Relationship of in vitro susceptibility to moxifloxacin and in vivo clinical outcome in bacterial keratitis.

BACKGROUND: For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation. METHODS: Data were collected as part of a National Eye Institute-funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation. RESULTS: Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040-.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010-.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86-.97; P = .005). CONCLUSIONS: In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC. CLINICAL TRIALS REGISTRATION: NCT00324168.

Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and protective effects against H2O2-induced oxidative damage to pBR322 DNA and red blood cells.

We evaluated the protective effects of subfractions of the ethyl acetate fraction (EAF) and the methanolic fraction (MF) from the crude ethanolic extract (CEE) of Azadirachta indica A. Juss (neem) leaves against various free radicals and hydrogen peroxide (H2O2)-induced oxidative damage to red blood cells (RBCs) and pBR322 DNA. Neem leaf fractions reduced DPPH(*), ABTS(*+), superoxide (O(*-)), hydroxyl (OH(*)), and nitric oxide radicals to nonradical forms in a concentration-dependent manner. Treatment with the benzene insoluble fraction from EAF (EBIF), the chloroform insoluble fraction from EAF (ECIF), the chloroform insoluble fraction from MF (MCIF), and the ethyl acetate insoluble fraction from MF (MEIF) significantly mitigated H2O2-induced oxidative damage to RBCs and pBR322 DNA. Although we found low in vitro free radical scavenging activity for the benzene insoluble fraction from EAF (EBSF), the chloroform soluble fraction from EAF (ECSF), the chloroform soluble fraction from MF (MCSF), and the ethyl acetate soluble fraction from MF (MESF), these fractions showed no effect on H2O2-induced lipid peroxidation and pBR322 DNA damage. High-performance liquid chromatography (HPLC) and TLC-Iatroscan analysis revealed that the greater efficacy of EBIF, ECIF, MCIF, and MEIF may be due to the presence of more polar compounds such as nimbolide and quercetin. Our studies suggest that the antioxidant and protective effects of active neem leaf fractions against H2O2-induced lipid peroxidation and pBR322 DNA damage can be attributed to their ability to inhibit various free radicals.

Combinatorial chemopreventive effect of Azadirachta indica and Ocimum sanctum on oxidant-antioxidant status, cell proliferation, apoptosis and angiogenesis in a rat forestomach carcinogenesis model.

INTRODUCTION: We investigated the combinatorial chemopreventive efficacy of Azadirachta indica (AI) and Ocimum sanctum (OS) against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis, based on changes in oxidant-antioxidant status, cell proliferation, apoptosis and angiogenesis. METHODS: Male Wistar rats were assigned to four groups. Rats in groups 1 and 2 received MNNG (150 mg/kg body weight i.g.) three times with a gap of two weeks in between the treatment. Group 2 rats additionally received ethanolic AI (100 mg/kg body weight i.g.) and OS (150 mg/kg body weight i.g.) leaf extract three times per week for 26 weeks. Group 3 animals were given AI and OS leaf extract alone, whereas group 4 served as the control. RESULTS: Lipid and protein oxidation and status of the antioxidants, superoxide dismutases, catalase, reduced glutathione (GSH) and GSH-dependent enzymes together with markers of proliferation (proliferating cell nuclear antigen [PCNA], glutathione S-transferase-Pi [GST-P]), invasion (cytokeratin [CK]), angiogenesis (vascular endothelial growth factor [VEGF]) and apoptosis (Bcl-2, Bax, cytochrome C and caspase-3) were used to biomonitor chemoprevention. Rats administered MNNG developed forestomach carcinomas that displayed low lipid and protein oxidation coupled to enhanced antioxidant activities, and overexpression of PCNA, GST-P, CK, VEGF and Bcl-2 with downregulation of Bax, cytochrome C and caspase-3. Coadministration of AI and OS extract suppressed MNNG-induced gastric carcinomas accompanied by modulation of the oxidant-antioxidant status, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. CONCLUSION: The results of the present study suggest that chemoprevention by AI and OS combination may be mediated by their antioxidant, antiangiogenic, antiproliferative and apoptosis inducing properties.

Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and in vivo modulation of biomarkers of chemoprevention in the hamster buccal pouch carcinogenesis model.

We evaluated the chemopreventive potential of Azadirachta indica (neem) leaf fractions based on in vitro antioxidant assays, and in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. In addition we also identified the major constituents in neem leaf fractions by HPLC. Analysis of the free radical scavenging activities and reducing potential of crude ethanolic extract (CEE), ethyl acetate fraction (EAF) and methanolic fraction (MF) of neem leaf revealed a concentration-dependent increase in antioxidant potential that was in the order EAF>MF>CEE. Administration of neem leaf fractions reduced the incidence of DMBA-induced HBP carcinomas at a lower concentration compared to the crude extract. Chemoprevention by neem leaf fractions was associated with modulation of phase I and phase II xenobiotic-metabolising enzymes, lipid and protein oxidation, upregulation of antioxidant defences, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. However, EAF was more effective than MF in terms of antiproliferative and antiangiogenic effects, and expression of CYP isoforms. The greater efficacy of EAF may be due to higher content of constituent phytochemicals as revealed by HPLC analysis. The results of the present study suggest that the antioxidant properties of neem leaf fractions may be responsible for modulating key hallmark capabilities of cancer cells such as cell proliferation, angiogenesis and apoptosis in the HBP carcinogenesis model.

