A study to evaluate antioxidant and hepatoprotective activity of aqueous extract of roots of Valeriana wallichii in CCl4 induced hepatotoxicity in rats

Background: Drugs for liver ailments have been important in research, but still the number of drugs acting on various hepatic diseases is very limited. This study, for the first time, evaluates the hepatoprotective activity of aqueous extract of the roots of Valeriana Wallichii in albino rats.Methods: The hepatotoxicity was induced by CCl4. Animals were divided into 5 groups of 6 animals each. Group I (Normal control) was given only distilled water. Group II (Negative control)was administered CCl4 for 7 days while Group III (Positive control) was given silymarin and CCl4 for 7 days. The test groups (Group IV & V) were given an aqueous extract of roots of V. Wallichii in a dose of 300 mg and 500 mg/kg, respectively. The animals were sacrificed on 8 days and blood was collected for biochemical analysis (aspartate aminotransferase [AST], alanine transaminase (ALT) and alkaline phosphatase). Liver tissue was extracted for histopathological examination and in vivo antioxidant tests Catalase [CAT], glutathione and malondialdehyde. The extract was also subjected to in vitro antioxidant tests (Total reducing power and total phenolic content).Results: The test extracts in the dose of 500 mg/kg were shown a significant decrease in the levels of AST and ALT (p>0.05) and CAT activity. 300 mg/kg dose of extract showed minimal hepatoprotection. The findings were confirmatory to histopathology. Conclusion: The aqueous extract of roots of V. Wallichii in a dose of 500 mg/kg offers partial protection against hepatotoxicity produced by CCl4 in albino rats

IN VITRO ANTIOXIDANT AND IN VIVO HEPATOPROTECTIVE ACTIVITY OF LEAVE EXTRACT OF RAPHANUS SATIVUS IN RATS USING CCL4 MODEL

Background: Raphanus sativus is reported to have a variety of biological activities. This work screened the hepato-protective and antioxidant activity of ethanol (ERS), and aqueous (ARS), extracts of leaves of Raphanus sativus in Carbon tetrachloride (CCl4), model in rats. Material and Methods: The extracts were subjected to antioxidant tests (Total reducing power and Total phenolic content), and preliminary phytochemical screening. A pilot study was done on 100 and 300 mg/kg extracts, form which 300 mg was chosen for further experiments. The albino rats (200-250 grams), were divided into 5 groups of 6 animals each (n=6). There were three control groups comprising of normal control (normal saline -1ml/kg), negative control group (CCl4 1ml/kg in olive oil in a ratio of 1:1 v/v), and positive control group (Silymarin 50mg/kg). The Test drugs were given in a dose of 300 mg/kg for both ERS and ARS extract for 7 days. Biochemical parameters (AST, ALT, Alkaline phosphatase, Total Bilirubin), histo-pathological examination of liver and in vivo antioxidant tests [CAT, GSH and MDA] were done. Results: The phytochemical study showed the presence of flavanoids, terpenoids, alkaloids, saponins and sterols. A dose dependent increase in the oxidative potential was observed in both the extracts with total phenolic content 70.1 and 44.4 GAE/g extract for ERS and ARS respectively. ERS 300mg/kg showed a significant (

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

Riboflavin Ameliorates Cisplatin Induced Toxicities under Photoillumination

BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone

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

Lactobacillus rhamnosus cell-free extract targets virulence and antifungal drug resistance in Candida albicans

Candidiasis caused by multidrug-resistant Candida species continues to be difficult to eradicate. The use of live probiotic bacteria has gained a lot of interest in the treatment of candidiasis; however, whole-cell probiotic use can often be associated with a high risk of sepsis. Strategies manipulating cell-free methods using probiotic strains could lead to the development of novel antifungal solutions. Therefore, we evaluated the effect of three probiotic cell-free extracts (CFEs) on the growth, virulence traits, and drug efflux pumps in C. albicans. On the basis of its minimum inhibitory concentration, Lactobacillus rhamnosus was selected and assessed against various virulence traits and drug resistance mechanisms. The results showed that L. rhamnosus CFE significantly inhibited hyphae formation and reduced secretion of proteinases and phospholipases. Moreover, L. rhamnosus inhibited the drug efflux proteins in resistant C. albicans strains thus reversing drug resistance. Gene expression data confirmed downregulation of genes associated with microbial virulence and drug resistance following treatment of C. albicans with L. rhamnosus CFE. Through gas chromatography – mass spectrometry chemical characterization, high contents of oleic acid (24.82%) and myristic acid (13.11%) were observed in this CFE. Collectively, our findings indicate that L. rhamnosus may potentially be used for therapeutic purposes to inhibit C. albicans infections.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Central Bank Independence and its Impact on Fiscal Deficit: Evidence from India

