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Background: The toxic effect of sodium arsenate on nervous system has been shown; but the protective effects of several compounds against sodium arsenate are not clear. This study aimed to investigate the protective effects of nicotine and bucladesine, two positive modulators of neuronal function, on sodium arsenate toxicity against avoidance memory impairment. Methods: Male mice (N=154) were assigned to 22 groups (12 experimental and 10 control) of seven animals each and were treated as follows: sodium arsenate (2.5, 5, or 10 mg/kg) for 28 days, nicotine (1 mg/kg) for either 1, 2, or 4 days, bucladesine (600 nM/mouse) for either 1, 2, or 4 days, and nicotine (1 mg/kg)+bucladesine (600 nM/mouse)+sodium arsenate (2.5 mg/kg). The last group was treated with 2.5 mg/kg sodium arsenate first, and then received the combination of nicotine and bucladesine for 1, 2, or 4-days. The corresponding control groups did not receive any drug but either saline, deionized water, or combination of deionized water and DMSO, but went through the same procedure as other animals. All mice were trained 24 h in the step-through passive avoidance task. The avoidance memory retention was assessed at 24, 48, 96, and 168 h after the training period by measuring the time they stayed in a dark chamber. Results: All sodium arsenate doses significantly reduced the time stayed in the dark chamber regardless of the treatment duration (24, 48, 96 & 168 h) after training. Both nicotine and bucladesine, whether used singly or combined for 1, 2, and 4 days significantly enhanced the time latency compared to the controls at all of the experimental timepoints following the training. Conclusion: Nicotine and bucladesine showed synergistic effects and reversed the sodium arsenate-induced avoidance memory deficits in mice.

The assay presented here was designed to assess the immediate effects of ethanol (EtOH) exposure on intracellular signaling activated by BMPs (Bone Morphogenetic Proteins). Previous reports of the relationship between EtOH exposure and BMP-dependent signaling have primarily assessed the expression of individual BMPs, changes in BMP target genes or effects on the phosphorylation level of key downstream mediators after days or weeks of

This study explores the effect of acute Ethanol (EtOH) exposure on Bone Morphogenetic Protein (BMP)-evoked intracellular signaling, and the concomitant morphological changes induced by EtOH in C2C12 cells and DRG (Dorsal root ganglion) neurons in an in vitro model related to Fetal Alcohol Syndrome Disorder (FASD). All assays were performed within 30 min of BMP stimulation to specifically investigate the earliest events occurring in BMP-evoked intracellular signaling pathways. We show that Smad phosphorylation and nuclear translocation stimulated by BMPs was not altered following acute exposure to EtOH. In contrast, acute EtOH exposure alone caused a striking concentration-dependent decrease in Akt phosphorylation, as well as a loss of adhesion in C2C12 cells. The addition of BMPs before exposure to EtOH was associated with maintenance of Akt phosphorylation, greater cell adhesion in C2C12 cells, and preservation of growth cone complexity in DRG neurons. Thus, for both C2C12 cells and DRG neurons, BMPs, acting through non-canonical BMP signaling pathways, appear to impart some protection against the profound effects of acute EtOH exposure on cellular adhesion and structure.

Autophagy is an evolutionarily conserved cellular mechanism in eukaryotes that plays an important role in the maintenance of cellular homeostasis. The autophagy process maintains protein homeostasis by recycling damaged organelles and degrading many long-lived proteins in conjunction with the ubiquitin-proteasome system. Cytokines are low molecular weight secreted proteins that regulate a broad range of biological activities. For instance, pro-inflammatory cytokines such as tumor necrosis factor-α (TNFα) induce inflammation, autophagy, and apoptotic cell death. In this chapter, we discuss experimental techniques such as immunoblotting and fluorescence microscopy that can be utilized to measure autophagy in response to TNFα treatment.

