing A549/PTX drug-resistant human lung cancer xenografts. The size of the PTX-BCL NPs was approximately 90 nm, with a positive zeta potential of +3.3. The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations. The prepared PTX-BCL NP drug-delivery system was proven efficient by its targeting of drug-resistant human lung cancer cells and delivering of BCL and PTX prodrugs. Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine.

  8. Delivery of baicalein and paclitaxel using self-assembled nanoparticles: synergistic antitumor effect in vitro and in vivo

    PubMed Central

    Wang, Wei; Xi, Mei; Duan, Xuezhong; Wang, Yong; Kong, Fansheng

    2015-01-01

    Purpose Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance. The aim of the study reported here was to develop multifunctional, dual-ligand, modified, self-assembled nanoparticles (NPs) for the combination delivery of baicalein (BCL) and paclitaxel (PTX) prodrugs. Methods Prodrug of PTX and prodrug of BCL, containing dual-targeted ligands of folate (FA) and hyaluronic acid (HA), were synthesized. Multifunctional self-assembled NPs for combination delivery of PTX prodrug and BCL prodrug (PTX-BCL) were prepared and the synergistic antitumor effect was evaluated in vitro and in vivo. The in vitro transfection efficiency of the novel modified vectors was evaluated in human lung cancer A549 cells and drug-resistant lung cancer A549/PTX cells. The in vivo antitumor efficiency and systemic toxicity of different formulations were further investigated in mice bearing A549/PTX drug-resistant human lung cancer xenografts. Results The size of the PTX-BCL NPs was approximately 90 nm, with a positive zeta potential of +3.3. The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations. Conclusion The prepared PTX-BCL NP drug-delivery system was proven efficient by its targeting of drug-resistant human lung cancer cells and delivering of BCL and PTX prodrugs. Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine. PMID:26045664

  9. New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images

    PubMed Central

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K.; Schad, Lothar R.; Zöllner, Frank Gerrit

    2015-01-01

    Background Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. Methods and Results In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin—3,3’-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. Validation To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Context Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics. PMID:26717571

  10. New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images.

    PubMed

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K; Schad, Lothar R; Zöllner, Frank Gerrit

    2015-01-01

    Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin-3,3'-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics.

  11. 3D prostate histology image reconstruction: Quantifying the impact of tissue deformation and histology section location

    PubMed Central

    Gibson, Eli; Gaed, Mena; Gómez, José A.; Moussa, Madeleine; Pautler, Stephen; Chin, Joseph L.; Crukley, Cathie; Bauman, Glenn S.; Fenster, Aaron; Ward, Aaron D.

    2013-01-01

    Background: Guidelines for localizing prostate cancer on imaging are ideally informed by registered post-prostatectomy histology. 3D histology reconstruction methods can support this by reintroducing 3D spatial information lost during histology processing. The need to register small, high-grade foci drives a need for high accuracy. Accurate 3D reconstruction method design is impacted by the answers to the following central questions of this work. (1) How does prostate tissue deform during histology processing? (2) What spatial misalignment of the tissue sections is induced by microtome cutting? (3) How does the choice of reconstruction model affect histology reconstruction accuracy? Materials and Methods: Histology, paraffin block face and magnetic resonance images were acquired for 18 whole mid-gland tissue slices from six prostates. 7-15 homologous landmarks were identified on each image. Tissue deformation due to histology processing was characterized using the target registration error (TRE) after landmark-based registration under four deformation models (rigid, similarity, affine and thin-plate-spline [TPS]). The misalignment of histology sections from the front faces of tissue slices was quantified using manually identified landmarks. The impact of reconstruction models on the TRE after landmark-based reconstruction was measured under eight reconstruction models comprising one of four deformation models with and without constraining histology images to the tissue slice front faces. Results: Isotropic scaling improved the mean TRE by 0.8-1.0 mm (all results reported as 95% confidence intervals), while skew or TPS deformation improved the mean TRE by <0.1 mm. The mean misalignment was 1.1-1.9° (angle) and 0.9-1.3 mm (depth). Using isotropic scaling, the front face constraint raised the mean TRE by 0.6-0.8 mm. Conclusions: For sub-millimeter accuracy, 3D reconstruction models should not constrain histology images to the tissue slice front faces and should be

  12. Simultaneous determination of baicalin, wogonoside, baicalein, wogonin, oroxylin A and chrysin of Radix scutellariae extract in rat plasma by liquid chromatography tandem mass spectrometry.

    PubMed

    Tong, Ling; Wan, Meixu; Zhang, Lihua; Zhu, Yonghong; Sun, He; Bi, Kaishun

    2012-11-01

    A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of baicalin, wogonoside, baicalein, wogonin, oroxylin A and chrysin in rat plasma, using naringin as an internal standard. After acidifying with HCl, plasma samples were pretreated by liquid-liquid extraction with acetone. Chromatographic separation was accomplished on a Hypersil Gold-C(18) analytical column (2.1×150 mm, 5 μm) utilizing a gradient elution profile and a mobile phase consisting of (A) 0.1% formic acid in water and (B) acetonitrile. Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. All analytes showed good linearity over the investigated concentration range (r>0.9900). The lower limit of quantification was 0.5 ng/ml for baicalin, wogonoside, wogonin and oroxylin A, and 1.0 ng/ml for baicalein and chrysin. Intra-day and inter-day precisions (RSD%) were less than 15% and accuracy (RE%) ranged from -6.7% to 5.8%. The validated method was successfully applied to investigate the pharmacokinetics of the major flavonoids of Radix scutellariae extract after oral administration to rats. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Anticancer activity of baicalein and luteolin studied in colorectal adenocarcinoma LoVo cells and in drug-resistant LoVo/Dx cells.

    PubMed

    Palko-Labuz, Anna; Sroda-Pomianek, Kamila; Uryga, Anna; Kostrzewa-Suslow, Edyta; Michalak, Krystyna

    2017-04-01

    Due to the type-specific diversity of cancer cells, an analysis and elucidation of molecular mechanisms responsible for anticancer properties of biologically active compounds are essential. Plant-derived polyphenolic compounds such as flavonoids may be useful in cancer chemoprevention or treatment because they influence diverse molecular pathways in cancer cells. In these studies anticancer activity of natural occurring flavones, baicalein and luteolin was investigated in colon cancer cells LoVo and in their drug resistant subline LoVo/Dx. Inhibitory activity of these flavones on cells growth and their ability to induce apoptosis were observed. A less pronounced influence of studied flavones on proliferation and apoptosis of LoVo/Dx as compared with LoVo cells well correlated with significantly lower cytotoxicity of these compounds in drug-resistant cells. These effects may be related to overexpression of multidrug transporter P-glycoprotein in drug-resistant LoVo/Dx cells. Our studies indicated that baicalein could be a substrate of this drug transporter. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Mécano-Stimulation™ of the skin improves sagging score and induces beneficial functional modification of the fibroblasts: clinical, biological, and histological evaluations

    PubMed Central

    Humbert, Philippe; Fanian, Ferial; Lihoreau, Thomas; Jeudy, Adeline; Elkhyat, Ahmed; Robin, Sophie; Courderot-Masuyer, Carol; Tauzin, Hélène; Lafforgue, Christine; Haftek, Marek

    2015-01-01

    Background Loss of mechanical tension appears to be the major factor underlying decreased collagen synthesis in aged skin. Numerous in vitro studies have shown the impact of mechanical forces on fibroblasts through mechanotransduction, which consists of the conversion of mechanical signals to biochemical responses. Such responses are characterized by the modulation of gene expression coding not only for extracellular matrix components (collagens, elastin, etc.) but also for degradation enzymes (matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]). A new device providing a mechanical stimulation of the cutaneous and subcutaneous tissue has been used in a simple, blinded, controlled, and randomized study. Materials and methods Thirty subjects (aged between 35 years and 50 years), with clinical signs of skin sagging, were randomly assigned to have a treatment on hemiface. After a total of 24 sessions with Mécano-Stimulation™, biopsies were performed on the treated side and control area for in vitro analysis (dosage of hyaluronic acid, elastin, type I collagen, MMP9; equivalent dermis retraction; GlaSbox®; n=10) and electron microscopy (n=10). Furthermore, before and after the treatment, clinical evaluations and self-assessment questionnaire were done. Results In vitro analysis showed increases in hyaluronic acid, elastin, type I collagen, and MMP9 content along with an improvement of the migratory capacity of the fibroblasts on the treated side. Electron microscopy evaluations showed a clear dermal remodeling in relation with the activation of fibroblast activity. A significant improvement of different clinical signs associated with skin aging and the satisfaction of the subjects were observed, correlated with an improvement of the sagging cheek. Conclusion Mécano-Stimulation is a noninvasive and safe technique delivered by flaps microbeats at various frequencies, which can significantly improve the skin

  15. GRAPHIE: graph based histology image explorer

    PubMed Central

    2015-01-01

    Background Histology images comprise one of the important sources of knowledge for phenotyping studies in systems biology. However, the annotation and analyses of histological data have remained a manual, subjective and relatively low-throughput process. Results We introduce Graph based Histology Image Explorer (GRAPHIE)-a visual analytics tool to explore, annotate and discover potential relationships in histology image collections within a biologically relevant context. The design of GRAPHIE is guided by domain experts' requirements and well-known InfoVis mantras. By representing each image with informative features and then subsequently visualizing the image collection with a graph, GRAPHIE allows users to effectively explore the image collection. The features were designed to capture localized morphological properties in the given tissue specimen. More importantly, users can perform feature selection in an interactive way to improve the visualization of the image collection and the overall annotation process. Finally, the annotation allows for a better prospective examination of datasets as demonstrated in the users study. Thus, our design of GRAPHIE allows for the users to navigate and explore large collections of histology image datasets. Conclusions We demonstrated the usefulness of our visual analytics approach through two case studies. Both of the cases showed efficient annotation and analysis of histology image collection. PMID:26330277

  16. Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways.

    PubMed

    Li, Yue; Wang, Qi; Yao, Xiaomin; Li, Yan

    2010-08-25

    The herbal products baicalin, baicalein, chlorogenic acid, and ginsenoside Rf have multiple pharmacological effects and are extensively used in alternative and/or complementary therapies. The present study investigated whether baicalin, baicalein, chlorogenic acid, and ginsenoside Rf induced the expression of the cytochrome P450 3A4 (CYP3A4) and multi-drug resistance 1 (MDR1) genes through the pregnane X receptor and constitutive androstane receptor pathways. Real time PCR, western blotting, and a luminescent assay were used to assess the induction of gene expression and activity of CYP3A4 and MDR1 by the test compounds. The interactions of baicalein/chlorogenic acid/ginsenoside Rf with constitutive androstane receptor and pregnane X receptor were evaluated using luciferase reporter and gel shift assays. Baicalein induced the expression of CYP3A4 and MDR1 mRNA by activating pregnane X receptor and constitutive androstane receptor. Chlorogenic acid and ginsenoside Rf showed a relatively weak effect on CYP3A4 promoter activation only in HepG2 cells cotransfected with constitutive androstane receptor and demonstrated no effects on MDR1 via either the constitutive androstane receptor or pregnane X receptor pathway. Baicalin had no effect on either CYP3A4 or MDR1 gene expression. In conclusion, baicalein has the potential to up-regulate CYP3A4 and MDR1 through the direct activation of the constitutive androstane receptor and pregnane X receptor pathways. Chlorogenic acid and ginsenoside Rf only induced constitutive androstane receptor-mediated CYP3A4 expression.

  17. Validation of histology image registration

    NASA Astrophysics Data System (ADS)

    Shojaii, Rushin; Karavardanyan, Tigran; Yaffe, Martin; Martel, Anne L.

    2011-03-01

    The aim of this paper is to validate an image registration pipeline used for histology image alignment. In this work a set of histology images are registered to their correspondent optical blockface images to make a histology volume. Then multi-modality fiducial markers are used to validate the alignment of histology images. The fiducial markers are catheters perfused with a mixture of cuttlefish ink and flour. Based on our previous investigations this fiducial marker is visible in medical images, optical blockface images and it can also be localized in histology images. The properties of this fiducial marker make it suitable for validation of the registration techniques used for histology image alignment. This paper reports on the accuracy of a histology image registration approach by calculation of target registration error using these fiducial markers.

  18. Histologic effects of resurfacing lasers.

    PubMed

    Freedman, Joshua R; Greene, Ryan M; Green, Jeremy B

    2014-02-01

    By utilizing resurfacing lasers, physicians can significantly improve the appearance of sun-damaged skin, scars, and more. The carbon dioxide and erbium:yttrium-aluminum-garnet lasers were the first ablative resurfacing lasers to offer impressive results although these earlier treatments were associated with significant downtime. Later, nonablative resurfacing lasers such as the neodymium:yttrium-aluminum-garnet laser proved effective, after a series of treatments with less downtime, but with more modest results. The theory of fractional photothermolysis has revolutionized resurfacing laser technology by increasing the safety profile of the devices while delivering clinical efficacy. A review of the histologic and molecular consequences of the resurfacing laser-tissue interaction allows for a better understanding of the devices and their clinical effects.

  19. Contrast enhanced phototrichogram (CE-PTG): an improved non-invasive technique for measurement of scalp hair dynamics in androgenetic alopecia--validation study with histology after transverse sectioning of scalp biopsies.

    PubMed

    Van Neste, D J

    2001-01-01

    Global changes of scalp hair represent the cumulative end result of discrete changes of individual hair follicle structure and/or function. Monitoring of such changes requires an accurate non-invasive method. The phototrichogram (PTG) appears to be an appropriate choice to do so. However, a known weakness of the method is the lack of detection of less pigmented or thinning hair. Balding scalp of male subjects with androgenetic alopecia (AGA) was analysed with our previously published PTG method and with contrast enhanced (CE-)PTG followed by biopsy and transverse section examination with the light microscope. As compared with PTG, the CE-PTG method significantly improved detection not only of thin but also of thick hair. Equal numbers of thick (diameter > 40 mm) hair were detected with CE-PTG and with histology. CE-PTG was also able to detect the severely miniaturised hair fiber (down to 8 mm diameter) and was comparable to scalp biopsy analysis. The latter could identify hair fibres, which did not reach the scalp surface, a measure that is considered as not clinically significant. All growth stages - anagen, catagen and telogen - as well as the empty follicle stage could clearly be observed with CE-PTG. Staging of the more severely affected hair follicles was not always possible neither with CE-PTG nor histology - even with serial sectioning. The finding of such technological advantages makes the CE-PTG a first choice method for detailed analysis of hair cycling in androgenetic alopecia - a scalp disorder characterised by extreme hair follicle miniaturisation, decreased hair pigmentation and hair thinning.

  20. Post-trauma administration of the pifithrin-α oxygen analogue improves histological and functional outcomes after experimental traumatic brain injury

    PubMed Central

    Yang, L-Y; Chu, Y-H; Tweedie, D.; Yu, Q-S; Pick, CG; Hoffer, BJ; Greig, NH; Wang, J-Y

    2016-01-01

    -α (O) administration after TBI. PFT-α (O) treatment also decreased phospho-p53 positive neurons in the cortical contusion region. Our data suggest that PFT-α (O) provided a significant reduction of cortical cell death and protected neurons from glutamate-induced excitotoxicity in vitro, as well as improved neurological functional outcome and reduced brain injury in vivo via anti-apoptotic mechanisms. The inhibition of p53-induced apoptosis by PFT-α (O) provides a useful tool to evaluate reversible apoptotic mechanisms and may develop into a novel therapeutic strategy for TBI. PMID:25819102

  1. Histology without xylene.

    PubMed

    Buesa, René J; Peshkov, Maxim V

    2009-08-01

    After the hazardous effects of xylene became indisputable in the 1970s, many potential substitutes became available, some with as many if not more hazards. This article discusses the inadequacy of 5 vegetable oils as substitutes, as well as the characteristics of 22 D-limonene-based substitutes, all less effective in their chemical role, some capable of inducing health problems, and costing more than twice as much as xylene. Some of the 35 alkane-based substitutes discussed are effective for tissue processing, less toxic, with a cost about the same as xylene, but are not very effective for dewaxing and other staining tasks. Isopropanol (2-propanol) alone or mixed with molten paraffin is a technically acceptable and cost-effective substitute for xylene for tissue processing, but in this study, we demonstrate that the best clearing agents from the sectioning quality and diagnostic value point of view, with automated or manual protocols, are mixtures of 5:1 and 2:1 isopropanol and mineral oil, followed by undiluted mineral oil, all at 50 degrees C, making them a safer and cheaper substitute than xylene. Using a 1.7% dishwasher soap aqueous solution at 90 degrees C to dewax before staining and oven drying the stained sections before coverslipping will eliminate xylene from the staining tasks. Tissue processors retorts and conduits can be dewaxed with a 2% solution of a strong glassware laboratory detergent. These 4 methodologies will make the histology laboratory xylene-free but, due to the natural resistance to change, many histotechs will be reluctant to adopt them if they think that their technical expertise could be jeopardized, and the only way these changes will succeed is if the pathologists, as stewards of the histology laboratory, commit to their implementation.

  2. Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures.

    PubMed

    Bend, John Richard; Xia, Xue Yan; Chen, Daofeng; Awaysheh, Abudi; Lo, Andrea; Rieder, Michael John; Rylett, Rebecca Jane

    2015-01-01

    Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer's. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells. Endpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status. At low µM concentrations, each of the TCM constituents and mixtures effectively attenuated intracellular toxicity due to exposure of HEK 293 cells to 50 or 250 µM tBHP for 30 min to 3 h. Confocal microscopy of HEK 293 cells transfected with mutated green fluorescent protein (roGFP2) showed effective attenuation of tBHP oxidation by baicalein in real time. Three redox-regulated proteins prominent in the disulfide proteome of HEK 293 cells were identified by MALDI-TOF mass spectrometry. We conclude that single TCM chemicals and their simple mixtures have potential for use in adjunct chemoprotective therapy. Advantages of mixtures compared to single TCM constituents include the ability to combine compounds with varying molecular mechanisms of cytoprotection for enhanced biological activity; and to combine chemicals with complementary pharmacokinetic properties to increase half-life and prolong activity in vivo. This article is open to POST-PUBLICATION REVIEW. Registered

  3. [Histologic studies on otomycosis].

    PubMed

    Vennewald, Irina; Schönlebe, J; Klemm, E

    2002-01-01

    Fungal infections of the ear are mostly described as mycoses of the auditory canal. The aim of our investigations was to find out how fungi colonize the ear in immunocompetent patients. In the years from 1993 to 2000, 128 patients suspected of having otomycosis were examined. Of these 115 patients suffered from chronic otitis media with persisting tympanum perforation and otorrhea. A further 13 patients had clinical signs of otitis externa only. In 54 out of 139 samples, fungi were found in the auditory canal, in five on the tympanic membrane, and in five in the middle ear. Two-thirds were isolated as moulds and one-third as yeasts. Dominating species were Aspergillus niger and Candida parapsilosis. Samples of 15 patients suspected of having mastoiditis or cholesteatoma were examined histologically. Fungal hyphae were observed in the middle ear cavity and/or between horny lamellae of cholesteatoma in 4 patients. In the middle ear of immunocompetent patients chronic-hyperplastic (polypous) inflammation was detected with increased production of mucus, which probably promotes the colonization with pathogenic fungi as in the middle ear just like in the auditory canal.

  4. Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome.

    PubMed

    Corrales, Andrea; Parisotto, Eduardo B; Vidal, Verónica; García-Cerro, Susana; Lantigua, Sara; Diego, Marian; Wilhem Filho, Danilo; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

    2017-09-15

    Melatonin administered during adulthood induces beneficial effects on cognition and neuroprotection in the Ts65Dn (TS) mouse model of Down syndrome. Here, we investigated the effects of pre- and post-natal melatonin treatment on behavioral and cognitive abnormalities and on several neuromorphological alterations (hypocellularity, neurogenesis impairment and increased oxidative stress) that appear during the early developmental stages in TS mice. Pregnant TS females were orally treated with melatonin or vehicle from the time of conception until the weaning of the offspring, and the pups continued to receive the treatment from weaning until the age of 5 months. Melatonin administered during the pre- and post-natal periods did not improve the cognitive impairment of TS mice as measured by the Morris Water maze or fear conditioning tests. Histological alterations, such as decreased proliferation (Ki67+ cells) and hippocampal hypocellularity (DAPI+ cells), which are typical in TS mice, were not prevented by melatonin. However, melatonin partially regulated brain oxidative stress by modulating the activity of the primary antioxidant enzymes (superoxide dismutase in the cortex and catalase in the cortex and hippocampus) and slightly decreasing the levels of lipid peroxidation in the hippocampus of TS mice. These results show the inability of melatonin to prevent cognitive impairment in TS mice when it is administered at pre- and post-natal stages. Additionally, our findings suggest that to induce pro-cognitive effects in TS mice during the early stages of development, in addition to attenuating oxidative stress, therapies should aim to improve other altered processes, such as hippocampal neurogenesis and/or hypocellularity. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Colorectal tumors: the histology report.

    PubMed

    Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

    2011-03-01

    Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed.

  6. Prenylated derivatives of baicalein and 3,7-dihydroxyflavone: synthesis and study of their effects on tumor cell lines growth, cell cycle and apoptosis.

    PubMed

    Neves, Marta Perro; Cidade, Honorina; Pinto, Madalena; Silva, Artur M S; Gales, Luís; Damas, Ana Margarida; Lima, Raquel T; Vasconcelos, M Helena; de São José Nascimento, Maria

    2011-06-01

    Fourteen baicalein and 3,7-dihydroxyflavone derivatives were synthesized and evaluated for their inhibitory activity against the in vitro growth of three human tumor cell lines. The synthetic approaches were based on the reaction with prenyl or geranyl bromide in alkaline medium, followed by cyclization of the respective monoprenylated derivative. Dihydropyranoflavonoids were also obtained by one-pot synthesis, using Montmorillonite K10 clay as catalyst combined with microwave irradiation. In vitro screening of the compounds for cell growth inhibitory activity revealed that the presence of one geranyl group was associated with a remarkable increase in the inhibitory activity. Moreover, for the 3,7-dihydroxyflavone derivatives a marked increase in growth inhibitory effect was also observed for compounds with furan and pyran fused rings. The most active compounds were also studied regarding their effect on cell cycle profile and induction of apoptosis. Overall the results point to the relevant role of the prenylation of flavone scaffold in the growth inhibitory activity of cancer cells.

  7. Involvement of GABAergic non-benzodiazepine sites in the anxiolytic-like and sedative effects of the flavonoid baicalein in mice.

    PubMed

    de Carvalho, Rebeca Santos Marques; Duarte, Filipe Silveira; de Lima, Thereza Christina Monteiro

    2011-08-01

    Baicalein (BA), one of the main flavonoids obtained from the Chinese medicinal herb Scutellaria baicalensis, usually exerts several pharmacological effects. In the central nervous system (CNS), BA exerts a protective effect on neurons against several neuronal insults among other effects, but it is not clear if this effect is due to its metabolite, baicalin. The purpose of the present study was to assess the anxiolytic-like and related properties of BA following its central administration (i.c.v.) in mice. BA (0.02, 0.2pmol) exerted an anxiolytic-like effect at low doses, increasing the time spent in open arms and the head-dipping whereas reducing the stretched-attend postures in the elevated plus-maze. BA also increased the duration of ether-induced sleep without affecting the pentylenetetrazol (PTZ)-induced convulsions. In addition, pretreatment with flumazenil (FMZ), PTZ, dehydroepiandrosterone sulfate (DHEAS), and dl-p-chlorophenilalanine ethyl ester (PCPA) were conducted in order to investigate its mechanism of action. PTZ and DHEAS, but not FMZ or PCPA, antagonized the BA's anxiolytic-like effect. Taken together our results showed that BA, when directly injected into the CNS, promotes anxiolytic-like and sedative effects, pharmacological activities dependent on GABAergic non-benzodiazepine sites but not on the 5-HT system.

  8. Mitigating role of baicalein on lysosomal enzymes and xenobiotic metabolizing enzyme status during lung carcinogenesis of Swiss albino mice induced by benzo(a)pyrene.

    PubMed

    Naveenkumar, Chandrashekar; Raghunandakumar, Subramanian; Asokkumar, Selvamani; Binuclara, John; Rajan, Balan; Premkumar, Thandavamoorthy; Devaki, Thiruvengadam

    2014-06-01

    The lungs mainly serve as a primary site for xenobiotic metabolism and constitute an important defense mechanism against inhalation of carcinogens. Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss albino mice exposed to tobacco-specific carcinogen benzo(a)pyrene [B(a)P] for its ability to mitigate pulmonary carcinogenesis. Here, we report that altered activities/levels of lysosomal enzymes (cathepsin-D, cathepsin-B, acid phosphatase, β-D-galactosidase, β-D-glucuronidase, and β-D-N-acetyl glucosaminidase), phase I biotransformation enzymes (cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase, and NADH-cytochrome b5 reductase), and phase II enzymes (glutathione S-transferase, UDP-glucuronyl transferase, and DT-diaphorase) were observed in the B(a)P-induced mice. Treatment with BE significantly restored back the activities/levels of lysosomal enzymes, phase I and phase II biotransformation enzymes. Moreover, assessment of lysosomal abnormalities by transmission electron microscopic examination revealed that BE treatment effectively counteract B(a)P-induced oxidative damages. Protein expression levels studied by immunohistochemistry, immunofluorescence, and immunoblot analysis of CYP1A1 revealed that BE treatment effectively negate B(a)P-induced upregulated expression of CYP1A1. Further analysis of scanning electron microscopic studies in lung was carried out to substantiate the anticarcinogenic effect of BE. The overall data suggest that BE treatment significantly inhibits lysosomal and microsomal dysfunction, thus revealing its potent anticarcinogenic effect.

  9. Histologic chorioamnionitis: different histologic features at different gestational ages.

    PubMed

    Torricelli, Michela; Voltolini, Chiara; Toti, Paolo; Vellucci, Francesca Letizia; Conti, Nathalie; Cannoni, Alice; Moncini, Irene; Occhini, Rossella; Severi, Filiberto Maria; Petraglia, Felice

    2014-06-01

    The aim of this study was to investigate the rate of the different histological chorioamnionitis (HCA) grade in relation to the gestational age in term and preterm delivery. Three hundred and ninety-two women with singleton pregnancy with spontaneous onset of labor either prematurely or at term, with histologic diagnosis of HCA, were enrolled. Placentas were classified as: deciduitis and/or histologic chorioamnionitis within the membranes (HCA1); amnionitis or inflammation of the chorionic plate without funisitis (HCA2); and histologic chorioamnionitis with funisitis (HCA3). Microbiological culture was performed on both placental and fetal membrane samples. HCA1 was more frequent in women delivering at term than in preterm (p < 0.001). HCA2 was more represented in women delivering between 32 and 36 weeks (p < 0.001) and HCA3 occurred more frequently in those delivering within 32 weeks (p < 0.001). The positive bacterial culture was higher (p = 0.008) in presence of HCA3 in comparison with HCA1 and HCA2. This study showed a significantly different distribution of HCA grades in relation to gestational age at delivery. HCA may represent the expression of different subtending etiologies and may also reflect specific immune competence of gestational tissues at different gestational ages, strengthening as pregnancy advances.

  10. Reordering Histology to Enhance Engagement

    ERIC Educational Resources Information Center

    Amerongen, Helen

    2011-01-01

    In redesigning the preclinical curriculum and shifting from a discipline-based approach to an organ system-based approach, faculty at the University of Arizona College of Medicine in Tucson took the opportunity to restructure the sequence of introductory histology content to make it more engaging and relevant. In this article, the author describes…

  11. [Histology of keratoglobus (author's transl)].

    PubMed

    Knieper, P; Rochels, R; Nover, A

    1980-07-01

    The authors examined four cases of keratoglobus and report here on the histological changes found: degenerative alterations of the epithelium, characteristic changes of Bowman's membrane, such as thinning, detachment and wrinkling, alterations of the stroma and secondary alterations of the Descemet's membrane. These results indicate that keratoglobus is nearly an extreme variant of keratoconus.

  12. Reordering Histology to Enhance Engagement

    ERIC Educational Resources Information Center

    Amerongen, Helen

    2011-01-01

    In redesigning the preclinical curriculum and shifting from a discipline-based approach to an organ system-based approach, faculty at the University of Arizona College of Medicine in Tucson took the opportunity to restructure the sequence of introductory histology content to make it more engaging and relevant. In this article, the author describes…

  13. Histological Stains: A Literature Review and Case Study.

    PubMed

    Alturkistani, Hani A; Tashkandi, Faris M; Mohammedsaleh, Zuhair M

    2015-06-25

    The history of histology indicates that there have been significant changes in the techniques used for histological staining through chemical, molecular biology assays and immunological techniques, collectively referred to as histochemistry. Early histologists used the readily available chemicals to prepare tissues for microscopic studies; these laboratory chemicals were potassium dichromate, alcohol and the mercuric chloride to harden cellular tissues. Staining techniques used were carmine, silver nitrate, Giemsa, Trichrome Stains, Gram Stain and Hematoxylin among others. The purpose of this research was to assess past and current literature reviews, as well as case studies, with the aim of informing ways in which histological stains have been improved in the modern age. Results from the literature review has indicated that there has been an improvement in histopathology and histotechnology in stains used. There has been a rising need for efficient, accurate and less complex staining procedures. Many stain procedures are still in use today, and many others have been replaced with new immunostaining, molecular, non-culture and other advanced staining techniques. Some staining methods have been abandoned because the chemicals required have been medically proven to be toxic. The case studies indicated that in modern histology a combination of different stain techniques are used to enhance the effectiveness of the staining process. Currently, improved histological stains, have been modified and combined with other stains to improve their effectiveness.

  14. Histological Stains: A Literature Review and Case Study

    PubMed Central

    Alturkistani, Hani A; Tashkandi, Faris M; Mohammedsaleh, Zuhair M

    2016-01-01

    The history of histology indicates that there have been significant changes in the techniques used for histological staining through chemical, molecular biology assays and immunological techniques, collectively referred to as histochemistry. Early histologists used the readily available chemicals to prepare tissues for microscopic studies; these laboratory chemicals were potassium dichromate, alcohol and the mercuric chloride to harden cellular tissues. Staining techniques used were carmine, silver nitrate, Giemsa, Trichrome Stains, Gram Stain and Hematoxylin among others. The purpose of this research was to assess past and current literature reviews, as well as case studies, with the aim of informing ways in which histological stains have been improved in the modern age. Results from the literature review has indicated that there has been an improvement in histopathology and histotechnology in stains used. There has been a rising need for efficient, accurate and less complex staining procedures. Many stain procedures are still in use today, and many others have been replaced with new immunostaining, molecular, non-culture and other advanced staining techniques. Some staining methods have been abandoned because the chemicals required have been medically proven to be toxic. The case studies indicated that in modern histology a combination of different stain techniques are used to enhance the effectiveness of the staining process. Currently, improved histological stains, have been modified and combined with other stains to improve their effectiveness. PMID:26493433

  15. Anal anatomy and normal histology.

    PubMed

    Pandey, Priti

    2012-12-01

    The focus of this article is the anatomy and histology of the anal canal, and its clinical relevance to anal cancers. The article also highlights the recent histological and anatomical changes to the traditional terminology of the anal canal. The terminology has been adopted by the American Joint Committee on Cancer, separating the anal region into the anal canal, the perianal region and the skin. This paper describes the gross anatomy of the anal canal, along with its associated blood supply, venous and lymphatic drainage, and nerve supply. The new terminology referred to in this article may assist clinicians and health care providers to identify lesions more precisely through naked eye observation and without the need for instrumentation. Knowledge of the regional anatomy of the anus will also assist in management decisions.

  16. The effects of baicalein or baicalin on the colloidal stability of ZnO nanoparticles (NPs) and toxicity of NPs to Caco-2 cells.

    PubMed

    Li, Yining; Zhang, Cao; Liu, Liangliang; Gong, Yu; Xie, Yixi; Cao, Yi

    2017-09-03

    Recent study suggested that the presence of phytochemicals in food could interact with nanoparticles (NPs) and consequently reduce the toxicity of NPs, which has been attributed to the antioxidant properties of phytochemicals. In this study, we investigated the interactions between ZnO NPs and two flavonoids baicalein (Ba) or baicalin (Bn) as well as the influence of the interactions on the toxicity of ZnO NPs to Caco-2 cells. The antioxidant properties of Ba and Bn were confirmed by DPPH and ABTS assays, with Ba being stronger. However, the presence of Ba or Bn did not significantly affect cytotoxicity, intracellular superoxide or release of inflammatory cytokines of Caco-2 cells after ZnO NP exposure. When Ba was present, the cellular viability of Caco-2 cells after exposure to ZnO NPs was slightly increased, associated with a modest decrease of intracellular Zn ions, but these effects were not statistically different. Ba was more effective than Bn at changing the hydrodynamic sizes, Zeta potential and UV-Vis spectra of ZnO NPs, which indicated that Ba might increase the colloidal stability of NPs. Taken together, the results of the present study indicated that the anti-oxidative phytochemical Ba might only modestly protected Caco-2 cells from the exposure to ZnO NPs associated with an insignificant reduction of the accumulation of intracellular Zn ions. These results also indicated that when assessing the combined effects of NPs and phytochemicals to cells lining gastrointestinal tract, it might be necessary to evaluate the changes of colloidal stability of NPs altered by phytochemicals.

  17. HistoLogical, a computer atlas and drill of histology.

    PubMed

    Alper, E J; Cardasis, C

    1991-01-01

    An educational program has been developed to aid the instruction of Histology, a required course for the first year medical student. The program was developed using SuperCard on an Apple Macintosh IIci computer. It incorporates high quality color images with a hypermedia format, i.e. the student can jump from topic to topic as he/she wishes. The program has an "atlas," which provides information about each image and topic being discussed, and a "drill," which presents to the student a question about an image and provides feedback tailored to the student's answer. In the drill, the student is asked to type in responses to the questions; the answer is judged by text recognition. For each question, feedback is written for the correct answer, incorrect answer, and up to 10 "accessory answers" (answers which might be expected although they are not correct). The faculty of the UMMS Histology course has encouraged the use of this program in this years' course, and evaluation received from faculty and students has been quite positive.

  18. The relationship between premedical coursework in gross anatomy and histology and medical school performance in gross anatomy and histology.

    PubMed

    Forester, Joseph P; McWhorter, David L; Cole, Maria S

    2002-03-01

    Many premedical students enroll in courses whose content will be encountered again during their medical education. Presumably, students believe this practice will lead to improved academic performance in corresponding medical school courses. Therefore, this study was undertaken to determine whether a premedical gross anatomy and/or histology course resulted in increased performance in corresponding medical school courses. A second aim of the study was to examine whether the type of premedical gross anatomy and/or histology course differentially affected medical school performance. A survey that assessed premedical gross anatomy and histology coursework was administered to 440 first-year medical students. The results from this survey showed that students with premedical gross anatomy (n = 236) and/or histology (n = 109) earned significantly more points in the corresponding medical school course than students without the premedical coursework (P < 0.05). Analysis of premedical course types revealed that students who took a gross anatomy course with prosected specimens (n = 35) earned significantly more points that those students without premedical gross anatomy coursework (P < 0.05). The results from this study suggest: 1) premedical gross anatomy and/or histology coursework improves academic performance in corresponding medical school courses, and 2) a premedical gross anatomy course with prosected specimens, a specific type of undergraduate course, significantly improves academic performance in medical gross anatomy.

  19. Staffing benchmarks for histology laboratories.

    PubMed

    Buesa, René J

    2010-06-01

    This article summarizes annual workloads for staff positions and work flow productivity (WFP) values from 247 human pathology, 31 veterinary, and 35 forensic histology laboratories (histolabs). There are single summaries for veterinary and forensic histolabs, but the data from human pathology are divided into 2 groups because of statistically significant differences between those from Spain and 6 Hispano American countries (SpHA) and the rest from the United States and 17 other countries. The differences reflect the way the work is organized, but the histotechnicians and histotechnologists (histotechs) from SpHA have the same task productivity levels as those from any other country (Buesa RJ. Productivity standards for histology laboratories. [YADPA 50,552]). The information is also segregated by groups of histolabs with increasing workloads; this aspect also showed statistical differences. The information from human pathology histolabs other than those from SpHA were used to calculate staffing annual benchmarks for pathologists (from 3700 to 6500 cases depending on the histolab annual workload), pathology assistants (20,000 cases), staff histotechs (9900 blocks), cutting histotechs (15,000 blocks), histotechs doing special procedures (9500 slides if done manually or 15,000 slides with autostainers), dieners (100 autopsies), laboratory aides and transcriptionists (15,000 cases each), and secretaries (20,000 cases). There are also recommendations about workload limits for supervisory staff (lead techs and supervisors) and when neither is required. Each benchmark was related with the productivity of the different tasks they include (Buesa RJ. Productivity standards for histology laboratories. [YADPA 50,552]) to calculate the hours per year required to complete them. The relationship between workload and benchmarks allows the director of pathology to determine the staff needed for the efficient operation of the histolab.

  20. Coeliac disease: the histology report.

    PubMed

    Villanacci, Vincenzo; Ceppa, Paola; Tavani, Enrico; Vindigni, Carla; Volta, Umberto

    2011-03-01

    To this day intestinal biopsy is justly considered the "gold standard" for the diagnosis of coeliac disease (CD). The aim of the authors in setting up these guidelines was to assist pathologists in formulating a more precise morphological evaluation of a duodenal biopsy in the light of clinical and laboratory data, to prepare histological samples with correctly oriented biopsies and in the differential diagnosis with other pathological entities and complications of the disease. A further intention was to promote the conviction for the need of a close collaborative relationship between different specialists namely the concept of a "multidisciplinary team".

  1. [Histology in diagnosis of parasitic diseases].

    PubMed

    Papparella, S

    2004-06-01

    Many pathogenic organisms cause inflammatory lesions and microscopic findings are a useful diagnostic tool for the aetiological diagnosis. However, the histological lesions are limited in respect to many biological agents that can damage the tissues. The histologic hallmark of parasitic diseases is mostly granulomatous inflammation. It is characterized by a focal infiltration of macrophages and epithelioid cells. Many giant cells, lymphocytes, plasma cells, fibroblasts and granulocytes can be found. Agents inducing granulomas include helminths and parasites that replicate intracellularly. Some special stains are utilized in histopathology, for example Giemsa's stain is useful to identify Leishmania. Using specific antibodies, immunohistochemical methods provide an aetiological diagnosis. Sometimes, tissue damage can be immuno-mediated depending on deposit of circulating immunocomplexes or T-lymphocytes involvement rather than by direct parasitic injury. Generally, the lesions which can be observed are respectively vasculitis and inflammatory reactions predominantly composed of mononuclear cells, as observed in many viral or bacterial diseases. In these cases, aetiological diagnosis is improved by in situ-PCR. For microscopic identification of parasites in tissues it is also important to be familiar with the kind of parasites most likely to be found in the examined tissue and in that particular host. Localization of parasites can induce hyperplastic-neoplastic lesions. Many parasites have been associated with the occurrence of specific types of neoplasms, but the mechanisms involved are still not well defined. Chronic inflammation and/or immune suppression seem to induce neoplastic proliferation.

  2. Classification of Tumor Histology via Morphometric Context.

    PubMed

    Chang, Hang; Borowsky, Alexander; Spellman, Paul; Parvin, Bahram

    2013-06-23

    Image-based classification of tissue histology, in terms of different components (e.g., normal signature, categories of aberrant signatures), provides a series of indices for tumor composition. Subsequently, aggregation of these indices in each whole slide image (WSI) from a large cohort can provide predictive models of clinical outcome. However, the performance of the existing techniques is hindered as a result of large technical and biological variations that are always present in a large cohort. In this paper, we propose two algorithms for classification of tissue histology based on robust representations of morphometric context, which are built upon nuclear level morphometric features at various locations and scales within the spatial pyramid matching (SPM) framework. These methods have been evaluated on two distinct datasets of different tumor types collected from The Cancer Genome Atlas (TCGA), and the experimental results indicate that our methods are (i) extensible to different tumor types; (ii) robust in the presence of wide technical and biological variations; (iii) invariant to different nuclear segmentation strategies; and (iv) scalable with varying training sample size. In addition, our experiments suggest that enforcing sparsity, during the construction of morphometric context, further improves the performance of the system.

  3. When machine vision meets histology: A comparative evaluation of model architecture for classification of histology sections☆

    PubMed Central

    Zhong, Cheng; Han, Ju; Borowsky, Alexander; Parvin, Bahram; Wang, Yunfu; Chang, Hang

    2016-01-01

    Classification of histology sections in large cohorts, in terms of distinct regions of microanatomy (e.g., stromal) and histopathology (e.g., tumor, necrosis), enables the quantification of tumor composition, and the construction of predictive models of genomics and clinical outcome. To tackle the large technical variations and biological heterogeneities, which are intrinsic in large cohorts, emerging systems utilize either prior knowledge from pathologists or unsupervised feature learning for invariant representation of the underlying properties in the data. However, to a large degree, the architecture for tissue histology classification remains unexplored and requires urgent systematical investigation. This paper is the first attempt to provide insights into three fundamental questions in tissue histology classification: I. Is unsupervised feature learning preferable to human engineered features? II. Does cellular saliency help? III. Does the sparse feature encoder contribute to recognition? We show that (a) in I, both Cellular Morphometric Feature and features from unsupervised feature learning lead to superior performance when compared to SIFT and [Color, Texture]; (b) in II, cellular saliency incorporation impairs the performance for systems built upon pixel-/patch-level features; and (c) in III, the effect of the sparse feature encoder is correlated with the robustness of features, and the performance can be consistently improved by the multi-stage extension of systems built upon both Cellular Morphmetric Feature and features from unsupervised feature learning. These insights are validated with two cohorts of Glioblastoma Multiforme (GBM) and Kidney Clear Cell Carcinoma (KIRC). PMID:27644083

  4. Histology of the first fish

    USGS Publications Warehouse

    Smith, M.P.; Sansom, I.J.; Repetski, J.E.

    1996-01-01

    THE first description of Anatolepis Bockelie & Fortey was from early Ordovician sediments of Ny Friesland, Spitsbergen1,2, but the genus is now known from many localities in North America and Greenland, ranging in age from the Late Cambrian period to the Early Ordovician3-6. Although initially interpreted as an agnathan fish2,3 that predated other representatives7, this has been widely disputed because the available histological data were unconvincing6,8-10 and the scales fell outside the known morphological range of other accepted early vertebrates9-11. Further doubt was cast upon the vertebrate affinity of Anatolepis when specimens from East Greenland were interpreted as the cuticular fragments of aglaspid arthropods6, although this interpretation has also been refuted12. Here we report on the morphology and histology of large collections of Anatolepis, and demonstrate the presence of dentine, a tissue unique to vertebrates, confirming that the taxon is both a vertebrate and the oldest known fish.

  5. Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

    SciTech Connect

    Chandrashekar, Naveenkumar; Selvamani, Asokkumar; Subramanian, Raghunandhakumar; Pandi, Anandakumar; Thiruvengadam, Devaki

    2012-05-15

    The objective of the present study is to investigate the therapeutic efficacy of baicalein (BE) on inflammatory cytokines, which is in line with tumor invasion factors and antioxidant defensive system during benzo(a)pyrene [B(a)P] (50 mg/kg body weight) induced pulmonary carcinogenesis in Swiss albino mice. After experimental period, increased levels of total and differential cell count in bronchoalveolar lavage fluid were observed. Accompanied by marked increase in immature mast cell by toluidine blue staining and mature mast cell by safranin–alcian blue staining in B(a)P-induced lung cancer bearing animals. Protein expression levels studied by immunohistochemistry and immunoblot analysis of cytokines such as tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were also found to be significantly increased in lung cancer bearing animals. B(a)P-exposed mice lung exhibits activated expression of nuclear transcription factor kappa-B as confirmed by immunofluorescence and immunoblot analysis. Administration of BE (12 mg/kg body weight) significantly counteracted all the above deleterious changes. Moreover, assessment of tumor invasion factors on protein levels by immunoblot and mRNA expression levels by RT-PCR revealed that BE treatment effectively negates B(a)P-induced upregulated expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and cyclo-oxygenase-2. Further analysis of lipid peroxidation markers such as thiobarbituric acid reactive substances, hydro-peroxides and antioxidants such as glutathione-S-transferase and reduced glutathione in lung tissue was carried out to substantiate the antioxidant effect of BE. The chemotherapeutic effect observed in the present study is attributed to the potent anti-inflammatory and antioxidant potential by BE against pulmonary carcinogenesis. -- Highlights: ► BE treatment protects from inflammatory cells and mast-cells accumulation in lungs. ► BE altered the expressions of TNF

  6. Baicalein inhibition of oxidative-stress-induced apoptosis via modulation of ERKs activation and induction of HO-1 gene expression in rat glioma cells C6

    SciTech Connect

    Chen, Y.-C. . E-mail: yc3270@tmu.edu.tw; Chow, J.-M.; Lin, C.-W.; Wu, C.-Y.; Shen, S.-C.

    2006-10-15

    In the present study, we examined the protective mechanism of baicalein (BE) and its glycoside, baicalin (BI), on hydrogen-peroxide (H{sub 2}O{sub 2})-induced cell death in rat glioma C6 cells. Results of the MTT assay, LDH release assay, and morphological observation showed that H{sub 2}O{sub 2} addition reduced the viability of C6 cells, and this was prevented by the addition of BE but not BI. Incubation of C6 cells with BE significantly decreased the intracellular peroxide level induced by H{sub 2}O{sub 2} according to flow cytometric analysis using DCHF-DA as a fluorescent substrate. Suppression of H{sub 2}O{sub 2}-induced apoptotic events including DNA ladders, hypodiploid cells, and activation of caspases 3, 8, and, 9 by BE but not BI was identified in C6 cells. The cytotoxicity and phosphorylation of ERK proteins induced by H{sub 2}O{sub 2} were blocked by the ERK inhibitor PD98059. Catalase addition prevented H{sub 2}O{sub 2}-induced ROS production, ERKs protein phosphorylation, and cell death, and BE dose-dependently inhibited H{sub 2}O{sub 2}-induced ERK protein phosphorylation in C6 cells. These data suggest that ROS-scavenging activity is involved in BE prevention of H{sub 2}O{sub 2}-induced cell death via blocking ERKs activation. Additionally, BE but not BI induced heat shock protein 32 (HSP32; HO-1) protein expression in both time- and dose-dependent manners, but not heme oxygenase 2 (HO-2), heat shock protein 70 (HSP70), or heat shock protein 90 (HSP90) protein expression. In the absence of H{sub 2}O{sub 2}, BE induces ERKs protein phosphorylation, and HO-1 protein expression induced by BE was blocked by the addition of cycloheximide, actinomycin D, and the ERK inhibitor PD98059. The addition of the HO inhibitor ZnPP inhibited the protective effect of BE against H{sub 2}O{sub 2}-induced cytotoxicity in C6 cells according to the MTT assay and apoptotic morphology under microscopic observation, accompanied by blocking the ROS-scavenging activity of BE

  7. A catenary model to study transport and conjugation of baicalein, a bioactive flavonoid, in the Caco-2 cell monolayer: demonstration of substrate inhibition.

    PubMed

    Sun, Huadong; Zhang, Li; Chow, Edwin Chiu Yuen; Lin, Ge; Zuo, Zhong; Pang, K Sandy

    2008-07-01

    The transport and metabolism of baicalein (Ba) was studied in vitro and in Caco-2 cells. Protein binding of Ba with Caco-2 lysate showed that Ba was bound to two classes of sites: a higher affinity, lower capacity site (K(A1) = 27.6 +/- 4.7 microM(-1), n(1) = 10.6 +/- 0.6 nmol/mg) and lower affinity, higher capacity site (K(A2) = 0.015 +/- 0.0013 microM(-1), n(2) = 413 +/- 21 nmol/mg). Incubation studies of Ba with Caco-2 lysate showed substrate inhibition of both glucuronidation and sulfation, with K(m) values of 0.14 +/- 0.034 and 0.015 +/- 0.0053 microM, and K(I) values of 6.75 +/- 1.70 and 0.37 +/- 0.16 microM, respectively. In the Caco-2 monolayer, Ba (8-47 microM) displayed good apparent permeabilities (P(app)) across the membrane; P(app) was found to be increased with elevated loading concentration in both the absorptive and secretory directions. However, the efflux ratio was less than unity, negating the involvement of apical efflux transporters. The concentration ratios of Ba sulfate (BS) and glucuronide (BG) decreased with increased loading Ba concentration, suggesting that BS and BG are apically excreted via transporters, likely breast cancer resistance protein and multidrug resistance-associated protein 2, respectively. Data fit to the catenary model, composed of basolateral, cellular, and apical compartments, showed a low cellular unbound fraction (0.0019 +/- 0.00018), a high passive diffusion clearance (0.012 +/- 0.00029 ml/min/mg), and substrate inhibition, with sulfation being more readily saturated and inhibited than glucuronidation, as evidenced by smaller K(m) value (0.35 +/- 0.078 versus 1.95 +/- 0.57 microM) and K(I) value (0.58 +/- 0.20 versus 7.90 +/- 1.10 microM); these patterns paralleled those observed in the lysate incubation studies. The results showed that the catenary model aptly predicts substrate inhibition kinetics and offers significant and mechanistic insight into the transport and atypical metabolism of drugs in the Caco-2

  8. Robust Cell Segmentation for Histological Images of Glioblastoma

    PubMed Central

    Kong, Jun; Zhang, Pengyue; Liang, Yanhui; Teodoro, George; Brat, Daniel J.; Wang, Fusheng

    2016-01-01

    Glioblastoma (GBM) is a malignant brain tumor with uniformly dismal prognosis. Quantitative analysis of GBM cells is an important avenue to extract latent histologic disease signatures to correlate with molecular underpinnings and clinical outcomes. As a prerequisite, a robust and accurate cell segmentation is required. In this paper, we present an automated cell segmentation method that can satisfactorily address segmentation of overlapped cells commonly seen in GBM histology specimens. This method first detects cells with seed connectivity, distance constraints, image edge map, and a shape-based voting image. Initialized by identified seeds, cell boundaries are deformed with an improved variational level set method that can handle clumped cells. We test our method on 40 histological images of GBM with human annotations. The validation results suggest that our cell segmentation method is promising and represents an advance in quantitative cancer research.

  9. Multi-class texture analysis in colorectal cancer histology

    NASA Astrophysics Data System (ADS)

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Bianconi, Francesco; Melchers, Susanne M.; Schad, Lothar R.; Gaiser, Timo; Marx, Alexander; Zöllner, Frank Gerrit

    2016-06-01

    Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no published results on multiclass texture separation. In this paper we present a new dataset of 5,000 histological images of human colorectal cancer including eight different types of tissue. We used this set to assess the classification performance of a wide range of texture descriptors and classifiers. As a result, we found an optimal classification strategy that markedly outperformed traditional methods, improving the state of the art for tumour-stroma separation from 96.9% to 98.6% accuracy and setting a new standard for multiclass tissue separation (87.4% accuracy for eight classes). We make our dataset of histological images publicly available under a Creative Commons license and encourage other researchers to use it as a benchmark for their studies.

  10. Multi-class texture analysis in colorectal cancer histology

    PubMed Central

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Bianconi, Francesco; Melchers, Susanne M.; Schad, Lothar R.; Gaiser, Timo; Marx, Alexander; Zöllner, Frank Gerrit

    2016-01-01

    Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no published results on multiclass texture separation. In this paper we present a new dataset of 5,000 histological images of human colorectal cancer including eight different types of tissue. We used this set to assess the classification performance of a wide range of texture descriptors and classifiers. As a result, we found an optimal classification strategy that markedly outperformed traditional methods, improving the state of the art for tumour-stroma separation from 96.9% to 98.6% accuracy and setting a new standard for multiclass tissue separation (87.4% accuracy for eight classes). We make our dataset of histological images publicly available under a Creative Commons license and encourage other researchers to use it as a benchmark for their studies. PMID:27306927

  11. Oral features in Apert syndrome: a histological investigation.

    PubMed

    Surman, T L; Logan, R M; Townsend, G C; Anderson, P J

    2010-02-01

    The number of publications on the oral features in Apert syndrome is limited. The present study investigated dental tissues in Apert syndrome histologically, to determine the nature and extent of anomalies, to provide some insight into the nature of the condition, and to explain how observed anomalies may affect the dental management of individuals with Apert syndrome. Extracted primary and secondary teeth were collected from patients with Apert who had attended the Australian Craniofacial Unit, Adelaide, South Australia. The total study sample comprised 13 individuals, aged from 14 to 21 , with nine men and four women. A total of 40 teeth were available for histological examination (the number belonging to each individual varied from 2 to 5 per patient). The teeth were sectioned longitudinally, and one-half of each tooth underwent decalcification. Sections were stained with H&E for routine histological examination. Ground sections were prepared from undecalcified tooth halves. Histological assessment of the dental hard tissues revealed an intact enamel and dentinal structure but some irregularities were noted in the region of the dentino-enamel junction (DEJ), which could affect caries progression and also make dental management more difficult. This study identified histological anomalies of the DEJ of Apert syndrome teeth. An improved appreciation of the nature and extent of dental anomalies in Apert syndrome should assist clinicians when undertaking management of affected individuals.

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

    PubMed

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

    2017-09-01

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

  13. Histologic analysis of postmeniscectomy osteonecrosis.

    PubMed

    Higuchi, Hiroshi; Kobayashi, Yasukazu; Kobayashi, Atsushi; Hatayama, Kazuhisa; Kimura, Masashi

    2013-05-01

    Bone marrow signal changes on magnetic resonance imaging (MRI) after meniscectomy have been reported as evidence of postmeniscectomy osteonecrosis, but this pathology is unclear. We conducted a study to follow-up cases with bone marrow signal changes on MRI after meniscectomy and investigate the pathology of underlying lesions. Of 136 patients with no presurgical evidence of osteonecrosis, 29 had juxta-articular bone marrow signal changes on MRI after arthroscopic meniscectomy and subsequently underwent conservative therapy. In 6 of these 29 patients, clinical symptoms and radiographic changes began deteriorating. Based on the Koshino classification, 4 of the 6 patients had Stage-2 knee osteonecrosis and 2 had Stage-3. Arthroscopic and pathologic examinations were performed. Arthroscopic findings were fibrillation (all 6 cases), fissuring (4), ulceration (2), and eburnation (2). Histologic analysis confirmed subchondral bone fractures in all 6 cases, but osteonecrotic lesions were detected only in 2 cases with obvious radiologic deterioration. Postmeniscectomy osteonecrosis might result from subchondral bone fractures. Fracture healing is worse in patients with comorbidities than in those without it; comorbidities might be a risk factor for osteonecrosis.

  14. Tumor tissue protein signatures reflect histological grade of breast cancer

    PubMed Central

    Skoog, Petter; Ohlsson, Mattias; Fernö, Mårten; Rydén, Lisa; Borrebaeck, Carl A. K.

    2017-01-01

    Histological grade is one of the most commonly used prognostic factors for patients diagnosed with breast cancer. However, conventional grading has proven technically challenging, and up to 60% of the tumors are classified as histological grade 2, which represents a heterogeneous cohort less informative for clinical decision making. In an attempt to study and extend the molecular puzzle of histologically graded breast cancer, we have in this pilot project searched for additional protein biomarkers in a new space of the proteome. To this end, we have for the first time performed protein expression profiling of breast cancer tumor tissue, using recombinant antibody microarrays, targeting mainly immunoregulatory proteins. Thus, we have explored the immune system as a disease-specific sensor (clinical immunoproteomics). Uniquely, the results showed that several biologically relevant proteins reflecting histological grade could be delineated. In more detail, the tentative biomarker panels could be used to i) build a candidate model classifying grade 1 vs. grade 3 tumors, ii) demonstrate the molecular heterogeneity among grade 2 tumors, and iii) potentially re-classify several of the grade 2 tumors to more like grade 1 or grade 3 tumors. This could, in the long-term run, lead to improved prognosis, by which the patients could benefit from improved tailored care. PMID:28650989

  15. Tumor tissue protein signatures reflect histological grade of breast cancer.

    PubMed

    Skoog, Petter; Ohlsson, Mattias; Fernö, Mårten; Rydén, Lisa; Borrebaeck, Carl A K; Wingren, Christer

    2017-01-01

    Histological grade is one of the most commonly used prognostic factors for patients diagnosed with breast cancer. However, conventional grading has proven technically challenging, and up to 60% of the tumors are classified as histological grade 2, which represents a heterogeneous cohort less informative for clinical decision making. In an attempt to study and extend the molecular puzzle of histologically graded breast cancer, we have in this pilot project searched for additional protein biomarkers in a new space of the proteome. To this end, we have for the first time performed protein expression profiling of breast cancer tumor tissue, using recombinant antibody microarrays, targeting mainly immunoregulatory proteins. Thus, we have explored the immune system as a disease-specific sensor (clinical immunoproteomics). Uniquely, the results showed that several biologically relevant proteins reflecting histological grade could be delineated. In more detail, the tentative biomarker panels could be used to i) build a candidate model classifying grade 1 vs. grade 3 tumors, ii) demonstrate the molecular heterogeneity among grade 2 tumors, and iii) potentially re-classify several of the grade 2 tumors to more like grade 1 or grade 3 tumors. This could, in the long-term run, lead to improved prognosis, by which the patients could benefit from improved tailored care.

  16. Comparative histology of pineal calcification.

    PubMed

    Vígh, B; Szél, A; Debreceni, K; Fejér, Z; Manzano e Silva, M J; Vígh-Teichmann, I

    1998-07-01

    The pineal organ (pineal gland, epiphysis cerebri) contains several calcified concretions called "brain sand" or acervuli (corpora arenacea). These concretions are conspicuous with imaging techniques and provide a useful landmark for orientation in the diagnosis of intracranial diseases. Predominantly composed of calcium and magnesium salts, corpora arenacea are numerous in old patients. In smaller number they can be present in children as well. The degree of calcification was associated to various diseases. However, the presence of calcified concretions seems not to reflect a specific pathological state. Corpora arenacea occur not only in the actual pineal tissue but also in the leptomeninges, in the habenular commissure and in the choroid plexus. Studies with the potassium pyroantimonate (PPA) method on the ultrastructural localization of free calcium ions in the human pineal, revealed the presence of calcium alongside the cell membranes, a finding that underlines the importance of membrane functions in the production of calcium deposits. Intrapineal corpora arenacea are characterized by a surface with globular structures. Meningeal acervuli that are present in the arachnoid cover of the organ, differ in structure from intrapineal ones and show a prominent concentric lamination of alternating dark and light lines. The electron-lucent lines contain more calcium than the dark ones. There is a correlation between the age of the subject and the number of layers in the largest acervuli. This suggests that the formation of these layers is connected to circannual changes in the calcium level of the organ. The histological organization of the human pineal is basically the same as that of mammalian experimental animals. Pineal concretions present in mammalian animal species are mainly of the meningeal type. Meningeal cells around acervuli contain active cytoplasmic organelles and exhibit alkaline phosphatase reaction in the rat and mink, an indication of a presumable

  17. Inframammary fold: a histologic reappraisal.

    PubMed

    Muntan, C D; Sundine, M J; Rink, R D; Acland, R D

    2000-02-01

    The inframammary fold is a defining element in the shape and structure of the female breast. It should be preserved whenever possible in ablative procedures and recreated accurately when the breast is reconstructed after mastectomy. To date, no accurate anatomic description of this essential structure exists. Previous studies have suggested that the fold is produced by a supporting ligament running from the dermis in the fold region to a variety of locations on the rib cage. This clinic's experience with mastectomy, augmentation mammaplasty, and breast reconstruction does not support the existence of a ligamentous structure. To define the structure of the inframammary fold, 10 female and 2 male cadavers were studied. The anterior chest wall was removed en bloc and frozen in orthostatic position. Parasagittal sections were made of the inframammary fold with the chest wall intact. After decalcification of the ribs and routine histologic preparation, thin sections were stained with Gomori's trichrome. On light microscopic examination, no demonstrable ligamentous structure of dense regular connective tissue could be identified in the fold region in any of the 12 specimens. Superficial and deep fascial layers were uniformly observed anterior to the pectoralis major and serratus anterior muscles. The superficial fascia was connected to the dermis in the fold region in a variety of configurations. In some cases, the deep fascia fused with the superficial fascia and dermis at the fold level. In other cases, bundles of collagen fibers arising from the superficial fascial layer were found to insert into the dermis at the inframammary fold, slightly inferior to it, or both. These bundles were observed consistently in sections from the sternum to the middle axillary line. They were distinct from Cooper's suspensory ligaments, which are seen more superiorly in the glandular tissue.

  18. Productivity standards for histology laboratories.

    PubMed

    Buesa, René J

    2010-04-01

    The information from 221 US histology laboratories (histolabs) and 104 from 24 other countries with workloads from 600 to 116 000 cases per year was used to calculate productivity standards for 23 technical and 27 nontechnical tasks and for 4 types of work flow indicators. The sample includes 254 human, 40 forensic, and 31 veterinary pathology services. Statistical analyses demonstrate that most productivity standards are not different between services or worldwide. The total workload for the US human pathology histolabs averaged 26 061 cases per year, with 54% between 10 000 and less than 30 000. The total workload for 70% of the histolabs from other countries was less than 20 000, with an average of 15 226 cases per year. The fundamental manual technical tasks in the histolab and their productivity standards are as follows: grossing (14 cases per hour), cassetting (54 cassettes per hour), embedding (50 blocks per hour), and cutting (24 blocks per hour). All the other tasks, each with their own productivity standards, can be completed by auxiliary staff or using automatic instruments. Depending on the level of automation of the histolab, all the tasks derived from a workload of 25 cases will require 15.8 to 17.7 hours of work completed by 2.4 to 2.7 employees with 18% of their working time not directly dedicated to the production of diagnostic slides. This article explains how to extrapolate this productivity calculation for any workload and different levels of automation. The overall performance standard for all the tasks, including 8 hours for automated tissue processing, is 3.2 to 3.5 blocks per hour; and its best indicator is the value of the gross work flow productivity that is essentially dependent on how the work is organized. This article also includes productivity standards for forensic and veterinary histolabs, but the staffing benchmarks for histolabs will be the subject of a separate article. Copyright 2010 Elsevier Inc. All rights reserved.

  19. [Calcifying periarthropathy (radiologic-histological synopsis, terminology)].

    PubMed

    Dihlmann, W

    1981-01-01

    On the basis of a case of radiologically and histologically investigated calcifying periarthropathy in the tendon of the glutaeus medius muscle the histological appearance and the pathogenesis of pain associated with this process is considered. The transformation of tendon tissue into fibrous cartilage is emphasized.

  20. Comparative research on stability of baicalin and baicalein administrated in monomer and total flavonoid fraction form of Radix scutellariae in biological fluids in vitro.

    PubMed

    Feng, Zhiqiang; Zhou, Jie; Shang, Xueying; Kuang, Guojun; Han, Jian; Lu, Liping; Zhang, Lei

    2017-12-01

    Baicalin (BL) and baicalein (B) as the major flavonoids of Scutellaria baicalensis Georgi (Lamiaceae) have been investigated intensively, and shown to possess a multitude of pharmacological activities. This study systematically evaluates the stability of BL and B in monomer and total flavonoid fraction (FSR) form in vitro, and further studies whether the protective measures are effective to make B and BL stable enough to meet the requirement of quantitative analysis in various biological samples. The stability of BL and B was evaluated by investigating the influence factors such as pH (2.0, 3.0, 4.5, 6.8, 7.4 and 9.0), temperature (4, 25 and 40 °C), antioxidant (vitamin C and Na2SO3) and sunlight. After the protective measures were taken, stability of BL and B in plasma, urine and tissue homogenates was evaluated through post-preparative stability (stored at 4 °C for 24 h), three freeze-thaw cycles stability and long-term stability test (stored in refrigerator at -20 °C for 15 days). In addition, by comparing the degradation parameters of BL and B obtained from the monomer administration group with those of the FSR administration group, drug-drug interaction of coexistent components in FSR on the stability of BL and B was discussed. The degradation of BL and B was both pH- and temperature-dependent with their correlation coefficents for first-order kinetics equation larger than 0.99, and acidic environment (pH 2-4.5), lower temperature (<4 °C) and acidic antioxidant (e.g. vitamin C) were conducive to stabilize B and BL. Furthermore, coexistent components in FSR were proved to have function on inhibiting the degradation of BL and B in our study for the first time, which was characteristic of prolonging their biological half-life (t1/2) significantly, e.g., from 2.89 h to indefinite for BL (pH 6.8, 25 °C), from 2.63 h to 4.48 h for B (pH 6.8, 25 °C) and so on. Antioxidant of Na2SO3 could inhibit the degradation of BL with t1/2 increasing

  1. A revised method for the preparation of dry bone samples used in histological examination: Five simple steps.

    PubMed

    García-Donas, J G; Dalton, A; Chaplin, I; Kranioti, E F

    2017-07-15

    Histology of dry bone tissue has many scientific applications. The histological analysis of bone requires the production of good quality thin sections. Many researchers have developed new histological techniques and/or they have refined existing ones. In this paper, we describe a revision of histological techniques for obtaining thin sections from modern dry bone. The method is easy to apply and the equipment required is commonly found in a histology laboratory. In comparison to other techniques presented in the literature, this adapted method reduces the number of consumables and steps, thereby improving the efficiency and cost-effectiveness of the procedure. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. Are histological alterations observed in the gallbladder precancerous lesions?

    PubMed Central

    Meirelles-Costa, Adriana Lúcia Agnelli; Bresciani, Claudio José Caldas; Perez, Rodrigo Oliva; Bresciani, Barbara Helou; Siqueira, Sheila Aparecida C.; Cecconello, Ivan

    2010-01-01

    INTRODUCTION Gallbladder cancer, which is characterized by rapid progression and a poor prognosis, is a complex disease to treat. Unfortunately, little is known currently about its etiology or pathogenesis. A better understanding of its carcinogenesis and determining risk factors that lead to its development could help improve the available treatment options. METHOD Based on this better understanding, the histological alterations (such as acute cholecystitis, adenomyomatosis, xanthogranulomatous cholecystitis, polyps, pyloric metaplasia, intestinal metaplasia, dysplasia, cancer and others) in gallbladders from 1,689 patients who underwent laparoscopic cholecystectomy for cholecystolithiasis were analyzed. The association of these gallbladder histological alterations with clinical data was studied. RESULTS Gender analysis revealed a greater incidence of inflammatory changes in males, while dysplasia and cancer were only found in women. The incidence of cholesterolosis was greater in the patients 60 years of age and under, and the incidence of adenomyomatosis and gangrene was greater in the elderly patients. A progressive increase in the average age was observed as alterations progressed through pyloric metaplasia, intestinal metaplasia, dysplasia and then cancer, suggesting that the metaplasia-dysplasia-carcinoma sequence may occur in gallbladder cancer. Gallbladder histological alterations were also observed in asymptomatic patients. CONCLUSION The results of this study suggest that there could be an association between some histological alterations of gallbladder and cancer, and they also suggest that the metaplasia-dysplasia-carcinoma sequence could in fact be true in the case of gallbladder cancer. Nevertheless, further studies directed towards a perfect understanding of gallbladder carcinogenesis are required. PMID:20186297

  3. Accuracy of Faecal Immunochemical Test to Predict Endoscopic and Histological Healing in Ulcerative Colitis: A Prospective Study Based on Validated Histological Scores.

    PubMed

    Shi, Hai Yun; Chan, Francis K L; Chan, Anthony W H; Higashimori, Akira; Kyaw, Moe; Ching, Jessica Y L; Luk, Arthur K C; Wong, Sunny H; Wu, Justin C Y; Sung, Joseph J Y; Ng, Siew C

    2017-09-01

    Endoscopic and histological healing are associated with improved clinical outcomes in ulcerative colitis [UC]. We aimed to investigate the predictive value of faecal immunochemical test [FIT] for endoscopic and histological healing in UC. We measured quantitative FIT and faecal calprotectin [FC] in 140 consecutive UC patients who underwent colonoscopy. We assessed the diagnostic accuracy of FIT for predicting endoscopic healing using the Mayo endoscopic subscore [MES 0/1] and for histological healing using the Geboes score [< 2.0] and Nancy index [grade ≤ 1]. The predictive abilities of FIT were compared with those of FC. FIT had an area under the curve [AUC] of 0.77 (95% confidence interval [CI] 0.67-0.86, p < 0.001) for endoscopic healing, an AUC of 0.77 [95% CI 0.67-0.86, p < 0.001] using the Geboes score, and 0.77 [95% CI 0.66-0.85, p < 0.001] using the Nancy Index for histological healing. The AUC of FIT was comparable to that of FC for endoscopic healing [p = 0.773] and histological healing [p = 0.767-0.960], and was comparable to colonoscopy for histological healing [p = 0.384-0.673]. FIT < 50 ng/ml predicted endoscopic healing with a sensitivity, specificity, and positive predictive value [PPV] of 72%, 68%, and 82%, respectively, and for histological healing with a sensitivity, specificity, and PPV of 73-75%, 67%, and 78-80%, respectively. Combining FIT with FC led to a higher specificity [90%] for histological healing. Over 85% of patients with FIT < 50 ng/ml and FC < 50 μg/g achieved histological healing. FIT is highly sensitive and accurate to predict endoscopic and histological healing in UC. It represents a promising non-invasive tool for monitoring mucosal healing in UC.

  4. Histologic progression in non-hodgkin's lymphoma

    SciTech Connect

    Hubbard, S.M.; Chabner, B.A.; DeVita, V.T., Jr.; Simon, R.; Berard, C.W.; Jones, R.B.; Garvin, A.J.; Canellos, G.P.; Osborne, C.K.; Young, R.C.

    1982-02-01

    The clinical course and biopsy specimens from 515 consecutive non-Hodgkin's lymphoma patients was evaluated retrospectively in an attempt to determine the clinical importance of documented changes in histology over time. Two-hundred and five of these patients has an initial diagnosis of nodular lymphoma and were reviewed for this anaysis. Sixty-three underwent a repeat biopsy greater than 6 mo after initial diagnosis. In 23 patients, these repeat biopsies revealed a change in histology to a diffuse pattern and/or a change to a larger ''histiocytic'' cell type, while repeat biopsies for the other 40 (63%) disclosd persistence of a nodular pattern and no clear change in basic cell type. Progression from nodular lymphoma to diffuse histiocytic, mixed, or undifferentiated types of lymphomas of Rappaport was found in repeate biopsies obtained from 19 patients (30%). Prognosis for survival following a biopsy that demonstrated histologic change was related to the histology demonstrated at the most recent biopsy and to the response to subsequent drug treatment. Survival following repeat biopsy for these 19 patients was significantly shorter than for the 40 patients whose histology remained nodular (p < 0.001). However, attainment of a complete remission with intensive combination chemotherapy was associated with prolonged survival in eight patients and prolonged disease-free survival in one patient. Since prior treatment may compromise the ability to achieve a complete response to chemotherapy in patients with nodular lymphoma who develop an aggressive diffuse histology, the likelihood of histologic progression must be considered in the design of future clinical trials in nodular lymphoma. Histologic progression does not preclude attainment of a complete response to intensive chemotherapy.

  5. Graphs and Grammars for Histology: An Introduction

    PubMed Central

    Prewitt, Judith M. S.

    1979-01-01

    The invention of the microscope disclosed a whole new world, that of the hitherto invisibly small. Histologic evidence as revealed by the microscope has become a cornerstone of medical diagnosis, and efforts are now being made to lay foundations so that the medical visual information processing burden can be alleviated significantly by cost-effective automation. This paper lays image processing foundations by presenting a graph-theoretic and syntactic model for the analysis of histologic patterns, and presents results to date.

  6. [Histological findings in an irradiated choroidal melanoma].

    PubMed

    Koinzer, S; Hasselbach, H; Bräsen, J H; Leuschner, I; Roider, J

    2011-06-01

    Histological findings of choroidal melanomas after proton beam irradiation have been reported for complicated cases after enucleation. We present specimens of a tumor after transretinal probe excision. One year after irradiation, the biopsy was examined histologically. The specimens showed pigmented, spindle-shaped cells staining positively for Melan-A and HMB-45. Ki-67 showed low proliferation. Caspase-3 staining was normal. The melanoma still contained vital and even single proliferating cells, but regressed afterwards without additional therapy.

  7. Chondrosarcoma: correlation of radiological and histological grade

    SciTech Connect

    Rosenthal, D.I.; Schiller, A.L.; Mankin, H.J.

    1984-01-01

    The radiographic and CT appearance of 20 cases of chondrosarcoma were correlated with histological grade and type of matrix. Features which were useful in predicting histological grade included 1) margins between bone and tumor (radiograph), 2) morphology of calcification (radiograph, CT), 3) distribution of calcification within the lesion (radiograph, CT), 4) pattern of tumor growth within soft tissues (CT), and 5) presence of necrosis (CT). Tumor/soft-tissue margins were usually well defined on the CT scan regardless of grade.

  8. Diagnostic dry bone histology in human paleopathology.

    PubMed

    de Boer, H H Hans; Van der Merwe, A E Lida

    2016-10-01

    Paleopathology is the study of trauma and disease as may be observed in ancient (human) remains. In contrast to its central role in current medical practice, microscopy plays a rather modest role in paleopathology. This is at least partially due to the differences between fresh and decomposed (i.e., skeletonized or "dry bone") tissue samples. This review discusses these differences and describes how they affect the histological analysis of paleopathological specimens. First, we provide a summary of some general challenges related to the histological analysis of palaeopathological specimens. Second, the reader is introduced in bone tissue histology and bone tissue dynamics. The remainder of the paper is dedicated to the diagnostic value of dry bone histology. Its value and limitations are illustrated by comparing several well-studied paleopathological cases with similar contemporary, clinical cases. This review illustrates that due to post-mortem loss of soft tissue, a limited number of disorders display pathognomonic features during histological analysis of skeletonized human remains. In the remainder of cases, histology may help to narrow down the differential diagnosis or is diagnostically unspecific. A comprehensive, multidisciplinary diagnostic approach therefore remains essential. Clin. Anat. 29:831-843, 2016. © 2016 Wiley Periodicals, Inc.

  9. Echocardiographic versus histologic findings in Marfan syndrome.

    PubMed

    Gu, Xiaoyan; He, Yihua; Li, Zhian; Han, Jiancheng; Chen, Jian; Nixon, J V Ian

    2015-02-01

    This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery. We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients. Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The echocardiographic findings in 18 patients with mitral involvement included mitral prolapse in 15. Of 11 patients with moderate or severe mitral regurgitation as determined by echocardiography, 4 underwent mitral valve repair and 7 mitral valve replacement. Histologic findings among mitral valve replacement patients showed thickened valve tissue and myxomatous degeneration. Tricuspid involvement was seen echocardiographically in 8 patients, all of whom had tricuspid prolapse. Two patients had severe tricuspid regurgitation, and both underwent repair. Both mitral and tricuspid involvement were seen echocardiographically in 7 patients. Among the 73 patients undergoing cardiac surgery for Marfan syndrome, 66 had moderate or severe aortic regurgitation, although their valves manifested few histologic changes. Eighteen patients had mitral involvement (moderate or severe mitral regurgitation, prolapse, or both), and 8 had tricuspid involvement. Mitral valves were most frequently found to have histologic changes, but the tricuspid valve was invariably involved.

  10. Bone marrow histology in monoclonal macroglobulinemia.

    PubMed

    Rywlin, A M; Civantos, F; Ortega, R S; Dominguez, C J

    1975-06-01

    Rywlin, Arkadi, M., Civantos, Francisco, Ortega, Rolando S., and Dominguez, Carlos J.: Bone marrow histology in monoclonal macroglobulinemiamam J Clin Pathol 63. 769-778, 1975. Histologic sections and smears of aspirated bone marrow particles in 26 cases of monoclonal macroglobulinemia were studied. The bone marrows did not show uniform histologic features. Twenty-two patients had various degrees of lymphoid infiltration of the marrow, including nodules of malignant lymphoma, diffuse lymphocytic infiltration, nodular lymphoid hyperplasia, and normal lymphoid nodules. Four patients had no demonstrable lymphoid collections in the marrow. Additional histologic features of the marrows are summarized. A variant of a Dutcher body consisting of multiple PAS-positive inclusions that by light microscopy appear intranuclear is described. Even though the average macroglobulin levels were higher in patients with abnormal lymphoid infiltrates than in patients with noraml or no lymphoid collections, there was considerable overlap between individual patients values in the different groups. Similarly, no correlation between macroglobulin levels and other histologic features could be established. Patients with monoclonal macroglobulinemia represent a spectrum including benign monoclonal gammopathy, lymphoproliferative disorders of the marrow, nodal or extranodal lymphomas. The separation of Waldenström's macroglobulinemia by arbitrary criteria does not appear justified. (key words: Bone marrow; Monoclonal macroglobulinemia.

  11. Clinical and Histologic Mimickers of Celiac Disease.

    PubMed

    Kamboj, Amrit K; Oxentenko, Amy S

    2017-08-17

    Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

  12. Echocardiographic versus Histologic Findings in Marfan Syndrome

    PubMed Central

    Gu, Xiaoyan; Li, Zhian; Han, Jiancheng; Chen, Jian; Nixon, J.V. (Ian)

    2015-01-01

    This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery. We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients. Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The echocardiographic findings in 18 patients with mitral involvement included mitral prolapse in 15. Of 11 patients with moderate or severe mitral regurgitation as determined by echocardiography, 4 underwent mitral valve repair and 7 mitral valve replacement. Histologic findings among mitral valve replacement patients showed thickened valve tissue and myxomatous degeneration. Tricuspid involvement was seen echocardiographically in 8 patients, all of whom had tricuspid prolapse. Two patients had severe tricuspid regurgitation, and both underwent repair. Both mitral and tricuspid involvement were seen echocardiographically in 7 patients. Among the 73 patients undergoing cardiac surgery for Marfan syndrome, 66 had moderate or severe aortic regurgitation, although their valves manifested few histologic changes. Eighteen patients had mitral involvement (moderate or severe mitral regurgitation, prolapse, or both), and 8 had tricuspid involvement. Mitral valves were most frequently found to have histologic changes, but the tricuspid valve was invariably involved. PMID:25873795

  13. Comprehensive histological evaluation of bone implants

    PubMed Central

    Rentsch, Claudia; Schneiders, Wolfgang; Manthey, Suzanne; Rentsch, Barbe; Rammelt, Stephan

    2014-01-01

    To investigate and assess bone regeneration in sheep in combination with new implant materials classical histological staining methods as well as immunohistochemistry may provide additional information to standard radiographs or computer tomography. Available published data of bone defect regenerations in sheep often present none or sparely labeled histological images. Repeatedly, the exact location of the sample remains unclear, detail enlargements are missing and the labeling of different tissues or cells is absent. The aim of this article is to present an overview of sample preparation, staining methods and their benefits as well as a detailed histological description of bone regeneration in the sheep tibia. General histological staining methods like hematoxylin and eosin, Masson-Goldner trichrome, Movat’s pentachrome and alcian blue were used to define new bone formation within a sheep tibia critical size defect containing a polycaprolactone-co-lactide (PCL) scaffold implanted for 3 months (n = 4). Special attention was drawn to describe the bone healing patterns down to cell level. Additionally one histological quantification method and immunohistochemical staining methods are described. PMID:24504113

  14. Actual Drawing of Histological Images Improves Knowledge Retention

    ERIC Educational Resources Information Center

    Balemans, Monique C. M.; Kooloos, Jan G. M.; Donders, A. Rogier T.; Van der Zee, Catharina E. E. M.

    2016-01-01

    Medical students have to process a large amount of information during the first years of their study, which has to be retained over long periods of nonuse. Therefore, it would be beneficial when knowledge is gained in a way that promotes long-term retention. Paper-and-pencil drawings for the uptake of form-function relationships of basic tissues…

  15. Actual Drawing of Histological Images Improves Knowledge Retention

    ERIC Educational Resources Information Center

    Balemans, Monique C. M.; Kooloos, Jan G. M.; Donders, A. Rogier T.; Van der Zee, Catharina E. E. M.

    2016-01-01

    Medical students have to process a large amount of information during the first years of their study, which has to be retained over long periods of nonuse. Therefore, it would be beneficial when knowledge is gained in a way that promotes long-term retention. Paper-and-pencil drawings for the uptake of form-function relationships of basic tissues…

  16. Histology image search using multimodal fusion.

    PubMed

    Caicedo, Juan C; Vanegas, Jorge A; Páez, Fabian; González, Fabio A

    2014-10-01

    This work proposes a histology image indexing strategy based on multimodal representations obtained from the combination of visual features and associated semantic annotations. Both data modalities are complementary information sources for an image retrieval system, since visual features lack explicit semantic information and semantic terms do not usually describe the visual appearance of images. The paper proposes a novel strategy to build a fused image representation using matrix factorization algorithms and data reconstruction principles to generate a set of multimodal features. The methodology can seamlessly recover the multimodal representation of images without semantic annotations, allowing us to index new images using visual features only, and also accepting single example images as queries. Experimental evaluations on three different histology image data sets show that our strategy is a simple, yet effective approach to building multimodal representations for histology image search, and outperforms the response of the popular late fusion approach to combine information.

  17. Subchondral bone histology and grading in osteoarthritis

    PubMed Central

    Aho, Olli-Matti; Finnilä, Mikko; Thevenot, Jerome; Saarakkala, Simo; Lehenkari, Petri

    2017-01-01

    Objective Osteoarthritis (OA) has often regarded as a disease of articular cartilage only. New evidence has shifted the paradigm towards a system biology approach, where also the surrounding tissue, especially bone is studied more vigorously. However, the histological features of subchondral bone are only poorly characterized in current histological grading scales of OA. The aim of this study is to specifically characterize histological changes occurring in subchondral bone at different stages of OA and propose a simple grading system for them. Design 20 patients undergoing total knee replacement surgery were randomly selected for the study and series of osteochondral samples were harvested from the tibial plateaus for histological analysis. Cartilage degeneration was assessed using the standardized OARSI grading system, while a novel four-stage grading system was developed to illustrate the changes in subchondral bone. Subchondral bone histology was further quantitatively analyzed by measuring the thickness of uncalcified and calcified cartilage as well as subchondral bone plate. Furthermore, internal structure of calcified cartilage-bone interface was characterized utilizing local binary patterns (LBP) based method. Results The histological appearance of subchondral bone changed drastically in correlation with the OARSI grading of cartilage degeneration. As the cartilage layer thickness decreases the subchondral plate thickness and disorientation, as measured with LBP, increases. Calcified cartilage thickness was highest in samples with moderate OA. Conclusion The proposed grading system for subchondral bone has significant relationship with the corresponding OARSI grading for cartilage. Our results suggest that subchondral bone remodeling is a fundamental factor already in early stages of cartilage degeneration. PMID:28319157

  18. Natal primary molar: clinical and histological aspects.

    PubMed

    Ruschel, Henrique C; Spiguel, Monica H; Piccinini, Daniela D; Ferreira, Simone H; Feldens, Eliane G

    2010-06-01

    The authors report a case of natal primary molar in a healthy 14-day-old child. The diagnosis of the case and the treatment plan are discussed, as well as histological analyses of the natal tooth. The tooth presented an immature appearance, with high mobility and insertion only in soft tissue, and therefore the clinical option adopted was dental extraction. Histological analyses revealed enamel hypoplasia and dentin showing a typical tubular pattern without alterations. The soft tissue had young and richly vascularized pulp with areas of chronic inflammatory infiltration.

