Correlation of renin angiotensin system (RAS) candidate gene polymorphisms with response to Ramipril in patients with essential hypertension.

BACKGROUND: The renin-angiotensin system (RAS) is an important facet of blood pressure regulation physiology. Treatment of essential hypertension targets the RAS using Angiotensin Converting Enzyme Inhibitors (ACEIs). However, ACEIs are not uniformly effective and show inter-individual pharmacodynamic variations. AIM: To assess the correlation between genetic polymorphisms in the genes coding for RAS components (angiotensin converting enzyme (ACE I/D), α-adducin (ADD1) and ß1 -adrenoreceptor (ß1-ADR)) and response to Ramipril. MATERIALS AND METHODS: We recruited 120 patients with essential hypertension who were administered Ramipril monotherapy initially, followed by combination therapy, if needed, based on their responses. Relationship between genotypes of the three candidate genes and decrease in the blood pressure (BP) was analyzed. RESULTS: One hundred and six patients were evaluable at the end of the study period and 21 different genotypes were observed among them. Seven of them were classified as responders after 8 weeks and at the end of 12 weeks, an additional 77 (72.64%) were deemed responders. 19/22 non-responders were treated with combination therapy and 7/19 (36.84%) showed a response to the same. There was a significant difference between the proportions of responders and non-responders among the genotypes of the ADD1 and ß1-ADR genes (P=0.005 and 0.003, respectively). The best predictors of response to Ramipril 5 mg daily were the II/GG/SS, II/TG/SS, II/GG/SG, ID/GG/SS, ID/GG/SG and ID/TT/SS and DD/GG/SS; II/GG/GG, II/TT/SG, ID/TG/SG, ID/TT/SG, DD/GG/SG and DD/GG/GG were moderately predictive and II/TT/SS, II/TG/GG, ID/TG/GG, DD/TG/SG and DD/TG/GG were poorly predictive of response. DISCUSSION: Variable responses to Ramipril may be the result of genetic factors. CONCLUSION: Pre-prescription genotyping may help individualize treatment.

In vivo healing potential of Aegle marmelos in excision, incision, and dead space wound models.

The study incorporates the wound healing potential of Aegle marmelos fruit pulp extract (AME) on excision, incision, and dead space wound models in rats. AME (200 mg/kg) was administered orally once daily for variable days depending on the type of wound ulcer study. AME was studied for its wound breaking strength (incision wound), rate of contraction, period of epithelization and histology of skin (excision model), and granulation tissue free radicals, antioxidants, acute inflammatory marker, and connective tissue markers and deep connective tissue histology (dead space wound). Complete wound contraction and epithelization were observed at the 20th day after treatment with AME as compared to the 24th day in control rats. Mean epithelization period and scar area were decreased while wound breaking strength was increased with AME compared with control. Granulation tissue showed increased levels of collagen determinants (33.7 to 64.4%, P < 0.001) and antioxidants (13.0 to 38.8%, P < 0.05 to P < 0.001), whereas markers of oxidative stress (55.0 to 55.6%, P < 0.001) and myeloperoxidase (21.3%, P < 0.001) were decreased in AME treated group. A. marmelos seems to promote wound healing by enhancing connective tissue formation and antioxidants status with decrease in free radicals and myeloperoxidase having tissue damaging effects.

Antioxidant capacity and radical scavenging effect of polyphenol rich Mallotus philippenensis fruit extract on human erythrocytes: an in vitro study.

Mallotus philippinensis is an important source of molecules with strong antioxidant activity widely used medicinal plant. Previous studies have highlighted their anticestodal, antibacterial, wound healing activities, and so forth. So, present investigation was designed to evaluate the total antioxidant activity and radical scavenging effect of 50% ethanol fruit glandular hair extract (MPE) and its role on Human Erythrocytes. MPE was tested for phytochemical test followed by its HPLC analysis. Standard antioxidant assays like DPPH, ABTS, hydroxyl, superoxide radical, nitric oxide, and lipid peroxidation assay were determined along with total phenolic and flavonoids content. Results showed that MPE contains the presence of various phytochemicals, with high total phenolic and flavonoid content. HPLC analysis showed the presence of rottlerin, a polyphenolic compound in a very rich quantity. MPE exhibits significant strong scavenging activity on DPPH and ABTS assay. Reducing power showed dose dependent increase in concentration absorption compared to standard, Quercetin. Superoxide, hydroxyl radical, lipid peroxidation, nitric oxide assay showed a comparable scavenging activity compared to its standard. Our finding further provides evidence that Mallotus fruit extract is a potential natural source of antioxidants which have a protective role on human Erythrocytes exhibiting minimum hemolytic activity and this justified its uses in folklore medicines.

