Objectives: The islet vascular system is critical for β-cell function. This study investigated the antidiabetic effect of the Chinese Pu-Ren-Dan (PRD) recipe by regulating the pancreatic angiogenic factors in T2DM rats. Materials Methods: High fat diet/streptozotocin-induced obese type-2 diabetes mellitus rats were developed and treated with PRD for 4 weeks. Then glucolipid metabolism, insulin secretion, pancreatic blood flow, ultrastructure of islet β-cell, histological changes of islet and protein expressions of pancreatic angiogenic factors were investigated. Results: PRD-reduced T2DM rats' body weight and blood glucose level resisted the lipid metabolism disturbance, and ameliorated the insulin resistance and β-cell function. In addition, the histological and morphological studies proved that PRD could maintain the normal distribution of endocrine cell in islet and normal ultrastructure of β cell. An increased pancreatic blood flow was observed after the PRD treatment. In the investigation of pancreatic angiogenic factors, PRD inhibited the decreased expression of VEGF and Ang-1, and reversed the reduction of VEGFR2 and Tie2 phosphorylation in T2DM rats; the Ang-2 and TGFβ expression were up-regulated by PRD while PKC was activated; endostatin and angiostatin were down-regulated by PRD. Conclusions: The results suggest that increasing VEGF expression, regulating VEGF/VEGFR2 signaling, stimulating Ang-1/Tie-2 signaling pathway, and inhibiting PKC-TGFβ signaling and antiangiogenic factors might be the underlying mechanism of PRD's antidiabetic effect.

Objectives: Present study was undertaken to elucidate the ameliorating potential of Withania somnifera root extract (WRE) against lead-induced augmentation of adrenergic response in rat portal vein. Materials and Methods: In-vitro studies were conducted on effect of lead alone and lead+WRE on rat-isolated portal vein while in-vivo studies were done in three groups of 12 rats each; Group-II and III received 0.5% lead acetate and 1.0% WRE + 0.5% lead acetate, respectively, in drinking water for 12 weeks whereas group-I served as control. Adrenaline and noradrenaline levels in brain and blood were determined by HPLC assay while vascular reactivity of portal vein to lead and WRE was determined by measuring the isometric tension. Results: Following in-vitro exposure, lead did not alter the contractile effect of phenylephrine. In-vivo studies revealed that contractile effect of lead on portal vein was significantly potentiated and it was antagonized by prazosin (10 ^-7 M) and WRE (1%). WRE treatment significantly reduced elevated blood noradrenaline (37.80%) and restored noradrenaline level in brain (39.39%) in lead-exposed animals. These values were almost comparable to the control group. But it failed to significantly affect the blood and brain adrenaline levels. Conclusions: Results suggest that following pre-exposure of rats to WRE, lead-induced augmentation of alpha ₁ -adrenoceptors mediated response was reversed possibly by regulating catecholamine release from nerve endings. Thus, WRE may be useful in therapeutic management of lead-induced hypertension.

Objective: algae isolates obtained from fresh and marine resources could be one of the richest sources of novel bioactive secondary metabolites expected to have pharmaceutical significance for new drug development. This study was conducted to evaluate the antiangiogenic and antiproliferative activity of Chlorella pyrenoidosa in experimental models of angiogenesis and by MTT assay. Materials and Methods: lyophilized extract of C. pyrenoidosa was extracted using dichloromethane/methanol (2:1), concentrated and vacuum evaporated to obtain the dried extract. The crude extract was evaluated in the vascular endothelial growth factor (VEGF)-induced angiogenesis in in ovo chick chorioallantoic membrane assay (CAM) at various concentrations (n = 8) using thalidomide and normal saline as positive and untreated control groups, respectively. The crude extract was also subjected to the antiangiogenic activity in the silver nitrate/potassium nitrate cautery model of corneal neovascularization (CN) in rats where topical bevacizumab was used as a positive control. The vasculature was photographed and blood vessel density was quantified using Aphelion imaging software. The extract was also evaluated for its anti proliferative activity by microculture tetrazolium test (MTT) assay using HeLa cancer cell line (ATCC). Results: VEGF increased the blood vessel density by 220% as compared to normal and thalidomide treatment decreased it to 67.2% in in ovo assay. In the in-vivo CN model, the mean neovascular density in the control group, the C. pyrenoidosa extract and bevacizumab group were found to be 100%, 59.02%, and 32.20%, respectively. The Chlorella pyrenoidosa extract negatively affected the viability of HeLa cells. An IC ₅₀ value of the extract was 570 μg/ml, respectively. Conclusion: a significant antiangiogenic activity was observed against VEGF-induced neovascularization and antiproliferative activity by MTT assay. In this study, it could be attributed that the activity may be due to the presence of secondary metabolites in the C. pyrenoidosa extract.

