Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.     

Laparoscopic colorectal surgery in Great Britain and Ireland – Where are we now?

OBJECTIVE: We aimed to gather information from the members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to assess trends in the current practice of laparoscopic colorectal surgery. METHODS: A postal questionnaire survey of the members of ACPGBI. RESULTS: The response rate was 37% (200/540). Only 45 surgeons currently perform laparoscopic colorectal work in Great Britain and Ireland mainly right hemicolectomy and laparoscopic stoma formation, of these about one third practiced laparoscopy for benign colorectal conditions only. The majority (68%) of surgeons had enough resources at their place of work, but further training seemed to be a major issue. Nearly 22% of surgeons had not had any formal training. Only 50% of surgeons trained their specialist registrars. The incidence of conversion rate was not different for benign or malignant conditions and also did not appear to be related to the duration of experience. Only four surgeons had noted port a site recurrence during the past 10 years. Seventy-five percent (150/200) felt that laparoscopic colorectal work could be carried out safely in a District General Hospital. CONCLUSION: Laparoscopic colorectal surgery was being performed by a small minority of members of the ACPGBI although more surgeons had started to work in this field in recent years. The main areas of concern appeared to be a wide variation in the range of experience as indicated by the number of operations performed and limited formal training for consultants.     

Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis

Chronic hepatitis C virus (HCV) infection develops in 85% of exposed individuals and 20% develop cirrhosis. However, the pathogenesis of this process is not well-understood. The objective of this study was to determine whether HCV-reactive T cells play a role in the process of development of cirrhosis during chronic HCV infection. We analyzed 21 human leukocyte antigen (HLA)-A2 patients with chronic HCV infection (9 with histology of inflammation and 12 with histology of fibrosis/cirrhosis). The frequency of CD8(+) T cells reactive to 12 HCV-derived epitopes was determined by an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. The frequency of CD4(+) Th1 and Th2 cells reactive to the HCV core antigen was determined by interferon-gamma and interleukin-5 ELISPOT assays, respectively. Patients with histology of inflammation showed a significantly higher CD8(+) T-cell response to five HCV-derived epitopes (YLLPRRGPRL [core], CINGVCWTV [NS3], LLCPAGHAV [NS3], ILAGYGAGV [NS4B], and GLQDCTMLV [NS5B]) as compared with patients with histology of fibrosis/cirrhosis. Also, patients with histology of inflammation showed a significantly higher CD4(+) Th1 response to the HCV core antigen as compared to patients with histology of fibrosis/cirrhosis. These results indicate that a lack of an optimal T-cell response to HCV is associated with the development of cirrhosis during chronic HCV infection.     

Proliferating cell nuclear antigen expression and the progression of cervical intraepithelial neoplasia

Cell proliferation is an important biological aspect of a tumor cell population which can affect clinical outcome. In addition to other well established clinical and histopathological prognostic criteria? cell kinetic data have significant predictive value. This study evaluates the proliferative activity of benign, premalignant and malignant cervical tissue by analyzing the expression of the proliferating cell nuclear antigen (PCNA). PCNA is a 36 kD nuclear protein associated with the cell cycle and is directly involved in DNA synthesis during cell proliferation. A total of 122 subjects were included in the study. This included 30 benign tissue samples, 30 low grade lesions (CIN 1), 30 high grade lesions (CIN 2/3) and 32 invasive squamous carcinomas. There was significant difference in PCNA index between benign and high grade lesions as well as benign and invasive cancer. The percentage of PCNA positive cells were significantly higher in invasive carcinoma when compared with non malignant lesions. Moreover, there was also good correlation between increasing histological abnormality and PCNA expression. These results suggest that cell proliferation index as detected by PCNA expression may be useful in the evaluation of alterations in cell kinetics of various grades of cervical lesions. Such data could also possibly help explain the biological behaviour of these lesions and be useful in planning of radiotherapy for invasive cervical cancer.     

Consequences of xenoestrogen exposure on male reproductive function in spottail shiners (Notropis hudsonius).

There is limited information on the physiological consequences associated with exposure to xenoestrogens under field conditions. The objectives of this study were to determine the presence of estrogenic chemicals in the St. Lawrence River and their effects on male reproduction in the spottail shiner (Notropis hudsonius). Hepatic vitellogenin (VTG) mRNA levels in immature shiners indicate extensive estrogenic contamination spanning almost 50 km both upstream and downstream from the island of Montreal. Stages of spermatogenesis were assessed in fish captured at sites having varying levels of estrogenic contamination. In control fish, 95% had testis of either stage IV (50%) or stage V (45%) of spermatogenesis. At Ile Dorval, where VTG mRNA levels are moderate, fish had testes of stage III (38%) and IV (45%) and only 15% of fish were at spermatogenic stage V. In contrast, at Ilet Vert and Ile Beauregard, located in the sewage effluent plume from the City of Montreal and where hepatic VTG mRNA levels are high in fish, none of the fish were at stage V and 8% of fish at Ilet Vert were at stage II of development. Sperm concentration and various motility parameters were significantly lower in shiners from Ilet Vert as compared with those from Iles de la Paix (reference). Histological analyses of testes revealed that more than one-third of the fish captured at sites with the highest estrogenic contamination displayed intersex, a condition in which ovarian follicles were developing within the testis. These data indicate that there is significant estrogenic contamination in the St. Lawrence River that is associated with impaired reproductive function in male fish.     

Evaluation of in silico,in vitro α-amylase inhibition potential and antidiabetic activity of Pterospermum acerifolium bark

Context: Pterospermum acerifolium (L.) Willd (Sterculiaceae) has been traditionally used in the treatment of diabetes mellitus but no scientific data has been published supporting the claimed ethnomedical use.

Objective: The present study was designed to estimate the in silico, in vitro α-amylase inhibition potential and anti-diabetic activity of Pterospermum acerifolium bark.

Materials and methods: In silico studies were performed between human pancreatic α-amylase (HPA) and β-sitosterol by using autodock 4.2 software. In vitro α-amylase inhibition study was carried out with 50% ethanol extract of the bark (PABEE) and its various fractions. The active ethyl acetate fraction (PABEF) was sub-fractionated into three fractions (PABE1, PABE2 and PABE3). Two doses (15 and 30?mg/kg) based on acute toxicity studies, of the above fractions were subjected to antidiabetic screening in vivo by STZ-nicotinamide induced type II diabetic rats.

Results: In silico studies showed the potent inhibition of β-sitosterol on human pancreatic amylase (HPA) with an estimated inhibition constant (K_i) of 269.35?nmol and two hydrogen bond interactions. PABEF showed marked α-amylase inhibition (69.94%) compared to other fractions. Diabetic rats treated with PABE3 (30?mg/kg) reduced the levels of fasting blood glucose, HbA1c, ALT, AST, ALP, triglycerides, total cholesterol, TBARS significantly (p?p?Conclusion: The present study confirmed the antihyperglycemic activity along with its status on hepatic biomarkers, antihyperlipidemic and antioxidant properties of Pterospermum acerifolium bark.