Aim: To compare the efficacy and safety of gabapentin (GBP), duloxetine (DLX), and pregabalin (PGB) in patients with painful diabetic peripheral neuropathy (DPNP). Methods: A prospective, randomized, open label, 12-week study was conducted. A total of 152 patients with history of pain attributed to DPNP with a minimum 40-mm score on visual analogue scale (VAS) were randomized to receive GBP, DLX, or PGB. The primary efficacy measure was pain severity as measured on 11 point VAS. Secondary efficacy measures included sleep interference score, Patient Global Impression of Change (PGIC), and Clinical Global Impression of Change (CGIC). Assessment of safety was done by recording the occurrence of adverse drug reactions. Data was analyzed using descriptive statistics, Chi square test, analysis of variance (ANOVA), and repeated measures ANOVA. Results: Of total 152 patients, 50 patients received GBP, DLX each while 52 received PGB. A significant reduction in pain score (VAS), sleep interference score, PGIC, and CGIC was seen in all the three treatment groups across time (P<0.05) with no statistically significant difference between the groups. There was a significant interaction between the time and treatment groups (P<0.001) for pain score (VAS), sleep interference score, and PGIC. The improvement in pain scores (VAS) and sleep interference score was higher with PGB compared to DLX and GBP. Adverse drug reactions were mild and occurred in 9.2% of all cases. Conclusions: Monotherapy with GBP, DLX, or PGB Produced a clinically and subjectively meaningful pain relief in patients with DPNP with onset of pain relief being faster and superior with PGB.

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Pulmonary arterial hypertension (PAH) is a heterogeneous, hemodynamic, and pathophysiological state which is commonly found throughout the world, but the disease burden is greater in India and in other developing countries. It is a disease characterized by vascular obstruction and vasoconstriction leading to progressive increase in pulmonary vascular resistance and right ventricular failure. PAH is a progressive disorder carrying a poor prognosis; however, dramatic progress has occurred in our knowledge of its pathogenesis and consequently, its treatment over the last two decades. In this article, we attempt to provide an overview of the etiology, pathophysiology, and current therapeutic modalities in the treatment of PAH. Patients suspected to have PAH should be submitted to a battery of investigations which help in establishing the diagnosis, identifying the etiology, guiding in treatment and informing the prognosis. All patients should be considered for standard therapy with oxygen, anticoagulation, and diuretics for right heart failure. Oral calcium channel blockers should be used in patients with a favorable response to acute vasodilator challenge. Disease targeted therapies include prostacyclines, endothelin receptor blockers, and phosphodiesterase-5 inhibitors. A brief mention of new and potential therapeutic strategies is also included.

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Acamprosate with dual mechanism of action as glutamate antagonist and GABA agonist can be a potential target to decrease the severity of sensorineural tinnitus. Objective: (1)To study the effectiveness of acamprosate in providing subjective relief and objective improvement in patients having tinnitus of sensorineural origin. (2) To evaluate the adverse events related to the use of acamprosate and also determine the change in quality of life (QOL) parameters. Materials and Methods: The study was randomized double-blind, placebo controlled, crossover. Forty adult subjects (>18 years of age), of either sex with tinnitus of sensorineural origin, were administered either acamprosate 333 mg TDS or matched placebo for a period of six weeks followed by a washout period of one week. Drug therapy was switched for another six weeks in consonance with the crossover design. The effect of acamprosate and placebo on subjective relief and objective improvement was evaluated by using modified tinnitus severity, QOL scores and audiometry with tinnitus matching in frequency and loudness. Results: At the end of the study, the drug had shown a statistically significant improvement in reducing the tinnitus score in 92.5% of the patients and placebo with an improvement in 12.5% of the patients. The drug was well tolerated without any serious drug reactions. Conclusion: Acamprosate is an effective drug in treating the severity of sensorineural tinnitus without causing much of the side effects.

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Biosimilars are biological products that are the replicas of their innovator biopharmaceuticals. These are developed after patent expiration of innovator biopharmaceuticals and are submitted for separate marketing approval. In view of the structural and manufacturing complexities of biopharmaceuticals, biosimilars should not be considered as "biological generics". These are rather unique molecules with limited data at time of approval, so there are concerns about the safety and efficacy of biosimilars. This article will address the differences between biosimilars and chemical generics, issues of concern with the use of biosimilars and need of appropriate regulations for their approval.

