Development and Maintenance of the Gut-Associated Lymphoid Tissue (Galt): the Roles of Enteric Bacteria and Viruses

GALT can be subdivided into several compartments: (a) Peyer's patches (PP); (b) lamina propria (LP); and (c) intraepithelial leukocyte (IEL) spaces. The B-cell follicles of PP are quiescent in neonatal and germ-free (GF) adult mice. Germinal centers (GC), including sIgA(+) blasts, appear in the B follicles of formerly GF adult mice about 10-14 days after monoassociation with various gut commensal bacteria. The GC wax and wane over about a 3-week period, although the bacterial colonizers remain in the gut at high density. Neonatal mice, born of conventionally reared (CV), immunocompetent mothers, display GC reactions in PP postweaning, although pups of SCID mothers display precocious GC reactions at about 14 days of life. Normally, gut colonization of neonates with segmented filamentous bacteria (SFB) leads to explosive development of IgA plasmablasts in LP shortly after weaning. Commensal gut bacteria and the immunocompetency of mothers also appears to control the rate of accumulation of primary B cells from “virgin” B cells in neonates. Enteric reovirus infection by the oral route can cause the activation of CD8(+) T cells in the interfollicular regions of PP and the appearance of virus-specific precursor cytotoxic T lymphocytes (pCTL) in the IEL spaces. Such oral stimulation can also lead to “activation” of both CTL and natural killer (NK) cells in the IEL spaces. More normally, colonization of the gut with SFB also leads to similar activations of NK cells and “constitutively” cytotoxic T cells

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Spectral analysis of hexane leaf extract of balamkheera (Kigelia pinnata) using gas chromatography-mass spectrometry

1162-1166Kigelia pinnata (Jacq.) is an important medicinal plant belonging to the family bignoniaceae. Leaf sample of the plant have been subjected to phytochemical investigation through gas chromatography – mass spectrometry (GC-MS). Twenty two phytochemical compounds have been identified in the hexane extract of K. pinnata leaves. The identification of phytochemical compounds is based on the peak area, retention time, molecular weight and molecular formula

Synthesis of some novel pyrido[2,3-<i>d</i>]pyrimidine derivatives and their antimicrobial investigations

448-452A series of pyrido[2,3-d]pyrimidine derivatives viz 4-amino-5,7-disubstituted pyrido[2,3-d]pyrimidines 3a-d, 4-amino-5,7-disubstituted pyrido[2,3-d]pyrimidin-2(1H)-ones 4a-d and 4-amino-5,7-disubstituted pyrido[2,3-d]pyrimidin-2(1H)-thione 5a-d have been synthesized by the condensation reaction of 2-amino-3-cyano-4,6-disubstituted pyridines 2a-d with formamide, urea and thiourea, respectively. The newly synthesized compounds have been established by elemental analysis, IR, 1H and 13C NMR. All the synthesized compounds have been screened for their antibacterial and antifungal activity

Comparison of the effect of positive end expiratory pressure on respiratory mechanics and arterial oxygenation in laproscopic cholecystectomy

Objective: To study and compare the effects of PEEP on Respiratory Mechanics, Oxygenation Index and Heamodynamic changes at different intervals. Methods :This prospective study was done to evaluate the effects of extrinsic PEEP on respiratory mechanics, haemodynamics and arterial blood gases during laproscopic cholecystectomy in obese patients. Results: Primary outcome variable was ratio of arterial oxygen partial pressure to inspiratory oxygen concentration Pa02/Fi02 and other variables related to gas exchange, oxygenation, ventilation, respiratory mechanics and haemodynamics were reported separately for patients randomized to PEEP application as well as control group. &nbsp;All continuous data are expressed as mean ± SD. &nbsp;Comparison of two groups were done by using student's test. ConclusionPEEP improves oxygenation in morbidly obese patients without causing hemodynamic instability. This improved oxygenation persists throughout the surgery but it promptly dissipates after tracheal extubation. Keywords:Positive End Expiratory Pressure ,Respiratory Mechanics ,Arterial Oxygenation , Laproscopic Cholecystectomy