Objectives: The study aimed at examining the role of oxidative stress in cadioprotective effects of oleuropein in a rat model of simultaneous type 2 diabetes and renal hypertension. Materials and Methods: Five groups of male Sprague-Dawley rats including a control group, a diabetic-hypertensive group receiving vehicle, and three diabetic-hypertensive groups receiving oleuropein at 20, 40, or 60 mg/kg/day were used. Blood pressure and glucose, serum malondialdehyde, and erythrocyte superoxide dismutase were measured, and animal's hearts with ischemia/reperfusion injuries were used using Langendorff technique. Results: Blood pressure, blood glucose, serum malondialdehyde, infarct size, coronary effluent creatine kinase-MB, and coronary resistance of diabetic-hypertensive group were significantly higher than those of the control group, while those of the oleuropein-receiving groups were significantly lower than those of the diabetic hypertensive group receiving the vehicle. Erythrocyte superoxide dismutase, left ventricular developed pressure, and rate of rise and rate of decrease of ventricular pressure of diabetic-hypertensive group were significantly lower than those of the control group. These parameters as well as heart rate of oleuropein-receiving groups were significantly higher than those of the diabetic-hypertensive group. Conclusion: The findings indicate that oleuropein offered cardioprotection, which might be partly mediated by its antioxidant properties.

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Objectives: The study was conducted to assess knowledge, attitude, and practice regarding insulin use among diabetic patients in tertiary care hospitals. Materials and Methods: Type 1 and 2 diabetic patients, aged 18 years and above, attending the Medicine/Endocrinology out-patient department or admitted as in-patients in three hospitals in and around Kolkata were enrolled. A pretested structured questionnaire comprising of 51 items was administered through face-to-face interview. Responses from 385 subjects were analyzed. Results: Both higher educational and higher economic standards were associated with better understanding of insulin use. Longer duration of diabetes and its treatment (oral anti-diabetic drugs and insulin) were associated with better knowledge of some parameters. Female subjects were less aware of HbA _1c as a monitoring tool. Among current insulin users, 70% had never used a glucometer; only 27.33% carried simple carbohydrates for use in hypoglycemic attacks; and 32% failed to rotate sites for insulin injection. Conclusion: Knowledge and attitude were satisfactory on the whole but deficiencies in practice were pronounced, which can potentially be removed through appropriate counseling.

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India is among the important megabiodiversity centers of the world with nearly 45,000 known plant species. This diversity coupled with a rich heritage of traditional knowledge has made India a home to several important time-honored systems of health care such as Ayurveda, Siddha and Unani. Herbal medicines, however, are associated with a number of shortcomings including uniform efficacy and lack of appropriate quality control measures at various stages of product development. The review intends to outline the importance of fostering quality parameters towards standardization and manufacturing of botanicals for India to emerge as a leader in global market of herbal products. Literature survey was carried out on important parameters for processing and manufacturing of botanicals. The review highlights that there have been constant efforts for developing state of the art technologies in the field of herbal research. It also reflects that Government authorities have also taken a number of initiatives to formulate appropriate guidelines from standardization of raw materials to obtaining botanical products. However, in the Indian context, there exist certain lacunae in the current regulatory mechanisms which need to be strengthened and stringently implemented to ensure safety, purity and efficacy of herbal medicines. Towards this the approaches being developed globally can be adopted. Based on the literature reviewed, in our opinion, four areas viz., benefit sharing, investment by industry, standardization and national/international networking structure need immediate attention for strengthening Traditional Systems of Medicine in India.

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Restless leg syndrome (RLS) is a common disorder causing sleep impairment. Antipsychotics particularly belonging to the first generation are a common cause of RLS. Whereas, RLS induced by olanzapine is rare, there are only a few cases reported earlier. We report a 38-year-old lady suffering from persistent delusional disorder who was prescribed olanzapine. She developed RLS after initiation of olanzapine which improved when switched over to risperidone. This report will caution clinicians about this side effect of a very commonly prescribed antipsychotic drug.