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Objectives: To study the preventive role of curcumin against doxorubicin (Dox)-induced myocardial toxicity in rats. Materials and Methods: Cardiotoxicity was produced by cumulative administration of Dox (15 mg/kg for two weeks). Curcumin (200 mg/kg, po) was administered as pretreatment for two weeks and then for two alternate weeks with Dox. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), biochemical parameters such as aspartate aminotransferase (AST) alanine aminotransferase (ALT) and alkaline phosphatase (ALP), antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were monitored after three weeks of last dose. Results: The repeated administration of Dox induced cardiomyopathy associated with an antioxidant deficit and increased level biomarkers. Pretreatment with the curcumin significantly protected myocardium from the toxic effects of Dox by reducing the elevated level of biomarker enzymes like LDH and CPK and biochemical parameters such as AST, ALT and ALP back to normal. Curcumin increased the reduced level of GSH, SOD and CAT and decreased the elevated level of malondialdehyde (MDA) in cardiac tissue. Conclusion: The biochemical and histopathology reports support the cardioprotective effect of curcumin which could be attributed to antioxidant.

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Background: Free radicals or highly reactive oxygen species are capable of inducing oxidative damage to human body. Antioxidants are the compounds which terminate the attack of reactive species and reduce the risk of diseases. Both Baccopa monnieri and Centella asiatica are used in treatment of brain disorders in humans and have almost similar effects. Objective: The study was conducted to determine the antioxidant properties of two well-known memory enhancer medicinal plants Baccopa monnieri and Centella asiatica. Results: The antioxidant activity of these two medicinal plants was evaluated by measuring reducing ability, free radical scavenging activity by DPPH and hydrogen peroxide methods. The antioxidants compounds like ascorbic acid, total phenols and tannins were also evaluated in these plants. Baccopa monnieri and Centella asiatica exhibited significant differences (P<0.05) in their antioxidant values. The methanolic extract of whole leaf powder of Baccopa monnieri exhibited significantly higher antioxidant activity than the Centella asiatica. The antioxidant components viz. ascorbic acid, total phenols and tannins were also found in a higher concentration in Baccopa monnieri as compared to Centella asiatica. Conclusion: It can be concluded from the study that regular use of Baccopa monnieri as a supplement could be more helpful compared to Centella asiatica in treatment of neurological disorders caused by free radical damage.

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Objectives: Wen-pi-tang-Hab-Wu-ling-san (WHW) is an oriental herbal prescription formulated using 14 herbs and has been used to cure chronic renal failure in Korean oriental medicine. In this study, we investigated the anti-diabetic effect of WHW in the streptozotocin-induced diabetic rats. Materials and Methods: Diabetes was induced by streptozotocin (STZ, 60 mg/kg, i.p.) in rats. WHW extract (100 mg/kg) was orally dosed once a day for four weeks. The results were compared with standard antidiabetic drug, glibenclamide (3 mg/kg, p.o). Results: Significant decrease in body weight and insulin levels and increase in blood glucose, triglycerides, urea nitrogen (BUN), and creatinine were detected in STZ-induced diabetic rats with disruption and disappearance of pancreatic and kidney cells and decrease in insulin producing beta cells. However, these diabetic changes were significantly inhibited by treatment with WHW extract. In the oral glucose tolerance test, the extract produced a significant decrease in glycemia 60 minutes after the glucose pulse. Conclusions: Based on these results, we suggest that WHW extract has favorable effects in protecting the STZ-induced hyperglycemia, renal damage, and beta-cell damage in rats.