  19. Meniscal allograft sterilisation: effect on biomechanical and histological properties.

    PubMed

    Bui, David; Lovric, Vedran; Oliver, Rema; Bertollo, Nicky; Broe, David; Walsh, William R

    2015-09-01

    Sterilisation of allografts are a crucial step in ensuring safety and viability. Current sterilisation standards such as 25 kGy gamma irradiation (γ) can have adverse effects on the ultrastructure and biomechanical properties of allograft tissue. Supercritical CO2 (SCCO2) technology, represents an improved sterilisation process that potentially preserves tissue properties. This study aimed to test the effect of SCCO2 sterilisation on the biomechanical and histological properties of the meniscus and compare this to the current standard of γ. Thirty-two 18-month old ovine menisci were randomly assigned into three groups for sterilisation (SCCO2, γ and control). After treatment, biomechanical indentation testing (stiffness and stress relaxation) or histological analysis [percentage of void, cells and extracellular matrix (ECM) per slide] was undertaken. Both SCCO2 and gamma groups displayed an increase in stiffness and stress relaxation as compared to control, however, this difference was lesser in samples treated with SCCO2. No significant histological quantitative differences were detected between SCCO2 and control specimens. Gamma-treated samples demonstrated a significant increase in void and decrease in ECM. Interestingly, both treatment groups demonstrated a decreasing mean void and increasing ECM percentage when analysed from outer to inner zones. No significant differences were detected in all-endpoints when analysed by section. SCCO2 sterilisation represents a potential feasible alternative to existing sterilization techniques such as γ.

  20. Histological Comparison of Two Cryopeeling Methods for Photodamaged Skin

    PubMed Central

    Mulinari-Brenner, Fabiane A.

    2014-01-01

    Background. Cryopeeling is a technique that uses cryotherapy not only on actinic keratoses lesions, but also all over the photodamaged skin. Objectives. To investigate the histological changes induced by two cryopeeling methods (liquid nitrogen (LN) and portable system (PS)). Methods. Sixteen patients (n = 16) with multiple actinic keratoses on the forearms were treated with cryopeeling technique using LN for one forearm and PS for the other, randomly. Skin biopsies were taken before and after the procedures. Results. There was no statistical difference between the epidermal and Grenz zone thicknesses or density of elastic fibers after treatments. The amount of melanin pigment was lower after PS treatment (P < 0.05). In a blind analysis of paired pre- and postprocedure slides, it was not possible to identify cases which underwent treatment, both in global analysis of quality of the skin and in specific analysis (considering only the aspect of stratum corneum). Discussion. The results indicate the inconsistency of histological improvement after treatments, and, likely, since the method causes superficial exfoliation, a reliable marker was not found in the analysis. Conclusions. Despite cosmetic benefits on photodamaged skin and efficient treatment of actinic keratoses lesions, cryopeeling was not able to induce measurable histological changes in solar elastosis, epidermal organization, or epidermal and Grenz zone thicknesses. One should keep in mind the possibility of hypopigmentation risk of the method. PMID:25006489

  1. Histological analysis of the tibial anterior cruciate ligament insertion.

    PubMed

    Oka, Shinya; Schuhmacher, Peter; Brehmer, Axel; Traut, Ulrike; Kirsch, Joachim; Siebold, Rainer

    2016-03-01

    This study was performed to investigate the morphology of the tibial anterior cruciate ligament (ACL) by histological assessment. The native (undissected) tibial ACL insertion of six fresh-frozen cadaveric knees was cut into four sagittal sections parallel to the long axis of the medial tibial spine. For histological evaluation, the slices were stained with haematoxylin and eosin, Safranin O and Russell-Movat pentachrome. All slices were digitalized and analysed at a magnification of 20×. The anterior tibial ACL insertion was bordered by a bony anterior ridge. The most medial ACL fibres inserted from the medial tibial spine and were adjacent to the articular cartilage of the medial tibial plateau. Parts of the bony insertions of the anterior and posterior horns of the lateral meniscus were in close contact with the lateral part of the tibial ACL insertion. A small fat pad was located just posterior to the functional ACL fibres. The anterior-posterior length of the medial ACL insertion was an average of 10.8 ± 1.1 mm compared with the lateral, which was only 6.2 ± 1.1 mm (p < 0.001). There were no central or posterolateral inserting ACL fibres. The shape of the bony tibial ACL insertion was 'duck-foot-like'. In contrast to previous findings, the functional mid-substance fibres arose from the most posterior part of the 'duck-foot' in a flat and 'c-shaped' way. The most anterior part of the tibial ACL insertion was bordered by a bony anterior ridge and the most medial by the medial tibial spine. No posterolateral fibres nor ACL bundles have been found histologically. This histological investigation may improve our understanding of the tibial ACL insertion and may provide important information for anatomical ACL reconstruction.

  2. The caspase-independent algorithm of programmed cell death in Leishmania induced by baicalein: the role of LdEndoG, LdFEN-1 and LdTatD as a DNA 'degradesome'.

    PubMed

    BoseDasgupta, S; Das, B B; Sengupta, S; Ganguly, A; Roy, A; Dey, S; Tripathi, G; Dinda, B; Majumder, H K

    2008-10-01

    In the post-genomic perspective, the quest of programmed cell death (PCD) mechanisms in kinetoplastid parasites lies in the identification and characterization of cell death executer proteins. Here, we show that baicalein (BLN), a potent topoisomerase IB inhibitor, generates an oxidative stress in the parasites leading to altered physiological and morphological parameters, which are characteristic of PCD. For the first time we elucidate that, caspase-independent activation of a novel effector molecule, endonuclease G (LdEndoG), mediates BLN-induced cell death. Functional characterization of LdEndoG identifies Flap endonuclease-1 (LdFEN-1) and LdTatD-like nuclease as other effector molecules. BLN treatment translocates LdEndoG from mitochondria to nucleus, where it forms separate complexes with LdFEN-1 and LdTatD to constitute a DNA 'degradesome' unique to these parasites. Conditional antisense knockdown of LdEndoG provides protection against PCD. This knowledge paves the path toward a better understanding of the PCD pathway in simpler systems, which could be exploited in anti-leishmanial chemotherapy.

  3. Simultaneous determination of baicalin, baicalein, wogonoside, wogonin, scutellarin, berberine, coptisine, ginsenoside Rb1 and ginsenoside Re of Banxia xiexin decoction in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

    PubMed

    Wang, Ying; Zhang, Yifan; Xiao, Juan; Xu, Ranchi; Wang, Qiangli; Wang, Xinhong

    2017-08-28

    A rapid and high sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous determination of nine active constituents, baicalin, baicalein, wogonoside, wogonin, scutellarin, berberine, coptisine, ginsenoside Rb1 and ginsenoside Re in rat plasma after oral administration of Banxia xiexin decoction(BXD). Biological samples were processed wtih acetone-ethyl acetate (4:1, v/v). The mobile phase consisted of methanol and water (containing 0.1% formic acid) with gradient elution at a flow rate of 0.3 mL/min. Detection was performed on a triple quadrupole mass spectrometer using positive ion and negative ESI in the multiple reaction monitoring(MRM) mode. The calibration curves for all analytes had good linearity (r > 0.9933). The mean recovery of all the nine active ingredients was more than 75.2 %, and the intra- and inter-day precisions (RSD) were within 12.0%, the accuracy was between 87.4% and 110.4%. This method was successfully applied to the pharmacokinetic study after administration of BXD. The results of pharmacokinetic study might be helpful for BXD clinical reasonable application and further studies on mechanism. This article is protected by copyright. All rights reserved.

  4. Histology. Notes for Students of Animal Husbandry.

    ERIC Educational Resources Information Center

    Price, Charles J.; Reed, Josephine E.

    This document approaches the subject of Histology by way of simple independent unicellular organisms through the lower levels of cell organization and specialization to a detailed study of the highly complex tissues of vertebrate animals. Emphasis is placed on structure, but function is explained in some detail. The relationships between tissues…

  5. Abdominal and pelvic tumors with musculoskeletal histology.

    PubMed

    Dyrstad, Sara W; Fowler, Amy M; Jokerst, Clint E; Baker, Jonathan C; Hillen, Travis J; Menias, Christine

    2014-01-01

    This article is a case-based review of the broad spectrum of tumors with musculoskeletal histology that can arise in the abdomen or pelvis and involve the soft tissues, muscle, and bone. In this article, pathology-proven cases are presented with a focus on radiographic, computed tomography, magnetic resonance imaging, and positron emission tomography-computed tomography findings. The imaging features that differentiate tumors with musculoskeletal histology from more common abdominal tumors are discussed. Representative cases include malignant fibrous histiocytoma, chondrosarcoma, Ewing sarcoma, hemangiopericytoma, desmoplastic fibroma, neurofibrosarcoma, osteosarcoma, intimal sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, teratoma, and chordoma. A variety of tumors with musculoskeletal histology can arise in the abdomen and pelvis. In some cases, unique imaging characteristics allow a confident diagnosis, whereas other cases have a more nonspecific appearance. Recognition of imaging features that suggest a musculoskeletal tumor including direct extension from a bone or neural foramen, the presence of cartilaginous or osseous matrix, or macroscopic fat would allow the radiologist to suggest the proper diagnosis. Recognizing imaging characteristics of tumors with musculoskeletal histology is important clinically as management and prognosis differ from that of more common abdominal tumors. © 2013 Published by Elsevier Inc.

  6. The histological diagnosis of toxoplasmic lymphadenitis

    PubMed Central

    Stansfeld, A. G.

    1961-01-01

    The commonest presenting sign of acquired toxoplasmosis in man is enlargement of superficial lymph nodes. The persistence of the nodes may lead to a suspicion of malignant lymphoma and the diagnosis then hinges on the lymph node biopsy. Three cases of toxoplasmic lymphadenitis are described in each of which the diagnosis was unsuspected clinically. The chance discovery of a toxoplasma cyst in the lymph node section of Case 1 led to the correct diagnosis, after an initial diagnosis of Hodgkin's disease had been made. In the other two, strikingly similar histological changes in the lymph node biopsies suggested the diagnosis, which was confirmed serologically in each case. The histological changes are described and the clinical and pathological aspects of toxoplasmic lymphadenitis are briefly reviewed, with special reference to the differentiation from malignant lymphomatous conditions and to the specificity of the histological picture. It is concluded that the histology is, in many instances, sufficiently distinctive for a tentative diagnosis of toxoplasmic lymphadenitis to be made on the lymph node biopsy. The diagnosis should always be confirmed by isolation of the parasite or by serological tests. It is exceedingly rare for toxoplasma cysts to be found in lymph nodes and only one previous observation of this kind has been reported. Images PMID:16810977

  7. Developing the eHistology Atlas.

    PubMed

    Richardson, Lorna; Graham, Liz; Moss, Julie; Burton, Nick; Roochun, Yogmatee; Armit, Chris; Baldock, Richard A

    2015-01-01

    The eMouseAtlas project has undertaken to generate a new resource providing access to high-resolution colour images of the slides used in the renowned textbook 'The Atlas of Mouse Development' by Matthew H. Kaufman. The original histology slides were digitized, and the associated anatomy annotations captured for display in the new resource. These annotations were assigned to objects in the standard reference anatomy ontology, allowing the eHistology resource to be linked to other data resources including the Edinburgh Mouse Atlas Gene-Expression database (EMAGE) an the Mouse Genome Informatics (MGI) gene-expression database (GXD). The provision of the eHistology Atlas resource was assisted greatly by the expertise of the eMouseAtlas project in delivering large image datasets within a web environment, using IIP3D technology. This technology also permits future extensions to the resource through the addition of further layers of data and annotations to the resource. Database URL: www.emouseatlas.org/emap/eHistology/index.php.

  8. Histology. Notes for Students of Animal Husbandry.

    ERIC Educational Resources Information Center

    Price, Charles J.; Reed, Josephine E.

    This document approaches the subject of Histology by way of simple independent unicellular organisms through the lower levels of cell organization and specialization to a detailed study of the highly complex tissues of vertebrate animals. Emphasis is placed on structure, but function is explained in some detail. The relationships between tissues…

  9. Developing the eHistology Atlas

    PubMed Central

    Richardson, Lorna; Graham, Liz; Moss, Julie; Burton, Nick; Roochun, Yogmatee; Armit, Chris; Baldock, Richard A.

    2015-01-01

    The eMouseAtlas project has undertaken to generate a new resource providing access to high-resolution colour images of the slides used in the renowned textbook ‘The Atlas of Mouse Development’ by Matthew H. Kaufman. The original histology slides were digitized, and the associated anatomy annotations captured for display in the new resource. These annotations were assigned to objects in the standard reference anatomy ontology, allowing the eHistology resource to be linked to other data resources including the Edinburgh Mouse Atlas Gene-Expression database (EMAGE) an the Mouse Genome Informatics (MGI) gene-expression database (GXD). The provision of the eHistology Atlas resource was assisted greatly by the expertise of the eMouseAtlas project in delivering large image datasets within a web environment, using IIP3D technology. This technology also permits future extensions to the resource through the addition of further layers of data and annotations to the resource. Database URL: www.emouseatlas.org/emap/eHistology/index.php PMID:26500249

  10. Histological subtypes of periocular basal cell carcinoma.

    PubMed

    Wu, Albert; Sun, Michelle T; Huilgol, Shyamala C; Madge, Simon; Selva, Dinesh

    2014-01-01

    To determine the proportion of different subtypes of periocular BCC in South Australia. Retrospective review. One thousand seven hundred thirteen consecutive periocular basal cell carcinoma (BCC) excision specimens. Histological analysis of consecutive periocular BCC specimens. Date of resection, patient age at resection, gender, tumour location, histological subtype and perineural invasion. From 2006 to 2012, a total of 1713 consecutive periocular BCC excision specimens were analysed. The mean age at resection was 68.8 years (median: 71, range: 21-101). Most specimens (56.4%) were removed from male patients. 52.7% involved the lower eyelid, 29.0% the medial canthus, 10.9% the lateral canthus and 7.5% the upper eyelid. The main histological subtypes identified were nodular (65.7%), infiltrative (17.5%), superficial (12.6%) and micronodular (4.2%). Of the specimens, 25.6% had more than one subtype. The most common subtype combinations were nodular with infiltrative (49.7%), and nodular with superficial (26.0%). The majority of periocular BCC were located on the lower lid and classified histologically as nodular. Infiltrative BCC occurred more frequently than the superficial subtype. As the proportion of mixed BCC containing aggressive subtypes is high, surgical excision with margin control should be considered for periocular BCC. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

  11. Segmentation of histological structures for fractal analysis

    NASA Astrophysics Data System (ADS)

    Dixon, Vanessa; Kouznetsov, Alexei; Tambasco, Mauro

    2009-02-01

    Pathologists examine histology sections to make diagnostic and prognostic assessments regarding cancer based on deviations in cellular and/or glandular structures. However, these assessments are subjective and exhibit some degree of observer variability. Recent studies have shown that fractal dimension (a quantitative measure of structural complexity) has proven useful for characterizing structural deviations and exhibits great potential for automated cancer diagnosis and prognosis. Computing fractal dimension relies on accurate image segmentation to capture the architectural complexity of the histology specimen. For this purpose, previous studies have used techniques such as intensity histogram analysis and edge detection algorithms. However, care must be taken when segmenting pathologically relevant structures since improper edge detection can result in an inaccurate estimation of fractal dimension. In this study, we established a reliable method for segmenting edges from grayscale images. We used a Koch snowflake, an object of known fractal dimension, to investigate the accuracy of various edge detection algorithms and selected the most appropriate algorithm to extract the outline structures. Next, we created validation objects ranging in fractal dimension from 1.3 to 1.9 imitating the size, structural complexity, and spatial pixel intensity distribution of stained histology section images. We applied increasing intensity thresholds to the validation objects to extract the outline structures and observe the effects on the corresponding segmentation and fractal dimension. The intensity threshold yielding the maximum fractal dimension provided the most accurate fractal dimension and segmentation, indicating that this quantitative method could be used in an automated classification system for histology specimens.

  12. Reptilian spermatogenesis: A histological and ultrastructural perspective.

    PubMed

    Gribbins, Kevin M

    2011-07-01

    Until recently, the histology and ultrastructural events of spermatogenesis in reptiles were relatively unknown. Most of the available morphological information focuses on specific stages of spermatogenesis, spermiogenesis, and/or of the mature spermatozoa. No study to date has provided complete ultrastructural information on the early events of spermatogenesis, proliferation and meiosis in class Reptilia. Furthermore, no comprehensive data set exists that describes the ultrastructure of the entire ontogenic progression of germ cells through the phases of reptilian spermatogenesis (mitosis, meiosis and spermiogenesis). The purpose of this review is to provide an ultrastructural and histological atlas of spermatogenesis in reptiles. The morphological details provided here are the first of their kind and can hopefully provide histological information on spermatogenesis that can be compared to that already known for anamniotes (fish and amphibians), birds and mammals. The data supplied in this review will provide a basic model that can be utilized for the study of sperm development in other reptiles. The use of such an atlas will hopefully stimulate more interest in collecting histological and ultrastructural data sets on spermatogenesis that may play important roles in future nontraditional phylogenetic analyses and histopathological studies in reptiles.

  13. [A method of preparing sections for express histological diagnosis].

    PubMed

    Zubkova, T V; Tarnopol'skaia, O V; Makarov, V L; Nemykin, V I; Marmarova, T Iu

    2000-01-01

    The method of improving quality of histological slides for intrasurgical diagnosis is proposed. The method consists in preliminary microwave processing of the slice of surgical material before putting in into cryostat for freezing and sections preparation. A slice of surgical material was first immersed in 10 ml of physiological solution (pH = 7.2). Then it was exposed to microwave radiation (2.45 GHz, 1 W/cm2) for 1.5 min. After that the slice was put into cryostat and frozen. Microwave processing is done in a home microwave oven or working chamber of microwave histoprocessor. Essential advantage in quality of slides is obtained.

  14. Polarimetric characterisation of histological section of skin with pathological changes

    NASA Astrophysics Data System (ADS)

    Rovira, Ronald H.; Tuzhanskyy, Stanislav Ye.; Pavlov, Sergii V.; Savenkov, Sergii N.; Kolomiets, Ivan S.; Stasenko, Vladyslav A.; Bayas, Marsia M.; Omiotek, Zbigniew; Małecka-Massalska, Teresa; DzierŻak, RóŻa

    2016-09-01

    This work focuses on the further development of the optical methods based on polarization detection to improve the reliability of the results of evaluation of structural changes in biological tissues. The paper presents an experimental study of tissues with pathological alterations to assess the capacity of differentiation of pathological conditions when using averaged local Mueller matrix elements. Experiments were carried out in direct scattering mode in histological samples of human epidermis. The practical significance of the results is the widespread application of the methodology for laser polarimetric analysis of structural changes in anisotropic tissues to identify and assess the degree of pathology in medical diagnosis of skin diseases.

  15. Clinical and Histologic Evaluations of SLA Dental Implants.

    PubMed

    Nevins, Myron; Parma-Benfenati, Stefano; Quinti, Franco; Galletti, Prima; Sava, Cosmin; Sava, Catalin; Kim, David M

    The goal of this investigation was to evaluate the efficacy of dental implants with a surface that was sandblasted with large grit and acid etched in a human model. Seven patients volunteered to allow the biopsy of a small implant in exchange for complete dental rehabilitation at no cost. All biopsy sites received soft and hard tissue reconstruction, and this report provides observation of successful bone-to-implant contact and successful prosthesis construction for the patient. The patients enthusiastically reported improved quality of life as a result of participation in this study. The surgeons’ confidence in this implant was reflected by the clinical and histologic result of the study.

  16. A histological study of cerebral aqueduct.

    PubMed

    Stanković, Gordana; Nikolić, Valentina; Puskas, Laslo; Filipović, Branislav; Stojsić-Dzunja, Ljubica; Krivokuća, Dragan

    2005-01-01

    Cerebral (sylvian) aqueduct is a narrow channel in the mesencephalon. It lies between the tectum and the tegmentum of the mesencephalon and is surrounded by the periaqueductal gray matter. The aim of this study was to determine the shape of the aqueduct of sylvius and the structure of its walls in a series of transverse histological sections. Serial transverse sections of the mesencephalon were examined in twenty adult brains of both sexes. Six sections were stained by the hematoxylin-eosin method. The rostral part of the the aqueduct has a triangular shape with dorsal concavity caused by retrocommissural fossae. In the middle, its shape is oval to irregular, the rostral part has a T shape due to isthmic recess on the floor. Walls of the aqueduct are coated with a layer of prismatic cells. Determination of the morphological and histological features of the mesencephalic aqueduct is important for differentiation between physiological and pathological processes in this region.

  17. Histological structure affects recellularization of decellularized arteries.

    PubMed

    Negishi, Jun; Hashimoto, Yoshihide; Yamashita, Akitatsu; Kimura, Tsuyoshi; Kishida, Akio; Funamoto, Seiichi

    2017-01-01

    Decellularized arteries were prepared to evaluate the in vivo recellularization of biological material after implantation. Porcine aortas and radial arteries were decellularized using high-hydrostatic pressure to form materials with histologically-different structures. Successful removal of cells from decellularized arteries was evaluated by hematoxylin-eosin staining and measurement of residual DNA. Cell remnants were eliminated completely from the decellularized arteries, and histological structures were preserved. Cells adhered to all decellularized artery samples, but infiltration of cells was observed only from the adventitial side of the decellularized radial artery. Rats were implanted subcutaneously with a decellularized aorta or radial artery to evaluate in vivo performance. Decellularized aortic tissue prevented cell infiltration better than that of the decellularized radial artery, suggesting that the elastin lamina in decellularized tissues prevents cell infiltration and suppresses recellularization. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Graves' disease associated with histologic Hashimoto's thyroiditis.

    PubMed

    Falk, S A; Birken, E A; Ronquillo, A H

    1985-02-01

    The microscopic slides of 16 patients who underwent bilateral subtotal thyroidectomy for hyperthyroid Graves' disease were reviewed and classified into three groups: I, Hashimoto's thyroiditis; II, Graves' disease; and III, both Hashimoto's thyroiditis and Graves' disease. Three patients were classified as group I, 10 as group II, and three as group III. In 38% of the patients with clinical Graves' disease the histologic evidence of Hashimoto's thyroiditis could be found either alone or in combination with histologic evidence of Graves' disease (groups I and III). One patient in group I, four in group II, and three in group III had infiltrative ophthalmopathy (50% of total). Hyperthyroid Graves' disease, Graves' ophthalmopathy, and Hashimoto's thyroiditis can occur all together, in duads, or individually at a specific time in a patient's life.

  19. Histologic changes in previously irradiated thyroid glands

    SciTech Connect

    Valdiserri, R.O.; Borochovitz, D.

    1980-03-01

    Thyroid tissue from 90 patients with a history of therapeutic irradiation to the head and neck in childhood and adolescence was examined microscopically. In addition to the well-known observation that these individuals have an increased incidence of primary thyroid carcinoma, it was also demonstrated that they have an increased incidence of benign histologic changes. These changes represent a spectrum from nonspecific hyperplastic lesions to benign neoplasis and thyroidltis.

  20. Bone welding--a histological evaluation in the jaw.

    PubMed

    Mai, Ronald; Lauer, Günter; Pilling, Eckart; Jung, Roland; Leonhardt, Henry; Proff, Peter; Stadlinger, Bernd; Pradel, Winnie; Eckelt, Uwe; Fanghänel, Jochen; Gedrange, Tomas

    2007-01-01

    The expansion of biodegradable osteosynthesis systems in clinical application correlates well to the progress in development of new materials as to the improvement of application methods. One of those new application methods is the ultrasound-aided insertion of Resorb-X pins. The aim of this study was the histological evaluation of possible thermal damage to bone due to the ultrasound insertion. For this purpose, condylar neck fractures in 12 sheep were produced, repositioned and fixed by Resorb-X plates and pins. The animals were sacrificed in two groups, one after 2 weeks and one after 9 weeks. The bone-pin interlinkage and the structure of the bone were histologically evaluated. After 2 weeks a tight bone-polymer interlinkage was seen. Neither a pronounced foreign body reaction nor an interposition of fibrous tissue at the interface or a thermally induced necrosis was observed. The late phase of wound healing after 9 weeks showed pathomorphological characteristics within the normal range of bone healing. The bone seemed to be free of any alteration caused by process engineering. We conclude that thermal stress caused by ultrasound-aided pin insertion does not lead to cellular reaction in the bone. The fast and easy application of this improved biodegradable osteosynthesis system will bring a clear advantage in clinical use.

  1. Normal Vulvar Histology: Variation by Site.

    PubMed

    Day, Tania; Holland, Seán M; Scurry, James

    2016-01-01

    The aim of the study was to assess the histology of normal vulvar skin with attention to anatomic location and epithelium type. We performed a retrospective histologic review of 118 vulvar biopsies and excisions obtained between 2010 and 2014 with adjacent normal skin or mucosa. Exclusions included age younger than 18 years, vestibulectomy, labiaplasty, inflammatory dermatoses, and insufficient normal tissue for assessment. Stratum corneum morphology was assessed as basket weave, compact, or intermediate. Stratum granulosum cell layer number and epithelial thickness were recorded. Dermal lymphocytic infiltrate was described as nil, sparse, moderate, or dense. Fischer exact test, Pearson χ, and Student t test were used for statistical analysis. There were 7 cases from mons pubis, 11 from perineum, 83 from labia, and 17 from vestibule. In the skin, the stratum corneum morphology was basket weave in 31%, compact in 35%, and intermediate in 34%. Stratum corneum at the mons pubis was uniformly basket weave, whereas at perineum, it was either compact or intermediate (7/7 vs 0/11; p < .001); the labia demonstrated all 3 morphologies. Parakeratosis (PK) was identified at the specimen edge in 4 cases of hairless skin and 7 cases of squamous mucosa. Mean epithelial thickness and dermal lymphocytic infiltration were similar in specimens with and without PK. Compact stratum corneum of vulvar skin and a zone of PK at the mucocutaneous junction may be normal histological findings. Pathologists need to be aware of site-related differences of the vulvar epithelium to avoid overdiagnosis of pathological conditions.

  2. Reoperative pulmonary metastasectomy for sarcomatous pediatric histologies.

    PubMed

    Temeck, B K; Wexler, L H; Steinberg, S M; McClure, L L; Horowitz, M A; Pass, H I

    1998-09-01

    The role for reoperative pulmonary metastasectomy in patients with "pediatric sarcomas" (osteosarcoma, nonrhabdomyosarcoma-soft tissue sarcoma, and Ewing's sarcoma) is undefined. We reviewed our results for patients with these histologic presentations (median age, 17.5 years; range, 6 to 32 years) having two (70), three (27), or four (10) metastasectomies between January 1965 and March 1995 to define postresection survival and potential prognostic factors. Simple wedges (88 thoracotomies, 84%) were performed more frequently than anatomic (17 thoracotomies, 16%) resections. With a median potential follow-up of 12.7 years, median survival was 2.25, 3.60, and 0.96 years from the second, third, and fourth explorations, respectively. Primary tumor site, sex, histology, age, maximal metastasis size, and systemic chemotherapy did not influence survival. Resectability was the most important prognostic factor (5.6 versus 0.7 years, 5.2 versus 2.5 years, 2.2 versus 0.2 years, resectable versus unresectable, median survival from second, third, and fourth thoracotomy, respectively). Unresectability, disease-free interval less than 6 months between initial (ie, first) pulmonary resection and the second thoracotomy, and two or more preoperative nodules noted on the right were simultaneously negatively associated with survival from the second thoracotomy. Unresectability or finding two or more metastases negatively affected survival from the third thoracotomy. These data imply that repeat metastasectomy can salvage a subset of patients with sarcomatous pediatric histologic presentations who retain favorable prognostic determinants.

  3. Anatomy and histology of Virchow's node.

    PubMed

    Mizutani, Masaomi; Nawata, Shin-ichi; Hirai, Ichiro; Murakami, Gen; Kimura, Wataru

    2005-12-01

    A regional lymphatic system is composed of the first, second, third and even fourth or much more intercalated nodes along the lymptatic route from the periphery to the venous angle or the thoracic duct. The third or fourth node is usually termed the last-intercalated node or end node along the route. Similarly, one of the supraclavicular nodes is known to correspond to the end node along the thoracic duct. It is generally called 'Virchow's node', in which the famous 'Virchow's metastasis' of advanced gastric cancer occurs. The histology of this node has not been investigated, although region-specific differences in histology are evident in human lymph nodes. We found macroscopically the end node in five of 30 donated cadavers. Serial sections were prepared for these five nodes and sections stained with hematoxylin and eosin. Histological investigation revealed that, on the inferior or distal side of the end node, the thoracic duct divided into three to 10 collateral ducts and these ducts surrounded the node. The node communicated with the thoracic duct and its collaterals at multiple sites in two to three hilus-like portions, as well as along the subcapsular sinus. Thus, the end node was aligned parallel to the thoracic duct. Moreover, the superficial and deep cortex areas of the end node were fragmented to make an island-like arrangement, which may cause the short-cut intranodal shunt. Consequenly, the filtration function of most of Virchow's node seemed to be quite limited.

  4. Histological changes of kidney in diabetic nephropathy

    PubMed Central

    Pourghasem, Mohsen; Shafi, Hamid; Babazadeh, Zahra

    2015-01-01

    Diabetes mellitus is the most common cause of chronic renal disorders and end-stage kidney disease in developed countries. It is the major cause of dialysis and transplantation. Failure in renal function causes wide disorders in the body. Diabetes results in wide range of alterations in the renal tissue. It is believed that early histological changes in diabetic nephropathy are detectable 2 years after diabetes is diagnosed. The glomerular alterations are the most important lesions in the diabetic nephropathy (DN). The Renal Pathology Society provides a new pathological classification for the detection of histopathology of DN. It divides diabetic nephropathy into four hierarchical glomerular lesions. Alloxan or streptozotocin induced diabetic rat is the one most widely used specie to study DN. Histological changes in the rat DN closely resemble the human disease and the most information of this review was obtained through the study of rat DN. All cell types of the kidney such as mesangial cells, podocytes and tubulointerstitial cells are liable to be affected in the event of DN. Severity of renal lesions is associated to the clinical aspect of renal outcome, but the aim of this article was only to review the histological changes of kidney in diabetes mellitus. PMID:26644877

  5. Development of a 2D Image Reconstruction and Viewing System for Histological Images from Multiple Tissue Blocks: Towards High-Resolution Whole-Organ 3D Histological Images.

    PubMed

    Hashimoto, Noriaki; Bautista, Pinky A; Haneishi, Hideaki; Snuderl, Matija; Yagi, Yukako

    2016-01-01

    High-resolution 3D histology image reconstruction of the whole brain organ starts from reconstructing the high-resolution 2D histology images of a brain slice. In this paper, we introduced a method to automatically align the histology images of thin tissue sections cut from the multiple paraffin-embedded tissue blocks of a brain slice. For this method, we employed template matching and incorporated an optimization technique to further improve the accuracy of the 2D reconstructed image. In the template matching, we used the gross image of the brain slice as a reference to the reconstructed 2D histology image of the slice, while in the optimization procedure, we utilized the Jaccard index as the metric of the reconstruction accuracy. The results of our experiment on the initial 3 different whole-brain tissue slices showed that while the method works, it is also constrained by tissue deformations introduced during the tissue processing and slicing. The size of the reconstructed high-resolution 2D histology image of a brain slice is huge, and designing an image viewer that makes particularly efficient use of the computing power of a standard computer used in our laboratories is of interest. We also present the initial implementation of our 2D image viewer system in this paper. © 2016 S. Karger AG, Basel.

  6. Long bone histology and growth patterns in ankylosaurs: implications for life history and evolution.

    PubMed

    Stein, Martina; Hayashi, Shoji; Sander, P Martin

    2013-01-01

    The ankylosaurs are one of the major dinosaur groups and are characterized by unique body armor. Previous studies on other dinosaur taxa have revealed growth patterns, life history and evolutionary mechanisms based on their long bone histology. However, to date nothing is known about long bone histology in the Ankylosauria. This study is the first description of ankylosaurian long bone histology based on several limb elements, which were sampled from different individuals from the Ankylosauridae and Nodosauridae. The histology is compared to that of other dinosaur groups, including other Thyreophora and Sauropodomorpha. Ankylosaur long bone histology is characterized by a fibrolamellar bone architecture. The bone matrix type in ankylosaurs is closest to that of Stegosaurus. A distinctive mixture of woven and parallel-fibered bone together with overall poor vascularization indicates slow growth rates compared to other dinosaurian taxa. Another peculiar characteristic of ankylosaur bone histology is the extensive remodeling in derived North American taxa. In contrast to other taxa, ankylosaurs substitute large amounts of their primary tissue early in ontogeny. This anomaly may be linked to the late ossification of the ankylosaurian body armor. Metabolically driven remodeling processes must have liberated calcium to ossify the protective osteodermal structures in juveniles to subadult stages, which led to further remodeling due to increased mechanical loading. Abundant structural fibers observed in the primary bone and even in remodeled bone may have improved the mechanical properties of the Haversian bone.

  7. Long Bone Histology and Growth Patterns in Ankylosaurs: Implications for Life History and Evolution

    PubMed Central

    Stein, Martina; Hayashi, Shoji; Sander, P. Martin

    2013-01-01

    The ankylosaurs are one of the major dinosaur groups and are characterized by unique body armor. Previous studies on other dinosaur taxa have revealed growth patterns, life history and evolutionary mechanisms based on their long bone histology. However, to date nothing is known about long bone histology in the Ankylosauria. This study is the first description of ankylosaurian long bone histology based on several limb elements, which were sampled from different individuals from the Ankylosauridae and Nodosauridae. The histology is compared to that of other dinosaur groups, including other Thyreophora and Sauropodomorpha. Ankylosaur long bone histology is characterized by a fibrolamellar bone architecture. The bone matrix type in ankylosaurs is closest to that of Stegosaurus. A distinctive mixture of woven and parallel-fibered bone together with overall poor vascularization indicates slow growth rates compared to other dinosaurian taxa. Another peculiar characteristic of ankylosaur bone histology is the extensive remodeling in derived North American taxa. In contrast to other taxa, ankylosaurs substitute large amounts of their primary tissue early in ontogeny. This anomaly may be linked to the late ossification of the ankylosaurian body armor. Metabolically driven remodeling processes must have liberated calcium to ossify the protective osteodermal structures in juveniles to subadult stages, which led to further remodeling due to increased mechanical loading. Abundant structural fibers observed in the primary bone and even in remodeled bone may have improved the mechanical properties of the Haversian bone. PMID:23894321

  8. A practical hybrid model of application, integration, and competencies at interactive table conferences in histology (ITCH).

    PubMed

    Ettarh, Rajunor

    2016-05-06

    Significant changes have been implemented in the way undergraduate medical education is structured. One of the challenges for component courses such as histology in medical and dental curricula is to restructure and deliver training within new frameworks. This article describes the process of aligning the purpose and experience in histology laboratory to the goal of applying knowledge gained to team-based medical practice at Tulane University School of Medicine. Between 2011 and 2015, 711 medical students took either a traditional laboratory-based histology course (353 students) or a team-based hybrid histology course with active learning in laboratory (358 students). The key difference was in the laboratory component of the hybrid course - interactive table conferences in histology-during which students developed new competencies by working in teams, reviewing images, solving problems by applying histology concepts, and sharing learning. Content, faculty and online resources for microscopy were the same in both courses. More student-student and student-faculty interactions were evident during the hybrid course but student evaluation ratings and grades showed reductions following introduction of table conferences when compared to previous ratings. However, outcomes at National Board of Medical Examiners(®) (NBME(®) ) Subject Examination in Histology and Cell Biology showed significant improvement (72.4 ± 9.04 and 76.44 ± 9.36 for percent correct answers, traditional and hybrid courses, respectively, P < 0.0001). This model of table conferences to augment the traditional histology laboratory experience exemplifies the extent that restructuring enhancements can be used in currently taught courses in the undergraduate medical curriculum. Anat Sci Educ 9: 286-294. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

  9. Anatomy and histology of the frontalis muscle.

    PubMed

    Costin, Bryan R; Plesec, Thomas P; Sakolsatayadorn, Natta; Rubinstein, Tal J; McBride, Jennifer M; Perry, Julian D

    2015-01-01

    To determine the gross and histologic configurations of the medial and lateral frontalis muscle. After making a midcoronal incision and bluntly dissecting to the orbital rim, the frontalis muscle was marked and measured. A protractor was used to measure the frontalis-orbicularis angle (FOA) and, when present, the angle of central bifurcation (AOB). Three strips of full-thickness forehead soft tissue measuring 0.5 cm × 8 cm were excised 3, 4.5, and 6 cm above the supraorbital notch and analyzed histologically for the presence of skeletal muscle fibers. Data were analyzed using 2-sample t tests, paired t tests, Pearson correlations, and mixed effect models. A p value of ≤ 0.05 was considered statistically significant. Sixty-four hemifaces of 32 cadavers (16 males) were dissected. All specimens were Caucasian. The average age was 78.2 years (range, 56-102 years). The average FOA was 88.7° (13.0°), and the average AOB was 90.0° (26.4°). A visible midline bifurcation occurred in 28 of 32 subjects (88%) at an average height of 4.7 cm (range, 2.4-7.2 cm) superior to the supraorbital notch. Continuous skeletal muscle fibers were present within the midline bifurcation histologically in 89%, 75%, and 11% of specimens 3.5, 5.0, and 6.5 cm above the supraorbital notch, respectively. In 46% of individuals, skeletal muscle fibers were continuously present microscopically within the gross bifurcation. While a medial frontalis muscle bifurcation occurs grossly in most senescent Caucasians, muscle fibers exist microscopically within this zone in nearly half of individuals.

  10. Histological characteristics of diffuse idiopathic skeletal hyperostosis.

    PubMed

    Kuperus, Jonneke S; Westerveld, L Anneloes; Rutges, Joost P H J; Alblas, Jacqueline; van Rijen, Mattie H P; Bleys, Ronald L A W; Öner, F Cumhur; Verlaan, Jorrit-Jan

    2017-01-01

    Diffuse idiopathic skeletal hyperostosis (DISH) is a predominantly radiographic diagnosis and histological knowledge of DISH is limited. The aim of this study was to describe the histological characteristics of DISH in the spinal column and to study the relation between DISH and intervertebral disc (IVD) degeneration. Therefore, 10 human cadaveric spines with fluoroscopic evidence of DISH were compared with 10 controls. Plain radiographs and computed tomography (CT) scans were obtained and tissue blocks were resected from three predefined levels of all specimens. The microscopic sections were scored by two blinded observers using a newly developed scoring system specific for characteristics of DISH and a validated scoring system for IVD degeneration. Maximum IVD height was measured on the CT scans. Analyses were performed using Fisher's exact test and Student's t-test. When compared to controls, the right sided sections from DISH specimens showed partial or complete bone bridges, consisting of cortical woven bone, accompanied by morphological changes in the adjoining part of the IVD. Using the histological scoring system for DISH, all parameters were significantly different between the DISH and control group (p < 0.01). The contralateral location did not show differences between the groups. The overall degree of IVD degeneration and height of IVD was comparable for the two groups. The histopathological changes observed in spines with DISH corresponded to the fluoroscopic images and CT scans. The degree of IVD degeneration and IVD height was comparable for both groups, suggesting a limited role for IVD degeneration in the pathogenesis of DISH. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:140-146, 2017.

  11. Understanding the molecular basis of histologic grade.

    PubMed

    Ignatiadis, M; Sotiriou, C

    2008-01-01

    Histologic grading in breast cancer is based on the evaluation of 3 morphologic features (tubule formation, nuclear pleomorphism and mitotic count), is essentially describing proliferation and differentiation in breast cancer, and is considered an important prognostic factor for this disease. It has been suggested that histologic grade 1 and 3 breast tumors are 2 different diseases that may have distinct molecular origins, pathogenesis and natural history. Different single markers like Ki-67, thymidine labeling index and S phase fraction/flow cytometry have been studied as markers of proliferation, but none of them, with the possible exception of Ki-67, is currently employed routinely in clinical practice. The advent of the powerful microarray technology has enabled scientists to comprehensively study proliferation in breast cancer on a genome-wide scale. A gene expression grade index (GGI) was developed that challenges the existence and clinical relevance of an intermediate grade 2 classification. The GGI could reclassify patients with histologic grade 2 tumors into 2 groups with high versus low risks of recurrence. GGI has also been used to define 2 clinically relevant subgroups in estrogen receptor-positive breast carcinomas. Finally, in the largest meta-analysis of publicly available gene expression and clinical data, 4 stable molecular subgroups of breast cancer have been identified, namely ER-/HER-, HER2+ and ER+/HER2-, which was divided into 2 subgroups (ER+/low proliferation and ER+/high proliferation). In this same meta-analysis, proliferation was shown to be the common driving force responsible for the performance of various breast cancer prognostic signatures.

  12. Mouse redox histology using genetically encoded probes.

    PubMed

    Fujikawa, Yuuta; Roma, Leticia P; Sobotta, Mirko C; Rose, Adam J; Diaz, Mauricio Berriel; Locatelli, Giuseppe; Breckwoldt, Michael O; Misgeld, Thomas; Kerschensteiner, Martin; Herzig, Stephan; Müller-Decker, Karin; Dick, Tobias P

    2016-03-15

    Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation.