Curative effect of Terminalia chebula extract on acetic acid-induced experimental colitis: role of antioxidants, free radicals and acute inflammatory marker.

The present study has evaluated the healing effects of extract of dried fruit pulp of Terminalia chebula (TCE) on acetic acid (AA)-induced colitis in rats. TCE (600 mg/kg) showed healing effects against AA-induced colonic damage score and weight when administered orally daily for 14 days. TCE was further studied for its effects on various physical (mucus/blood in stool and stool frequency, food and water intake and body weight changes), histology, antibacterial activity and free radicals (NO and LPO), antioxidants (SOD, CAT and GSH) and myeloperoxidase in colonic tissue. Intra-colonic AA administration increased colonic mucosal damage and inflammation, mucus/bloody diarrhoea, stool frequency, but decreased body weight which were reversed by TCE and sulfasalazine (SS, positive control) treatments. TCE showed antibacterial activity and both TCE and SS enhanced the antioxidants, but decreased free radicals and myeloperoxidase activities affected in acetic acid-induced colitis. TCE indicated the presence of active principles with proven antioxidants, anti-inflammatory, immunomodulatory, and free radical scavenging and healing properties. Thus, TCE seemed to be safe and effective in healing experimental colitis.

Healing effects of Aegle marmelos (L.) Correa fruit extract on experimental colitis.

Graded doses of 50% ethanolic extract of dried fruit pulp of Aegle marmelos (AME) (100, 200 and 400 mg/kg) daily for 14 days in acetic acid (AA)-induced colitis in rats showed 200 mg/kg of AME as an optimal effective dose against AA-induced colonic damage score and weight. This dose (200 mg/kg; po) was further studied in AA-induced colitis for its effects on various physical (mucous/blood in stool, food and water intake and body weight changes), histology, antibacterial activity and biochemical parameters like free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase (acute-inflammatory marker) activities in rat colonic tissue. AME decreased colonic mucosal damage and inflammation (macroscopic and microscopic), mucous/bloody diarrhea, fecal frequency and increased body weight affected in AA-induced colitis. AME showed significant antibacterial activity and enhanced the antioxidants but decreased free radicals and myeloperoxidase activities thereby decreasing tissue damage and inflammation and thus, affording ulcer healing. The above effects of A. marmelos authenticated its use in indigenous system of Medicine.

Organic carbon effect on nitrifying bacteria in a mixed culture.

This study investigated the effect of organic carbon source on ammonia oxidizing community in single sludge laboratory scale sequencing batch reactors (SBR). Two sequencing batch reactors performing simultaneous carbon oxidation and nitrification were operated. Operationally and functionally, these two reactors were identical, except that one reactor was fed peptone and sodium acetate, and the other was fed glucose and sodium acetate as external organic carbon sources. The peptone-fed reactor had 98.1 + or - 1.84% COD removal and 97.3 + or - 6.69% NH(3)-N oxidation. The glucose-fed reactor had 99.1 + or - 1.29% COD removal and 99.4 + or - 0.76% NH(3)-N oxidation. The reactor fed with peptone, a complex organic carbon source comprised of enzymatic digests of animal proteins, had greater diversity in both the heterotrophic bacterial community and the ammonia oxidizing bacteria community than in the reactor fed with glucose, a simple sugar as evidenced by automated ribosomal intergenic spacer analysis (ARISA) and terminal restriction fragment length polymorphism (TRFLP) experiments respectively.

Immunomodulatory effect of Moringa oleifera Lam. extract on cyclophosphamide induced toxicity in mice.

