Pathomorphological effects of Alloxan induced acute hypoglycaemia in rabbits

Alloxan is one of the frequently used beta-cytotoxic agents for the induction of Type-1 diabetes mellitus in animal models and is the drug of choice in rabbits. Its beta-cytotoxic action results in a sudden release of insulin leading to severe hypoglycaemia and even mortality if glucose therapy is not given. In the present investigation the pathological effects of alloxan induced acute hypoglycaemia were studied in rabbits. New Zealand White rabbits, 1–1.5 kg body weight, were administered alloxan @100 mg/kg b.w., as a single intravenous dose. Blood glucose levels were monitored (0 h, 20 min, 1 h, and then hourly up to 5 h) and clinical signs noted. Rabbits dead due to hypoglycaemia were necropsied and histopathology performed. Severe histopathological changes were observed especially in the brain (neuronal degeneration and necrosis), kidneys (nephrosis, nephritis) and liver (hepatosis, hepatitis) and also, other organs. Histopathological observation of beta-cytolysis was suggestive that the drug induced hypoglycaemia is insulin mediated. It was concluded that acute hypoglycaemia causes severe pathological changes and the alloxan induced immediate hypoglycaemia if not managed in time, might exacerbate the pathological effects of hyperglycaemia in the induced diabetic models.Keywords: Alloxan hypoglycaemia; Pathology; Rabbit

Enhancing Nutrient Use Efficiencies in Rainfed Systems

Successful and sustained crop production to feed burgeoning population in rainfed areas, facing soil fertility-related degradation through low and imbalanced amounts of nutrients, requires regular nutrient inputs through biological, organic or inorganic sources of fertilizers. Intensification of fertilizer (all forms) use has given rise to concerns about efficiency of nutrient use, primarily driven by economic and environmental considerations. Inefficient nutrient use is a key factor pushing up the cost of cultivation and pulling down the profitability in farming while putting at stake the sustainability of rainfed farming systems. Nutrient use efficiency implies more produce per unit of nutrient applied; therefore, any soil-water-crop management practices that promote crop productivity at same level of fertilizer use are expected to enhance nutrient use efficiency. Pervasive nutrient depletion and imbalances in rainfed soils are primarily responsible for decreasing yields and declining response to applied macronutrient fertilizers. Studies have indicated soil test-based balanced fertilization an important driver for enhancing yields and improving nutrient use efficiency in terms of uptake, utilization and use efficiency for grain yield and harvest index indicating improved grain nutritional quality. Recycling of on-farm wastes is a big opportunity to cut use and cost of chemical fertilizers while getting higher yield levels at same macronutrient levels. Best management practices like adoption of high-yielding and nutrient-efficient cultivars, landform management for soil structure and health, checking pathways of nutrient losses or reversing nutrient losses through management at watershed scale and other holistic crop management practices have great scope to result in enhancing nutrient and resource use efficiency through higher yields. The best practices have been found to promote soil organic carbon storage that is critical for optimum soil processes and improve soil health and enhance nutrient use efficiency for sustainable intensification in the rainfed systems

Structure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor

Albumin is the most abundant protein in blood where it has a pivotal role as a transporter of fatty acids and drugs. Like IgG, albumin has long serum half-life, protected from degradation by pH-dependent recycling mediated by interaction with the neonatal Fc receptor, FcRn. Although the FcRn interaction with IgG is well characterized at the atomic level, its interaction with albumin is not. Here we present structure-based modelling of the FcRn–albumin complex, supported by binding analysis of site-specific mutants, providing mechanistic evidence for the presence of pH-sensitive ionic networks at the interaction interface. These networks involve conserved histidines in both FcRn and albumin domain III. Histidines also contribute to intramolecular interactions that stabilize the otherwise flexible loops at both the interacting surfaces. Molecular details of the FcRn–albumin complex may guide the development of novel albumin variants with altered serum half-life as carriers of drugs

Analysis of Mitochondrial DNA Sequences in Childhood Encephalomyopathies Reveals New Disease-Associated Variants

BACKGROUND: Mitochondrial encephalomyopathies are a heterogeneous group of clinical disorders generally caused due to mutations in either mitochondrial DNA (mtDNA) or nuclear genes encoding oxidative phosphorylation (OXPHOS). We analyzed the mtDNA sequences from a group of 23 pediatric patients with clinical and morphological features of mitochondrial encephalopathies and tried to establish a relationship of identified variants with the disease. METHODOLOGY/PRINCIPLE FINDINGS: Complete mitochondrial genomes were amplified by PCR and sequenced by automated DNA sequencing. Sequencing data was analyzed by SeqScape software and also confirmed by BLASTn program. Nucleotide sequences were compared with the revised Cambridge reference sequence (CRS) and sequences present in mitochondrial databases. The data obtained shows that a number of known and novel mtDNA variants were associated with the disease. Most of the non-synonymous variants were heteroplasmic (A4136G, A9194G and T11916A) suggesting their possibility of being pathogenic in nature. Some of the missense variants although homoplasmic were showing changes in highly conserved amino acids (T3394C, T3866C, and G9804A) and were previously identified with diseased conditions. Similarly, two other variants found in tRNA genes (G5783A and C8309T) could alter the secondary structure of Cys-tRNA and Lys-tRNA. Most of the variants occurred in single cases; however, a few occurred in more than one case (e.g. G5783A and A10149T). CONCLUSIONS AND SIGNIFICANCE: The mtDNA variants identified in this study could be the possible cause of mitochondrial encephalomyopathies with childhood onset in the patient group. Our study further strengthens the pathogenic score of known variants previously reported as provisionally pathogenic in mitochondrial diseases. The novel variants found in the present study can be potential candidates for further investigations to establish the relationship between their incidence and role in expressing the disease phenotype. This study will be useful in genetic diagnosis and counseling of mitochondrial diseases in India as well as worldwide

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic