In vitro antibacterial activity of the volatile oil of Nigella sativa seeds against multiple drug-resistant isolates of Shigella spp. and isolates of Vibrio cholerae and Escherichia coli

The antibacterial activity of the volatile oil of Nigella sativa seeds was studied against 37 isolates of Shigella dysenteriae 1, Shigella flexneri, Shigella sonnei and Shigella boydii and 10 strains of Vibrio cholerae and Escherichia coli. Most of the strains were clinically resistant to ampicillin, co-trimoxazole and tetracycline. All the strains tested showed promising sensitivity to the volatile oil. The minimum inhibitory concentration (MIC) of the volatile oil for Shigella, Vibrio and Escherichia strains tested was between 50–400 μg/mL.     

Redox-linked signal transduction pathways for protein tyrosine kinase activation

The signaling for activation of protein tyrosine kinases (PTKs) is usually started by binding of ligands to cell-surface receptors. However, recent evidence suggests the presence of ligand binding-independent signaling pathways that are mediated by oxidative stress. Oxidation and reduction of protein cysteine sulfhydryl (SH) groups may work as a molecular switch to start or to stop the signaling. It is known that oxidation of cysteine SH groups on protein tyrosine phosphatases switches off the action of protein tyrosine phosphatases. This event may not, however, signal for initial autophosphorylation of previously unphosphorylated PTKs, whereas it certainly prevents dephosphorylation of once-phosphorylated PTKs. We have suggested new mechanisms for oxidative stress-mediated PTK activation. First, cell-surface glycosylphosphatidylinositol-anchoring proteins and a phosphoglycolipid/cholesterol-enriched membrane microdomain termed a "raft" can be the direct targets of oxidative stress for inducing their clustering through an S-S-bonded or S-X-S-bonded crosslinking of cell-surface proteins and subsequent activation of raft-associating Src family PTKs. Second, intracellular specific cysteine SH groups on PTK proteins can be another target of oxidative stress for inducing a conformational change necessary for initial activation of PTKs. A possible relationship between cell-surface and intracellular events is that the former frequently induces superoxide production as the second messenger for the latter.     

Haematological Reconstitution after Autografting for Chronic Granulocytic Leukaemia in Transformation: the Influence of Previous Splenectomy

S ummary Peripheral blood values and bone marrow appearances were monitored in eight patients treated for chronic granulocytic leukaemia in transformation by cytotoxic drugs with or without total body irradiation followed by autografting with cryopreserved-thawed peripheral blood nucleated cells. One of the patients was 'autografted' on two occasions. Five patients had been splenectomized early in the first chronic phase and the other three patients had their spleens intact. Recovery of peripheral blood values was more rapid in the splenectomized than in the non-splenectomized patients. CFUc were present in the circulation immediately after autografting in each case but subsequently the pattern of CFUc changes differed between patients. The bone marrow was hypocellular at the time of autografting but the rate at which it returned to a typical chronic phase picture varied. Peripheral blood nucleated cells collected at the time of diagnosis include stem cells with the capacity to repopulate the marrow after 'ablative' therapy for transformation. Elective splenectomy in the chronic phase may promote more rapid recovery of peripheral blood values but its long-term importance is unknown.     

Induction treatment of acute myeloid leukemia in an elderly patient with intramarrow injection/administration of cytarabine: first report of a case

We have used intramarrow injection/administration of cytarabine (Ara‐C) instead of conventional intravenous approach to induce remission in an elderly patient with acute myelogenous leukemia. We show for the first time that the intramarrow injection of chemotherapeutic agents such as Ara‐C can be used safely and effectively.     

Effect of nutrition counselling with a digital job aid on child dietary diversity: Analysis of secondary outcomes from a cluster randomised controlled trial in rural Bangladesh