Background Pharmacists' interventions to improve outcomes of diabetes management have been promising. However, evidence on using telephone-based interventions in pharmacy practice are limited, particularly in developing countries. Objective To evaluate the efficacy of a telephone-based intervention to improve care and clinical outcomes in type-2 diabetes. Setting A referral community pharmacy and drug information center. Method We conducted a two-armed randomized controlled trial on 100 patients with type-2 diabetes. The intervention consisted of 16 telephone calls in 3 month by a trained pharmacist working in an academic drug information center, while the control group received usual care. Before random allocation, patients attended a live education session delivered by pharmacists to learn the basics of diabetes care and to confirm the eligibility criteria. Assessments were performed at baseline, month-3 (after intervention), and month-9 (follow-up). Main outcome measure Hemoglobin A1c (HbA1c). Results Eighty four patient completed the trial. Baseline variables were comparable between the two groups and the baseline value of hemoglobin A1c was 8.00 ± 1.44 in the study population. HbA1c was significantly improved in both groups at month-3 (6.97 ± 1.41 vs. 7.09 ± 1.78) and remained steady at month-9 (6.96 ± 1.44 vs. 7.26 ± 1.85). Lipid profile showed small improvements in the intervention group but was not significant. The adherence score and self-care score improvement was significantly higher in the intervention group at month-3 and were maintained at month-9. Conclusion Medication adherence and self-care significantly improved in the telephone-based intervention group. However, the improvement of clinical outcomes might have been diluted due to the live diabetes education session.

Plasma medicine is an innovative and emerging field used in a broad range of medical conditions. The present study focused on consumption and documentation pattern of plasma-derived medicines in a teaching hospital. A two-step study was conducted from October to December 2015. During the first phase, the patient records receiving plasma-derived medicines including Coagulation Factor VIII, IX, Prothrombin Complex Concentrate, Factor VIII/Von Wilberand Complex, Anti-Hepatitis B Immunoglobulin, Intravenous Immunoglobulin, Anti-Tetanus Immunoglobulin, and Albumin were checked to assess recording details of these medications at the time of administration. Adverse events reported with the mentioned products were examined from traceability viewpoint. The second step concentrated on practical strategies to improve documentation status of plasma-derived medicines in the hospital. We proposed national guideline as the first strategy and a new barcoding system to track and identify drug information of plasma medicines. Of the expected drug information, only generic name, dosage from, and strength were recorded after administration. Post-marketing safety surveillance of the plasma products was poor similarly. Unavailability of suitable instructions was the main reason for documentation deficiency. A guideline was designed and implemented to inform healthcare professionals about essentials of appropriate documentation for plasma-derived medicines. Updated results of the ongoing phase will be submitted soon. Our survey highlights the importance of documentation as a key component of plasma-derived medicines surveillance within the hospitals.

Introduction Accumulated evidence shows that the cAMP-PKA signaling pathway plays a key role in memory functions. Cyclooxygenase-2, a critical player in neuroinflammation, has been confirmed in the pathogenesis of neurodegenerative diseases. This study is aimed to assess the effect of the interaction of cAMP-PKA and cyclooxygenase pathways on spatial memory acquisition in animal models. Material and methods In the present study, the effects of the four-day bilateral intra-hippocampal infusions of H-89 as a protein kinase AII inhibitor (10 µM/side), celecoxib (0.1 M/side) as a selective cyclooxygenase-2 inhibitor, cele-coxib/H-89 and bucladesine (10 µM/side)/celecoxib/H-89 on spatial memory acquisition in the Morris water maze were investigated. Control animals received bilateral intra-hippocampal infusions of dimethyl sulfoxide. Rats were trained for 4 days; each day included one block of four trials. Post-training probe trial tests were performed on day five. Results A bilateral intra-hippocampal infusion of H-89 and celecoxib led to a significant impairment in spatial learning compared to the controls through a notable decrease in escape latency and traveled distance. But, combination treatment of animals with celecoxib/H-89 and bucladesine/celecoxib/H-89 could considerably reverse celecoxib and H-89-induced spatial memory acquisition impairments in the Morris water maze. Conclusions These results indicate the probable regulatory effects of cAMP/PKA and cyclooxygenase-2 signaling pathways on spatial memory acquisition in the Morris water maze.

