Effect of N-benzoyl-D-phenylalanine on streptozotocin-induced changes in the lipid and lipoprotein profile in rats

The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin combination treatment on circulatory lipids, lipoproteins and lipid peroxidation markers were studied in neonatal streptozotocin (nSTZ) non-insulin dependent diabetic rats. Non-insulin dependent diabetes mellitus (NIDDM) was induced by a single dose injection of streptozotocin (100 mg kg(-1), i. p.) to two-day-old rats. After 10-12 weeks, rats weighing above 150 g were selected for screening for the NIDDM model. The rats were checked for fasting blood glucose levels to confirm the status of NIDDM. NBDP (50,100 or 200 mg kg(-1) ) was administered orally for six weeks to the confirmed diabetic rats (to evaluate the effective dose). The levels of serum lipids and lipid peroxidation markers were significantly increased, whilst the activity of glucose-6-phosphate dehydrogenase was significantly decreased in nSTZ diabetic rats. NBDP and metformin were able to restore the altered serum lipids, lipoproteins, lipid peroxidation marker levels and glucose-6-phosphate dehydrogenase activity to almost control levels. The results showed the antihyperlipidaemic properties of NBDP and metformin in addition to its antidiabetic action. Combination treatment was more effective then either drug alone. The results indicated that the coadministration of NBDP with metformin to nSTZ diabetic rats normalized blood glucose and caused marked improvement in altered serum lipids, lipoproteins and lipid peroxidation markers during diabetes. The data indicated that NBDP represented an effective antihyperglycaemic and antihyperlipidaemic adjunct for the treatment of diabetes, and may be a potential source of new orally active agents for future therapy.     

N-Benzoyl-D-phenylalanine attenuates brain acetylcholinesterase in neonatal streptozotocin-diabetic rats

The effect of hyperglycaemia due to experimental diabetes in male Wistar rats causes a decrease in the level of acetylcholinesterase (AChE) with significant increase in lipid peroxidative markers: thiobarbituric acid-reactive substances (TBARS) and hydroperoxides in brains of experimental animals. The decreased activity of both salt soluble and detergent soluble acetylcholinesterase observed in diabetes may be attributed to lack of insulin which causes specific alterations in the level of neurotransmitter, thus causing brain dysfunction. Administration of non-sulfonylurea drug N-benzoyl-D-phenylalanine (NBDP) could protect against direct action of lipid peroxidation on brain AChE and in this way it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes.     

Antihyperglycemic, antihyperlipidemic, and renoprotective effects of Chlorella pyrenoidosa in diabetic rats exposed to cadmium

Objective: The objective of the present study is to evaluate the antihyperlipidemic effect of Chlorella pyrenoidosa in diabetic rats exposed to cadmium (Cd). Materials and methods: Group 1 and 2 rats were treated as control and C. pyrenoidosa control. Group 3 and 4 rats were given single injection of streptozotocin (40?mg/kg b.w; i.p) followed by Cd (0.6?mg/kg b.w; s.c) for 5 days per week for a total period of 90 days. In addition, group 4 rats alone were treated with C. pyrenoidosa throughout the study period of 90 days. Assessments of plasma glucose, insulin, lipid profile and renal function markers were performed in control and experimental rats along with histological examination of kidney tissues. Results: Diabetic rats exposed to Cd showed increased levels of plasma glucose and decreased levels of plasma insulin accompanied by the significantly elevated levels of tissue lipids viz., total cholesterol, triglyceride, free fatty acid, and phospholipids compared with control rats. Alterations in lipoproteins (low density lipoprotein-C, very low density lipoprotein-C, and high density lipoprotein-C) levels were also observed. Discussion: Elevated levels of urinary albumin, creatinine, and blood urea nitrogen confirmed the onset of renal dysfunction in unsupplemented diabetic rats exposed to Cd. Conclusion: C. pyrenoidosa (100?mg/kg body weight) supplemented diabetic nephropathic rats showed near normal biochemical profile and well preserved renal histology that substantiate the antihyperglycemic, antihyperlipidemic, and renoprotective effects of C. pyrenoidosa in diabetic rats exposed to Cd.     

Synoptic tool for reporting of hematological and lymphoid neoplasms based on World Health Organization classification and College of American Pathologists checklist

Background  

Synoptic reporting, either as part of the pathology report or replacing some free text component incorporates standardized data elements in the form of checklists for pathology reporting. This ensures the pathologists make note of these findings in their reports, thereby improving the quality and uniformity of information in the pathology reports.     

Effect of N-benzoyl-D-phenylalanine and metformin on carbohydrate metabolic enzymes in neonatal streptozotocin diabetic rats

BACKGROUND: The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin was studied on the activities of carbohydrate metabolic enzymes in neonatal streptozotocin (nSTZ) non-insulin-dependent diabetic rats. METHODS: To induce non-insulin-dependent diabetes mellitus (NIDDM), single dose injection of streptozotocin (STZ; 100 mg/kg body weight; i.p.) was given to 2-day old rats. After 10-12 weeks, rats weighing >150 g were selected for screening in NIDDM model, they were checked for fasting blood glucose concentrations to conform the status of NIDDM. NBDP (50,100 and 200 mg/kg body weight) was administered orally for 6 weeks into the confirmed diabetic rats. RESULTS: The activities of gluconeogenic enzymes were significantly increased, whereas the activities of hexokinase and glucose-6-phosphate dehydrogenase were significantly decreased in nSTZ diabetic rats. Both NBDP and metformin were able to restore the altered enzyme activities to almost control concentrations. Combination treatment was more effective than either drug alone. CONCLUSION: The administration of NBDP along with metformin to nSTZ diabetic rats normalizes blood glucose and causes marked improvement of altered carbohydrate metabolic enzymes during diabetes.     

A loss‐of‐function homozygous mutation in DDX59 implicates a conserved DEAD‐box RNA helicase in nervous system development and function

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD‐box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient‐derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies‐associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss‐of‐function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD‐box RNA helicase in neurological function.     

Profile of the Pleximmune blood test for transplant rejection risk prediction

The Pleximmune^TM test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein–Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in a 5-year graft loss rate of up to 50%. Such outcomes seem increasingly unacceptable because children can experience rejection-free survival with reduced immunosuppression. Pleximmune test sensitivity and specificity for predicting acute cellular rejection is 84% and 80% respectively in training set–validation set testing of 214 children. Among existing gold standards, the biopsy detects but cannot predict rejection. Anti-donor antibodies, which presage antibody-mediated injury, reflect late-stage allosensitization as a downstream effect of engagement between recipient and donor cells. Therefore, durable graft and patient outcomes also require accurate management of cellular immune responses in clinical practice.