  13. Investigating histological aspects of scars in children.

    PubMed

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

    2017-05-02

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

  14. Skin: histology and physiology of wound healing.

    PubMed

    Gantwerker, Eric A; Hom, David B

    2011-08-01

    It is important to understand the histology and physiology of skin for the prediction and optimization of wound healing. Optimal postoperative wound healing to minimize scarring entails minimizing local, systemic, and environmental factors that lead to poor wound healing. Keeping the wound clean and moist, minimizing trauma, and infection are the local wound tenets. Systemic tenets include minimizing medications that inhibit processes of wound healing, maintaining adequate nutrition, pain palliation, UV protection, and smoking cessation. This article presents the dynamic process of wound healing and the basic tenets to minimize scarring. 2011 Elsevier Inc. All rights reserved.

  15. [Histological and molecular classification of gliomas].

    PubMed

    Figarella-Branger, D; Colin, C; Coulibaly, B; Quilichini, B; Maues De Paula, A; Fernandez, C; Bouvier, C

    2008-01-01

    Gliomas are the most frequent tumors of the central nervous system. The WHO classification, based on the presumed cell origin, distinguishes astrocytic, oligodendrocytic and mixed gliomas. A grading system is based on the presence of the following criteria: increased cellular density, nuclear atypias, mitosis, vascular proliferation and necrosis. The main histological subtype of grade I gliomas are pilocytic astrocytomas, which are benign. Diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas are low-grade (II) or high-grade (III and IV) tumors. Glioblastomas correspond to grade IV astrocytomas. C. Daumas-Duport et al. have proposed another classification based on histology and imaging data, which distinguishes oligodendrogliomas and mixed gliomas of grade A (without endothelial proliferation and/or contrast enhancement), oligodendrogliomas and mixed gliomas of grade B (with endothelial proliferation or contrast enhancement), glioblastomas and glioneuronal malignant tumors. Both classifications lack reproducibility. Many studies have searched for a molecular classification. Recurrent abnormalities in gliomas have been found. They encompassed recurrent chromosomal alterations, such as lost of chromosome 10, gain of chromosome 7, deletion of chromosome 1p and 19q, but also activation of the Akt pathway (amplification of EGFR), dysregulation of the cell cycle (deletion of p16, p53). These studies have enabled the description of two molecular subtypes for glioblastomas. De novo glioblastomas, which occur in young patients without of a prior history of brain tumor and harbor frequent amplification of EGFR, deletion of p16 and mutation of PTEN while mutation of p53 is infrequent. Secondary glioblastomas occur in the context of a preexisting low-grade glioma and are characterized by more frequent mutation of p53. On the other side, combined complete deletion of 1p and 19q as the result of the translocation t(1;19)(q10;p10) is highly specific of oligodendrogliomas

  16. Integration of Histology Lectures and Practical Teaching in China

    ERIC Educational Resources Information Center

    Lu, Xiaoye; Cheng, Xin; Li, Ke; Lee, Kenneth Ka Ho; Yang, Xuesong

    2016-01-01

    Objectives: Human histology is a discipline concerning the study of microscopic structures of human tissues and organs--with the aid of light or electron microscopes. Traditional teaching of histology is composed of two separated components, theory and practice. The main disadvantage with traditional histology teaching is the detachment of theory…

  17. Histological evaluation of a replanted tooth retained for 49 years.

    PubMed

    Keklikoglu, Nurullah; Asci, Selmin Kaan

    2006-06-01

    A maxillary incisor that had been replanted immediately after avulsion 49 years previously was evaluated histologically after extraction. The histological evaluation revealed resorption of the apical root surface, depositions in cement with different phases and mineral density, and histological changes in the periodontal ligament.

  18. Histological healing in inflammatory bowel disease: A still unfulfilled promise

    PubMed Central

    Villanacci, Vincenzo; Antonelli, Elisabetta; Geboes, Karel; Casella, Giovanni; Bassotti, Gabrio

    2013-01-01

    Treatment of inflammatory bowel disease (IBD) is traditionally based on several drugs, including salicylates, corticosteroids, and antibiotics; in addition, the therapeutic armamentarium has considerably evolved with the advent of newer, effective therapeutic measures (such as the biological agents) that are able to improve in a considerable manner both the clinical and endoscopic variables. Thus, mucosal healing, at least considered from an endoscopic point of view, is today regarded as the ultimate endpoint for treatment of these conditions. However, it is also increasingly clear that endoscopic healing is not necessarily paralleled by histological healing; There are few doubts that the latter should be considered as a true, objective healing and the ultimate goal to reach when treating patients with IBD. Unfortunately, and surprisingly, only a few, incomplete, and somewhat conflicting data exist on this topic, especially because there is still the need to standardize both histological assessment and the severity grading of these disorders; Issues that have not been yet been resolved for clinical practice and therapeutic trials. Hopefully, with the help of an increased awareness on the clinical researchers’ side, and the availability of dedicated pathologists on the other side, this matter will be effectively faced and resolved in the near future. PMID:23467585

  19. Technique for histological control of surgical margins in lip cancer.

    PubMed

    Aoyagi, Satoru; Hata, Hiroo; Homma, Erina; Shimizu, Hiroshi

    2014-04-01

    To preserve oral function and achieve acceptable cosmetic results, intraoperative control of surgical margins with frozen section evaluation may help to determine surgical technique in lip cancer. However, frozen section analysis is usually limited to suspicious areas and has not been systematically performed among surgeons. The accuracy of such analysis for detecting histological surgical margins is highly dependent on the methods used to obtain and analyze the margins. Improving the pathodiagnostic reliability of conventional intraoperative frozen section evaluation is the most important goal of surgical management in our method. We describe the successful use of the "double-blade method" in lip cancer treatment. The technique we describe has the advantage of histologically confirming clear margins in lip cancer. This method appears to be time-saving and easy to apply with existing surgical systems. In addition, this method may be used as an alternative to complete evaluation of lateral surgical margins that is important in planning a suitable surgical reconstruction procedure in lip cancer at many institutions where Mohs micrographic surgery is difficult to perform. © 2014 Japanese Dermatological Association.

  20. NDER: A Novel Web Application for Teaching Histology to Medical Students.

    PubMed

    Parker, Elizabeth U; Reder, Nicholas P; Glasser, Daniel; Henriksen, Jonathan; Kilgore, Mark R; Rendi, Mara H

    2017-01-01

    Medical students require a strong foundation in normal histology. However, current trends in medical school curricula have diminished time devoted to histology. Thus, there is a need for more efficient methods of teaching histology. We have developed a novel software program (Novel Diagnostic Educational Resource; https://pcs-webtest0.pathology.washington.edu/academics/pattern/) that uses annotated whole slide images to teach normal histology. Whole slide images of a wide variety of tissues were annotated by a trainee and validated by an experienced pathologist. Still images were extracted and transferred to the Novel Diagnostic Educational Resource web application. In Novel Diagnostic Educational Resource, an image was displayed briefly and the user was forced to identify the tissue type. The display time changed inversely based on cumulative accuracy to challenge the user and maintain engagement. A total of 129 second-year medical students completed the 30-minute Novel Diagnostic Educational Resource module. Surveys showed an increase in confidence from premodule (0% extremely confident, 4% very, 47% somewhat, and 49% not) to postmodule (9% extremely confident, 57% very, 32% somewhat, and 2% not), P < .0001. Accuracy increased from 72.6% pretest to 95.7% posttest, P < .002. The effect size (Cohen d = 2.30) was very large, where 0.2 is a small effect, 0.5 moderate, and 0.8 large. Ninety-six percent of students would recommend Novel Diagnostic Educational Resource to other medical students, and 98% would use Novel Diagnostic Educational Resource to further enhance their histology knowledge. Novel Diagnostic Educational Resource drastically improved medical student accuracy in classifying normal histology and improved confidence. Additional study is needed to determine knowledge retention, but Novel Diagnostic Educational Resource has great potential for efficient teaching of histology given the curriculum time constraints in medical education.

  1. Regional Variations in Orbicularis Oculi Histology.

    PubMed

    Costin, Bryan R; Plesec, Thomas P; Kopplin, Laura J; Chundury, Rao V; McBride, Jennifer M; Levine, Mark R; Perry, Julian D

    2015-01-01

    To investigate and compare the histologic compositions of the pretarsal, preseptal, and orbital orbicularis oculi muscle (OOM) using nonpreserved, fresh-frozen, human cadavers. The OOM was exposed using sharp and blunt dissection. A metric ruler was used to measure and mark 0.5 cm × 1 cm samples from each portion of the right, superior OOM. Samples were excised, fixed in formalin, and completely embedded in paraffin. Five-micrometer-thick, hematoxylin- and eosin-stained sections were generated for each sample and analyzed by an anatomical pathologist. The relative percentages of the 4 main tissue types (skeletal muscle, fibrous tissue, adipose tissue, and neurovascular tissue) were quantified. Forty-two samples were obtained from 14 Caucasian cadavers. On average, the pretarsal samples were composed of 83.5% skeletal muscle, 0.0% adipose, 5.0% neurovascular, and 11.5% fibrous tissue. Average preseptal OOM was 46.5% skeletal muscle, 12.7% adipose, 9.2% neurovascular, and 31.5% fibrous tissue. The orbital OOM was, on average, 42.7% skeletal muscle, 32.7% adipose tissue, 6.9% neurovascular, and 17.7% fibrous tissue. The OOM represents a histologically heterogeneous structure.

  2. Histologic differentiation of desmoplastic melanoma from cicatrices.

    PubMed

    Kaneishi, N K; Cockerell, C J

    1998-04-01

    Desmoplastic malignant melanoma (DMM) is a rare variant of melanoma that can be very difficult to diagnose correctly both clinically and histologically. The problem is compounded by the fact that many lesions persist at previous biopsy or excision sites so that scar tissue is often present admixed with or adjacent to the spindle cell neoplasm which may exhibit fibroblastic differentiation itself. In order to assess this problem, we compared and contrasted the histologic features of six DMM with 15 examples of cicatrices from various sources. Mature scars were readily differentiated from DMM by light microscopy. In contrast, immature scar and DMM had many features in common including hypercellularity, nodular lymphoid infiltrates, myxoid stroma, and atypical nuclei. The presence of a melanocytic proliferation within the epidermis above the dermal component, neurotropism, and S-100 and/or HMB-45 positivity of neoplastic cells were the only features that permitted reliable differentiation between the two. Clinical correlation and review of previous biopsy specimens are crucial in preventing a delayed diagnosis of DMM. Re-excision is advised in all questionable cases.

  3. [Histological and molecular alterations in inflammatory myopathies].

    PubMed

    Vázquez Del Mercado Espinosa, Mónica; Arana Argaez, Víctor; Petri, Marcelo Heron; Aguilar Arreola, Jorge

    2009-11-01

    The histological findings in muscle biopsies of inflammatory myopathies have been divided into 2 groups: A) Endomisial infiltrates mainly by T CD8+, CD4+ and macrophages and B) Perivascular infiltrates by CD4+, B cells and macrophages. The first kind of infiltrate suggests an immune reaction against muscle fibers very common in PM and inclusion body myositis, On the other hand the perivascular infiltrate is a hallmark of DM. It has ben shown that autoantigens related with myopathies such as Mi-2, Jo-1, OJ, PL12, Ku, PM/Scl are able to suffer proteolytic cleavage by granzyme B and other stimulus induced by cytotoxic T cells. In this chapter we will review the histological and molecular findings of inflammatory myopathies but we will also discuss a special group of myopathies related to the presence of antibodies against the SRP complex, in particular the SRP72 and SRP54 antibodies, which are associated with a poor prognosis and clinical outcome and present an inadequate response to conventional treatment. Copyright © 2009 Elsevier España, S.L. All rights reserved.

  4. Histological Organization in Hepatocyte Organoid Cultures

    PubMed Central

    Michalopoulos, George K.; Bowen, William C.; Mulè, Karen; Stolz, Donna Beer

    2001-01-01

    Hepatocytes and other cellular elements isolated by collagenase perfusion of the liver and maintained in defined culture conditions undergo a series of complex changes, including apoptosis and cell proliferation, to reconstruct tissue with specific architecture. Cultures in collagen-coated pleated surface roller bottles, with hepatocyte growth medium medium and in the presence of hepatocyte growth factor (HGF) and epidermal growth factor (EGF), form characteristic and reproducible tissue architecture composed of a superficial layer of biliary epithelial cells, an intermediate layer of connective tissue and hepatocytes, and a basal layer of endothelial cells. Dexamethasone, EGF, and HGF are required for the complete histological organization. Analysis of the structures formed demonstrates that the receptor tyrosine kinase ligands HGF and EGF are required for the presence, growth, and phenotypic maturation of the biliary epithelium on the surface of the cultures and for the formation of connective tissue in the cultures. Dexamethasone, in the presence of HGF and EGF, was required for the phenotypic maturation of hepatocytes. The results demonstrate the role of these molecules for the formation and phenotypic maturation of specific histological elements of the liver and suggest roles for these signaling molecules in the formation and structure of the in vivo hepatic architecture. PMID:11696448

  5. Tooth ankylosis. Clinical, radiographic and histological assessments.

    PubMed

    Andersson, L; Blomlöf, L; Lindskog, S; Feiglin, B; Hammarström, L

    1984-10-01

    Ankylosis is a serious condition for the affected teeth as such teeth form part of the remodelling process of the alveolar bone and are therefore progressively resorbed. There are, however, very few clinical studies on tooth ankylosis and the reason for this may be due to the difficulties that are encountered in the diagnosis of minor areas of ankylosis. In the present study, the radiographs, percussion sound and mobility of experimentally extracted and replanted monkey incisors were compared with a morphometric histological study of ankylosis. Ankylotic areas were evident radiographically when the ankylosis was located on the proximal surfaces of the root, but were not evident when the ankylosis occurred on the lingual and labial surfaces. The percussion sound was dull and the mobility normal in all non-ankylotic teeth as well as in those teeth which histologically demonstrated ankylosis on less than 10% of the root surface. When the ankylosis affected 10-20% of the root surface, 2 out of 4 teeth changed their percussion sound from dull to high and these teeth no longer possessed normal mobility. When more than 20% of the root surface was affected with ankylosis, the percussion sound was characteristically high in all teeth and no mobility was present.

  6. Light microscopic histology of supraspinatus tendon ruptures.

    PubMed

    Longo, Umile Giuseppe; Franceschi, Francesco; Ruzzini, Laura; Rabitti, Carla; Morini, Sergio; Maffulli, Nicola; Forriol, Francisco; Denaro, Vincenzo

    2007-11-01

    We analysed the morphological features of the human surgical specimens of supraspinatus tendon from patients with rotator cuff tears. Tendon samples were harvested from 31 subjects (21 men and 10 women; mean age 51 years, range 38-64) who underwent arthroscopic repair of a rotator cuff tear, and from five male patients who died of cardiovascular events (mean age, 69.6 years). Histological examination was performed using Haematoxylin and Eosin, Masson's Trichrome and Van Gieson's connective tissue stain. The specimens were examined twice by the same examiner under white light and polarized light microscopy. Particular effort was made to assess any evidence of the changes associated with tendinopathy. Within each specific category of tendon abnormalities, the chi-square test showed significant differences between the control and ruptured tendons (P < 0.05). Using the kappa statistics, the agreement between the two readings ranged from 0.57 to 0.84. We found thinning and disorientation of collagen fibres and chondroid metaplasia to be more pronounced on the articular side of the specimens from patients with rotator cuff tear (P < 0.05). The present study provides a description of the histological architecture of human surgical specimens of normal supraspinatus tendon from patients with rotator cuff tears and demonstrates more frequent tendon changes on the articular side of the rotator cuff.

  7. Light microscopic histology of quadriceps tendon ruptures.

    PubMed

    Maffulli, Nicola; Del Buono, Angelo; Spiezia, Filippo; Longo, Umile Giuseppe; Denaro, Vincenzo

    2012-11-01

    To assess histological changes and possible differences in the quadriceps of patients undergoing open repair of the tendon after spontaneous rupture, and subjects with no history of tendon pathology. Biopsies were harvested from the quadriceps tendon of 46 patients (34 men, 12 women) who had reported unilateral atraumatic quadriceps tendon rupture and had undergone surgical repair of the tendon. Samples were also harvested from both the tendons in 11 (N = 11 × 2) patients, nine males and two females, dying from cardiovascular disorders. For each tendon, three slides were randomly selected and examined under light microscopy, and assessed using a semiquantitative grading scale (range 0-21) which considers fibre structure, fibre arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, and hyalinisation. The pathological sum-score averaged 19.2 ± 3.7 in ruptured tendons and 5.6 ± 2.0 in controls, and all variables considered were significantly different between the two groups, showing an association between tendon abnormalities and rupture (0.05 < P < 0.001). This study confirms that the presence of histological degenerative changes in torn quadriceps tendons increases the risk of rupture.

  8. Campylobacter pylori: clinical, histological, and serological studies.

    PubMed Central

    Musgrove, C; Bolton, F J; Krypczyk, A M; Temperley, J M; Cairns, S A; Owen, W G; Hutchinson, D N

    1988-01-01

    The presence of Campylobacter pylori, histologically diagnosed gastritis, and antibodies to C pylori were determined in a series of 113 patients undergoing endoscopy. Paired biopsy specimens from the fundus, body, and antrum were collected from 59 patients and from the antrum of 54 patients. The presence of C pylori was confirmed by either culture or silver stain in 30 of 59, 31 of 59, and 54 of 103 biopsy specimens from the fundus, body, and antrum, respectively. Of the specimens which contained C pylori 20 of 30 (66%) from the fundus, 25 of 31 (80%) from the body, and 54 (100%) from the antrum showed gastritis. C pylori and gastritis were shown in seven of nine (78.1%) of patients with gastric ulcers and in nine of 11 (82%) of patients with duodenal ulcers. Using an enzyme linked immunosorbent assay (ELISA) technique to detect IgG antibody to C pylori, all patients with histologically diagnosed gastritis and organisms present had titres of greater than or equal to 640; eight of 39 (21%) of patients without gastritis and without organisms gave similar titres. Hence the presence of C pylori was associated with gastritis and with raised titres of IgG antibody. Images Fig 1 Fig 2 PMID:3225334

  9. Are We Throwing Histology out with the Microscope? A Look at Histology from the Physician's Perspective

    ERIC Educational Resources Information Center

    Pratt, Rebecca L.

    2009-01-01

    A trend in medical schools across the United States is the refurbishing of histology laboratories with digital microscopy systems. Although such systems may reduce curricular time, they do not teach basic microscope skills, and students who learn solely with these systems may be less prepared for their practices or specialties, particularly in…

  10. Are We Throwing Histology out with the Microscope? A Look at Histology from the Physician's Perspective

    ERIC Educational Resources Information Center

    Pratt, Rebecca L.

    2009-01-01

    A trend in medical schools across the United States is the refurbishing of histology laboratories with digital microscopy systems. Although such systems may reduce curricular time, they do not teach basic microscope skills, and students who learn solely with these systems may be less prepared for their practices or specialties, particularly in…

  11. Liposoluble vitamins in Crustacean feed: Metabolic and Histological responses.

    PubMed

    Fernández-Gimenez, Analía Verónica

    2016-05-01

    Vitamins are vital for normal growth and survival of living organisms and they are distributed in feedstuffs in small quantities. This review is focused on the liposoluble vitamins (A, D, E and K) in the diets and metabolic responses of the Argentine penaeoid shrimps Pleoticus muelleri and Artemesia longinaris, distributed along the South American coast line. Growth, survival and histological analyses serve as indicators of the nutritional value derived from vitamin deficiency. Liposoluble vitamins are also related to stress, antioxidant defense and immune response of shrimps. Effective diet for shrimp culture that provide not only macronutrients including protein and lipid but also micronutrients such as vitamins for optimal growth is an ever improving subject. This review may help formulating suitable feeds for shrimps.

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

    PubMed Central

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

    2017-01-01

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

  13. Rheumatoid neuropathy: a histological and electrophysiological study

    PubMed Central

    Weller, R. O.; Bruckner, F. E.; Chamberlain, M. Anne

    1970-01-01

    Peripheral nerves in five patients with rheumatoid neuropathy were examined electrophysiologically and by sural nerve biopsy. There was close correlation between the clinical severity of the disease and the degree of nerve damage found histologically and by EMG. Group 1 patients with a mild distal sensory neuropathy showed varying degrees of axonal degeneration in the large myelinated fibres and some segmental demyelination. Group 2 patients with a severe, rapidly progressive sensori-motor neuropathy had extensive loss of myelinated fibres. In one case all the large fibres had degenerated. The second case had lost both large and small myelinated fibres together with many of the non-myelinated axons. The major nerve damage in both groups appeared to be axonal degeneration but some segmental demyelination was detected. Occlusive vascular disease in the vasa nervorum was considered to be the major cause of the nerve damage. Images PMID:4320255

  14. The Histological Slides and Drawings of Cajal

    PubMed Central

    Garcia-Lopez, Pablo; Garcia-Marin, Virginia; Freire, Miguel

    2009-01-01

    Ramón y Cajal's studies in the field of neuroscience provoked a radical change in the course of its history. For this reason he is considered as the father of modern neuroscience. Some of his original preparations are housed at the Cajal Museum (Cajal Institute, CSIC, Madrid, Spain). In this article, we catalogue and analyse more than 4,500 of Cajal's histological preparations, the same preparations he used during his scientific career. Furthermore, we catalogued Cajal's original correspondence, both manuscripts and personal letters, drawings and plates. This is the first time anyone has compiled an account of Cajal's enormous scientific production, offering some curious insights into his work and his legacy. PMID:20339483

  15. Chronic tonsillitis: histological and immunohistochemical aspects.

    PubMed

    Mogoantă, Carmen Aurelia; Ioniţă, Elena; Pirici, D; Mitroi, Mihaela; Anghelina, Fl; Ciolofan, S; Pătru, Emilia

    2008-01-01

    Chronic tonsillitis represents the most common inflammatory lesions of the pharynx determining numerous local or distant evolutive complications. We decided to study the histological and especially immunohistochemical expression of this pathology. We have studied 112 surgical samples representing tonsils resected from 56 patients with chronic tonsillitis. The tonsillectomies were performed in the ENT Clinic of the Emergency County Hospital of Craiova, between 01.01.2007--31.12.2007. The processed histological samples were stained using Hematoxylin-Eosin, light green trichromic and argental impregnation. For the immunohistochemical study, we used LSAB method with CD20, CD45 RO, CD68 antibodies in order to reveal and differentiate T- and B-lymphocytes and also the macrophages. In all samples, we found hyperplasia and hypertrophy of the lymphoid follicle with excessive developing of the clear germinal center as a normal reaction to antigens presence. In some cases, we remarked micro hemorrhages and hematic extravasations inside the follicles, probably due to the excessive virulence of the pathogens causing endothelial lesions. The conjunctive stroma was enriched in collagen fibbers, in some cases organized in strong fascicles with an obvious tendency to divide the tonsils in lobules. The young fibroblastic type cells were numerous. The specific reticulin fibbers had a low representation being disorganized. The immunohistochemical study proved that the clear center of the lymphoid follicles was occupied by B-lymphocytes, but the T-lymphocytes were present in the cortical region of the follicles, perifollicles and in the surface epithelium. In some pathological cases, the predominant cellular population of the clear center was formed by T-lymphocytes.

  16. The histological assessment of cutaneous vasculitis.

    PubMed

    Carlson, J Andrew

    2010-01-01

    Vasculitis is defined as inflammation directed at vessels, which compromises or destroys the vessel wall leading to haemorrhagic and/or ischaemic events. Skin biopsy is the gold standard for the diagnosis of cutaneous vasculitis, whose manifestations include urticaria, infiltrative erythema, petechiae, purpura, purpuric papules, haemorrhagic vesicles and bullae, nodules, livedo racemosa, deep (punched out) ulcers and digital gangrene. These varied morphologies are a direct reflection of size of the vessels and extent of the vascular bed affected, ranging from a vasculitis affecting few superficial, small vessels in petechial eruptions to extensive pan-dermal small vessel vasculitis in haemorrhagic bullae to muscular vessel vasculitis in lower extremity nodules with livedo racemosa. Skin biopsy, extending to subcutis and taken from the earliest, most symptomatic, reddish or purpuric lesion is crucial for obtaining a high-yielding diagnostic sample. Based on histology, vasculitis can be classified on the size of vessels affected and the dominant immune cell mediating the inflammation (e.g. neutrophilic, granulomatous, lymphocytic, or eosinophilic). Disruption of small vessels by inflammatory cells, deposition of fibrin within the lumen and/or vessel wall coupled with nuclear debris allows for the confident recognition of small vessel, mostly neutrophilic vasculitis (also known as leukocytoclastic vasculitis). In contrast, muscular vessel vasculitis can be identified solely by infiltration of its wall by inflammatory cells. Extravasation of red blood cells (purpura) and necrosis are supportive, but not diagnostic of vasculitis as they are also seen in haemorrhagic and/or vaso-occlusive disorders (pseudovasculitis). Vasculitic foci associated with extravascular granulomas (palisaded neutrophilic and granulomatous dermatitis), tissue eosinophilia, or tissue neutrophilia signal the risk for, or co-existence of systemic disease. This essential histological information

  17. High Speed Data Processing for Imaging MS-Based Molecular Histology Using Graphical Processing Units

    NASA Astrophysics Data System (ADS)

    Jones, Emrys A.; van Zeijl, René J. M.; Andrén, Per E.; Deelder, André M.; Wolters, Lex; McDonnell, Liam A.

    2012-04-01

    Imaging MS enables the distributions of hundreds of biomolecular ions to be determined directly from tissue samples. The application of multivariate methods, to identify pixels possessing correlated MS profiles, is referred to as molecular histology as tissues can be annotated on the basis of the MS profiles. The application of imaging MS-based molecular histology to larger tissue series, for clinical applications, requires significantly increased computational capacity in order to efficiently analyze the very large, highly dimensional datasets. Such datasets are highly suited to processing using graphical processor units, a very cost-effective solution for high speed processing. Here we demonstrate up to 13× speed improvements for imaging MS-based molecular histology using off-the-shelf components, and demonstrate equivalence with CPU based calculations. It is then discussed how imaging MS investigations may be designed to fully exploit the high speed of graphical processor units.

  18. Mammoth tooth enamel growth rates inferred from stable isotope analysis and histology

    NASA Astrophysics Data System (ADS)

    Metcalfe, Jessica Z.; Longstaffe, Fred J.

    2012-05-01

    Mammoth (Mammuthus sp.) teeth are relatively abundant in Quaternary deposits from Eurasia and North America, and their isotopic compositions can be used to reconstruct past seasonal patterns in precipitation, diet, and migration. Strategies for collecting and interpreting such data, however, are strongly dependent on growth rates, which can vary among species, individuals, and within teeth. In this study, we use histological and isotopic measurements to determine enamel growth rates for a Columbian mammoth (Mammuthus columbi) tooth in two directions. Using histology, the growth rate through the enamel thickness (ET; perpendicular to the height of the tooth) is estimated at 0.8 to 1.5 mm/yr. Isotopic sampling through the innermost 0.36 mm of the ET recovered less than half a period of variation (i.e., half an inferred year of growth), which is consistent with the histological estimate for ET growth rate. A combination of histological and isotopic measurements suggests that the enamel extension rate (growth in the height of the tooth) is 13-14 mm/yr. Knowledge of enamel growth rates should improve the design and interpretation of future isotopic studies of mammoth teeth. The combination of histological and isotopic measurements may also prove useful in determining growth rates for other extinct taxa.

  19. Optimized SIFTFlow for registration of whole-mount histology to reference optical images.

    PubMed

    Shojaii, Rushin; Martel, Anne L

    2016-10-01

    The registration of two-dimensional histology images to reference images from other modalities is an important preprocessing step in the reconstruction of three-dimensional histology volumes. This is a challenging problem because of the differences in the appearances of histology images and other modalities, and the presence of large nonrigid deformations which occur during slide preparation. This paper shows the feasibility of using densely sampled scale-invariant feature transform (SIFT) features and a SIFTFlow deformable registration algorithm for coregistering whole-mount histology images with blockface optical images. We present a method for jointly optimizing the regularization parameters used by the SIFTFlow objective function and use it to determine the most appropriate values for the registration of breast lumpectomy specimens. We demonstrate that tuning the regularization parameters results in significant improvements in accuracy and we also show that SIFTFlow outperforms a previously described edge-based registration method. The accuracy of the histology images to blockface images registration using the optimized SIFTFlow method was assessed using an independent test set of images from five different lumpectomy specimens and the mean registration error was [Formula: see text].

  20. Histological study of the external, middle and inner ear of horses.

    PubMed

    Blanke, A; Aupperle, H; Seeger, J; Kubick, C; Schusser, G F

    2015-12-01

    Clinical, anatomical and histological aspects of the equine acoustic organ have been poorly investigated and illustrated in literature so far. It is understood that an intact acoustic organ and hearing function are of vital importance for the well-being of flight animals like horses. The knowledge of the acoustic organ is usually transferred analogously from other mammals to horses. The purpose of this study was to provide a detailed and complete histological description of the healthy equine auditory organ, and to determine its congruity to other mammalians. Anatomical dissections and histological preparations were carried out on ten cadaver heads. Specimens of various parts of the equine acoustic organ were taken and evaluated histologically. The histological composition of external, middle and inner ear structures are predominantly congruent to those of other mammals, especially to human beings. Unique inwardly directed rete pegs within the osseous ear canal and the prominent tensor tympani muscle are described for the first time. Results obtained in this study can be employed as references for further research on the equine acoustic organ and improve the understanding of the clinical development of hearing loss, otitis externa/media/interna or tympanosclerosis. © 2014 Blackwell Verlag GmbH.

  1. Insight into the Dissociation of Behavior from Histology in Synucleinopathies and in Related Neurodegenerative Diseases.

    PubMed

    Sekiyama, Kazunari; Takamatsu, Yoshiki; Koike, Wakako; Waragai, Masaaki; Takenouchi, Takato; Sugama, Shuei; Hashimoto, Makoto

    2016-03-31

    Recent clinical trials using immunization approaches against Alzheimer's disease (AD) have failed to demonstrate improved cognitive functions in patients, despite potent suppression in the formation of both senile plaques and other amyloid-β deposits in postmortem brains. Similarly, we observed that treatment with ibuprofen, a non-steroidal anti-inflammatory drug, was effective in improving the histopathology, such as reducing both protein aggregation and glial activation, in the brains of transgenic mice expressing dementia with Lewy bodies-linked P123H β-synuclein. In contrast, only a small improvement in cognitive functions was observed in these mice. Collectively, it is predicted that histology does not correlate with behavior that is resilient and resistant to therapeutic stimuli. Notably, such a 'discrepancy between histology and behavior' is reminiscent of AD-like pathologies and incidental Lewy bodies, which are frequently encountered in postmortem brains of the elderly who had been asymptomatic for memory loss and Parkinsonism during their lives. We suggest that 'the discrepancy between histology and behavior' may be a universal feature that is associated with various aspects of neurodegenerative diseases. Furthermore, given that the cognitive reserve is specifically observed in human brains, human behavior may be evolutionally distinct from that in other animals, thus, contributing to the differential efficiency of therapy between human and lower animals, an important issue in the therapy of neurodegenerative diseases. Overall, it is important to better understand 'the discrepancy between histology and behavior' in the mechanism of neurodegeneration for the development of effective therapies against neurodegenerative diseases.

  2. A histological ontology of the human cardiovascular system.

    PubMed

    Mazo, Claudia; Salazar, Liliana; Corcho, Oscar; Trujillo, Maria; Alegre, Enrique

    2017-10-02

    In this paper, we describe a histological ontology of the human cardiovascular system developed in collaboration among histology experts and computer scientists. The histological ontology is developed following an existing methodology using Conceptual Models (CMs) and validated using OOPS!, expert evaluation with CMs, and how accurately the ontology can answer the Competency Questions (CQ). It is publicly available at http://bioportal.bioontology.org/ontologies/HO and https://w3id.org/def/System . The histological ontology is developed to support complex tasks, such as supporting teaching activities, medical practices, and bio-medical research or having natural language interactions.

  3. Lymphoma Heterogeneity: Three Different Histological Pictures and One Unique Clone

    PubMed Central

    Alonso-Alvarez, Sara; Blanco, Óscar; Alcoceba, Miguel; Balanzategui, Ana; Caballero, Juan C.; Dávila, Julio; González, Marcos; Caballero, María D.; Martín, Alejandro; García-Sanz, Ramón

    2016-01-01

    We report a patient who developed up to three different lymphomas with the same clonal IGH rearrangement. She was first diagnosed of splenic zone marginal lymphoma and relapsed for the first time with Hodgkin lymphoma histology and later with diffuse large B-cell lymphoma histology. Subsequent biopsies and analysis of clonally rearranged IGH genes helped to elucidate the clonal relationship between the three histologies and to confirm a common origin from the three tissue histologies. An integrated diagnosis should always be performed in order to achieve the most accurate diagnosis and be able to choose the best therapeutic options for our patients. PMID:27867670

  4. Anatomy and Histology of an Epicanthal Fold.

    PubMed

    Park, Jae Woo; Hwang, Kun

    2016-06-01

    The aim of this study is to elucidate the precise anatomical and histological detail of the epicanthal fold.Thirty-two hemifaces of 16 Korean adult cadavers were used in this study (30 hemifaces with an epicanthal fold, 2 without an epicanthal fold). In 2 patients who had an epicanthoplasty, the epicanthal folds were sampled.In a dissection, the periorbital skin and subcutaneous tissues were removed and the epicanthal fold was observed in relation to each part of the orbicularis oculi muscle. Specimens including the epicanthal fold were embeddedin in paraffin, sectioned at 10 um, and stained with Hematoxylin-Eosin. The horizontal section in the level of the paplebral fissure was made and the prepared slides were observed under a light microscope.In the specimens without an epicanthal fold, no connection between the upper preseptal muscle and the lower preseptal muscle was found. In the specimens with an epicanthal fold, a connection of the upper preseptal muscle to the lower preseptal muscle was observed. It was present in all 15 hemifaces (100%). There was no connection between the pretarsal muscles. In a horizontal section, the epicanthal fold was composed of 3 compartments: an outer skin lining, a core structure, and an innerskin lining. The core structure was mainly composed of muscular fibers and fibrotic tissue and they were intermingled.Surgeons should be aware of the anatomical details of an epicanthal fold. In removing or reconstructing an epicanthal fold, the fibromuscular core band should also be removed or reconstructed.

  5. Comparative anatomy and histology of xenarthran osteoderms.

    PubMed

    Hill, Robert V

    2006-12-01

    Reconstruction of soft tissues in fossil vertebrates is an enduring challenge for paleontologists. Because inferences must be based on evidence from hard tissues (typically bones or teeth), even the most complete fossils provide only limited information about certain organ systems. Osteoderms ("dermal armor") are integumentary bones with high fossilization potential that hold information about the anatomy of the skin in many extant and fossil amniotes. Their importance for functional morphology and phylogenetic research has recently been recognized, but studies have focused largely upon reptiles, in which osteoderms are most common. Among mammals, osteoderms occur only in members of the clade Xenarthra, which includes armadillos and their extinct relatives: glyptodonts, pampatheres, and, more distantly, ground sloths. Here, I present new information on the comparative morphology and histology of osteoderms and their associated soft tissues in 11 extant and fossil xenarthrans. Extinct mylodontid sloths possessed simple, isolated ossicles, the presence of which is likely plesiomorphic for Xenarthra. More highly derived osteoderms of glyptodonts, pampatheres, and armadillos feature complex articulations and surface ornamentation. Osteoderms of modern armadillos are physically associated with a variety of soft tissues, including nerve, muscle, gland, and connective tissue. In some cases, similar osteological features may be caused by two or more different tissue types, rendering soft-tissue inferences for fossil osteoderms equivocal. Certain osteological structures, however, are consistently associated with specific soft-tissue complexes and therefore represent a relatively robust foundation upon which to base soft-tissue reconstructions of extinct xenarthrans. Copyright 2006 Wiley-Liss, Inc.

  6. Lost caps in histological counting methods.

    PubMed

    Hedreen, J C

    1998-03-01

    In methods with the goal of counting objects in a sectioned tissue volume by examining their profiles or segments in the sections, lost caps, i.e., small object fragments unnoticed or missing at the section surfaces, are an unavoidable issue. The problem of lost caps is examined as it applies to four methods for counting in histological sections, the method usually referred to as the Abercrombie correction, the empirical method, the optical disector, and the physical disector. Lost caps are an insoluble problem in the Abercrombie method; the lost caps error correction factor should be incorporated into the Abercrombie equation. Lost caps cancel out in the optical disector. The empirical method logically requires, to avoid lost caps error, either a preliminary blind identification of object segments in the serial sections or identification of segments with reference to adjacent sections in the counting sections. Similarly, the physical disector method requires either a preliminary blind identification of object segments in both look-up and sampling sections, or use of three sections rather than two.

  7. Histology of the central nervous system.

    PubMed

    Garman, Robert H

    2011-01-01

    The intent of this article is to assist pathologists inexperienced in examining central nervous system (CNS) sections to recognize normal and abnormal cell types as well as some common artifacts. Dark neurons are the most common histologic artifact but, with experience, can readily be distinguished from degenerating (eosinophilic) neurons. Neuron degeneration stains can be useful in lowering the threshold for detecting neuron degeneration as well as for revealing degeneration within populations of neurons that are too small to show the associated eosinophilic cytoplasmic alteration within H&E-stained sections. Neuron degeneration may also be identified by the presence of associated macroglial and microglial reactions. Knowledge of the distribution of astrocyte cytoplasmic processes is helpful in determining that certain patterns of treatment-related neuropil vacuolation (as well as some artifacts) represent swelling of these processes. On the other hand, vacuoles with different distribution patterns may represent alterations of the myelin sheath. Because brains are typically undersampled for microscopic evaluation, many pathologists are unfamiliar with the circumventricuar organs (CVOs) that represent normal brain structures but are often mistaken for lesions. Therefore, the six CVOs found in the brain are also illustrated in this article.

  8. Chronic viral hepatitis: the histology report.

    PubMed

    Guido, Maria; Mangia, Alessandra; Faa, Gavino

    2011-03-01

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

  9. Image analysis of vocal fold histology

    NASA Astrophysics Data System (ADS)

    Reinisch, Lou; Garrett, C. Gaelyn

    2001-05-01

    To visualize the concentration gradients of collagen, elastin and ground substance in histologic sections of vocal folds, an image enhancement scheme was devised. Slides stained with Movat's solution were viewed on a light microscope. The image was digitally photographed. Using commercially available software, all pixels within a color range are selected from the mucosa presented on the image. Using the Movat's pentachrome stain, yellow to yellow-brown pixels represented mature collagen, blue to blue-green pixels represented young collagen (collagen that is not fully cross-linked) and black to dark violet pixels represented elastin. From each of the color range selections, a black and white image was created. The pixels not within the color range were black. The selected pixels within the color range were white. The image was averaged and smoothed to produce 256 levels of gray with less spatial resolution. This new grey-scale image showed the concentration gradient. These images were further enhanced with contour lines surrounding equivalent levels of gray. This technique is helpful to compare the micro-anatomy of the vocal folds. For instance, we find large concentration of the collagen deep in the mucosa and adjacent to the vocalis muscle.

  10. Histological study of white rhinoceros integument

    PubMed Central

    Ruiz, Saul; Rodriguez-Sosa, José R.

    2017-01-01

    In this study, we report findings from a microscopic analysis of the white rhinoceros (Ceratotherium simum) integumentary ultrastructure. Skin samples from the cheek, shoulder, flank and rump were taken from a 46-year-old female southern white rhinoceros and examined using H&E and elastic histological stains. The epidermis was thickest in the flank (1.003 mm) followed by the rump, cheek and shoulder. The stratum corneum comprised more than half the epidermal thickness. Numerous melanin granules were found in the basal and spinosum layers. The epidermal-dermal junction was characterized by abundant papillary folds increasing surface contact between integument layers. Most of the dermal thickness consisted of organized collagen bundles with scattered elastic fibers. Collagen fiber bundles were thickest in the flank (210.9 μm) followed by shoulder, rump and cheek. Simple coiled sweat glands were present in the dermis, but hair and sebaceous glands were absent. Together, these data suggest the white rhinoceros has a unique integumentary system among large terrestrial herbivores. PMID:28441468

  11. Histological study of white rhinoceros integument.

    PubMed

    Plochocki, Jeffrey H; Ruiz, Saul; Rodriguez-Sosa, José R; Hall, Margaret I

    2017-01-01

    In this study, we report findings from a microscopic analysis of the white rhinoceros (Ceratotherium simum) integumentary ultrastructure. Skin samples from the cheek, shoulder, flank and rump were taken from a 46-year-old female southern white rhinoceros and examined using H&E and elastic histological stains. The epidermis was thickest in the flank (1.003 mm) followed by the rump, cheek and shoulder. The stratum corneum comprised more than half the epidermal thickness. Numerous melanin granules were found in the basal and spinosum layers. The epidermal-dermal junction was characterized by abundant papillary folds increasing surface contact between integument layers. Most of the dermal thickness consisted of organized collagen bundles with scattered elastic fibers. Collagen fiber bundles were thickest in the flank (210.9 μm) followed by shoulder, rump and cheek. Simple coiled sweat glands were present in the dermis, but hair and sebaceous glands were absent. Together, these data suggest the white rhinoceros has a unique integumentary system among large terrestrial herbivores.