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Objectives: Application of vitamin K to the skin has been used for suppression of pigmentation and resolution of bruising. However, in rats, no study was reported on its effect regarding wound healing. Thus, the present study was designed to examine the healing effects of creams prepared from vitamin K ₁ on full-thickness wound in rats. Materials and Methods: For inducing full-thickness wound in rats, the excisional wound model was used. Five groups consisting of 8 rats each were used. Vitamin K cream (1% and 2%, w/w) was prepared in eucerin base and applied on the wound once a day until complete healing had occurred. Healing was defined by decreased wound margin (wound contraction), re-epithelialization, tensile strength and hydroxyproline content. Histopathological examination was also done. Results: The effects produced by the topical vitamin K showed significant (P < 0.01) healing when compared with control group in parameters such as wound contraction, epithelialization period, hydroxyproline content and tensile strength. Histopathological studies also showed improvement with vitamin K. Conclusions: Topical vitamin K demonstrates wound healing potential in full-thickness wound model.

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Drug-induced acute pancreatitis (AP) is under-reported, and a large number of drugs are listed as offenders, but are often overlooked. Knowledge about the possible association of medications in causing AP is important, and needs a high index of suspicion, especially with drugs that have been reported to be the etiology only rarely. Dapsone, a commonly used drug, can cause various hypersensitivity reactions including AP collectively called "dapsone syndrome." Here, we report dapsone-induced AP in a young man. Our case shows certain dissimilarities like associated acute renal failure and acute hemolysis not previously described.

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Objective: To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Materials and Methods: Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. Results: At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Conclusions: Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.

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Though there is ample evidence for the association between selective serotonin reuptake inhibitors and hyponatremia, evidence for the relationship between mirtazapine and hyponatremia is scarce. We present a case of mirtazapine-induced hyponatremia in an adult patient, which was dose related.

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Dapsone is a drug commonly used in the treatment of various dermatological diseases. Here, we report the case of a 45-year-old female prescribed dapsone for chronic urticaria after which she developed extensive livedo reticularis in the limbs, abdomen, and trunk. The use of dapsone may be associated with a plethora of adverse effects including rash but livedo reticularis has been very rarely reported. Emphasis should be laid on the possible drug etiology in any patient who develops new signs and symptoms while on medications, even if it may not be supported by enough literature.

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Aims: To measure impact of information, education, and communication intervention (IEC) on rational medicine use, purchase, and stocking behavior. Materials and Methods: This was a pre- and post-design, interventional study. Base data were collected in first visit, using pre tested questionnaire from 500 respondents, who were of either gender, English speaking, at least graduates, permanent residents, and willing to participate. IEC was framed based on problems identified from this data. First intervention was handouts distributed in the second visit, containing information on cost saving in medicine purchase. Second intervention was a lecture session on medicine prices, rational use of medicines, and tips on saving on medicine purchase. Five articles about medicine use and price differences were published in the local newspaper, over 10 days, formed third intervention. After 1 month, post-intervention data was collected using same instrument with some additional questions. Results were analyzed by Chi-square test using Graph Pad prism Version 3.0. Results: Awareness about price variation, self-medication, expiry period, generic and brand quality increased post-intervention. Attitudes toward new, costly, brands, injections, sharing and reusing old prescriptions changed post-intervention. Behavioral changes in stocking habits, adherence to doctors' advice, getting cash memo, comparing prices, reading labels, were seen post-intervention. Conclusion: People carry false notions about medicines which influence their use and habits. This intervention successfully changed behavior and could bring awareness on many aspects of medicine use.