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Objective: The objective of the present study is to investigate the anti-proliferation activity of Astragalus on human hepatocellular carcinoma (HCC) cells and its mechanism. Materials and Methods: Hepatic cancer H22 bearing mice were used to study the anti-hepatocarcinoma activity of Astragalus in vivo. The growth curve and inhibitory rate of tumor growth were measured. Cell apoptosis of each group was measured by flow cytometry (FCM). Protein expression of Bax and Bcl-2 were analyzed by immunohistochemistry (IHC). The Statistical Package for Social Sciences version 13.0 (SPSS Inc, Chicago, IL) was used for standard statistical analysis including one-way ANOVA and Student's t-test. A value of P<0.05 was considered to be statistically significant. Results: Astragalus significantly inhibited the growth of H22 carcinoma, with an inhibitory rate of 17.28-52.36%. FCM and immunohistochemical assay show that the cell apoptosis rate and protein expression of Bax and Bax/Bcl-2 ratio of H22 transplanted tumor in Astragalus treated group were significantly higher than the control group (P<0.05). The protein expression of Bcl-2 was significantly lower than control (P<0.05). Conclusion: The results of the present study suggest that Astragalus has significant anti-tumor effect in vivo in inducing apoptosis of H22 tumor cells by promoting protein expression of Bax, decreasing protein expression of Bcl-2 gene, and markedly increasing the Bax/Bcl-2 ratio.

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Objective: To study the anxiolytic activity of methanol extract of Achyranthes aspera Linn (Amaranthaceae). Materials and Methods: Male Swiss albino mice were used. Methanolic extract of Achyranthes aspera (MEAA) was administered in the doses of 100, 300 and 600 mg/kg p.o. Hole board (HB), open field (OF), elevated plus maze (EPM) and light/dark exploration (LDE) tests were used for determination of anxiolytic activity. Results: The methanolic extract of Achyranthes aspera significantly increased the number and duration of head poking in HB test. The extract also significantly increased the time spent and the number of entries in open arm in EPM. In LDE test, the extract produced significant increase in time spent and number of crossings and decreased the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearing, assisted rearing and the squares crossed. Conclusion: In the present study, MEAA exhibited anxiolytic activity which might be attributed to its phyto-constituents viz. alkaloid, steroid and triterpenes. Since Achyranthes aspera is ubiquitous and abundantly grown, it could be a fairly economical therapeutic agent for management of anxiety disorders.

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Objective: Memory loss is universal and is the first symptom to manifest in majority of the patients suffering from Alzheimer's disease. This study is designed to investigate the effect of Ferula asafoetida linn. (F. foetida) extract on learning and memory in rats. Materials and Methods: Learning and memory were evaluated using elevated plus maze and passive avoidance paradigm after the oral administration of two doses (200 mg/kg and 400 mg/kg) of F. foetida aqueous extract with rivastigmine as positive control. Brain cholinesterase activity, serum thiols and cholesterol were also estimated. Results: Extract produced significant improvement in memory score i.e. step through latency at 400 mg/kg dose in passive avoidance model (P< 0.05) and dose-dependent improvement of transfer latency in elevated plus maze model (P< 0.001). Dose-dependent inhibition of brain cholinesterase (P< 0.001) and significant improvement in antioxidant levels (P< 0.05) were also noted. Conclusions: Memory enhancing potential of F. foetida can be attributed to acetylcholinesterase inhibiting and antioxidant properties. Hence, dietary usage of F. foetida is beneficial and can also be employed as an adjuvant to existing anti-dementia therapies.

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Objectives: The aim of this study has been to investigate the possible antihyperlipidemic effect of Salacia chinensis root extract in triton (400mg/kg b.w.)-induced and atherogenic diet-induced hyperlipidemic rats. Materials and Methods: Petroleum ether (60-80^°C), chloroform, ethanol and aqueous extracts of Salacia chinensis roots were evaluated for antihyperlipidemic activity in triton- and atherogenic diet-induced hyperlipidemic rats. A comparison was also made between the action of Salacia chinensis root extract and a known antihyperlipidemic drug simvastatin (10 mg/kg body wt.). The results of the study were expressed as mean΁ S.E. and data was analyzed by using one way analysis of variance test (ANOVA) followed by Dunnett's t-test for multiple comparisons. Values with P < 0.05 were considered as significant. Results: Oral administration of 500 mg/kg body wt. of the chloroform extract and alcoholic extract of Salacia chinensis root exhibited a significant reduction (P<0.01) in serum lipid parameters like total cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipopreotein (VLDL) and increase in high density lipoprotein (HDL) in hyperlipidemic rats of both models as compared to hyperlipidemic control statistically. These extracts were found to possess better antihyperlipidemic potential as compared to pet ether and aqueous extract. Conclusions: Our results demonstrated that chloroform and alcoholic extract of Salacia chinensis roots possessed significant antihyperlipidemic activity and hence it could be a potential herbal medicine as adjuvant with existing therapy for the treatment of hyperlipidemia.

