Increased plasma protein binding and lower metabolic clearance rate of aldosterone in plasma of low cortisol concentration.

During ACTH or cortisol infusion in ten recumbent normal men taking dexamethasone, the metabolic clearance rate of aldosterone increased by 50% as plasma cortisol was raised from low (2 mug/dl) to high concentration (50 mug/dl). Since splanchnic blood flow did not change, a greater efficiency of removal of aldosterone must have occurred, by means of displacement of aldosterone from high-affinity sites on plasma protein. At 37 C, equilibrium dialysis of low-cortisol plasma showed one-third of plasma aldosterone bound to albumin, and 24 to 28% bound to higher-affinity sites on other protein. As plasma cortisol increased, a progressively smaller fraction was tightly bound, approaching zero as transcortin was saturated with cortisol. The addition of large amounts of aldosterone to low-cortisol plasma displaced 14C-cortisol from transcortin binding sites. The results support earlier evidence that a significant fraction of plasma aldosterone is bound to transcortin, from which it is readily displaced by cortisol, resulting in an increased metabolic clearance rate of aldosterone by making a larger fraction available for removal from plasma.     

Design and optimization of a subunit vaccine targeting COVID-19 molecular shreds using an immunoinformatics framework

COVID-19 has been declared as a global health emergency and exposed the world to a deadly virus, which has dramatically changed the lives of humans for an unknown period of time. In the battleground with the virus, we have employed an immunoinformatics framework to design a robust vaccine as an insurance plan for the future. The pathogenic sequence with cryptic epitope taken from patients in Wuhan, China, was harnessed to design a promiscuous cytotoxic T-lymphocyte, helper T-lymphocyte, and B-cell epitope based subunit vaccine, engineered with adjuvants and conformational linkers. The reported vaccine has high antigenicity and immunogenicity profiles with potential TAP affinity, which ensures elevated antigen processing capability. It has strong binding with major histocompatibility complex (MHC) receptors (MHC-1 and MHC-2) and virus-specific membrane receptor TLR-2, with scores of −1010.7, −1035.7, and −1076.3 kcal mol⁻¹, respectively. Molecular dynamics simulation analysis was used to assess the stable binding with TLR-2 with minimal atomic motions through a deformation plot, covariance matrix, and elastic network. Importantly, an in silico immunization assay showed the reliable elicitation of key players in terms of immune cells together with memory cells to evoke adaptive immune responses upon administration of the construct. In view of favorable outcomes, we also propose a plausible vaccine mechanism to elicit an immune response to fight coronavirus.

COVID-19 has been declared as a global health emergency and exposed the world to a deadly virus, which has dramatically changed the lives of humans for an unknown period of time.     

Infliximab in patients with severe steroid-refractory ulcerative colitis: Indian experience

Introduction

The role of infliximab in the treatment of acute severe ulcerative colitis is established. However, all the data available in the literature are from western countries. This is the first report on the use of infliximab in patients with severe steroid-refractory ulcerative colitis from India.

Methods

Retrospective analysis of 28 patients who had received infliximab therapy for induction of remission, with three doses of 5 mg/kg at 0, 2, and 6 weeks, was performed.

Results

Twenty-four (85.6 %) patients had shown a clinical response by week 8 and, hence, avoided urgent colectomy. In 2 years of follow up, 9/16 (56 %) patients had not required colectomy.

Conclusion

Infliximab averted colectomy in a proportion of patients with severe steroid-refractory ulcerative colitis.     

