Modifying role of apigenin in angiogenesis and anti-oxidant status in experimentally induced breast cancer in rats

Background: Angiogenesis and agents which inhibit it are currently an alternative approach to anti-cancer therapy. Tumor metastasis and resistance to chemotherapy are factors to be considered in the management of breast cancer. Apigenin, a flavone is documented to possess anti-inflammatory, anti-oxidant, and anti-proliferative effects in vitro studies, but activity in vivo is still hypothetical.Methods: Apigenin at doses of 50,100, 200 mg/kg body weight and tamoxifen at 50 mg/kg was administered to female albino Wistar rats and 7,12, dimethylbenzanthracene was used to induce mammary carcinogenesis. The anti-oxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase were estimated in breast tissue and erythrocyte lysate with thiobarbituric acid reactive substances as an indicator of lipid peroxidation. Immunohistochemical staining for vascular endothelial growth factor (VEGF) protein expression was done to study its role in angiogenesis. The statistical significance of the data was determined using one-way analysis of variance and Dunnett’s multiple range test.Results: Apigenin at doses of 100 mg/kg and 200 mg/kg (<0.05) was most effective in modifying the anti-oxidant status in breast tissue and in inhibiting VEGF expression in the immunohistochemical analysis in comparison with tamoxifen.Conclusion: The results of our study implicate that apigenin, an innocuous agent could help alleviate the oxidative stress in breast cancer tissues, minimize toxicity of anti-cancer drugs and also slow down the process of angiogenesis in breast cancer

ROLE OF EBSELEN, A SELENOORGANO COMPOUND IN CISPLATIN INDUCED NEPHROTOXICITY IN WISTAR RATS

Objective: Nephrotoxicity is encountered worldwide, irrespective of several factors, but drug induced nephrotoxicity is a complication that is attributed to the high dose and even low dose of drugs. Cisplatin, a platinum complex used in the chemotherapy of several solid tumors was found to have a chief dose limiting side effect namely nephrotoxicity, which occurred due to lipid peroxidation and formation of reactive oxygen species. Ebselen, a eleno organo compound, a glutathione peroxidase mimic with anti-oxidant activity was used in our study to evaluate its nephro protective potential. Methods: Male wistar rats, 6-8 wks old, weighing 180-200 grams were used for the study, which was carried out for a period of 7 wks. Animals were divided into five groups; each group consisting of 6 animals. Group I served as control. Group IV &amp; V received the test drug Ebselen in doses of 10 mg/kg &amp; 20 mg/kg respectively. Group III received Amifostine at 50 mg/kg. The drugs were administered once a week intraperitoneally for 5 wks. Nephrotoxicity was induced at a dose of 5 mg/kg single dose for groups II to V in the 6th wk and the drugs in group III, IV &amp; V continued for 5 days post induction. In the 7th wk blood samples were collected for biochemical analysis and kidney tissues for histopathological study. Results: The serum urea, creatinine levels were significantly increased in Cisplatin group compared to other groups. The estimation of antioxidant levels (catalase, superoxide dismutase and glutathione peroxidise) was significantly decreased in cisplatin group and increased in other groups. The estimation of Malondialdehyde an indicator of lipid peroxidation was significantly increased in group II and decreased in drug treated group. Histopathology results of animals treated with Cisplatin showed inflammatory changes such as tubular degeneration, edema, and necrosis, infiltration of cells in tubular interstitum, mild intertubular hemorrhage and atrophy of glomeruli which was severe in group II. Some changes were also observed in Group III, IV and V animals but with less severity. Conclusion: The result of our study effectively proves the antioxidant potential of Ebselen in ameliorating Cisplatin induced nephrotoxicity

Study on nephroprotective effect of Ebselen in cisplatin induced renal damage in rats