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Objective: To assess the pharmacokinetics of venlafaxine (VEN) and its major metabolite o-desmethylvenlafaxine (ODV) in freely moving mice using automated dosing/infusion (ADI) and automated blood sampling (ABS) systems. In addition, concentration of VEN and its metabolite ODV were also measured in brain by microdialysis. Materials and Methods: Venlafaxine was administered directly via jugular vein or gastric catheterization and blood samples were collected through carotid artery. A series of samples with 10 μl of blood was collected from the mouse using ADI/ABS and analyzed with a validated LC-MS/MS system. Extracellular concentrations of VEN and ODV in brain were investigated by using microdialysis procedure. Results: The bioavailability of VEN was 11.6%. The percent AUC ratios of ODV to VEN were 18% and 39% following intravenous and intragastric administration, respectively. The terminal half-life of venlafaxine was about two hours. Extracellular concentration of VEN contributed 3.4% of the blood amount, while ODV was not detected in dialysate. Conclusion: This study suggests that besides rapid absorption of VEN, the first-pass metabolism is likely to contribute for its lower bioavailability in the mouse. The proposed automated technique can be used easily to conduct pharmacokinetic studies and is applicable to high-throughput manner in mouse model.

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Introduction: Epilepsy is a chronic disease and neurocysticercosis is an important cause of secondary seizures. Its therapy is modified by a number of parameters and thus the pattern of anti-epileptic drugs used varies in different clinical settings. It was our objective to evaluate clinico-demographic and treatment profile of epilepsy patients attending neurology outpatient department, efficacy and side-effect profile of anti-epileptic drugs with special emphasis on epilepsy resulting from neurocysticercosis. Materials and Methods: This was a cross-sectional descriptive study of epilepsy patients over four months in neurology outpatient department. Clinico-biological data were obtained by interrogating patients and from recorded data using standard case-report form. Results: 79 patients were studied with 54.43% having primary etiology, 40.51% having seizures secondary to neurocysticercosis. 81% had generalized tonic-clonic seizure, 17.7% partial and 1.3% myoclonic seizures. Phenytoin (86.08%), valproate (30.38%), clobazam (26.58%) and carbamazepine (10.13%) were used either alone or in combination, with no use of anthelmintics even in cases of neurocysticercosis. Control of seizure was obtained in 79.7% with significant decrease in seizure frequency from 2.92 to 0.51 (P < 0.0001). Weight loss, nausea, decreased appetite, increased sleep, drowsiness, tremors were found to be significantly associated (P < 0.05) with phenytoin use. Conclusion: Phenytoin is the primary antiepileptic in spite of its side effects; though addition of other anti-epileptic drugs (valproate, clobazam) was required for better seizure control. Cases of neurocysticercosis respond to anti-epileptic drugs without addition of anthelmintics. Side effects observed were mostly neurological in nature.

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Objective: Broussonetia papyrifera is used as a traditional medicine to treat few diseases. However, the antiinflammatory effect of B. papyrifera stem bark has not been evaluated. The aim of this study is to investigate the effects of n-hexane fraction from methanol extract of B. papyrifera stem bark on lipopolysaccharide (LPS)-stimulated inflammation using RAW 264.7 cells. Materials and Methods: Methanol extract was obtained from B. papyrifera stem bark and its sequential fractions (hexane, dichloromathane, ethyl acetate, butanol, and aqueous) were obtained by extraction in solvents with increasing polarity and were examined in RAW 264.7 cells. Results: The secretion profiles of pro-inflammatory parameters, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were found to be significantly reduced in 10-80 μg/ml dose ranges of n-hexane fraction (BP-H) from methanol extract of B. papyrifera stem bark. The expressions of inducible NO synthase (iNOS) was also significantly inhibited by BP-H. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that BP-H treatment decreased LPS-induced iNOS mRNA expression in RAW 264.7 cells. Conclusion: The results suggest that the B. papyrifera stem bark has anti-inflammatory activity which inhibits the NO production and proinflammatory cytokines in RAW 264.7 cells. B. papyrifera stem bark might act as a potential therapeutic agent for inflammatory diseases.

