Miracle-dz/UniFAR-FTUs huggingface dataset:
D-thyroxine reduces lipoprotein(a) serum concentration in dialysis patients.

Uremia raises lipoprotein(a) (Lp(a)) serum concentration and the risk of arteriosclerosis in dialysis patients. The treatment of high Lp(a) levels is not satisfactory today. The decrease of Lp(a) in hypothyroid patients on L-T4 therapy raised the question of whether dextro-thyroxine (D-thyroxine) reduces not only serum cholesterol, but also Lp(a) serum concentration. In a single-blind placebo-controlled study, the influence of D-thyroxine therapy on Lp(a) serum concentration was evaluated in 30 hemodialysis patients with elevated Lp(a) serum levels. Lp(a) was quantified in parallel by two methods, i.e., rocket immunoelectrophoresis and nephelometry, and apo(a) isoforms were determined by a sensitive immunoblotting technique. Regardless of the apo(a) isoforms, 6 mg/d D-thyroxine reduced elevated Lp(a) levels significantly by 27 +/- 13% in 20 dialysis patients (P < 0.001) compared with 10 control subjects (-9.9 +/- 8.4%). In parallel, D-thyroxine therapy significantly lowered total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and LDL cholesterol/HDL cholesterol ratio (P < 0.01); raised T4 and T3 serum levels; and suppressed thyroid-stimulating hormone secretion without causing clinical symptoms of hyperthyroidism in any of the patients. D-Thyroxine reduces elevated serum Lp(a) concentration in dialysis patients. The effect in nondialysis patients can be expected but remains to be proven.
Antimalarial compounds in Phase II clinical development

Introduction: Malaria is a major health problem in endemic countries and chemotherapy remains the most important tool in combating it. Treatment options are limited and essentially rely on a single drug class – the artemisinins. Efforts are ongoing to restrict the evolving threat of artemisinin resistance but declining sensitivity has been reported. Fueled by the ambitious aim of malaria eradication, novel antimalarial compounds, with improved properties, are now in the progressive phase of drug development. Areas covered: Herein, the authors describe antimalarial compounds currently in Phase II clinical development and present the results of these investigations. Expert opinion: Thanks to recent efforts, a number of promising antimalarial compounds are now in the pipeline. First safety data have been generated for all of these candidates, although their efficacy as antimalarials is still unclear for most of them. Of particular note are KAE609, KAF156 and DSM265, which are of chemical scaffolds new to malaria chemotherapy and would truly diversify antimalarial options. Apart from SAR97276, which also has a novel chemical scaffold that has had its development stopped, all other compounds in the pipeline belong to already known substance classes, which have been chemically modified. At this moment in time, there is not one standout compound that will revolutionize malaria treatment but several compounds that will add to its control in the future.
The influence of feeding enrichment on the behavior of small felids (Carnivora: Felidae) in captivity

Animals in captivity are frequently exposed to environmental deprivation resulting in abnormal behaviors that indicate distress. The aim of the present study was to evaluate the effect of the "surprise pack" environmental enrichment technique in improving the welfare of small neotropical felids in captivity. In order to accomplish this, we used five individuals from the Rio de Janeiro Zoo. The experiment was divided into three steps corresponding to: I) period prior to the enrichment, II) period in which the animals were being submitted to enrichment stimuli, and III) period after the enrichment. In phase II, we observed a significant reduction in abnormal behavior compared to phases I and III. Only in phase II did the animals demonstrate the following behaviors: predation, social interaction and territory demarcation. However, in this same phase, the mean time spent interacting with the enrichment throughout the day showed a decrease.
Overview of the Pancreatic Toxicity and Carcinogenesis Session