Immunomodulatory effect of ethanolic extract (50%) of M. oleifera leaves (MOE) has been studied in normal and immunosuppressed mice models. Different doses of MOE i.e. 125, 250 and 500 mg/kg body weight of mice were administered orally for 15 days. Cyclophosphamide at a dose of 30 mg/kg body weight was administered orally for the next 3 days. On day 16 and 19, hematological parameters like white blood cell (WBC) count, red blood cell (RBC) count, haemoglobin level (Hb), percent neutrophils and organ weight were recorded. Effect of MOE on phagocytic activity of mice macrophages was determined by carbon clearance test. MOE showed significant dose dependent increase in WBC, percent neutrophils, weight of thymus and spleen along with phagocytic index in normal and immunosuppressed mice. The results indicate that MOE significantly reduced cyclophosphamide induced immunosuppression by stimulating both cellular and humoral immunity.

Anti-inflammatory, analgesic and antipyretic activity of aqueous extract of fresh leaves of Coccinia indica.

This study was aimed to evaluate both post- and pre-treatment anti-inflammatory activities of the aqueous extract of fresh leaves of Coccinia indica in rats using the carrageenan-induced paw oedema method at various dose levels. Analgesic and antipyretic properties were evaluated using tail flick model and yeast-induced hyperpyrexia, respectively. Ceiling effect of the extract was observed at 50 mg/kg in pre-treatment carrageenan test. In post-treatment studies, a dose-dependent anti-inflammatory effect was observed in the dose range of 25-300 mg/kg. The effect was equivalent to diclofenac (20 mg/kg) at 50 mg/kg but it was significantly pronounced at higher doses. Effectiveness of extract in the early phase of inflammation suggests the inhibition of histamine and serotonin release. The extract produced marked analgesic activity comparable to morphine at 300 mg/kg, which suggests the involvement of central mechanisms. A significant reduction in hyperpyrexia in rats was also produced by all doses of extract with maximum effect at 300 mg/kg comparable to paracetamol. In conclusion, this study has established the anti-inflammatory activity, analgesic and antipyretic activity of C. indica and, thus, justifies the ethnic uses of the plant.

Evaluation of wound healing activity of extracts of plantain banana (Musa sapientum var. paradisiaca) in rats.

Plantain banana (M. sapientum var. paradisiaca, MS) has been shown to possess ulcer healing activity. The present work with plantain banana was undertaken with the premise that the drug promoting ulcer healing could have effect on wound healing also. Wound healing activity of MS was studied in terms of (i) percent wound contraction, epithelization period and scar area; (ii) wound breaking strength and (iii) on granulation tissue antioxidant status [estimation of superoxide dismutase (SOD) and reduced glutathione (GSH), free radical (lipid peroxidation, an indicator of tissue damage) and connective tissue formation and maturation (hexuronic acid, hydroxyproline and hexosamine levels)] in excision, incision and dead space wound models respectively. The rats were given graded doses (50-200 mg/kg/day) of aqueous (MSW) and methanolic (MSE) extracts of MS orally for a period of 10-21 days depending upon the type of study. Both extracts (100 mg/kg) when studied for incision and dead space wounds parameters, increased wound breaking strength and levels of hydroxyproline, hexuronic acid, hexosamine, superoxide dismutase, reduced glutathione in the granulation tissue and decreased percentage of wound area, scar area and lipid peroxidation when compared with the control group. Both the extracts showed good safety profile. Plantain banana thus, favoured wound healing which could be due to its antioxidant effect and on various wound healing biochemical parameters.

Effect of methanolic extract of Pongamia pinnata Linn seed on gastro-duodenal ulceration and mucosal offensive and defensive factors in rats.