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Aim: We investigated the role of adenosine in citalopram-induced cardiotoxicity. Materials and Methods: Protocol 1: Rats were randomized into four groups. Sodium cromoglycate was administered to rats. Citalopram was infused after the 5% dextrose, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; A ₁ receptor antagonist), 8-(-3-chlorostyryl)-caffeine (CSC; A _2a receptor antagonist), or dimethyl sulfoxide (DMSO) administrations. Protocol 2: First group received 5% dextrose intraperitoneally 1 hour prior to citalopram. Other rats were pretreated with erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; inhibitor of adenosine deaminase) and S-(4-Nitrobenzyl)-6-thioinosine (NBTI; inhibitor of facilitated adenosine transport). After pretreatment, group 2 received 5% dextrose and group 3 received citalopram. Adenosine concentrations, mean arterial pressure (MAP), heart rate (HR),  QRS duration and QT interval were evaluated. Results: In the dextrose group, citalopram infusion caused a significant decrease in MAP and HR and caused a significant prolongation in QRS and QT. DPCPX infusion significantly prevented the prolongation of the QT interval when compared to control. In the second protocol, citalopram infusion did not cause a significant change in plasma adenosine concentrations, but a significant increase observed in EHNA/NBTI groups. In EHNA/NBTI groups, citalopram-induced MAP and HR reductions, QRS and QT prolongations were more significant than the dextrose group. Conclusions: Citalopram may lead to QT prolongation by stimulating adenosine A ₁ receptors without affecting the release of adenosine.

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Objectives: To evaluate the antipsoriatic activity of Givotia rottleriformis bark in rats. Materials and Methods: The antipsoriatic activity of the ethanol extract was investigated using ultraviolet B (UV-B)-induced photodermatitis model in rats. The animals were divided into four groups (6/groups). The vehicle-control group animals received normal saline (10 ml/kg, p.o.) and standard group received retinoic acid (0.5 mg/kg, p.o.). Remaining groups were treated orally with the ethanolic extract of bark of Givotia rottleriformis (200 and 400 mg/kg, p.o.) and data were analyzed using one-way analysis of variance (ANOVA). The extract was standardized using chemical markers by high-performance liquid chromatography (HPLC) analysis. Results: In case of psoriasis model, histopathological analysis revealed that in the section, there were absence of Munro's microabscess, elongation of rete ridges, and capillary loop dilation in ethanol extract (400 mg/Kg) and standard group. The ethanolic extract (200 and 400 mg/Kg) exhibited significant reduction (P < 0.01) in percentage of relative epidermal thickness as compared with positive control. In the HPLC analysis, 4 flavonoids were quantified by comparison to a calibration curve derived from the standard, rutin (0.215 mg/gm) quercetin (1.36 mg/gm), kaempferol (6.36 mg/gm) and luteolin (8.64 mg/gm). Conclusion: The crude extract containing ethanolic extract of Givotia rottleriformis bark have potent antipsoriatic activity in UV-B-induced psoriasis in rat.

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Objectives: To investigate the antiplatelet activity of alpha-lipoic acid (α-LA) and dihydroquercetin (DHQ). Materials and Methods: Antiplatelet activity of the α-LA and DHQ was evaluated in rich platelet plasma of rat. The platelet aggregation was induced by adenosine diphosphate (ADP) in concentration of 4 Χ 10 ^-5 Μ. Results: α-LA and DHQ inhibited platelet aggregation in concentration-dependent manner. The antiplatelet activity of α-LA was more pronounced than DHQ. DHQ also increased the antiplatelet activity of α-LA by 1.4 times. Conclusion: Combined simultaneous use of α-LA and DHQ possessed the high antiplatelet activity, and DHQ potentiated the activity of α-LA.

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Aim : Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are effective in treating anxiety disorders associated with major depressive disorder (MDD). This randomized, controlled, parallel-group, open-label, phase 4 trial (CTRI/2012/08/002895) was undertaken to compare the effectiveness and safety of desvenlafaxine versus escitalopram, a standard antidepressant. Materials and Methods : Effectiveness was assessed using the Hamilton Depression Rating Scale (HAM-D ₁₇ ) and Hamilton Anxiety Rating Scale (HAM-A). Response to treatment was assessed by ≥50% decrease of baseline scores (responder rate). Safety and tolerability was evaluated by changes in routine laboratory parameters, vital signs, and adverse events reported by the subject and/or observed by the clinician. Results: Responder rates for both HAM-A and HAM-D scores at 8 weeks were better in the escitalopram group compared to the desvenlafaxine group (HAM-A 76.92% vs. 71.05%; HAM-D 79.48% vs73.68%) but the differences were not statistically significant (P = 0.59 and P = 0.61). Within group changes of both scores, from baseline to subsequent visits in both treatment arms were statistically significant (P < 0.01). Conclusion: The effectiveness of desvenlafaxine was comparable to escitalopram, but escitalopram was better tolerated.

