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Mesotherapy involves the use of multiple intradermal or subcutaneous injections of a mixture of compounds in minute doses, by means of very fine needles, directly over/near the affected sites. Originally invented in France to manage painful medical conditions, it is presently the buzz word in the field of cosmetic dermatology, chiefly to get rid of disfiguring fat. Depending upon the condition treated, the drugs injected, the techniques followed and the number of sessions involved vary. The wider reception of mesotherapy by its stakeholders are probably due to factors like inexpensive equipments, relatively minimal training for providers, much reduced dosage need of the drugs with resultant minimal untoward effects, quicker realization of benefits, minimal invasiveness/pain involved and not the least it is an outpatient procedure. Despite so many plus points, it has to be noted that currently there is a dearth of rigorous scientific studies to prove its efficacy and safety. Further, the average cost per session alone ranges from 200 USD to 600 USD.

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Objective: To determine the protective role of Punica granatum L. (Punicaceae) seed juice extract and its butanolic fraction on heart rate, electrocardiographic patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphologic and histopathological changes in isoproterenol-induced myocardial infarction in male Wistar rats. Materials and Methods: The effects of Punica granatum seed juice extract (100 mg/kg, p.o. and 300 mg/kg, p.o.) and butanolic fraction of Punica granatum seed juice extract (100 mg/kg., p.o.) on cardiac parameters were studied. Isoproterenol hydrochloride was used to induce myocardial infarction in Wistar rats. At the end of the experiment, heart rate, ECG, pressure rate index and cardiac marker enzyme levels were assessed. Results: Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate, ST elevation in ECG, pressure rate index and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum. Isoproterenol significantly reduced superoxide dismutase and catalase activity and increased vascular reactivity to various catecholamines. Pretreatment with PJ (100 mg/kg, p.o. and 300 mg/kg, p.o.) and B-PJ (100 mg/kg., p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, PRI, ECG patterns, levels of LDH, CK, SOD, CAT, and vascular reactivity changes. Treatment with PJ (100 mg/kg and 300 mg/kg) and B-PJ (100 mg/kg., p.o.) alone did not alter any of the parameters as compared to vehicle-treated Wistar rats. Punica granatum-treated animals showed a lesser degree of cellular infiltration in histopathological studies. Conclusion: Punica granatum ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of MI.

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Toxicity testing of new compounds is essential for drug development process. The preclinical toxicity testing on various biological systems reveals the species-, organ- and dose- specific toxic effects of an investigational product. The toxicity of substances can be observed by (a) studying the accidental exposures to a substance (b) in vitro studies using cells/ cell lines (c) in vivo exposure on experimental animals. This review mainly focuses on the various experimental animal models and methods used for toxicity testing of substances. The pre-clinical toxicity testing helps to calculate "No Observed Adverse Effect Level" which is needed to initiate the clinical evaluation of investigational products.

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Even though there have been major advances in therapy, atherosclerosis and coronary artery disease retain their lead as one of the major causes of morbidity and mortality in the first decade of 21 ^st century. To add to the woes, we have diabetes, obesity and insulin resistance as the other causes. The adipose tissue secretes several bioactive mediators that influence inflammation, insulin resistance, diabetes, atherosclerosis and several other pathologic states besides the regulation of body weight. These mediators are mostly proteins and are termed "adipocytokines". Adiponectin, resistin, visfatin, retinol binding protein-4 (RBP-4) and leptin are a few such proteins. Adiponectin is a multimeric protein, acting via its identified receptors, AdipoR1 and AdipoR2. It is a potential biomarker for metabolic syndrome and has several antiinflammatory actions. Adiponectin increases insulin sensitivity and ameliorates obesity. Resistin, another protein secreted by the adipose tissue, derived its name due to its involvement in the development of insulin resistance. It plays a role in the pathophysiology of several conditions because of its robust proinflammatory activity mediated through the activation of extracellular signal regulated kinases 1 and 2 (ERK 1/2). In 2007, resistin was reported to have protective effect in ischemia-reperfusion injury and myocyte-apoptosis in the setting of myocardial infarction (MI). RBP-4 is involved in the developmental pathology of type 2 diabetes mellitus and obesity. Visfatin has been described as an inflammatory cytokine. Increased expression of visfatin mRNA has been observed in inflammatory conditions like atherosclerosis and inflammatory bowel disease. Leptin mainly regulates the food intake and energy homeostasis. Leptin resistance has been associated with development of obesity and insulin resistance. Few drugs (thiazolidinediones, rimonabant, statins, etc.) and some lifestyle modifications have been found to improve the levels of adipocytokines. Their role in therapy has a lot in store to be explored upon.

