Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut

BACKGROUND & AIMS: Paracellular transport varies widely among epithelia of the gastrointestinal tract. We determined whether members of the claudin family of tight junction proteins are differentially expressed consistent with a potential role in creating these variable properties. METHODS: Rabbit polyclonal antibodies were produced against peptides from claudins 2 through 5. The distribution of individual claudins was detected by immunoblotting, and their cell type and subcellular localization were determined by immunofluorescence on cryosections of rat liver, pancreas, stomach, and small and large intestine. RESULTS: All antibodies detected single bands of the expected size on immunoblots and were monospecific based on peptide competition studies. Immunoblotting detected strong differences among tissues in the expression level of each claudin. Immunolocalization confirmed these differences and revealed striking variations in expression patterns. In the liver, claudin 2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, claudin 3 is uniformly expressed, claudin 4 is absent, and claudin 5 is only expressed in endothelial junctions. In the pancreas, claudin 2 is only detected in junctions of the duct epithelia, claudin 5 only in junctions of acinar cells, whereas claudin 3 and 4 are in both. Among differences in the gut are a crypt-to-villus decrease in claudin 2, a highly restricted expression of claudin 4 to colonic surface cells, and the finding that some claudins can be junctional, lateral, or show a gradient in junctional vs. lateral localization along the crypt-to-villus surface axis. CONCLUSIONS: Claudins have very different expression patterns among and within gastrointestinal tissues. We propose these patterns underlie differences in paracellular permeability properties, such as electrical resistance and ion selectivity that would complement known differences in transcellular transport.     

The oncology treatment of patients who use oral anticoagulants is connected with high risk of bleeding complications

The data about risk for bleeding complications during anticoagulation in cancer patients with different oncology treatment are conflicting. To investigate the rate of bleeding in the course of oral anticoagulants, during treatment of malignant diseases, we conducted a retrospective study including 75 patients on stable anticoagulation prior to commencing their different oncology treatment. All patients were treated according to the consiliar decision, made based on the localization and pathohistological findings of the malignant disease. During their treatment the regular laboratory monitoring of INR was done. Every dose of oral anticoagulants, INR changes, as well as the size and localization of bleeding were recorded. During all the malignancy treatment 22 (30%) of patients were overanticoagulated. In 15 (20%) patients it was associated with bleeding, while 3 (4%) of them had to be transfused with fresh frozen plasma to stop the major bleeding. Most bleeding complications occurred in the group of patients treated with chemotherapy or with analgesics in the group with advanced disease. None of the bleeding complications were observed in patients treated with irradiation and surgery alone, where the bridging of oral anticoagulants with low molecular weight heparin was done before surgery. The oncology treatment of patients who take oral anticoagulants was connected with high risk for bleeding especially if chemotherapy as a therapeutic options was used. Therefore physicians should be aware of this risk and carefully monitor the intensity of anticoagulant therapy, especially during the first treatment weeks when the risk of bleeding is greatest.     

What differs former,light and heavy smokers? Evidence from a post-conflict setting

BackgroundEvidence suggests that people who live in regions affected by the armed conflict are more likely to smoke.ObjectiveThe purpose of this study was to assess factors associated with smoking status in a sample of students in the northern Kosovo province.Materials and methodsA total of 514 students enrolled in University in Kosovska Mitrovica, Kosovo, were recruited between April to June 2015 at Student Public Health Center during mandatory health checks. Participants filled in socio-demographic and behavioral questionnaire and Beck Depression Inventory (BDI). Based on responses about smoking, students were categorized in non-smokers, former smokers, light smokers (1–13 cigarettes/day) and heavy smokers (> 13 cigarettes/day).ResultsOf 514 students, 116 (22.6%) classified themselves as smokers. Higher education level of fathers (Odds ratio [OR]=2.89, 95% confidence interval [CI] 1.30–6.44, p=0.009), not living with smokers (OR=0.42, 95%CI 0.15–0.97, p=0.017) and longer exposure to second hand smoke (OR=1.07, 95%CI 1.01–1.13, p=0.036) was associated with former smoking. Studying medical and natural sciences (OR=2.07, 95%CI 1.05–4.18, p=0.040), consuming alcohol (OR=2.98, 95%CI 1.19–10.03, p=0.020), living with smokers (OR=2.88, 95%CI 1.49–5.56, p=0.002), longer exposure to second hand smoke (OR=1.06, 95%CI 1.01–1.11, p=0.019) and having a more intense depressive symptoms (OR=1.08, 95%CI 1.03–1.13, p=0.002) was associated with light smoking. Being male (OR=0.22, 95%CI 0.07–0.41, p=0.001), older (OR=1.47, 95%CI 1.21–1.78, p=0.001), living with smokers (OR=3.78, 95%CI 1.69–8.07, p=0.001), longer daily exposure to second-hand smoke (OR=1.10, 95%CI 1.04–1.16, p=0.001), and having more severe depressive symptoms (OR=1.12, 95%CI 1.07–1.18, p=0.001) were associated with heavy smoking.ConclusionSmoking prevention and cessation programs should include the entire community, because exposure to environmental second hand smoke may facilitate initiation and more intense smoking. Screening of student smokers for depression should be prioritized in the process of rebuilding the framework for primary and secondary prevention in the post-conflict period.     