The paper explores the relationship between Central bank independence (CBI) and fiscal deficit in India. Moreover, the study tries to assess the impact of CBI on the levels of fiscal deficit. The study incorporates other variables like Gross Domestic Product, financial development, and trade openness to analyze their impact on the fiscal deficit. The study employed Auto-regressive distributed lag model (ARDL) Bounds test developed by Pesaran, Shin, and Smith (2001) to examine the long-run relationship between CBI and fiscal deficit. The study also employs a legal index for measuring CBI developed by Jasmine et al (2019) as well as an actual measure of independence developed by Cukierman (1992) to measure CBI in India. The study confirms the long-run relationship between the CBI and fiscal deficit as well as among other variables. An increase in the levels of CBI leads to falling in the levels of fiscal deficit. The other explanatory variables used in the study also confirm the long-run relationship and impact fiscal deficit negatively except for trade openness, which positively impacts the fiscal deficit

Dosimetric comparative study of conformal radiation techniques in patients with glioblastoma multiforme

Purpose: The purpose of the current study is to determine whether patients diagnosed with glioblastoma multiforme (GBM) who underwent radiotherapy (RT) using intensity-modulated RT (IMRT) technique were benefitting from this highly conformal treatment in terms of doses received by planning target volume (PTV) and organs at risk (OARs) in comparison to three-dimensional conventional RT (3DCRT). Materials and Methods: Twelve patients treated with IMRT for GBM were selected for dosimetric comparison with 3DCRT. The prescribed dose was 60 Gy in 30 fractions and seven non-coplanner beams were used in IMRT to cover 95% of target volume. The irradiated patients of GBM were retrieved and replanned with 3DCRT techniques. Dosimetric comparison was done by performing two plans for the same patient; prescription dose and normal tissue constraints were identical for both plans. The dose–volume histograms of target volumes and OAR, dose conformity, and dose homogeneity with 3DCRT and IMRT planning were compared. Statistical analysis was performed to determine the differences. Results: The mean conformity index was 0.99 ± 0.001 for IMRT and 0.97 ± 0.002 for 3DCRT, P = 0.001. The mean homogeneity index was 1.03 ± 0.02 for IMRT and 1.06 ± 0.009 for 3DCRT, P = 0.003, which is statistically significant. The IMRT technique enables dose reduction of normal tissues including brainstem (Dmean by 33.78 ± 5.34 and Dmax 51.84 ± 4.43), optic chiasm (Dmean by 36.92 ± 1.99 and Dmax 44.61 ± 3.72), left optic nerve (Dmean by 28.97 ± 6.51 and Dmax 46.08 ± 10.58), right optic nerve (Dmean by 31.93 ± 11.68 and Dmax 44.63 ± 13.54), left eye (Dmean by 18.66 ± 8.92 and Dmax 37.43 ± 13.47), right eye (Dmean by 14.40 ± 4.87 and Dmax 40.37 ± 11.37), left lens (by Dmax 5.45 ± 1.85), and right lens (Dmax 5.07 ± 0.63). Conclusion: The IMRT provides a real dosimetric advantage, especially for normal brain tissue, and in terms of target coverage. It allows treatment of tumors while respecting OARs' dose constraints. The IMRT technique shows significant advantage in PTV coverage, dose homogeneity, and conformity. In IMRT, the coverage is better where PTV was overlapping with critical OARs

Dosimetric Comparison between Intensity Modulated Radiation Therapy (IMRT) and Three-Dimensional Conformal Radiation Therapy (3DCRT) in Mid Lower esophageal Carcinoma: An Analytical Observational Study

Esophageal cancer (EC) is a common cancer with high mortality because of its rapid progression and poor prognosis. One of the most successful therapies for EC is radiotherapy. Two recently created radiation methods are intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). In terms of target coverage, dose homogeneity, and lowering toxicity to healthy organs, IMRT is thought to be superior to 3D-CRT. These benefits haven't been proven in the treatment of EC, though. This study was performed to investigate if intensity modulated radiation therapy (IMRT) offers a better planning target volume (PTV) coverage and/or lower dose to organs at risk in comparison to three-dimensional conformal radiation therapy (3DCRT). 30 patients with locally advanced histo-pathologically proven mid and lower oesophageal carcinoma, not reaching gastro-esophageal junction were treated with chemoradiation using IMRT technique. 3DCRT plans were generated for those 30 patients. The IMRT and 3DCRT plans were compared in terms of PTV coverage and doses to organs at risk. Our results revealed that IMRT is better than 3DCRT comparing PTV coverage and doses to organs at risk having statistically significant difference between both techniques (p<0.001). As for the organs at risk (OAR), the V20 for the IMRT plans delivered lesser lung volume irradiation also the mean dose to the heart and the V30 were both higher in the 3DCRT plans.Keywords: esophageal cancers (ECs), Organs at risk (OAR), Intensity modulated radiation therapy (IMRT), Three-dimensional conformal radiation therapy (3DCRT), Planned target volume (PTV)

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