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.     

A study of 10 cases of velopharyngeal incompetence treated by flap pharyngoplasty

Velopharyngeal incompetence (VPI) is a condition of incomplete closure of V.P. port area, normally formed by velum and posterior pharyngeal watt. The condition primarily results in various types of speech defects, which form- the main complaint of the patient. We have studied 10 cases of VPI due to various causes and the speech improvement obtained by flap pharyngoplasty procedures. The results have been evaluated with a follow-up of six months. Highly encouraging results only indicate a more frequent need to undertake such surgery without any hesitation if the ENT surgeon is familiar with and has an adequate exposure to this simple and effective procedure.     

Middle-Down Fragmentation for the Identification and Quantitation of Site-Specific Methionine Oxidation in an IgG1 Molecule

A middle-down LC/MS approach, for the rapid quantitation and characterization of site-specific methionine oxidation in a recombinant monoclonal IgG1 molecule, is described. An IgG1 antibody was digested with endoprotease LysC under limited proteolytic conditions to produce two major components; an antigen binding fragment (Fab) and a crystallizable fraction (Fc). These fractions were then reduced to produce three major species; light chain (LC), Fc/2 which is the C terminal region of the heavy chain (HC) and the N-terminal heavy chain region (Fd). These three fragments were separated by reversed-phase HPLC using a diphenyl column. The diphenyl column resolved site-specific methionine oxidation in all three subunits. Middle- down N-terminal sequencing with a LCT premier mass spectrometer was used to identify the sites of oxidation in the LC. Sites of oxidation in the Fc/2 were identified using middle-down collision-induced dissociation (CID) on a Qtof premier. This method allowed for the rapid quantitation and identification of oxidation on each methionine residue in an IgG1 molecule.     

Scleromyxoedema with features of systemic sclerosis.

The case is described of a patient with scleromyxoedema with features typical of systemic sclerosis. The features were so characteristic that the disease was misdiagnosed as systemic sclerosis. A brief review of the association of the two diseases is given.     

Salmonellosis in Goa.

During the period 1982-86, a total of 657 Salmonella strains were isolated from various clinical samples processed in the Microbiology laboratory of Goa Medical College, Bambolim, Goa. The strains were distributed amongst 23 different Salmonella serotypes. The commonest serotypes encountered were S.typhimurium (66%) and S.typhi (24%), the other serotypes were S.bareilly (5.4%), S.paratyphi B (1.2%), S.newport (1.2%) and S.chester (0.8%). Stool samples yielded the maximum Salmonella isolates of which the S.typhimurium was the highest followed by S.bareilly.     

Persistence of heart reactive antibodies (HRA) in acute rheumatic fever (ARF) and rheumatic heart disease (RHD) patients

Heart Reactive Antibodies (HRA) of IgG and IgM classes were investigated in 79 patients in four clinically classified groups. Group I comprised of 16 children with Acute Rheumatic Fever (ARF) and Group II consisted of 15 cases with active Rheumatic Heart Disease (RHD). Twenty seven cases of ARF and RHD in remission and 21 adults with quiescent RHD were included in Groups III and IV respectively. Control groups comprised of 14 normal, healthy, donors and eight Post Streptococcal Acute Glomerular Nephritis (PSAGN) cases. Low levels of HRA of IgG and IgM classes were detected in control groups. The overall incidence of HRA of IgG and IgM classes was 82.28 and 39.24% respectively in the patient group. An increased frequency of HRA-IgM antibodies was observed in Groups I, III and IV (p less than 0.01, 0.001 and 0.025 respectively). All the four groups demonstrated a highly significant increase in incidence of HRA--IgG class (p less than 0.0005). Persistence of high titres of HRA-IgG class in ARF and RHD is reported in the paper.     

Filtration of fentanyl is not the cause of the elevation of arterial blood pressure associated with post-bypass ultrafiltration in children

Modified ultrafiltration after cardiopulmonary bypass in children has been shown to be associated with an increase in arterial blood pressure. As part of a series of studies to investigate the possible causes of this blood pressure elevation, the hypothesis that if filtration was removing a significant amount of fentanyl, then the increase in blood pressure might be due to pain was proposed. Ten children, aged between 0.5 and 9.3 years (median 3.8 years), weighing 5.9 to 25..5 kg (median 15.7 kg), underwent corrective cardiac surgery (incorporating modified ultrafiltration). A standard anesthetic protocol was followed, with up to 78 μg/kg of fentanyl given prebypass for analgesia. After completion of cardiopulmonary bypass, modified ultrafiltration was commenced at 100 mL/min until a hematocrit of 35% was reached. Samples were taken of arterial blood (prefiltration, 3, 10, and 20 minutes postfiltration), the venous reservoir blood (prefiltration) and the filtrate (5 and 10 minutes into filtration). Hemodynamic data were recorded both prefiltration and postfiltration. The hemodynamic data showed the expected rise in both systemic arterial pressure and cardiac index after ultrafiltration. The plasma fentanyl concentrations did not significantly change after ultrafiltration: 1.59 to 12.39 ng/mL (median 6.27 ng/mL) prefiltration and 2.05 to 15.59 ng/mL (6.29 ng/mL) at 3 minutes, 2.22 to 12.64 ng/mL (6.87 ng/mL) at 10 minutes, and 1.83 to 11.52 ng/mL (5.85 ng/mL) at 20 minutes postfiltration. The concentration of fentanyl in the venous reservoir, 2.06 to 11.64 ng/mL (7.04 ng/mL), was not significantly different from the plasma levels. The level of fentanyl in the filtrate was significantly less than the plasma levels, 0.243 to 1.87 ng/mL (0.894 ng/mL) at 5 minutes and 0.385 to 1.688 ng / mL (0.952 ng / mL) at 10 minutes into filtration; (P < 0.02 by the Wilcoxon signed-rank method). The data show that the plasma fentanyl concentration was not significantly reduced by modified ultrafiltration. The fentanyl levels found prefiltration were maintained postfiltration, and the observed changes in systemic arterial pressure were not due to an acute fall in the plasma concentration of analgesic drug.     

Anticancer activity of new 3-amino-pyrrolidinedione-nitrogen mustard derivatives on murine sarcoma 180

A 2,5-pyrrolidinedione linked nitrogen mustard derivative, (R,S)3-[N,N-bis(2-chloroethyl)]-amino-1-(2'-methoxyphenyl)pyrrolidine- 2,5-dione hydrochloride (I) showed a marked antiproliferative effect on mouse Sarcoma 180. Since (I) is also active against L1210 and P388 leukaemias, its toxicity in mice was evaluated. A study of acute toxicity revealed focal liver cell necrosis. Another derivative, (R,S)3-[N,N-bis-(2-chloroethyl)]amino-1-(4'-n-butoxyphenyl)pyrrolidine- 2,5-dione dihydrate (II), which also possessed significant anticancer effect on P388 and L1210 leukaemias, was inactive against Sarcoma 180.