The theme of the Society of Toxicologic Pathology Annual Symposium 2013 was “Toxicologic Pathology of the Digestive Tract and Pancreas. ” The last session focused on pancreatic toxicity and carcinogenesis. This overview highlights the various presentations in this session, focusing on pancreatic toxicologic pathology, responses of the pancreas to xenobiotics, and current understanding on pancreatic carcinogenesis. The objective of this symposium overview and the subsequent articles from this session is to enable the audience to develop a better appreciation for the pancreas as a target organ in toxicological studies.
Regulation of Type II Collagen Expression by Histone Deacetylase in Articular Chondrocytes*

Histone deacetylase (HDAC) regulates various cellular processes by modulating gene expression. Here, we investigated the role of HDAC in the expression of type II collagen, a marker of differentiated chondrocytes. We found that HDAC activity in primary articular chondrocytes decreases during dedifferentiation induced by serial monolayer culture and that the activity recovered during redifferentiation induced by three-dimensional culture in a cell pellet. Inhibition of HDAC with trichostatin A or PXD101 was sufficient to block type II collagen expression in primary culture chondrocytes. HDAC inhibition also blocked the redifferentiation of dedifferentiated chondrocytes by suppressing the synthesis and accumulation of type II collagen. HDAC inhibition promoted the expression of Wnt-5a, which is known to inhibit type II collagen expression, and knockdown of Wnt-5a blocked the ability of HDAC inhibitors to suppress type II collagen expression. In addition, the induction of Wnt-5a expression by HDAC inhibitors was associated with acetylation of the Wnt-5a promoter. Taken together, our results suggest that HDAC promotes type II collagen expression by suppressing the transcription of Wnt-5a.
Exogenous 17β-Estradiol Blocks Alpha and Mu but Not Pi Class Glutathione S-Transferase Immunoreactivity in Epithelium of Syrian Hamster Vas Deferens

Members of the glutathione S-transferase (GST) family of detoxification enzymes play a role in chemotherapy resistance in certain cancers but have not been directly implicated as agents whose absence may predispose tissues to hormonally induced tumorigenesis. Here we report the development of a polyclonal antiserum to a hamster mu class GST, and immunohistochemical analysis of alpha, mu, and pi class GSTs to study the effects of hormone treatment on their expression in reproductive tract tissues of male golden Syrian hamsters. These animals develop leiomyosarcomas in the vas deferens after treatment with testosterone propionate (TP) and 17β-estradiol (E2). High levels of all three GST classes were detected throughout the reproductive tract epithelium of control animals. In 100% of the experimental animals, 4 weeks of treatment either with E2 alone, or with E2 plus TP promoted a complete loss of immunostaining for alpha and mu class GSTs, but not for pi class GSTs, only in the epithelial lining of the vas deferens. In contrast, treatment with TP alone resulted in moderate hyperplasia of smooth muscle in the proximal vas deferens, with no cellular atypia and no changes in immunoreactivity of any of the GST classes. The consistent and site-specific nature of these results strongly suggests a functional role for GSTs in hormonally induced carcinogenic process.
Polycythemia vera: current pharmacotherapy and future directions

Introduction: In the past, management of polycythemia vera (PV) was built upon a cornerstone of control over erythrocytosis, through therapeutic phlebotomy, as well as the use of low-dose aspirin. Historically, selected patients were managed with additional cytoreductive therapies to decrease the risk of vascular events, with the recognition that these therapies likely did not impede progression. Areas covered: Recent clinical trials have demonstrated, in a randomized fashion, that optimal control of the hematocrit to target levels < 45% are important for decreasing the risk of vascular events. We are identifying that our historical set of cytoreductive agents, such as hydroxyurea, may be replaced in the future. The first candidate is pegylated interferon alpha-2a, which is demonstrating the ability to control vascular events and control extended hematopoiesis, while potentially having impact on fibrotic progression and Janus kinase 2 (JAK2) V1617F mutant allele burden. Ruxolitinib, as well as other JAK2 inhibitors in development, are demonstrating that this class of agents is making a very meaningful impact on the risk of vascular events in PV, controlling expanded hematopoiesis, as well as helping with symptomatic burden. Expert opinion: Future goals include attaining a better understanding of the specific roles of JAK inhibitor therapy and whether their use in combination with standard therapies offers greater efficacy than single agents alone.
Propidium iodide compares favorably with histology and triphenyl tetrazolium chloride in the assessment of experimentally-induced infarct size.

Quantitative assessment of infarct size after histology processing or by tetrazolium staining requires long reperfusion times to facilitate the delineation of the injured tissue. We evaluated the nucleic acid stain propidium iodide as an alternate technique for assessment of infarct size because it does not require extended reperfusion and is accomplished with more simple tissue processing. Eight mice underwent 45 min of coronary artery occlusion and 24 h of reperfusion, after which propidium iodide was administered and allowed to circulate for 15 min. Hearts were excised, sliced into transverse slices approximately 620 micro m thick, and photographed for determination of infarction with propidium iodide. Slices were processed by standard histology techniques, and infarction was evaluated using classical criteria of necrosis. In four other mice, infarct size was assessed by both triphenyl tetrazolium chloride and propidium iodide staining. A total of 46 slices were analysed and infarction was described as a percentage of the cross-sectional area of the slice. The correlation (r=0.94), orthogonal regression line (y=0.9x+1.8), and the percentage of the cross-section infarcted (histology 17.5+/-3.0%v propidium iodide 18.5+/-3.0%), demonstrates that infarct size assessment after propidium iodide staining or histology processing yields the same results. Similarly, propidium iodide measurement of infarct size was comparable to that obtained with TCC staining (22.5+/-4.1%v 25.4+/-5.4%, respectively, r=0.84). We conclude that propidium iodide staining yields accurate infarct size assessment and is a simpler alternative to tetrazolium staining or histologic processing.
Diverse roles for the Eph family of receptor tyrosine kinases in carcinogenesis

The Eph family of receptor tyrosine kinases and their cell‐presented ligands, the ephrins, are frequently overexpressed in a wide variety of cancers, including breast, small‐cell lung and gastrointestinal cancers, melanomas, and neuroblastomas. In particular, one Eph family member, EphA2, is overexpressed in many cancers, including 40% of breast cancers. EphA2 can also transform breast epithelial cells in vitro to display properties commonly associated with the development of metastasis. Remarkably, the oncogenic properties of EphA2 contravene traditional dogma with regard to the oncogenic properties of a growth factor and its receptor tyrosine kinase: while stimulation of EphA2 by its ligand (ephrin‐A1) results in EphA2 autophosphorylation, the stimulation reverses the oncogenic transformation. As will be discussed in this review, the apparent dependence of oncogenicity on the dephosphorylated state of EphA2 most probably reflects the unique nature of Eph signaling. In particular, oncogenecity may depend on the capacity of unactivated EphA2 to interact with a variety of signaling molecules. As well as acting in oncogenic transformation, a growing body of evidence supports the importance of the concerted actions of ephrins and Eph molecules in tumor angiogenesis. Genetic studies, using targeted mutagenesis in mice, reveal that ephrin‐B1, ephrin‐B2, and EphB4 are essential for the normal morphogenesis of the embryonic vasculature into a sophisticated network of arteries, veins, and capillaries. Initial studies indicate that these molecules are also angiogenic in tumors, and as such represent important new targets for the development of chemotherapeutic treatments. Microsc. Res. Tech. 59:58–67, 2002. © 2002 Wiley‐Liss, Inc.
Facilitating clinical transition in the midst of cultural diversity: Challenges and strategies

