Safety evaluation of standardized Ayurvedic formulation-Panchvalkala, by subacute toxicity study.

ETHNOPHARMACOLOGICAL RELEVANCE: Panchvalkala is a conventional Ayurvedic medicine used as a douche in gynecological disorders such as leucorrhea, infertility, and endometriosis. Recently, we have reported the anticancer activity of Panchvalkala aqueous extract (PVaq) in cervical cancer cell lines, SiHa (HPV16+), HeLa (HPV18+), and mouse papilloma models. AIM OF THE STUDY: Here, we have evaluated the safety of the aqueous extract of Ayurvedic formulation, Panchvalkala (PVaq), in Swiss albino mice by performing subacute toxicity study. MATERIALS AND METHODS: Male and female Swiss albino mice (n = 5/sex/group) were gavaged orally with different doses of PVaq for 28 consecutive days. The mice were distributed into six groups: I (vehicle control), II (vehicle control reversal), III (PVaq 250 mg/kg), IV (PVaq 500 mg/kg), V (1000 mg/kg) and VI (1000 mg/kg high dose reversal). Animals were observed periodically to record any clinical signs of toxicity or mortality. After completion of treatment and recovery periods, animals were evaluated for the effect of PVaq on urine parameters, followed by hematological and biochemical parameters. Animals were sacrificed on day 29 for gross observation of vital organs and to study their histopathology. Reversal groups were maintained for further 14 days to observe any delayed onset of toxic side effects or reversal of toxicity, followed by sacrificing the mice on day 43. RESULTS: In the subacute toxicity study, PVaq did not show any significant change in food, water consumption, and body weights. There were no significant alterations in hematology, biochemistry, urine parameters, and histopathology of the analyzed tissues (brain, heart, liver, lung, spleen, thymus, kidney, epididymis/ovaries, and testis/uterus). The parameters were comparable to their respective controls in both the female as well as the male mice groups. Upon macroscopic and microscopic observation of vital organs, no abnormality was detected compared to the respective control groups. CONCLUSION: The subacute toxicity study demonstrated that oral administration of PVaq was safe in female and male Swiss albino mice.

Nanoparticles of biotite mica as KrishnaVajraAbhraka Bhasma: synthesis and characterization.

BACKGROUND: Bio-inorganic nanoparticles or metal nanoparticles are used in medicine for diagnostic and treatment purposes. The nanomedicines from traditional Ayurvedic system are termed as bhasma. Rasashastra, the branch of inorganic medicines of Ayurveda, has documented monographs of metal-mineral bhasmas as potent drugs. However there is lack of scientific analytical data of the end products. OBJECTIVES: Present study was aimed at finding out the morphological, structural, elemental and chemical composition of the Krishna vajra abhraka bhasma (KVB). MATERIALS AND METHODS: Bhasma of KVB (Biotite Mica) was prepared in our laboratory using biotite mica sheets befitting selection criteria and carrying out further processes with strict SOPs as per AFI. RESULTS: The bhasma complied with the confirmatory tests from Rasashastra. The physical and physicochemical tests correlate with the results obtained by instrumental analytical methods. SEM revealed square shaped nanoparticles of mean size of 92.3 nm. EDAX showed presence of Si, Mg, O, Fe, Ca, Na, C, K and Al. XRD revealed the crystalline nature of bhasma with mixture of various individual oxides and spinel shape of the crystal. DLS showed that the nanoparticles are unimodal in nature. FTIR and NMR showed the organic functional groups obtained from cow milk and selected herbs, indicating unique bio-inorganic nature of the KVB. CONCLUSION: The therapeutic potential imparted to the formulation could be due to the cow milk and specific herbs utilized during the manufacturing process.

Synergistic Effect of Omega-3 Fatty Acids and Oral-Hypoglycemic Drug on Lipid Normalization through Modulation of Hepatic Gene Expression in High Fat Diet with Low Streptozotocin-Induced Diabetic Rats.

