Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation.

OBJECTIVE--To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN--Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING--Patients attending diabetic outpatient clinic of city hospital. PATIENTS--Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS--After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT--Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS--Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS--Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.     

An extensive review on antifungal approaches in the treatment of mucormycosis

During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B ( 1 ) and isavuconazole ( 2 ) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole ( 3 ) and deferasirox ( 4 ) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 ( 5 ) and APX001A ( 6 ), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.     

Saikosaponin-d,a novel SERCA inhibitor,induces autophagic cell death in apoptosis-defective cells

Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase pump, leading to autophagy induction through the activation of the Ca²⁺/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells.     

Comparative effects of trichothecene mycotoxins on bovine platelet function: Acetyl T-2 toxin,a more potent inhibitor than T-2 toxin

The effects of the trichothecene mycotoxins (acetyl T-2 toxin, T-2 toxin, HT-2 toxin, palmityl T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON), and T-2 tetraol) on bovine platelet function were examined in homologous plasma stimulated with platelet activating factor (PAF). The mycotoxins inhibited platelet function with the following order of potency: acetyl T-2 toxin > palmityl T-2 toxin = DAS > HT-2 toxin = T-2 toxin. While T-2 tetraol was completely ineffective as an inhibitor, DON exhibited minimal inhibitory activity at concentrations above 10×10^?4M. The stability of the platelet aggregates formed was significantly reduced in all mycotoxin treated platelets compared to that of the untreated PAF controls. It is suggested that the increased sensitivity of PAF stimulated bovine platelets to the more lipophilic mycotoxins may be related to their more efficient partitioning into the platelet membrane compared to the more hydrophilic compounds.     

Monoclonal antibodies to rabbit liver cytochrome P-448

Cytochrome P-448 (mol wt 55,000 Daltons) from rabbit liver was purified to a specific content of 16.6 nmol/mg. Mice were immunised with this preparation, their spleens removed and dissociated lymphocytes hybridised with myeloma cells. Four monoclonal antibodies against cytochrome P-448 were raised and partially characterised. All four antibodies interacted with cytochrome P-448 in intact microsomal fractions and selectively immunoadsorbed cytochrome P-448 from solubilised microsomal preparations. One of the antibodies inhibited benzo[a] pyrene hydroxylase activity in a reconstituted system, one had no effect on activity and two increased activity. The possible applications of such antibodies are discussed.     

Incidence of Male-Killing Rickettsia spp. (α-Proteobacteria) in the Ten-Spot Ladybird Beetle Adalia decempunctata L. (Coleoptera: Coccinellidae)

The diversity of endosymbiotic bacteria that kill male host offspring during embryogenesis and their frequencies in certain groups of host taxa suggest that the evolution of male killing and the subsequent spread of male-killing symbionts are primarily determined by host life history characteristics. We studied the 10-spot ladybird beetle, Adalia decempunctata L. (Coleoptera: Coccinellidae), in which male killing has not been recorded previously, to test this hypothesis, and we also assessed the evolution of the male killer identified by DNA sequence analysis. Our results show that A. decempunctata harbors male-killing Rickettsia (α-proteobacteria). Male-killing bacteria belonging to the genus Rickettsia have previously been reported only for the congeneric two-spot ladybird beetle, Adalia bipunctata L. Phylogenetic analysis of Rickettsia DNA sequences isolated from different populations of the two host species revealed a single origin of male killing in the genus Rickettsia. The data also indicated possible horizontal transfer of symbionts between host species. In addition, A. bipunctata is known to bear at least four different male-killing symbionts in its geographic range two of which coexist in the two locations from which A. decempunctata specimens were obtained for the present study. Since only a single male-killing taxon was found in A. decempunctata, we assume that the two closely related ladybird beetle species must differ in the number and/or geographic distribution of male killers. We discuss the importance of these findings to our understanding of the evolution and dynamics of symbiotic associations between male-killing bacteria and their insect hosts.     

Response of patients to upper gastrointestinal endoscopy: effect of inherent personality traits and premedication with diazepam.

The influence of personality traits on the reaction of patients to upper gastrointestinal endoscopy was studied prospectively in 86 patients. High N (neuroticism) scores on the Eysenck personality inventory were associated with poor tolerance to and future compliance with the procedure. Although premedication with diazepam did not affect the degree of discomfort and distress during the procedure, it guaranteed acceptance of repeat endoscopy by virtue of its strong amnesic effect. By contrast, not giving premedication to patients who were anxious and had high N scores jeopardized future compliance. These findings suggest that a version of the Eysenck personality inventory should be used to assess patients'' neurotic phenotype and their need for premedication before endoscopy. Alternatively, all patients might be given premedication.