The clinical facilitator (CF) role has evolved to enable the clinical transition of the growing numbers of culturally and linguistically diverse overseas qualified (CALD OSQ) nurses who have brought nursing experience and knowledge to Australia. The presence of CALD OSQ nurses in Australia reflected globalisation patterns of nursing which contributed to the imbalance of the distribution of global health service delivery. The continued reliance on CALD OSQ nurses has added to the overwhelming health workforce shortages in developing nations. However the World Health Organisation (2010) proposed the origins of the health workforce crisis stemmed from the gulf between health professional education and standards of health service delivery. This study aimed to describe participant CFs’ views of the clinical transition challenges faced by CALD OSQ nurses during clinical practicum and their views on strategies to address these challenges. A gap in research was found on this topic.
Measuring the impact of multiple sclerosis on psychosocial functioning: the development of a new self-efficacy scale

Objective: To develop a scale to measure self-efficacy in neurologically impaired patients with multiple sclerosis and to assess the scale' s psychometric properties. Design: Cross-sectional questionnaire study in a clinical setting, the retest questionnaire returned by mail after completion at home. Setting: Regional multiple sclerosis (MS) outpatient clinic or the Clinical Trials Unit (CTU) at a large neuroscience centre in the UK. Subjects: One hundred persons with MS attending the Walton Centre for Neurology and Neurosurgery and Clatterbridge Hospital, Wirral, as outpatients. Methods: Cognitively impaired patients were excluded at an initial clinic assessment. Patients were asked to provide demographic data and complete the self-efficacy scale along with the following validated scales: Hospital Anxiety and Depression Scale, Rosenberg Self-Esteem Scale, Impact, Stigma and Mastery and Rankin Scales. The Rankin Scale and Barthel Index were also assessed by the physician. Results: A new 11-item self-efficacy scale was constructed consisting of two domains of control and personal agency. The validity of the scale was confirmed using Cronbach' s alpha analysis of internal consistency (α = 0.81). The test–retest reliability of the scale over two weeks was acceptable with an intraclass correlation coefficient of 0.79. Construct validity was investigated using Pearson' s product moment correlation coefficient resulting in significant correlations with depression (r = –0.52) anxiety (r = –0.50) and mastery (r = 0.73). Multiple regression analysis demonstrated that these factors accounted for 70% of the variance of scores on the self-efficacy scale, with scores on mastery, anxiety and perceived disability being independently significant. Conclusion: Assessment of the psychometric properties of this new selfefficacy scale suggest that it possesses good validity and reliability in patients with multiple sclerosis. Address for correspondence: SJ Smith, Astley Ainslie Hospital, 133 Grange Loan, Edinburgh EH9 2HL, Scotland, UK.
Correlation of Skin Changes with Hormonal Changes in Polycystic Ovarian Syndrome: A Cross-sectional Study Clinical Study

Background: Polycystic ovarian syndrome (PCOS) is a heterogenous collection of signs and symptoms that when gathered, form a spectrum of disorder with disturbance of reproductive, endocrine and metabolic functions. Aim: The aim of this study is to correlate the skin manifestations with hormonal changes and to know the incidence and prevalence of skin manifestations in patients with PCOS. Materials and Methods: A total of 40 patients with PCOS were examined during 1 year time period from May 2008 P to May 2009. Detailed clinical history was taken from each patient. PCOS was diagnosed on the basis of ultrasonography. Hormonal assays included fasting blood sugar, postprandial blood sugar, follicle-stimulating hormone, luteinizing hormone, thyroid stimulating hormone, dehydroepiandrostenedione, prolactin, free testosterone, fasting lipid profile and sex hormone binding globulin. The results obtained were statistically correlated. Results: In our study, the prevalence of cutaneous manifestations was 90%. Of all the cutaneous manifestations acne was seen in highest percentage (67.5%), followed by hirsutism (62.5%), seborrhea (52.5%), androgenetic alopecia (AGA) (30%), acanthosis nigricans (22.5%) and acrochordons (10%). Fasting insulin levels was the most common hormonal abnormality seen in both acne and hirsutism, whereas AGA was associated with high testosterone levels. Conclusion: The prevalence of cutaneous manifestations in PCOS was 90%. Hirsutism, acne, seborrhea, acanthosis nigricans and acrochordons were associated with increased levels of fasting insulin, whereas AGA showed higher levels of serum testosterone.
The prevalence of co‐prescription of clinically relevant CYP enzyme inhibitor and substrate drugs in community‐dwelling elderly Australians