Background Irrational use of medicines is a widespread problem in healthcare and imposes huge costs on health systems. Purpose To promote rational drug prescription and expenditure, we performed a study on albumin and pantoprazole expenditure in our hospital. Material and methods A cross sectional study was conducted to examine the role of a restrictive protocol on intravenous pantoprazole and albumin consumption. The protocol was designed by clinical pharmacists and after approval by a drug and therapeutics committee, was presented to hospital wards. The pharmacists from the hospital pharmacy approved dispensing of pantoprazole and albumin to medical wards only if the physician’s order accompanied a signed paper protocol and the prescription conformed to the protocol. Otherwise, the pharmacist consulted with the physician to prescribe appropriate alternatives. The average consumption and cost of albumin and pantoprazole were analysed, comparing 3 months before with 3 months after protocol enforcement. The average number of consumed vials per month and related expenditure were obtained from the hospital information system. Results The average monthly consumption of albumin was 1832 vials before and 858 vials after the intervention. The mean albumin cost per hospital bed day was $2.6 before and $1.5 after the intervention, leading to a cost difference of about $1.1 per hospital bed day with a mean monthly saving of about $29 751 (43% decline in albumin expenditure). The mean monthly consumption of intravenous pantoprazole was 6043 vials before and 4713 vials after the intervention. The mean expenses per hospital bed day was $7.6 before and $6.2 after implementing the intervention. The protocol successfully decreased pantoprazole consumption by $1.4 per hospital bed day with a mean monthly saving of about $38 803. (Approximately 19% reduction in monthly pantoprazole expenditure.) Conclusion Our study confirms that our protocol may substantially reduce albumin and pantoprazole use and lead to significant cost savings. No conflict of interest

Background Acetaminophen is an analgesic and antipyretic agent, recommended worldwide as a firstline treatment for the management of mild to moderate pain. There is a significant cost difference between parenteral and oral/rectal preparations of acetaminophen in Iran. Additionally, intravenous (IV) administration imposes an extra preparation and nursing burden. Invasive procedure complications is another concern. Although acetaminophen relieves mild to moderate pain and has a synergistic effect with other analgesics, the IV route should only be used if the oral or rectal dosage form cannot be utilised. Purpose The primary objective of this study was to evaluate the utilisation of IV acetaminophen and clarify the role of protocol enforcement in decreasing the cost of pharmacotherapy and progressing to rational drug usage. Material and methods A pilot study was conducted in February 2015 to evaluate the prescribing appropriateness of IV acetaminophen. Data were obtained from a randomly selected group of 230 patients. A protocol for appropriate use of parenteral acetaminophen was designed by the pharmaceutical care department in accordance with drug monograph and reliable guidelines. The protocol was implemented in two phases: in phase one, the protocol was introduced to healthcare professionals via a newsletter, text messaging and face to face meetings with influential physicians. In the second phase, the pharmacists approved dispensing of IV acetaminophen to medical wards only if the physician’s order accompanied a signed paper protocol. The trend of IV acetaminophen utilisation was assessed during the intervention. Results During February 2015, 5139 acetaminophen injections were prescribed for 1631 patients. Inappropriate orders were revealed in 41% of the dosage forms, 38% for duration and 50% for dosages. Only in 27% of patients were all three parameters correct. Following phase one, the number of prescribed IV acetaminophen doses decreased to 3152 for 932 patients in one month (approximate 38% reduction). After the second phase, the use of acetaminophen was 2328 injections in 808 patients after protocol enforcement. The net reduction was 55% after the two phase intervention. Conclusion Development and implementation of drug protocols could improve appropriate prescribing and reduce cost in hospital settings. No conflict of interest

Background: Cardiovascular disease is a major health concern around the world. Objective: To assess the outcomes and feasibility of a pharmacy-based cardiovascular screening in an urban referral community pharmacy in Iran. Methods: A cross sectional study was conducted in a referral community pharmacy. Subjects aged between 30-75 years without previous diagnose of cardiovascular disease or diabetes were screened. Measurement of all major cardiovascular risk factors, exercise habits, medical conditions, medications, and family history were investigated. Framingham risk score was calculated and high risk individuals were given a clinical summary sheet signed by a clinical pharmacist and were encouraged to follow up with their physician. Subjects were contacted one month after the recruitment period and their adherence to the follow up recommendation was recorded. Results: Data from 287 participants were analyzed and 146 were referred due to at least one abnormal laboratory test. The results showed 26 patients with cardiovascular disease risk greater than 20%, 32 high systolic blood pressure, 22 high diastolic blood pressures, 50 high total cholesterol levels, 108 low HDL-C levels, and 22 abnormal blood glucose levels. Approximately half of the individuals who received a follow up recommendation had made an appointment with their physician. Overall, 15.9% of the individuals received medications and 15.9% received appropriate advice for risk factor modification. Moreover, 7.5% were under evaluation by a physician. Conclusion: A screening program in a community pharmacy has the potential to identify patients with elevated cardiovascular risk factor. A plan for increased patient adherence to follow up recommendations is required.

Nitric oxide (NO) is thought to be involved in spatial learning and memory in several brain areas such as hippocampus. This study examined the effects of post-training intrahippocampal microinjections of 1400W as a selective iNOS inhibitor on spatial memory, in anesthetized and non-anesthetized situations in rats. In the present work, 4-day training trials of animals were conducted. Spatial memory was tested 48 hours after the drug infusions. For microinjection of 1400W into CA1 region of the hippocampus in conscious animals, guide cannula was implanted into the CA1 area and 1400W was infused after recovery from surgical anesthesia. In anesthetized animals, 1400W was microinjected directly into CA1 region by Hamilton syringe during anesthesia. After completion of training, 1400W (10, 50 and 100 μM/side) were microinjected bilaterally (1 μL/side) and testing trials were performed 48 h after drug infusions in both groups of cannulated and non-cannulated rats. Significant reduction was observed in escape latency and traveled distance in animals that received 1400W (100 μM/side, *p < 0.05) via cannula after recovery in comparison with control group. Also, microinjection of 1400W (100 μM/side) in post recovery phase caused a significant (***p < 0.001) reduction in time and distance of finding the hidden platform in comparison with anesthetized situation. These findings suggest that 1400W has a significant improvement on spatial memory and memory enhancement induced by iNOS inhibitor can be affected by anesthesia in a period of time.

Several lines of evidence show that cAMP-PKA signaling pathway plays critical role in memory functions and suggest nitric oxide as an important modulator in learning and memory. In this study, we assessed the effects of intra-hippocampal infusion of H-89, a selective PKAII inhibitor, and 1400 W, a selective inducible nitric oxide synthase (iNOS) inhibitor, on spatial memory in rats. By using the Morris water maze, spatial memory retention parameters were examined 48 h after the infusions through measuring escape latency, traveled distance, and swimming speed. The rats receiving intra-hippocampal infusions of 1400 W (100 µM/side) showed a significant reduction (*P0.05) in escape latency and traveled distance in comparison with the control saline group. In contrast, a significant increase (**P0.01) in escape latency and traveled distance was observed after infusion of 10 µM H-89. Moreover, among combination groups, co-administration of 1400 W (400 µM/side) with 10 µM/side of H-89 caused a significant reduction (*P0.05) in escape latency and traveled distance in comparison with the H-89 group. Also, we evaluated the molecular effects of 1400 W on the expression of choline acetyltransferase (ChAT), a cholinergic marker, in the CA1 region of the hippocampus and medial septal area (MSA). Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400 W revealed a significant increase in ChAT immunoreactivity levels in both the CA1 and the MSA regions. Overall, the results suggest that 1400 W has protective effect against H89-induced spatial memory impairment. Moreover, the observed memory improvements caused by 1400 W infusions, might be due to interaction of iNOS with the cholinergic system.

Nitric oxide (NO) is thought to be involved in spatial learning and memory in several brain areas such as hippocampus. This study examined the effects of post-training intrahippocampal microinjections of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor on spatial memory, in both anesthetized and non-anesthetized situations in rats. In the present work, 4-day training trials of animals were conducted. Spatial memory was tested 48 h after the drug infusions. For microinjection of 1400W into CA1 region of the hippocampus in conscious animals, guide cannula was implanted into the CA1 area and 1400W was infused after recovery from surgical anesthesia. In anesthetized animals, 1400W was microinjected directly into CA1 region by Hamilton syringe during anesthesia. After completion of training, 1400W (10, 50 and 100 μM/side) were microinjected bilaterally (1 μL/side) and testing trials were performed 48 h after drug infusions in both groups of cannulated and non-cannulated rats. Significant reduction was observed in escape latency and traveled distance in animals that received 1400W (100 μM/side, * P < 0.05) via cannula after recovery in comparison with control group. Moreover, microinjection of 1400W (100 μM/side) in post recovery phase also caused a significant (*** P < 0.001) reduction in time and distance of finding the hidden platform in comparison with anesthetized situation. These results suggest that 1400W has a significant improvement on spatial memory, and memory enhancement induced by iNOS inhibitor can be affected by anesthesia in a period of time.