Type 2 diabetes mellitus, which an outcome of impaired insulin action and its secretion, is concomitantly associated with lipid abnormalities. The study was designed to evaluate the combinational effect of omega-3 fatty acids (flax and fish oil) and glibenclamide on abnormal lipid profiles, increased blood glucose, and impaired liver and kidney functions in a high fat diet with low streptozotocin (STZ)-induced diabetic rats, including its probable mechanism of action. The male Wistar rats (n = 48) were distributed into eight groups. All animal groups except the healthy received a high fat diet (HFD) for 90 days. Further, diabetes was developed by low dose STZ (35 mg/kg). Diabetic animals received, omega-3 fatty acids (500 mg/kg), along with glibenclamide (0.25 mg/kg). Both flax and fish oil intervention decreased (p ≤ 0.001) serum triglycerides and very low density lipoprotein and elevated (p ≤ 0.001) high density lipoprotein levels in diabetic rats. Total cholesterol and low-density lipoprotein level was decreased (p ≤ 0.001) in fish oil-treated rats. However, it remained unaffected in the flax oil treatment group. Both flax and fish oil intervention downregulate the expression of fatty acid metabolism genes, transcription factors (sterol regulatory element-binding proteins-1c and nuclear factor-κß), and their regulatory genes i.e., acetyl-coA carboxylase alpha, fatty acid synthase, and tumor necrosis factors-α. The peroxisome proliferator-activated receptor gamma gene expression was upregulated (p ≤ 0.001) in the fish oil treatment group. Whereas, carnitine palmitoyltransferase 1 and fatty acid binding protein gene expression were upregulated (p ≤ 0.001) in both flax and fish oil intervention group.

Bioequivalence of generic and branded amoxicillin capsules in healthy human volunteers.

CONTEXT: The Medical Council of India urges doctors to prescribe generic drugs as far as possible. The Indian Medical Association had responded earlier saying that it requires guarantees on the quality of generic forms of drugs. Although no published scientific reports are available on the issue of therapeutic inequivalence, unconfirmed clinician accounts and newspaper reports of therapeutic inequivalence exist. AIM: This study was planned to ascertain whether bioequivalence of branded and generic amoxicillin capsule is comparable. SETTINGS AND DESIGN: An open-label, randomized, single-dose, two-treatment, two-sequence, two-period crossover oral bioequivalence study was conducted in 12 healthy, adult human subjects under fasting condition. MATERIALS AND METHODS: Serum samples, collected at 8 time points, were analyzed by a validated ultraviolet spectrophotometer method. Pharmacokinetic (PK) parameters such as area under the curve (AUC)0-t, AUC0-∞, Cmax, and Tmax were determined along with time above minimum inhibitory concentration (MIC). STATISTICAL ANALYSIS USED: The log-transformed PK parameters (Cmax, AUC0-t, AUC0-∞) were analyzed using a Two One-Sided Test ANOVA in SAS for each parameter. Tmax and MIC were analyzed by Wilcoxon rank-sum test in GraphPad Prism. RESULTS: Geometric mean ratio of Cmax fell within bioequivalence criteria. The upper and lower confidence limits of both AUC0-t and AUC0-∞ geometric mean ratio fell below bioequivalence criteria. Time above MIC of generic preparation was significantly lower than that of branded version. CONCLUSIONS: The generic capsule was not bioequivalent to the branded amoxicillin capsule.

Hepatoprotective Activity of Satwa, an Ayurvedic Formulation, Against Alcohol-induced Liver Injury in Rats.

