Coeliac Disease and Microscopic Colitis: The Largest Study Assessing Prognosis and Risk of Hospital Admission.

Microscopic colitis (MC) and coeliac disease (CD) are common associated gastrointestinal conditions. We present the largest study assessing hospitalisation in patients with MC and the effect of a concomitant diagnosis of CD. Data were retrospectively collected between January 2007 and December 2021 from all patients diagnosed with MC and compared to a database of patients with only CD. In total, 892 patients with MC (65% female, median age 65 years (IQR: 54-74 years) were identified, with 6.4% admitted to hospital due to a flare of MC. Patients admitted were older (76 vs. 65 years, p < 0.001) and presented with diarrhoea (87.7%), abdominal pain (26.3%), and acute kidney injury (17.5%). Treatment was given in 75.9% of patients, including intravenous fluids (39.5%), steroids (20.9%), and loperamide (16.3%). Concomitant CD was diagnosed in 3.3% of patients and diagnosed before MC (57 versus 64 years, p < 0.001). Patients with both conditions were diagnosed with CD later than patients with only CD (57 years versus 44 years, p < 0.001). In conclusion, older patients are at a higher risk of hospitalisation due to MC, and this is seen in patients with a concomitant diagnosis of CD too. Patients with MC are diagnosed with CD later than those without.

Single Serum Cortisol Value as a Prognostic Marker in Acute Ischemic Stroke.

BACKGROUND: Stroke is a major global burden with significant morbidity, mortality, and long-term disability. Acute ischemic stroke (AIS) is a stressful condition causing stimulation of the hypothalamic-pituitary-adrenal (HPA) axis resulting in numerous endocrinal alterations in the body. We evaluated the serum cortisol as a prognostic marker in AIS. METHODS: This was a prospective observational study comprising 100 cases suffering from AIS, and serum cortisol at the baseline was measured. Severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) during admission, and functional outcome was assessed at 1, 4, and 24 weeks using a modified Rankins score (mRS). Statistical analysis was performed to find the relationship between serum cortisol and the severity of stroke, outcome, and mortality at 1, 4, and 24 weeks of stroke. RESULTS: In our study, we found positive correlations between random blood sugar and serum cortisol (r = 0.273, p = 0.006); stroke severity (NIHSS) and serum cortisol (r = 0.785, p < 0.001); stroke outcome (mRS) at 1, 4, and 24 weeks; and serum cortisol (p < 0.001 and r = 0.676, 0.654, 0.650 for all three intervals, respectively). We also found higher serum cortisol among patients who died at 1, 4, and 24 weeks compared to those who survived with a p-value being <0.001 for all three intervals. CONCLUSIONS: A stress response causing an increase in serum cortisol occurs in AIS. This response is detrimental to the patient. The serum cortisol at baseline can be considered a marker of severity, short- and long-term prognosis, and mortality after AIS.

Causes of Pre-hospital Delay in Acute Stroke in Punjab.

Background Pre-hospital delay, which refers to the time delay between the development of symptoms in the patient and the start of treatment, is one of the major factors impacting the treatment of stroke. This study aimed to identify patient characteristics and factors causing a pre-hospital delay in acute stroke (both ischemic and hemorrhagic) cases. Methodology This prospective follow-up study included 100 patients who presented with clinical features of acute stroke within 48 hours of symptom onset. A pre-designed questionnaire was administered within 72 hours of hospital admission to every patient. Results The mean time to hospital presentation was 7.73 hours. Only 2% of patients were thrombolysed. Age group, gender, education status, occupation, and socioeconomic status were not significantly (p > 0.05) associated with the mean symptom onset time to hospital arrival. Rural area (p < 0.001), nuclear family (p = 0.004), distance from the tertiary care center (p < 0.001), being alone at the time of symptom onset (p < 0.001), lack of knowledge about symptoms of stroke in patient/attendant (p < 0.001), and mode of transport were the factors that emerged as significant predictors of pre-hospital delay on univariate analysis. Living in a nuclear family, distance from the tertiary care center, and mode of transport were the factors that emerged as independent predictors of pre-hospital delay on multiple linear regression analysis. Conclusions In this study, factors associated with delayed hospital presentation including living in a nuclear family, distance from the tertiary care center, and use of public transport to reach the hospital emerged as independent predictors of pre-hospital delay.

Potential role of EphrinA2 receptors in postconditioning induced cardioprotection in rats.

