4^th International Conference and Exhibition on Pharmacovigilance & Clinical Trials August 10-12, 2015 London, UK

Giulia Milano received a Bachelor's degree from Genoa University School of Medicine. She is currently pursuing her specialization in Medical Toxicology at the Department of Internal Medicine, Clinical Pharmacology and Toxicology Unit at the University of Genoa. She has published several papers and is speaker in different conferences.

Diosmin is a natural bioflavonoid isolated from various plants or derived from the flavonoid hesperidin. It is used to relieve symptoms of venous insufficiency and hemorrhoidal syndrome. Short-term administration of diosmin is usually considered safe, with only minor side effects occasionally observed. During a period of about 4 years, a general practitioner noticed 17 cases of mild diosmin-induced side effects, two of which showed particular interest. The first case is about a 55-year-old Caucasian woman with chronic leg venous insufficiency. Five days after starting diosmin treatment, the patient complained of diffuse leg pain, and, for this reason, she stopped diosmin therapy and her myalgias disappeared. She made a rechallenge and her myalgias reappeared. So the physician prescribed her some blood tests: Serum creatine phosphokinase (CPK) dosage was the only out-of-range biochemical value. The second case concerns a 79-year-old Caucasian man, who was diagnosed with acute hemorrhoidal syndrome. After 21 days of continuous diosmin treatment, increased levels of serum lactic dehydrogenase (LDH) were observed. After 1 month, blood tests showed a normalization of LDH values. In this case, rechallenge was not performed. In both cases a comprehensive analysis of all possible causes for enzyme elevation was made. We ascribe these reported ADRs to a concurrence of events: An individual predisposition and the presence of severe comorbidities that may have enhanced noradrenaline tone on microcirculation, leading to an excessive peripheral vasoconstriction and subsequent ischemic damage.

Michelle Perry has completed her MPhil at the age of 25 from the University of Portsmouth in collaboration with the Drug Safety Research Unit, Southampton. She also has a BSc (Hons) in Applied Pharmacology from Queen Margaret University, Edinburgh and is currently a Pharmacovigilance Associate at Aspen Pharmacare Trading Limited, based in Dublin, Ireland.

Pharmacovigilance (PV) works towards ensuring the safe use of all medicinal products on the market today in line with an acceptable benefit risk balance for each product. Marketing authorisation is passed when there is sufficient evidence that a medicinal product is; of good quality, effective and safe for the intended purpose. The benefit risk balance must be continuously assessed throughout the products lifespan, taking into account all available information. Recent legislative changes introduced risk minimisation plans, ensuring that PV has a proactive approach to identifying, communicating and managing any potential safety risks. PV has developed considerably over the past 50 years and continues to do so as the range of medicinal products on the market increases. Thalidomide resulted in international efforts to address drug safety in early 1960s. As technology advances, various opportunities arise further to re-evaluate current medicinal products, both on and off the market, improving overall knowledge of mechanisms of action and therefore safety. Even those off the market have the potential to benefit many people if used with caution and awareness of identified and potential adverse effects. Thalidomide is re-emerging for treatment in dermatology, multiple myeloma and other cancers including oral and prostate, highlighting the importance of a continuous attempt to gain a complete understanding and improve drug safety monitoring. Non-steroidal anti-inflammatories have highlighted the challenges and need for on-going monitoring over recent years, with PV monitoring in the UK leading to a change in diclofenac to a prescription only medicine in January 2015.

Zerizer S has a Master degree from University of Salford Manchester England in 1987 Department of Biochemistry, and completed PhD in 2006 from Faculty of Natural Sciences University of Frères Mentouri, Constantine, Algeria, and got Master’s and PhD students at the University of Frères Mentouri, Algeria. She is a teacher since 1988 until now and also is the Director of Research. She has published some papers in reputed journals in the field of pharmacy and immunology.

Homocysteine may mediate long-term oxidative damage at the vascular interface through the generation of potent reactive oxygen intermediates. In this study, we evaluated the effect of the anti-inflammatory and antioxidant Stachys mialhesi extract on the inflammation induced by hyperhomocysteinemia and damages in the aorta, heart and liver of mice. Adult male Mus Musculus mice were systematically divided into four groups of similar mean body weights and fed for 21 days with control and experimental diets. The control group (F) was fed with white bread (0.50mg/mice), group (M) was fed with L-methionine (200mg/kg/day), group (MP) was fed with L-methionine (200mg/kg/day) plus S. mialhesi extract (50mg/kg), and the positive control group (P) was treated with S. mialhesi extract (50mg/kg/day). The experimental diets were given in white bread (0.50mg/mice). The plasma hs-CRP concentrations were elevated significantly after the administration of methionine in high doses to mice. This was associated with the loss and degeneration of endothelium, fenestration and formation of foam cells in the media of aorta, also the alteration of the cardiac muscle and liver necrosis. This is due to the angiotoxic action of homocysteine directed to the aorta, and its toxicity on the heart and liver. These changes were not observed in mice treated with methionine plus the antioxidant and anti-inflammatory S. mialhesi extract. Homocysteine initiated inflammation and mediated early atherogenesis lesions through increased oxidant stress, and the treatment with S. mialhesi extract prevented the endothelial and heart alteration. So, combined to vitamin therapy, natural phytochemicals are sources for natural antioxidants and could be used to protect against the homocysteine mediated free oxygen radicals damages.

Aida Sefidani Forough has received her PharmD degree at the age of 24 from Shahid Beheshti University of Medical Sciences which is ranked as the second best medical university in Iran. Currently, she is the chief manager at a hospital pharmacy after a 3-year experience of community pharmacy work. She serves not only as a part of the medical team but also is engaged in tasks such as drug utilization evaluation program, antibiotic resistance program and also is a member of the hospital's drugs and therapeutics committee. She has one published paper and one under review.

Adverse drug events are mostly dose dependent and preventable. About 50% of these adverse effects are due to inappropriate dosing especially in patients with renal failure. We aimed to determine the impact of short message alerting on physicians' drug dosing of patients with decreased renal function. Eighteen physicians accepted to enroll in the study. Their patients who received at least one of the six selected drugs were selected for evaluation. The patients with an estimated glomerular filtration rate of 50 ml/minute or lower were randomly divided into two groups of case and control. An alert was sent to the physician in charge of the intervention (case) group. Physicians' reactions was recorded as "dose adjustment", "discontinuation of medication" or "none" and were compared in both groups. The reaction time of physicians before and after receiving alerts was recorded as well.One hundred and thirty seven patients entered the study. The study results showed a significant difference in overall changes between the two groups (*** P<0.001). The rate of dose adjustment increased significantly after sending alerts to physicians (*** P<0.001). However, there was not a significant difference regarding discontinuation of medication between groups (P=0.76). On the other hand, prompt reaction of physicians (0-6 hours after sending short message) significantly increased after intervention (* P<0.05). Nevertheless, physicians' reaction time in 6-24 hours and 24-48 hours was not changed significantly after intervention. The results of this study show that informing physicians about the renal function of the patients leads to appropriate dosing.