Context • Guduchi Satwa is an Ayurvedic formulation prepared from Tinospora species. It has been used since ancient times to treat liver disorders. Objectives • The study intended to assess the hepatoprotective potential of Satwa prepared from 3 forms of Tinospora against alcohol-induced hepatotoxicity. Design • Male, albino Wistar rats were divided into 6 groups, with 6 rats each: 3 control groups-healthy controls, negative controls, and positive controls-and 3 intervention groups-Tinospora cordifolia, Tinospora sinensis, and Neem-Guduchi. Setting • The study was carried out at the Animal House facility of Bharati Vidyapeeth Deemed University's Medical College (Maharashtra, India). Intervention • Hepatotoxicity was induced by repeated dosing with alcohol for 15 d for all groups except for the healthy controls. To induce hepatotoxicity, the 5 groups received 1 mL of 30% alcohol PO per 100 g of body weight per day. The healthy controls and the negative controls received no hepatoprotective treatments. The other 4 groups received the dosing with alcohol 30 min after the hepatoprotective treatment, which they also received for 15 d: (1) positive controls-100 mg of silymarin per kg of body weight per day PO; (2) intervention group 1 (T cordifolia group)-200 mg of T cordifolia per kg of body weight per day PO; (3) intervention group 2 (T sinensis group)-200 mg of T sinensis per kg of body weight per day PO; and (4) intervention group 3 (Neem-Guduchi group)-200 mg of Neem-Guduchi per kg of body weight per day PO. Outcome Measures • Serum and liver tissue were used for biochemical analysis. Results • For the negative and positive control groups and the 3 intervention groups, the repeated dosing with alcohol produced elevations in the levels of liver-marker enzymes and changes in the lipid-profile status of the animals. Satwa from T cordifolia had a specific action in maintaining the lipid profile: total cholesterol, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein. Improvement in the hepatic function, normalization of the lipid profile in the serum and liver, and improvements in the levels of antioxidant enzymes and oxidative-stress markers were observed in the animals treated with T sinensis Satwa. Neem-Guduchi Satwa was found to have a specific action in maintaining the lipid profile. The differential hepatoprotective effect of that Satwa was also evident from the liver histology. Conclusions • The data suggest that the 3 Satwa might be used in combination as a liver tonic that can help restore and strengthen the liver functions. The current study shows that the combination has the potential to be an effective liver tonic in animals. Scientific data from clinical trials of the 3 Satwa are not available. Systematic clinical trials are required that can yield information on their effects in humans.

Antidiabetic, Lipid Normalizing, and Nephroprotective Actions of the Strawberry: A Potent Supplementary Fruit.

The study was designed to assess the effect of different strawberry extracts on glucose levels, lipid profiles, and oxidative stress in nicotinamide-streptozotocin (NIC-STZ) induced diabetic rats. The associated changes were evaluated through biochemical, molecular, and histological assays. Diabetes was induced by intraperitoneal injection of STZ to albino Wistar rats after treatment with nicotinamide. Aqueous, hydroalcoholic, and alcoholic strawberry extracts were administrated orally to diabetic rats. Treatment of strawberry extracts improved lipid profile, liver function, and serum creatinine and led to a significant increase in antioxidant status in diabetic rats. Real-time PCR expression analysis of genes from the liver of animals treated with strawberry extracts exhibited downregulation of several fatty acid synthesis genes, transcription factors, such as Sterol regulatory Element Binding Transcription factor (SREBP) and Nuclear Factor-κß (NF-κß), and inflammatory markers, like Interleukin 6 (IL6) and Tumor Necrosis Factor-α (TNF-α). Strawberry extracts also upregulated liver Peroxisome Proliferator Activated Receptor-γ (PPAR-γ). Histological examination confirmed the nephroprotective and ß-cell regeneration/protection effects of strawberry extracts. The present study demonstrates several beneficial effects of strawberry extracts along with its probable mechanism of action.

Evaluation of Effect of Nishamalaki on STZ and HFHF Diet Induced Diabetic Neuropathy in Wistar Rats.

INTRODUCTION: Diabetic neuropathy is one of the most common complications affecting 50% of diabetic patients. Neuropathic pain is the most difficult types of pain to treat. There is no specific treatment for neuropathy. Nishamalaki (NA), combination of Curcuma longa and Emblica officinalis used to treat Diabetes Mellitus (DM). So, efforts were made to test whether NA is useful in prevention of diabetic neuropathy. AIM: To evaluate the effect of NA on diabetic neuropathy in type 2 diabetic wistar rats. MATERIALS AND METHODS: Group I (Control) vehicle treated consists of 6 rats. Diabetes induced in 36 wistar rats with Streptozotocin (STZ) (35mg/kg) intra-peritoneally followed by High Fat High Fructose diet. After confirmation of development of diabetes; rats divided into six groups (n=6). Group II - VII Diabetic Control, NA low dose, NA High dose, Glibenclamide, Pioglitazone and Epalrestat. Animals received drug treatment for next 12 weeks. Monitoring of Blood Sugar Level (BSL) done every 15 days and lipid profile at the end. Eddy's hot plate and tail immersion test performed to assess thermal hyperalgesia and cold allodynia. Walking function test performed to assess motor function. RESULTS: Diabetic rats exhibited significant (p<0.001) hyperalgesia and increased BSL compared to control rats. Dose-dependent improvement was observed in thermal hyperalgesia & cold allodynia in NA groups. Activity of NA was more than Glibenclamide, Epalrestat and Pioglitazone in high dose and comparable in low dose. Nishamalaki improved lipid profile. CONCLUSION: Apart from controlling hyperglycaemia and reducing lipid levels, NA effectively prevented the development of diabetic neuropathy.