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Aim: To evaluate the antinociceptive activity of acute and chronic administration of petroleum ether extract of Murraya koenigii L. leaves (PMK) and total alkaloids separated from petroleum ether extract of Murraya koenigii leaves (AMK) in mice. Materials and Methods: PMK was subjected for isolation of total alkaloid fraction AMK. The antinociceptive activity of PMK (100 and 300 mg/kg, p.o.) and AMK (100 and 300 mg/kg, p.o.), after acute and chronic administration (for 15 days), was evaluated using peripheral model like acetic acid-induced writhing method and central model like hot plate method and tail immersion method. Statistical analysis was carried out by one-way ANOVA followed by Dunnett's test. Result: In acute studies, PMK and AMK significantly and dose-dependently reduced the number of acetic acid-induced writhing, significantly increased the latency of paw licking in hot plate method, and significantly increased the basal reaction time in tail immersion method. With chronic administration of PMK and AMK, highest activity was observed on day 9 in acetic acid-induced writhing model. In hot plate and tail immersion method, chronic administration of PMK and AMK initially showed fluctuating responses but produced highest degree of antinociception on day 9 of the study. Conclusion: The degree of antinociception produced by PMK and AMK at the end of 15 days study suggest that Murraya koenigii has potential to use as an analgesic.

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Objectives: Chronic venous insufficiency (CVI) in lower limbs manifest as stasis dermatitis. The anti-collagenase, anti-inflammatory and immunomodulatory effects of doxycycline and the T-cell inhibitory effects of tacrolimus could theoretically modify the disease pathophysiology. This study was undertaken to evaluate the efficacy and safety of four weeks combination therapy of oral doxycycline 100 mg with topical tacrolimus 0.1% for stasis dermatitis associated with CVI. Materials and Methods: A single-arm, interventional pilot study was conducted on subjects with CVI of C4 to C6 category (CEAP classification: clinical, etiology, anatomical, pathophysiology). Treatment duration was four weeks with fortnightly follow-ups. Primary efficacy was assessed as changes from baseline of pigmentation, erythema, edema, itching and hair loss of the affected area evaluated on Likert scale scores. Secondary efficacy parameters were percentage improvement of the dermatitis area and changes in ulcer dimensions (maximum length and breadth), if present. Safety evaluation included all treatment emergent clinical signs and symptoms reported by the patients and/or observed by the physician. Results: Out of 19 recruited subjects, 15 completed the study for analysis. Significant (P<0.01) improvement in pain, edema, pigmentation, erythema and exudation were observed. Reduction of ulcer dimensions was also statistically significant (P<0.01). 86.6% showed improvement of the dermatitis area, 6.7% patients failed to show any improvement and 6.7% showed worsening. Adverse effects were observed in only two subjects. Conclusion: This pilot study suggests efficacy of this combination therapy in controlling features of stasis dermatitis but further studies are needed for validation.

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Objective: To study the analgesic activity of ash of silver used in Indian system of medicine and to explore its safety. Materials and Methods: Albino mice of either sex (20-30 gm) were used to investigate the role of ash of silver against noxious stimuli: thermal (Eddy's hot plate and analgesiometer), mechanical (tail clip), and chemical (0.6% acetic acid induced writhing). An effort was made to find nature and site of action of ash of silver following naloxone pre-treatment. Maximum tolerated dose (MTD) and lethal dosage 50 (LD50) were also studied along with toxicological aspects of ash of silver. Results: Test drug (ash of silver) at a dose of 50 mg/kg p.o exhibited analgesic activity against thermal, mechanical, and chemical stimuli. Analgesic effects were compared with the standard drug, morphine, in thermal and mechanical noxious stimuli and to aspirin in chemical stimulus. Analgesic activity of the test drug was reduced following naloxone pre-treatment. MTD was found out to be greater than 1.5 g/kg p.o. LD50 was 2 g/kg p.o. Fraction of mice showed symptoms of argyria as explained by autopsy reports. Conclusion: Test drug exhibited moderate analgesic activity at 50 mg/kg p.o against all type of noxious stimuli, also suggesting a role of opioidergic system. The ash of silver was been found to be safe upto a dose of 1.5 g/kg p.o. in mice without any untoward toxicity. Further studies are required to explore the effect of ash of silver on pain mediators and excitatory neurotransmitters like glutamate, aspartate, or N-methyl-D-aspartic acid (NMDA).