The elderly are at increased risk of adverse effects resulting from drug interactions due to decreased drug clearance and polypharmacy. This study examines the prevalence of the co‐administration of clinically relevant cytochrome P450 (CYP) enzyme inhibitors with drugs that are substrates for these enzymes, in the community‐dwelling elderly in Australia.
Posttransplant diabetes mellitus in kidney allograft recipients: incidence, risk factors, and management.

BACKGROUND Posttransplant diabetes mellitus (PTDM), associated with the use of immunosuppressants, occurs at varying rates in kidney transplant recipients. METHODS Five transplant centers conducted a retrospective review of 435 kidney recipients completing at least 6 months of follow-up to determine risk factors, incidence, and management strategies for posttransplant glucose intolerance. A distinction was made between hyperglycemia and diabetes. RESULTS The incidence of PTDM was found to be 4.9%. Among tacrolimus-treated patients it was 5.7%, compared with 3.3% among cyclosporine-treated patients (P=0.453). Mean daily maintenance doses of prednisone and mycophenolate mofetil (MMF) were significantly lower in tacrolimus-treated patients. Significantly more tacrolimus-treated patients were prednisone-free (9.0%/0%; P<0.001). Logistic regression analysis revealed that the absence of an antiproliferative agent correlated with the development of PTDM (odds ratio=3.56; P=0.01). CONCLUSIONS Based on this study, we propose management guidelines specifically for glucose intolerance developing after renal transplantation. Maintenance of blood glucose levels within strict limits is recommended, and the contribution of immunosuppressive agents to the development of PTDM is accounted for. Gradual tapering of prednisone and tacrolimus is proposed for patients who develop PTDM but also bear minimal risk of rejection. Tapering and eventual withdrawal of insulin should be attempted once blood glucose levels normalize. Switching to the alternative calcineurin inhibitor should only be considered as a late intervention. Tacrolimus therapy should be considered even in patients at high risk for diabetes, because the benefit of reduced acute rejection incidence and severity, as demonstrated in other studies, outweighs the risk of PTDM.
Neoplasia without dysplasia: lessons from Barrett esophagus and other tubal gut neoplasms.

CONTEXT Classic pathology teaching emphasizes that neoplastic lesions of the gastrointestinal tract are characterized by architectural and cytologic abnormalities that distinguish it from normal tissue. Recent studies suggest that many important-and in some cases clonal-molecular abnormalities that lead to dysregulation of cell proliferation and differentiation (neoplasia) occur before morphologic expression of dysplasia. OBJECTIVE To summarize the biologic and pathologic features of preneoplastic conditions of the tubal gut that reveal evidence of neoplastic alteration, but without the traditional morphologic features of dysplasia, in order to provide guidance on how to identify these lesions. Particular attention is given to Barrett esophagus, a chronic inflammatory condition in which early molecular and morphologic events that drive carcinogenesis are best understood. DATA SOURCES Selected references and abstracts were obtained by a PubMed (US National Library of Medicine) search by using the search headings neoplasia, preneoplasia, dysplasia, adenoma, serrated polyps, and Barrett's esophagus between the years 1980 and 2009. CONCLUSIONS Many types of lesions throughout the tubal gut fulfill the most basic and classic principles of a neoplastic precursor lesion but lack conventional morphologic evidence of dysplasia and/or maintain the capacity for cell differentiation and maturation. All of these lesions, such as squamous dysplasia of the esophagus, dysplasia in Barrett esophagus, and hyperplastic/serrated polyps of the colon, represent early neoplastic precursor lesions but without conventional histologic features of dysplasia. It is important for pathologists to be aware of these lesions, both for diagnostic and prognostic purposes, but also so that future studies can be performed with regard to risk stratification of patients.