Julia Laín-Abril is a PharmD student graduated in CEU San Pablo University in Spain, currently finishing her MSc in Drug Discovery and Pharma Management at the School of Pharmacy from University College London; she is also trained in Clinical Trials Management and Regulatory Compliance at University of Chicago. She has participated in the X National Undergraduate Congress in Health Sciences in Spain to present her work on “Current status of the ethical codes in the Official Schools of Pharmacists of Spain”. Today she works as a Product Stewardship and Regulatory Affairs Scientist in London

Counterfeit drugs are a worldwide issue and its impact on public health is very well documented, being responsible for not only resistance to medicines but also patient deaths. Regulatory authorities are responsible for ensuring patients’ safety through the establishment of regulations that protect the four basic bioethical principles (autonomy, beneficence, non-maleficence and justice) and fighting against the counterfeit market. It is a fact that Internet has increased the breaches in the supply chains of highly regulated markets through online pharmacies that may be illicit or poorly regulated. The WHO states that medicines obtained from illegal Internet sites that obscure their physical address are counterfeit in more than 50% of cases. After studying the measures taken by regulatory authorities to ensure the safety of medicines and carefully analysing the current bioethical situation of the online market, it has been observed that Internet does not have an ethical code and most anti-counterfeit actions taken are focused on increasing the awareness of the consumer, reassuring the principle of autonomy. However, there are no actions detected to protect the principles of beneficence, non-maleficence and justice. It is suggested that further online anti-counterfeit measures focus on avoiding the reach of counterfeits to the online market instead of solely warning the consumers to prevent the purchase. For this, it will be necessary the collaboration of different parties -police, customs, government, pharmaceutical companies, regulatory authorities and healthcare professionals and patients- as well as a stronger will to promote an ethical online behaviour

Martie S Lubbe is currently the leader of the research niche area, Medicine Usage in South Africa (MUSA) at the North-West University (NWU), Potchefstroom campus in South Africa. She obtained her Bachelor’s, MPharm and PhD degrees in Pharmacy Practice at the Potchefstroom University for CHE. She has devoted 25 years of her career to pharmacy education and practice-related research and contributed significantly towards the development of Pharmacy practice. From 2004 to 2009 she acted as Subject Head of Pharmacy Practice at the NWU.

Background: Despite the progress made in recent years regarding our understanding of the neurobiology of major depressive disorder (MDD), approximately one third of patients remain unresponsive to treatment. Co-prescribing of GABA-ergic drugs (GDs), such as sedative hypnotics, with antidepressants (ADs) is not uncommon, although how they benefit the outcome, if at all, remains controversial. Adequate compliance is central to a positive outcome, although its impact with respect to drug usage patterns has not been considered. The aim of the current study is to establish how the co-prescribing of GDs is associated with altered antidepressant compliance and which antidepressants (ADs) are associated with the worst compliance in combination with GDs. Methods: A prospective, cohort study design was used to analyse nationally representative medicine claims data submitted to a privately-owned South African Pharmaceutical Benefit Management (PBM) company. Three groups were distinguished over a six-year study period, namely patients treated only with ADs, those treated only with GDs and those treated with both ADs and GDs. The study population was determined by means of the following inclusion criteria: AD and/or GDs prescribed, patients older than 18 years, and MDD diagnosed by a psychiatrist supported by an appropriate ICD-10 code. The medicine possession ratio (MPR) was used as proxy to determine patient compliance for both AD and GD medication. Results: The overall AD compliance of patients taking both ADs and GDs (35.19% acceptable compliance; n=42869) was weak, and no statistically significant difference (p=0.657) was observed compared to patients taking only ADs (35.44% acceptable compliance; n=8247). The lowest percentage of patients taking amitriptyline (29.57%), mirtazapine (31.36%) and fluoxetine (32.29%) in addition with GDs were associated with compliance, with a higher percentage of duloxetine (40.67%), venlafaxine (38.62%), and citalopram (38.50%) that were compliant. ADs with the highest non-compliance were associated with a significant increase in GDs prescribing. Conclusion: The addition of GDs does not increase AD compliance. The class of AD is not always a risk factor for non-compliance. Different ADs show differences with respect to GD co-prescribing, which may be related to side effect burden and patient acceptability. Non-compliance and associated use of GD may correlate with ADS.

Nazanin Namazi Sarvestani currently is a PhD student at University of Tehran, Iran at the age of 26 with her former research and scientific articles being based on Neuroscience and her recent thesis on cancer. In her current thesis on cancer under supervision of Professor Houri Sepehri, they focus on natural products derived from plants and their effects on cancer treatment to reduce the side effects of chemotherapy drugs. She has finished the second year and has successfully defended her dissertation proposal. She has published 3 papers in reputed journals and wrote a book about medical physiology.

Many of dietary flavonoids have been known to possess beneficial effects in the human body due to their antioxidative and tumor growth inhibitory activities. Natural agents could be a useful strategy to reduce the dose of hazardous chemotherapy drug. In this study, SW948 and HT-29 human colon cancer cells treated with IC50 dose of salvigenin and eupatorin for 24 h with or without doxorubicin presence. The extent of proliferation was assessed by MTT test. To determine apoptotic cells morphologically DAPI staining done by fluorescent microscopy. Cell cycle analysis, Annexin V-FITC/PI staining and western blot analyses were measured too. It was shown in cell cycle analysis that, these cell lines which treated with salvigenin or eupatorin with non-effective dose of doxorubicin, arrested in G1 phase about 40 and 30% more than doxorubicin treated cells, respectively. Moreover G2 arrest was induce by flavonoids too. On the other hand, Annexin V-FITC/PI staining confirms that combination of salvigenin or eupatorin with lower dose of doxorubicin induce greater apoptosis in colon cancer cell lines compare to doxorubicin treated cells. In addition, caspase-3 and PARP expression increased significantly in these groups to confirm that flavonoids enhanced apoptotic feature of doxorubicin in colon cancer cell lines. Synergistic effect was calculated by computer software. Natural therapeutic flavonoids regimens such as salvigenin and eupatorin, able to potentiate doxorubicin effects in lower doses, with protecting non-tumoral cells are needed to improve treatment of colon cancer patients. Because, most colon cancer patients treated with combination therapies have only temporary responses to treatment, associated with the side effects of the therapies.

Dr. Deepti Chopra Current Position: Associate Professor, Department of Pharmacology, Hamdard Institute of Medical Sciences and Research, New Delhi . Qualifications MD (Pharmacology), Lady Hardinge Medical College. April 2006. DTCD (Diploma in Tuberculosis and Chest Diseases), Vallabhbhai Patel Chest Institute. April 2002. MBBS, Lady Hardinge Medical College. 1998. Work Experience Worked as Assistant Professor in Hamdard Institute of Medical Sciences and Research (w.e.f- 21 Jan 2013- dec 2014). Worked as Assistant Professor in Lady Hardinge Medical College (wef- Nov 2010- 19 Jan 2013) Worked as a Senior lecturer in Manav Rachna Dental College (wef- Sep 2009- Nov 2010). Worked as a Senior Resident (post M.D) in the Department of Pharmacology, Lady Harding medical College, New Delhi for a period of 3 years (wef-13.6.06 to 12.7.09). Experience/expertise in clinical research Published 28 original and review articles in various indexed international and national journals. Presented Posters at national conferences and delivered guest lectures at workshops and CMEs.

Background: Therapeutic treatment is often impeded with adverse drug reactions (ADRs). Among these ADRs cutaneous reactions are the major class being easily identified and reported. If not noted early and offending drug not stopped it has potential to develop into serious lesions. Thus, the present study was done to evaluate the clinical patterns of various drug induced cutaneous adverse reactions. Methods: All suspected cutaneous reactions to systemic drugs which were submitted to the ADR monitoring centre under the pharmacovigilance programme of India (Hakeem Abdul Hameed Centenary Hospital, Jamia Hamdard) during a 6-month period (March 2014 - August 2014) were analyzed. Causality relationship, severity assessment and preventability assessment was also done. Results: Out of 134 cutaneous ADRs, 56% were females, majority of cases were found in the age group of 41-50 years. The most common type of ADR observed was maculopapular rash (46.3%) and majorly implicated drug class was antibiotics (51.3%). Most (72.3%) cases were mild, 27.7% were moderate. Polypharmacy and multiple comorbid conditions were important predisposing factors. Over half (58%) cases were not preventable. Conclusion: Adverse cutaneous drug reactions correspond to a noteworthy burden on the health care system. It is the responsibility of every healthcare professional to be vigilant to possible ADRs & their effects in patients and hence take the relevant decisions which can prevent them from happening or causing some serious ill effects.