Background: Renal dysfunction arises as a result of exposure to medicines, industrial or environmental chemicals. Cisplatin is a major antineoplastic drug used for the treatment of solid tumors. Its chief dose limiting side effect is nephrotoxicity; 20% of patients receiving high-dose cisplatin have severe renal dysfunction. Ebselen a promising antioxidant, was used to explore the nephroprotective effect.Methods: The rats were divided into five groups; each group consisting of 6 animals. The experimental design included one control group and four experimental groups. The study was carried out for a period of 7 wks. The test drug Ebselen in group 4 and 5 and the reference standard drug Amifostine in group 3 was administered once a week intraperitoneally for 5 weeks. Nephrotoxicity was induced by cisplatin (5mg/kg IP) in the 6th week, following this the drug Amifostine in group 3 and Ebselen in group 4 and 5 will be continued twice a day for 5 consecutive days post induction. Urine samples were collected and sent for determination of urine creatinine and albumin.Results: The Urine creatinine level and albumin level estimation in group II show significant renal damage as compared to control group. The statistical reduction in urine creatinine and urine albumin level in Ebselen treated group I (10mg/kg), Ebselen group V (20mg/kg) as compared to Cisplatin group II show a potential reduction in renal damage. Ebselen treated group V showed a reduction in urine creatinine and urine albumin as same as in group III.Conclusions: This study brings to a close that Ebselen lessens Cisplatin induced renal damage

COMPARATIVE STUDY OF EFFICACY AND SAFETY OF AZITHROMYCIN ALONE AND IN COMBINATION WITH PROBIOTIC IN THE TREATMENT OF IMPETIGO IN CHILDREN

Objective: Impetigo is a superficial infection of the skin that involves only the epidermis. It affects mostly children, usually on exposed areas of the body (eg. The face and the legs). Staphylococcus aureus is the most important causative organism. Streptococcus pyogenes (i.e.) group A beta-hemolytic streptococcus) causes fewer cases, either alone or in combination with S. aureus. The objective of this study is to find out the efficacy and safety of azithromycin alone and in combination with probiotic among children suffering from impetigo.Methods: This prospective, randomized, single-blinded interventional study was conducted for a period of 6 mo in pediatric OPD and dermatology OPD in Rajah Muthiah Medical College and Hospital. A total of 100 patients, randomly divided into two groups with 50 patients in each group. Group, I patients treated with Azithromycin 10 mg/kg/d for 5 d. Group II patients treated with Azithromycin 10 mg/kg/d for 5 d with probiotic (50 million spores of Lactobacillus sporegens, Streptococcus faecalis 30 million spores, clostridium butyricum 2 million spores, Bacillus mesentericus 1 million spores) twice daily for 5ds.Results: Reduction in a number of lesions and wound area, clinical response were highly significant in Azithromycin with the probiotic-treated group.Conclusion: In this study, probiotic bacteria may counteract the inflammatory process beyond the intestinal milieu. The results of this study indicate that Azithromycin with probiotic is effective in the treatment of impetigo

COMPARATIVE ANALYSIS OF EFFICACY AND SAFETY OF DIACEREIN VERSUS S-ADENOSYL METHIONINE IN THE MANAGEMENT OF OSTEOARTHRITIS OF KNEE JOINT

Objective: Osteoarthritis (OA) the most common type of arthritis is a degenerative joint disease primarily affecting the articular cartilage and its surrounding tissue. Drugs like Diacerein and S-adenosyl methionine (SAMe) are used to remodel the cartilage and slow the progression of the disease, by acting through different mechanisms. Though there is documented evidence of the efficacy of both agents used individually in several clinical trials only a few studies report a comparison. To analyse the efficacy and safety of Diacerein Versus S-adenosyl methionine in the treatment of Osteoarthritis of knee joint.Methods: A prospective randomised interventional study was planned comparing diacerein with SAMe for 12 w in the management of OA of the knee. 40 patients in each group were randomly assigned to receive either diacerein 50 mg twice daily or S-adenosyl methionine 200 mg thrice daily for 12 w. Both groups received a short course of diclofenac 50 mg bd for one week, to tide over the acute symptoms.Results: Assessment of both drugs individually showed an equieffective potential in reducing osteoarthritis pain over a period of 12 w. But the comparison between the two groups showed a marginal improvement in pain relief from the 4th to 12th week of assessment in the diacerein group.Conclusion: Both the drugs for the treatment of OA, were shown to be effective in relieving pain but with a slower onset of action. Since no radiological changes were observed during the 12-week protocol, studies of longer duration are needed to evaluate the long-term effectiveness of these drugs