  12. Assessing Tumor Angiogenesis in Histological Samples.

    PubMed

    Pang, Jia-Min; Jene, Nicholas; Fox, Stephen B

    2016-01-01

    Tumor neovascularization acquires their vessels through a number of processes including angiogenesis, vasculogenesis, vascular remodeling, intussusception, and possibly vascular mimicry in certain tumors. The end result of the tumor vasculature has been quantified by counting the number of immunohistochemically identified microvessels in areas of maximal vascularity, so-called hot spot. Other techniques have been developed such as Chalkley counting and the use of image analysis systems that are robust and reproducible as well as being more objective. Many of the molecular pathways that govern tumor neovascularization have been identified and many reagents are now available to study these tissue sections. These include angiogenic growth factors and their receptors and cell adhesion molecules, proteases, and markers of activated, proliferating, cytokine-stimulated, or angiogenic vessels, such as CD105. It is also possible to differentiate quiescent from active vessels. Other reagents that can identify proteins involved in microenvironmental influences such as hypoxia have also been generated. Although the histological assessment of tumor vascularity is used mostly in the research context, it may also have clinical applications if appropriate methodology and trained observers perform the studies.

  13. Quantitative Neuromorphometry Using Magnetic Resonance Histology

    PubMed Central

    Johnson, G. Allan; Badea, Alexandra; Jiang, Yi

    2010-01-01

    Magnetic resonance imaging (MRI), now common in the clinical domain, has been adapted for use by the neuropathologist by increasing the spatial resolution over 100,000-times what is common in human clinical imaging. This increase in spatial resolution has been accomplished through a variety of technical advances—higher magnetic fields, more sensitive receivers, and clever encoding methods. Magnetic resonance histology (MRH), i.e. the application of MRI to study tissue specimens, now makes three-dimensional imaging of the fixed brain in the cranium routine. Active staining (perfusion fixation with a paramagnetic contrast agent) has allowed us to reduce the scan time by more than 8-times over earlier methods. The result is a three-dimensional isotropic image array that can be viewed along any direction without loss of spatial resolution. Homologous slices can be chosen interactively. Since the tissue is still fully hydrated in the cranium, tissue shrinkage and distortion are virtually eliminated. Volume measurements of neural structures can be made with a high degree of precision and accuracy. MRH will not replace more traditional methods, but it promises enormous value in choosing particular areas and times for more traditional sectioning and assessment. PMID:21119052

  14. Are histologic studies of adenotonsillectomy really necessary?

    PubMed

    Rebechi, Giseli; Pontes, Thiago Euênio; Braga, Elias Lobo; Matos, Willian Maduel; Rebechi, Fernando; Matsuyama, Cícero

    2013-10-01

    Introduction In most ear, nose, and throat services, it is routine to send the material extracted from tonsillectomy for histologic study to research malignancy, to analyze suspect material, or to provide medical-legal documentation. Recent studies have shown that this routine analysis is dispensable. Objective To evaluate the actual need and perform a cost-benefit analysis of routine histopathologic examination in tonsillectomy with no signs or symptoms of malignancy. Methods A retrospective observational study evaluated the charts of patients undergoing adenotonsillectomy, tonsillectomy, or adenoidectomy from January 2008 to September 2009 at the Institute of Otorhinolaryngology CEMA-SP. Costs of this test for the public health system were analyzed and the literature reviewed. Results We studied 281 patients between 2 and 22 years of age; 142 (50.5%) were male and 139 (49.5%) were female. Of the surgeries, 201 were adenotonsillectomies (71.5%), 41 were tonsillectomies (14.5%), and 39 were adenoidectomies (14%). The most common indication for surgery was recurrent infection (63.3%). None of study patients had clinical suspicion of malignancy. The tests showed a cost of R$20.03 per tonsil analyzed. Conclusion Routine histopathologic examination in patients undergoing adenotonsillectomy with no signs or symptoms of malignancy is dispensable and increases the cost of the surgeries.

  15. Are Histologic Studies of Adenotonsillectomy Really Necessary?

    PubMed Central

    Rebechi, Giseli; Pontes, Thiago Euênio; Braga, Elias Lobo; Matos, Willian Maduel; Rebechi, Fernando; Matsuyama, Cícero

    2013-01-01

    Introduction In most ear, nose, and throat services, it is routine to send the material extracted from tonsillectomy for histologic study to research malignancy, to analyze suspect material, or to provide medical-legal documentation. Recent studies have shown that this routine analysis is dispensable. Objective To evaluate the actual need and perform a cost–benefit analysis of routine histopathologic examination in tonsillectomy with no signs or symptoms of malignancy. Methods A retrospective observational study evaluated the charts of patients undergoing adenotonsillectomy, tonsillectomy, or adenoidectomy from January 2008 to September 2009 at the Institute of Otorhinolaryngology CEMA-SP. Costs of this test for the public health system were analyzed and the literature reviewed. Results We studied 281 patients between 2 and 22 years of age; 142 (50.5%) were male and 139 (49.5%) were female. Of the surgeries, 201 were adenotonsillectomies (71.5%), 41 were tonsillectomies (14.5%), and 39 were adenoidectomies (14%). The most common indication for surgery was recurrent infection (63.3%). None of study patients had clinical suspicion of malignancy. The tests showed a cost of R$20.03 per tonsil analyzed. Conclusion Routine histopathologic examination in patients undergoing adenotonsillectomy with no signs or symptoms of malignancy is dispensable and increases the cost of the surgeries. PMID:25992042

  16. Two neutrophilic dermatoses captured simultaneously on histology

    PubMed Central

    Wlodek, Christina; Bhatt, Nidhi; Kennedy, Cameron

    2016-01-01

    A number of neutrophilic dermatoses are associated with malignancies and their treatment. These rarely occur together in the same patient. A Caucasian 72-year-old male was treated for acute myeloid leukemia (AML) with chemotherapy including daunorubicin and cytarabine. Within 48 hours of commencing treatment, he developed pyrexia and, two days later, disseminated non-tender pink plaques on the limbs and trunk. A skin biopsy showed a dermal interstitial infiltrate of lymphocytes, histiocytoid cells and predominantly neutrophils. This extended into the subcutis, where a neutrophilic lobular panniculitis was seen. These findings are consistent with Sweet’s syndrome. In addition, a neutrophilic and lymphocytic infiltrate was also present around eccrine coils and lower ducts. The eccrine epithelium showed squamous metaplasia with dyskeratosis and sloughing into the lumen. These latter findings are consistent with neutrophilic eccrine hidradenitis (NEH). These two histologically distinct entities form part of the neutrophilic dermatoses that have been described in oncology patients with reports of concurrent or sequential occurrence of various neutrophilic dermatoses in the same patient. Ours, however, is only the second reported case of simultaneously captured Sweet’s and NEH in the setting of AML. The most likely explanation is that of an epiphenomenon, whereby the neutrophilic infiltrate extended around the sweat glands in the context of the neutrophilic dermatosis. PMID:27648385

  17. Automatic morphometry of nerve histological sections.

    PubMed

    Romero, E; Cuisenaire, O; Denef, J F; Delbeke, J; Macq, B; Veraart, C

    2000-04-15

    A method for the automatic segmentation, recognition and measurement of neuronal myelinated fibers in nerve histological sections is presented. In this method, the fiber parameters i.e. perimeter, area, position of the fiber and myelin sheath thickness are automatically computed. Obliquity of the sections may be taken into account. First, the image is thresholded to provide a coarse classification between myelin and non-myelin pixels. Next, the resulting binary image is further simplified using connected morphological operators. By applying semantic rules to the zonal graph axon candidates are identified. Those are either isolated or still connected. Then, separation of connected fibers is performed by evaluating myelin sheath thickness around each candidate area with an Euclidean distance transformation. Finally, properties of each detected fiber are computed and false positives are removed. The accuracy of the method is assessed by evaluating missed detection, false positive ratio and comparing the results to the manual procedure with sampling. In the evaluated nerve surface, a 0.9% of false positives was found, along with 6.36% of missed detections. The resulting histograms show strong correlation with those obtained by manual measure. The noise introduced by this method is significantly lower than the intrinsic sampling variability. This automatic method constitutes an original tool for morphometrical analysis.

  18. H2O2 Improves Quality of Radix scutellariae Through Anti-oxidant Effect.

    PubMed

    Qi, Song; Wu-Lin, Cao; Hua, Jiang; Ai-Hua, Zhang; Xiang-Cai, Meng

    2016-01-01

    The correlation between the quality and geographical origin of herbal medicine was traced back to Tang Dynasty in China, more than 1200 years, and the effects of ecological environments on the secondary metabolites such as flavonoids have been confirmed. However, little is known about how the adversity impacts on the quality. Reactive oxygen species (ROS) may be medium between the ecological environment and the secondary metabolism. The fresh roots of Scutellaria baicalensis Georgi were treated with 0.002 μmol/L, 0.2 μmol/L, and 20 μmol/L H2O2, respectively. A stress model was established to elucidate the change of secondary metabolism, anti-oxidant enzyme system, and enzymes relating to flavonoids. The activities of superoxide dismutase, catalase and peroxidase decreased. Too much H2O2, firstly, boosted transformation of flavonoids glycoside into aglucon with the most remarkable activities through UDP-glucuronate baicalein 7-O-glucuronosyltransferase (UBGAT), and β-glucuronidase (GUS), then regulated the gene expression of phenylalanine ammonialyase, GUS, and UBGAT, and increased the contents of flavones, motivated the flavonoid glycoside converting into aglucon. With this action, the flavones displaced the anti-oxidant enzymes. The higher the dosage, the more baicalein and wogonin increased, the later they took action. The plant secondary metabolites to keep ROS constant are identical to the effective materials in clinic. They are closely linked. H2O2 can improve flavones, especially the aglucon, and further increased the quality of herbal medicine, which possesses very important value in medical practice. H2O2 decreasing the activities of CAT and POD lead to accumulation of more H2O2. Excess of H2O2 up-regulated PAL, BUG, promote biosynthesis of flavones, and enhance the nonenzyme system. "↑" and "↓" represent activity or content "up" and "down" respectively.

  19. H2O2 Improves Quality of Radix scutellariae Through Anti-oxidant Effect

    PubMed Central

    Qi, Song; Wu-lin, Cao; Hua, Jiang; Ai-hua, Zhang; Xiang-cai, Meng

    2016-01-01

    Introduction: The correlation between the quality and geographical origin of herbal medicine was traced back to Tang Dynasty in China, more than 1200 years, and the effects of ecological environments on the secondary metabolites such as flavonoids have been confirmed. However, little is known about how the adversity impacts on the quality. Reactive oxygen species (ROS) may be medium between the ecological environment and the secondary metabolism. Materials and Methods: The fresh roots of Scutellaria baicalensis Georgi were treated with 0.002 μmol/L, 0.2 μmol/L, and 20 μmol/L H2O2, respectively. A stress model was established to elucidate the change of secondary metabolism, anti-oxidant enzyme system, and enzymes relating to flavonoids. Results: The activities of superoxide dismutase, catalase and peroxidase decreased. Too much H2O2, firstly, boosted transformation of flavonoids glycoside into aglucon with the most remarkable activities through UDP-glucuronate baicalein 7-O-glucuronosyltransferase (UBGAT), and β-glucuronidase (GUS), then regulated the gene expression of phenylalanine ammonialyase, GUS, and UBGAT, and increased the contents of flavones, motivated the flavonoid glycoside converting into aglucon. With this action, the flavones displaced the anti-oxidant enzymes. The higher the dosage, the more baicalein and wogonin increased, the later they took action. Conclusion: The plant secondary metabolites to keep ROS constant are identical to the effective materials in clinic. They are closely linked. H2O2 can improve flavones, especially the aglucon, and further increased the quality of herbal medicine, which possesses very important value in medical practice. SUMMARY H2O2 decreasing the activities of CAT and POD lead to accumulation of more H2O2. Excess of H2O2 up-regulated PAL, BUG, promote biosynthesis of flavones, and enhance the nonenzyme system. “↑” and “↓” represent activity or content “up” and “down” respectively. PMID:27019566

  20. Histological Validity and Clinical Evidence for Use of Fractional Lasers for Acne Scars

    PubMed Central

    Sardana, Kabir; Garg, Vijay K; Arora, Pooja; Khurana, Nita

    2012-01-01

    Though fractional lasers are widely used for acne scars, very little clinical or histological data based on the objective clinical assessment or the depth of penetration of lasers on in vivo facial tissue are available. The depth probably is the most important aspect that predicts the improvement in acne scars but the studies on histology have little uniformity in terms of substrate (tissue) used, processing and stains used. The variability of the laser setting (dose, pulses and density) makes comparison of the studies difficult. It is easier to compare the end results, histological depth and clinical results. We analysed all the published clinical and histological studies on fractional lasers in acne scars and analysed the data, both clinical and histological, by statistical software to decipher their significance. On statistical analysis, the depth was found to be variable with the 1550-nm lasers achieving a depth of 679 μm versus 10,600 nm (895 μm) and 2940 nm (837 μm) lasers. The mean depth of penetration (in μm) in relation to the energy used, in millijoules (mj), varies depending on the laser studied. This was statistically found to be 12.9–28.5 for Er:glass, 3–54.38 for Er:YAG and 6.28–53.66 for CO2. The subjective clinical improvement was a modest 46%. The lack of objective evaluation of clinical improvement and scar-specific assessment with the lack of appropriate in vivo studies is a case for combining conventional modalities like subcision, punch excision and needling with fractional lasers to achieve optimal results. PMID:23060702

  1. Histological evaluation and optimization of surgical vessel sealing systems

    NASA Astrophysics Data System (ADS)

    Lathrop, Robert; Ryan, Thomas; Gaspredes, Jonathan; Woloszko, Jean; Coad, James E.

    2017-02-01

    Surgical vessel sealing systems are widely used to achieve hemostasis and dissection in open surgery and minimally invasive, laparoscopic surgery. This enabling technology was developed about 17 years ago and continues to evolve with new devices and systems achieving improved outcomes. Histopathological assessment of thermally sealed tissues is a valuable tool for refining and comparing performance among surgical vessel sealing systems. Early work in this field typically assessed seal time, burst rate, and failure rate (in-situ). Later work compared histological staining methods with birefringence to assess the extent of thermal damage to tissues adjacent to the device. Understanding the microscopic architecture of a sealed vessel is crucial to optimizing the performance of power delivery algorithms and device design parameters. Manufacturers rely on these techniques to develop new products. A system for histopathological evaluation of vessels and sealing performance was established, to enable the direct assessment of a treatment's tissue effects. The parameters included the commonly used seal time, pressure burst rate and failure rate, as well as extensions of the assessment to include its likelihood to form steam vacuoles, adjacent thermal effect near the device, and extent of thermally affected tissue extruded back into the vessel lumen. This comprehensive assessment method provides an improved means of assessing the quality of a sealed vessel and understanding the exact mechanisms which create an optimally sealed vessel.

  2. The development of confocal arthroscopy as optical histology for rotator cuff tendinopathy.

    PubMed

    Wu, J-P; Walton, M; Wang, A; Anderson, P; Wang, T; Kirk, T B; Zheng, M H

    2015-09-01

    MRI, ultrasound and video arthroscopy are traditional imaging technologies for noninvasive or minimal invasive assessment of the rotator cuff tendon pathology. However, these imaging modalities do not have sufficient resolution to demonstrate the pathology of rotator cuff tendons at a microstructural level. Therefore, they are insensitive to low-level tendon diseases. Although traditional histology can be used to analyze the physiology of rotator cuff tendons, it requires biopsy that traumatizes the rotator cuff, thus, potentially comprising the mechanical properties of tendons. Besides, it cannot offer real-time histological information. Confocal endoscopy offers a way to assess the microstructural disorder in tissues without biopsy. However, the application of this useful technique for detecting low-level tendon diseases has been restricted by using clinical grade fluorescent contrast agent to acquire high-resolution microstructural images of tendons. In this study, using a clinical grade sodium fluorescein contrast agent, we have reported the development of confocal arthroscopy for optical histological assessment without biopsy. The confocal arthroscopic technique was able to demonstrate rotator cuff tendinopathy in human cadavers, which appeared macroscopically normal under video arthroscopic examinations. The tendinopathy status of the rotator cuff tendons was confirmed by corresponding traditional histology. The development of confocal arthroscopy may provide a minimally invasive imaging technique for real-time histology of rotator cuff without the need for tissue biopsy. This technique has the potential for surgeons to gain in real time the histological information of rotator cuff tendons, which may assist planning repair strategies and potentially improve intervention outcomes. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  3. Histological evidence for muscle insertion in extant amniote femora: implications for muscle reconstruction in fossils.

    PubMed

    Petermann, Holger; Sander, Martin

    2013-04-01

    Since the 19th century, identification of muscle attachment sites on bones has been important for muscle reconstructions, especially in fossil tetrapods, and therefore has been the subject of numerous biological and paleontological studies. At the microscopic level, in histological thin sections, the only features that can be used reliably for identifying tendon-bone or muscle-tendon-bone interactions are Sharpey's fibers. Muscles, however, do not only attach to the bone indirectly with tendons, but also directly. Previous studies failed to provide new indicators for muscle attachment, or to address the question of whether muscles with direct attachment can be identified histologically. However, histological identification of direct muscle attachments is important because these attachments do not leave visible marks (e.g. scars and rugosities) on the bone surface. We dissected the right hind limb and mapped the muscle attachment sites on the femur of one rabbit (Oryctolagus cuniculus), one Alligator mississippiensis, and one turkey (Meleagris cuniculus). We then extracted the femur and prepared four histological thin sections for the rabbit and the turkey and five histological thin sections for the alligator. Sharpey's fibers, vascular canal orientation, and a frayed periosteal margin can be indicators for indirect but also direct muscle attachment. Sharpey's fibers can be oriented to the cutting plane of the thin section at high angles, and two Sharpey's fibers orientations can occur in one area, possibly indicating a secondary force axis. However, only about 60% of mapped muscle attachment sites could be detected in thin sections, and frequently histological features suggestive of muscle attachment occurred outside mapped sites. While these insights should improve our ability to successfully identify and reconstruct muscles in extinct species, they also show the limitations of this approach.

  4. Histological evidence for muscle insertion in extant amniote femora: implications for muscle reconstruction in fossils

    PubMed Central

    Petermann, Holger; Sander, Martin

    2013-01-01

    Since the 19th century, identification of muscle attachment sites on bones has been important for muscle reconstructions, especially in fossil tetrapods, and therefore has been the subject of numerous biological and paleontological studies. At the microscopic level, in histological thin sections, the only features that can be used reliably for identifying tendon–bone or muscle–tendon-bone interactions are Sharpey's fibers. Muscles, however, do not only attach to the bone indirectly with tendons, but also directly. Previous studies failed to provide new indicators for muscle attachment, or to address the question of whether muscles with direct attachment can be identified histologically. However, histological identification of direct muscle attachments is important because these attachments do not leave visible marks (e.g. scars and rugosities) on the bone surface. We dissected the right hind limb and mapped the muscle attachment sites on the femur of one rabbit (Oryctolagus cuniculus), one Alligator mississippiensis, and one turkey (Meleagris cuniculus). We then extracted the femur and prepared four histological thin sections for the rabbit and the turkey and five histological thin sections for the alligator. Sharpey's fibers, vascular canal orientation, and a frayed periosteal margin can be indicators for indirect but also direct muscle attachment. Sharpey's fibers can be oriented to the cutting plane of the thin section at high angles, and two Sharpey's fibers orientations can occur in one area, possibly indicating a secondary force axis. However, only about 60% of mapped muscle attachment sites could be detected in thin sections, and frequently histological features suggestive of muscle attachment occurred outside mapped sites. While these insights should improve our ability to successfully identify and reconstruct muscles in extinct species, they also show the limitations of this approach. PMID:23439026

  5. Could magnetic resonance provide in vivo histology?

    PubMed

    Dominietto, Marco; Rudin, Markus

    2014-01-13

    THE DIAGNOSIS OF A SUSPECTED TUMOR LESION FACES TWO BASIC PROBLEMS: detection and identification of the specific type of tumor. Radiological techniques are commonly used for the detection and localization of solid tumors. Prerequisite is a high intrinsic or enhanced contrast between normal and neoplastic tissue. Identification of the tumor type is still based on histological analysis. The result depends critically on the sampling sites, which given the inherent heterogeneity of tumors, constitutes a major limitation. Non-invasive in vivo imaging might overcome this limitation providing comprehensive three-dimensional morphological, physiological, and metabolic information as well as the possibility for longitudinal studies. In this context, magnetic resonance based techniques are quite attractive since offer at the same time high spatial resolution, unique soft tissue contrast, good temporal resolution to study dynamic processes and high chemical specificity. The goal of this paper is to review the role of magnetic resonance techniques in characterizing tumor tissue in vivo both at morphological and physiological levels. The first part of this review covers methods, which provide information on specific aspects of tumor phenotypes, considered as indicators of malignancy. These comprise measurements of the inflammatory status, neo-vascular physiology, acidosis, tumor oxygenation, and metabolism together with tissue morphology. Even if the spatial resolution is not sufficient to characterize the tumor phenotype at a cellular level, this multiparametric information might potentially be used for classification of tumors. The second part discusses mathematical tools, which allow characterizing tissue based on the acquired three-dimensional data set. In particular, methods addressing tumor heterogeneity will be highlighted. Finally, we address the potential and limitation of using MRI as a tool to provide in vivo tissue characterization.

  6. Large Deformation Diffeomorphic Metric Mapping Registration of Reconstructed 3D Histological Section Images and in vivo MR Images

    PubMed Central

    Ceritoglu, Can; Wang, Lei; Selemon, Lynn D.; Csernansky, John G.; Miller, Michael I.; Ratnanather, J. Tilak

    2009-01-01

    Our current understanding of neuroanatomical abnormalities in neuropsychiatric diseases is based largely on magnetic resonance imaging (MRI) and post mortem histological analyses of the brain. Further advances in elucidating altered brain structure in these human conditions might emerge from combining MRI and histological methods. We propose a multistage method for registering 3D volumes reconstructed from histological sections to corresponding in vivo MRI volumes from the same subjects: (1) manual segmentation of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) compartments in histological sections, (2) alignment of consecutive histological sections using 2D rigid transformation to construct a 3D histological image volume from the aligned sections, (3) registration of reconstructed 3D histological volumes to the corresponding 3D MRI volumes using 3D affine transformation, (4) intensity normalization of images via histogram matching, and (5) registration of the volumes via intensity based large deformation diffeomorphic metric (LDDMM) image matching algorithm. Here we demonstrate the utility of our method in the transfer of cytoarchitectonic information from histological sections to identify regions of interest in MRI scans of nine adult macaque brains for morphometric analyses. LDDMM improved the accuracy of the registration via decreased distances between GM/CSF surfaces after LDDMM (0.39 ± 0.13 mm) compared to distances after affine registration (0.76 ± 0.41 mm). Similarly, WM/GM distances decreased to 0.28 ± 0.16 mm after LDDMM compared to 0.54 ± 0.39 mm after affine registration. The multistage registration method may find broad application for mapping histologically based information, for example, receptor distributions, gene expression, onto MRI volumes. PMID:20577633

  7. Promoting Rapid Learning in the Histology Laboratory by Integrating Technology

    ERIC Educational Resources Information Center

    Shields, Vonnie

    2008-01-01

    This paper describes the results of incorporating technology in the histology laboratory by using high-resolution video-imaging equipment (VIE). The study sought to determine if (1) the VIE would allow students to more easily and rapidly find histological structures over more conventional methods, and (2) if they could find the structures with the…

  8. [Intestinal lipodystrophy (M. Whipple). Synopsis of radiology, endoscopy and histology].

    PubMed

    Tremmel, K; Hoffmann, R; Weiss, J; Dahm, H H

    1986-01-01

    The case of a 48 years old man with intestinal lipodystrophy (Whipple's disease) is clinically, roentgenologically, endoscopically and histologically documented. The diagnosis was established by endoscopic biopsy and laparatomy. The patho-histologic changes of the mucosa of the proximal small bowel are pathognomonic. Roentgenologically the characteristic mucosal and lymphadenoid changes can be demonstrated as well as the extent of the process.

  9. Promoting Rapid Learning in the Histology Laboratory by Integrating Technology

    ERIC Educational Resources Information Center

    Shields, Vonnie

    2008-01-01

    This paper describes the results of incorporating technology in the histology laboratory by using high-resolution video-imaging equipment (VIE). The study sought to determine if (1) the VIE would allow students to more easily and rapidly find histological structures over more conventional methods, and (2) if they could find the structures with the…

  10. Image-based histologic grade estimation using stochastic geometry analysis

    NASA Astrophysics Data System (ADS)

    Petushi, Sokol; Zhang, Jasper; Milutinovic, Aladin; Breen, David E.; Garcia, Fernando U.

    2011-03-01

    Background: Low reproducibility of histologic grading of breast carcinoma due to its subjectivity has traditionally diminished the prognostic value of histologic breast cancer grading. The objective of this study is to assess the effectiveness and reproducibility of grading breast carcinomas with automated computer-based image processing that utilizes stochastic geometry shape analysis. Methods: We used histology images stained with Hematoxylin & Eosin (H&E) from invasive mammary carcinoma, no special type cases as a source domain and study environment. We developed a customized hybrid semi-automated segmentation algorithm to cluster the raw image data and reduce the image domain complexity to a binary representation with the foreground representing regions of high density of malignant cells. A second algorithm was developed to apply stochastic geometry and texture analysis measurements to the segmented images and to produce shape distributions, transforming the original color images into a histogram representation that captures their distinguishing properties between various histological grades. Results: Computational results were compared against known histological grades assigned by the pathologist. The Earth Mover's Distance (EMD) similarity metric and the K-Nearest Neighbors (KNN) classification algorithm provided correlations between the high-dimensional set of shape distributions and a priori known histological grades. Conclusion: Computational pattern analysis of histology shows promise as an effective software tool in breast cancer histological grading.

  11. Technical note: a histological technique for detecting the cryptic preservation of erythrocytes and soft tissue in ancient human skeletonized remains.

    PubMed

    Setzer, Teddi J; Sundell, Inger Birgitta; Dibbley, Susan K; Les, Clifford

    2013-12-01

    Bone samples from a Middle Bronze Age (ca., 1600-1300 BC) site were prepared for histological analysis. Preliminary results suggested that components of bone marrow remained preserved. To verify these findings and optimize the sample preparation procedure, we conducted experiments varying the type of acid used to decalcify the bones for histology preparation, as well as the exposure time to the demineralizing agents and thickness of sections taken from the samples for slide preparation. Subsequent examination of the slides revealed the presence of well-preserved erythrocytes and other cellular structures consistent with bone marrow. Our results demonstrate that the traditional methods used to prepare bone samples for histology may be adjusted to improve the quality of the soft tissue architecture and cellular morphology for histological observation. Copyright © 2013 Wiley Periodicals, Inc.

  12. Histological patterns of muscle in infants with developmental brain abnormalities.

    PubMed

    Curless, R G; Nelson, M B; Brimmer, F

    1978-04-01

    The histology of muscle obtained from 23 hypotonic infants without neuromuscular disease is presented. Long-term follow-up neurological examinations were carried out to determine the site of the lesion. 18 cases have strong evidence of cerebral dysfunction, 12 of whom have histologial abnormalities of fiber-type distribution and diameter. Of the remaining five patients without obvious cerebral abnormality, four also had histological changes, but individual circumstances partially explain the cause of the abnormal histological patterns in these four. No single histological abnormality could be identified, but the results indicate that histological abnormalities of muscle in hypotonic infants without clinical or microscopic evidence of neuromuscular disease may be useful in predicting a cerebral cause for the hypotonia.

  13. MMF and calcineurin taper in recurrent hepatitis C after liver transplantation: impact on histological course.

    PubMed

    Bahra, Marcus; Neumann, U I F P; Jacob, Dietmar; Puhl, Gero; Klupp, Jochen; Langrehr, Jan M; Berg, Thomas; Neuhaus, Peter

    2005-02-01

    Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal. The optimal immunosuppression for these patients is still under discussion. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) treatment in patients with recurrent hepatitis C. Forty patients with histologically proven hepatitis C recurrence after OLT were treated with MMF and calcineurin inhibitor (CNI) taper for 24 months and matched with 40 non-MMF-treated positive liver transplant recipients. Liver biopsies were obtained prior to MMF treatment and after a mean follow-up of 24 months. Histological changes were evaluated utilizing the Metavir score. Comparison of fibrosis/inflammation showed no impairment of histological findings during MMF treatment. In contrast, histological findings of the 40 non-MMF patients showed a significant increase of severity for inflammation/fibrosis. Viral load was similar in both groups. The course of alanin amino transferase (ALT) levels measured during MMF treatment showed a significant decrease. MMF in combination with CNI taper showed a positive effect on fibrosis progression, graft inflammation and ALT levels and may improve the clinical course of HCV after OLT, however, the antiviral properties of MMF are still unconfirmed.

  14. Automated image analysis of placental villi and syncytial knots in histological sections.

    PubMed

    Kidron, Debora; Vainer, Ifat; Fisher, Yael; Sharony, Reuven

    2017-05-01

    Delayed villous maturation and accelerated villous maturation diagnosed in histologic sections are morphologic manifestations of pathophysiological conditions. The inter-observer agreement among pathologists in assessing these conditions is moderate at best. We investigated whether automated image analysis of placental villi and syncytial knots could improve standardization in diagnosing these conditions. Placentas of antepartum fetal death at or near term were diagnosed as normal, delayed or accelerated villous maturation. Histologic sections of 5 cases per group were photographed at ×10 magnification. Automated image analysis of villi and syncytial knots was performed, using ImageJ public domain software. Analysis of hundreds of histologic images was carried out within minutes on a personal computer, using macro commands. Compared to normal placentas, villi from delayed maturation were larger and fewer, with fewer and smaller syncytial knots. Villi from accelerated maturation were smaller. The data were further analyzed according to horizontal placental zones and groups of villous size. Normal placentas can be discriminated from placentas of delayed or accelerated villous maturation using automated image analysis. Automated image analysis of villi and syncytial knots is not equivalent to interpretation by the human eye. Each method has advantages and disadvantages in assessing the 2-dimensional histologic sections representing the complex, 3-dimensional villous tree. Image analysis of placentas provides quantitative data that might help in standardizing and grading of placentas for diagnostic and research purposes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Spatial Statistics for Segmenting Histological Structures in H&E Stained Tissue Images.

    PubMed

    Nguyen, Luong; Tosun, Akif Burak; Fine, Jeffrey L; Lee, Adrian V; Taylor, D Lansing; Chennubhotla, S Chakra

    2017-07-01

    Segmenting a broad class of histological structures in transmitted light and/or fluorescence-based images is a prerequisite for determining the pathological basis of cancer, elucidating spatial interactions between histological structures in tumor microenvironments (e.g., tumor infiltrating lymphocytes), facilitating precision medicine studies with deep molecular profiling, and providing an exploratory tool for pathologists. This paper focuses on segmenting histological structures in hematoxylin- and eosin-stained images of breast tissues, e.g., invasive carcinoma, carcinoma in situ, atypical and normal ducts, adipose tissue, and lymphocytes. We propose two graph-theoretic segmentation methods based on local spatial color and nuclei neighborhood statistics. For benchmarking, we curated a data set of 232 high-power field breast tissue images together with expertly annotated ground truth. To accurately model the preference for histological structures (ducts, vessels, tumor nets, adipose, etc.) over the remaining connective tissue and non-tissue areas in ground truth annotations, we propose a new region-based score for evaluating segmentation algorithms. We demonstrate the improvement of our proposed methods over the state-of-the-art algorithms in both region- and boundary-based performance measures.

  16. Histologic and clinical response to varying density settings with a fractionally scanned carbon dioxide laser.

    PubMed

    Saluja, Raminder; Khoury, Jane; Detwiler, Susan P; Goldman, Mitchel P

    2009-01-01

    An evaluation of the histological and clinical response to varying density settings (-10%, 0, and 10% overlap) with a fractionally scanned CO2 laser. Clinical and histological study evaluating abdominoplasty excised tissue for depth of penetration and width of tissue ablated with varying density and energy settings utilizing a scanned microsecond pulsed CO2 laser. These parameters were correlated clinically with patients treated with similar density settings. Fifteen patients were enrolled with 5 patients in each group: group 1 (density 1 settings), group 2 (density 2 settings) and group 3 (density 3 settings). Histological differences of width and depth of tissue ablated with varying density settings and correlation with photodamage improvement clinically. Six samples of excised abdominoplasty tissue were treated with increased energy and density settings and were evaluated histologically. Clinically, 15 patients with photodamage to the face were randomized to receive a fractional CO2 laser treatment with density levels ranging from 1 to 3. Microarrays of tissue injury were visualized with multiple areas of superficial to full-thickness epidermal thermal damage. As energy increased (90 W to 100 W), the width of basophilic coagulation of the subepidermal collagen increased. Increased density paralleled increased depth of penetration of subepidermal coagulation. Patient assessment of discomfort, erythema, edema, and satisfaction with the procedure was proportional to increasing densities. A fractional CO2 laser produces photorejuvenation, erythema, edema and discomfort in proportion with the depth and extent of epidermal and subepidermal thermal damage.

  17. Effectiveness of histology and cytology on musculoskeletal tumor diagnosis

    PubMed Central

    Lima, Pablo Moura de Andrade; Oliveira, Marcelo Parente; Ferreira, George Rocha; Lima, Túlio Paes de Medeiros; Lima, Jairo de Andrade; de Mello, Roberto José Vieira

    2014-01-01

    OBJECTIVE: To compare cytology and histology on the diagnosis of musculoskeletal neoplasms. METHOD: Fifty eight cases available to evaluation were analyzed both by cytology and histology. The results of the biopsies studied by histology and cytology were compared to the results obtained on the surgical specimen or immunohistochemistry. We determined the percentage of correct results, sensitivity, specificity, positive and negative predictive values and accuracy of each method. RESULTS: Twelve per cent of biopsies were inconclusive by cytology. The percentage of correct diagnosis was 70.7% and 81% (p=.179), the ability to differentiate benign lesions from malignant ones was 84.5% and 93.1% (p=0.18) respectively, for cytology and histology. Cytology showed sensitivity of 87.8%, specificity of 76.5%, positive predictive value of 90%, negative predictive value of 72% and accuracy 84.5%. Histology showed sensitivity of 90.2%, specificity of 100%, positive predictive value of 100%, negative predictive value of 81% and accuracy of 93.1%. The Youden index for cytology was 64.3% and for histology it was 90.2%. CONCLUSION: Despite promising, cytology obtained by thin needle aspiration is less accurate and reliable than the histological evaluation on musculoskeletal tumors diagnosis. Level of Evidence II, Diagnostic Studies. PMID:25061418

  18. Dental students' evaluations of an interactive histology software.

    PubMed

    Rosas, Cristian; Rubí, Rafael; Donoso, Manuel; Uribe, Sergio

    2012-11-01

    This study assessed dental students' evaluations of a new Interactive Histology Software (IHS) developed by the authors and compared students' assessment of the extent to which this new software, as well as other histology teaching methods, supported their learning. The IHS is a computer-based tool for histology learning that presents high-resolution images of histology basics as well as specific oral histologies at different magnifications and with text labels. Survey data were collected from 204 first-year dental students at the Universidad Austral de Chile. The survey consisted of questions for the respondents to evaluate the characteristics of the IHS and the contribution of various teaching methods to their histology learning. The response rate was 85 percent. Student evaluations were positive for the design, usability, and theoretical-practical integration of the IHS, and the students reported they would recommend the method to future students. The students continued to value traditional teaching methods for histological lab work and did not think this new technology would replace traditional methods. With respect to the contribution of each teaching method to students' learning, no statistically significant differences (p>0.05) were found for an evaluation of IHS, light microscopy, and slide presentations. However, these student assessments were significantly more positive than the evaluations of other digital or printed materials. Overall, the students evaluated the IHS very positively in terms of method quality and contribution to their learning; they also evaluated use of light microscopy and teacher slide presentations positively.

  19. A histological study of scala communis with radiological implications.

    PubMed

    Makary, Chadi; Shin, Jennifer; Caruso, Paul; Curtin, Hugh; Merchant, Saumil

    2010-01-01

    Scala communis or interscalar septum (IS) defect is a developmental abnormality of the inner ear characterized by a dehiscence in the partition separating the turns of the cochlea. The goals of the present study were to (1) study this anomaly and describe its characteristics compared to control ears using a histological analysis of temporal bones, (2) discuss radiological implications regarding its diagnosis, and (3) describe its embryological derivation. Out of 1775 temporal bones assessed, 22 specimens were found to have scala communis in cochleae containing all 3 turns (basal, middle and apical). These 22 ears were studied in detail by qualitative and quantitative methods using light microscopy. Scala communis occurred as an isolated inner ear anomaly, or in association with other congenital cochlear and/or vestibular anomalies. The defect occurred most often between the middle and apical turns of the cochlea. Compared to control ears, scala communis ears were found to have a smaller modiolar area (p < 0.0001) and flattening of the interscalar ridge (point of attachment of the IS to the inner lumen of the cochlea; p < 0.0001). Scala communis was compatible with normal hearing. Flattening of the interscalar ridge has the potential to improve the diagnosis of scala communis in patients using CT scanning. The anomaly may result from a mesodermal defect such as excessive resorption of mesenchyme during the formation of the scalae, an error in the formation of bone, or both. Copyright © 2010 S. Karger AG, Basel.

  20. Breast carcinoma, intratumour heterogeneity and histological grading, using geostatistics.

    PubMed

    Sharifi-Salamatian, V; de Roquancourt, A; Rigaut, J P

    2000-01-01

    Tumour progression is currently believed to result from genetic instability. Chromosomal patterns specific of a type of cancer are frequent even though phenotypic spatial heterogeneity is omnipresent. The latter is the usual cause of histological grading imprecision, a well documented problem, without any fully satisfactory solution up to now. The present article addresses this problem in breast carcinoma. The assessment of a genetic marker for human tumours requires quantifiable measures of intratumoral heterogeneity. If any invariance paradigm representing a stochastic or geostatistic function could be discovered, this might help in solving the grading problem. A novel methodological approach using geostatistics to measure heterogeneity is used. Twenty tumours from the three usual (Scarff-Bloom and Richardson) grades were obtained and paraffin sections stained by MIB-1 (Ki-67) and peroxidase staining. Whole two-dimensional sections were sampled. Morphometric grids of variable sizes allowed a simple and fast recording of positions of epithelial nuclei, marked or not by MIB-1. The geostatistical method is based here upon the asymptotic behaviour of dispersion variance. Measure of asymptotic exponent of dispersion variance shows an increase from grade 1 to grade 3. Preliminary results are encouraging: grades 1 and 3 on one hand and 2 and 3 on the other hand are totally separated. The final proof of an improved grading using this measure will of course require a confrontation with the results of survival studies.

  1. The atlas of mouse development eHistology resource.

    PubMed

    Graham, Elizabeth; Moss, Julie; Burton, Nick; Roochun, Yogmatee; Armit, Chris; Richardson, Lorna; Baldock, Richard

    2015-06-01

    The Atlas of Mouse Development by Professor Mathew Kaufman is an essential text for understanding mouse developmental anatomy. This definitive and authoritative atlas is still in production and is essential for any biologist working with the mouse embryo, although the last revision dates back to 1994. Here, we announce the eHistology online resource that provides free access to high-resolution colour images digitized from the original histological sections (www.emouseatlas.org/emap/eHistology/index.php) used by Kaufman for the Atlas. The images are provided with the original annotations and plate numbering of the paper atlas and enable viewing the material to cellular resolution.

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

    PubMed

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

    2016-12-01

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

  3. From cytology to histology: diagnosis of a relapsed mediastinal lymphoma by endobronchial ultrasound transbronchial histological needle

    PubMed Central

    Ariza-Prota, Miguel Angel; Bango Álvarez, Antonio; Pérez, Liliana; Pando-Sandoval, Ana; Fuentes, Nelson; Casan, Pere

    2015-01-01

    Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is highly accurate in diagnosing mediastinal lymphadenopathies of lung cancer and benign disorders, with the advantage that it is a minimally invasive technique, unlike open surgery and mediastinoscopy. However, the diagnostic accuracy of EBUS-TBNA for the diagnosis of lymphoma in patients with mediastinal lymphadenopathy is not well defined. The lack of tissue architecture obtained by cytological needles decreases the diagnostic accuracy for diagnosis and subtyping of de novo and relapsed mediastinal lymphomas. We present the first described case in the literature of an anaplastic large cell lymphoma relapsed, diagnosed on tissue fragments obtained by EBUS-TBNA with the particularity of using a histological needle. PMID:26090115

  4. Magnetic resonance imaging, ultrasonography and histology of the suspensory ligament origin: a comparative study of normal anatomy of warmblood horses.

    PubMed

    Bischofberger, A S; Konar, M; Ohlerth, S; Geyer, H; Lang, J; Ueltschi, G; Lischer, C J

    2006-11-01

    The diagnosis of lameness caused by proximal metacarpal and metatarsal pain can be challenging. Magnetic resonance imaging (MRI) offers the possibility for further diagnosis but there have been no studies on the normal MRI appearance of the origin of the suspensory ligament (OSL) in conjunction with ultrasonography and histology. To describe the MRI appearance of the OSL in fore- and hindlimbs of sound horses and compare it to the ultrasonographic and histological appearance. The findings can be used as reference values to recognise pathology in the OSL. The OSL in the fore- and hindlimbs of 6 sound horses was examined by ultrasonography prior to death, and MRI and histology post mortem. Qualitative evaluation and morphometry of the OSL were performed and results of all modalities compared. Muscular tissue, artefacts, variable SL size and shape complicated ultrasonographic interpretation. In MRI and histology the forelimb OSL consisted of 2 portions, the lateral being significantly thicker than medial. The hindlimb SL had a single large area of origin. In fore- and hindlimbs, the amount of muscular tissue was significantly larger laterally than medially. Overall SL measurements using MRI were significantly higher than using histology and ultrasonography and histological higher than ultrasonographic measurements. Morphologically, there was a good correlation between MRI and histology. MRI provides more detailed information than ultrasonography regarding muscle fibre detection and OSL dimension and correlates morphologically well with histology. Therefore, ultrasonographic results should be regarded with caution. MRI may be a diagnostic aid when other modalities fail to identify clearly the cause of proximal metacarpal and metatarsal pain; and may improve selection of adequate therapy and prognosis for injuries in this region.

  5. The Clinical and Histological Spectrum of Idiopathic Inflammatory Myopathies.

    PubMed

    Cavazzana, Ilaria; Fredi, Micaela; Selmi, Carlo; Tincani, Angela; Franceschini, Franco

    2017-02-01

    Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of myositis, characterised by chronic muscle weakness, cutaneous features, different extra-muscular manifestations and circulating autoantibodies. IIMs included classical polymyositis (PM), dermatomyositis (DM) and other different types of myositis with a wide range of muscle involvement. A complete autoantibody profile and a muscle biopsy are mandatory to correctly diagnose different clinical entities and to define their different prognosis. Bohan and Peter's criteria included five items to diagnose adult onset PM and DM. The sensitivity was 74-100 %, while the specificity is low, due to a poor ability to differentiate PM from neuromuscular diseases. Other criteria included a more accurate histological definition of PM, DM or amyopathic DM, obtaining a higher specificity. Autoantibodies' association, interstitial lung disease and clinical cardiac involvement represent the main items that could define the prognosis of these patients. On the other hand, inclusion body myositis is a different myopathy characterised by a peculiar muscle mass involvement, muscle atrophy and progressive loss of function, due to complete failure to all immunosuppressive drugs used. Treatment of IIMs is based on corticosteroids (CS), which show rapid clinical response and functional improvement. Different immunosuppressant drugs are given to obtain a better control of the disease during CS tapering dose. No controlled double blind trials demonstrated the superiority of one immunesuppressant on another. The occurrence of interstitial lung involvement requires the immediate introduction of immunosuppressants in addiction to CS. Severe dysphagia seems to improve with intravenous immunoglobulins (Ig). Physical therapy could be started after the acute phase of diseases and seems to have a beneficial role in muscle strength recovery.

  6. Intramedullary reamings for the histological diagnosis of suspected pathological fractures.

    PubMed

    Hassan, K; Kalra, S; Moran, C

    2007-08-01

    The aim of this study was to evaluate how effective reamings taken at the time of surgery for fracture were in the diagnosis of malignancy. All histology reports over a five-year period were examined. Ninety cases, where reamings were taken, were identified and included. Reamings are commonly sent for histological diagnosis in orthopaedic practice. A definitive tissue diagnosis was established in 55 samples (60%). No diagnosis was established in 30 (33%), as the tissue sample was deemed inadequate, 17 of which were known to have a malignancy elsewhere. Five case reports were lost. The process by which the bone samples were obtained is believed to be very destructive, making histological diagnosis difficult and unreliable. Our study does not support the use of reamings for histology. An alternative technique should be used such as biopsy with the Harlow-Wood trephine.

  7. OOGENESIS AND OVARIAN HISTOLOGY OF THE AMERICAN ALLIGATOR ALLIGATOR MISSISSIPPIENSIS

    EPA Science Inventory

    Although folliculogenesis and oogenesis have been observed in numerous reptiles, these phenomena have not been described in detail in a crocodilian. Oogenesis and histological features of the adult ovary of Alligator mississippiensis are described. Using a complex process, the ov...

  8. PREPARATION OF WHOLE SMALL FISH FOR HISTOLOGICAL EVALUATION

    EPA Science Inventory

    Toxicologic pathology, which is primarily concerned with chemically-induced structural changes in cells or tissues, depends on the proper histological processing of test specimens. In fishes, histopathological examination is widely recognized as a reliable method for disease diag...

  9. Hormonal and histologic findings in human cryopreserved ovarian autografts.

    PubMed

    Dittrich, Ralf; Mueller, Andreas; Maltaris, Theodoros; Hoffmann, Inge; Magener, Achim; Oppelt, Patricia G; Beckmann, Matthias W

    2009-04-01

    This is the first report showing a hormonal and histologic discrepancy in cryopreserved human ovarian tissue 11 months after orthotopic autotransplantation. The presence of antral follicles was observed although the hormonal values had returned to castrated levels.

  10. Clinical implications of rhinoceros reproductive tract anatomy and histology.

    PubMed

    Schaffer, N E; Foley, G L; Gill, S; Pope, C E

    2001-03-01

    Reproductive tracts or tissues from five male black rhinoceroses (Diceros bicornis), two male white rhinoceroses (Ceratotherium simum), two male one-horned Asian rhinoceroses (Rhinoceros unicornis), seven female black rhinoceroses, and six female white rhinoceroses from multiple institutions were examined to characterize their anatomy and histology. Some observations and measurements were obtained from in situ tracts of intact animals before or during necropsy. Formalin-fixed tissues were dissected and examined histologically. Retrospective reproductive data from each rhinoceros was obtained from the institutions of origin. Reproductive histology of these species was similar to that of other mammals. Male accessory gland structure varied among species, and the Asian rhinoceros epididymis was more loosely attached and had larger duct diameters than did the epididymides of the African species. Although histology was typically mammalian, rhinoceros reproductive morphology combined characteristics of several different mammals. Defining this unique morphology of rhinoceroses may help in understanding their reproductive physiology and will effect the development of appropriate reproductive techniques.

  11. OOGENESIS AND OVARIAN HISTOLOGY OF THE AMERICAN ALLIGATOR ALLIGATOR MISSISSIPPIENSIS

    EPA Science Inventory

    Although folliculogenesis and oogenesis have been observed in numerous reptiles, these phenomena have not been described in detail in a crocodilian. Oogenesis and histological features of the adult ovary of Alligator mississippiensis are described. Using a complex process, the ov...

  12. PREPARATION OF WHOLE SMALL FISH FOR HISTOLOGICAL EVALUATION

    EPA Science Inventory

    Toxicologic pathology, which is primarily concerned with chemically-induced structural changes in cells or tissues, depends on the proper histological processing of test specimens. In fishes, histopathological examination is widely recognized as a reliable method for disease diag...

  13. Joint curettage arthrodesis technique in the foot: a histological analysis.

    PubMed

    Johnson, Justin T; Schuberth, John M; Thornton, Sean D; Christensen, Jeffrey C

    2009-01-01

    Arthrodesis via joint contour preservation using the curettage method has become popular in foot and ankle surgery to avoid segmental shortening and the need to bone graft. Despite its popularity, the effect of joint curettage has never been histologically evaluated. Knowledge of the histological appearance after joint curettage would be helpful to the foot and ankle surgeon to better understand the function of joint surface preparation for arthrodesis. Five cadaver specimens were used to harvest the first metatarsocuneiform and subtalar joints for routine histological analysis after performing joint curettage technique. One specimen was used as a reference, whereas the remaining specimens were processed after joint surface preparation. Results show a residual layer of calcified cartilage overlying the subchondral plate interface on all osteochondral specimens after joint curettage. This suggests there is a natural histological barrier that may interfere with arthrodesis consolidation. 5.

  14. Magnetic resonance diffusion tensor imaging for the pedunculopontine nucleus: proof of concept and histological correlation.

    PubMed

    Alho, A T D L; Hamani, C; Alho, E J L; da Silva, R E; Santos, G A B; Neves, R C; Carreira, L L; Araújo, C M M; Magalhães, G; Coelho, D B; Alegro, M C; Martin, M G M; Grinberg, L T; Pasqualucci, C A; Heinsen, H; Fonoff, E T; Amaro, E

    2017-03-10

    The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ post-mortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.

  15. Magnetic resonance imaging in experimental stroke and comparison with histology: systematic review and meta-analysis.

    PubMed

    Milidonis, Xenios; Marshall, Ian; Macleod, Malcolm R; Sena, Emily S

    2015-03-01

    Because the new era of preclinical stroke research demands improvements in validity and generalizability of findings, moving from single site to multicenter studies could be pivotal. However, the conduct of magnetic resonance imaging (MRI) in stroke remains ill-defined. We sought to assess the variability in the use of MRI for evaluating lesions post stroke and to examine the possibility as an alternative to gold standard histology for measuring the infarct size. We identified animal studies of ischemic stroke reporting lesion sizes using MRI. We assessed the degree of heterogeneity and reporting of scanning protocols, postprocessing methods, study design characteristics, and study quality. Studies performing histological evaluation of infarct size were further selected to compare with corresponding MRI using meta-regression. Fifty-four articles undertaking a total of 78 different MRI scanning protocols met the inclusion criteria. T2-weighted imaging was most frequently used (83% of the studies), followed by diffusion-weighted imaging (43%). Reporting of the imaging parameters was adequate, but heterogeneity between studies was high. Twelve studies assessed the infarct size using both MRI and histology at corresponding time points, with T2-weighted imaging-based treatment effect having a significant positive correlation with histology (; P<0.001). Guidelines for standardized use and reporting of MRI in preclinical stroke are urgently needed. T2-weighted imaging could be used as an effective in vivo alternative to histology for estimating treatment effects based on the extent of infarction; however, additional studies are needed to explore the effect of individual parameters. © 2015 American Heart Association, Inc.

  16. Integration of ultra-high field MRI and histology for connectome based research of brain disorders

    PubMed Central

    Yang, Shan; Yang, Zhengyi; Fischer, Karin; Zhong, Kai; Stadler, Jörg; Godenschweger, Frank; Steiner, Johann; Heinze, Hans-Jochen; Bernstein, Hans-Gert; Bogerts, Bernhard; Mawrin, Christian; Reutens, David C.; Speck, Oliver; Walter, Martin

    2013-01-01

    Ultra-high field magnetic resonance imaging (MRI) became increasingly relevant for in vivo neuroscientific research because of improved spatial resolutions. However, this is still the unchallenged domain of histological studies, which long played an important role in the investigation of neuropsychiatric disorders. While the field of biological psychiatry strongly advanced on macroscopic levels, current developments are rediscovering the richness of immunohistological information when attempting a multi-level systematic approach to brain function and dysfunction. For most studies, histology sections lost information on three-dimensional reconstructions. Translating histological sections to 3D-volumes would thus not only allow for multi-stain and multi-subject alignment in post mortem data, but also provide a crucial step in big data initiatives involving the network analyses currently performed with in vivo MRI. We therefore investigated potential pitfalls during integration of MR and histological information where no additional blockface information is available. We demonstrated that strengths and requirements from both methods can be effectively combined at a spatial resolution of 200 μm. However, the success of this approach is heavily dependent on choices of hardware, sequence and reconstruction. We provide a fully automated pipeline that optimizes histological 3D reconstructions, providing a potentially powerful solution not only for primary human post mortem research institutions in neuropsychiatric research, but also to help alleviate the massive workloads in neuroanatomical atlas initiatives. We further demonstrate (for the first time) the feasibility and quality of ultra-high spatial resolution (150 μm isotopic) imaging of the entire human brain MRI at 7T, offering new opportunities for analyses on MR-derived information. PMID:24098272

  17. Radiological versus histological diagnosis in UIP and NSIP: survival implications

    PubMed Central

    Flaherty, K; Thwaite, E; Kazerooni, E; Gross, B; Toews, G; Colby, T; Travis, W; Mumford, J; Murray, S; Flint, A; Lynch, J; Martinez, F

    2003-01-01

    Background: High resolution computed tomography (HRCT) has an important diagnostic role in idiopathic interstitial pneumonia (IIP). We hypothesised that the HRCT appearance would have an impact on survival in patients with IIP. Methods: HRCT scans from patients with histological usual interstitial pneumonia (UIP; n=73) or histological non-specific interstitial pneumonia (NSIP; n=23) were characterised as definite UIP, probable UIP, indeterminate, probable NSIP, or definite NSIP. Cox regression analysis examined the relationships between histopathological and radiological diagnoses and mortality, controlling for patient age, sex, and smoking status. Results: All 27 patients with definite or probable UIP on HRCT had histological UIP; 18 of 44 patients with probable or definite NSIP on HRCT had histological NSIP. Patients with HRCT diagnosed definite or probable UIP had a shorter survival than those with indeterminate CT (hazards ratio (HR) 2.43, 95% CI 1.06 to 5.58; median survival 2.08 v 5.76 years) or HRCT diagnosed definite or probable NSIP (HR 3.47, 95% CI 1.58 to 7.63; median survival 2.08 v 5.81 years). Patients with histological UIP with no HRCT diagnosis of probable or definite UIP fared better than patients with histological UIP and an HRCT diagnosis of definite or probable UIP (HR 0.49, 95% CI 0.25 to 0.98; median survival 5.76 v 2.08 years) and worse than those with a histological diagnosis of NSIP (HR 5.42, 95% CI 1.25 to 23.5; median survival 5.76 v >9 years). Conclusions: Patients with a typical HRCT appearance of UIP experience the highest mortality. A surgical lung biopsy is indicated for patients without an HRCT appearance of UIP to differentiate between histological UIP and NSIP. PMID:12554898

  18. Radiologic and histologic presentation of male mammary myofibroblastoma.

    PubMed

    Omar, Lena A; Rojanapremsuk, Theera; Saluja, Karan; Merchant, Kanwal A; Sharma, Pooja B

    2016-07-01

    Mammary myofibroblastoma is a rare mesenchymal neoplasm that typically presents in older men and women. Less commonly, these benign tumors may also occur in soft tissues located outside of the breast, in which case they are referred to as mammary-type myofibroblastomas. The histologic composition of this benign spindle cell tumor can be markedly varied. We present a case of a large mammary myofibroblastoma in a male patient and discuss the typical imaging and histologic makeup of these tumors.

  19. Renal cell carcinoma: histological classification and correlation with imaging findings.

    PubMed

    Muglia, Valdair F; Prando, Adilson

    2015-01-01

    Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes.

  20. Renal cell carcinoma: histological classification and correlation with imaging findings*

    PubMed Central

    Muglia, Valdair F.; Prando, Adilson

    2015-01-01

    Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes. PMID:26185343

  1. Subperiosteal preparation using a new piezoelectric device: a histological examination

    PubMed Central

    Stoetzer, Marcus; Magel, Anja; Kampmann, Andreas; Lemound, Juliana; Gellrich, Nils-Claudius; von See, Constantin

    2014-01-01

    Introduction: Subperiosteal preparation using a periosteal elevator leads to disturbances of local immunohistochemistry and periosteal histology due to a microtrauma. Usually soft-tissue damage can be considerably reduced by using piezoelectric technology. For this reason, the effects of a novel piezoelectric device on immunohistochemistry and periosteal histology were examined and compared to conventional preparation of the periosteum using a periosteal elevator. Material and methods: Lewis rats were randomly assigned to one of five groups (n=50). Subperiosteal preparation was performed using either a piezoelectric device or a periosteal elevator. Immunohistochemical and histological analyses were performed immediately after preparation as well as three and eight days postoperatively. A statistical analysis of the histological colouring was performed offline using analysis of variance (ANOVA) on ranks (p<0.05). Results: At all times, immunohistochemical and histological analysis demonstrated a significantly more homogenous tissue structure in the group of rats that underwent piezosurgery than in the group of rats that underwent treatment with a periosteal elevator. Conclusion: The use of a piezoelectric device for subperiosteal preparation is associated with more harmonious immunohistochemical and histological results for the periosteum than the use of a conventional periosteal elevator. As a result, piezoelectric devices can be expected to have a positive effect primarily on soft tissue, in particular of the periosteal as well as on surrounding tissues. PMID:26504729

  2. Subperiosteal preparation using a new piezoelectric device: a histological examination.

    PubMed

    Stoetzer, Marcus; Magel, Anja; Kampmann, Andreas; Lemound, Juliana; Gellrich, Nils-Claudius; von See, Constantin

    2014-01-01

    Subperiosteal preparation using a periosteal elevator leads to disturbances of local immunohistochemistry and periosteal histology due to a microtrauma. Usually soft-tissue damage can be considerably reduced by using piezoelectric technology. For this reason, the effects of a novel piezoelectric device on immunohistochemistry and periosteal histology were examined and compared to conventional preparation of the periosteum using a periosteal elevator. Lewis rats were randomly assigned to one of five groups (n=50). Subperiosteal preparation was performed using either a piezoelectric device or a periosteal elevator. Immunohistochemical and histological analyses were performed immediately after preparation as well as three and eight days postoperatively. A statistical analysis of the histological colouring was performed offline using analysis of variance (ANOVA) on ranks (p<0.05). At all times, immunohistochemical and histological analysis demonstrated a significantly more homogenous tissue structure in the group of rats that underwent piezosurgery than in the group of rats that underwent treatment with a periosteal elevator. The use of a piezoelectric device for subperiosteal preparation is associated with more harmonious immunohistochemical and histological results for the periosteum than the use of a conventional periosteal elevator. As a result, piezoelectric devices can be expected to have a positive effect primarily on soft tissue, in particular of the periosteal as well as on surrounding tissues.

  3. Histology of a Harris line in a human distal tibia.

    PubMed

    Miszkiewicz, Justyna J

    2015-07-01

    Identification and diagnosis of Harris lines (HLs) is usually achieved using radiography. To date, histological methods have been mainly implemented in research exploring the underlying processes of HL deposition using longitudinal sections taken from animal bone. Here, a new insight into HL formation is provided following transverse histological sectioning in a human specimen. A distinct HL was identified macroscopically, and from a radiograph, in a left distal tibia taken from an adult human male. Transverse sections were taken through the HL, and also from trabeculae immediately superior and inferior to the HL. Thin sections were produced following standard histological procedures. Micrographs were captured using a digital microscope camera. Trabeculae immediately superior and inferior to the HL displayed no indication of abnormal growth, exhibiting abundant osteocyte lacunae and a lamellar structure. However, the micro-anatomy of the HL was characterised by the following three main features: (1) non-lamellar appearance, (2) a complete lack of osteocyte lacunae, and (3) presence of irregularly distributed tubular structures. These three histological features indicate a specific process of bone deposition, implying that trapping of osteoblasts may not take place during HL formation. Pictorial and descriptive records of HL histology are provided, aiding current understanding about the nature of HL, its identification from histology, and serving as a reference point for future comparative research.

  4. Advances in MRI-based computational neuroanatomy: from morphometry to in-vivo histology.

    PubMed

    Weiskopf, Nikolaus; Mohammadi, Siawoosh; Lutti, Antoine; Callaghan, Martina F

    2015-08-01

    Current computational neuroanatomy based on MRI focuses on morphological measures of the brain. We present recent methodological developments in quantitative MRI (qMRI) that provide standardized measures of the brain, which go beyond morphology. We show how biophysical modelling of qMRI data can provide quantitative histological measures of brain tissue, leading to the emerging field of in-vivo histology using MRI (hMRI). qMRI has greatly improved the sensitivity and specificity of computational neuroanatomy studies. qMRI metrics can also be used as direct indicators of the mechanisms driving observed morphological findings. For hMRI, biophysical models of the MRI signal are being developed to directly access histological information such as cortical myelination, axonal diameters or axonal g-ratio in white matter. Emerging results indicate promising prospects for the combined study of brain microstructure and function. Non-invasive brain tissue characterization using qMRI or hMRI has significant implications for both research and clinics. Both approaches improve comparability across sites and time points, facilitating multicentre/longitudinal studies and standardized diagnostics. hMRI is expected to shed new light on the relationship between brain microstructure, function and behaviour, both in health and disease, and become an indispensable addition to computational neuroanatomy.

  5. Quantitative Histological Validation of Diffusion MRI Fiber Orientation Distributions in the Rat Brain

    PubMed Central

    de Crespigny, Alex; Bolstad, Ingeborg; D'Arceuil, Helen; Bjaalie, Jan G.; Dale, Anders M.

    2010-01-01

    Diffusion MRI (dMRI) is widely used to measure microstructural features of brain white matter, but commonly used dMRI measures have limited capacity to resolve the orientation structure of complex fiber architectures. While several promising new approaches have been proposed, direct quantitative validation of these methods against relevant histological architectures remains missing. In this study, we quantitatively compare neuronal fiber orientation distributions (FODs) derived from ex vivo dMRI data against histological measurements of rat brain myeloarchitecture using manual recordings of individual myelin stained fiber orientations. We show that accurate FOD estimates can be obtained from dMRI data, even in regions with complex architectures of crossing fibers with an intrinsic orientation error of approximately 5–6 degrees in these regions. The reported findings have implications for both clinical and research studies based on dMRI FOD measures, and provide an important biological benchmark for improved FOD reconstruction and fiber tracking methods. PMID:20062822

  6. Development of a fluorescent microsphere technique for rapid histological determination of cerebral blood flow

    PubMed Central

    Eucker, Stephanie A.; Hoffman, Brenton D.; Natesh, Rahul; Ralston, Jill; Armstead, William M.; Margulies, Susan S.

    2010-01-01

    The purpose of this study was to develop a more efficient fluorescent microsphere method to facilitate the rapid use of the histological technique and to enable its use in large tissue regions. Using fluorescent plate/slide imaging technology and automated detection and analysis software, we were able to rapidly image, detect, and count 3 separate microsphere colors in 200 μm-thick tissue sections from piglet brain. In resting newborn piglets (n = 6) on isoflurane anesthesia, we measured a median total cerebral blood flow (CBF) of 105 ml/min/100g (range 27–206 ml/min/100g). Compared with other FM analysis methods, our method reduces the time required to determine blood flow, improves accuracy in lipid-rich tissues and large tissue regions and, unlike the radiolabeled microsphere method, can be combined with histological analysis. PMID:20193669

  7. Development of a fluorescent microsphere technique for rapid histological determination of cerebral blood flow.

    PubMed

    Eucker, Stephanie A; Hoffman, Brenton D; Natesh, Rahul; Ralston, Jill; Armstead, William M; Margulies, Susan S

    2010-04-22

    The purpose of this study was to develop a more efficient fluorescent microsphere method to facilitate the rapid use of the histological technique and to enable its use in large tissue regions. Using fluorescent plate/slide imaging technology and automated detection and analysis software, we were able to rapidly image, detect, and count 3 separate microsphere colors in 200 microm thick tissue sections from piglet brain. In resting newborn piglets (n=6) on isoflurane anesthesia, we measured a median total cerebral blood flow (CBF) of 105 ml/min/100g (range 27-206 ml/min/100 g). Compared with other FM analysis methods, our method reduces the time required to determine blood flow, improves accuracy in lipid-rich tissues and large tissue regions and, unlike the radiolabeled microsphere method, can be combined with histological analysis. Copyright 2010 Elsevier B.V. All rights reserved.

  8. Diagnostic criteria for selenium toxicosis in aquatic birds: histologic lesions

    USGS Publications Warehouse

    Green, D.E.; Albers, P.H.

    1997-01-01

    Chronic selenium toxicosis was induced in 1-year-old male mallard ducks (Anas platyrhynchos) by feeding selenium, as seleno-DL-methionine, in amounts of 0, 10, 20, 40, and 80 parts per million (ppm) to five groups of 21 ducks each for 16 wk during March to July 1988. All mallards in the 80 ppm group, three in the 40 ppm group, and one in the 20 ppm group died. Histologic lesions in mallards that died of selenosis were hepatocellular vacuolar degeneration progressing to centrolobular and panlobular necrosis, nephrosis, apoptosis of pancreatic exocrine cells, hypermaturity and avascularity of contour feathers of the head with atrophy of feather follicles, lymphocytic necrosis and atrophy of lymphoid organs (spleen, gut-associated lymphoid tissue, and lumbar lymph nodes), and severe atrophy and degeneration of fat. Histologic lesions in surviving mallards in the 40 ppm group, which had tissue residues of selenium comparable to mallards that died, were fewer and much milder than mallards that died; lesions consisted of atrophy of lymphoid tissue, hyalinogranular swelling of hepatocytes, atrophy of seminiferous tubules, and senescence of feathers. No significant histologic lesions were detected in euthanized mallards in the 0, 10 and 20 ppm groups. Based on tissue residues and histologic findings, primarily in the liver, there was a threshold of selenium accumulation above which pathophysiologic changes were rapid and fatal. Pathognomonic histologic lesions of fatal and nonfatal selenosis were not detected. Criteria for diagnosis of fatal selenosis in aquatic birds include consistent histologic lesions in the liver, kidneys, and organs of the immune system. Although histologic changes were present in cases of chronic non-fatal selenosis, these were inconsistent. Consistent features of fatal and non-fatal chronic selenosis were marked weight loss and elevated concentrations of selenium in organs.

  9. Histology-directed MALDI mass spectrometry for the diagnostic pathology

    NASA Astrophysics Data System (ADS)

    Kim, Hark Kyun; Kim, In-Hoo

    2012-10-01

    With the advent of targeted agents, it has become clinically important to distinguish histologic types of non-small cell lung cancers (NSCLCs) using biopsy samples. We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may classify histology of NSCLCs. Twentyone pairs of frozen, resected NSCLCs were analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Squamous cell carcinomas and adenocarcinomas, two major histologic types of NSCLC, were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set, suggesting that lipid profiles can classify NSCLCs according to the histologic type. We also found that protein and lipid MALDI MS profiles can classify 30 breast cancers according to the intrinsic subtypes. Immunohistochemistry-defined, luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by cross validation P values < 0.01. Discriminatory proteins and lipids classified tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in 100 random test sets. Potential advantages of this label-free approach may include small tissue requirement, relatively rapid procedure, and low reagent cost. Day-today variation of this technology is also acceptable, with the Pearson correlation of 0.95. Taken together, these results suggest the possible clinical utility of histology-directed, lipid and protein MALDI MS.

  10. Multimodality Treatment of Skull Base Chondrosarcomas: The Role of Histology Specific Treatment Protocols.

    PubMed

    Raza, Shaan M; Gidley, Paul W; Meis, Jeanne M; Grosshans, David R; Bell, Diana; DeMonte, Franco

    2017-09-01

    Limited data exist to guide the multimodality management of chondrosarcomas (CSAs) arising in the skull base. To determine the impact of histological subtype/grade on progression-free survival (PFS) and the indications for surgery, radiation, and chemotherapy based on histology. A retrospective review was performed of 37 patients (conventional type: 81%, mesenchymal: 16.2%, dedifferentiated: 2.7%) treated at The University of Texas M.D. Anderson Cancer Center. Of the conventional subtype, 23% were grade 1, 63% were grade 2, and 14% were grade 3. In addition to surgery, mesenchymal/dedifferentiated CSAs (18% of the cohort) underwent neoadjuvant chemotherapy and 48.6% of the overall cohort received adjuvant radiotherapy. Histological grade/subtype and treatment factors were assessed for impact on median PFS (primary outcome). Conventional subtype vs mesenchymal/dedifferentiated was positively associated with median PFS (166 vs 24 months, P < .05). Increasing conventional grade inversely correlated with median PFS ( P < .05). Gross total resection positively impacted PFS in conventional CSAs (111.8 vs 42.9 months, P = .201) and mesenchymal/dedifferentiated CSAs (58.2 vs 1.0 month, P < .05). Adjuvant radiotherapy significantly impacted PFS in conventional grades 2 and 3 (182 vs 79 months, P < .05) and a positive trend with mesenchymal/dedifferentiated CSAs (43.5 vs 22.0 months). Chemotherapy improved PFS for mesenchymal/dedifferentiated CSAs (50 vs 9 months, P = .089). There is a potential need for histological subtype/grade specific treatment protocols. For conventional CSAs, surgery alone provides optimal results grade 1 CSAs, while resection with adjuvant radiotherapy yields the best outcome for grade 2 and 3 CSAs. Improvements in PFS seen with neoadjuvant therapy in mesenchymal/dedifferentiated CSAs indicate a potential role for systemic therapies. Larger studies are necessary to confirm the proposed treatment protocols.

  11. Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability*

    PubMed Central

    Bravo, Bruna Souza Felix; Azulay, David Rubem; Luiz, Ronir Raggio; Mandarim-De-Lacerda, Carlos Alberto; Cuzzi, Tullia; Azulay, Mônica Manela

    2015-01-01

    BACKGROUND The off-label use of oral isotretinoin in photoaging is a therapeutic tool that has been used by dermatologists. There are few studies to corroborate its effectiveness and durability. OBJECTIVES To assess, both clinically and histologically, the changes caused by the use of oral isotretinoin in skin photoaging as well as the duration of the effects. METHODS 20 female patients, aged 45-50 years, with phototypes II-VI, none of whom had experienced menopause, were treated with 20mg oral isotretinoin, 3 days a week, for 12 weeks. They underwent clinical analysis and skin biopsies in the pre-auricular region, while histologic cuts enabled assessment of the solar elastosis level and morphologic analysis. RESULTS Clinically, patients, as well as the researching and the assessor physicians, noticed improvement in skin quality. One patient presented severe solar elastosis, 11 manifested the moderate form, while 8 presented the discreet type. According to histological analysis, 65% of the patients revealed alteration in the distribution and thickness of the elastic fibers, which can be interpreted as a histological improvement, while 60% showed an increase in collagen density. We observed an increase in collagen density, from 51.2% to 57.4%, (p=0.004). At the end of the 12-week follow-up period, this density decreased to 54.7% (p=0.050). There was an increase in the density of elastic fibers, from 26.5% to 31.3%, (p=0.02), which had dropped to 27.5% at the end of the 12-week follow-up period. CONCLUSIONS The study confirmed the role of oral isotretinoin in remodeling the extracellular matrix against photoaging, as well as its durability after 12 weeks, especially when we consider collagen fibers. PMID:26375216

  12. Magnetic resonance imaging and histology correlation in Cushing's disease.

    PubMed

    Masopust, Václav; Netuka, David; Beneš, Vladimír; Májovský, Martin; Belšán, Tomáš; Bradáč, Ondřej; Hořínek, Daniel; Kosák, Mikuláš; Hána, Václav; Kršek, Michal

    We continuously look for new techniques to improve the radicality of resection and to eliminate the negative effects of surgery. One of the methods that has been implemented in the perioperative management of Cushing's disease was the combination of three magnetic resonance imaging (MRI) sequences: SE, SPGR and fSPGR. We enrolled 41 patients (11 males, 30 females) diagnosed with Cushing's disease. A 3D tumour model with a navigation console was developed using each SPGR, fSPGR and SE sequence. The largest model was then used. In all cases, a standard four-handed, bi-nostril endoscopic endonasal technique was used. Endocrinological follow-up evaluation using morning cortisol sampling was performed for 6-34 months in our study. In total, 36 patients (88%) were disease-free following surgery. Our results indicate we achieved 100% sensitivity of MR. Overall, the conformity of at least one donor site, as compared with the places designated on MR, was in 78% of patients. We searched the place of compliance in individual locations. There is a consensus in individual locations in 63 of the 123 cases (or 56%). The correlation gamma function at a 5% significance level was then 0.27. The combination of MR sequences (SE, SPGR, fSPGR), neuronavigation system and iMRI led to increased sensitivity of up to 100%. Specificity reached 56% in our study. We found a high success rate in surgical procedure in terms of the correlation between MR findings and histology, which leads to remission of Cushing's disease. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  13. Endoscopic and histologic characteristics of serrated lesions

    PubMed Central

    Moussata, Driffa; Boschetti, Gilles; Chauvenet, Marion; Stroeymeyt, Karine; Nancey, Stéphane; Berger, Françoise; Lecomte, Thierry; Flourié, Bernard

    2015-01-01

    In recent years, a second pathway for colonic carcinogenesis, distinct from the adenomatous pathway, has been explored. This is referred to as serrated pathway and includes three types of polyp, characterised by a serrated appearance of the crypts: hyperplastic polyps (HP), sessile serrated adenomas (SSA) or lesions, and traditional serrated adenomas. Each lesion has its own genetic, as well as macroscopic and microscopic morphological features. Because of their flat aspect, their detection is easier with chromoendoscopy (carmin indigo or narrow-band imaging). However, as we show in this review, the distinction between SSA and HP is quite difficult. It is now recommended to resect in one piece as it is possible the serrated polyps with a control in a delay depending on the presence or not of dysplasia. These different types of lesion are described in detail in the present review in general population, in polyposis and in inflammatory bowel diseases patients. This review highlights the need to improve characterization and understanding of this way of colorectal cancerogenesis. PMID:25780286

  14. Prognostic value of skin histology in GVHD after intestinal transplantation.

    PubMed

    Pintar, T; Zorc-Pleskovic, R; Alessiani, M; Milutinović, A; Pleskovic, A

    2007-12-01

    Intestinal transplantation (Itx) is increasingly being performed to treat patients with irreversible intestinal failure. Acute graft-versus-host disease (GVHD) after Itx is a life-threatening complication which can progress to organ failure, systemic complications and death. The purpose of this study was to assess the diagnostic and prognostic role of histological changes as demonstrated by skin biopsy for acute GVHD after Itx. A porcine model of orthotropic Itx and bone marrow transplantation with tacrolimus-based immunosuppression was used to assess any correlation between acute graft cellular rejection and skin histological findings for the prediction of GVHD. Skin and small intestinal biopsies were histologically assessed on postoperative days 0, 15, 30, 45, and 60 and analyzed and classified as grade 1 to 4. A linear correlation was observed between the histological grading values of skin biopsy changes and the histological grading values of small intestinal biopsy changes (Kendall's tau_b was 0.855 for the Itx group and 0.730 for the Itx BM group. In conclusion, our findings emphasize the diagnostic and prognostic value of skin biopsy analysis for acute GVHD after Itx.

  15. Comparative histology of mouse, rat, and human pelvic ligaments.

    PubMed

    Iwanaga, Ritsuko; Orlicky, David J; Arnett, Jameson; Guess, Marsha K; Hurt, K Joseph; Connell, Kathleen A

    2016-11-01

    The uterosacral (USL) and cardinal ligaments (CL) provide support to the uterus and pelvic organs, and the round ligaments (RL) maintain their position in the pelvis. In women with pelvic organ prolapse (POP), the connective tissue, smooth muscle, vasculature, and innervation of the pelvic support structures are altered. Rodents are commonly used animal models for POP research. However, the pelvic ligaments have not been defined in these animals. In this study, we hypothesized that the gross anatomy and histological composition of pelvic ligaments in rodents and humans are similar. We performed an extensive literature search for anatomical and histological descriptions of the pelvic support ligaments in rodents. We also performed anatomical dissections of the pelvis to define anatomical landmarks in relation to the ligaments. In addition, we identified the histological components of the pelvic ligaments and performed quantitative analysis of the smooth muscle bundles and connective tissue of the USL and RL. The anatomy of the USL, CL, and RL and their anatomical landmarks are similar in mice, rats, and humans. All species contain the same cellular components and have similar histological architecture. However, the cervical portion of the mouse USL and RL contain more smooth muscle and less connective tissue compared with rat and human ligaments. The pelvic support structures of rats and mice are anatomically and histologically similar to those of humans. We propose that both mice and rats are appropriate, cost-effective models for directed studies in POP research.

  16. Histological investigation of resected dura mater attached to spinal meningioma.

    PubMed

    Yamamuro, Kenichi; Seichi, Atsushi; Kimura, Atsushi; Kikkawa, Ichiro; Kojima, Masahiro; Inoue, Hirokazu; Hoshino, Yuichi

    2012-10-15

    Histological observational study of patients with spinal meningioma. To clarify the status of tumor cell invasion into the dura mater and to provide fundamental information for appropriate management of dural attachment. Histological appearance of the dura attached to spinal meningioma has not been sufficiently evaluated. Dura mater resected in a Simpson Grade 1 manner from 25 consecutive patients with spinal meningiomas (World Health Organization grade 1) was histologically observed to determine the status of tumor cell invasion. As no clear borders such as a tumor capsule between tumor and dura mater were observed, histological findings of the dura mater were classified into the following 3 categories: grade 1, no dural invasion, with only inflammation of the dura; grade 2: dural invasion below the zone between the inner and outer layers; and grade 3, dural invasion into or over the zone between the inner and outer layers (full-thickness invasion). In our microscopic study, 19 of the 25 cases of spinal meningioma showed evidence of dural invasion and 15 cases showed full-thickness invasion. This histological investigation of resected dura mater attached to spinal meningioma showed a high rate of full-thickness tumor invasion into the dura mater.

  17. Cysts in the rat adenohypophysis: incidence and histology.

    PubMed

    Quintanar-Stephano, A; Muñoz Fernández, L; Quintanar, J L; Kovacs, K

    2001-01-01

    The incidence and histology of cysts in the adenohypophysis of adult male Wistar rats are reported. Of sixty pituitaries studied 13 of them (21.6%) presented a single cyst located in the pars distalis. The cysts varied in shape and size and were usually multilocular. Two of them were connected with the subdural space at the ventral surface of the adenohypophysis. Histology demonstrated that the cysts were filled with mucinous material and foamy macrophages and were lined by flat and cuboidal ciliated and nonciliated epithelial cells, goblet cells as well as several adenohypophysial endocrine cells such as somatotrophs, thyrotrophs, and gonadotrophs. The ciliated cells were the most numerous. Histologic and immunohistochemical studies of the uninvolved areas of the adenohypophysis showed no abnormalities and the weights and histology of the adenohypophyses and peripheral endocrine glands were within normal range, suggesting that the cysts did not impair the adenohypophysial endocrine activity. Although the morphogenesis of the cysts remained obscure, the histological and immunohistochemical findings support the hypothesis that during embryonic development, the future cysts coming from the pharyngeal epithelium is fused with the stomodeum before or during the formation of the Rathke's pouch.

  18. Mandibular histology and growth of the nonmammaliaform cynodont Tritylodon

    PubMed Central

    Jasinoski, Sandra C; Chinsamy, Anusuya

    2012-01-01

    An investigation of bone microstructure of nonmammalian therapsids has revealed distinctive signals pertaining to their ontogenetic growth and biology. Until now, histological studies of the nonmammaliaform cynodonts have focused only on postcranial material. Through the examination of micro-computed tomography (micro-CT) scans and serial thin sections, the current study provides a novel perspective on the structure and growth of the mandible of Tritylodon, a derived herbivorous cynodont from southern Africa. By tracking histological features across the serial thin sections, trends in relocation and modelling are documented for the growing Tritylodon mandible. For example, during growth, localized changes in the cross-sectional shape of the mandible occurred. Localized deposits of new lamellar and fibrolamellar bone on the lateral edge indicate widening of the mandible during different episodes of growth. The presence of radial channels indicates the deepening of the mandible at its anterior and posterior ends. The relocation of the paired mental foramina suggests that the mandibular body lengthened mainly in the posterior direction. The medial movement of a posterior postcanine tooth during growth and eruption is recorded in the histology. This histological assessment also documents the presence of Sharpey’s fibres in the cellular cementum of the first incisor, providing novel and unequivocal evidence that it was attached to the Tritylodon jaw by a periodontal ligament. This is the first comprehensive study that uses histological analysis to document the growth dynamics of the mandible of a nonmammalian therapsid, thus providing a unique perspective of localized mandibular growth in a fossil animal.

  19. Atypical fibroxanthoma: a histological and immunohistochemical review of 171 cases.

    PubMed

    Beer, Trevor W; Drury, Paul; Heenan, Peter J

    2010-08-01

    The clinical and histological features of 171 atypical fibroxanthomas (AFX) from a single institution in Western Australia are outlined. This area experiences high levels of solar radiation, and all assessable biopsies showed solar elastosis. Patients were aged between 41 and 97 years (median age 74), with 76% of tumors occurring in men (male to female ratio approximately 3 to 1). Most tumors were small, with a median diameter of 10 mm and a range of 4-35 mm. Only 5% exceeded 20 mm in diameter. Most AFX were well-circumscribed dermal lesions, with limited invasion of subcutis in a minority. Histological variants identified included keloidal (n = 8), clear cell (n = 3), and granular cell (n = 3), plaque like (n = 4), and myxoid (n = 1). Bland cytological appearances (spindle cell nonpleomorphic AFX) were noted in 5 tumors, with osteoclast-like giant cells in 2. Features suggesting regression were present in 22 cases. Two cases recurred locally, none metastasized. No tumors expressed melanocytic or epithelial markers. Seventy-four percent of cases expressed smooth muscle actin, typically strongly and diffusely. No AFX stained with desmin. Only 1 of 50 cases was CD117 positive. In conclusion, AFX may show a wide range of histological appearances, and a panel of immunohistochemical markers is essential to make the correct diagnosis. Histological mimics, such as poorly differentiated squamous cell carcinoma, must be carefully excluded. Specific diagnosis is important because there seems to be a very low risk of recurrence or metastasis despite the frequently alarming histology.

  20. Histological skin morphology enhancement base on molecular hyperspectral imaging technology.

    PubMed

    Li, Q; Sun, Z; Wang, Y; Liu, H; Guo, F; Zhu, J

    2014-08-01

    Most traditional skin histological analysis methods are based on the light microscopy images, which can only provide limited information and low contrast results for pathology evaluation. Molecular hyperspectral imaging technology can provide both spatial and spectral information of skin sections, which is a new method for histological skin analysis. The molecular hyperspectral imaging system was developed by coupling an acousto-optic tunable filters adapter to microscopy and the molecular hyperspectral images were analyzed by home-written software with image processing algorithms. Then, the histological structures in skin sections were investigated in several locations to evaluate the potential application of the molecular hyperspectral imaging technique to dermatology. Molecular hyperspectral images of skin sections were obtained. Single-band images, false color images, virtual 3D surface view images, and color-coded spectral clustering results were produced to highlight the skin structures for histological evaluation. Unlike traditional histological analysis with light microscopy, the molecular hyperspectral imaging technology can enhance the visualization of skin structures using their spectral signatures and their gray values. This technology has potential for the diagnosis and histopathologic characterization of different kind of skin cells. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Use of interactive live digital imaging to enhance histology learning in introductory level anatomy and physiology classes.

    PubMed

    Higazi, Tarig B

    2011-01-01

    Histology is one of the main subjects in introductory college-level Human Anatomy and Physiology classes. Institutions are moving toward the replacement of traditional microscope-based histology learning with virtual microscopy learning amid concerns of losing the valuable learning experience of traditional microscopy. This study used live digital imaging (LDI) of microscopic slides on a SMART board to enhance Histology laboratory teaching. The interactive LDI system consists of a digital camera-equipped microscope that projects live images on a wall-mounted SMART board via a computer. This set-up allows real-time illustration of microscopic slides with highlighted key structural components, as well as the ability to provide the students with relevant study and review material. The impact of interactive LDI on student learning of Histology was then measured based on performance in subsequent laboratory tests before and after its implementation. Student grades increased from a mean of 76% (70.3-82.0, 95% CI) before to 92% (88.8-95.3, 95% CI) after integration of LDI indicating highly significant (P < 0.001) enhancement in students' Histology laboratory performance. In addition, student ratings of the impact of the interactive LDI on their Histology learning were strongly positive, suggesting that a majority of students who valued this learning approach also improved learning and understanding of the material as a result. The interactive LDI technique is an innovative, highly efficient and affordable tool to enhance student Histology learning, which is likely to expand knowledge and student perception of the subject and in turn enrich future science careers. Copyright © 2011 American Association of Anatomists.

  2. Multimodal image registration of ex vivo 4 Tesla MRI with whole mount histology for prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Chappelow, Jonathan; Madabhushi, Anant; Rosen, Mark; Tomaszeweski, John; Feldman, Michael

    2007-03-01

    In this paper we present novel methods for registration and subsequent evaluation of whole mount prostate histological sections to corresponding 4 Tesla ex vivo magnetic resonance imaging (MRI) slices to complement our existing computer-aided diagnosis (CAD) system for detection of prostatic adenocarcinoma from high resolution MRI. The CAD system is trained using voxels labeled as cancer on MRI by experts who visually aligned histology with MRI. To address voxel labeling errors on account of manual alignment and delineation, we have developed a registration method called combined feature ensemble mutual information (COFEMI) to automatically map spatial extent of prostate cancer from histology onto corresponding MRI for prostatectomy specimens. Our method improves over intensity-based similarity metrics (mutual information) by incorporating unique information from feature spaces that are relatively robust to intensity artifacts and which accentuate the structural details in the target and template images to be registered. Our registration algorithm accounts for linear gland deformations in the histological sections resulting from gland fixing and serial sectioning. Following automatic registration of MRI and histology, cancer extent from histological sections are mapped to the corresponding registered MRI slices. The manually delineated cancer areas on MRI obtained via manual alignment of histological sections and MRI are compared with corresponding cancer extent obtained via COFEMI by a novel registration evaluation technique based on use of non-linear dimensionality reduction (locally linear embedding (LLE)). The cancer map on MRI determined by COFEMI was found to be significantly more accurate compared to the manually determined cancer mask. The performance of COFEMI was also found to be superior compared to image intensity-based mutual information registration.

  3. The frequency of histologically confirmed Barrett’s esophagus varies by the combination of ethnicity and gender

    PubMed Central

    Chisholm, Sian S.; Khoury, Joe E.; Jamal, M. Mazen; Palacio, Carlos; Pudhota, Sunitha

    2017-01-01

    Background Barrett’s esophagus (BE) is the primary risk factor for esophageal adenocarcinoma (EAC). Limited data exists regarding the frequency of histologically confirmed BE by both gender and ethnicity in the United States. The study aim was to determine whether the frequency of histologically confirmed BE varies by ethnicity and gender. Methods The University of Florida-Jacksonville endoscopy database was reviewed for all cases of salmon colored esophageal mucosa from September 2002 to August 2007. Histologic BE was diagnosed only if salmon colored esophageal mucosa was seen endoscopically and biopsy confirmed intestinal metaplasia with goblet cells. Data collected included: age at diagnosis, self-reported ethnicity [non-Hispanic white (nHw) or African American (AA)], gender, procedure indication, gastroesophageal reflux disease (GERD) history, atypical manifestations, cigarette smoking, alcohol use, proton pump inhibitor (PPI) use, BE endoscopic length, absence/presence of hiatal hernia, stricture or ulcer, and absence/presence/grade of dysplasia. Results Salmon colored esophageal mucosa was identified in 391/7,308 patients, distributed ethnically as 306 nHw and 85 AA. Histologic BE was confirmed in 111/391 patients with ethnic distribution of: 95 nHw and 16 AA. Histologically confirmed BE frequency varied both by gender and ethnicity with nHw males having the highest (42.3%) and AA females the lowest (12.3%). Histologically confirmed BE frequency differed significantly between nHw males and nHw/AA females only (P<0.005). Conclusions Histologically confirmed BE frequency varies by ethnicity and gender with nHw males having the highest frequency/risk and AA females the lowest. Investigation to improve understanding of the impact of race and gender in BE formation should be performed. PMID:28280615

  4. Histological changes in vocal fold growth and aging.

    PubMed

    Kuhn, Maggie A

    2014-12-01

    Sophisticated descriptions of the highly specialized vocal fold microarchitecture have been available for over three decades, but how this anatomy evolves with growth and aging remains an area of active investigation and, at times, a source of controversy. As our aging population expands and interest in pediatric voice disorders blossoms, it is timely to consider our contemporary understanding of evolving vocal fold histology and its implications for voice production. Novel applications of existing and emerging biotechnology, development of animal models and skillful use of human specimens have afforded greater insights into the histologic vocal fold changes seen throughout the lifespan in health and disease. Burgeoning knowledge has laid the foundation for more comprehensive models of vocal fold histology and has led to the development of innovative therapies for challenging voice disorders.

  5. Aspiration biopsy of testis: another method for histologic examination

    SciTech Connect

    Nseyo, U.O.; Englander, L.S.; Huben, R.P.; Pontes, J.E.

    1984-08-01

    The most important method for evaluating the pathogenesis of male infertility is open testicular biopsy. Herein the authors describe a method of aspiration biopsy of testis for histologic examination. Sexually mature dogs and rats treated with chemotherapeutic agents and ionizing radiation were followed with periodic testicular aspiration biopsy during and after treatment. The histologic findings from the aspiration biopsy compare with the results of routine histologic examination in assessing spermatogenetic activity and delineating pathologic changes. The puncture in the experimental animals was performed under general anesthesia. In human patients testicular biopsy could be done under local anesthesia in an outpatient clinic. The procedure would be less painful, minimally invasive, and more cost-effective.

  6. Effects of aleurone layer on rice cooking: A histological investigation.

    PubMed

    Wu, Jianyong; Chen, Jun; Liu, Wei; Liu, Chengmei; Zhong, Yejun; Luo, Dawen; Li, Zhongqiang; Guo, Xiaojuan

    2016-01-15

    Understanding how aleurone layer (AL) affects rice cooking behaviour is important for rice processing. Individual effects of AL on rice cooking behaviour were evaluated and histological characters of AL before and after cooking were investigated. AL slightly affected rice cooking quality (optimum cooking time, water absorption, volume expansion ratio and total solids loss) while remarkably affected rice texture (hardness and adhesiveness) and peak viscosity. Histological investigation showed that channels were formed in AL during cooking. The channels facilitated the penetration of water, which could explain why AL exhibited slight effects on rice cooking quality. In addition, thick cell walls and thermally stable aleurone grains were widely distributed in AL. Leached components accumulated on them and formed a reinforced coated film on rice surface during cooking, which may be a possible mechanism accounting for the remarkable effect of AL on rice texture. Histological characters of AL are closely related with rice cooking behaviour. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Microscopic esophagitis and Barrett's esophagus: the histology report.

    PubMed

    Fiocca, Roberto; Mastracci, Luca; Milione, Massimo; Parente, Paola; Savarino, Vincenzo

    2011-03-01

    Gastro-esophageal reflux disease (GERD) is the most common digestive disease in industrialized countries (Europe and North America) and is associated with microscopic changes in the squamous epithelium. However, biopsy is not presently included in the routine diagnostic flow chart of GERD. In contrast, esophageal biopsy is mandatory when diagnosing Barrett's esophagus. High quality histology reports are necessary to provide information on diagnosis and can also be important for research and epidemiological studies. It has been evident for decades that pathology reports vary between institutions and even within a single institution. Standardization of reporting is the best way to ensure that information necessary for patient management is included in pathology reports. This paper details the histological criteria for diagnosing GERD-associated microscopic esophagitis, other forms of esophagitis with specific features and columnar metaplasia in the lower esophagus (Barrett's esophagus). It provides a detailed description of appropriate sampling criteria, individual lesions and how they contribute to the histology report.

  8. Porokeratosis ptychotropica: a rare manifestation with typical histological exam*

    PubMed Central

    Veasey, John Verrinder; Dalapicola, Monique Coelho; Lellis, Rute Facchini; Campaner, Adriana Bittencourt; Manzione, Thiago da Silveira; Rodrigues, Maria Clarissa de Faria Soares

    2016-01-01

    Porokeratosis is a disorder of epidermal keratinization characterized clinically by a distinctive ridge-like border, and histologically by cornoid lamellae. The known clinical variants of porokeratosis are: classic porokeratosis of Mibelli, disseminated superficial (actinic) porokeratosis (DSAP), porokeratosis palmaris et plantaris disseminata, linear porokeratosis and punctate porokeratosis. In 1995, a seventh form was described as porokeratosis ptychotropica: a verrucous form resembling psoriasis involving the gluteal cleft presenting on the histological exam multiple cornoid lamellae. There are very few reports in the literature of this clinical variant. The present study describes the case of a healthy male presenting gluteal hyperkeratotic plaques for 22 years. He had been to several dermatologists, none of them had achieved a definitive diagnosis. We present a typical clinical presentation and its dermoscopy findings, in addition to histological examination that confirmed the diagnosis. PMID:27579746

  9. [Use of polyvinyl alcohol for preparing frozen histological sections].

    PubMed

    Serga, V A; Bykov, L A; Kasatonov, V G

    1982-01-01

    The authors developed a new method for preparation of frozen histological sections. It consists in the use of glycerin-plastified polymer, polyvinyl alcohol, and distilled water for impregnation of tissue pieces and subsequent freezing of them in the same medium. This produces histological sections of high quality. The frozen sections are sufficiently thin (3--5 micrometers). The method excludes cell structure destruction by ice crystals and overfreezing of blocks; the sections do not crumble. Losses of free cell elements, extraction of substances and other artifacts are minimized. The frozen histological sections are firmly glued to the glass without using protein with glycerin. The method saves time and reagents for the preparation of the sections and allows their wide use in morphological and histochemical studies.

  10. Intestinal Preparation Techniques for Histological Analysis in the Mouse.

    PubMed

    Williams, Jonathan M; Duckworth, Carrie A; Vowell, Kate; Burkitt, Michael D; Pritchard, D Mark

    2016-06-01

    The murine intestinal tract represents a difficult organ system to study due to its long convoluted tubular structure, narrow diameter, and delicate mucosa which undergoes rapid changes after sampling prior to fixation. These features do not make for easy histological analysis as rapid fixation in situ, or after simple removal without careful dissection, results in poor postfixation tissue handling and limited options for high quality histological sections. Collecting meaningful quantitative data by analysis of this tissue is further complicated by the anatomical changes in structure along its length. This article describes two methods of intestinal sampling at necropsy that allow systematic histological analysis of the entire intestinal tract, either through examination of cross sections (circumferences) by the gut bundling technique or longitudinal sections by the adapted Swiss roll technique, together with basic methods for data collection. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  11. Histology-based simulations of ultrasound imaging: methodology.

    PubMed

    Gyöngy, Miklós; Balogh, Lajos; Szalai, Klára; Kalló, Imre

    2013-10-01

    Simulations of ultrasound (US) images based on histology may shed light on the process by which microscopic tissue features translate to a US image and may enable predictions of feature detectability as a function of US system parameters. This technical note describes how whole-slide hematoxylin and eosin-stained histology images can be used to generate maps of fractional change in bulk modulus, whose convolution with the impulse response of the US system yields simulated US images. The method is illustrated by two canine mastocytoma histology images, one with and the other without signs of intra-operative hemorrhaging. Quantitative comparisons of the envelope statistics with corresponding clinical US images provide preliminary validation of the method.

  12. Porokeratosis ptychotropica: a rare manifestation with typical histological exam.

    PubMed

    Veasey, John Verrinder; Dalapicola, Monique Coelho; Lellis, Rute Facchini; Campaner, Adriana Bittencourt; Manzione, Thiago da Silveira; Rodrigues, Maria Clarissa de Faria Soares

    2016-01-01

    Porokeratosis is a disorder of epidermal keratinization characterized clinically by a distinctive ridge-like border, and histologically by cornoid lamellae. The known clinical variants of porokeratosis are: classic porokeratosis of Mibelli, disseminated superficial (actinic) porokeratosis (DSAP), porokeratosis palmaris et plantaris disseminata, linear porokeratosis and punctate porokeratosis. In 1995, a seventh form was described as porokeratosis ptychotropica: a verrucous form resembling psoriasis involving the gluteal cleft presenting on the histological exam multiple cornoid lamellae. There are very few reports in the literature of this clinical variant. The present study describes the case of a healthy male presenting gluteal hyperkeratotic plaques for 22 years. He had been to several dermatologists, none of them had achieved a definitive diagnosis. We present a typical clinical presentation and its dermoscopy findings, in addition to histological examination that confirmed the diagnosis.

  13. Arsenic-induced Histological Alterations in Various Organs of Mice

    PubMed Central

    Noman, Abu Shadat Mohammod; Dilruba, Sayada; Mohanto, Nayan Chandra; Rahman, Lutfur; Khatun, Zohora; Riad, Wahiduzzaman; Al Mamun, Abdullah; Alam, Shahnur; Aktar, Sharmin; Chowdhury, Srikanta; Saud, Zahangir Alam; Rahman, Zillur; Hossain, Khaled; Haque, Azizul

    2015-01-01

    Deposition of arsenic in mice through groundwater is well documented but little is known about the histological changes of organs by the metalloid. Present study was designed to evaluate arsenic-induced histological alterations in kidney, liver, thoracic artery and brain of mice which are not well documented yet. Swiss albino male mice were divided into 2 groups and treated as follows: Group 1: control, 2: arsenic (sodium arsenite at 10 mg/kg b.w. orally for 8 wks). Group 2 showed marked degenerative changes in kidney, liver, thoracic artery, and brain whereas Group 1 did not reveal any abnormalities on histopathology. We therefore concluded that arsenic induces histological alterations in the tested organs. PMID:26740907

  14. [Clinical, hormonal and histological features in ovarian stromal hyperthecosis].

    PubMed

    Abuladze, M V; Sharabidze, N G

    2006-10-01

    The aim of our study was to investigate clinical, hormonal and histological features of ovarian stromal hyperthecosis We have studied 104 patients with a histological diagnosis of ovarian stromal hyperthecosis and hyperplasia. Analyzing the results we can conclude that clinical features of ovarian stromal hyperthecosis and hyperplasia with polycystic ovarian disease and without it were identical and characterised by virilization syndrome, disorders of menstrual cycle and reproductive function; metabolic and vegeto-vascular disorders; breast and endometrial hyperplasias, high blood level of testosterone . The histological study of ovarian stromal hyperthecosis has showed that superficial part of ovarian cortex is hypocellular and fibrotic, contains scattered follicles with few granulosa cells, luteinized internal theca cells, hyperplasia of deep cortex and medulla, corpus luteus is absent.

  15. Spatial mapping of metals in tissue-sections using combination of mass-spectrometry and histology through image registration

    NASA Astrophysics Data System (ADS)

    Anyz, Jiri; Vyslouzilova, Lenka; Vaculovic, Tomas; Tvrdonova, Michaela; Kanicky, Viktor; Haase, Hajo; Horak, Vratislav; Stepankova, Olga; Heger, Zbynek; Adam, Vojtech

    2017-01-01

    We describe a new procedure for the parallel mapping of selected metals in histologically characterized tissue samples. Mapping is achieved via image registration of digital data obtained from two neighbouring cryosections by scanning the first as a histological sample and subjecting the second to laser ablation inductively coupled plasma mass spectrometry. This computer supported procedure enables determination of the distribution and content of metals of interest directly in the chosen histological zones and represents a substantial improvement over the standard approach, which determines these values in tissue homogenates or whole tissue sections. The potential of the described procedure was demonstrated in a pilot study that analysed Zn and Cu levels in successive development stages of pig melanoma tissue using MeLiM (Melanoma-bearing-Libechov-Minipig) model. We anticipate that the procedure could be useful for a complex understanding of the role that the spatial distribution of metals plays within tissues affected by pathological states including cancer.

  16. Spatial mapping of metals in tissue-sections using combination of mass-spectrometry and histology through image registration

    PubMed Central

    Anyz, Jiri; Vyslouzilova, Lenka; Vaculovic, Tomas; Tvrdonova, Michaela; Kanicky, Viktor; Haase, Hajo; Horak, Vratislav; Stepankova, Olga; Heger, Zbynek; Adam, Vojtech

    2017-01-01

    We describe a new procedure for the parallel mapping of selected metals in histologically characterized tissue samples. Mapping is achieved via image registration of digital data obtained from two neighbouring cryosections by scanning the first as a histological sample and subjecting the second to laser ablation inductively coupled plasma mass spectrometry. This computer supported procedure enables determination of the distribution and content of metals of interest directly in the chosen histological zones and represents a substantial improvement over the standard approach, which determines these values in tissue homogenates or whole tissue sections. The potential of the described procedure was demonstrated in a pilot study that analysed Zn and Cu levels in successive development stages of pig melanoma tissue using MeLiM (Melanoma-bearing-Libechov-Minipig) model. We anticipate that the procedure could be useful for a complex understanding of the role that the spatial distribution of metals plays within tissues affected by pathological states including cancer. PMID:28071735

  17. Confocal mosaicing microscopy of human skin ex vivo: spectral analysis for digital staining to simulate histology-like appearance

    NASA Astrophysics Data System (ADS)

    Bini, Jason; Spain, James; Nehal, Kishwer; Hazelwood, Vikki; Dimarzio, Charles; Rajadhyaksha, Milind

    2011-07-01

    Confocal mosaicing microscopy enables rapid imaging of large areas of fresh tissue, without the processing that is necessary for conventional histology. Mosaicing may offer a means to perform rapid histology at the bedside. A possible barrier toward clinical acceptance is that the mosaics are based on a single mode of grayscale contrast and appear black and white, whereas histology is based on two stains (hematoxylin for nuclei, eosin for cellular cytoplasm and dermis) and appears purple and pink. Toward addressing this barrier, we report advances in digital staining: fluorescence mosaics that show only nuclei, are digitally stained purple and overlaid on reflectance mosaics, which show only cellular cytoplasm and dermis, and are digitally stained pink. With digital staining, the appearance of confocal mosaics mimics the appearance of histology. Using multispectral analysis and color matching functions, red, green, and blue (RGB) components of hematoxylin and eosin stains in tissue were determined. The resulting RGB components were then applied in a linear algorithm to transform fluorescence and reflectance contrast in confocal mosaics to the absorbance contrast seen in pathology. Optimization of staining with acridine orange showed improved quality of digitally stained mosaics, with good correlation to the corresponding histology.

  18. Discordance of Histologic Grade Between Primary and Metastatic Neuroendocrine Carcinomas.

    PubMed

    Adesoye, Taiwo; Daleo, Marie A; Loeffler, Agnes G; Winslow, Emily R; Weber, Sharon M; Cho, Clifford S

    2015-12-01

    The prognosis and management of neuroendocrine carcinoma are largely driven by histologic grade as assessed by mitotic activity. The authors reviewed their institutional experience to determine whether the histologic grade of neuroendocrine carcinoma can differ between primary and metastatic tumors. This study examined patients who underwent operative resection of both primary and metastatic foci of neuroendocrine carcinoma. Resected tumors were independently reviewed and categorized as low, intermediate, or high grade as determined by mitotic count. The authors identified 20 patients with metastatic neuroendocrine carcinoma treated at their institution between 1997 and 2013 for whom complete pathologic review of primary and metastatic tumors was possible. Primary lesions were found in the small intestine (n = 12), pancreas (n = 7), ampulla (n = 1), stomach (n = 1), and rectum (n = 1). The timing of hepatic metastasis was synchronous in 15 cases and metachronous in 5 cases. The histologic grade was concordant between primary and metastatic tumors in 9 cases and discordant in 11 cases. Among the discordant cases, 7 had a higher metastatic grade than primary grade, and 4 had a lower metastatic grade than primary grade. Metachronous presentation was associated with a higher likelihood of grade discordance (p = 0.03). The histologic grade of all metachronous metastases differed from that of the primary tumors. There is a high prevalence of histologic grade discordance between primary and metastatic foci of neuroendocrine carcinoma, particularly among patients with a metachronous metastatic presentation. Given the importance of histologic grade in disease prognostication and treatment planning, this finding may be informative for the management of patients with metastatic neuroendocrine carcinoma.

  19. Acute Histologic Chorioamnionitis at Term: Nearly Always Noninfectious

    PubMed Central

    Roberts, Drucilla J.; Celi, Ann C.; Riley, Laura E.; Onderdonk, Andrew B.; Boyd, Theonia K.; Johnson, Lise Carolyn; Lieberman, Ellice

    2012-01-01

    Background The link between histologic acute chorioamnionitis and infection is well established in preterm deliveries, but less well-studied in term pregnancies, where infection is much less common. Methodology/Principal Findings We conducted a secondary analysis among 195 low-risk women with term pregnancies enrolled in a randomized trial. Histologic and microbiologic evaluation of placentas included anaerobic and aerobic cultures (including mycoplasma/ureaplasma species) as well as PCR. Infection was defined as ≥1,000 cfu of a single known pathogen or a ≥2 log difference in counts for a known pathogen versus other organisms in a mixed culture. Placental membranes were scored and categorized as: no chorioamnionitis, Grade 1 (subchorionitis and patchy acute chorioamnionitis), or Grade 2 (severe, confluent chorioamnionitis). Grade 1 or grade 2 histologic chorioamnionitis was present in 34% of placentas (67/195), but infection was present in only 4% (8/195). Histologic chorioamnionitis was strongly associated with intrapartum fever >38°C [69% (25/36) fever, 26% (42/159) afebrile, P<.0001]. Fever occurred in 18% (n = 36) of women. Most febrile women [92% (33/36)] had received epidural for pain relief, though the association with fever was present with and without epidural. The association remained significant in a logistic regression controlling for potential confounders (OR = 5.8, 95% CI = 2.2,15.0). Histologic chorioamnionitis was also associated with elevated serum levels of interleukin-8 (median = 1.3 pg/mL no histologic chorioamnionitis, 1.5 pg/mL Grade 1, 2.1 pg/mL Grade 2, P = 0.05) and interleukin-6 (median levels = 2.2 pg/mL no chorioamnionitis, 5.3 pg/mL Grade 1, 24.5 pg/mL Grade 2, P = 0.02) at admission for delivery as well as higher admission WBC counts (mean = 12,000cells/mm3 no chorioamnionitis, 13,400cells/mm3 Grade 1, 15,700cells/mm3 Grade 2, P = 0.0005). Conclusion/Significance Our results suggest histologic

  20. A case of secondary erythromelalgia with unusual histological findings.

    PubMed

    Bakkour, Waseem; Motta, Luisa; Stewart, Elizabeth

    2013-06-01

    Erythromelalgia clinically presents with episodic burning, erythema, and warmth of acral sites. It can be divided into primary and secondary associated with myeloproliferative and autoimmune conditions. Histology commonly shows capillary proliferation, swelling of endothelial cells, perivascular edema, and chronic inflammation with sparse lymphocytic infiltrate. We report a case of a 55-year-old man with classical secondary erythromelalgia clinically; however, he had unusual histological findings on biopsy comprising of acute perivascular infiltrate and perivascular mucin. This is the first report of such findings in the context of secondary erythromelalgia.

  1. Behavioral and histological effects of acrylamide in rainbow trout

    SciTech Connect

    Petersen, D.W.; Cooper, K.R.; Friedman, M.A.; Lech, J.J.

    1987-01-01

    A histological and behavioral study was used to assess whether acrylamide produced neurotoxic effects in rainbow trout. Swimming performance of trout exposed to 0, 12.5, or 25 mg/liter acrylamide for 15 days was unaffected. Swimming performance of animals exposed to 50 mg/liter acrylamide for a similar time period was compromised by morbidity and mortality of the animals in this treatment group. The absence of dose-related histological lesions in central neurons, peripheral neurons or muscle suggested that the observed deficit in swimming performance was due to a generalized toxic response. Acrylamide treatment produced dose-related lesions in the gill and liver of rainbow trout.

  2. DNA analysis of abortion material assisted by histology screening.

    PubMed

    Karger, B; Rand, S P; Duchesne, A

    2001-12-01

    In cases of rape leading to fertilization, paternity testing can retrospectively identify the assailant. Abortion material commonly represents a mixture of maternal and fetal tissue and blood, which cannot be differentiated with the naked eye. Consequently, DNA typing of abortion material may be complicated, including band overlap if maternal tissue predominates. Therefore, histology screening of the abortion content for typical fetal tissue components, such as chorionic villi, followed by selected DNA typing of this sample is suggested. This combined approach is illustrated by a selected case demonstrating the reliability and concurrence of the histology and genetic results.

  3. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy.

    PubMed

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008-2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC.

  4. Evaluation of Coils for Imaging Histological Slides: Signal-to-Noise Ratio and Filling Factor

    PubMed Central

    Hoang, Dung Minh; Voura, Evelyn B.; Zhang, Chao; Fakri-Bouchet, Latifa; Wadghiri, Youssef Zaim

    2013-01-01

    Purpose To investigate the relative gain in sensitivity of five histology coils designed in-house to accommodate tissue sections of various sizes and compare with commercial mouse head coils. Methods The coil set was tailored to house tissue sections ranging from 5 to 1000 μm encased in either glass slides or coverslips. Results Our simulations and experimental measurements demonstrated that although the sensitivity of this flat structure consistently underperforms relative to a birdcage head coil based on the gain expected from their respective filling factor ratios, our results demonstrate that it can still provide a remarkable gain in sensitivity. Our study also describes preparation protocols for freshly excised sections, as well as pre-mounted tissue slides of both mouse and human specimens. Examples of the exceptional level of tissue detail and the near-perfect magnetic resonance imaging to light microscopic image coregistration are provided. Conclusion The increase in filling factor achieved by the histology radiofrequency (RF) probe overcomes the losses associated with electric leaks inherent to this structure, leading to a 6.7-fold improvement in performance for the smallest coil implemented. Alternatively, the largest histology coil design exhibited equal sensitivity to the mouse head coil while nearly doubling the RF planar area coverage. PMID:23857590

  5. Histological study on the protective role of vitamin B complex on the cerebellum of diabetic rat.

    PubMed

    Eltony, Sohair A

    2016-08-01

    Disorder in cerebellar structure was reported in diabetes mellitus. B vitamins are involved in many significant metabolic processes within the brain. To detect the protective role of vitamin B complex on the histological structure of the cerebellum of experimentally induced diabetic rat. Eighteen adult male Wistar rats were divided into two groups. Group I: normal vehicle control (n=6). Group II: streptozotocin-induced diabetic rats (n=12), which was equally divided into two subgroups; IIA (diabetic vehicle control), IIB (diabetic vitamin B complex-treated): streptozotocin-induced diabetic rats treated with vitamin B complex (1mg/kg/day) for 6 weeks. Specimens from the cerebellum were processed for light and electron microscopy. In vitamin B complex treated group, the histological changes in Purkinje cells, astrocytes and oligodendrocytes were improved compared with the diabetic non-treated group. The white matter revealed intact myelinated axons. Inducible nitric oxide synthase (iNOS) and caspase-3 expression reduced. Glial fibrillary acidic protein (GFAP) expression revealed less activated astroglia. The number of Purkinje cells/mm(2) significantly increased. While, the number of GFAP positive astrocytes/mm(2) significantly decreased. In addition, the blood glucose level was reduced. Vitamin B complex protected the cerebellum from the histological changes which occurred in STZ- induced diabetic rats. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Evaluation of coils for imaging histological slides: signal-to-noise ratio and filling factor.

    PubMed

    Hoang, Dung Minh; Voura, Evelyn B; Zhang, Chao; Fakri-Bouchet, Latifa; Wadghiri, Youssef Zaim

    2014-05-01

    To investigate the relative gain in sensitivity of five histology coils designed in-house to accommodate tissue sections of various sizes and compare with commercial mouse head coils. The coil set was tailored to house tissue sections ranging from 5 to1000 µm encased in either glass slides or coverslips. Our simulations and experimental measurements demonstrated that although the sensitivity of this flat structure consistently underperforms relative to a birdcage head coil based on the gain expected from their respective filling factor ratios, our results demonstrate that it can still provide a remarkable gain in sensitivity. Our study also describes preparation protocols for freshly excised sections, as well as premounted tissue slides of both mouse and human specimens. Examples of the exceptional level of tissue detail and the near-perfect magnetic resonance imaging to light microscopic image coregistration are provided. The increase in filling factor achieved by the histology radiofrequency (RF) probe overcomes the losses associated with electric leaks inherent to this structure, leading to a 6.7-fold improvement in performance for the smallest coil implemented. Alternatively, the largest histology coil design exhibited equal sensitivity to the mouse head coil while nearly doubling the RF planar area coverage. Copyright © 2013 Wiley Periodicals, Inc.

  7. Association of Metabolic Syndrome With Kidney Function and Histology in Living Kidney Donors

    PubMed Central

    Ohashi, Y.; Thomas, G.; Nurko, S.; Stephany, B.; Fatica, R.; Chiesa, A.; Rule, A. D.; Srinivas, T.; Schold, J. D.; Navaneethan, S. D.; Poggio, E. D.

    2013-01-01

    The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m2 instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome. PMID:23865821

  8. Histologic effects of University of Wisconsin two-layer method preservation of rat pancreas.

    PubMed

    Gioviale, M C; Damiano, G; Puleio, R; Bellavia, M; Cassata, G; Palumbo, V D; Spinelli, G; Altomare, R; Barone, R; Cacciabaudo, F; Buscemi, G; Lo Monte, A I

    2013-06-01

    Marginal donors represent a poorly utilized source of organs for transplantation despite their availability. The key is to reduce the ischemic damage in the effort to improve organ quality. This study investigated the histologic effects after in situ perfusion of preservation with a two-layer method compared with the classic University of Wisconsin preservation in term of tissue integrity and number of viable exocrine cells in the rat pancreas both after exsanguination and at 8 weeks of cryopreservation. Pancreata harvested from 60 rats were collected using 3 methods: two-layer method following University of Wisconsin perfusion; exsanguination; and classic University of Wisconsin perfusion/storage. In addition to histologic analysis of collected pancreata, we analyzed the number of CK19(+) cells and their viability using chi-square tests with values P < .05 considered to be significant. Rat pancreas histology showed as University of Wisconsin in situ perfusion and preservation by the two-layer method to be more effective to maintain the morphologic integrity of both exocrine and endocrine tissues. There were a larger number of CK19(+) cells with good viability. Moreover, the effects of oxygenation were visible in pancreas biopsies preserved after exsanguination. In situ University of Wisconsin perfusion and preservation for 240 minutes with the two-layer method yielded greater numbers and viability of CK19(+) cells even after 8 weeks of cryopreservation.

  9. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

    PubMed Central

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

  10. Plaque characterization in ex vivo MRI evaluated by dense 3D correspondence with histology

    NASA Astrophysics Data System (ADS)

    van Engelen, Arna; de Bruijne, Marleen; Klein, Stefan; Verhagen, Hence; Groen, Harald; Wentzel, Jolanda; van der Lugt, Aad; Niessen, Wiro

    2011-03-01

    Automatic quantification of carotid artery plaque composition is important in the development of methods that distinguish vulnerable from stable plaques. MRI has shown to be capable of imaging different components noninvasively. We present a new plaque classification method which uses 3D registration of histology data with ex vivo MRI data, using non-rigid registration, both for training and evaluation. This is more objective than previously presented methods, as it eliminates selection bias that is introduced when 2D MRI slices are manually matched to histological slices before evaluation. Histological slices of human atherosclerotic plaques were manually segmented into necrotic core, fibrous tissue and calcification. Classification of these three components was voxelwise evaluated. As features the intensity, gradient magnitude and Laplacian in four MRI sequences after different degrees of Gaussian smoothing, and the distances to the lumen and the outer vessel wall, were used. Performance of linear and quadratic discriminant classifiers for different combinations of features was evaluated. Best accuracy (72.5 +/- 7.7%) was reached with the linear classifier when all features were used. Although this was only a minor improvement to the accuracy of a classifier that only included the intensities and distance features (71.6 +/- 7.9%), the difference was statistically significant (paired t-test, p<0.05). Good sensitivity and specificity for calcification was reached (83% and 95% respectively), however, differentiation between fibrous (sensitivity 85%, specificity 60%) and necrotic tissue (sensitivity 49%, specificity 89%) was more difficult.

  11. Robust registration of sparsely sectioned histology to ex-vivo MRI of temporal lobe resections

    NASA Astrophysics Data System (ADS)

    Goubran, Maged; Khan, Ali R.; Crukley, Cathie; Buchanan, Susan; Santyr, Brendan; deRibaupierre, Sandrine; Peters, Terry M.

    2012-02-01

    Surgical resection of epileptic foci is a typical treatment for drug-resistant epilepsy, however, accurate preoperative localization is challenging and often requires invasive sub-dural or intra-cranial electrode placement. The presence of cellular abnormalities in the resected tissue can be used to validate the effectiveness of multispectralMagnetic Resonance Imaging (MRI) in pre-operative foci localization and surgical planning. If successful, these techniques can lead to improved surgical outcomes and less invasive procedures. Towards this goal, a novel pipeline is presented here for post-operative imaging of temporal lobe specimens involving MRI and digital histology, and present and evaluate methods for bringing these images into spatial correspondence. The sparsely-sectioned histology images of resected tissue represents a challenge for 3D reconstruction which we address with a combined 3D and 2D rigid registration algorithm that alternates between slice-based and volume-based registration with the ex-vivo MRI. We also evaluate four methods for non-rigid within-plane registration using both images and fiducials, with the top performing method resulting in a target registration error of 0.87 mm. This work allows for the spatially-local comparison of histology with post-operative MRI and paves the way for eventual registration with pre-operative MRI images.

  12. Bilateral adrenal tumors from different histology: case report and literature review.

    PubMed

    Zhang, Yushi; Li, Hanzhong; Xiao, Jianchun; Zhou, Yi; Zhou, Zhien; Tong, Anli

    2015-01-01

    Bilateral adrenal tumors are very uncommon in clinical practice and all originate from the same histology. We presented here a case report and literature review of bilateral adrenal tumors from different histology: pheochromocytoma in one side and adrenocortical adenoma in the other side. The patient was a 37 years old female suffered from Cushing's syndrome form 3 years. One year ago she was diagnosed as ACTH-independent Cushing's syndrome and received Laparoscopic adrenalectomy for right adrenal tumor which diagnosed as a pheochromocytoma by the pathological reports. After the operation, patient's clinical manifestation was not change, then half-year later the lab test showed no improvement in the blood biochemical parameters. Finally, CT detected a mass in left adrenal gland. Thereafter, this patient received Laparoscopic adrenalectomy for left adrenal tumor. The tumor was diagnosed as adrenocortical adenoma by the pathologists. One week after operation, the blood biochemical parameters became normal. In conclusion, bilateral adrenal tumors from different histology are very rare, adrenalectomy for both side tumors and preserving the normal adrenal glands is necessary.

  13. Facial augmentation with porous polyethylene (Medpor)--histological evidence of intense foreign body reaction.

    PubMed

    Gosau, Martin; Draenert, Florian G; Ihrler, Stefan

    2008-10-01

    In a previous study by our group evaluating the clinical use of Medpor implants as augmentation material in the facial skeleton, we examined cases with unexpected intense foreign body reaction and focal disintegration of the implant material. The present study evaluates the histological findings in the largest series of explanted Medpor samples from human beings so far. Altogether 10 samples were harvested during revision surgery due to aesthetic contouring or due to infection. The average time from implantation to removal of the implants was 8.1 months. Paraffin embedding was employed for improved histological analysis. Chronic inflammation and foreign body giant cell reaction were seen in all cases. Intracytoplasmatic phagocytosis of disintegrated pieces of Medpor was seen as well as focal destruction of the material. From the histological point of view it is no longer justified to regard Medpor as an immunologically inert material. Nevertheless the reaction does not seem to be severe enough to compromise the stability and volume of the implant from a clinical point of view. (c) 2008 Wiley Periodicals, Inc.

  14. Pulmonary capillaritis: a possible histologic form of acute pulmonary allograft rejection.

    PubMed

    Badesch, D B; Zamora, M; Fullerton, D; Weill, D; Tuder, R; Grover, F; Schwarz, M I

    1998-04-01

    Acute rejection after lung transplantation occurs commonly and is usually characterized histologically by a perivascular mononuclear infiltrate. We report five cases of pulmonary capillaritis with a histologic appearance distinct from typical rejection, occurring in patients ranging in age from 18 to 45 years, with a variety of underlying diseases including alpha1 antitrypsin deficiency, pulmonary hypertension, cystic fibrosis, and rheumatoid arthritis. Four of the five patients had alveolar hemorrhage histologically, and two had frank hemoptysis. Time of onset ranged from 3 weeks to many months after transplantation. Three cases were fulminant, and there were two deaths. In only one case, with methicillin-resistant Staphylococcus aureus bronchitis, could infection be established. All were treated with intensification of immunosuppressive therapy. Plasmapheresis was carried out in two cases and coincided with temporary improvement, but its efficacy was questionable because of concurrent immunosuppressive therapy. Two had recurrent biopsy-proven acute rejection within 6 weeks of treatment, and one had recurrent severe pulmonary hemorrhage that abated with total lymphoid irradiation. Our experience suggests that pulmonary capillaritis in lung transplant recipients can be an acute, fatal illness with the potential for recurrence in the survivors. We speculate that it represents a form of acute vascular rejection. Early pathologic diagnosis and aggressive immunosuppressive therapy are recommended. Although a humoral component was not documented, the possible response to plasmapheresis requires continued evaluation.

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

    PubMed

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

    2008-11-01

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

  16. The prognostic value of uNK cell count and histological dating in the mid-luteal phase of women with reproductive failure.

    PubMed

    Liu, Beiyu; Mariee, Najat; Laird, Susan; Smith, John; Li, Jie; Li, T C

    2014-10-01

    Histological dating has been used for decades to evaluate the histological maturation of the endometrium. Uterine natural killer cells are thought to play a significant role in pregnancy. While several studies have shown an increased number of uNK cells in women with recurrent reproductive failure, its prognostic value of pregnancy outcome remains uncertain. The aim of this study was to determine whether or not the prognostic value of uNK measurement on pregnancy outcome is improved when it is combined with histological dating of the same endometrial specimen. This is a retrospective study. Histological dating and uNK cell count was performed on endometrial biopsies taken from women with either recurrent miscarriage (RM, n=94) or recurrent implantation failure (RIF, n=72). Women who conceived within a year of the biopsy (n=83) were included in a further analysis to examine the prognostic value of uNK cell count and histological dating on the outcome of a subsequent pregnancy. There was a significant (p=0.01) association between uNK cells and histological dating; retarded endometrium was less likely to have a high uNK cell count (16/58, 28%) than normally developed endometrium (52/108, 48%). Whilst uNK cell count on its own did not have a significant correlation to the pregnancy outcome, a retarded endometrium is significantly (p=0.01) associated with a higher miscarriage rate (68%, 13/19) than normally developed endometrium (35%, 23/64) in women with reproductive failure. Regardless of the result of uNK cell count (normal or abnormal), combining the results of histological dating appeared to have significantly improved the prognostic value. We found that the prognostic value of uNK cell count is significantly increased when the result is combined with histological dating, primarily because histological dating is significantly correlated with pregnancy outcome. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

    PubMed

    Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

    2012-01-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  18. Nasopharyngeal carcinoma risk by histologic type in central China: impact of smoking, alcohol and family history.

    PubMed

    Ji, Xuemei; Zhang, Weidong; Xie, Conghua; Wang, Bicheng; Zhang, Gong; Zhou, Fuxiang

    2011-08-01

    The role of cigarette smoking, alcohol use, family history of cancer and the interaction of cigarettes and family history in the etiology of Nasopharyngeal carcinoma (NPC) in general and within each histologic type are unclear. We conducted a case-control study among 1,044 Han Chinese patients with NPC and 1,095 Han Chinese cancer-free control subjects. Logistic regression was used to analyze the association between histologic type of NPC and cigarette smoking, alcohol drinking and family history. The results indicated that NPC was significantly associated with cigarette smoking [adjusted odds ratio (OR) = 2.97, 95% confidence interval (CI), 2.38-3.70], and the association exhibited a dose-response relationship for intensity, duration, and cumulative consumption of cigarettes (p(trend) < 0.0001 for intensity, duration and cumulative consumption of cigarettes). Positive family history of cancer led to a significant 12-fold elevated risk of NPC (adjusted OR = 12.95, 95% CI, 7.12-23.54) and acted jointly with cigarettes in contributing to NPC risk (adjusted OR = 56.68, 95% CI, 17.25-186.19). The association of NPC risk with cigarettes was stronger for nonkeratinizing carcinoma than for keratinizing squamous cell carcinoma (KSCC), whereas family history was more closely associated with KSCC. NPC risk was not associated with alcohol consumption. Our study demonstrated that cigarette smoking and family history of cancer could serve independently and jointly as risk factors for etiology of NPC and might affect the risk of histology-specific NPC differently. This knowledge may help facilitate comprehension of NPC etiology in general as well as within each histologic type, and thereby improve prevention efforts. Copyright © 2010 UICC.

