Search

In this study, the reduction of ranitidine (RNT) was studied on a carbon nanofiber modified glassy carbon sensor (CNF/GC). The method developed for the analysis is selective, reliable, and also env...

Nizatidine is a histamine H2 receptor antagonist which act by inhibiting the production of stomach acid, thereby, finds its application in treating various diseases related to the gastrointestinal tract. Studying albumin-drug interaction is important for understanding the pharmacokinetics and pharmacodynamics of therapeutic candidates. In the present work, the interaction of nizatidine with BSA was investigated by employing multi-spectroscopic and computational studies. The formation of BSA-nizatidine complex was characterised by UV-visible and fluorescence based-spectroscopic studies. Steady-state fluorescence demonstrated the static mode of quenching of BSA by nizatidine. The interaction was spontaneous and nizatidine binds to BSA with a stoichiometry of 1:1. Forster resonance energy transfer calculations revealed that there was a high possibility of energy transfer between nizatidine and BSA. The resultant secondary structural change in BSA on the addition of nizatidine was studied by circular dichroism spectroscopy. Moreover, synchronous and three-dimensional fluorescence spectroscopy was used to determine the conformational changes occurred in the structure of albumin on the binding of nizatidine. Competitive-site marker experiments suggested that nizatidine binds in the Sudlow site II of BSA. Additionally, the effect of β-cyclodextrin as an inclusion compound on the interaction was studied. Furthermore, molecular modelling and simulation studies were performed to corroborate the results obtained above.Communicated by Ramaswamy H. Sarma.

Background: Myocardial H2 receptor activation may promote cardiac fibrosis and apoptosis in pre-clinical models and histamine H2 receptor antagonist (H2RA) use may improve symptoms in parti...

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The panel consisted of five sections: hemodynamics infection adjunctive therapies metabolic and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality. © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objective: To evaluate Qatari pharmacists' prescribing, labeling, dispensing and counseling practices in response to acute community-acquired gastroenteritis. Methods: The simulated patient method was used in this study. Thirty pharmacies in Doha were randomly selected and further randomized into two groups: Face-to-Face (n=15) vs. Telephone-call (n=15) per simulated patient; 2 simulated patients were involved. Prescribing, labeling, dispensing and counseling practices were assessed. Data analysis was performed using Mann-Whitney and chi square tests at alpha=0.05. Results: Most pharmacists prescribed and dispensed medicines (96%), including antimicrobials (43.9%), antidiarrheals (36%), antiemetics (5.1%) and antipyretics (3%). Counseling practices were poor (62.1% in the face-to-face group vs 70% in the telephone-call group did not counsel simulated patients about the dispensed medicines; p-value=0.50). In more than one-third of the encounters, at least one labeling parameter was missing. The duration of each interaction in minutes was not significantly different between the groups [median (IQR); 3(4.25) in the face-to-face group versus 2(0.25) in the telephone-call group; p-value=0.77]. No significant differences in prescribing or dispensing behaviors were present between groups (p-value>0.05). Conclusion: Qatar community pharmacists' labeling, dispensing, and counseling practices were below expectation, thus urging the need for continuous professional development Funding: This research has been funded by Qatar University student research grant (Grant No.: QUST-CPHFALL-12/13-2). Scopus

Background and Aim: The attenuated antisecretory activity of H2-receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. A previous study indicated that Helicobacter pylori (H. pylori) infection prevents the occurrence of tolerance to H2RA. In the present study, we investigated whether intermittent (every other day) administration prevents the tolerance phenomenon in H. pylori-negative patients. Methods: Ten H. pylori-negative, healthy volunteers were included in the study. All of the patients underwent two courses of H2RA (lafutidine) administration: 21-day continuous administration (every day), followed by 21-day intermittent administration (every other day), with at least a 21-day lafutidine-free period between the first and second courses. All of the patients were examined by ambulatory intragastric pH monitoring five times: before medication, and on days 1 and 21 of the first (continuous) and second (intermittent) courses of lafutidine (10 mg b.d.) in a crossover fashion. Results: The continuous administration of lafutidine had a significantly attenuated, acid-suppressing effect in H. pylori-negative patients, and showed evidence of the tolerance phenomenon. However, the tolerance phenomenon was not observed through intermittent administration. Conclusions: These results demonstrated that in H. pylori-negative patients, tolerance to H2RA, induced by continuous lafutidine administration, was reversed by subsequent intermittent administration.