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Sugar is an inseparable part of the food we consume. But too much sugar is not ideal for our teeth and waistline. There have been some controversial suggestions that excessive sugar may play an important role in certain degenerative diseases. So artificial sweeteners or artificially sweetened products continue to attract consumers. A sugar substitute (artificial sweetener) is a food additive that duplicates the effect of sugar in taste, but usually has less food energy. Besides its benefits, animal studies have convincingly proven that artificial sweeteners cause weight gain, brain tumors, bladder cancer and many other health hazards. Some kind of health related side effects including carcinogenicity are also noted in humans. A large number of studies have been carried out on these substances with conclusions ranging from "safe under all conditions" to "unsafe at any dose". Scientists are divided in their views on the issue of artificial sweetener safety. In scientific as well as in lay publications, supporting studies are often widely referenced while the opposing results are de-emphasized or dismissed. So this review aims to explore the health controversy over perceived benefits of sugar substitutes.

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Objective: To evaluate the protective effect of glibenclamide against the experimental diabetes-induced nuclear damage in Wistar rats. Materials and Methods: The anti-mutagenic effect of glibenclamide (0.5, 5 and 50 mg/kg, p.o daily for 4 weeks) was evaluated against the nicotinamide (NA)-streptozotocin (STZ) induced type-2 diabetes mellitus using bone marrow micronucleus and sperm abnormalities tests. The antioxidant status was tested by estimating the serum levels of lipid peroxidation (LPO), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Results: The results indicated that glibenclamide at 50 mg/kg decreased the frequency of micronuclei in erythrocytes (P < 0.05) and sperm shape abnormality (P < 0.01) besides enhancing the antioxidant status (P < 0.05) in the diabetic rats. However, glibenclamide treatment did not enhance the polychromatic and normochromatic erythrocytes (P/N) ratio and sperm count in the diabetic condition. Conclusion: The observations indicate that the glibenclamide has anti-mutagenic potential which could be related to the antioxidant effect and might also possess anti-proliferative property.

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Objective: To compare the efficacy and safety of rabeprazole and esomeprazole in mild-to-moderate erosive gastroesophageal reflux disease (GERD). Materials and Methods: A randomized, single-blinded, outdoor-based clinical study was conducted on 60 patients of mild-to-moderate erosive GERD. After baseline clinical assessment and investigations, rabeprazole (40 mg) was prescribed to 30 patients and esomeprazole (40 mg) to another 30 patients for 4 weeks. The efficacy variables were change in GERD symptom scoring, endoscopic findings, and Quality of Life in Reflux and Dyspepsia (QOLRAD) scoring over 4 weeks. Result: Heartburn, acid regurgitation, and overall GERD symptom scoring (P = 0.01) were significantly decreased with rabeprazole in comparison to esomeprazole. The comparative study of all five domains of the QOLARD questionnaire including overall scoring revealed a statistically significant improvement in the rabeprazole group. Endoscopic findings in the rabeprazole group showed an absolute improvement of 30% and relative improvement of 55% over esomeprazole. Both the drugs were well tolerated having no significant difference in the incidence of adverse effects. Conclusion: Rabeprazole (40 mg) is a better choice for mild-to-moderate GERD compared with esomeprazole (40 mg) because of its better efficacy and safety profile.

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Objective: To determine the in vitro free radical scavenging property and in vivo diuretic effect of Triglize ^TM , a marketed polyherbal formulation in experimental models. Materials and Methods: The aqueous extract of polyherbal formulation (PHF) triglize was used for the experiment. The free radical scavenging property and antioxidant effect of PHF were studied by LPS-induced free radicals in rat macrophages cells and DPPH (2, 2-Diphenyl-1-Picrylhydrazyl) methods, respectively. The diuretic effect of a PHF was studied with Lipschitz model using male Wistar rats. Results: PHF significantly inhibited lipopolysaccharide -induced free radicals in rat macrophages and it showed moderate antioxidant potential in DPPH model. Polyherbal formulation at 50, 200 and 400 mg/ kg significantly increased potassium excretion in urine at 0-5 h and 5-24 h. The diuretic effect of PHF was as similar as furosemide. Conclusion: The PHF has significant diuretic effect and free radical scavenging properties.