High sputum total adiponectin is associated with low odds for asthma

Objective: Adipose tissue produces adiponectin, an anti-inflammatory protein. High systemic total adiponectin is associated with a low risk for incident asthma but the association with lung adiponectin is not known. Our objective was to evaluate the association between sputum total adiponectin and asthma. Methods: This case-control study included 44 cases with objectively-confirmed asthma and an equal number of body mass index (BMI) and sex-matched controls. Serum and sputum adiponectin were estimated by ELISA and Western Blot technique, respectively. While Fisher’s exact test, t-test and Spearman’s correlations were used for univariate analyses, Spearman and regression analyses were performed for multivariable analyses. Results: While high-molecular-weight adiponectin was the dominant isoform in serum, medium-molecular-weight isoform was dominant in sputum. Sputum total adiponectin was not correlated with serum adiponectin or BMI. Sputum total adiponectin was lower among asthmatics than controls (p?=?0.03), although individual sputum isoforms were not similarly associated. High sputum total adiponectin was associated with lower odds for asthma (OR 0.33, 95% C.I. 0.12, 0.91), even after adjustment for systemic adiposity measures including serum adiponectin. Conclusions: High sputum total adiponectin predicted lower odds for asthma, even after adjustment for serum adiponectin. Although not studied, it is possible that pharmacological modulation of sputum adiponectin may suggest new ways to prevent and/or treat asthma.     

An economic assessment model for in-center, conventional home, and more frequent home hemodialysis

More intensive and/or frequent hemodialysis may provide clinical benefits to patients with end-stage renal disease; however, these dialysis treatments are more convenient to the patients if provided in their homes. Here we created a standardized model, based on a systematic review of available costing literature, to determine the economic viability of providing hemodialysis in the home that arrays costs and common approaches for assessing direct medical and nonmedical costs. Our model was based on data from Australia, Canada, and the United Kingdom. The first year start-up costs for all hemodialysis modalities were higher than in subsequent years with modeled costs for conventional home hemodialysis lower than in-center hemodialysis in subsequent years. Modeled costs for frequent home hemodialysis was higher than both in-center and conventional home hemodialysis in the United Kingdom, but lower than in-center hemodialysis and higher than conventional home hemodialysis in Australia and Canada in subsequent years. The higher costs of frequent compared to conventional home hemodialysis were because of higher consumable usage due to dialysis frequency. Thus, our findings reinforce the conclusions of previous studies showing that home-based conventional and more frequent hemodialysis may provide clinical benefit at reasonable costs.     

Small bowel obstruction induced by spontaneous partial deflation of an intragastric balloon

The intragastric balloon (IGB) has been used for decades as a temporary measure for weight reduction in the morbidly obese. Serious complications related to the device remain rare. We present the case of a 23-year-old Caucasian man who developed signs of bowel obstruction following spontaneous partial deflation of an air filled IGB with subsequent migration and impaction in the jejunum. We discuss the role of the IGB in the treatment of obesity, side effects and the serious complications that can occur.     

Role of killer immunoglobulin-like receptor-ligand interactions in human leukocyte antigen-matched sibling hematopoietic stem cell transplantation

Introduction

Killer immunoglobulin-like receptor (KIR)-ligand mismatches lead to natural killer cell alloreactivity after hematopoietic stem cell transplantation (HSCT). However, their clinical impact on HSCT outcomes is controversial due to complexity of KIR haplotypes, genotypes, and phenotypes as well as their diversity among patient populations. The present study investigated the role of KIR-ligand interactions in human leukocyte antigen (HLA)-matched sibling transplants.

Methods

The recipient cohort, which included patients diagnosed with aplastic anemia, acute leukemia, and myelodysplastic syndrome, received granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells. HLA typing was performed using polymerase chain reaction - sequence specific oligo probes (PCR-SSO). The KIR genotype of the donors and the ligands C1 (Asparagine 80), C2 (Lysine 80), and Bw4 recipient typings were performed using polymerase chain reaction - sequence specific primers (PCR-SSP). We assessed acute and chronic graft-versus-host disease (GVHD), relapse, and overall survival.

Results

While 84.5% of donors carried a Bx KIR, 15.5% carried the AA haplotype. The effect of a recipient's lack of ligands among 88.5% of cases was associated with 39% of subjects developing GvHD. Lack of C1 may lead to manifestations of acute GvHD and lack of C2 to manifestation of chronic GvHD. The presence of both C1 and C2 seemed to be protective against both forms of GvHD. The role of two Bw4 alleles, threonine (T) or isoleucine (I) at position 80, was evaluated. 73% of recipients who carried Bw4 80(I) versus 27% with the Bw4 80(T) allele. The presence of Bw4-80(T) allele appeared to reduce the risk of GvHD, indicating its stronger inhibitory effect than its 80(I) counterpart.

Conclusion

KIR-ligand interactions influenced HSCT outcomes.