EphA2 receptor has emerged as a novel cardioprotective target against myocardial infarction by preserving cardiac function, limiting infarct size and inflammation and enhancing cell survival via elevating phosphorylated Akt protein levels. However, the role of Eph receptors in postconditioning remains to be elucidated. Thus, the present study was designed to explore the role of EphA2 receptors in cardioprotective mechanism of postconditioning by employing Doxazosin as EphA2 receptor agonist, Lithocholic acid as antagonist and Wortmannin as specific phosphoinositide 3-kinase (PI3K) inhibitor. In Langendorff perfused isolated rat hearts, exposure of ischemia for 30 min succeeded by reperfusion for 2 h produced cardiac damage as determined by increase in size of infarct, LVDP, liberation of LDH and CK in effluent from coronary arteries. The reperfused hearts were homogenized and tissue concentrations of TBARs, reduced GSH and Catalase were determined. A marked rise in infarct size, liberation of LDH and CK in effluent and TBARs in myocardial tissue was observed in ischemic and reperfused hearts. Ischemic postconditioning comprising of 6 alternate episodes of 10 s ischemia and 10 s reperfusion and pharmacological post-conditioning by Doxazosin infusion for 5 min Before reperfusion confers significant protection against myocardial injury as manifested by remarkably decreased infarct size, levels of LDH, CK and tissue TBARs along with increase in GSH and Catalase activity. Pre-treatment of EphA2 antagonist, Lithocholic acid and PI3K inhibitor, Wortmannin attenuated the cardioprotective effect of postconditioning. Our results suggest that EphA2 receptors may be involved in postconditioning mediated cardioprotection probably through PI3K/Akt pathway.

Metagenomics analysis reveals features unique to Indian distal gut microbiota.

Various factors including diet, age, geography, culture and socio-economic status have a role in determining the composition of the human gut microbiota. The human gut microbial composition is known to be altered in disease conditions. Considering the important role of the gut microbiome in maintaining homeostasis and overall health, it is important to understand the microbial diversity and the functional metagenome of the healthy gut. Here, we characterized the microbiota of 31 fecal samples from healthy individuals of Indian ethnic tribes from Ladakh, Jaisalmer and Khargone by shotgun metagenomic sequencing. Sequence analysis revealed that Bifidobacterium and Prevotella were the key microbes contributing to the differences among Jaisalmer, Khargone and Ladakh samples at the genus level. Our correlation network study identified carbohydrate-active enzymes and carbohydrate binding proteins that are associated with specific genera in the different Indian geographical regions studied. Network analysis of carbohydrate-active enzymes and genus abundance revealed that the presence of different carbohydrate-active enzymes is driven by differential abundance of genera. The correlation networks were different in the different geographical regions, and these interactions suggest the role of less abundant genera in shaping the gut environment. We compared our data with samples from different countries and found significant differences in taxonomic composition and abundance of carbohydrate-active enzymes in the gut microbiota as compared to the other countries.

Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats.

OBJECTIVES: Reperfusion of ischaemic myocardium results in reduced nitric oxide (NO) biosynthesis by endothelial nitric oxide synthase (eNOS) leading to endothelial dysfunction and subsequent tissue damage. Impaired NO biosynthesis may be partly due to increased levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of eNOS. As dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme responsible for degradation of ADMA, the present study was designed to explore the role of DDAH/ADMA/NO pathway in cardio-protective mechanism of ischaemic postconditioning. MATERIALS AND METHODS: Isolated rat hearts were subjected to myocardial ischaemia for 30 min followed by reperfusion for 2 hours in control group. Myocardial injury was assessed by measurement of infarct size, left ventricular developed pressure (LVDP), lactate dehydrogenase (LDH) and creatine kinase (CK) enzymes in coronary effluents. The reperfused hearts were homogenised and tissue concentration of nitrite, ADMA level and DDAH enzyme activity was determined. RESULTS: A significant increase in infarct size, LDH, CK release in coronary effluents and ADMA level in myocardial tissue was observed in control group. The increase in tissue ADMA coincided with reductions of NO tissue concentrations and DDAH activity. Ischaemic postconditioning significantly attenuated ischaemia-reperfusion induced myocardial injury manifested in the terms of decreased infarct size, LDH, CK, tissue ADMA along with increase in NO levels and DDAH enzyme activity. Pretreatment with L-Homocysteine (300 µM), a competitive inhibitor of DDAH, and L-NG-nitroarginine methyl ester (L-NAME; 100 µM), an inhibitor of eNOS, completely abolished ischaemic postconditioning-induced myocardial protection. CONCLUSION: Enhancing DDAH activity by postconditioning may be a novel target to reduce ADMA level and increase NO bioavailability to prevent myocardial ischaemia-reperfusion injury.

Pharmacotherapeutic potential of phytochemicals: Implications in cancer chemoprevention and future perspectives.

