Intestinal Epithelial CD98 Directly Modulates the Innate Host Response to Enteric Bacterial Pathogens

CD98 is a type II transmembrane glycoprotein whose expression increases in intestinal epithelial cells (IECs) during intestinal inflammation. Enteropathogenic Escherichia coli (EPEC) is a food-borne human pathogen that attaches to IECs and injects effector proteins directly into the host cells, thus provoking an inflammatory response. In the present study, we investigated CD98 and EPEC interactions in vitro and ex vivo and examined FVB wild-type (WT) and villin-CD98 transgenic mice overexpressing human CD98 in IECs (hCD98 Tg mice) and infected with Citrobacter rodentium as an in vivo model. In vivo studies indicated that CD98 overexpression, localized to the apical domain of colonic cells, increased the attachment of C. rodentium in mouse colons and resulted in increased expression of proinflammatory markers and decreased expression of anti-inflammatory markers. The proliferative markers Ki-67 and cyclin D1 were significantly increased in the colonic tissue of C. rodentium-infected hCD98 Tg mice compared to that of WT mice. Ex vivo studies correlate with the in vivo data. Small interfering RNA (siRNA) studies with Caco2-BBE cells showed a decrease in adherence of EPEC to Caco2 cells in which CD98 expression was knocked down. In vitro surface plasmon resonance (SPR) experiments showed direct binding between recombinant hCD98 and EPEC/C. rodentium proteins. We also demonstrated that the partial extracellular loop of hCD98 was sufficient for direct binding to EPEC/C. rodentium. These findings demonstrate the importance of the extracellular loop of CD98 in the innate host defense response to intestinal infection by attaching and effacing (A/E) pathogens.     

Chromatographic analysis of Hb S for the diagnosis of various sickle cell disorders in Pakistan

Sickle cell disease remains a relatively obscure theme in research on haemoglobinopathies in Pakistan. Limited data is available regarding its prevalence in the country. The objective of our study was not only to estimate the frequency of different sickle cell diseases but also to provide quantitative estimation of haemoglobin S and other haemoglobin variants using an automated high-performance liquid chromatography (HPLC) system. For this purpose, we retrospectively evaluated the results of HPLC performed on all patients with suspected haemoglobinopathies during the years 2005 and 2006. Information derived from various sources was used to identify a particular genotype by analysing each sample containing Hb S with respect to haemoglobin, red cell indices and levels of various associated haemoglobin variants. Analysis of 15,699 samples identified 302 patients with Hb S (1.92%). The genotypes identified included Sbeta(0) (46.7%), SS (19.2%), SA (11.6%), Sbeta(+) (8.6%) and SD (2.3%). Thirty-five cases could not be categorised and were labelled 'unclassified'. Majority of the patients (62.3%) were below the age of 18 years. Balochistan, which is the largest province based on the area, yielded the highest number of patients (n = 140). In the Sbeta(0) group, the mean haemoglobin and Hb S were lower in children compared to adults (p value of 0.001 and 0.016, respectively). We conclude that sickle cell disorders are prevalent in Pakistan to a significant extent, being concentrated in certain areas of the country. We present the first report of various haemoglobin S genotypes from our population. It is hoped that it will act as a database to characterise the same for our population.     

Assessment of the seroprevalence of viral hepatitis B, viral hepatitis C and HIV in multitransfused thalassaemia major patients in Karachi, Pakistan

This cross-sectional study reveals the seroprevalence of hepatitis B, hepatitis C and HIV in multi-transfused thalassemia major patients. Thirty-four out of 79 (43.0%) patients enrolled in the study serologically tested positive for hepatitis C (mean ± standard deviation age = 12 ± 4.1 years), four (5.1%) for hepatitis B and none for HIV. Some of the measures that should be adapted are: safe blood transfusions; awareness programmes through print and electronic media; and the early screening of such hazardous infections.     