Comparative anti-inflammatory and lipid-normalizing effects of metformin and omega-3 fatty acids through modulation of transcription factors in diabetic rats.

BACKGROUND: Emerging evidence suggests beneficial effects of omega-3 fatty acids on diabetic complications. The present study compared the progressive effects of metformin and flax/fish oil on lipid metabolism, inflammatory markers, and liver and renal function test markers in streptozotocin-nicotinamide-induced diabetic rats. METHODS: Streptozotocin-induced diabetic rats were randomized into control and four diabetic groups: streptozotocin (STZ), metformin (200 mg/kg body weight (b.w)/day (D)), flax and fish oil (500 mg/kg b.w/D). RESULTS: Metformin and flax and fish oil exhibited increased expression of transcription factor peroxisome proliferator-activated receptor γ while the treatment downregulated sterol regulatory element-binding protein 1 and nuclear factor kß as compared to those of the STZ group. Apart from modulation of transcription factor expression, the expression of fatty acid synthase, long chain acyl CoA synthase, and malonyl-CoA-acyl carrier protein transacylase was lowered by flax/fish oil treatment. Serum cholesterol, triglycerides, and VLDL were also significantly reduced in the treatment groups as compared to those in the STZ group. Although pathological abnormalities were seen in the liver and kidneys of rats on metformin, no significant changes in liver/renal function markers were observed at day 15 and day 30 of the treatment groups. Flax/fish oil had protective effects toward pathological abnormalities in the liver and kidney. Flax/fish oil improved lipid profile and alkaline phosphatase at day 30 as compared to that at day 15. CONCLUSIONS: The present study demonstrates potential beneficial effects of metformin and flax/fish oil intervention in improving serum lipid profile by regulating the expression of transcription factors and genes involved in lipid metabolism in diabetic rats. In addition, these interventions also lowered the expression of atherogenic cytokines. The protective effects of flax/fish oil are worth investigating in human subjects on metformin monotherapy.

Preventive and Protective Effect of Nishamalaki in STZ Induced Diabetic Complications in Wistar Rats.

INTRODUCTION: Diabetes is a metabolic disease of vital health importance because of the complications associated with it. Clinical trials and animal studies have demonstrated the anti-hyperglycaemic effect of Nishamalaki. Present study was planned to evaluate the protective potential of Nishamalaki on diabetic complication in rats. AIM: To study the Nephro-protective effect and to assess the protective potential on retinal changes of Nishamalaki in diabetic wistar rats. MATERIALS AND METHODS: Diabetes induced with 60 mg/kg of Streptozotocin and 110 mg/kg Nicotinamide IP. Nishamalaki, a combination of Curcuma longa and Emblica officinalis administered orally with honey. Rats divided into six groups, control and diabetic rats with blood glucose above 250 mg/dl were divided into 5 groups. After 8 weeks test animals were treated with Nishamalaki, Enalapril and control with saline for 30 days. Biochemical parameters measured like Serum BSL, BUN and Creatinine and rats were observed for development of cataract. Rats sacrificed and kidney samples were taken to examine histopathological changes. RESULTS: Blood Urea Nitrogen and Creatinine values were significantly (p<0.01) reduced in Nishamalaki group than control group. Nishamalaki showed the protective effect on kidney pathology as seen on histopathology by near normal glomerular and tubular structures. Control group showed shrunken glomerulus and tubular vacuolations. In Nishamalaki group immature sub capsular cataract with mild lenticular opacity were seen compared to the mature cataract with significant lenticular opacity and corneal vascularisation in control group. CONCLUSION: Nishamalaki showed protective effect on development of Nephrotoxicity and it has also delayed the progression of cataract in rats.

Antibiotic Prescribing Pattern in a Tertiary Level Neonatal Intensive Care Unit.