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Here we report a case of a 63-year-old male diagnosed with recurrent depressive disorder and current episode of severe depression with psychotic symptoms, developed hyponatremia soon after addition of olanzapine and increasing the dose of escitalopram. A possible causality association was established with olanzapine, and the possible etiological reasons of this clinically significant risk were discussed.

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An emergency intervention was performed in a 75-year-old male patient with hypoglycemic attack and blackout. Although he was diagnosed with prediabetes before 2 years, he did not take any anti-diabetic drug or follow dietary advice. He drank Vaccinium corymbosum L (VC) juice daily with a belief that it increases sexual potency. Before the development of hypoglycemia, the patient had consumed about 500 ml VC juice in addition to eating 200-300 gram of Laurocerasus officinalis (LO) fruit. The measured plasma glucose (PG) level during loss of consciousness was 30 mg/dl. The profound hypoglycemia may be an unexpected side effect of an interaction between the chemical compositions of the two plants, occurred as a result of LO fruit intake that may have a strong PG-lowering effect or related to excessive intake of VC juice. Both plants may be considered in the alternative treatment of diabetes.

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Objective: To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). Materials and Methods: AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. Results: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. Conclusion: SXND may antagonize the renin-angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1.

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Aim: The study investigated the direct effects of tramadol on the coagulation status of women with gynecologic malignancies in vitro. Materials and Methods: Citrated whole-blood samples from 21 patients with gynecologic tumors were spiked ex vivo with 2 or 6 μl/ml tramadol. Thrombelastography (TEG) analysis was performed using ROTEM^® to assess clotting time (CT), clot formation time (CFT) and maximum clot formation (MCF). Results: In the INTEM assay, CT (P < 0.05) and CFT (P < 0.01) were significantly prolonged with tramadol at a 6 μl/ml concentration compared with baseline. There were no significant differences in MCF values between the baseline and the tramadol-treated samples (P > 0.05). Blood medicated with tramadol (6 μl/ml) clotted slowly (increased CT and CFT). Conclusion: The changes observed by TEG demonstrated that tramadol impairs hemostasis in a concentration-dependent manner in the whole blood of women with gynecologic malignancies in vitro.

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The case presented is the first patient with concurrent acute interstitial pneumonia and pulmonary embolism associated with combined treatment of peginterferon and ribavirin for hepatitis C.

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An elderly male with Bipolar Affective Disorder (BPAD) developed reversible ototoxicity, manifesting as bilateral sensory-neural hearing loss (SNHL) with administration of olanzapine.

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Objective: Ellagic acid (EA), a major polyphenolic compound of pomegranate juice, produces antinociceptive effects, which are mediated through opioidergic and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathways. The present study was conducted to elucidate the peripheral antinociceptive effect of EA alone and in combination with sildenafil in the rat formalin test. Materials and Methods: Pain was produced by intraplantar injection of formalin (2.5%) in rats and nociceptive behavior was measured as the number of flinches every 5 min in 60 min after injection. Results: Local administration of EA and sildenafil dose-dependently increased the nociception threshold in both phases of the test. Moreover, sub-effective doses of sildenafil (25 or 50 mcg/paw, i.p.) significantly and dose-dependently enhanced the antinociception induced by a sub-effective dose of EA (60 mcg/paw, i.pl.) in both phases of the test. The antinociception produced by these drugs alone, or in combination, was due to a peripheral site of action, since the administration in the contralateral paw was ineffective. Conclusion: Our results suggest that EA has local peripheral antinociceptive activity, and enhancement of this effect with sildenafil probably occurs through the inhibition of cGMP metabolism.

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Objectives: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acid _B (GABA _B ) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods : This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective. Results : The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03). Conclusion : Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide.

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