Patient Awareness of Stent Type,Risk of Cardiac Events,and Symptoms of Myocardial Infarction Among PCI patients: A Missed Educational Opportunity?

Background: Timely and successful treatment of myocardial infarction (MI) requires accurate recognition by the patient of the signs and symptoms. As patients who have undergone percutaneous coronary intervention (PCI) remain at risk for cardiac events, it is important that they have a basic understanding of their cardiac status. Methods: We surveyed 80 consecutive patients following elective PCI using a simple multiple‐choice questionnaire. Type of stent (bare metal or drug‐eluting), how they perceive the procedure would affect their cardiovascular health, their perceived risk of a future MI, and whether they recalled specific education on how to recognize symptoms of an MI were queried. Results: 45% (n = 36) of patients were unaware of stent type. 10% stated PCI was performed to relieve symptoms of angina, 30% (n = 24) stated it would prevent MI, 56.3% (n = 45) stated that it would both prevent MI and reduce symptoms of angina, while 3.8% stated it would do neither. 86.3% (n = 69) stated they remained at risk for MI despite the procedure. However, 42.5% (n = 34) of patients did not perceive to have received specific education on the signs and symptoms of MI during their hospital stay. Conclusions: Patient understanding of stent type, expected cardiovascular outcomes, and recognition of MI post‐PCI appears low in the real‐world setting. A systematic approach to post‐PCI education should be incorporated into routine care, in order to capitalize on the educational opportunity afforded by this high risk population. (J Interven Cardiol 2011;24:144–148)     

Performance evaluation of ion exchange and affinity chromatography for HbA1c estimation in diabetic patients with HbD: a study of 129 samples

ObjectivesTo compare ion exchange and boronate affinity chromatography for HbA_1c estimation in patients with type I and II diabetes having hemoglobin D.Design and methodsSystems based on ion exchange and boronate affinity chromatography were evaluated and compared for their performance for HbA_1c estimation in patients with homozygous and heterozygous D disease.ResultsBoronate affinity chromatography shows least interference by HbD in heterozygous as well as homozygous diabetic patients for HbA_1c estimation.ConclusionsThe use of boronate affinity chromatography was found to be helpful in evaluating glycemic control in diabetic subjects with HbD.     

Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects

CONTEXT: The mechanisms underlying weight loss after Roux-en-Y gastric bypass (RYGBP) are not well understood. OBJECTIVE: The objective of the study was to assess the changes in active glucagon-like peptide 1 (GLP-1) and total peptide YY (PYY) after RYGBP and examine their relationship with changes in hunger and satiety. DESIGN: This was a prospective study on the changes in active GLP-1, PYY, hunger, and satiety in response to a standardized test meal in nine normal-glucose-tolerant obese subjects [body mass index (BMI) 47.4 +/- 6.1 kg/m(2)] before and 6 wk after RYGBP. RESULTS: Before surgery, meal ingestion failed to stimulate GLP-1 and PYY secretion. Six weeks after surgery, despite subjects still being markedly obese (BMI 43.6 +/- 7.8 kg/m(2)), the area under the curve(0-120') of GLP-1 and of PYY in response to the standardized test meal were significantly elevated (P < 0.05 and P < 0.01, respectively). These hormonal responses were significantly larger (P < 0.01) than those observed in a group matched for the BMI attained 6 wk after surgery. The 2.9 +/- 1.2- and 1.6 +/- 1.9-fold increase, respectively, in the area under the curve(0-120') of GLP-1 and PYY were accompanied by a significant decrease in fasting (P < 0.05) and postprandial hunger (P = 0.05) and a significant increase in satiety (P < 0.05) after meal intake. Nevertheless, a significant correlation between changes in the hormonal and eating behavior parameters was not found. CONCLUSION: Our data show that RYGBP is associated with an improvement in the active GLP-1 and total PYY response to a liquid-meal intake. Moreover, we provide circumstantial evidence for a potential role of these gastrointestinal hormones on the decreased appetite after RYGBP.