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Introduction: Gentamicin is an essential drug for the treatment of sepsis in neonates. The current work aims to optimize the use of gentamicin in neonates during the first week of life. Materials and Methods: The study was done at King Abdul-Aziz university hospital. Seventy-three neonates who received gentamicin 4-5 mg/kg and dosing interval at 24-48 hr were enrolled. Peak and trough serum levels of gentamicin were determined by immunoassay. Pharmacokinetic parameters were estimated assuming one compartment model and first order elimination kinetic. Analysis of variance was used to test the difference between means using Statistical Package for the Social Sciences (SPSS) Version 13. Results: About 73% of the patients attained peak gentamicin level within therapeutic range (6-12μg/ml), while 12% showed potentially toxic trough level (>2 μg /ml). The incidence of trough level was higher among patients receiving the drug every 24 hr. There was no clear correlation between high trough level and serum creatinine. High volume of distribution (Vd) of gentamicin (0.40-0.45) L/kg was observed. Neonates with proven sepsis showed higher mean Vd. Those with extremely low birth weight showed significantly longer half life of 11.5 h. Other neonates showed half life of (8-9) hr. Conclusions: Gentamicin dose of 4.5 mg/kg every 36 hr is recommended as simple empirical regimen during the 1 ^st week of life for neonates with normal or LBW and every 48 hr for those with ELBW.

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Aim: As injection is not an ideal means for insulin delivery, various attempts have been made to administer insulin orally until now. The development of an oral dosage form of insulin would help diabetic patients and make the treatment more convenient. The aim of the present study is to evaluate the effectiveness of an oral insulin formulation containing polar and non-polar ingredients. Materials and Methods: New excipient for oral insulin administration in normal and diabetic rats was evaluated by measuring blood glucose concentrations in two groups (10 rats each) of normal and streptozotocin-induced diabetic rats. Oral insulin was administrated and blood glucose was measured by glucometer at 0, 1, 2, 3 and 4 h post-feeding. The data was compared by Student's t test. Results: Oral insulin formulation significantly (P<0.05) reduced blood glucose from 100 mg/dl to 33.73 mg/dl and 451.66 mg/dl to 200.83 mg/dl at 4 h in normal and diabetic rats, respectively. Conclusion: The novel excipient used could protect insulin from gastric and pancreatic enzymes and reduce blood glucose concentration in both healthy and diabetic rats suggesting that oral delivery of insulin is feasible in a near future.

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Objectives: Ischemic preconditioning (IPC) has been demonstrated to make myocardium transiently more resistant to deleterious effect of prolonged ischemia. The opening of the mitochondrial permeability transition pore (mPTP) at the time of myocardial reperfusion is a critical determinant of cell death. L-thyroxine pre-treatment increases the tolerance of the heart to ischemia and produces cardioprotection similar to ischemic precondition. This study has been designed to investigate the mechanism involved in L-thyroxine-induced cardiomyocyte protection against ischemia-reperfusion (I/R) injury in rats. Materials and Methods: L-thyroxine (T ₄ ) was administered to Wistar rats (n=6) (25 μg/100 g/day s.c.) for two weeks. Hearts from normal and L-thyroxine-treated rats were perfused in Langendorff's mode and subjected to 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was analyzed in coronary effluent. Results: IPC and pharmacological preconditioning (PPC) significantly decreased (P<0.05) myocardial infarct size, release of LDH and CK-MB in rat heart. Perfusion of atractyloside, an opener of mPTP, significantly (P<0.05) attenuated the cardioprotective effect of IPC and L-thyroxine-induced pharmacological preconditioning (PPC) in normal rat heart. Conclusion: The cardioprotective effect of L-thyroxine-induced preconditioning may be mediated through inhibition of mPTP opening during reperfusion phase.