Pongamia pinnata has been advocated in Ayurveda for the treatment of various inflammatory conditions and dyspepsia. The present work includes initial phytochemical screening and study of ulcer protective and healing effects of methanolic extract of seeds of P. pinnata (PPSM) in rats. Phytochemical tests indicated the presence of flavonoids in PPSM. PPSM when administered orally (po) showed dose-dependent (12.5-50 mg/kg for 5 days) ulcer protective effects against gastric ulcer induced by 2 h cold restraint stress. Optimal effective dose of PPSM (25 mg/kg) showed antiulcerogenic activity against acute gastric ulcers (GU) induced by pylorus ligation and aspirin and duodenal ulcer induced by cysteamine but not against ethanol-induced GU. It healed chronic gastric ulcer induced by acetic acid when given for 5 and 10 days. Further, its effects were studied on various parameters of gastric offensive acid-pepsin secretion, lipid peroxidation (LPO) and nitric oxide (NO) and defensive mucosal factors like mucin secretion and mucosal cell shedding, glycoproteins, proliferation and antioxidants; catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) levels. PPSM tended to decrease acid output and increased mucin secretion and mucosal glycoproteins, while it decreased gastric mucosal cell shedding without any effect on cell proliferation. PPSM significantly reversed the increase in gastric mucosal LPO, NO and SOD levels caused by CRS near to the normal level while it tended to increase CAT and GSH level decreased by CRS and ethanol respectively. Thus, the ulcer protective effects of PPSM may be attributed to the presence of flavonoids and the actions may be due to its effects both on mucosal offensive and defensive factors.

Antidiabetic and antiulcer effects of extract of Eugenia jambolana seed in mild diabetic rats: study on gastric mucosal offensive acid-pepsin secretion.

Diabetes has been reported to increase propensity to peptic ulceration through its effect both on offensive and defensive mucosal factors. Seeds of Eugenia jambolana (EJ) have been reported to have both antidiabetic as well as ulcer protective effects. The present study evaluates the antidiabetic effects of ethanolic extract of dried seed kernel of Eugenia jambolana (EJE) and its comparative effect on gastric ulceration and acid-pepsin secretion with standard antisecretory FL-blocker. Ranitidine and antidiabetic glibenclamide with a premise that Eugenia jambolana may show better ulcer healing effects by promoting defensive or reducing offensive mucosal factors in mild diabetes (MD) rats. MD was produced in adult rats by administration of streptozotocin (45 mg/kg, ip). EJE was given orally in the doses of 100-400 mg/kg for 10 days and in the dose of 200 mg/kg for 30 days respectively to study its dose- and time-dependent effects on various diabetic parameters like blood glucose, serum cholesterol and triglycerides, insulin level and glycosylated hemoglobin. For ulcer protective and gastric secretion studies, EJE (200 mg/kg) was given orally for 10 days against 2 h cold restraint stress (CRS)-, 4 h pylorus ligation (PL), aspirin (ASP, 200 mg/kg, 4 h)--and 95% ethanol (EtOH, 1 ml/200 g, 1 h)-induced gastric ulcers and offensive acid-pepsin secretion after 4 h PL with co-occurring MD in rats. EJE showed dose-dependent decrease in blood glucose level in MD rats. Blood glucose level remained stable in mild diabetic rats from 3rd day onwards after streptozotocin administration (taken as 1st day for treatment) and EJE (200 mg/kg) showed anti-hyperglycemic effect on 10th day of its administration. Further, EJE in the above dose also decreased cholesterol level with little or no effect on triglycerides level and reversed the decrease and increase in insulin and glycosylated hemoglobin level near to the normal level as observed alter 30 days treatment in MD rats. MD rats exhibited an increased propensity to gastric ulceration induced by CRS, ASP, EtOH and PL and caused increase in acid-pepsin secretion. EJE was not only effective in reversing the increased propensity to ulceration in diabetic rats but also decreased the acid-pepsin output better than glibenclamide. The ulcer protective effect of Eugenia jambolana seems to be due to its antidiabetic and gastric antisecretory effects.

Ulcer healing properties of ethanolic extract of Eugenia jambolana seed in diabetic rats: study on gastric mucosal defensive factors.