Objective: To analyze prescribing patterns of chronic psychiatric patients living in sheltered housing facilities, to identify the extent of polypharmacy and to estimate associated risks in this patient group. Methods: In a retrospective cross-sectional study the prescription data of 323 chronic psychiatric patients (average age 48.5 years) living in sheltered housing facilities in Rotterdam, The Netherlands, were analyzed. Prescription data were obtained from pharmacy-dispensing records. Results: Patients received on average 4.6 drugs (95% CI, 4.3-4.9). The most frequently prescribed drugs were as expected antipsychotics, benzodiazepines and antimuscarinic drugs. Overall 25% (n = 81) of patients received two or more antipsychotic drugs. A high proportion of patients (38%, n = 124) received one benzodiazepine, and 15% (n = 50) received two or more benzodiazepines. Conclusion: Patients in our study received a worryingly high number of drugs, and a quarter of the population was subject to antipsychotic polypharmacy. This increases the risk that drug-drug interactions, adverse drug reactions and noncompliance occur. Our study indicates potentially low quality of prescribing and shows the need for reviewing and special monitoring of pharmacotherapy in this patient group. © 2008 Dustri-Verlag Dr. K. Feistle.

I read the paper by Leary et al. [(1)][1] with great interest, and I congratulate the authors on their excellent work. As the authors correctly state, histamine H2 receptor antagonist (H2RA) use is associated with a lower risk for incident heart failure (HF) in a multiethnic cohort without

Background: Research on the benefits of clinical medication reviews (CMRs) performed by pharmacists has been conducted mostly in controlled settings and has been widely published. Less is known of the effects after large scale implementation in community pharmacies. An online CMR tool enabled the systematic registration of drug-related problems (DRPs) and implemented interventions derived from CMRs in daily practice. Objective: To describe the effects of CMRs on pharmacy practice after large-scale implementation in the Netherlands. Setting: 268 community pharmacies. Pharmacists were trained on CMRs with a patient centred approach. Method: Retrospective analyses of DRPs, pharmacists' proposals and implemented interventions recorded between January 1st and September 1st 2012. Main outcome measure: Frequencies of DRPs, intervention proposals, implemented interventions, and drugs involved. Results: 4,579 CMRs were analysed. On average 2.9 (SD 2.1) DRPs per review were identified. 4,123 (31 %) of the DRPs led to medication changes. Stopping a drug (16 %) was more frequent than starting a drug (8.1 %). Drugs related to cardiovascular risk management, diabetes and osteoporosis were most frequently involved. Conclusion: This study is the largest analysis of pharmacists- initiated CMRs in the Netherlands to date. The findings demonstrate the potential to reduce medication-related errors through pharmacist involvements in complex pharmacotherapy and the positive impact on the quality of drug therapy through making necessary medication changes. The data also support the need for large-scale implementation of pharmacists-initiated CMRs in the presence of proper training programmes. © 2014 Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie.

The effect of different doses of the newly developed histamine H2 receptor antagonist ranitidine on the sodium taurocholate-induced decrease of the potential difference across the human gastric mucosa was investigated in 18 healthy persons. It was shown that ranitidine protects the human mucosal epithelium against this agent both in acid-inhibitory and non-acid-inhibitory dosages. The results suggest that besides the prostaglandins histamine H2 receptor antagonists possess cytoprotective properties at least against bile acids.

The effect of roxatidine, a histamine H 2 -receptor antagonist, on acute gastric mucosal injury induced by aspirin-HCl was investigated from the standpoint of lipid peroxidation and neutrophil accumulation in rats. Acute mucosal injury was produced on the rat stomach by intragastric administration of aspirin and HCl. Pretreatment with roxatidine at doses of 3 and 10 mg/kg significantly reduced the lesion area induced by aspirin-HCl. The increase in lipid peroxides in the gastric mucosa 3 h after aspirin-HCl treatment was significantly inhibited by roxatidine, and the concentration of lipid peroxides closely paralleled the increase in total area of erosions. Tissue-associated myeloperoxidase (MPO) activity, an index of neutrophil accumulation, in the gastric mucosa increased significantly 3 h after aspirin-HCl administration, and the increase in MPO activity was significantly inhibited by roxatidine and paralleled the increase in total area of erosions. An in vitro study demonstrated that roxatidine scavenged hydroxyl radicals, inhibited superoxide production from activated neutrophils, and inhibited lipid peroxidation of the rat gastric mucosal homogenates. These results indicate that the protective effect of roxatidine against gastric injury induced by aspirin-HCl may result, in part, from its antioxidative properties.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:27:05Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:42:26Z : No. of bitstreams: 1 2-s2.0-84867497122.pdf: 5299696 bytes, checksum: 5b61eafd007a65441b108e512134c902 (MD5) Made available in DSpace on 2014-05-27T11:27:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-10-01 Cimetidine, an H2 receptor antagonist used for treatment of gastric ulcers, exerts antiandrogenic and antiangiogenic effects. In the testes cimetidine impairs spermatogenesis, Sertoli cells and peritubular tissue, inducing apoptosis in the myoid cells. Regarding the importance of histamine and androgens for vascular maintenance, the effect of cimetidine on the structural integrity of the testicular vasculature was evaluated. Adult male rats received cimetidine (CMTG) and saline (CG) for 50 days. The testes were fixed in buffered 4% formaldehyde and embedded in historesin and paraffin. In the PAS-stained sections, the microvascular density (MVD) and the vascular luminal area (VLA) were obtained. TUNEL method was performed for detection of cell death. Testicular fragments embedded in Araldite were analyzed under transmission electron microscopy. A significant decrease in the MVD and VLA and a high number of collapsed blood vessel profiles were observed in CMTG. Endothelial cells and vascular muscle cells were TUNEL-positive and showed ultrastructural features of apoptosis. These results indicate that cimetidine induces apoptosis in vascular cells, leading to testicular vascular atrophy. A possible antagonist effect of cimetidine on the H2 receptors and/or androgen receptors in the vascular cells may be responsible for the impairment of the testicular microvasculature. Department of Morphology and Genetics Federal University of São Paulo (UNIFESP), São Paulo/SP Department of Morphology Laboratory of Histology and Embryology Dental School - São Paulo State University (UNESP/FOAr), Rua Humaitá 1680, 14801-903, Araraquara/SP Department of Morphology Laboratory of Histology and Embryology Dental School - São Paulo State University (UNESP/FOAr), Rua Humaitá 1680, 14801-903, Araraquara/SP

Aim: The purpose of this study was to compare two single agents paclitaxel (intravenous) versus vinorelbine (oral) in non-small cell lung cancer (NSCLC) patients with performance status (PS):2. Patients and Methods: The patients were randomized to receive either oral vinorelbine 60 mg/m 2 on days I, 8, 15 every 4 weeks for 4 cycles (group A) or paclitaxel 90 mg/m 2 intravenously for 1 h on days 1, 8, 15 every 4 weeks for a total of 4 cycles (group B). Results: Among the 74 eligible patients (36 in arm A and 38 in arm B) in arm A, two (6%) had a partial response (95% Cl, 0.7-18.7) and 5 (14%) had stable disease (95% CI, 4.7-29.5). In arm B, five (13%) had a partial response (95% CI, 4.4-28.1) and 7 (18%) had stable disease (95% CI, 7.7-34.3). No significant difference was found in terms of clinical benefit between the two groups after two cycles of treatment except for appetite in favour of paclitaxel (p=0.01). Median survival was 3.1 months (95% CI, 2.2-4.0) for arm A and 5.1 months (95% CI, 2.7-7.6) for arm B (p=0.95). Toxicity was mild and only alopecia was more profound in the patients of arm B (p=0.008). Conclusion: No significant difference was found in clinical benefit between PS:2 NSCLC patients treated with either vinorelbine or paclitaxel. 32 1 175 181

Objective: To analyze prescribing patterns of chronic psychiatric patients living in sheltered housing facilities, to identify the extent of polypharmacy and to estimate associated risks in this patient group. Methods: In a retrospective cross-sectional study the prescription data of 323 chronic psychiatric patients (average age 48.5 years) living in sheltered housing facilities in Rotterdam, The Netherlands, were analyzed. Prescription data were obtained from pharmacy-dispensing records. Results: Patients received on average 4.6 drugs (95% CI, 4.3-4.9). The most frequently prescribed drugs were as expected antipsychotics, benzodiazepines and antimuscarinic drugs. Overall 25% (n = 81) of patients received two or more antipsychotic drugs. A high proportion of patients (38%, n = 124) received one benzodiazepine, and 15% (n = 50) received two or more benzodiazepines. Conclusion: Patients in our study received a worryingly high number of drugs, and a quarter of the population was subject to antipsychotic polypharmacy. This increases the risk that drug-drug interactions, adverse drug reactions and noncompliance occur. Our study indicates potentially low quality of prescribing and shows the need for reviewing and special monitoring of pharmacotherapy in this patient group. © 2008 Dustri-Verlag Dr. K. Feistle.

Crystal structure of a novel cobalt(III) complex with antiulcer drug famotidine and ethylenediamine was determined. This is the second structure of a transition metal complex with famotidine resolved by a single crystal X-ray analysis, in which famotidine shows different mode of coordination than that observed in the other cases. Drug molecule is coordinated to metal ion as a tetradentate ligand through guanidine N6, thiazole N4, thioether S2 and terminal N3 atom. Two NH2 groups (N3H(2) and N6H(2)) are deprotonated and drug coordinates as dianion. In the asymmetric unit, one chloride anion and one water molecule were found to complete the complex stoichiometry. The structure of the complex is abundant in atoms, which can be involved in hydrogen bond formation either as hydrogen acceptors or hydrogen donors. Because of that, a great number of hydrogen bonds dominates the crystal packing. Beside the hydrogen bonds, there are two interesting noncovalent interactions: CH...pi and NH...pi within the famotidine anion, which stabilize the complex structure. The pi...pi stacking interactions between neighboring complex cations are also observed. Antibacterial and antifungal activity of famotidine and its newly synthesized complex against representative bacteria: Escherichia coli, Staphilococcus aureus and Micrococcus lysodeikticus and fungi: Aspergillus niger and Candida albicans were examined. The results indicate a higher selectivity of the famotidine-Co(III) complex, as well as better growth inhibitory activity (lower MIC values (MIC, minimal inhibitory concentration)) in comparison with the drug alone. (c) 2006 Elsevier Inc. All rights reserved.

11 7

The effect of zolantidine dimaleate (ZOL), the first brain-penetrating histamine H2 receptor antagonist, was determined on morphine (MOR) antinociception (ANC) in rhesus monkeys. ZOL (0.75 mg/kg, s.c., given every 30 min), completely attenuated the ANC resulting from the lowest dose of MOR tested (1.0 mg/kg), with no effect on the responses to higher doses (3-10 mg/kg). ZOL had no effect on baseline nociceptive responses in the absence of MOR. Taken with previous studies on the pharmacological specificity of ZOL, the ANC properties of histamine, and more extensive studies in rodents, the present results suggest that opiates like MOR relieve pain in primates by mechanisms that include activation of brain H2 receptors.