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Aims: To find out the pharmacokinetic and pharmacodynamic drug interaction of carbamazepine, a protype drug used to treat painful diabetic neuropathy with glibenclamide in healthy albino Wistar rats following single and multiple dosage treatment. Materials and Methods: Therapeutic doses (TD) of glibenclamide and TD of carbamazepine were administered to the animals. The blood glucose levels were estimated by GOD/POD method and the plasma glibenclamide concentrations were estimated by a sensitive RP HPLC method to calculate pharmacokinetic parameters. Results: In single dose study the percentage reduction of blood glucose levels and glibenclamide concentrations of rats treated with both carbamazepine and glibenclamide were significantly increased when compared with glibenclamide alone treated rats and the mechanism behind this interaction may be due to inhibition of P-glycoprotein mediated transport of glibenclamide by carbamazepine, but in multiple dose study the percentage reduction of blood glucose levels and glibenclamide concentrations were reduced and it may be due to inhibition of P-glycoprotein mediated transport and induction of CYP2C9, the enzyme through which glibenclamide is metabolised. Conclusions: In the present study there is a pharmacokinetic and pharmacodynamic interaction between carbamazepine and glibenclamide was observed. The possible interaction involves both P-gp and CYP enzymes. To investigate this type of interactions pre-clinically are helpful to avoid drug-drug interactions in clinical situation.

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Objective: To find out the most common bacterial pathogens responsible for post-operative wound infection and their antibiotic sensitivity profile. Materials and Methods: This prospective, observational study was carried out in patients of postoperative wound infection. Samples from wound discharge were collected using a sterile swab and studied for identification of isolates by Gram stains and culture growth followed by in vitro antibiotic susceptibility testing performed by disc diffusion method on Mueller Hinton agar. Results: Out of 183 organisms, 126 (68.85%) isolated organisms were gram negative. Staphylococcus aureus, 48 (26.23%), was the predominant organism. S. aureus was sensitive to rifampicin (89.58%), levofloxacin (60.42%), and vancomycin (54.17%). Pseudomonas aeruginosa was sensitive to ciprofloxacin (83.78%), gatifloxacin (51.35%), and meropenem (51.35%). Escherichia coli was sensitive to levofloxacin (72.41%) and ciprofloxacin (62.07%). Klebsiella pneumoniae was sensitive to ciprofloxacin (63.16%), levofloxacin (63.16%), gatifloxacin (63.16%), and linezolid (56.52%). Proteus mirabilis was sensitive to ciprofloxacin (75%) and linezolid (62.50). Proteus vulgaris was sensitive to ampicillin+sulbactam (57.14%) followed by levofloxacin (50%). Conclusions: There is an alarming increase of infections caused by antibiotic-resistant bacteria, particularly in the emergence of VRSA/VISA, meropenem, and third generation cephalosporin resistant Pseudomonas aeruginosa. Linezolid showing sensitivity against Gram negative bacteria.

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Objective: To study the effect of calcium channel blockers (CCBs) cinnarizine and nifedipine on maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-induced convulsions and also their effect in combination with conventional antiepileptic drugs (CAED). Materials and Methods: For this study, Swiss albino mice were used. Effects of cinnarizine (30 mg/kg), nifedipine (5 mg/kg), sodium valproate (300 mg/kg) and carbamazepine (8 mg/kg) alone and in combination were studied in MES and PTZ seizure models. Abolition of hind limb tonic extension was an index of anticonvulsant activity in MES, while for PTZ seizures, failure to observe even a single episode of tonic spasm for 5 s duration for 1 h was the index. With this, percentage protection was calculated and statistical analysis was carried out using Fisher's exact test (Ovvind Langsrud software, German version). Results: In MES seizures, augmented effects were obtained when cinnarizine was combined with sodium valproate, i.e. 100%. In PTZ-induced seizures, augmented effects were obtained when nifedipine was combined with sodium valproate, i.e. 100%. Thus, cinnarizine added to sodium valproate therapy produces significant protection against MES seizures while nifedipine added to sodium valproate therapy produces significant protection against PTZ seizures. Conclusion: The results provide a lead for potential benefit of adding CCBs to sodium valproate in the treatment of epilepsy, which needs to be explored further.