Naif Al-Hazmi completed PhD from School of Pharmacy at Bradford University and Master's degree with (Merit) 2008 from the same University. His area of interest is Pharmacovigilance especially "Adverse Drug Reactions Reporting". He has published more than 5 papers and posters in reputed journals like Drug Safety and attended many conferences and workshop in different countries in the world. He is a member of several societies and organizations.

Introduction: The increasing prevalence of Adverse Drug Reaction (ADR) has been reported by many countries and to develop a good ADR reporting system is the need of present time. Aim & Objective: To assess attitude and awareness towards ADR reporting and factors that influences their reporting by health professionals. Materials & Method: The present cross-sectional study was conducted in seven hospitals in Makkah. All the health professionals were invited to participate in the study. A prescribed questioner was used to collect basic information, professional information and knowledge about ADR reporting system. Results & Conclusion: It was observed that most of the professionals were aware of ADR. They were having positive attitude to report ADRs. But major factor found as obstacle in ADR reporting were lack of training, non availability of forms, insufficient clinical knowledge and fear to report ADR.

Prof Martie Lubbe is currently the leader of the research niche area, Medicine Usage in South Africa (MUSA) at the North-West University (NWU), Potchefstroom campus in South Africa. Prof Lubbe obtained her Bachelor’s, MPharm and PhD degrees in Pharmacy Practice at the Potchefstroom University for CHE. She has devoted 25 years of her career to pharmacy education and practice-related research and contributed significantly towards the development of Pharmacy practice. From 2004 to 2009 she acted as Subject head of Pharmacy Practice at the NWU.

One of the main reasons for the failure of pharmacovigilance systems is under-reporting, and this has a direct effect on the universal pharmacovigilance system. Professional and personal barriers were identified as a cause for under-reporting of adverse effects. The question arises as to whether these barriers can be drawn to South Africa or if there are other factors that influence the standard of reporting of adverse drug reactions (ADR) in South Africa. The aim is to describe to methodology that will be followed to evaluate the public health pharmacovigilance system in the Dr Kenneth Kaunda District (DKKD) in the North West Province in South Africa. Two steps will be followed: i) Determination from the perception of health care professionals the possible factors that can contribute to the successful implementation of a pharmacovigilance system; and ii) Evaluation of the completeness of the content of the filled-in ADR forms available in the DKKD. A quantitative, non-experimental, cross-sectional research design will be followed to conduct the study in the DKKD in the North West Province in South Africa. The study population for step 1 will include all healthcare professionals (medical practitioners, pharmacists, professional nurses) in the Tlokwe Local Municipality, in the public health sector (hospitals and primary health care clinics) on a permanent or temporary contract. All the completed ADR forms independent of pharmacological category or drug use, from 2010 to 2014 available at the hospitals and primary health care clinics in DKKD will be used as study population for step 2. A self-completion questionnaire will be used to determine the perception of healthcare professionals in Step 1. The focus of the questionnaire will be on the following aspects: i) Demographic information, ii) Adverse drug reaction system and structure, iii) Healthcare professionals’ perceptions regarding adverse drug reaction reporting; iv) Adverse drug reaction reporting in practice; v) Factors that may influence adverse drug reporting; v) Challenges of adverse drug reaction reporting. A checklist, based on the standard set by the South African Department of Health for an ADR report, will be used by the researcher to evaluate the completeness of the ADR reports in the DKKD. The study will help to identify current problems with the ADR documentation system on district level in South Africa.

Jong Hwan Sung has completed his PhD at the age of 31 years from Cornell University and postdoctoral studies from Biological and Environmental Engineering at Cornell University. He is an assistant professor in Hongik University. He has published more than 30 papers in reputed journals.

Due to the difficulty of directly testing animal or human subjects, cell-based in vitro model systems are widely used in pharmaceutical industry. However, currently available in vitro systems are far from a faithful reproduction of an organism. For example, the effect of a xenobiotic compounds is tested in vitro by incubating a monolayer of cells in the presence of the drug, whereas in human body the drug goes through a dynamic process of metabolism and excretion, which result in complex whole-body response. Combination of microscale technology, mathematical PK modeling can contribute to developing an in vitro model system that mimics the human body better. Herein we introduce the concept of combining microfluidics with mathematical modeling that allows us to test the dynamics of multi-organ response to xenobiotic compounds. Termed as ‘multi-organ-on-a-chip’, this device has multiple chambers for different organs, which are connected by microfluidic channels mimicking blood circulation. Being a physical realization of a physiologically-based pharmacokinetic (PBPK) model, this type of device can contribute to improving the accuracy of screening for pharmaceutical and health-promoting compounds.

Meri Koluaçık is a student in Business and Technology Management at Istanbul Technical University. She was graduated from Yeditepe University School of Pharmacy. Last year in faculty, she went to Rome for Erasmus program. By this program, she had a chance to make a research about cancer in Regina Elena National Cancer Institute. For graduation project, she made training about pharmacovigilance on faculties related to healthcare which include pharmacy, nursing, nutrition and dietetics, physiotherapy and rehabilitation. This project was orally presented in Fourth International Meeting on Pharmacy and Pharmaceutical Sciences (IMPPS-4) in 2014.

Spontaneous reporting of adverse drug reactions (ADRs) has a critical role on public health. Pharmacovigilance (PV) system tries to minimize the potential health risks, outcomes of medicine consumption for public. The aim the study is to raise the knowledge and awareness of the health care professional students on PV. An education presentaion is prepared by the researchers and approvels and appointments are done via faculty professors. Between February 2014 and April 2014 trainings have been conducted. The 3rd and 4th class students of the pharmacy, nursing, nutrition and dietetics, physiotherapy and rehabilitation departments have participated. 8 different conference each took 20 minutes and 234 students have participated. A survey was applied, awareness and opinions of the PV before and after the education was measured. The knowledge of PV, reasons for not reporting, appreciated to the education were evaluated. According to results, 50% of students declared that theyhave never heardPV system. After the training section, 91% of the students reported that PV system/spontaneous reporting is helpful for detection and protection from ADRs. Academic researchers should not only conduct scientific study but also inform and involve in social interactions so as to promote public health. The results suggest that PV training and education sessions for health care professional students are needed to be increased for the knowledge of PV and to foster positive attitudes toward adverse effects of drugs.