Cancer is a leading cause of disease burden throughout the world. Many cancers develop as a result of exposure to both lifestyle and environmental factors that are potentially modifiable. In the last few years, much of the scientific attention has drawn to the discovery of new and effective chemopreventive agents from natural sources. A multitude of phytoconstituents have been explored for their potential to prevent the occurrence of carcinogenesis both in vitro and in vivo by means of diverse cellular and molecular approaches. Key focus of this review is to highlight some significant and new information about different molecular aspects of chemopreventive ability of plant based phytochemicals in terms of their inhibitory potential on cancer growth. In addition, information regarding certain limiting factors such as whole animal physiology, tumour microenvironment and bioavailability of active components of phytoconstituents used in pre/clinical trials are further explored. This review would further assist the scientific community involved in designing efficacious chemopreventive approaches using these phytochemicals in treating cancer.

Gleaning evolutionary insights from the genome sequence of a probiotic yeast Saccharomyces boulardii.

BACKGROUND: The yeast Saccharomyces boulardii is used worldwide as a probiotic to alleviate the effects of several gastrointestinal diseases and control antibiotics-associated diarrhea. While many studies report the probiotic effects of S. boulardii, no genome information for this yeast is currently available in the public domain. RESULTS: We report the 11.4 Mbp draft genome of this probiotic yeast. The draft genome was obtained by assembling Roche 454 FLX + shotgun data into 194 contigs with an N50 of 251 Kbp. We compare our draft genome with all other Saccharomyces cerevisiae genomes. CONCLUSIONS: Our analysis confirms the close similarity of S. boulardii to S. cerevisiae strains and provides a framework to understand the probiotic effects of this yeast, which exhibits unique physiological and metabolic properties.

Emergence of multiple drug resistance Vibrio cholerae O1 in East Delhi.

INTRODUCTION: Considering the changing geographical and temporal occurrence of Vibrio cholerae, there is a continuing need to monitor the strain characteristics and antibiotic resistance patterns of this pathogen. The present study was conducted to document the changing biology of V. cholerae isolates in and around Delhi, India, and the development of antibiotic resistance. METHODOLOGY: A total of 1,424 stool samples or rectal swabs from patients with acute secretory diarrhoea admitted to Guru Teg Bahadur Hospital, Delhi, between January 2007 and December 2009 were processed using standard bacteriological methods. Strains identified as V. cholerae were further subjected to serogrouping, phage typing and antimicrobial susceptibility testing. Minimum inhibitory concentration (MIC) of gentamicin and tetracycline was determined. RESULTS: V. cholerae was isolated in 242/1,424 (17.0%) specimens. Of these, the majority were V. cholerae O1 serotype (98.3%) and serovar Ogawa. The drugs to which V. cholerae O1 isolates showed high levels of resistance were nalidixic acid, furazolidone, and cotrimoxazole throughout the study period, whereas strains were usually susceptible to chloramphenicol and cefotaxime. In 2007, there was a sudden increase of resistance to gentamicin and tetracycline, followed by a slow reversal to previous levels in subsequent years. The phage typing pattern (Basu and Mukherjee scheme) showed a dominance of phage type 2 throughout the study period. CONCLUSION: The importance of reporting all cases of V. cholerae, should be greatly emphasized, with the ultimate goal of understanding the constantly changing resistance patterns of this pathogen.

Possible mechanism of rottlerin induced modulation of ischemia reperfusion injury in isolated rat hearts.

The present study was designed to investigate the modulatory effects of rottlerin on ischemia reperfusion induced myocardial injury. Isolated rat hearts were exposed to 30 min of global ischemia followed by 120 min of reperfusion using Langendorff apparatus. Myocardial injury was assessed in the terms of infarct size, release of lactate dehydrogenase (LDH), creatine kinase (CK) enzymes. Rottlerin, a selective PKCdelta inhibitor, did not modulate ischemia-reperfusion (I/R) induced myocardial injury at low dose (3 microM). However, at moderate dose (6 microM) it significantly produced cardioprotective effects. On the contrary, rottlerin at high dose (12 microM) significantly enhanced I/R induced myocardial injury. However, administration of FR-167653 (1.1 microM, 2.2 microM), a selective p-38 mitogen activated protein kinase (p-38 MAPK) inhibitor, attenuated rottlerin (12 microM) mediated enhancement in I/R induced myocardial injury in a dose dependent manner. Per se administration of FR-167653 (1.1 microM, 2.2 microM) also attenuated I/R induced myocardial injury in a dose dependent manner. Pretreatment with rottlerin (6 microM) did not enhance the cardioprotective effects of FR-167653 (2.2 microM). It may be concluded that rottlerin mediated cardioprotective effects at moderate dose, possible due to inhibition of PKCdelta; while at high dose it enhanced I/R induced myocardial injury which may be attributed to activation of p-38 MAPK.