Harm reduction: concepts and practice. A policy discussion paper

This paper provides an overview of the context, definition, and key features of the harm reduction approach, and provides several examples of current programs in various countries. Both licit and illicit drugs are included in these illustrations. Some of the critical issues, and the strategies needed to advance harm reduction, are discussed. [Translations are provided in the International Abstracts Section of this issue.]     

Residual renal function and erectile dysfunction in patients on hemodialysis

Introduction

Residual renal function and erectile dysfunction are important parameters of quality of life in dialysis patients.

Goal

The purpose of our investigation was to determine correlations between erectile dysfunction and residual diuresis in patients on hemodialysis.

Methods

The survey was organized as a cross-sectional study in men aged up to 65?years on hemodialysis. All respondents voluntarily completed the questionnaire of the International Index of Erectile Function (IIEF)-5. Demographic and anthropometric characteristics, the duration of dialysis, smoking, alcohol consumption, residual renal function, comorbidity, and routine biochemical parameters were determined for all patients. The adequacy of dialysis was calculated as Kt/V. Based on residual renal function, the patients were divided into a group without residual diuresis and a group with preserved residual renal function.

Results

Nearly two-thirds of our patients did not have preserved diuresis, while 82.8% of our respondents had erectile dysfunction. Patients with preserved residual renal function were heavier (P?=?0.047) and had higher body mass index (P?=?0.047), but the prevalence of cardiovascular disease (P?<?0.0001) and erectile dysfunction (P?<?0.0015) was lower, compared to patients without residual diuresis. The regression model also demonstrated a statistically significant relationship between the residual diuresis and the total IIEF score (b?=?4.74; P?<?0.001).

Conclusion

Hemodialysis patients with preserved diuresis retain erectile function better.     

Assessment of sialic acid diversity in cancer- and non-cancer related CA125 antigen using sialic acid-binding Ig-like lectins (Siglecs)

This study was aimed at obtaining insight into the diversity of sialic acids in cancer- and non-cancer-related CA125 antigen, tumour marker of serous ovarian cancer. Starting from available data suggesting the possible relevance of sialic acids for discriminating CA125 antigens of different origin, we have employed a new experimental approach based on the use of human sialic acid-binding Ig-like lectins, Siglecs, as tools for the investigation of sialylation. Siglec-2, belonging to the group of evolutionarily conserved Siglecs, and Siglec-3, -6, -7, -9 and -10, which are CD33-like Siglecs, were probed in solid-phase binding assays with cancer-related CA125 antigens from pleural fluid of patients with ovarian carcinoma (pfCA125), the OVCAR-3 ovarian carcinoma cell line (clCA125) and a non-cancer-related CA125 antigen, i.e. pregnancy-associated pCA125 antigen. All Siglecs used showed detectable binding to pCA125 antigen. Siglec-3, Siglec-7 and Siglec-2 exhibited moderately stronger binding to pCA125 antigen than the others. In contrast to this, Siglec-2 and Siglec-3 preferentially recognized pfCA125 with greater total binding than for pCA125, whereas Siglec-9 and Siglec-10 were highly selective for clCA125. Siglecs promise to be powerful tools for discriminating CA125 of different origin and could propagate further research on other molecular markers of biomedical and diagnostic importance.     

Miconazole and nystatin used as topical antifungal drugs interact equally strongly with warfarin

What is known and Objective: Medline search disclosed 10 case reports of interactions between oral anticoagulants and miconazole oral gel, but none so far between nystatin solution and anticoagulants. We report on change in anticoagulant activity with use of different topical antifungal drugs, miconazole oral gel and vaginal suppositories, and nystatin solution. Methods: We conducted a retrospective study that included 43 patients on stable anticoagulation before the introduction of topical antifungal drugs. Miconazole oral gel was prescribed for 32 patients, nystatin solution for eight patients and miconazole vaginal suppositories for three patients. Results and Discussion: Nineteen (44·2%) of the patients reported bleeding complications and some of these were severe. Fifteen of 32 who used miconazole oral gel and four of 8 of those who used nystatin solution were affected. Before use of the antifungal drugs, the mean weekly warfarin dose in the nystatin group was 14·5 mg, and after antifungal drugs, 9 mg, P = 0·038, while the mean international normalized ratio (INR) before antifungal drugs was 2·5 (range 1·9–3·5) and afterwards it was 10·6 (range 4·5–19·3), P = 0·0001. In the miconazole oral gel group the mean weekly warfarin dose was 15·7 mg, and after 10·8 mg, P = 0·008, while the mean INR before antifungal drugs was 2·44 (range 1·92–3·18) and afterwards it was 8·8 (range 4·9–16·9), P < 0·0001. What is new and Conclusion: Miconazole oral gel and topically applied nystatin solution have equally strong effects on warfarin activity and can provoke major bleeding. Prospective evaluation of this effect is called for. However, based on our results the warfarin dose adjustment appears necessary when the anticoagulant is used concomitantly with those topical antifungals.