Pharmacological evaluation of tacrolimus (FK-506) on ischemia reperfusion induced vasculatic neuropathic pain in rats

<p>Abstract</p> <p>Background</p> <p>Ischemia reperfusion (I/R) is common in various pathological conditions like diabetic complication, rheumatic arthritis, necrotizing vascular occlusive disease and trauma.</p> <p>Methods</p> <p>We have evaluated the effect of tacrolimus (1, 2 and 3 mg/kg, <it>p.o</it>. for 10 consecutive days) on femoral arterial ischemic reperfusion (I/R) induced neuropathic pain in rats. Behavioral parameters (i.e. hot plate, radiant heat, acetone drop, tail heat hyperalgesia, tail flick and tail cold allodynia tests) were assessed at different time intervals (i.e. 0, 1, 4, 7, 10, 13 and 16^thday) and biochemical analysis in serum and tissue samples were also performed along with histopathological studies.</p> <p>Results</p> <p>Behavioral pain assessment revealed increase in the paw and tail withdrawal threshold in tacrolimus treated groups against hyperalgesic and allodynic stimuli as compared to the sham control group. We observed a decrease in the serum nitrate and thiobarbituric acid reactive substance (TBARS) levels along with reduction in tissue myeloperoxidase (MPO) and total calcium levels, whereas, rise in tissue reduced glutathione levels in tacrolimus treated groups. However, significant results were obtained in medium and high dose treated group as compared to sham control group. Histopathological study had revealed the increase in the neuronal edema and axonal degeneration in the I/R group whereas, tacrolimus ameliorate these effects.</p> <p>Conclusion</p> <p>Our results indicate the anti-oxidative, anti-inflammatory and calcium modulatory actions of tacrolimus. Therefore, it can be used as a therapeutic agent for the treatment of vascular inflammatory related neuropathic pain.</p

Evaluation of antioxidant and anti-ulcerative potential of Citrullus lanatus seed extract in rats

In the present study antioxidant and antiulcer potential of Citrullus lanatus seeds were evaluated. Antioxidant activity of all the extracts (chloroform, ethylacetate and methanol) was measured by DPPH method. Methanolic extract of Citrullus lanatus (MECL) seeds showed maximum antioxidant potential and was evaluated for its anti-ulcerogenic activity by pyloric ligated (PL) and water immersion stress (WIS) induced ulcer models in rat. Gastric volume and free and total acidity were measured in PL model whereas; ulcerative index was measured in both the models at 100, 200 and 300 mg/kg doses of MECL. Rats treated with MECL (300 mg/kg) showed significant decrease in the gastric volume, free acidity and total acidity in case of PL model and showed significant percentage inhibition of ulcer as indicated by decrease in ulcerative index in both the models. The extract of Citrullus lanatus seeds possesses good antioxidant and anti-ulcer activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of antioxidant and anti-ulcerative potential of Citrullus lanatus seed extract in rats

In the present study antioxidant and antiulcer potential of Citrullus lanatus seeds were evaluated. Antioxidant activity of all the extracts (chloroform, ethylacetate and methanol) was measured by DPPH method. Methanolic extract of Citrullus lanatus (MECL) seeds showed maximum antioxidant potential and was evaluated for its anti-ulcerogenic activity by pyloric ligated (PL) and water immersion stress (WIS) induced ulcer models in rat. Gastric volume and free and total acidity were measured in PL model whereas; ulcerative index was measured in both the models at 100, 200 and 300 mg/kg doses of MECL. Rats treated with MECL (300 mg/kg) showed significant decrease in the gastric volume, free acidity and total acidity in case of PL model and showed significant percentage inhibition of ulcer as indicated by decrease in ulcerative index in both the models. The extract of Citrullus lanatus seeds possesses good antioxidant and anti-ulcer activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Therapeutic potential of Emblica officinalis L. fruit extract on ischemia reperfusion Injury induced acute renal failure in rat

The present study was designed to explore the ameliorative effect of hydroalcoholic extract of Emblica officinalis (HAE) on renal ischemia reperfusion (I/R) injury induced acute renal failure (ARF). Rats were subjected to administration of HAE (250 and 500 mg/kg, p.o. for 10 days) before one hour of the ischemia (30 min) reperfusion (24 h) process on the 10th day of experiment. For evaluating the effect of HAE on acute renal failure, Blood urea nitrogen (BUN) and creatinine (Cr) were estimated in serum sample whereas, N-acetyl β-d-glucosaminidase (NAG) was estimated in urine sample. Further, renal tissue was used to evaluate the oxidative stress markers and histopathological changes. The results demonstrated that I/R caused marked changes in various biomarker levels. However, treatment with HAE significantly attenuated these changes. Histopathological evaluation also revealed protective role of HAE on renal cortex and tubular cells. These effects clearly indicated that HAE produced renoprotective effect against I/R induced acute renal failureColegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of antioxidant and anti-ulcerative potential of Citrullus lanatus seed extract in rats