Objectives: The objective of this study is to evaluate the neuroprotective effect of gossypin (isolated from Hibiscus vitifolius) against global cerebral ischemia/reperfusion (I/R) injury-induced oxidative stress in rats. Materials and Methods: Sprague Dawlet rats of wither gender were used in the study. Evaluation of cerbroprotective activity of bioflavonoid gossypin (in 5, 10 and 20 mg/kg oral doses) isolated from H. vitifolius was carried out by using the global cerebral I/R model by bilateral carotid artery occlusion for 30 min, followed by 24 h reperfusion. The antioxidant enzymatic and non-enzymatic levels were estimated along with histopathological studies. Result: Gossypin showed dose-dependent neuroprotective activity by significant decrease in lipid peroxidation (P < 0.001) and increase in the superoxide dismutase, catalase, glutathione and total thiol levels in gossypin treated groups when compared to control group. Cerebral infarction area was markedly reduced in gossypin treated groups when compared to control group. Conclusion: Gossypin showed potent neuroprotective activity against global cerebral I/R injury-induced oxidative stress in rats.

Objectives: To compare the effect of melatonin and gabapentin on anxiety, pain, sedation scores, and satisfaction of surgeon in patients of cataract surgery. Materials and Methods: One hundred thirty patients aged between 35 and 85 years scheduled for cataract surgery were randomly allocated to three study groups to receive melatonin (6 mg), gabapentin (600 mg) or placebo 90 min before arrival in the operating room. Pain, anxiety, and sedation scores during block and surgery as well as the surgeon's satisfaction with the surgery were assessed. Results: Anxiety scores decreased significantly in melatonin and gabapentin groups compared to the placebo group after premedication and extended to early postoperative period. The level of anxiety showed no statistically significant difference between melatonin and gabapentin groups at any time of measurement. There were significant differences between the pain scores during retrobulbar placement in gabapentin versus placebo (95% CI 3 to 4; P = 0.001) and melatonin (95% CI 3 to 4; P = 0.040) groups. Also, there were significant differences between the sedation scores during retrobulbar placement in gabapentin and placebo groups (95% CI 2 to 2.5; P = 0.046). The difference in sedation scores during retrobulbar placement in melatonin versus gabapentin and placebo groups was not significant. Neither the intraoperative pain scores nor the postoperative pain scores were different between the three groups. The surgeon reported similar quality of operation conditions during surgery for the three study groups. Conclusion: The level of anxiety was significantly lower with both anxiolytic drugs compared to placebo. Furthermore, gabapentin decreased the pain and improved the sedation scores only during retrobulbar placement compared to the placebo.

Objectives: Safe parenteral drug administration includes preparation of safe medication for administration. Training medical students is crucial to minimize medication administration errors. The study aims to develop a module to teach drug preparation skills and to develop objective structured practical examination (OSPE) stations to assess these skills. Students' perceptions regarding the module were also assessed. Materials and Methods: A module was developed to teach following skills to 2 ^nd year medical students: Aspiration of a drug from the ampule, aspiration of the drug from the vial, aspiration of the drug in powdered form from vial (reconstitution), and setting up an intravenous (IV) infusion. A randomized case control study design was used to establish the validity of OSPE stations. Student volunteers were grouped into case (n = 20) and control groups (n = 20) by simple randomization. The test group watched videos of skills and received demonstration of skills and a practice session before OSPE, whereas the control group watched videos before the OSPE and received demonstration and a practice session only after the OSPE. Each student was assessed by two faculty members during OSPE using a validated checklist. Mean OSPE scores of control and test groups were compared using independent samples t-test. Interrater reliability and concurrent validity of stations were analyzed using interclass correlation coefficient (ICC) and Pearson correlation, respectively. Students' responses were expressed as median and interquartile range. Results: The response rate in the questionnaire was 100%. Significant difference between mean scores (P < 0.05) of test and control groups revealed fulfillment of construct validity of OSPE stations. Interrater reliability (ICC > 0.7) and concurrent validity (r value > 7) of all the stations was high. Perceptions revealed acceptability of module and OSPE stations by students (median 4, scale 1-5). Conclusions: A module to teach drug preparation skills was developed and along with valid and reliable OSPE stations that were acceptable to students. The study demonstrated that students acquire better skills through teaching than merely watching these skills in videos.