Background:The importance of correct administration of the treatment in bacterial infections is critical to modern medicine, in surgery, transplantation, cancer management and in various opportunistic infections agents. Antibiotics is the highest "revolution" in pharmaceutical history is considered the only "weapon" against bacterial infections. However, with the advent of penicillin in 1941, bacteria have developed new resistance mechanisms. 1980s represented a new stage in development, the emergence oxyimino-cephalosporins (carbapenems and fluoroquinolones) that appeared to be effective in the treatment of Gram-negative infections. Currently, the development of antibiotics has decreased, there are several reasons: first, technical difficulties in discovering new antibiotics to penetrate the cell wall of Gram-negative bacteria; second, obstacles to the regulation of new antibiotics that are increasingly complex. Gram-negative isolates glucose fermenters and non-fermentershave become the mostcommon cause ofsevere infectionsworldwide. Due to the development of new mechanisms of membrane resistance by efflux of antibiotics and remarkable tendency to alter resistance gene expression by β-lactamase enzyme producing extended spectrum (ESBLs), carbapenemases, aminoglycosides blockers pathogensGram-negativeis aglobalthreat. In this context, when the usefulness of antibiotics appears to be insufficient, finding ways antibacterial therapy is becoming increasingly important. The objective ofthis study is toexperimentallydetermine thein vitro antimicrobial activity of selected plants used to treat bacterial infections. Materials and method:Multidrug-resistant (MDR)strainsstudiedin this paper were isolated from patients hospitalizedinthe Urology Clinic"Prof.Dr.Th. Burghele"Bucharest. The study group has included 67 Gram-negative strains producing ESBL. The strains were identified with theVITEK®2 Compactautomatized system.Antibiotic susceptibilities of the isolates were determined by disk diffusion method (DDM) and ESBL production was confirmed by double-disc diffusion method.We detection of plasmid-mediated-lactamase genes in clinical isolates by using multiplex PCR.In order to test the antibacterial action of compounds derived from plants with potentialagainst bacterialdisc diffusion method was used adapted.PlantstestedJuglansnigra, Eugeniacariophillata and Artemisiaabsinthium were harvested in september2014 from BucharestBotanical Garden.Theactive compounds were obtained with high performance liquid chromatography(HPLC).Blendgrindedherb extractswere madeinethanolanddistilledwaterin theratio 1/ 5/2 for tendays,at 4°C, filtered,sterilized by filtration. Antimicrobial activity of the extracts of plant sample was evaluated by the paper disc diffusion method. Stock culture of test bacteria were grown in gledmedium at 37°C for 24 h. Final cell concentrations were 108CFU/ml with reference to the 0,5McFarlandturbidometrywere suspendedinMüller-Hintonmedium. The method usedis basedon the propertyof antimicrobialsto diffusea solid culture mediuminoculated withabacterial culture. Results:In vitro, the sensitivity to carbapenems was high, while foraminoglicosides and fluorochinolones there were obtained higher levels of resistence.We identified50strainsproducingblaCTX-M, 14 strainsproducingblaTEM and 3 strainsprodutingblaOXA48enzyme.The results of the phytochemical HPLC tests indicate that all tested extracts containedphenols and triterpenes,other classes of chemicals being selectively present. The studied extracts displayed various degrees of antibacterialactivities.The extracts ofJ.nigra, E.cariophillataand A.absinthiumshowed thebest spectra of activity, their inhibitoryeffects being recorded against 93.55%, 70.28%,54.30%,48.58%, and 39.89%of the67 tested bacteria, respectively.The results of the MICdetermination indicated that the crude extracts from J. nigra, E. cariophillataand A. absinthium were able to inhibit the growthof all the 76 studied bacteria within a concentration range of45 to 1950 μg/mL. The zone diameter of inhibition obtained duetoJ.nigra, E.cariophillataandA.absinthiumrangedbetween 23-26 mm, 18-22 mmand16-18 mm, respectively. In all qualitativetestingbydiscdiffusionmethod extracts showed antimicrobial activity, measured by the appearance of a zone of growth inhibition around the spot stock solution deposited onan agar medium seeded. The study was conductedfor allpathogens strains fromthecollection made with increased resistance to antibioticsand for all plant extractsstudied,J.nigra, E.cariophillataand A.absinthium. Conclusions:We appreciate thatresearch conductedopennew perspectivesin the use ofmedicinal and aromaticplant extractsrich inphenolic compoundsto combatMDR strains. These data maybe useful indeveloping newagainst bacterialformulaand settingthe protocol intheir clinical use.

Jie Wu has completed her PhD at the age of 35 years from Chinese PLA General Hospital and is a Doctor of the Department of Nephrology, Chinese PLA General Hospital, National Clinical Research Center of Kidney Diseases. She also is a committee member of the Chinese association of the integration of traditional and western medicine. She has published more than 15 papers in reputed journals and has organized two multi-center, double-blind, double-dummy clinical drug research.

Background: Chronic kidney disease is a common and frequently occurring disease, and most chronic kidney diseases have evolved from the primary glomerulonephritis. Proteinuria is an independent risk factor for chronic kidney disease progression, thus reduction of proteinuria is extremely important to improve the prognosis of chronic kidney disease. General consensus is that the therapy for decreasing proteinuria ought to apply steroids and/or immunosuppressants, angiotensin converting enzyme inhibitors and angiotensin-II receptor blockers, but side effects and adverse reactions reduce partial patients’ benefit and even cause harm. Meanwhile, the expenses of these drugs are relatively high and become economic burden for most Chinese patients; therefore, seeking out other cheap and effective drugs for decreasing proteinuria is urgently needed. In China, Shenyankangfu Tablets are widely applied Chinese patent medicines for many years which have demonstrated excellent efficacy and safety on decreasing proteinuria, but it has a lack of evidence from evidence-based medicine. Therefore, we have designed the present randomized controlled clinical trial aiming to evaluate the efficacy and safety of Shenyankangfu Tablets for controlling the proteinuria of patients with primary glomerulonephritis compared with losartan potassium. Methods/Design: The present study is a multicentre, prospective, double-blind, double-dummy, randomized controlled clinical trial. The present study will enroll 720 patients diagnosed with primary glomerulonephritis, blood pressure≤140/90mmHg, estimated glomerular filtration rate≥45ml/min/1.73m2, 0.5g≤24-hour proteinuria≤3.0g, traditional Chinese medicine syndrome conform Qi-Yin Deficiency in 43 sites. The eligible patients will be at 1:1:1:1:1 ratio randomly divided into Shenyankangfu Tablets group, losartan potassium 50 mg group, losartan potassium 100mg group, Shenyankangfu Tablets plus losartan potassium 50mg group and Shenyankangfu Tablets plus losartan potassium 100mg group. All groups will be followed up for 48 weeks and the seven visits will be performed in week 0, 4, 8, 12, 24, 36, 48. The primary efficacy outcome is change of 24-hour proteinuria after treatment; the secondary efficacy outcomes include changes of serum creatinine, estimated glomerular filtration rate, traditional Chinese medicine syndrome score and serum albumin after treatment. Adverse events will be monitored throughout the trial. Discussion: The result of the trial will provide solid evidence of evidence-based medicine to evaluate the efficacy and safety of Shenyankangfu Tablets for controlling the proteinuria of patients with primary glomerulonephritis compared with losartan potassium. Moreover, we infer that Shenyankangfu Tablets plus losartan potassium therapy can decrease proteinuria to relatively large extent compared with Shenyankangfu Tablets therapy alone orlosartan potassium therapy alone.

Virginia Noxon is a PhD candidate at the University of South Carolina in Clinical Pharmacy and Outcomes Sciences. She joined SONAR last year and contributed to several of their publications over the past year.

Natalizumab is an effective immunosuppressive therapy for multiple sclerosis that received its initial FDA approval in 2004. Its most notable toxicity is progressive multifocal leukoencephalopathy (PML); an opportunistic infection that is the focus of an FDA mandated Registry (the Tysabri Outreach Commitment to Health (TOUCH) Outcomes Registry). The Southern Network on Adverse Reactions identified a fatal case of Natalizumab associated urethral melanoma and undertook an extensive evaluation of all cases of Natalizumab-associated melanoma included in the FDA’s Adverse Event Reporting System (FAERS) (between 2005 and 2014). Characteristics of these patients and report quality were analyzed. Report quality was based on a 15 point scale of various components. The mean patient age at the time of diagnosis of melanoma was 46 (s.d. 11). Seventeen patients were diagnosed with cutaneous melanoma developing in non-sun-exposed areas. We found that cases reported through the TOUCH registry were of lower quality (mean score 7.7) compared to others that reported outside of the USA (mean score 8.5, p<0.008). Our findings suggest that in the United States, the TOUCH Registry should be expanded to require clinicians to report details of Natalizumab-associated melanoma, an opportunistic illness that frequently develops in immune-compromised persons. Also, the FDA-approved product label for Natalizumab should be revised to include information on occurrences of melanoma among Natalizumab-treated MS patients, particularly those who have cutaneous nevi prior to Natalizumab initiation. Natalizumab-treated MS patients and their physicians should be vigilant for changes in nevi’s appearances and development of new cutaneous lesions (particularly in non-sun-exposed cutaneous areas

This paper aimed to explore the protective effects of picroside II against the neuronal apoptosis and changes in morphology and structure that follow cerebral ischemic injury in rats. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion (MCAO) in 60 Wistar rats, and intraperitoneal injections of picroside II (20 mg/kg) were administered. The neurobehavioral functions were evaluated with the modified neurological severity score (mNSS) test. The cerebral infarct volumes were measured with tetrazolium chloride (TTC) staining. The morphology and ultrastructure of the cortical brain tissues were observed with hematoxylin-eosin staining and transmission electron microscopy, respectively. The apoptotic cells were counted with terminal deoxynucleotidyl transferase dUTP nick-end labeling and flow cytometry, and pERK1/2 expression was determined by immunohistochemical assay. The results indicated that neurological behavioral malfunctions and cerebral infarcts were present in the MCAO rats. In the model group, the damage to the structures of the neurons and the blood brain barrier (BBB) in the cortex was more severe, and the numbers of apoptotic cells, the early apoptotic ratio (EAR) and pERK1/2 expression were significantly increased in this group compared to the control group (P<0.05). In the treatment group, the neurological behavioral function and the morphology and ultrastructure of the neurons and the BBB were improved, and the cerebral infarct volume, the number of apoptotic cells, the EAR and pERK1/2 expression were significantly decreased compared to the model group (P<0.05). These results suggest that picroside II reduced apoptosis and improved the morphology and ultrastructure of the neurons and the BBB and that these effects resulted in the recovery of the neurobehavioral function of rats with cerebral ischemia.

Javeria Fazal will complete her Master’s Program in coming July (2015) at the age of 28 years from University of Calabria,Italy.She has successfully completed Pharm D (Doctor of Pharmacy) from Pakistan.After it she was entitled as a Quality Control Assistant leading to Quality Control Manager in Pharmaceutical firm and also performed duties of Hospital Pharmacist in hospital.In 2013 she came to Italy with great ambition of Clinical findings so this is her first research throughout her academic career and she wants to proceed it to her PhD Program.

The aim of the study was to investigate if the average Pakistanis and average Italian kidney post transplanted patients have same episodes of adverse events after intake of cyclosporine, tacrolimus and corticosteroids and also to green light the safest as well as hazardous drug among these three and to explain the appropriate reasons for effectiveness and ineffectiveness of the respective drug. The subjects were randomly selected including 706 Pakistani and 568 Italian patients both male and female with inclusion criteria of teen age and geriatric patients as well to estimate the clinical response. Blood sample was taken from each subject in order to determine the amount of creatinine, glucose, hemoglobin and cholesterol which are ultimate parameters for cardiovascular and cerebrovascular accidents..Urine sample was also taken in order to determine level of protein. Also DFG (Delayed Graft Function) was observed in these subjects. Thirty one percent of Italian men and 26% of Italian women (out of 568 Italian patients) suffered from hypercreatininemia and hyperproteinuria including hemoglobinemia and hypercholesterolemia and only a minority of sample population was subjected to hyperglycemia whereas 22% of Pakistani men experienced from same adverse effect but for Pakistani women the percentage was 21.50 (out of 706 Pakistani patients). The sample was selected from different age groups but it was observed that majority of adverse effects were found between age group 46-55 and the percentage of occurrence of adverse effects was found to be least between age group 17-25. It was observed that for immuno-compromised patients DGF, mortality rate and risk of transplant failure has been shown minimum for corticosteroids, intermediate for tacrolimus and maximum for cyclosporine and for immuno-competent patients, tacrolimus was effective drug. Abnormal kidney function gives favourable place for growth of many bacteria and ultimately level of protein become raise and there will start competitive binding between these proteins and cyclosporine as cyclosporine itself is composed of 11-amino acids so those having same ‘R’ functionality with the attaching side of cyclosporine will compete and finally cyclosporine will not be available to bind with its receptor and will give rise to series of adverse events. Also it was observed that patient’s adherence was maximum with corticosteroids as they produce synergistic effect with adrenal glands steroid production thereby suppressing immune system with diminished adverse effects and was gradually decreasing as we move from tacrolimus to cyclosporine. These data suggest that immuno-suppressant drugs should be monitored with special care depending upon the immune status of the patient.

Introduction: Minoxidil is a strong arterial vasodilator used in the treatment of hypertension. In dermatology, topic minoxidil is widely used to treat hair fall. Hypertrichosis may occur if this form is misused. Case report: A 5 year-old girl developed patchy alopecia areata of the scalp. She was treated by minoxidil 2% lotion. Parents did not observe medical prescription and applied treatment hazardously over 10 times a day. Regrowth of hair was rapidly obtained. However, the parents complained of extensive hypertrichosis covering the front and the back. Physical examination revealed no hypotension and hirsutism evaluated at 20/36 on the Ferriman and Gallwey scale. Serum levels of 17 hydroxyprogesterone, 17alfa progesterone, testosterone and cotisol were within normal ranges excluding hormonal disorder. Discontinuation of minoxidil was followed by progressive regression of hypertrichosis. Discussion: Systemic effects are rarely reported with minoxidil based lotions. Indeed, transcutaneous absorption is insignificant ranging from 0. 3 to 4.5%. The main systemic side effects include hypotension, tachycardia and ECG changes. Hypertrichosis to topical minoxidil solution has been reported more frequently in females than in males. This side effect is dose-related and is mainly localized in the face. Discontinuation of treatment makes this trouble reversible. However medical supervision must be considered for a long time because of the product’s very long action. Conclusion: Minoxidil is the best accompanying treatment of alopecia areata. It must be delivered on medical prescription to ensure the best results and the maximum security use especially in children and women.

Introduction: The drug reactions in children are very rare, even Lyell's (TEN)syndrome with a mortality rate estimated at 7.5%. Few cases of serious drug reactions secondary to paracetamol were reported. We report the case of a 5 year old girl with a Lyell's syndrome after taking paracetamol. Observation: JB, 5 years old , with no significant medical history, presented 24 hours after administration of 250 mg of paracetamol suppository conjunctivitis with early cheilitis. 48 hours later, the patient presented erythematous macules prominent on the trunk and limbs. The all evolving in a context of deterioration of general state and an encrypted fever 39. Physical examination revealed flanges bubbles with a body surface area estimated at 60%. A mucosal involvement was noted in type cheilitis, conjunctivitis and genital erosions. A type of drug eruption syndrome or Lyell syndrome scaled staphylococcical SSSS were discussed before this clinical picture. Cutaneous histology had highlighted a keratinocyte intraepidermal detachment with marked necrosis. Abnormal liver function was noted. Blood cultures were negative. The viral serology (hepatitis B and C and HIV) were negative. The diagnosis of Lyell syndrome paracetamol was retained on anamnestic elements, clinical and histological. After a 20-day ICU stay and symptomatic treatment, the outcome was favorable at the expense of hyperpigmented scars. Discussion: Paracetamol is one of the most widely used drugs in pediatrics. If hepatotoxicity is considered the main side effect of drug eruptions can see. Few cases of secondary TEN paracetamol have been reported. TEN is very rare in children (10%of TEN) its incidence increases with age (child mortality rate 7.5% / 20% to 25% for adults), delays of symptomatology occuring is 1 to 17 days of which is consistent with our case (48h). A significant association with acetaminophen in the Lyell child has been demonstrated recently. Several treatment were tried (corticosteroids, immunoglobulins, infliximab) without significant results. Stopping the causal medication and nursing care can minimize the effects. CONCLUSION: Our observation has special features for the occurrence Lyell's syndrome in a child of 5 years old induce by acetaminophen.

Michel Talla hailed from Cameroon, is a young and enthusiastic young researcher rounding up a Master degree in Public Health, at the School of Allied Health & Environmental Sciences, Public Health Unit, Kwara State University, Nigeria. He has completed his Bachelor Honor degree and Advanced diploma in Bioengineering at The Polytechnic Ibadan. He also holds an advanced Diploma in Computer Engineering from the University of Ibadan. His areas of particular interest include spatio-temporal mapping, forecasting and digital tracking of pathogen and disease interactions, understanding the impact of biotechnological and scientific innovations and discoveries on diseases epidemiologic transition interventions, the sociocultural, ethical and economic consequences of uneven disease/ outbreak preparedness on community, national and global health responses.

Background: The significance of early warning alert, preparedness, public health surveillance and response systems, has been shown through the most deadly Ebola outbreak, complex ever seen Ebola war in West African communities as new cases is increasing exponentially with high risk of exposure of population and medical staff alike. The late humanitarian and local nongovernment organisations emergency responses and challenges to curtail transmission dynamics and stop the ongoing spread in the Ebola outbreak in West Africa have led to an unprecedented toll of 21,724 reported Ebola cases in eight countries since the outbreak began, with 8,641 reported deaths including 828 health-care workers and 499 died as 14 January 2015. Methods: Non-conventional humanitarian interventions (NCHI) was declared in West Africa Ebola epicenters with major tasks at implementing relief logistics and the much-needed public health emergency responses and programmes to ultimately reduce and stamp out Ebola outbreak amidst the most remote and hard to reach vulnerable populations. Results & Discussions: Indications have prompted the need of further evaluation of monitoring of the effectiveness of non-conventional humanitarian interventions during and post Ebola outbreak crisis. This paper showed that NCHI has significantly support the reduction EVD new proportion of cases and drastically reduce case fatality in the context of Ebola epicentres through Ebola health centres building, mobile laboratory facilities, emergency medical evacuation capability, prompt treatment and care support and services delivery, and infection prevention and control quality assurance checks in these countries. At the same time, exhaustive NCHI efforts targeted ensuring timely and sufficient optimal supply personal protective equipment (PPE), building new Ebola emergency care centers and emergency stockpile supply and delivery and set strategic coordinated priorities to all Ebola treatment facilities, along with the provision of local training and empowerment using relevant guidelines to limit to the minimum possible level of risk and aftermath within the context of national sovereignty, peace and security. The paper highlights the effectiveness of NCHI in population in public health crisis and mitigates on medical, ethics and legal challenges in West Africa emergency responses. Conclusion: NCHI has successful supported operational containment efforts and lessons learnt in West Africa and lay foundation for accountable, transparent and innovative model for emergency response to global disease outbreaks in the most remote vulnerable populations. However, there lies a critical need to build up from the NCHI response and management in West Africa toward a more pragmatic and robust evidence based NCHI approaches and models that can transform and empower the huge natural and human resource potentials towards achieving universal coverage, the 2015–2030 Millennium Developing Goals (MDGs), sustainable growth and development in Africa and worldwide economic prosperity.

Ka-Chun Cheung is the project manager of innovations of personalized medication surveillance and the view of the future pharmaceutical patient care 2020 at the Royal Dutch Pharmacists Association (KNMP). He started his PhD thesis about reporting analysing medication errors in The Netherlands in June 2009 at the Scientific Institute for Quality of Healthcare and Department of Clinical Pharmacy at Radboud University Medical Centre in Nijmegen. He will defence his thesis in April 17, 2015.

Introduction: National reporting programmes usually collect and analyse medication error reports from healthcare providers in their own country and only disseminate guidance to healthcare providers within the borders of their country. It is unclear how many different national programmes could learn from each other. The aim of this study was therefore to explore to what extent alerts and newsletters about medication errors issued in other countries could also be relevant for the Netherlands. Methods: Ninety disseminated information items that had been issued by three national programmes (Canada, the USand the UK) in the period from June 2009 until June 2012 were collected. These items were compared with the national reporting programme, Central Medication Incidents Registration (CMR-NL) in The Netherlands. Each selected item was subsequently assessed independently with six assessment criteria: is the medicine available in the Netherlands? If so, could a similar error occur in the Netherlands? Did theCMR-NL reporting programme receive any reports about acomparable (or even identical) error? If so, did these reports include any errors with serious temporary or permanent harm? Did the CMR-NL disseminate output about it? If so,what was the dissemination date of CMR-NL? Results: From the 90 items, 87.8 % (n = 79) were relevant for Dutch healthcare. For 43 of the 90 items (47.8 %), the CMR-NL had received comparable (or even identical) errors but had not disseminated any alert or newsletter about these errors. The CMR-NL had disseminated an alert or newsletter for 14 of the 90 items (15.6 %). Conclusion: This study showed for a broad range of errorsthat the Dutch national reporting programme could learn from the three reporting programmes in Canada, the US and the UK. National reporting programmes can benefit from sharing alerts and newsletters that enhance the learning between countries.

Background: The clinical relevance of vitamin K antagonists (VKAs) has been widely demonstrated in several indications. Unfortunately, VKAs are not without drawbacks and risk of serious bleeding. The iatrogenic induced by these molecules represents a major public health problem. Aim: With this study we try to analyze the use of analgesics in patients under VKAs and their effects on the response to those molecules. Patients & Method: We conducted a retrospective study over a period extending from February 2012 to August 2013 in Clinical Pharmacology Unit of the pharmacovigilance’s service (Hospital and University establishment of Oran). We had examined the prescription of analgesics among the patients monitored in our unit and studied the influence of these analgesics on the evolution of the INR (excel curves). Results: We counted a total of 195 patients, among which 32 (16.41% of the total population) had received analgesic treatment. The frequency of different categories of analgesics administered was: • The analgesic opioids: 2% • The weak opioids analgesics: Tramadol: 21.87% (we had expose an interesting case ) • Non-opioid analgesics: AINS: 69.87% (indomethacin: 66.75%, Ibuprofen: 3.12% ;Paracetamol: 5.25%; salysilique acetyl acid: 1%). Conclusion: The management of pain in patients on VKAs has particularities, given their many drug interactions especially with analgesics. In addition to this, the influence of these classes of drugs on the evolution of the INR can have dramatic consequences engaging life-threatening; as such, special attention should be given to the use of analgesics with this type of patient.

Clément Delage is a French pharmacist resident. He graduated in Pharmacy from Nantes University and is doing his residency in Paris. He is currently in his third year of residency and is working for the Parisian Public Health Assistance. Besides, he has several University Diploma related to medicine and pharmacy. He did this study when he worked closely to the neonatal intensive care unit of Cochin Hospital which is one of the most important and renowned units in Paris.

PEDIAVEN® AP-HP NOUVEAU NE 2 (PNN2) is a newborns parenteral nutrition solution. In neonatology, the main interest of PNN2 is its possibility of peripheral venous administration (PVA). During PNN2 administration in the neonatal intensive care unit, several cases of extravasation have been reported, two with severe oedema and necrosis. We investigated the role PNN2 played in these extravasations, by three different ways: a pharmacovigilance (PV) report; a questionnaire to the main neonatal intensive care units in the Paris region; and the osmolarity and pH measurements. Five other reports have been compiled by the Pharmacovigilance Regional Center in Angers the last three years. After our report, the French Drug Agency ordered an investigation about PNN2. The questionnaire showed that the rate of extravasations has been trending up in most of the other units. If the responsibility of PNN2 is not clearly established, the cases are more severe with PNN2 than with other solutions. The manufacturer indicates an osmolarity “around 790 mOsm/L” (712 to 870 mOsm/L). Tested osmolarity varied from 778 to 782 mOsm/L and pH was 5.04. There are no guidelines for the osmolarity limits in preterm VPA. The limit used in our unit is 800 mOsm/L. Besides, the pH value for the best tolerance would be within 6.5 and 9. The extremely inaccurate osmolarity value led our unit to ban PNN2 use in PVA. The results of the French Drug Agency investigation and the High Health Authority guidelines on osmolarity limits will help us to improve our practices.

Marianne Rufiange has completed her PhD in 2004 and has been since then working in the Scientific and Regulatory Affairs Department at Algorithme Pharma Inc. based in Montreal, Canada.

Screening steps of unknown failure rate in a Phase I trial can lead to misestimation of study activity parameters such as recruitment, time, and cost. We set out to develop a model of study planning that would permit the iterative estimation of these activities.First estimates were based on a 53% success rate at Screening Visit 1 (medical history, study criteria), and 66% for Visits 2-3 (sleep problemscreening). Multi-step screening of participants with iterative, rolling wave planning was deployed to accurately adjust the flow of volunteers at Screening Visit 1 to adapt to the failure rate at each screening step. The goal was to maintain the right flow of eligible volunteers without surpassing the sleep center bed capacities as the study protocol allowed a strict time window between each visit. Reactivity of the recruitment team was paramount to promptly adjust study activities in response to screening rates communicated. In total, 640 subjects went through Screening Visit 1; of those, 190 qualified and completed Visit 2. Visit 3 was performed on 160 prequalified subjects as per Visits 1 and 2. Of those, 52 subjects were eligible and were randomized. Corrected screening statistics were: 30% success rate at Screening Visit 1, 84% at Visit 2, and 33% at Visit 3. This equates to a challenging overall 8% success rate for this healthy subject sleep trial. Challenges of a multi-step screening for a study with extreme filtering inclusion criteria and strict timelines were successfully met through rigorous communication, and rolling wave planning.

Introduction: The World Health Organization (WHO) currently recommends the use of artemisinin-based combinations (ACTs) for the treatment of uncomplicated P. falciparum malaria. With the first evidence of emergence of artemisinin resistance in South East Asia, it has now become critical to conduct robust surveillance of in vivo efficacy of ACTs in malaria-endemic areas where they have been deployed as first line treatment. Method: We conducted two consecutive clinical surveillance studies of the efficacy and safety of two ACTs (artemether-lumefantrine, AL and amodiaquine-artesunate AQ-AS, first and second line policy respectively) in five sentinel health posts across Mozambique. Directly observed administration of the study drugs to children aged 6 months- <5 years was conducted, followed by 3 days consecutive, and weekly visits for 28 days, following the WHO 2009 protocol. Results: Four-hundred and thirty-nine (AL cohort; five sites) and 261 (ASAQ cohort, three sites) children were recruited to the study. Day 28 PCR-corrected efficacy for AL was 96.0% (335/339; 95% CI: 93.4-97.8), while for ASAQ it was 99.6% (232/233; 95% CI: 97.6-99.9). The majority of recurring parasitaemia cases throughout follow-up were shown to be re-infections by PCR. Both drugs were well tolerated, with the most frequent adverse event being vomiting (AL 4.5% [20/439]; ASAQ 9.6% [25/261]) and no significant events deemed related to the study drugs. Conclusion: This study confirms that both AL and ASAQ remain highly efficacious and well tolerated for the treatment of uncomplicated malaria in Mozambican children. Studies such as these should be replicated regularly in the selected surveillance sentinel sites to continuously monitor the efficacy of these drugs and to rapidly detect any potential signs of declining efficacy to ACT, the mainstay of malaria treatment.

Background: Cancer chemotherapeutic drugs are associated with several adverse drug reactions. Thus, the present study was done to determine the prevalence of adverse events in patients treated with chemotherapy. Methods: Spontaneous ADR reports of patients on antineoplastic drugs were studied. These reports were analyzed for various carcinomas under treatment, medications used, types of ADRs, organ system involvement, severity, causality assessment and preventability. Results: Over a period of 2 years a total 591 cases were received. The prevalence of ADRs was more in female patients as compared to men. ADRs mostly occurred in the age group of 41-50 years (27.4%). Cisplatin (19.6%) was found to be the most common drug. The commonest ADR reported was nausea and vomiting. Gastroenterology (40.1%) was the most affected system. 12.9% ADRs were considered serious. Causality assessment revealed that 80% of the ADRs were possible. 86.97% cases were found to be mild and 51% were not preventable. Conclusion: Pharmacovigilance of these drugs needs to be explored and use of preventive measures needs to be enhanced in order to reduce the incidence and severity of ADRs.

Background: Prescription of antidepressants has been increased from the last decade. Also, they are responsible for producing so many ADRs such as dry mouth, blurred vision, weight gain and drowsiness, sleep disorders. Sleep disorders can generally be divided into 3 large groups: (1) Insomnia, (2) those with a primary complaint of daytime sleepiness, and (3) those associated with disruptive behaviors during sleep—the disorders of arousal. So, active surveillance is needed to access these ADRs. Aim & Objective: To analyze the sleep disturbances as an adverse drug reaction (ADRs) of various antidepressants prescribed to the patients attending the Psychiatry OPD at Teerthanker Mahaveer Medical College & Research Centre. Materials & Methods: The data were collected from the Red ADR boxes in the department of Psychiatry OPD at TMMC & RC, Moradabad, U.P. The patients, who were prescribed antidepressant drugs for duration of 10 months (Dec, 2013- July, 2014) were included in the study. Results: Total number of patients enrolled on the basis of inclusion and exclusion criteria = 50 Total number of ADRs=65. Total no of patients with sleep disturbances as ADRs=28 Conclusion: The drug most frequently implicated to cause sleep disturbances was Mirtazapine. Increased sleep was the commonest ADR found to occur. Unusual ADRs such as sleep talking was also seen. However, we assume that more robust reporting is needed as this shall enable us to detect the category of sleep disturbance, based on polysomnography.

Introduction The lichenoid drug eruptions are rare drug reactions. We report a patient who presented a lichenoid drug eruption induced nivaquine. Observation: Patient aged 60 years followed for rheumatoid arthritis as chloroquine 200mg / day, 1 month and a half after his administration the patient developed a lichenoid eruption objective .L'examen very itchy erythematous, scaly lesions brilliant curling update finely striated by confluent place at the forearm, legs and face and neck, evoking a lichenoid drug eruption. A skin biopsy performed objectified focal hyperkeratosis with interruptions of the granular layer, bodies colloids in granular layers and cornea; in the dermis we note the presence of eosinophils. A statement pharmacovigilance was made with discontinuation of the drug. The evolution is marked by its widespread vitiligo. Discussion In our patient, the study of accountability criteria calls for responsibility for chloroquine. Regressions can also occur in case of continuation of responsible medication, or change in intermittent spurts. This side effect is more frequently reported with gold salts, captopril, D-penicillamine, beta-blockers. Lichenoid drug eruptions pose differential diagnosis with lichen planus. However, some semiotic criteria proposed by some authors sometimes distinguish them. These elements are: The occurred at an older age (over 60 years), as was the case of our patient, lesion polymorphism, lack conventionally Wickham striae and more frequent progression to hyperpigmentation. Our observation is special share installing a lichenoid eruption but also by secondary installation of vitiligo.Toxiderma representing a state of stress can induce a generalized vitiligo on land prone .Histologically, lichenoid drug eruptions are characterized hyperkeratosis with focal disruptions of the stratum granulosum and the presence of colloids in the granular body layers and cornea. In the dermis, the presence of eosinophils would be specific for never observed in lichen planus. Conclusion We underline the interest to think of a lichenoid drug eruption before an eruption occurs in patients under nivaquine.

The natural resistance (intrinsic) defines the ability of a microorganism to be insensitive to an antibiotic. Intrinsic resistance genes are genetic apparatus of the cell and makes the very existence of bacteria in natural environments where there is a wide variety of substances that inhibit the growth or even toxic. The bacteria in natural environments have a reserve of any inhibitor resistance genes whose existence was revealed experimentally: Soil bacteria have the ability to metabolize biosynthesis inhibitors or chemical synthesis, they use as the sole source of C and N (aminoglycosides, fluoroquinolones, etc.). Target inaccessibility due to the impermeability of structures as the outer membrane of Gram-negative bacteria, is a passive resistance. But inaccessibility target can be an active process: For example, the activity of efflux pumps, energy dependency, which eliminates the drug against a concentration gradient. Antibiotic resistance is always a genetic substrate. The populations of bacterial pathogens and saprobionte, is an important reserve of resistance genes.Resistance is acquired by multiple genetic mechanisms: Activation of resistance genes in the presence of the inducer; by chromosomal mutations in genes that modify the target; as a result of expression of a chromosomal gene dormant; consecutive acquisition exogenous genes by gene transfer mechanisms. Knowledge of the mechanisms that determine antibiotic resistance and causes that contribute to their development, is the first step in preventing microbial infections and the development of new antimicrobial substances.PCR tests were performed on a total of 150 strains gram negative.

Gloria Sam has completed her Doctorate in Pharmacy (Pharm D) at the age of 23 years from JSS University, JSS College of Pharmacy, Ooty. She is currently working as an Assistant Professor in Bapuji Pharmacy College, Davangere. She has one international publication and is a member of Indian Pharmaceutical Association (IPA). She has done a poster presentation on “Overcoming depression: The role of pharmaceutical counseling among diabetes depressed patients” in the Indian Pharmaceutical Association students Congress-5 organized by the IPA. She has also got a two month working experience as a clinical pharmacist in Fortis hospital, Bangalore.

Stevens - Johnson syndrome (SJS) is a rare deadly skin disease that usually results from a drug reaction. The other form of SJS is Toxic Epidermal Necrolysis (TEN). In this study, a female patient of 36yrs old had experienced episodes of seizure and was prescribed with Tab. Phenytoin for one month which later developed into SJS and TEN. The patient did not experience SJS prior to phenytoin administration. During her previous admission her Sr Creatinine and Random blood sugar was normal, but her blood urea was slightly high. Her family history did not contain any seizure disorders or other diseases. Initially the patient experienced flu like symptoms (fever, cough, sore throat, runny nose and general aches and pains) followed by an abrupt onset of tender/painful red skin rash and blisters. The blisters then lead to skin detachment, exposing red dermis. After diagnosing it as phenytoin induced SJS, phenytoin was removed from her treatment plan and she was advised to have frequent fluid feeds to prevent dehydration. After 3 days of admission, the patient’s condition kept deteriorating. Medications such as ceftriaxone, dexamethasone, chlorpheniramine maleate and alprazolam were administered. On day 4, her BP was normal and antibiotics were stopped. Anemia was also seen in this patient, which is one of the major marker in SJS/TEN. The mechanism of SJS is very clear in this patient.

The present study was aimed to investigate the pharmacokinetics behavior and optimal dosage regimen of danofloxacin in 8 adult healthy buffaloes of local breed (Nili Ravi) following single intravenous administration at the dose of 2.5 mg/kg body weight. Plasma drug concentrations at various time intervals were measured by HPLC method. In vitro plasma protein binding was determined employing the ultra filtration technique. The distribution and elimination of danofloxacin was rapid, as indicated by the values (Mean±SD) of distribution half-life (t1/2α = 0.25±0.09 hours) and elimination half life (t1/2β=3.26±0.43 hours), respectively. Volume of distribution at steady state (Vss) was 1.14±0.12 L/kg, displaying its extensive distribution into various body fluids and tissues. The high value of AUC (9.80±2.14 µg/ml.hr) reflected the vast area of the body covered by drug concentration. The mean residence time was noted to be 4.78±0.52 hours. On the basis of pharmacokinetic parameters, a suitable intravenous regimen for danofloxacin in adult buffaloes would be 6.5 mg/kg to be repeated after 12 hours intervals. The present study is the foremost pharmacokinetic study of danofloxacin in the local species which would provide the valuable contribution in the local manufacturing of danofloxacin in Pakistan in the future.

Background: Polymorphism of CYP2C19 gene is one of the important factors in pharmacokinetics of CYP2C19 substrates. Omeprazole is a proton pump inhibitor which is mainly metabolized by cytochrome P450 2C19 (CYP2C19). The aim of present study was to assess omeprazole hydroxylation index as a measure of CYP2C19 activity considering new variant allele (CYP2C19*17) in Iranian population and also to see if this activity is sex dependent. Methods: One hundred and eighty healthy unrelated Iranian individuals attended in this study. Blood samples for genotyping and phenotyping were collected 3 hours after administration of 20 mg omeprazole orally. Genotyping of 2C19 variant alleles *2, *3 and *17 was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and semi-nested PCR methods. Plasma concentrations of omeprazole and hydroxyomeprazole were determined by high performance liquid chromatography (HPLC) technique and hydxroxylation index (HI) (omeprazole/ hydroxyomeprazole) was calculated. Results: The CYP2C19*17 was the most common variant allele in the studied population (21.6%). Genotype frequencies of CYP2C19*17*17, *1*17, and *2*17 were 5.5%, 28.8% and 3.3% respectively. The lowest and the highest median omeprazole HI was observed in *17*17 and *2*2 genotypes respectively (0.36 vs. 13.09). The median HI of omeprazole in subjects homozygous for CYP2C19*1 was 2.16-fold higher than individuals homozygous for CYP2C19*17 (P < 0.001) and the median HI of CYP2C19*1*17 genotype was 1.98-fold higher than CYP2C19 *17*17 subjects (P < 0.001). However, subjects with CYP2C19*2*17 (median HI: 1.74) and CYP2C19*1*2 (median HI: 1.98) genotypes and also CYP2C19*1*17 (median HI: 0.71) and CYP2C19*1*1 (mean HI: 0.78) did not show any significantly different enzyme activity. In addition, no statistically significant difference was found between women and men in distribution of CYP2C19 genotypes. Furthermore, the hydroxylation index of Omeprazole was not different between women and men in the studied population. Conclusion: Our data point out the importance of CYP2C19*2 and CYP2C19*17 variant alleles in metabolism of omeprazole and therefore CYP2C19 activity. Regarding the high frequency of CYP2C19*17 in Iranian population, the importance of this new variant allele in metabolism of CYP2C19 substrates shall be considered.

The aim of present study involves preparation and characterization of floating microspheres using gentamicin as a model drug to increase the residence time in the stomach without contact with the mucosa. Floating microspheres were prepared by the capillary extrusion technique using chitosan as polymer and sodium lauryl sulphate, sodium tripolyphosphate as cross linking agent. The surface morphology of the prepared microspheres was characterized by the optical microscopic and SEM method. The effect of the stirring rate during preparation, polymer concentration and cross-linking concentration on the percent yield, in vitro floating behavior, physical state of the incorporated drug, drug loading and in vitro drug release were studied. The prepared microspheres exhibited prolonged drug release (12 h) and remained buoyant for more than 11 h. The microspheres were found to be regular in shape and highly porous. The gentamicin release rate was higher in the case of microspheres prepared at a higher agitation speed and decreased with increasing the polymer and cross linking agent concentration. All formulations demonstrated favorable in vitro floating characteristics. The drug entrapment increased from 65.20 to 95.40% with increasing polymer to drug ratio. Diffusion was found to be the main release mechanism. No significant change was observed in swelling ratio, % drug content, buoyancy lag time or in vitro dissolution pattern after storage at accelerated stability condition for six months. Thus, the prepared floating microspheres may prove to be potential candidates for multiple-unit delivery devices adaptable to any intra-gastric conditions.