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Medication error is one of the important causes of preventable adverse drug reactions. It can occur in the form of administration of a wrong drug, in the wrong dose, to the wrong patient, in an unsuitable dosage form, for the wrong duration or by using an inappropriate route of administration. Intradermal skin testing for cloxacillin hypersensitivity is done at low doses to check for drug allergy. In this report, three patients were given 50 times higher dose of cloxacillin than recommended for skin testing, resulting in pain and necrosis at the site of injection. The error occurred due to wrong dilution of the drug as done by a nursing intern. Some reasons for this could be overtime working, under trained staff, unsupervised nursing interns, complicated and unclear protocols, interpersonal communication gap between health care professionals and also poor availability of ideal resources. Pharmacovigilance centers must alert health care professionals about the significance of reporting medication errors through bulletins and journals.

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Objective: To evaluate the effect of Ginkgo biloba extract (EGB) on the serum levels of cytokines in patients suffering from chronic, age-related neurological disorders (NDs). Materials and Methods: Patients received 9.6 mg of EGB twice daily for 8 weeks. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA) before and after treatment. Results: The serum level of IL-6 was significantly higher in ND patients as compared to the healthy controls. After these patients underwent 4 and 8 weeks of EGB treatment, their IL-6 levels were shown a statistically significant (P<0.05) decline to near normal values. No significant changes were observed in serum levels of IL-1β and TNF-α after EGB treatment. We also observed an inverse relationship between ND and serum cholesterol levels. Conclusions: EGB may exert its beneficial effects in patients suffering from NDs through down-regulation and suppression of IL-6 secretion.

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Ceftriaxone is a commonly used, third-generation cephalosporin. Encephalopathy is a rare side effect of third- and fourth-generation cephalosporins. Renal failure and previous disease of the central nervous system predispose to this neurotoxicity. We describe a case of acute transient encephalopathy in a patient treated with ceftriaxone for enteric fever infection. Early detection of this complication is relevant given that stopping the drug usually reverts the neurological syndrome.

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Objectives: To study the dose escalation pharmacokinetics and lipid lowering activity of a novel FXR modulator, 16-Dehydropregnenolone (DHP). Materials and Methods: The disposition of DHP following oral (36, 72, 100 and 150 mg/kg) and intravenous (1, 5 and 10 mg/kg) administration and its dose-response relationship were carried out in Sprague-Dawley rats. DHP and its metabolite 5-pregnene-3β-ol-16, 17-epoxy-20-one (M1) were analyzed by a validated LC-MS/MS method in plasma after intravenous and oral administration. Dose escalation lipid lowering activities were carried out by triton-induced hyperlipidemic model. Results: Oral administration resulted in higher amount of M1 formation as compared to intravenous administration. Dose escalation intravenous administration (1, 5 and 10 mg/kg) resulted in nonlinear increase in AUC of DHP. This was due to saturation of metabolism. On the contrary, systemic AUC and C _max after oral administration show non-linear pharmacokinetics where saturated systemic DHP and M1 pharmacokinetics was observed above 72 mg/kg, indicating saturated oral absorption. Lipid lowering activity by its oral route of administration was in accordance with its pharmacokinetic profile and reached saturation above 72 mg/kg. Conclusion: DHP exhibits route and dose-dependent pharmacokinetics. Pharmacokinetic and lipid lowering activity by oral route indicate saturation of oral absorption at higher doses. The study contributes to the understanding of the plasma disposition pharmacokinetics of DHP and its metabolite in rats by oral and intravenous route of administration.

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Objectives: This study was designed to investigate the gastroprotective effect of L-citrulline against gastric ischemia-reperfusion injury. Materials and Methods: Sodium pentobarbital-anesthetized rats underwent occlusion of the celiac artery for 30 min, followed by 60 min of reperfusion. Sixty minutes before ischemia, L-citrulline at doses of 300, 600, 900 mg/kg was administered intragastrically. Based on this animal model of gastric ischemia-reperfusion injury, the gastroprotective effect of L-citrulline was assessed by determining and comparing the ulcerative index and the estimation of myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in the gastric mucosal tissues. Moreover, the expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS) protein was also determined. Results: Intragastric administration of L-citrulline (600 and 900 mg/kg) 60 min before ischemia significantly ameliorated the gastric mucosal damage and inhibited the increase in MPO and MDA contents. Also, the increase in expression of iNOS protein was also prevented by L-citrulline. The expression of nNOS and eNOS was not affected significantly by I/R or L-citrulline. Conclusion: The results suggest that L-citrulline, administered exogenously, exhibits gastric protection by inhibition of neutrophil infiltration in rats, which may be related in prevention of the increase in iNOS activity.