In the present study antioxidant and antiulcer potential of Citrullus lanatus seeds were evaluated. Antioxidant activity of all the extracts (chloroform, ethylacetate and methanol) was measured by DPPH method. Methanolic extract of Citrullus lanatus (MECL) seeds showed maximum antioxidant potential and was evaluated for its anti-ulcerogenic activity by pyloric ligated (PL) and water immersion stress (WIS) induced ulcer models in rat. Gastric volume and free and total acidity were measured in PL model whereas; ulcerative index was measured in both the models at 100, 200 and 300 mg/kg doses of MECL. Rats treated with MECL (300 mg/kg) showed significant decrease in the gastric volume, free acidity and total acidity in case of PL model and showed significant percentage inhibition of ulcer as indicated by decrease in ulcerative index in both the models. The extract of Citrullus lanatus seeds possesses good antioxidant and anti-ulcer activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Potential effect of Citrus decumana extract on stress induced peptic ulcer in rat

The present study was designed to investigate the antiulcer activity of ethyl acetate extract of Citrus decumana (grapefruit) peels. The antiulcerogenic activity was evaluated in water immersion and hypothermic restraint stress models at different doses (150, 250 and 350 mg/kg). The antiulcer potential of the extract was assessed by determining and comparing the ulcerative index and biochemical estimation was carried out using various oxidative stress markers i.e., TBARS, GSH, SOD and CAT in the blood and tissue samples. The highest dose (350 mg/kg) of the extract showed significant decrease in the ulcerative index and TBARS level, whereas there was increase in the GSH, SOD and CAT levels. Whereas the lowest and medium dose (150 mg/kg and 250mg/kg) did not produce any significant results. Therefore, our study indicate that the Citrus decumana peel extract may be used as a natural therapeutic agent in the treatment of peptic ulcers.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Antioxidant, anti-inflammatory and analgesic potential of Cucumis sativus seed extract

In the present study antioxidant, anti-inflammatory and analgesic potential of the methanolic extract of Cucumis sativus seeds was evaluated. Extraction of the seeds was carried out using solvents of increasing polarity. The free radical scavenging activity of all the extracts was measured by DPPH and H2O2 methods. Methanolic extract of the seeds had shown significant antioxidant activity as compared to chloroform and ethyl acetate extract. Hence, methanolic extract of C. sativus seeds (MECS) at a dose level of 100, 200 and 300 mg/kg was further evaluated for its in vivo anti-inflammatory activity using carrageenan induced rat paw edema and analgesic activity by tail flick and tail immersion methods. Results were obtained in a dose dependent manner. MECS (300 mg/kg) had shown significant (p < 0.05) anti-inflammatory and analgesic activity as compared to diclofenac sodium and morphine, respectively. From the results it may be concluded that MECS have good antioxidant, anti-inflammatory and analgesic potential.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The antiinflammatory potential of phenolic compounds from Emblica officinalis L. in rat

Antiinflammatory effects of phenolic compounds from Emblica officinalis were evaluated in carrageenan and cotton pellet induced acute and chronic inflammatory animal model. Fractions of E. officinalis containing free (FPEO) and bounded (BPEO) phenolic compounds were assessed by HPLC technique. The free and bound phenolic compounds were studied for their acute and chronic antiinflammatory activity at dose level of 20 and 40 mg/kg. The carrageenan induced acute inflammation was assessed by measuring rat paw volume at different time of intervals. Further, cotton pellet induced chronic inflammation was assessed by granulomatous tissue mass estimation along with the estimation of tissue biomarker changes (i.e. lipid peroxidation, reduced glutathione, myeloperoxidase and plasma extravasation). The results indicated that in both acute and chronic inflammation, FPEO and BPEO show reduction in the inflammation, but significant effects was observed only at high doses of both fractions which was comparable to diclofenac treated group. In conclusion, phenolic compounds of E. officinalis may serve as potential herbal candidate for amelioration of acute and chronic inflammation due to their modulatory action of free radicals

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts