Anticancer efficacy of perillyl alcohol-bearing PLGA microparticles

In the present study, a novel poly-lactic glycolic acid (PLGA)-based microparticle formulation of perillyl alcohol (POH) was prepared and characterized. Further, its efficacy was evaluated against di-methyl benzo anthracene-induced skin papilloma in Swiss albino mice. The characterization studies showed that POH-bearing PLGA microparticles were of the size 768 ± 215 nm with a ζ-potential value of −7.56 ± 0.88 mV. The entrapment efficiency of the active drug in particles was 42.4% ± 3.5%. POH-bearing PLGA microparticles were stable and released entrapped drug gradually over an extended time period. The in vitro efficacy of POH-bearing PLGA microparticles was evaluated by examining their differential cytotoxicity and assessing their ability to inhibit epidermoid carcinoma cell line (A253). The POH-based microparticles when administered to tumor-bearing animals caused greater tumor regression and increased survival rate (∼80%) as compared with the group receiving free form of POH (survival rate 40%). The superiority of POH-PLGA microparticles over free form of POH was further evident from their ability to modulate apoptosis-regulating factors

Development and Standardization of the Gratitude Scale

Abstract The Gratitude Scale (GS) developed by the authors was administered to 456 adults to determine the psychometric characteristics i.e. reliability and validity. Cronbach’s Alpha of the scale was found 0.91. Content validity of the scale was verified by some experts, academicians, and professionals. For testing multicollinearity and singularity ‘Determinant’ of the R-matrix was estimated and it was greater than 0.00001. The items having factor loading greater than or equal to 0.40 were selected. Total 26 items with five dimensions emerged through Exploratory Factor Analysis explaining 58.14% of the variance, which provided the evidence of factorial/construct validity of the scale. The scale can be used for research and human resource development programs in school/university and organizations. Keywords: Gratitude, content validity, Factor analysis, Multicollinearity, R-matri

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

Cisplatin (CP) is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO) can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally) with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p.) respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism. Keywords: Cisplatin, Nigella sativa oil, Carbohydrate metabolism, Antioxidan

Amelioration of cisplatin-induced nephrotoxicity by ethanolic extract of Bauhinia purpurea: An in vivo study in rats

Our objective is to study the nephroprotective activity and antioxidant potential of Bauhinia purpurea unripe pods and bark against cisplatin-induced nephrotoxicity. Healthy adult albino rats of either sex (150-200 g) were randomly divided into six groups of six animals each Group I (vehicle control) and Group II (negative control). Group III (BBE200) and Group IV (BBE400) were administered the ethanolic extract of Bauhinia purpurea bark in doses of 200 and 400 mg/kg/day p.o., respectively, and Group V (BPE200) and Group VI (BPE400) were administered the ethanolic extract of Bauhinia purpurea unripe pods at doses of 200 and 400 mg/kg/day p.o., respectively. All the treatments were given for nine days. Cisplatin in a single dose of 6 mg/kg i.p. was given on the 4 th day to all groups, except the vehicle control group. On the 10 th day, blood and urine were collected for biochemical tests and the rats were sacrificed. The kidney was removed for histology and lipid peroxidation-antioxidant test. Cisplatin caused nephrotoxicity as evidenced by elevated blood urea, serum creatinine and urine glucose, and there was decreased creatinine clearance in Group II as compared with Group I. Administration of BBE and BPE at doses of 200 and 400 mg/kg in Group III and Group VI caused a dose-dependant reduction in the rise of blood urea, serum creatinine and urine glucose, and there was a dosedependant increase in creatinine clearance compared with Group II. There was increased catalase and glutathione and decreased malondialdehyde levels in Group II, while BBE 400 (Group IV) and BPE 400 (Group VI) treatments significantly reversed the changes toward normal values. Histological examination of the kidney revealed protection in Group IV and Group VI compared with Group II. The ethanolic extract of Bauhinia purpurea unripe pods and bark has a nephroprotective activity against cisplatin-induced nephrotoxicity in rats

Assessment of colorimetric, antibacterial and antifungal properties of woollen yarn dyed with the extract of the leaves of henna (Lawsonia inermis)

The extract of leaves of henna was applied on woollen yarn to investigate the dyeing characteristics and antimicrobial efficacy against common human pathogens such as Escherichia coli MTCC 443, Staphylococcus aureus MTCC 902 and Candida albicans ATCC 90028. Bioactivity of henna dyed woollen yarn was compared with commercial antibacterial (Ampicillin) and antifungal (Fluconazole) agents. Lawsonia inermis dyed woollen yarn samples were found considerably active against tested microorganisms. Dyed wool yarns were tested for fastness toward light, washing and crocking (dry and wet). Fastness properties of dyed woollen yarn samples were found considerably good. Effect of eco-friendly metallic salt mordants on bioactivity and color characteristics of dyed woollen yarn samples were also investigated. The results proved that mordanted wool yarn showed increase in dye uptake resulting in high color strength and better fastness properties but considerable decrease in antimicrobial activity and slight decrease in the case of antifungal activity were observed with the application of mordants. The results indicate that extract of leaves of henna can be applied on woollen yarns to produce colored clothings and textiles (sportswear, clothings for hospitals and babies) with semidurable antimicrobial properties

Assessment of antimicrobial activity of Catechu and its dyed substrate

The present study was undertaken to evaluate the antimicrobial activity of catechu in solution and % microbial reduction of dyed wool samples against Escherichia coli MTCC 443, Staphylococcus aureus MTCC 902, Candida albicans ATCC 10261 and Candida tropicalis ATCC 750, by using micro-broth dilution method, disc diffusion assay and growth curve studies. The dye showed the maximum antimicrobial activity at 20% w/v, inhibiting the microbial growth by more than 90%. In the next set of the experiments the antimicrobial activity of the dye was compared on woollen yarn alone and on pre-mordanted samples. The reduction in antimicrobial activity was observed when mordanted samples were examined. K/S, CIELab values and fastness properties of the dyed samples were assessed. The structural morphology of woollen yarn was also evaluated using scanning electron microscopy (SEM). Haemolytic activity on human erythrocytes was studied to exclude possibility of further associated cytotoxicity. The observed antimicrobial characteristics and negligible cytoxicity of catechu indicate that the dye might be a promising antimicrobial agent for developing bioactive textile materials and clothing

Antimicrobial activity of wool yarn dyed with Rheum emodi L. (Indian Rhubarb)

This work is an attempt to examine the effect of Rheum emodi L. as dye and its dyed wool yarns against two bacterial (Escherichia coli and Staphylococcus aureus) and two fungal (Candida albicans and Candida tropicalis) species. The dyeing was carried out using 5% and 10% o.w.f. dye concentration in presence and absence of ferrous sulphate, stannous chloride and alum mordants. The colour strength, CIELab values and fastness properties of dyed samples were also assessed. FTIR spectra of untreated, mordanted and dyed wool yarn were investigated to study the interaction between fibre, mordant and dye. The structural morphology of wool yarn was investigated by Scanning Electron Microscopy (SEM). The susceptibility tests for R. emodi L. were carried out in terms of disc diffusion, growth curve and viability assays against all the tested microorganisms. Dyed samples showed very effective antimicrobial properties showing more than 90% microbial reduction in both bacterial as well as fungal population