Ethno- medico - botanical studies of Badaga population In the Nilgiri district of Tamilnadu, South India.

The study grains to explore ethno-medicobotany of Badaga population in the Nilgiri hills of Tamilnadu, South India. Ethno botanical field survey and personal discussion methods have been adopted in the collection of data. A list of 71 flowering plants belonging to 42 families, 67 genera and 70 species are employed by the Badaga popu-lation in their native system of medicine for therapeutic purposes. In reviewing ethnomedical information, data on folk herbal remedies and their various methods of applications for treating a wide range of ailments have been furnished. A brief description of plants, their habitat, family and local Badaga names are outlined here.

Ocimum sanctum Linn. (Holy Basil) ethanolic leaf extract protects against 7,12-dimethylbenz(a)anthracene-induced genotoxicity, oxidative stress, and imbalance in xenobiotic-metabolizing enzymes.

The present study was designed to evaluate the protective effects of ethanolic Ocimum sanctum leaf extract against 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity, oxidative stress, and imbalance in xenobiotic-metabolizing enzymes. Four different concentrations of ethanolic O. sanctum leaf extract (100, 200, 300, and 400 mg/kg of body weight) were administered to Wistar rats by intragastric intubation for five consecutive days followed by intraperitoneal injection of DMBA (35 mg/kg of body weight) 90 minutes after the final dose of the extract. Administration of DMBA increased bone marrow micronuclei, phase I enzymes, lipid peroxidation, and protein carbonyl formation. This was accompanied by a significant decrease in the activities of phase II detoxification enzymes and antioxidants in the liver, erythrocytes, and bone marrow. Pretreatment with ethanolic O. sanctum leaf extract at a concentration of 300 mg/kg of body weight significantly reduced micronuclei formation and phase I enzymes as well as lipid and protein oxidation with enhanced antioxidant and phase II enzyme activities. The results of the present study suggest that ethanolic O. sanctum leaf extract inhibits DMBA-induced genotoxicity and oxidative stress by modulating xenobiotic-metabolizing enzymes, reducing the extent of lipid and protein oxidation and up-regulating antioxidant defenses.

Proliferation, angiogenesis and apoptosis-associated proteins are molecular targets for chemoprevention of MNNG-induced gastric carcinogenesis by ethanolic Ocimum sanctum leaf extract.

INTRODUCTION: This study was designed to evaluate the chemopreventive effects of ethanolic Ocimum sanctum (OS) leaf extract on cell proliferation, apoptosis and angiogenesis during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis. METHODS: The rats were divided into four groups of ten each. Rats in group one were given MNNG (150 mg/kg body weight) by intragastric intubation three times, with a two-week interval between treatments. Rats in group two were administered MNNG as in group one, and in addition, they received intragastric intubation of ethanolic OS extract (300 mg/kg body weight) three times per week, starting on the day following the first exposure to MNNG. The intubation of ethanolic OS extract continued until the end of the experimental period. Rats in group three were given ethanolic OS leaf extract only. Group four served as controls. All the rats were killed after an experimental period of 26 weeks. RESULTS: Intragastric administration of MNNG-induced well-differentiated squamous cell carcinomas that showed increased cell proliferation, and angiogenesis with evasion of apoptosis, as revealed by the upregulation of proliferating cell nuclear antigen (PCNA), glutathione S-transferase-pi (GST-pi), Bcl-2, cytokeratin (CK) and vascular endothelial growth factor (VEGF) and with downregulation of Bax, cytochrome C and caspase 3 protein expression. Administration of ethanolic OS leaf extract reduced the incidence of MNNG-induced gastric carcinomas. This was accompanied by decreased expression of PCNA, GST-pi, Bcl-2, CK and VEGF, and overexpression of Bax, cytochrome C, and caspase 3. CONCLUSION: This study provides evidence that, in MNNG-induced gastric carcinogenesis, the key proteins involved in the proliferation, invasion, angiogenesis and apoptosis, are viable molecular targets for chemoprevention using ethanolic OS leaf extract.

Folk herbal medicine: a survey on the paniya tribes of mundakunnu village of the nilgiri hills, South India.

The present paper represents the results of an ethnobotanical survey conducted in Mundakunnu village of Gudalur taluk, Nilgiri district of Tamil Nadu, India. It has been observed that the plant species are used to various ailments of analgesic, antidiarrhoeal, piles, antidiabetic, gynecological problems, vermifuge, antidandruff, venereal diseases, bone fracture and as vegetables. A total of 52 plants species belonging to 51 genera (33 dicot & 6 monocot) have been discussed.