Adequate dietary diversity among infants is often suboptimal in developing countries. We assessed the impact of nutrition counselling using a digital job aid on dietary diversity of children aged 6–23 months using data from a cluster randomised controlled trial in Bangladesh. The trial had five arms, each with 25 clusters. The four intervention arms provided counselling using a digital job aid and different prenatal and post-natal combinations of lipid-based supplements and the comparison arm with usual practice. We enrolled 1500 pregnant women and followed them until the children reached their second birthday. We developed a tablet-based system for intervention delivery, data collection and project supervision. We combined the four intervention arms (n = 855), in which community health workers (CHWs) provided age-appropriate complementary feeding counselling, to compare against the comparison arm (n = 403). We calculated the outcome indicators from the children's 24-h dietary recalls. Overall, the intervention increased the mean dietary diversity score by 0.09 (95% confidence interval [CI]: 0.2–0.16) and odds of minimum dietary diversity by 18% (95% CI: 0.99–1.40). However, there was a significant interaction on the effect of the intervention on dietary diversity by age. The mean dietary diversity score was 0.24 (95% CI: 0.11–0.37) higher in the intervention than in the comparison arm at 9 months and 0.14 (95% CI: 0.01–27) at 12 months of age. The intervention effect was non-significant at an older age. Overall, consumption of flesh food was 1.32 times higher in the intervention arm (odds ratio [OR] 1.32, 95% CI: 1.11–1.57) in 6–23 months of age. The intervention significantly improved child dietary diversity score in households with mild and moderate food insecurity by 0.27 (95% CI: 0.06–0.49) and 0.16 (0.05–27), respectively, but not with food-secure and severely food-insecure households. Although the study did not evaluate the impact of digital job aid alone, the findings indicate the utility of nutrition counselling by CHWs using a digital job aid to improve child feeding practices in broader programmes.     

Emblica officinalis improves glycemic status and oxidative stress in STZ induced type 2 diabetic model rats

Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P0.07)but reduced glutathione content was found to be increased significantly(P0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.     

Newly designed analogues from SARS-CoV inhibitors mimicking the druggable properties against SARS-CoV-2 and its novel variants

The emerging variants of SARS coronavirus-2 (SARS-CoV-2) have been continuously spreading all over the world and have raised global health concerns. The B.1.1.7 (United Kingdom), P.1 (Brazil), B.1.351 (South Africa) and B.1.617 (India) variants, resulting from multiple mutations in the spike glycoprotein (SGp), are resistant to neutralizing antibodies and enable increased transmission. Hence, new drugs might be of great importance against the novel variants of SARS-CoV-2. The SGp and main protease (M^pro) of SARS-CoV-2 are important targets for designing and developing antiviral compounds for new drug discovery. In this study, we selected seventeen phytochemicals and later performed molecular docking to determine the binding interactions of the compounds with the two receptors and calculated several drug-likeliness properties for each compound. Luteolin, myricetin and quercetin demonstrated higher affinity for both the proteins and interacted efficiently. To obtain compounds with better properties, we designed three analogues from these compounds and showed their greater druggable properties compared to the parent compounds. Furthermore, we found that the analogues bind to the residues of both proteins, including the recently identified novel variants of SARS-CoV-2. The binding study was further verified by molecular dynamics (MD) simulation and molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) approaches by assessing the stability of the complexes. MD simulations revealed that Arg457 of SGp and Met49 of M^pro are the most important residues that interacted with the designed inhibitors. Our analysis may provide some breakthroughs to develop new therapeutics to treat the proliferation of SARS-CoV-2 in vitro and in vivo.

Three designed inhibitors with potential inhibition efficacy against the emerging variants of SARS coronavirus-2 (SARS-CoV-2).     

Mechanisms underlying the antispasmodic and bronchodilatory properties of Terminalia bellerica fruit

AIM OF THE STUDY: The present investigation was carried out to provide the pharmacological basis for the medicinal use of Terminalia bellerica in hyperactive gastrointestinal and respiratory disorders. MATERIALS AND METHODS: Crude extract of Terminalia bellerica fruit (Tb.Cr) was studied in in vitro and in vivo. RESULTS: Tb.Cr caused relaxation of spontaneous contractions in isolated rabbit jejunum at 0.1-3.0mg/mL. Tb.Cr inhibited the carbachol (CCh, 1microM) and K(+) (80mM)-induced contractions in a pattern similar to that of dicyclomine, but different from nifedipine and atropine. Tb.Cr shifted the Ca(++) concentration-response curves to right, like nifedipine and dicyclomine. In guinea-pig ileum, Tb.Cr produced rightward parallel shift of acetylcholine-curves, followed by non-parallel shift at higher concentration with the suppression of maximum response, similar to dicyclomine, but different from nifedipine and atropine. Tb.Cr exhibited protective effect against castor oil-induced diarrhea and carbachol-mediated bronchoconstriction in rodents. In guinea-pig trachea, Tb.Cr relaxed the CCh-induced contractions, shifted CCh-curves to right and inhibited the contractions of K(+). Anticholinergic effect was distributed both in organic and aqueous fractions, while CCB was present in the aqueous fraction. CONCLUSIONS: These results indicate that Terminalia bellerica fruit possess a combination of anticholinergic and Ca(++) antagonist effects, which explain its folkloric use in the colic, diarrhea and asthma.