Background: The mechanism of action of sweet substance-induced analgesia is thought to involve activation of the endogenous opioid system. The nitric oxide (NO) pathway has a pivotal role in pain modulation of analgesic compounds such as opioids. Objectives: We investigated the role of NO and the opioid receptor-mediated system in the analgesic effect of sucrose ingestion in mice. Materials and Methods: We evaluated the effect of intraperitoneal administration of 10 mg/kg of NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) and 20 mg/kg of opioid receptor antagonist, naltrexone on the tail flick response in sucrose ingesting mice. Results: Sucrose ingestion for 12 days induced a statistically significant increase in the latency of tail flick response which was unmodified by L-NAME, but partially inhibited by naltrexone administration. Conclusions: Sucrose-induced nociception may be explained by facilitating the release of endogenous opioid peptides. Contrary to some previously studied pain models, the NO/cyclic guanosine monophosphate (cGMP) pathway had no role in thermal hyperalgesia in our study. We recommend further studies on the involvement of NO in other animals and pain models.

Objective: The objective of this study was to investigate the reversal effects of 5,5'-dimethoxylariciresinol-4'-O-β-D-glucoside (DMAG) extracted from traditional Chinese medicines Mahonia on multidrug resistance (MDR) of human leukemia cells to chemotherapeutic agents. Materials and Methods: MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine the effect of DMAG on doxorubicin sensitivity to K562/DOX cells. Propidium iodide /Hoechst 33342 double staining assay was used to investigate the effect of DMAG on doxorubicin-induced cellular apoptosis. Intracellular accumulation of doxorubicin and rhodamine 123 assay were performed to evaluate the effect of DMAG on drugs efflux activity of P-glycoprotein. Results: DMAG significantly enhanced the doxorubicin cytotoxicity to K562/DOX cells. In the presence of 1.0 μM of DMAG, the IC ₅₀ of doxorubicin decreased from 34.93 ± 1.37 μM to 12.51 ± 1.28 μM. DMAG of 1.0 μM significantly enhanced doxorubicin-induced cell apoptosis in K562/DOX cells and the enhancement was time-dependent. A significant increase in accumulation of doxorubicin in the presence of DMAG was observed. After treatment of the K562/DOX cells for 1 h with 15.0 μM doxorubicin alone, the fluorescence intensity was 33093.12. With the addition of 1.0 μM of DMAG, the fluorescence intensity of doxorubicin was 2.3-fold higher. A significant increase of accumulation of rhodamine 123 in the presence of DMAG was also observed. With the addition of 1.0 μM of DMAG, the fluorescence intensity was increased by 49.11% compared with rhodamine 123 alone. Conclusion: DMAG was shown to effectively enhance chemosensitivity of resistant cells, which makes it might be a suitable candidate for potential MDR-reversing agents.

Objectives: To detect the prevalence and pattern of use of Potentially inappropriate medications (PIMs) in hospitalized elderly patients of a tertiary care teaching hospital using Beers 2012 criteria and to compare the same with Beers 2003 criteria. Materials and Methods: Prescriptions of the elderly patients aged 65 years and above were collected from the medicine ward and analyzed. PIMs were identified with help of Beers 2003 and Beers 2012 criteria and comparison was made between the two criteria. Predictors associated with use of PIM were identified using bivariate and multivariate logistic regression analysis. Results: A total of 210 patients received 2,267 drugs. According to Beers 2003 criteria, 60 (28.57%) elderly patients received at least one PIM and 2.9% drugs were prescribed inappropriately. According to Beers 2012 criteria, 84 (40%) elderly received at least one PIM while 22 (10.47%) received multiple PIMs and about 5% drugs were prescribed inappropriately. The most commonly prescribed PIM was mineral oil-liquid paraffin (30, 14.3%) followed by spironolactone (25, 11.9%), digoxin (19, 9%), and benzodiazepines (14, 6.7%). There was a significant association between the number of patients receiving more than six drugs and the use of PIMs (P < 0.01). Use of more than 10 drugs was a significant predictor for use of PIMs in the elderly. Conclusion: The study shows high prevalence of prescribing PIMs in hospitalized elderly patients. Beers 2012 criteria are more effective in identifying PIMs than Beers 2003 criteria.