INTRODUCTION: Neonatal sepsis is a major cause of morbidity and mortality worldwide especially in developing countries, which justifies early diagnosis and prompt treatment with antibiotics. Antibiotics are the most frequently used medicines in Neonatal Intensive care units. Data regarding rational antibiotic use in neonates is very limited. Hence, it is essential that the antibiotic prescribing patterns be evaluated periodically for its rational use. Therefore, the present study been carried out to identify the prescribing patterns of antibiotics in neonatal intensive care unit of a tertiary care hospital, Western Maharashtra, India. MATERIALS AND METHODS: A prospective observational study was carried out for 6 months between April to September 2014. The data regarding patient demographics and antibiotic use was collected daily in a structured proforma. Collected data was subjected to statistical analysis. RESULTS: Out of total 528 neonates with male preponderance (62%), 370 received antibiotics. Mean gestational age and birth weight were 35±3.2 weeks and 2±0.7 kg respectively. Mean length of hospital stay was 14.26±15.36 days (range 1 to 136 days). A total of 1123 antibiotics were prescribed to 370 neonates. The majority of neonates (55.9%) received between 1-2 antibiotics, 37.3% had 3 to 5 antibiotics prescribed, while 6.7% neonates were prescribed more than 5 antibiotics. Number of antibiotics used had statistically significant inverse relationship with gestational age. Among antibiotics; Amikacin, Cefotaxime and Levofloxacin were the drugs most often prescribed. Amikacin and Cefotaxime were given more to term infants whereas other antibiotics like Levofloxacin, Pipercillin- tazobactam and Meropenem were prescribed more to preterm and outborn neonates. CONCLUSION: The use of a high number of antibiotics is a common practice. Although the indications for use of most antibiotics could be justified, the increased frequency of anbiotics use in some neonates was of concern. Guidelines for the use of antibiotics in neonates are required and larger studies are needed on this issue.

Add-on Effect of Levetiracetam on Cognitive Activity of Carbamazepine and Topiramate Treated Healthy Rats.

BACKGROUND: Many antiseizure drugs are used for non-epileptic indications like bipolar disorder, anxiety, neuropathic pain, prophylaxis of migraine, etc. Cognitive problems are known with many of these agents in epileptic situations but not to that extent in other situations. The antiepileptic Levetiracetam has been shown to improve a range of cognitive abilities. OBJECTIVE: To study the effect of levetiracetam, carbamazepine, topiramate and co-administration of levetiracetam with carbamazepine and topiramate on cognition in healthy rats. MATERIALS AND METHODS: Wistar albino rats of either sex were randomly assigned to 6 groups (n=6). Treatment groups: I - Normal saline; II, III & IV- Levetiracetam (180mg/kg), Carbamazepine (50mg/kg) and Topiramate (20mg/kg) respectively; V & VI- Levetiracetam + Carbamazepine and VI- Levetiracetam + Topiramate respectively orally for 21 days. Morris Water Maze was used to study the spatial learning and memory in rats and the change in Escape transfer latency (ETL) was recorded to see the effect of drugs on it. Data analyzed by ANOVA followed by Dunnett's post-hoc test. RESULTS: Twenty one days drug treatment significantly increased the ETL in rats treated with Topiramate (p=0.0001) and combination of Levetiracetam and Topiramate (p<0.0001) from their baseline values. At the same time, there was significant reduction in the time spent in target quadrant in Topiramate group (p= 0.033) and the combination group of Topiramate + Levetiracetam (p=0.026). No significant change was observed in the other groups when tested for both these parameters. CONCLUSION: Topiramate causes impairment of spatial memory in healthy rats after 21 days exposure and its combination with Levetiracetam could not overcome this cognitive deficit.

Perception of pharmacovigilance among doctors in a tertiary care hospital: influence of an interventional lecture.