A program to promote generic cimetidine as the preferred histamine H2-receptor antagonist (HRA) in the managed care organizations (MCOs) served by a pharmacy benefit management company is described. A pharmacy benefit management company conducted a literature review to substantiate the therapeutic equivalence of the HRAs and to set conservative criteria for identifying candidates for conversion to oral cimetidine therapy. During the third quarter of 1994, the prescriber for each patient identified was sent a document listing the patient's current HRA therapy, the date of his or her last prescription refill, and the name and telephone number of the dispensing pharmacy. A letter summarized the literature; outlined the criteria used to identify candidate patients; gave the current indications, dosages, and average wholesale prices of the HRAs; and asked the prescriber to switch the patient to generic cimetidine. HRA use in an MCO that participated in the program was compared with HRA use in a nonparticipating MCO for the second quarter of 1994 (the baseline period), the fourth quarter of 1994, and the first quarter of 1995. The nonparticipating MCO showed no change between baseline and 1995 in the proportion of HRA prescriptions accounted for by brand-name and generic cimetidine combined (14% for each period). The average acquisition cost per HRA prescription remained about $75 for each study quarter. In the participating MCO, the proportion of HRA prescriptions accounted for by brand-name plus generic cimetidine increased from 18% at baseline to 39% in the first quarter of 1995. The average acquisition cost per HRA prescription fell from $71 at baseline to $65 in the first quarter of 1995. A program to shift the use of brand-name HRAs to generic cimetidine in MCOs successfully altered prescribing patterns and reduced expenditures for these agents.

Contagious agalactiae (CA), caused by Mycoplasma agalactiae , is among the most significant diseases affecting small ruminants. CA is described as an endemic disease in the Mediterranean region, where it causes significant economic impact due to reduced milk production and increased lamb mortality rates (Nicholas 1995, Bergonier and ­others 1997). Killed M agalactiae vaccine is used for the control of CA, but the level of acquired immunity is relatively low (Leon and others 1995). Immunotherapy as an adjunct to vaccine application may improve the resulting immune response. Various immunostimulant drugs, such as recombinant growth factors, cytokines, levamisole and beta - glucan, have been tested and used in veterinary and human medicine (Suzuki and others 1990, Qureshi and others 2000, Senturk and others 2003). Levamisole has been used for the treatment of many nematode infections in animals. The immunostimulating activity of levamisole has been well documented in several experimental and clinical studies (Neveu 1970, Symoens and Rosenthal 1977, Sharma and others 1990, Obminska and Calkosinski 1994, Senturk and others 2003, Senturk and others 2009). It is hypothesised that levamisole restores cell-mediated immune function in peripheral T lymphocytes, and stimulates phagocytosis by monocytes (Barragy 1994). Sharma and others (1990) reported that haemorrhagic septicemia vaccination combined with the administration of levamisole hydrochloride resulted in higher serum antibody titres and longer-lasting immunity (Sharma and others 1990). One mode of action of levamisole is the promotion of T-cell activity and restoration of the activities of T-helper and T-suppressor cells (Gonsette and others 1982). Some studies have also indicated that the mode of action of levamisole as an immunomodulator is achieved by boosting cell-mediated immunity via the ­induction of type 1 cytokines (Szeto and others 2000). Additionally, Olusi and others (1979) reported that levamisole significantly restored the cell-mediated immune response in malnourished rats. Various animal and …

We examined the effects of FRG-8813, a new histamine H2-receptor antagonist with potent antisecretory activity, on gastric mucus in male SD rats (7w). In this study, the effects of FRG-8813 (1, 3, 10 mg/kg), given orally twice a day for 7 days, were investigated by histochemical and biochemical methods in comparison with those of cimetidine (CM, 30 mg/kg) and famotidine (FM, 1 mg/kg) in the fundic gland area (F. area) and pyloric gland area (P. area). In the histochemical study by alcian blue (pH 2.5)-PAS (AB-PAS) or high iron diamine-alcian blue (HID-AB) staining, the CM group showed a significant decrease in PAS and tended to show decreases in HID-AB positive mucus and mucous gel layer in the F. area; the FM group also showed a decrease in AB positive mucus in the P. area. On the other hand, the AB-PAS and HID-AB positive mucus of the FRG-8813 group were not affected. In the biochemical study, FRG-8813 increased the gastric mucosal hexose, hexosamine and sialic acid composing the mucus in a dose-dependent manner in the F. area. These results suggest that FRG-8813 does not cause a decrease in gastric mucus, unlike CM or FM, and it may be able to promote mucus secretion through increasing the mucous component in the F. area.