  19. The histology of skin treated with a picosecond alexandrite laser and a fractional lens array.

    PubMed

    Tanghetti, Emil A

    2016-09-01

    The treatment of acne scars and wrinkles with a picosecond Alexandrite laser was recently FDA cleared. In 2014 we presented our initial histologic findings with this device on in vivo and ex vivo skin. This current study expands on the 2014 pilot study with an investigation of different energy settings using histology and the confocal microscope to describe the changes observed in the skin. We used a 755 nm picosecond Alexandrite laser with a fractional optic with three different energy settings to treat in vivo. After treatment, the patients and skin samples were also evaluated with a confocal microscope followed by biopsies which were evaluated histologically. Histology revealed unique intra-epidermal cavities. The number, density, and the size of these cavities were dependent on the melanin index and delivered energy when evaluated with histopathology and the confocal microscope. These localized zones of injury appear to form microscopic epidermal injury zones which are exfoliated over a 3-week period. These intra-epidermal cavities result from areas of laser-induced optical breakdown (LIOB). This injury is most consistent with a localized plasma formation in the epidermis initiated by the melanin absorption of the high energy picosecond light. It appears that treatments with this device and optic result in improvements in dyspigmentation and acne scars with new collagen, elastic tissue, and mucin. The production of this LIOB could directly stimulate an epidermal repair mechanism that results in these clinical findings. Lasers Surg. Med. 48:646-652, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.

    PubMed

    Safroneeva, E; Coslovsky, M; Kuehni, C E; Zwahlen, M; Haas, N A; Panczak, R; Taft, T H; Hirano, I; Dellon, E S; Gonsalves, N; Leung, J; Bussmann, C; Woosley, J T; Yan, P; Romero, Y; Furuta, G T; Gupta, S K; Aceves, S S; Chehade, M; Straumann, A; Schoepfer, A M

    2015-10-01

    Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. To evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients. Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE-related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263. © 2015 John Wiley & Sons Ltd.

  1. Correlation of vitamin E, uric acid, and diet composition with histologic features of pediatric NAFLD.

    PubMed

    Vos, Miriam B; Colvin, Ryan; Belt, Patricia; Molleston, Jean P; Murray, Karen F; Rosenthal, Philip; Schwimmer, Jeffrey B; Tonascia, James; Unalp, Aynur; Lavine, Joel E

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children in the United States. Although changes in diet are often recommended to improve NAFLD, little is known regarding the influence of diet on histologic features of the disease. This was a prospective, cross-sectional registry-based study. Children (n = 149) enrolled in the multicenter nonalcoholic steatohepatitis (NASH) Clinical Research Network had demographic, anthropometric, clinical, laboratory, and histology data obtained, including the Block Brief Food Questionnaire. Subjects were grouped by presence or absence of steatohepatitis and grades of histologic features according to NASH Clinical Research Network criteria. No significant differences were found between children with steatosis compared with steatohepatitis for fraction of energy from fat, carbohydrates, and protein. Sugar-sweetened beverage consumption was low and did not correlate with histologic features, although uric acid, a surrogate marker for fructose intake, was significantly increased in those with definite NASH (P = 0.008). For all groups, vitamin E consumption was insufficient compared with the recommended daily allowance. Median consumption of vitamin E was lower in children with higher grade of steatosis (8.4 vs 6.1 vs 6.9 for grades I, II, and III, respectively, P = 0.05). Those consuming less vitamin C had increased ballooning degeneration (P = 0.05). Children with NAFLD have a diet that is insufficient in vitamin E and this may contribute to the pathophysiology of NAFLD. In children with NAFLD, reported sugar-sweetened beverage consumption is low; however, uric acid, which may reflect total fructose consumption, was significantly associated with NASH and should be further evaluated.

  2. Histological esophagitis before and after surgical treatment of morbid obesity (Capella technique): a prospective study.

    PubMed

    Reis, Galzuinda Maria Figueiredo; Savassi-Rocha, Paulo Roberto; Nogueira, Ana Margarida M F; Lima, Marcílio José Rodrigues; de Carvalho, Silas; Arantes, Vitor; Barros, Carlos Alberto; Cançado, Omar Lopes

    2008-04-01

    The effects of vertical banded gastroplasty/Roux-en-Y gastric bypass (Capella) on the esophageal mucosa of patients with histological esophagitis are poorly understood. To evaluate long-term effects, we investigated the persistence, aggravation or disappearance of histological esophagitis in patients with morbid obesity and reflux esophagitis (diagnosed by endoscopic biopsy) after Roux-en-Y gastric bypass. Twenty-one patients with morbid obesity and esophagitis (histological diagnosis) were submitted to gastric bypass (Fobi-Capella technique) and underwent upper endoscopy and esophageal biopsy during the late postoperative period. The mean age of the patients was 42.57 +/- 7.49 years (30 to 56). Nineteen (90.48%) patients were women, and two (9.52%) were men. Before surgery, the patients presented a mean weight of 124.26 +/- 19.09 kg and a mean body mass index (BMI) of 48.46 +/- 6.37 kg/m(2). Thirteen (61.90%) patients had endoscopic esophagitis before surgery. The mean weight and BMI were 81.65 +/- 13.16 kg and 31.91 +/- 4.99 kg/m(2), respectively, during the late postoperative period (29.80 +/- 8.91 months). The mean percentage of excess weight loss was 68.7 +/- 14.6%. Among the 21 patients with a preoperative histological diagnosis of reflux esophagitis, five (23.18%) had the same diagnosis after surgery, and four (19.04%) continued to present findings of endoscopic esophagitis. Vertical banded gastroplasty/Roux-en-Y gastric bypass (Capella technique) is effective in the treatment of reflux esophagitis. No association was observed between the percentage of excess weight loss and improvement of esophagitis.

  3. Microscopic histological characteristics of soft tissue sarcomas: analysis of tissue features and electrical resistance.

    PubMed

    Tosi, A L; Campana, L G; Dughiero, F; Forzan, M; Rastrelli, M; Sieni, E; Rossi, C R

    2017-07-01

    Tissue electrical conductivity is correlated with tissue characteristics. In this work, some soft tissue sarcomas (STS) excised from patients have been evaluated in terms of histological characteristics (cell size and density) and electrical resistance. The electrical resistance has been measured using the ex vivo study on soft tissue tumors electrical characteristics (ESTTE) protocol proposed by the authors in order to study electrical resistance of surgical samples excised by patients in a fixed measurement setup. The measurement setup includes a voltage pulse generator (700 V, 100 µs long at 5 kHz, period 200 µs) and an electrode with 7 needles, 20 mm-long, with the same distance arranged in a fixed hexagonal geometry. In the ESTTE protocol, the same voltage pulse sequence is applied to each different tumor mass and the corresponding resistance has been evaluated from voltage and current recorded by the equipment. For each tumor mass, a histological sample of the volume treated by means of voltage pulses has been taken for histological analysis. Each mass has been studied in order to identify the sarcoma type. For each histological sample, an image at 20× or 40× of magnification was acquired. In this work, the electrical resistance measured for each tumor has been correlated with tissue characteristics like the type, size and density of cells. This work presents a preliminary study to explore possible correlations between tissue characteristics and electrical resistance of STS. These results can be helpful to adjust the pulse voltage intensity in order to improve the electrochemotherapy efficacy on some histotype of STS.

  4. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    SciTech Connect

    Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.; Vitaz, Todd W.; Spalding, Aaron C.

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

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

    ERIC Educational Resources Information Center

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

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

  6. Rare breast cancer subtypes: histological, molecular, and clinical peculiarities.

    PubMed

    Dieci, Maria Vittoria; Orvieto, Enrico; Dominici, Massimo; Conte, PierFranco; Guarneri, Valentina

    2014-08-01

    Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some good-prognosis triple-negative histotypes, on the basis of gene expression profiling, can be classified among the poor-prognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies.

  7. Evaluation of Virtual Microscopy in Medical Histology Teaching

    ERIC Educational Resources Information Center

    Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

    2013-01-01

    Histology stands as a major discipline in the life science curricula, and the practice of teaching it is based on theoretical didactic strategies along with practical training. Traditionally, students achieve practical competence in this subject by learning optical microscopy. Today, students can use newer information and communication…

  8. Remote Histology Learning from Static versus Dynamic Microscopic Images

    ERIC Educational Resources Information Center

    Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

    2016-01-01

    Histology is the study of microscopic structures in normal tissue sections. Curriculum redesign in medicine has led to a decrease in the use of optical microscopes during practical classes. Other imaging solutions have been implemented to facilitate remote learning. With advancements in imaging technologies, learning material can now be digitized.…

  9. Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

    DTIC Science & Technology

    2012-09-01

    undergoing reduction mammoplasty surgeries . (A) A normal breast TDLU with normal length telomeres in all cell types present. (B) A normal breast TDLU...to severe telomere shortening is highly prevalent within histologically normal TDLUs obtained from women undergoing reduction mammoplasty surgeries ...specialize in the research and treatment of breast cancer. The trainee has attended weekly journal clubs, Oncology translational research seminars , breast

  10. Histology of periapical lesions obtained during apical surgery.

    PubMed

    Schulz, Malte; von Arx, Thomas; Altermatt, Hans Jörg; Bosshardt, Dieter

    2009-05-01

    The aim of this was to evaluate the histology of periapical lesions in teeth treated with periapical surgery. After root-end resection, the root tip was removed together with the periapical pathological tissue. Histologic sectioning was performed on calcified specimens embedded in methylmethacrylate (MMA) and on demineralized specimens embedded in LR White (Fluka, Buchs, Switzerland). The samples were evaluated with light and transmission electron microscopy (TEM). The histologic findings were classified into periapical abscesses, granulomas, or cystic lesions (true or pocket cysts). The final material comprised 70% granulomas, 23% cysts and 5% abscesses, 1% scar tissues, and 1% keratocysts. Six of 125 samples could not be used. The cystic lesions could not be subdivided into pocket or true cysts. All cysts had an epithelium-lined cavity, two of them with cilia-lined epithelium. These results show the high incidence of periapical granulomas among periapical lesions obtained during apical surgery. Periapical abscesses were a rare occasion. The histologic findings from samples obtained during apical surgery may differ from findings obtained by teeth extractions. A determination between pocket and true apical cysts is hardly possible when collecting samples by apical surgery.

  11. Craniofacial Dermoid Cysts: Histological Analysis and Inter-site Comparison

    PubMed Central

    Reissis, Dimitris; Pfaff, Miles J.; Patel, Anup; Steinbacher, Derek M.

    2014-01-01

    Introduction: Dermoid cysts are common, benign, embryologically derived soft tissue cysts that can arise at a variety of craniofacial sites. It is not known whether specific histological variations exist between the different craniofacial sites. This study aims to establish whether inter-site histologic differences exist between periorbital, nasal, scalp, and postauricular dermoid cysts and analyze these in context of their distinct embryological origin and varied clinical presentation. Methods: A retrospective review of craniofacial dermoid cysts was performed. Using light microscopy with hematoxylin and eosin staining, histological appearance was directly compared between craniofacial sites. Results: All (n = 16) cysts contained keratinizing, stratified squamous epithelial lining, intraluminal keratin, and hair. Sebaceous glands were commonly present (n = 13). Eccrine (sweat) glands were less common (n = 3). Structures of mesodermal origin were seen in three periorbital cysts. Only the six ruptured cysts showed evidence of inflammation. Conclusions: Histological properties of dermoid cysts are conserved between craniofacial sites (periorbital, nasal, scalp, and postauricular). This reflects the consistency of ectodermal inclusion during early embryological development, which is independent of specific craniofacial site or surrounding anatomical structures. PMID:25191150

  12. Remote Histology Learning from Static versus Dynamic Microscopic Images

    ERIC Educational Resources Information Center

    Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

    2016-01-01

    Histology is the study of microscopic structures in normal tissue sections. Curriculum redesign in medicine has led to a decrease in the use of optical microscopes during practical classes. Other imaging solutions have been implemented to facilitate remote learning. With advancements in imaging technologies, learning material can now be digitized.…

  13. Evaluation of Virtual Microscopy in Medical Histology Teaching

    ERIC Educational Resources Information Center

    Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

    2013-01-01

    Histology stands as a major discipline in the life science curricula, and the practice of teaching it is based on theoretical didactic strategies along with practical training. Traditionally, students achieve practical competence in this subject by learning optical microscopy. Today, students can use newer information and communication…

  14. Stacked Predictive Sparse Decomposition for Classification of Histology Sections.

    PubMed

    Chang, Hang; Zhou, Yin; Borowsky, Alexander; Barner, Kenneth; Spellman, Paul; Parvin, Bahram

    2015-05-01

    Image-based classification of histology sections, in terms of distinct components (e.g., tumor, stroma, normal), provides a series of indices for histology composition (e.g., the percentage of each distinct components in histology sections), and enables the study of nuclear properties within each component. Furthermore, the study of these indices, constructed from each whole slide image in a large cohort, has the potential to provide predictive models of clinical outcome. For example, correlations can be established between the constructed indices and the patients' survival information at cohort level, which is a fundamental step towards personalized medicine. However, performance of the existing techniques is hindered as a result of large technical variations (e.g., variations of color/textures in tissue images due to non-standard experimental protocols) and biological heterogeneities (e.g., cell type, cell state) that are always present in a large cohort. We propose a system that automatically learns a series of dictionary elements for representing the underlying spatial distribution using stacked predictive sparse decomposition. The learned representation is then fed into the spatial pyramid matching framework with a linear support vector machine classifier. The system has been evaluated for classification of distinct histological components for two cohorts of tumor types. Throughput has been increased by using of graphical processing unit (GPU), and evaluation indicates a superior performance results, compared with previous research.

  15. Comparison of three different techniques for histological tooth preparation.

    PubMed

    Keklikoglu, Nurullah; Akinci, Sevtap

    2013-01-01

    The histological processing of teeth is highly complicated because of containing both mineralized hard tissues and soft tissues. Depending on the type of decalcification agents used in processing, mild-to-severe deterioration in the tissue structure and inadequacies on clear staining of details by the histological stain may be observed. This study aims to compare the histological staining differences in the preparations from decalcified and undecalcified tooth roots by three different embedding materials and techniques. Following extraction, human single-rooted teeth crowns were cut off and roots were placed in 10% buffered neutral formalin. After fixation, roots were divided into two groups. One part of samples was decalcified in formic acid solution and the other was remained undecalcified. Decalcified roots were embedded in paraffin and glycol methacrylate (GMA)-based resin and undecalcified roots were embedded in methyl methacrylate (MMA)-based resin. Sections from all groups were stained with hematoxylin and eosin. The groups were compared in terms of general staining, brightness, density, density of the base stain, general morphology of cells, nuclear/cytoplasmic contrast, distinguish ability of pulp, odontoblast layer, predentin and dentin, preservation and traceability of dentinal tubule. In the preparations which were embedded into the MMA-based embedding material, an output lower than the paraffin group buthigher than the GMA-embedded group was provided. As a result, the best histological detail was obtained from the decalcified, paraffin-embedded sections.

  16. Histological Features of Melanoma Associated with CDKN2A Genotype

    PubMed Central

    Sargen, Michael R.; Kanetsky, Peter A.; Newton-Bishop, Julia; Hayward, Nicholas K.; Mann, Graham J.; Gruis, Nelleke A.; Tucker, Margaret A.; Goldstein, Alisa M.; Bianchi-Scarra, Giovanna; Puig, Susanna; Elder, David E.

    2014-01-01

    Background Inherited susceptibility genes have been associated with histopathologic characteristics of tumors. Objective To identify associations between histology of melanomas and CDKN2A genotype. Methods Case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N=81) and cases from melanoma families with (N=123) and without (N=120) CDKN2A germline mutations. Results Compared with CDKN2A-negative cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (ptrend=0.02) and increased pagetoid scatter (ptrend=0.07) after adjusting for age at diagnosis, sex, and AJCC thickness category. Similar associations were observed when comparing mutation carriers to a combined group of CDKN2A-negative (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the fifteen cases with this phenotype, none were observed to harbor a CDKN2A mutation. Limitations Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype. Conclusion Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase. PMID:25592620

  17. Histology image analysis for carcinoma detection and grading

    PubMed Central

    He, Lei; Long, L. Rodney; Antani, Sameer; Thoma, George R.

    2012-01-01

    This paper presents an overview of the image analysis techniques in the domain of histopathology, specifically, for the objective of automated carcinoma detection and classification. As in other biomedical imaging areas such as radiology, many computer assisted diagnosis (CAD) systems have been implemented to aid histopathologists and clinicians in cancer diagnosis and research, which have been attempted to significantly reduce the labor and subjectivity of traditional manual intervention with histology images. The task of automated histology image analysis is usually not simple due to the unique characteristics of histology imaging, including the variability in image preparation techniques, clinical interpretation protocols, and the complex structures and very large size of the images themselves. In this paper we discuss those characteristics, provide relevant background information about slide preparation and interpretation, and review the application of digital image processing techniques to the field of histology image analysis. In particular, emphasis is given to state-of-the-art image segmentation methods for feature extraction and disease classification. Four major carcinomas of cervix, prostate, breast, and lung are selected to illustrate the functions and capabilities of existing CAD systems. PMID:22436890

  18. Stacked Predictive Sparse Decomposition for Classification of Histology Sections

    PubMed Central

    Zhou, Yin; Borowsky, Alexander; Barner, Kenneth; Spellman, Paul

    2016-01-01

    Image-based classification of histology sections, in terms of distinct components (e.g., tumor, stroma, normal), provides a series of indices for histology composition (e.g., the percentage of each distinct components in histology sections), and enables the study of nuclear properties within each component. Furthermore, the study of these indices, constructed from each whole slide image in a large cohort, has the potential to provide predictive models of clinical outcome. For example, correlations can be established between the constructed indices and the patients’ survival information at cohort level, which is a fundamental step towards personalized medicine. However, performance of the existing techniques is hindered as a result of large technical variations (e.g., variations of color/textures in tissue images due to non-standard experimental protocols) and biological heterogeneities (e.g., cell type, cell state) that are always present in a large cohort. We propose a system that automatically learns a series of dictionary elements for representing the underlying spatial distribution using stacked predictive sparse decomposition. The learned representation is then fed into the spatial pyramid matching framework with a linear support vector machine classifier. The system has been evaluated for classification of distinct histological components for two cohorts of tumor types. Throughput has been increased by using of graphical processing unit (GPU), and evaluation indicates a superior performance results, compared with previous research. PMID:27721567

  19. Validation of Histologic Bone Analysis Following Microfil Vessel Perfusion

    PubMed Central

    Sarhaddi, D; Poushanchi, B; Merati, M; Tchanque-Fossuo, C; Donneys, A; Baker, J; Buchman, SR

    2015-01-01

    The ability to examine bone vascularity using Micro-Computed Tomography (μCT) following vessel perfusion with Microfil® and to subsequently perform histologic bone analysis in the same specimen would provide an efficient method by which the vascular and cellular environment of bone can be examined simultaneously. The purpose of this report is to determine if the administration of Microfil® precludes accurate histologic assessment of bone quality via osteocyte count and empty lacunae count. Sprague-Dawley rats (n=6) underwent perfusion with Microfil®. Left hemi-mandibles were harvested, decalcified and underwent vascular analysis via μCT prior to sectioning and staining with Gomori's Trichrome. Quantitative Histomorphometric evaluation was performed. Ninety-five percent confidence intervals were used to determine statistical differences from an established set of controls (n=12). Histologic analyses were successfully performed on specimens that had undergone previous perfusion. Quantitative measures of bone cellularity of perfused versus control specimens revealed no statistical difference in osteocyte count per high-power field (95.33 versus 94.66; 95 percent CI,-7.64 to 6.30) or empty lacunae per high-power field (2.73 versus 1.89, 95 percent CI, -1.81 to 0.13). Here we report a statistical validation allowing for histological analysis of cell counts in specimens in which Microfil® perfusion has previously been performed. PMID:26207077

  20. [Graves' disease: ultrasonographic, color Doppler and histological aspects].

    PubMed

    Messina, G; Viceconti, N; Trinti, B

    1997-11-01

    The aim of the present work was to study the relationship between thyroid low echogenicity, the thyroid blood flow by color-Doppler (CD) and histological features in patients with Graves' disease (GD). Thyroid ultrasonography and CD was performed on 28 patients with GD. In 5 patients has been compared CD with histology. The thyroid volume was higher in 100% of patients with GD at the onset rather than in euthyroidism. Diffuse hypoechogenicity of the thyroid was discovered in 100% of patients with GD at the onset and it persisted in 57.1% of patients that became euthyroid after therapy. Qualitative CD resulted in different patterns that were classified as follow: pattern A ("thyroid inferno") in 17 patients (60.7%); pattern B (mildly increased of parenchymal blood flow) in 11 patients (39.3%). In the 5 histological proven cases, in the pattern A (3 cases) there was a diffuse microfollicular hyperplasia with functional activation notes. There was lymphocytic infiltration. While in the pattern B (two cases) there were a non-follicular hypercellular nodule with pseudocapsule and rare colloid. We conclude that there are two different histological types with different CD patterns in GD.

  1. Histological reclassification of parotid gland carcinomas: importance for clinicians.

    PubMed

    Stodulski, Dominik; Majewska, Hanna; Skálová, Alena; Mikaszewski, Bogusław; Biernat, Wojciech; Stankiewicz, Czesław

    2016-11-01

    Reassessment of histological specimens of salivary gland carcinomas is associated with a change of primary diagnosis in a significant number of patients. The authors evaluated the relation between reclassification/verification of histological diagnosis and the clinical course of parotid gland carcinomas. Histological and immunohistochemical examinations of 111 specimens of parotid gland carcinomas operated on during the years 1992-2010 were revised and in some cases supplemented with cytogenetic tests (FISH), to verify the diagnosis and potentially reclassify the tumours. Analysis of the clinical documentation and follow-up data of patients whose diagnosis was changed was then carried out. The prognostic factors taken into account in the evaluation of the clinical course included the T and N stage, the tumour grade and the extent of resection. The primary diagnosis was changed on review in 28 patients (25.2 %). In 16 patients, the change involved a different histological type of cancer. In six cases, what was thought to be a primary salivary gland cancer was reclassified as a secondary tumour. In four other cases, the change was made from a malignant to a benign tumour and in one case to a non-neoplastic lesion (necrotizing sialometaplasia). Additionally, in two patients with carcinoma ex pleomorphic adenoma, the malignant component was found to be of in situ type. A potentially atypical clinical course was observed in 4 out of 28 patients whose diagnosis was changed. In the case of 2 patients, the course of disease was more aggressive (dissemination, death) than predicted and less aggressive in rest of the patients. Histological reclassification/verification of parotid gland carcinomas can explain the cause of an atypical clinical course in some patients and sometimes enables doctors to implement a change in therapy.

  2. Endoscopic atrophic classification before and after H. pylori eradication is closely associated with histological atrophy and intestinal metaplasia

    PubMed Central

    Kodama, Masaaki; Okimoto, Tadayoshi; Ogawa, Ryo; Mizukami, Kazuhiro; Murakami, Kazunari

    2015-01-01

    Background and study aims: The relationship between endoscopic atrophy classification (EAC) and histological gastric atrophy and intestinal metaplasia (IM) was examined before and after Helicobacter pylori (H. pylori) eradication in order to evaluate the usefulness of EAC for detecting the risk of gastric cancer following eradication. Patients and methods: A total of 230 patients (137 males, 93 females; mean age: 58.0 ± 11.8 y) with successful eradication were enrolled. EAC score was defined as follows: C0(none): 0, C1: 1, C2: 2, C3: 3, O1: 4, O2: 5, and O3(severe): 6. Histological atrophy and IM score (0 to 3) from the antrum and the corpus were evaluated with updated Sydney system for histological atrophy and IM. Results: The mean EAC scores were 3.46 before eradication and 3.20 after eradication (P = 0.026). The mean atrophy scores before and after eradication were 1.45 and 0.92 at the antrum (P < 0.001) and 0.50 and 0.07 at the corpus (P < 0.001), respectively. The mean IM scores before and after eradication were 0.55 and 0.47 at the antrum (P = 0.154), and 0.09 and 0.05 at the corpus (P = 0.096), respectively. The histological atrophy scores showed significant improvement after eradication, while IM showed no significant change. The Mantel-Haenszel test for trend indicated there was a significant correlation between EAC and histological atrophy and IM, except antral atrophy after eradication. Conclusions: EAC exhibited a significant correlation between histological atrophy and IM, and represents a noninvasive classification method. EAC may be beneficial in evaluating the risk of gastric cancer after H. pylori eradication. PMID:26357676

  3. Effects of Phlebotomy on Liver Enzymes and Histology of Patients with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Khodadoostan, Mahsa; Zamanidoost, Maryam; Shavakhi, Ahmad; Sanei, Hosein; Shahbazi, Masood; Ahmadian, Mehdi

    2017-01-01

    Background: Nonalcoholic fatty liver disease (NAFLD), defined as excessive liver fat deposition and one of end-stage liver disease causes. Increased ferritin levels are associated with insulin resistance and a higher hepatic iron and fat content. Hyperferritinemia has been associated with severity of liver damage in NAFLD. The study aimed to evaluate the effects of phlebotomy on liver enzymes and histology in such patients. Materials and Methods: Thirty-two eligible patients who had NAFLD and after 6 months of lifestyle modification still had NAFLD, and whose ferritin serum was above 250 mg/dl, were enrolled in this clinical trial study. After written informed consent was obtained, each patient's blood serum was taken for aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALK-P), complete blood count (CBC), total iron-binding capacity (TIBC), iron, and ferritin. Then the patients underwent liver biopsy. After that patients underwent phlebotomy, giving 350 cc blood monthly. Before every phlebotomy, hemoglobin and ferritin were checked. If they were in the goal range, phlebotomy was discontinued and the patient underwent liver biopsy. A serum sample was taken for testing at the beginning of the study. The results before and after phlebotomy were compared. The maximum duration of the study was 6 months. Results: Thirty-two patients (26 males and 6 females) were enrolled, and the mean average age was 33.7 ± 6.74 years. Phlebotomy improved liver enzymes and histology of liver significantly (P < 0.001) and induced reduction of ferritin. Conclusion: Phlebotomy is effective for the improvement of liver enzymes and histology in patients with NAFLD and hyperferritinemia. PMID:28299304

  4. Enhancements in localized classification for uterine cervical cancer digital histology image assessment

    PubMed Central

    Guo, Peng; Almubarak, Haidar; Banerjee, Koyel; Stanley, R. Joe; Long, Rodney; Antani, Sameer; Thoma, George; Zuna, Rosemary; Frazier, Shelliane R.; Moss, Randy H.; Stoecker, William V.

    2016-01-01

    Background: In previous research, we introduced an automated, localized, fusion-based approach for classifying uterine cervix squamous epithelium into Normal, CIN1, CIN2, and CIN3 grades of cervical intraepithelial neoplasia (CIN) based on digitized histology image analysis. As part of the CIN assessment process, acellular and atypical cell concentration features were computed from vertical segment partitions of the epithelium region to quantize the relative distribution of nuclei. Methods: Feature data was extracted from 610 individual segments from 61 images for epithelium classification into categories of Normal, CIN1, CIN2, and CIN3. The classification results were compared against CIN labels obtained from two pathologists who visually assessed abnormality in the digitized histology images. In this study, individual vertical segment CIN classification accuracy improvement is reported using the logistic regression classifier for an expanded data set of 118 histology images. Results: We analyzed the effects on classification using the same pathologist labels for training and testing versus using one pathologist labels for training and the other for testing. Based on a leave-one-out approach for classifier training and testing, exact grade CIN accuracies of 81.29% and 88.98% were achieved for individual vertical segment and epithelium whole-image classification, respectively. Conclusions: The Logistic and Random Tree classifiers outperformed the benchmark SVM and LDA classifiers from previous research. The Logistic Regression classifier yielded an improvement of 10.17% in CIN Exact grade classification results based on CIN labels for training-testing for the individual vertical segments and the whole image from the same single expert over the baseline approach using the reduced features. Overall, the CIN classification rates tended to be higher using the training-testing labels for the same expert than for training labels from one expert and testing labels from

  5. Histology and mucosubstance histochemistry of mongoose salivary glands.

    PubMed

    Poddar, S; Jacob, S

    1978-01-01

    The histology and mucosubstance histochemistry of the mongoose salivary glands were studied. Histologically, the mongoose salivary glands were generally similar to those in other carnivores (dog, cat and ferret). The mucosubstance histochemistry demonstrated considerable variations in the parotid, submandibular and sublingual glands in comparison to the other carnivores. The partoid gland contained carboxylated mucin which was sialidase-resistant. Granules in a few cells also contained sulphated mucin. Both submandibular and sublingual glands contained mainly carboxylated sialomucin which was sialidase-labile except in a few cell, some neutral mucin but no sulphated mucin. The molar and zygomatic glands were similar to those in the other carnivores. They contained both sulphated and carboxylated mucins but no neutral mucin. The carboxylated mucin was sialidase-resistant.

  6. Developmental palaeontology of Reptilia as revealed by histological studies.

    PubMed

    Scheyer, Torsten M; Klein, Nicole; Sander, P Martin

    2010-06-01

    Among the fossilized ontogenetic series known for tetrapods, only more basal groups like temnospondyl amphibians have been used extensively in developmental studies, whereas reptilian and synapsid data have been largely neglected so far. However, before such ontogenetic series can be subject to study, the relative age and affiliation of putative specimens within a series has to be verified. Bone histology has a long-standing tradition as being a source of palaeobiological and growth history data in fossil amniotes and indeed, the analysis of bone microstructures still remains the most important and most reliable tool for determining the absolute ontogenetic age of fossil vertebrates. It is also the only direct way to reconstruct life histories and growth strategies for extinct animals. Herein the record of bone histology among Reptilia and its application to elucidate and expand fossilized ontogenies as a source of developmental data are reviewed. (c) 2009 Elsevier Ltd. All rights reserved.

  7. [Histologic and anatomic correlation of the infraorbital region].

    PubMed

    Copin, H; Bremond-Gignac, D; Cirilie, K; Braun, M; Kohler, Ch

    2003-12-01

    The infra-orbital area has not been well studied although it represents an interesting area in plastic surgery because of its implication in malarplasty reduction or transplantation for facial tissue repair. This work comprises an anatomic dissection layer by layer and a histologic study describing the various structures of this area. It was performed on 10 heads taken from cadavers (mean age 70 years old). The anatomic and histologic study found four layers: a subcutaneous fat layer, a muscular layer, a deep fat layer and a deep muscular layer. The superficial fat layer constitutes the convexity of the cheek and can be removed in plastic surgery reduction or reconstituted after atrophy following nasolabial musculo cutaneous flaps.

  8. Endocrine Mucin-Producing Sweat Gland Carcinoma, a Histological Challenge

    PubMed Central

    Salama, Samih; Gohla, Gabriella; Alowami, Salem

    2017-01-01

    Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for the skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumor is seen more frequently in women and on average affects the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of the breast/endocrine ductal carcinoma in situ with a nodular, solid, papillary, and/or cribriforming architecture, neuroendocrine differentiation, and mucin production. Since it was first described by Flieder et al. in 1997, less than 60 cases have been reported in literature. We describe the morphological and immunohistochemical features of another case with a review of the common histological differential diagnoses and emphasize the salient features that help distinguish this rare neoplasm. PMID:28299221

  9. The histology of distraction osteogenesis using different external fixators.

    PubMed

    Aronson, J; Harrison, B H; Stewart, C L; Harp, J H

    1989-04-01

    The local biology of distraction osteogenesis using Ilizarov and Wagner external fixators was compared in unilateral tibial lengthenings in two groups of eight dogs. Serial roentgenograms with histological correlation revealed some basic similarities as well as distinct differences between the two groups. All dogs fully bridged the experimental gap by intramembranous ossification. Subtle histological changes in the alignment of collagen bundles and subsequent ossification reflected the mechanical configuration of each fixator. The multiplanar, full-pin Ilizarov system delivered concentric load to the site of osteogenesis, inducing perfectly parallel columns of new bone. The uniplanar, one-half pin Wagner system induced angulation of the collagen and subsequent bone columns on the basis of eccentric load to the osteogenic interface. Despite a significant difference in axial rigidity, the Ilizarov and Wagner external fixators induced osteogenesis of equal volume.

  10. Chronic idiopathic inflammatory bowel diseases: the histology report.

    PubMed

    Cornaggia, Matteo; Leutner, Monica; Mescoli, Claudia; Sturniolo, Giacomo Carlo; Gullotta, Renzo

    2011-03-01

    The incidence of chronic idiopathic inflammatory bowel diseases (IBD) is growing in western countries, making their histological diagnosis an everyday task for all pathologists. Reviews from the literature strongly suggest that such diagnosis cannot be performed on the histological ground alone but requires a clinical-pathological approach. Moreover, bewildering variations can be observed in the terminology employed to report either individual lesions or diagnostic categories. The aim of the present paper is to suggest a practical diagnostic algorithm summarizing the main data from the literature. Particular emphasis has been placed on minimum clinical information required and the accurate definition of individual lesions. Diagnostic categories to employ and to avoid in daily practice have furthermore been stressed.

  11. Histological evaluation of hair follicle due to papain's depilatory effect.

    PubMed

    Traversa, Eduardo; Machado-Santelli, Gláucia Maria; Velasco, Maria Valéria Robles

    2007-04-20

    Histological alterations in the skin and hair follicle of mice were evaluated as a result of the application of gel and cream formulas containing papain as a harmless treatment for hirsutism. Papain is a proteolytic enzyme and it has been used in pharmaceutical, cosmetic and nutrition areas. The purpose of this study was to evaluate the efficacy of a depilatory product, through histological analysis using light microscopy. Gel and cream formulas containing papain were developed and daily applied on the back of two groups of mice for 31 days. The depilatory effect of the gel formula applied on the first group was less evident. The second group treated with the cream formula presented an intensive depilatory effect; the morphometrical analysis showed dilation of about 55% of the hair follicle lumen and an increase of the thickness of epidermis. Papain cream had a significantly higher depilatory effect than the papain gel.

  12. [Histological detection of dried tiny thyroid tissue in health foods].

    PubMed

    Ichikawa, Tetsuro; Kobayashi, Yukari; Miyajima, Yoshifumi

    2008-12-01

    Two patients were diagnosed as having hyperthyroidism, and both had taken the same health food. We compared three kinds of histological methods to detect thyroid gland in this health food. The first method used cytology; the second applied the cell-block method; and the last is a modification of the cell particle (CPCB) method proposed by Ushijima. It is the third method that achieved superior results, and this enabled the morphological detection of thyroid gland. Certain kinds of health foods contain dried thyroid as a "slimming supplement", and intake of these products may damage health. Histological techniques are effective for detecting the existence of dried thyroid gland. A health food is very different from clinical specimen; therefore, we have to devise appropriate skills for examining it. Such examinations will be important in the future, because it is expected that the risks of damaging health by consuming certain kinds of health food will increase.

  13. Histological effects of calcium chloride in stored apples

    USDA-ARS?s Scientific Manuscript database

    Mature apples, Malus domestica Borkh., cv. 'Golden Delicious' were immersed for 2 min in 0, 0.14, 0.27, or 0.41 mol L-1 (0, 2%, 4%, or 6%, respectively) aqueous solutions (w/v) of CaCl2 at 0 or 68.95 Kpa, and stored at 0°C. Histological samples of peel/cortex were taken at harvest and at four month...

  14. Deep UV autofluorescence microscopy for cell biology and tissue histology.

    PubMed

    Jamme, Frédéric; Kascakova, Slavka; Villette, Sandrine; Allouche, Fatma; Pallu, Stéphane; Rouam, Valérie; Réfrégiers, Matthieu

    2013-07-01

    Autofluorescence spectroscopy is a powerful tool for molecular histology and for following metabolic processes in biological samples as it does not require labelling. However, at the microscopic scale, it is mostly limited to visible and near infrared excitation of the samples. Several interesting and naturally occurring fluorophores can be excited in the UV and deep UV (DUV), but cannot be monitored in cellulo nor in vivo due to a lack of available microscopic instruments working in this wavelength range. To fulfil this need, we have developed a synchrotron-coupled DUV microspectrofluorimeter which is operational since 2010. An extended selection of endogenous autofluorescent probes that can be excited in DUV, including their spectral characteristics, is presented. The distribution of the probes in various biological samples, including cultured cells, soft tissues, bone sections and maize stems, is shown to illustrate the possibilities offered by this system. In this work we demonstrate that DUV autofluorescence is a powerful tool for tissue histology and cell biology. To fulfil this need, we have developed a synchrotron-coupled DUV microspectrofluorimeter which is operational since 2010. An extended selection of endogenous autofluorescent probes that can be excited in DUV, including their spectral characteristics, is presented. The distribution of the probes in various biological samples, including cultured cells, soft tissues, bone sections and maize stems, is shown to illustrate the possibilities offered by this system. In this work we demonstrate that DUV autofluorescence is a powerful tool for tissue histology and cell biology. In this work we demonstrate that DUV autofluorescence is a powerful tool for tissue histology and cell biology. © 2013 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  15. Remote histology learning from static versus dynamic microscopic images.

    PubMed

    Mione, Sylvia; Valcke, Martin; Cornelissen, Maria

    2016-05-06

    Histology is the study of microscopic structures in normal tissue sections. Curriculum redesign in medicine has led to a decrease in the use of optical microscopes during practical classes. Other imaging solutions have been implemented to facilitate remote learning. With advancements in imaging technologies, learning material can now be digitized. Digitized microscopy images can be presented in either a static or dynamic format. This study of remote histology education identifies whether dynamic pictures are superior to static images for the acquisition of histological knowledge. Test results of two cohorts of second-year Bachelor in Medicine students at Ghent University were analyzed in two consecutive academic years: Cohort 1 (n = 190) and Cohort 2 (n = 174). Students in Cohort 1 worked with static images whereas students in Cohort 2 were presented with dynamic images. ANCOVA was applied to study differences in microscopy performance scores between the two cohorts, taking into account any possible initial differences in prior knowledge. The results show that practical histology scores are significantly higher with dynamic images as compared to static images (F (1,361) = 15.14, P < 0.01), regardless of student's gender and performance level. Several reasons for this finding can be explained in accordance with cognitivist learning theory. Since the findings suggest that knowledge construction with dynamic pictures is stronger as compared to static images, dynamic images should be introduced in a remote setting for microscopy education. Further implementation within a larger electronic learning management system needs to be explored in future research. Anat Sci Educ 9: 222-230. © 2015 American Association of Anatomists. © 2015 American Association of Anatomists.

  16. Histology of Infection of Hydrilla verticillata by Macrophomina phaseolina

    DTIC Science & Technology

    1991-10-01

    Macrophomina phaseolina. Plant Disease (Dec.): 1035-1036. Madkour , M. A., and Aly, M. H . 1981. Cell wall degrading enzymes produced during...a.efaqe I nour per response ncluding the t me for revewng instructions, sear( h ,nq ex sting data sources. gathering and nanta nin the data needed, and...L.f.) Royle in recent studies. The purpose of this study was to follow the histology of infection of H . verticillata by M. phaseolina with particular

  17. Trachyonychia: Review and Update on Clinical Aspects, Histology, and Therapy

    PubMed Central

    Haber, Jessica S.; Chairatchaneeboon, Manasmon; Rubin, Adam I.

    2017-01-01

    Trachyonychia is a disorder of the nail unit that most commonly presents with rough, longitudinally ridged nails (opaque trachyonychia) or less frequently, uniform, opalescent nails with pits (shiny trachyonychia). The term trachyonychia refers to ‘rough nails.’ This article comprehensively reviews the clinical, histologic, and therapeutic aspects of trachyonychia. The authors' preferred evaluation and management strategies of trachyonychia are included. PMID:28232917

  18. Histologic changes in transplanted expanded polytetrafluoroethylene in an animal model.

    PubMed

    Kim, Ji Heui; Park, Chan Hum; Lee, Ok Joo; Lee, Jun Ho; Hong, Seok Min

    2012-01-01

    Several materials have been used for nasal augmentation surgery. Expanded polytetrafluoroethylene (e-PTFE) (Gore-Tex; W. L. Gore & Associates, Flagstaff, AZ) has proven to be an ideal synthetic material for nasal augmentation. Gore-Tex contains numerous pores that stabilize an implant, but this advantage has been tempered by unpredictable outcomes. The purpose of this study was to evaluate morphologic and histologic changes in nonreinforced Gore-Tex in a rabbit model. In vivo study using a rabbit model. To analyze histologic changes, we used 20 New Zealand white rabbits. Gore-Tex was implanted into the nasal dorsum of the rabbits. Then, en bloc specimens containing the implant and surrounding soft tissues were sampled 1, 3, 6, and 12 months after implantation. We evaluated the three-dimensional size of the implants over time using light and electron microscopy to investigate histologic and morphologic changes. Following gross analysis, none of the implants were lost or extruded, and there was no evidence of wound infection. Diminution rates of thickness, width