INTRODUCTION: One of the important pillars of an efficient pharmacovigilance system is contribution by healthcare professionals in the form of spontaneous reporting. This study was aimed at investigating the knowledge, attitude and practice of spontaneous ADR reporting among doctors in a teaching hospital in Pune, and to analyze the effect of an informative lecture about Pharmacovigilance on the same. METHODOLOGY: This was an interventional study conducted among 220 doctors at a tertiary care teaching hospital, Pune. Each participant was explained the purpose of study and asked to fill in a questionnaire about their knowledge, attitude and practice of pharmacovigilance. Only 80 of them attended the interventional lecture on Pharmacovigilance and again filled up the questionnaire after a period of one month from this intervention. RESULTS: Merely 7.5% of the participants knew ADR reporting system in India. Majority of the respondents (95%) knew that, as doctors, they could report ADRs but were unaware about the methodology to report (92.5%) which affected their practice of Pharmacovigilance. All (100%) the participants expressed that proper training should be provided to clinicians for ADR reporting & 81% felt ADR reporting should be made mandatory. Only 80 participants (36.4%) attended the interventional lecture which reflected a poor response. Intervention improved their (96%) knowledge about ADR reporting system and now majority of them (92%) agreed that all sort of ADRs should be reported (p < 0.001). CONCLUSION: Attitude towards ADR reporting was positive but knowledge about ADR reporting system was inadequate among doctors working in a teaching hospital in Pune. Education helped in improving knowledge and had an impact on attitude of participants regarding pharmacovigilance.

The Pattern of Drug Use in Acute Fever by General Practitioners (GPs) in Pune City, India.

OBJECTIVES: 1) To determine the WHO Prescribing Core Drug Use (PCDU) indicators in the management of acute fever (of less than 2 weeks duration) of the MBBS (allopathic) and BAMS (ayurvedic) General Practitioners (GPs) in Pune city. 2) To verify the appropriateness of the treatment. and 3) To compare the above parameters of the MBBS and the BAMS practitioners. METHODS: Pune city was divided in five zones, north, south, east, west and central. A list of doctors was obtained from the Indian Medical Association and it was divided zone wise. 2 MBBS and 2 BAMS GPs. were selected per zone. An informed consent was obtained from the GPs. The sample size was 20 encounters per GP. The patients of all ages and both sexes, who suffered from fever of less than 2 weeks duration, were included in the study. The indicators which were studied were 1) the WHO Prescribing Core Drug Use indicators and 2) the complimentary drug use indicators for the appropriateness of the treatment. RESULTS: 1) The age, sex and diagnosis wise distribution of the patients was comparable in both the groups. 2) Among the WHO PCDU indicators, a highly significant difference was observed in the average number of drugs which was prescribed, the antibiotic usage and in the injections which were prescribed among the MBBS and the BAMS GPs 3) The use of the drugs from EDL and that of the generic drugs were comparable in both the groups.4) A marked irrationality was found in the injectable antimicrobials by the BAMS GPs.5) The selection of the antimicrobials was inappropriate in 64.14% and 17.5% of the encounters which were made by the BAMS and the MBBS GPs respectively. CONCLUSION: Among the BAMS GPs: the WHO prescribing core drug use indicators were all significantly abnormal and the percentage of the inappropriate prescriptions was alarmingly high (92%). Among the MBBS GPs: There was more use of the antimicrobials but the proportion of the inappropriate prescriptions was less (42%).

Anti-nociceptive Effect of Entada Phaseoloides Seeds Formulation after Topical Application in Arthritic Wistar Rats.

OBJECTIVES: To study the effect of topical application of different formulations of Entada phaseoloides seeds for analgesic activity in arthritic wistar rats. MATERIAL AND METHODS: EP (Entada Phaseoloides) seeds were powdered after removing the shell. Paste was prepared by adding water and ointment with polyethylene glycol (PEG 400) & Carbowax 3350. 32 Wister rats of either sex weighing 150-200 gms were divided into four groups ,Gr-I vehicle, Gr-II EP paste, Gr-III EP Ointment, Gr-IV Diclofenac Sodium Ointment. For induction of arthritis 0.1ml Complete Freund's Adjuvant (CFA) was given by intra-articular injection in left knee joint. Drug treatment was started on the same day by topical application in all groups respectively. Pain threshold for referred pain was measured on Randall Selitto analgesymeter before and after drug treatment. RESULTS: At 0 hours pain threshold of animals from all the groups was approximately similar. Pain threshold in control group was statistically significantly decreased at 72 hours. In comparison with control there was significant (p<0.001) increase in the pain threshold in the EP treated groups after 72 hours. CONCLUSION: Both the formulations of EP have analgesic activity comparable to Diclofenac sodium.

Understanding redox homeostasis and its role in cancer.