Objectives: Studies have established the effectiveness and safety of polymyxins in treating multidrug resistant (MDR) pathogens. However, the challenge is whether these nephrotoxic drugs can be administered in compromised renal states. The present study was undertaken to establish their role in such patients. The effectiveness and nephrotoxicity of polymyxins in critically ill-patients harboring MDR Gram-negative bacteria with already compromised renal functions was compared with those with normal renal functions. Materials and Methods: This retrospective cohort study (March 2008-March 2010) was conducted in the intensive care unit of a tertiary care hospital. A total of 48 eligible critically ill-patients receiving polymyxins were enrolled. A comparison was carried out (length of stay in hospital, mortality, renal function) between patients with acute kidney injury (AKI, n = 18; defined by the RIFLE classification) and patients with normal renal function (non-AKI, n = 30). Results: Patients with baseline AKI had a significantly higher adjusted mortality rate at admission when compared with the non-AKI group. At the end of therapy with polymyxins, 26.66% non-AKI patients developed renal dysfunction while 38.88% of patients in the AKI group had worsening of renal function (P = 0.006). However, there was no significant difference in the length of hospital stay (23.9 ± 13.24 vs. 30.5 ± 22.50; P = 0.406) and overall mortality (44.4% vs. 36.7%; P = 0.76) between two groups. Conclusion: Polymyxins can be administered in AKI patients with favorable results provided used judiciously with strict monitoring of renal functions, dose modification according to creatinine clearance and aggressive fluid management.

Introduction: The present study was designed to evaluate the effect of granulocyte-colony stimulating factor (G-CSF) in the treatment of Parkinson's disease (PD), the second most common neurodegenerative disease characterized by muscle and movement disorder, often associated with depression. PD is very difficult to treat. Hence, the present study was aimed to evaluate the effect of G-CSF in PD associated with depression. Materials and Methods: Adult Wistar male rats weighing about 180-250 g were selected and divided into five groups in parallel designed method namely; control group (n = 5); sham operated group (n = 5); Vehicle group (n = 5); G-CSF group (70 μg/kg, s.c.) (n = 5) and L-DOPA group (n = 5). The rats were treated with 6-hydroxydopamine (6-OHDA) on day 0 and then treatment was continued for 14 day of L-DOPA/carbidopa, whereas G-CSF (70 μg/kg, s.c.) was given from day 1 to 6. Thereafter, adhesive removal and forced swim tests were conducted to evaluate the behavioral outcome of G-CSF treatment. The finding was correlated and analyzed with Nissl staining findings for the final conclusion. Results: The behavioral parameters were assessed and found to be ameliorate the symptoms of Parkinson's and reduced the depression like behavior in PD. The histological findings were supported the behavioral findings and showed pathological improvement. Conclusion: As a preliminary work, the present study first time suggested that G-CSF have a potential role in PD and associated depression.

This study aimed to evaluate the awareness of nurse/midwives regarding pharmacovigilance as well as their knowledge and experience in identifying and reporting adverse reactions of drugs. Nurse/midwives (n = 329), working in four state hospitals, were provided a questionnaire with a view of identifying their knowledge and skills pertaining to pharmacovigilance. Around 45% of the participants claimed to have knowledge of pharmacovigilance but only 23.3% of them could define it correctly. Although 24.3% of the participants acknowledged that adverse reactions should be reported to a centre, only 1.2% of them named this centre (Turkey Pharmacovigilance Centre-TUFAM). The present study indicates that nurse/midwives have insufficient knowledge of pharmacovigilance practices. Hence, it is essential to include pharmacovigilance training in their undergraduate and graduate education programs, and to promote reporting of adverse reactions.

Objectives: The aim of this study was to investigate the efficacy of dezocine (DEZ) versus placebo control (CON) and 2% lidocaine (LID) in prevention of injection pain due to DEZ. Materials and Methods: A prospective randomized double-blind, placebo-CON study was conducted in 75 adults, American Society of Anesthesiologists physical status I or II, scheduled to undergo an elective surgery. A total of 25 patients were randomly assigned to one of the three groups, thus CON, group LID and group DEZ. The groups received either 2 ml of normal saline or 2 ml 2% LID or 2 mg/2 ml DEZ, respectively, as pre-treatment. Propofol was injected 1 min later. A blinded researcher assessed the patient's pain level using a four point verbal rating scale. Results: Less patients experienced pain due to propofol injection in the LID (40%) and DEZ (28%) groups compared with the CON (84%) group (P < 0.05). Six patients (24%) in the CON group reported severe pain during propofol injection but none in the other two groups. Conclusion: Pre-treatment with DEZ decreases propofol injection pain as effectively as LID.