Diabetes has been reported to cause an increase in offensive and decrease in defensive gastric mucosal factors, the imbalance of which can cause ulceration and delay the ulcer healing. Eugenia jambolana has been documented to have both antidiabetic and antiulcer activities. The present study evaluates the effects of ethanolic extract of E. jambolana on gastric ulcer healing and on rat gastric mucosal defensive factors in gastric ulcer with co-occurring diabetes. E. jambolana extract was administered orally in the dose of 200 mg/kg once daily for 10 days. E. jambolana extract increased mucin secretion, mucosal glycoprotein and glutathione levels and decreased the lipid peroxidation in gastric mucosa of diabetic rats. Its treatment also reversed the decrease in life span of gastric mucosal cells as indicated by decreased cell shedding in the gastric juice but found to have no effect on cell proliferation, indicating enhanced defensive status. E. jambolana extract was effective in reversing the delayed healing of gastric ulcer in diabetic rats near to the normal level. E. jambolana showed better ulcer healing effect than glibenclamide, because of its both antihyperglycemic and mucosal defensive actions. It could thus, be a better choice for treating gastric ulcers co-occurring with diabetes.

Ovarian steroid cell tumor, not otherwise specified.

Ovarian steroid cell tumours are rare virilizing tumours. They are three types of tumours of ovary which are characterized by steroid cell proliferation : Leydig cell tumour, steroid cell tumour, Not Otherwise Specified (NOS) and stromal luteoma. Here we present a case of 36 year old female, who presented with history of weight loss since last two and half months. There is history of amenorrhoea and hirsuitism. Her CA was 125: 11.4 IU/ml (0-35 U/mL). Blood Testosterone levels was elevated with value of 150 ng/ml (5.71-77 ng/ml). Serum Inhibin A, Inhibin B, FSH, LH and prolactin were within normal limits. The steroid cell tumour, NOS are mostly benign but few of them behave in malignant fashion. Hayes and Scully gave few histopathological features which favour malignant behavior. These tumours should be differentiated from leydig cell tumour by lack of cytoplasmic Reinkes' crystals as well as from other neoplasms like primary clear cell carcinoma, metastatic clear cell renal cell carcinoma and adrenocortical tumour.

Pharmacological repositioning of Achyranthes aspera as an antidepressant using pharmacoinformatic tools PASS and PharmaExpert: a case study with wet lab validation.

Traditional knowledge guides the use of plants for restricted therapeutic indications, but their pharmacological actions may be found beyond their ethnic therapeutic indications employing emerging computational tools. In this context, the present study was envisaged to explore the novel pharmacological effect of Achyranthes aspera (A. aspera) using PASS and PharmaExpert software tools. Based on the predicted mechanisms of the antidepressant effect for all analysed phytoconstituents of A. aspera, one may suggest its significant antidepressant action. The possible mechanism of this novel pharmacological effect is the enhancement of serotonin release, in particular caused by hexatriacontane. Therefore, pharmacological validation of the methanolic extract, hexatriacontane rich (HRF) and hexatriacontane lacking fraction (HLF) of A. aspera was carried out using the Forced Swimming Test and Tail suspension test in mice. The cortical and hippocampal monoamine and their metabolite levels were measured using high performance liquid chromatography (HPLC). A. aspera methanolic extract, HRF treatments showed a significant antidepressant effect comparable to imipramine. Further, the corresponding surge in cortical and hippocampal monoamine and their metabolite levels was also observed with these treatments. In conclusion, A. aspera has shown a significant antidepressant effect, possibly due to hexatriacontane, by raising monoamine levels.

Effect of ethanolic extract of root of Pongamia pinnata (L) pierre on oxidative stress, behavioral and histopathological alterations induced by cerebral ischemia--reperfusion and long-term hypoperfusion in rats.