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Acyclovir is an antiviral agent against herpes virus. Its local adverse effects are common and typically consist of inflammation or phlebitis at the site of intravenous infusion. Here we present a child with bullous eruptions away from infusion site due to acyclovir administration. It is exceptionally rare with only one adult case has been reported to date.

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The war against cancer has seen a proliferation in armamentarium over the last decades. A new antineoplastic agent, trastuzumab, was synthesized in 1991 and gained United States Food and Drug Administration approval in 1998 for treatment of metastatic breast cancer. Cardiotoxicity manifesting as dilated cardiomyopathy is a rarely reported adverse effect of trastuzumab. We hereby report a case of dilated cardiomyopathy, which occurred following trastuzumab chemotherapy in a 32-year-old female. The patient responded to discontinuation of trastuzumab and standard medical treatment. Extensive search of Indian literature revealed no reported case of dilated cardiomyopathy occurring due to trastuzumab.

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Steven-Johnson syndrome may be considered as a cytotoxic immune reaction to drugs, infections etc. This is a case report of Steven-Johnson syndrome due to an unknown preparation which was used in the treatment of mental retardation in a young girl.

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Objectives: The plasma-effect site equilibration rate constant (ke0) of propofol was determined with peak bispectral index (BIS) time (T _PEAK ) in our previous study. The present study has been conducted to evaluate the ke0's performance with effect site-controlled infusion algorithm. Materials and Methods: Forty unpremedicated patients were randomized to group TE1 (Schnider's pharmacokinetic model with ke0 adapted to T _PEAK = 74s) and TE2 (T _PEAK = 96s). In stage 1, all patients received propofol with effect-site concentration (Ce) controlled infusion. Once the pump had injected the mass of propofol necessary to achieve pre-set Ce and while the infusion was stopped, target was reset at 0 μg/ml. When BIS returned to 80 or above, then, in stage 2, the patients received plasma concentration controlled infusion for 10 min. The time of loss of responsiveness (LOR) and BIS were recorded. The differences of Ce at the time of LOR, lowest BIS between stages 1 and 2, hysteresis loop were used to evaluate the performance of ke0. Results: In both groups, the calculated propofol Ce at the time of LOR in stages 1 and 2 differed significantly (P<0.01); the mean lowest BIS in stage 1 were significantly higher than those in stage 2 (P < 0.05).The relations of propofol Ce versus BIS revealed the apparent hysteresis loop. Conclusions: The study cannot clinically validate the accuracy of application of ke0 derived from the T _PEAK = 74 s of BIS with Schnider propofol pharmacokinetic model.

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Valproate-induced hyperammonemic encephalopathy is a rare event clinically characterized by impaired sensorium, vomiting, headache, seizures and focal neurological deficits. The pathogenesis of this dreadful complication is not well understood, although hyperammonemia has been implicated in causation of encephalopathy. In this submission, we have highlighted a case of valproate-induced encephalopathy who presented mainly with bilateral cerebellar features and generalized slowing on electroencephalogram. High index of suspicion of valproate-induced hyperammonemic encephalopathy is required if diffuse ataxia is present as it is a potentially reversible clinical disorder.

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If virologic breakthrough is observed during chronic hepatitis B treatment, drug resistance or compliance problem should be considered. But in some cases, breakthrough depends on drug preservation conditions. We report the case of a 30-years-old man, who experienced viral breakthrough due to wrong preservation conditions of the drug.

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Voriconazole is a newer effective antifungal agent currently available for the treatment of invasive aspergillosis. The case we present describes an episode of serious persistent hypoglycemia after voriconazole therapy and we believe that this strongly contributed to this event. It is a warning to all that voriconazole has a propensity to alter glucose homeostasis in the presence of kidney disturbance.

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