When a cell is damaged or altered without repair to its system, it usually dies. But if such damaged or unrepaired cells do not die and proliferate with uncontrolled growth; a mass of cancer cells develop. Cancer has a complex aetiology with multiple risk factors that involve the interplay between genetic and environmental influences. The redox dysregulation originates from metabolic alterations and it is dependent on mitogenic and survival signalling through reactive oxygen species. There is a delicate balance between the production and the destruction of reactive species; for this, we need to understand the role of redox homeostasis in cancer. So, the specific vulnerability of the malignant cells can be selectively targeted. This article will outline the redox homeostasis and the relationship between the disturbances in it and cancer.

Experimental evaluation of anti-inflammatory effect of topical application of entada phaseoloides seeds as paste and ointment.

AIMS: The study was to study the anti-inflammatory effect of topical application of different formulations of seed pulp of entada phaseoloides. METHOD AND MATERIAL: After removing the shell, entada phaseoloides seeds were powdered. Paste was prepared with water and ointment with polyethylene glycol & Carbowax 3350. 32 Wister rats of either sex weighing 140-200 gram were divided into four groups, Group-I vehicle, Group-II entada phaseoloides paste, Group-III entada phaseoloides Ointment, Group-IV Diclofenac sodium Ointment. Arthritis was induced by injecting 0.1ml Complete Freund's adjuvant in sub plantar region of the left hind paw. Drug treatment was started on the same day and given for 12 days. Paw volume was measured with Plethysmometer on day 0, 1, 5, 12 and 21 for both the paws. Bodyweight and Gait was observed throughout the study. RESULTS: Localized inflammatory reaction developed in all the rats in 24 hours. In control group, there was no resolution of swelling even in 21 days. Both EP formulations showed significant (P < 0.001) anti-inflammatory activity as compared to control. entada phaseoloides ointment was equi-effective to that of Diclofenac sodium on 12(th) day. entada phaseoloides paste was significantly (P < 0.05) more effective than Diclofenac sodium on 21(st) day. CONCLUSION: Both the formulations of entada phaseoloides have anti-inflammatory activity and entada phaseoloides paste is significantly more effective than diclofenac sodium.

Effect of pretreatment with coenzyme Q10 on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats.

BACKGROUND: Coenzyme Q10 (CoQ10) is a lipid-soluble, vitamin-like substance found in the hydrophobic interior of the phospholipid bilayer of most cellular membranes. It appears to be involved in the coordinated regulation between oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions. OBJECTIVE: The objective of the present study was to investigate the effect of pretreatment with CoQ10 (100 mg/kg) on isoproterenol (ISO)-induced cardiotoxicity and cardiac hypertrophy in rats. METHODS: Albino male Wistar rats (250-300 g) were evenly divided by lottery method into 1 of the following 3 groups: the ISO group (olive oil 2 mL/kg orally for 18 days and ISO 1 mg/kg IP from days 9-18); the CoQ10 + ISO group (CoQ10 100 mg/kg orally for 18 days and ISO 1 mg/kg IP from days 9-18); and the control group (olive oil 2 mL/kg orally for 18 days and water IP from days 9-18). Twenty-four hours after the last dose of water or ISO, the rats were anesthetized and an ECG was recorded. Blood was withdrawn by retro-orbital puncture for estimation of serum creatine kinase-MB (CK-MB) isoenzyme levels, lactate dehydrogenase (LDH) levels, and aspartate aminotransferase activities. The animals were euthanized using an overdose of ether. The hearts of 6 animals from each group were used for estimation of superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, lipid peroxidation (LPO), malondialdehyde (MDA), and total protein concentration. Histopathology of the 2 remaining hearts in each group was carried out by a blinded technician. RESULTS: A total of 24 rats (8 in each group) were used in this study; all rats survived to study end. Compared with the control group, the ISO-treated rats had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly higher myocardial MDA concentration [P < 0.001]; significantly lower myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.01]); and significantly higher serum activities of marker enzymes (eg, CK-MB [P < 0.001] and LDH [P < 0.001]). Compared with the ISO group, the CoQ10 + ISO group had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly lower MDA concentration [P < 0.05]; significantly higher myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.05]); and significantly lower serum activities of marker enzymes (eg, CK-MB [P < 0.05] and LDH [P < 0.01]). CONCLUSION: Pretreatment with CoQ10 (100 mg/kg) for 18 days was associated with moderate protection against ISO-induced cardiotoxicity and cardiac hypertrophy, and with lower myocardial injury by preserving endogenous antioxidants and reducing LPO in rat heart.