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Background: The present study has been designed to evaluate the combined cardioprotective effect of vitamin E and lycopene on biochemical and histopathological alteration in isoproterenol-induced myocardial infarction in rats. Materials and Methods: Adult male albino rats of Wistar strain were treated with isoproterenol (200 mg/kg, s.c.) for 2 days at an interval of 24 h to develop myocardial infarction. Vitamin E (100 mg/kg/day, p.o.) and lycopene (10 mg/kg/day, p.o.) were administered alone and in combination for 30 days. Change in body weight and organ weight were monitored. Levels of serum marker enzymes (AST, ALT, LDH and CK-MB), lipid peroxidation, endogenous antioxidants (GSH, GPX, GST, SOD and CAT), membrane bound enzymes (Na ⁺ /K ⁺ ATPases, Mg ²⁺ ATPases and Ca ²⁺ ATPases) were evaluated. LDH isoenzyme separation was carried out using gel electrophoresis. Histopathology of heart tissue was performed. Results: Induction of rats with isoproterenol resulted in a significant elevation in organ weight, lipid peroxidation, serum marker enzymes (AST, ALT, CK-MB and LDH), and Ca ²⁺ ATPases, whereas it caused a significant (P < 0.001) decrease in body weight, activities of endogenous antioxidants (GSH, GP _X , GST, SOD and CAT), Na ⁺ /K ⁺ and Mg ²⁺ ATPases. ISO treated rats showed high intensity band of LDH1-LDH2 isoenzymes. Treatment with the combination of Vitamin E and lycopene for 30 days significantly attenuated these changes as compared to the individual treatment and ISO treated groups. Histopathological observations were also in correlation with the biochemical parameters. Conclusion: These findings indicate the synergistic cardioprotective effects of vitamin E and lycopene during ISO-induced myocardial infarction in rats.

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Objective: To evaluate the nootropic and neuroprotective effects of aspirin in Sprague Dawley rats. Materials and Methods: Retention of conditioned avoidance response (CAR) and central 5-HT-mediated behavior (lithium-induced head twitches) were assessed using repeated electroconvulsive shock (ECS) in rats. Rats were divided into eight groups: control (pretreated with distilled water), scopolamine (0.5 mg/kg i.p.), ECS (150 V, 50 Hz sinusoidal with intensity of 210 mA for 0.5 s) pretreated, aspirin (6.75 mg/kg orally) pretreated, combined scopolamine and aspirin pretreated, ondansetron (0.36 mg/kg orally) pretreated, combined ECS and ondansetron pretreated and combined ECS and aspirin pretreated groups. Data was analyzed by the chi-square test and ANOVA. Results: Findings show that administration of single ECS daily for consecutive 8 days results in enhancement of 5-HT-mediated behavior (lithium-induced head twitches) and in disruption of the retention of CAR. Aspirin and ondansetron administration significantly increased the retention of conditioned avoidance response compared to control. Ondansetron and aspirin significantly prevented ECS-induced attenuation of the retention of conditioned avoidance response also. On the other hand, ondansetron and aspirin significantly retarded the ECS-induced enhancement of 5-HT-mediated behavior. Conclusion: Inhibition of the serotonergic transmission by aspirin is responsible for its nootropic and neuroprotective actions.

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Objective: To find out incidence of adverse drug reactions (ADR) in patients of internal medicine wards and study various aspects of ADR, e.g., causality, mortality, drugs commonly causing ADR in internal medicine wards of Guru Gobind Singh Hospital, Jamnagar, a tertiary care hospital. Materials and Methods: This was prospective, observational study carried out at Department of Medicine, Shri Meghji Pethraj Shah Medical College attached with Guru Gobind Singh Hospital, a tertiary care teaching hospital, Jamnagar, Gujarat over a period of 6 months. For statistical analysis, ADR were analyzed by using Chi-square test. Results: Out of total 860 patients admitted, 830 were analyzed as they met the inclusion criteria. A total of 45 (5.42%) patients developed 47 ADR. Among them, 27 (3.25 %) (95% CI, 2.03%, 4.47%) patients due to ADR required hospital admission in medicine ward (ADR Ad), 18 (2.17%) (95% CI, 1.17%-3.17%) patients developed ADR while already hospitalized in medicine ward (ADR In). Most of the fatal and life-threatening reactions occurred due to chemotherapeutic agents. Majority of patients discontinued suspected drug and recovered from ADR. Conclusion: Fatal and life-threatening adverse reactions reported in the present as well as other studies underline the importance of such studies and need for creating awareness among health professionals about looking for and reporting such reactions.

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