Aims and Objectives: The aim of this study is to compare the efficacy, safety and cost-effectiveness of topical Whitfield's ointment plus oral fluconazole with topical 1% butenafine in tinea infections of the skin. Materials and Methods: Patients were randomly allocated to the two treatment groups and advised to apply either agent topically twice-a-day for 4 weeks on the lesions and fluconazole (150 mg) was administered once a week for 4 weeks in the study group applying Whitfield's ointment. Patients were followed-up at an interval of 10 days for clinical score and global evaluation response was assessed at baseline and during each follow-up. Results: Out of 120 patients enrolled in the study 103 completed the study. Patients treated with Whitfield's ointment and oral fluconazole reduced mean sign and symptom score from 8.81 ± 0.82 to 0.18 ± 0.59 while butenafine treated patients reduced it from 8.88 ± 0.53 to 0.31 ± 0.67 at the end of the treatment. Nearly, 98% patients were completely cleared of the lesion on the 3 ^rd follow-up with both treatments. Conclusion: Whitfield's ointment with oral fluconazole is as efficacious, safe and cost-effective as compared with 1% butenafine in tinea infections of the skin.

Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a severe cutaneous drug reaction with a high mortality. Immune response is the possible cause in its pathogenesis. Levofloxacin is one of the most commonly used quinolones and has been reported to cause of TEN. On the other hand, furazolidone was proposed to augment the action of immediate hypersensitivity of levofloxacin by its cytotoxic effect and by the generation of free radicals. Here, we present a case of TEN where, levofloxacin and furazolidone were the probable cause of these adverse drug reactions.

Allopurinol, a widely prescribed urate lowering agent is responsible for various adverse drug reactions, including erythroderma. A 45-year-old male patient was admitted with the complaints of fever, redness and scaling all over the body after 3-4 weeks of allopurinol treatment for asymptomatic hyperuricemia. Elevated liver enzymes were detected in his blood analysis. Skin biopsy was consistent with drug induced erythroderma. Allopurinol was stopped and steroids were started. Patient improved over a period of 2 weeks.

Priapism is defined as a prolonged and persistent, painful erection of the penis without sexual stimulation or arousal. There have been a few case report of priapism resulting from the use of antipsychotics. In our case, a 48-year-old male patient with a bipolar affective disorder was experiencing recurrent priapism with sodium valproate. The condition was found to resolve on stopping sodium valproate. There are no known case reports of similar complication with sodium valproate alone.

Methotrexate (MTX) may have adverse effects on multiple organs and system. A few cases of pulmonary tuberculosis in-patients with rheumatoid arthritis (RA) while receiving MTX monotherapy has been reported in the literature. We submit a case of vertebral tuberculosis with hypercalcemia in a patient receiving MTX monotherapy. Patient with RA taking MTX for 15 years developed pancytopenia, skin necrosis, tuberculous spondylodiscitis and hypercalcemia. The present case showed adverse effects of MTX therapy may occur even after years of continuous treatment. Due to pancytopenia in older patients, life-threatening tuberculosis at unusual sites may develop.

Imatinib, a specific tyrosine kinase inhibitor is a newer anticancer agent, which has shown excellent efficacy in managing chronic myeloid leukemia. It is generally well tolerated with few side effects. Most commonly reported adverse events are maculopapular eruptions and periorbital edema. Severe adverse reactions are seen in 5% of patients. Exfoliative dermatitis has been very rarely reported with this drug. We report a case of a 52-year-old male who initially presented with a maculopapular rash and developed erythroderma on continuation of the drug.

Epilepsy is an important health problem due to its high prevalence and potential for causing long-term morbidity. It is commonly treated in children with phenytoin sodium. It has wide pharmacokinetic variability and a narrow therapeutic range that leads to toxicity. Here, we report a case of phenytoin-induced cerebellar atrophy in a 16-year-old epileptic boy who presented to the hospital with a viral infection.

Antiepileptic Drugs (AEDs) such as lamotrigine, gabapentin, and oxcarbazepine may have the potential to increase the risk of self-harm or suicidal behavior. We report a case of pregabalin-induced self-inflicted multiple injuries on forearm after its continuous use. This is an interesting adverse drug reaction (ADR) that is rare, unusual, and potentially serious.