Possible effect of an ethanolic root extract of Pongamia pinnata (L) Pierre (P. pinnata) on oxidant-antioxidant status and histopathological changes in acute ischemia-reperfusion injury in the rat forebrain have been investigated. Further, its effect was also assessed on long-term cerebral hypoperfusion-induced changes in anxiety, cognitive and histopathological parameters. Cerebral post-ischemic reperfusion is known to be associated with generation of free radicals. In the present study, bilateral common carotid artery occlusion (BCCAO) for 30 min followed by 45 min reperfusion produced increases in lipid peroxidation, superoxide dismutase (SOD) activity and a fall in the total tissue sulfhydryl (T-SH) levels. The ethanolic extract of roots of P. pinnata (50 mg kg(-1), po for 5 days) attenuated the ischemia-reperfusion-induced increase in lipid peroxidation, SOD activity and a fall in T-SH levels. The extract also ameliorated histopathological changes and inflammatory cell infiltration in the frontoparietal region of the rat brain. The extract (50 mg kg(-1), po for 15 days) was also found to alleviate the long-term hypoperfusion-induced anxiety and listlessness (open field paradigm). There was an improvement of learning and memory deficits (Morris' water maze testing). It also attenuated reactive changes in forebrain histology like gliosis, lymphocytic infiltration, astrocytosis and cellular edema. Results suggest protective role of P. pinnata in ischemia-reperfusion injury and cerebrovascular insufficiency states.

Effect of ethanolic extract of Eugenia jambolana seeds on gastric ulceration and secretion in rats.

Eugenia jambolana (Jamun) fruit has been reported to give soothing effect on human digestive system. Present study includes the effect of ethanolic extract of seeds of E. jambolana (EJE) against gastric ulcers induced by 2 h cold restraint stress (CRS), aspirin (ASP, 200 mg/kg, 4 h), 95% ethanol (EtOH, 1 ml/200 g, 1 h) and 4 h pylorus ligation (PL) in rats. To ascertain the mechanism of action of EJE, its effect was studied on mucosal offensive acid-pepsin secretion, lipid peroxidation (LPO, free radical) and defensive mucin secretion, cell proliferation, glycoprotein and glutathione (GSH, an antioxidant). Acute and subacute toxicity studies were also conducted for the safety profile of Eugenia jambolana. EJE 200 mg/kg, when administered orally for 10 days in rats was found to reduce the ulcer index in all gastric ulcer models. It tended to decrease acid-pepsin secretion, enhanced mucin and mucosal glycoprotein and decreased cell shedding but had no effect on cell proliferation. It showed antioxidant properties indicated by decrease in LPO and increase in GSH levels in the gastric mucosa of rats. Acute toxicity study indicated LD50 to be more than 10 times (>2000 mg/kg) of the effective ulcer protective dose while subactue toxicity study (>1000 mg/kg) indicated no significant change in the general physiological and haematological parameters, liver and renal function tests. The result of the present study indicates that E. jambolana seed has gastro-protective properties mainly through promotion of mucosal defensive factors and antioxidant status and decreasing lipid peroxidation.

Adenoid cystic carcinoma: a rare breast carcinoma.

Adenoid cystic carcinoma is a rare neoplasm accounting for <0.1% of breast carcinomas. The mean age of presentation is fifth to sixth decade of life and it generally presents as a painful breast lump. The histological features are characteristic with cribriform and acinar pattern of basaloid cells. It is triple negative tumor with CD117 and p63 positivity and excellent prognosis.

How good are publicly available web services that predict bioactivity profiles for drug repurposing?

Drug repurposing provides a non-laborious and less expensive way for finding new human medicines. Computational assessment of bioactivity profiles shed light on the hidden pharmacological potential of the launched drugs. Currently, several freely available computational tools are available via the Internet, which predict multitarget profiles of drug-like compounds. They are based on chemical similarity assessment (ChemProt, SuperPred, SEA, SwissTargetPrediction and TargetHunter) or machine learning methods (ChemProt and PASS). To compare their performance, this study has created two evaluation sets, consisting of (1) 50 well-known repositioned drugs and (2) 12 drugs recently patented for new indications. In the first set, sensitivity values varied from 0.64 (TarPred) to 1.00 (PASS Online) for the initial indications and from 0.64 (TarPred) to 0.98 (PASS Online) for the repurposed indications. In the second set, sensitivity values varied from 0.08 (SuperPred) to 1.00 (PASS Online) for the initial indications and from 0.00 (SuperPred) to 1.00 (PASS Online) for the repurposed indications. Thus, this analysis demonstrated that the performance of machine learning methods surpassed those of chemical similarity assessments, particularly in the case of novel repurposed indications.