Activated networking of platelet activating factor receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium

Objectives It is essential to understand the molecular basis of ovarian cancer etiology and tumor development to provide more effective preventive and therapeutic approaches to reduce mortality. Particularly, the molecular targets and pathways involved in early malignant transformation are still not clear. Pro-inflammatory lipids and pathways have been reported to play significant roles in ovarian cancer progression and metastasis. The major objective of this study was to explore and determine whether platelet activating factor (PAF) and receptor associated networking pathways might significantly induce malignant potential in BRCA1-mutant at-risk epithelial cells. Methods BRCA1-mutant ovarian epithelial cell lines including (HOSE-636, HOSE-642), BRCA1-mutant ovarian cancer cell (UWB1.289), wild type normal ovarian epithelial cell (HOSE-E6E7) and cancerous cell line (OVCA429), and the non-malignant BRCA1-mutant distal fallopian tube (fimbria) tissue specimens were used in this study. Mutation analysis, kinase microarray, western blot, immune staining, co-immune precipitation, cell cycle, apoptosis, proliferation and bioinformatic pathway analysis were applied. Results We found that PAF, as a potent pro-inflammatory mediator, induced significant anti-apoptotic effect in BRCA1-mutant ovarian surface epithelial cells, but not in wild type HOSE cells. With kinase microarray technology and the specific immune approaches, we found that phosphor-STAT1 was activated by 100 nM PAF treatment only in BRCA1-mutant associated at-risk ovarian epithelial cells and ovarian cancer cells, but not in BRCA1-wild type normal (HOSE-E6E7) or malignant (OVCA429) ovarian epithelial cells. Co-immune precipitation revealed that elevated PAFR expression is associated with protein-protein interactions of PAFR-FAK and FAK-STAT1 in BRCA1-mutant ovarian epithelial cells, but not in the wild-type control cells. Conclusion Previous studies showed that potent inflammatory lipid mediators such as PAF and its receptor (PAFR) significantly contribute to cancer progression and metastasis. Our findings suggest that these potent inflammatory lipids and receptor pathways are significantly involved in the early malignant transformation through PAFR-FAK-STAT1 networking and to block apoptosis pathway in BRCA1 dysfunctional at-risk ovarian epithelium

CCR6-Dependent Positioning of Memory B Cells Is Essential for Their Ability To Mount a Recall Response to Antigen

Chemokine-dependent localization of specific B cell subsets within the immune microarchitecture is essential to insure successful cognate interactions. While cognate interactions between T cells and memory B cells (B(mem))() are essential for the secondary humoral immune responses, the chemokine response patterns of B(mem) cells are largely unknown. In contrast to naïve B cells, this study shows that antigen-specific B(mem) cells have heightened expression of CCR6 and a selective chemotactic response to the CCR6 ligand, CCL20. While CCR6 appears be non-essential for the initial clonal expansion and maintenance of B(mem), CCR6 is essential for the ability of B(mem) to respond to a recall response to their cognate antigen. This dependency was deemed intrinsic by studies in CCR6-deficient mice and in bone-marrow chimeric mice where CCR6 deficiency was limited to the B cell lineage. Finally, the mis-positioning of CCR6-deficient B(mem) was revealed by immunohistological analysis with an altered distribution of CCR6-deficient B(mem) from the marginal and perifollicular to the follicular/germinal center area