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First Administration (first + administration)
Selected AbstractsEvaluation of gastric toxicity of indomethacin acid, salt form and complexed forms with hydroxypropyl-,-cyclodextrin on Wistar rats: histopathologic analysisFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2009A.C. Ribeiro-Rama Abstract Indomethacin (IM) is a non-steroidal anti-inflammatory drug which inhibits prostaglandin biosynthesis. It is practically insoluble in water and has the capacity to induce gastric injury. Hydroxypropyl-,-cyclodextrin (HP-,-CD) is an alkylated derivative of ,-CD with the capacity to form inclusion complexes with suitable molecules. IM is considered to form partial inclusion complexes with HP-,-CD by enclosure of the p -chlorobenzoic part of the molecule in the cyclodextrin channel, reducing the adverse effects. The aim of this paper is to evaluate the gastric damage induced by the IM inclusion complex prepared by freeze-drying and spray-drying. A total of 135 Wistar rats weighing 224.4 ± 62.5 g were put into 10 groups. They were allowed free access to water but were maintained fasted for 18 h before the first administration until the end of the experiment. IM acid-form, IM trihydrated-sodium-salt and IM-HP-,-CD spray and freeze-dried, at normal and toxic doses, were administered through gastric cannula once/day for 3 days. Seventy-two hours after the first administration, the animals were sacrificed and the stomachs collected and prepared for morphological study by using the haematoxylin-eosin technique. Lesion indexes (rated 0/4) were developed and the type of injury was scored according to the severity of damage and the incidence of microscopic evidence of harm. Microscopic assessment demonstrated levels of injury with index one on 10,25%. The type of complexation method had different incidence but the same degree. The results show that IM inclusion complexation protects against gastric injury, reducing the incidence and the maximum degree of severity from 4 to 1, with a better performance of the spray-dried complex. [source] Safety pharmacology in the nonclinical assessment of new medicinal products: definition, place, interest and difficultiesFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2002Jean-Roger Claude Until the year 2000 there was no internationally-accepted definition for the terms used in nonclinical pharmacology (primary, secondary pharmacodynamics, discovery, safety pharmacology, etc). Now, after ICH5 (San Diego, November 2000), a harmonisation of the nomenclature is adopted: safety pharmacology is defined as the studies that investigate the potential undesirable pharmacodynamic effects of a medicinal product on physiological functions in relationship to exposure. Consequently, safety pharmacology studies are a part of the safety assessment for a new product, in the same way than toxicological studies, and a basic battery of tests (core battery) has to be conducted prior to the first administration to humans. Safety pharmacology studies are of peculiar interest: they show a good predictive potential for humans, they do not require a large number of laboratory animals, long-term studies, large amount of products and they are more dynamic and more flexible than toxicological studies. Nevertheless, many difficulties occur for the implementation in industry, related to practical and/or scientific problems: location of the studies, routine activity for the pharmacologists, sometimes difficulties in the relationship between toxicologists and pharmacologists, adaptation to the GLP requirements, elaboration of an early relevant scientific programme, necessity to go to contract-labs or to academic research for unusual or for up to date methods, etc. To conclude, a retrospective timetable of the regulatory evolution for the last 10 years will be provided, as an illustration of the worldwide progress in the concept of `harmonisation' for the assessment of new medicinal products. [source] Reliability and validity of the Youth Self-Report, Bangladesh versionINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 4 2005Takashi Izutsu Abstract The objectives of this study were to develop the Bangladesh version of the Youth Self-Report (YSR), and assess its reliability and validity in an adolescent population in Dhaka city, Bangladesh. One-hundred-and-eighty-seven boys (mean age: 14.6 years, SD: 2.1) and 137 girls (mean age: 15.2 years, SD: 2.0) from residential areas, and 27 boys (mean age: 17.0, SD: 1.4) and 14 girls (mean age: 15.4, SD: 2.8) from a psychiatric hospital, all within the range of 11,18 years, were interviewed using a questionnaire that consisted of the Bangla translation of the YSR and other questions. Thirty-eight randomly selected adolescents were administered the same questionnaire one week after the first administration. All the core scores and most of the subscales showed high internal consistency other than small item-number subscales, and satisfactory test- retest reliability. Good discriminant validity was shown for most of the scale scores. This study showed that the Bangla translation of the YSR had sufficient reliability and validity for use in Bangladesh. The cutoff scores of the scales were higher for the Bangla version than for the original English version, and further studies exploring this point would be an asset. Copyright © 2005 John Wiley & Sons, Ltd. [source] Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsulesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009Shouko Ono Abstract Background and Aim:, Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. Methods:, The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori -negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH < 4 and the median gastric pH were evaluated for 15 consecutive days by a Bravo capsule fixed to the stomach. Results:, On day 1, there was no significant difference between the acid-suppressing effects of the two drugs (ranitidine vs rabeprazole: not significant). Although rabeprazole sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P < 0.05), the effect of ranitidine hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). Conclusion:, In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride. [source] Candida albicans aggravates duodenal ulcer perforation induced by administration of cysteamine in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2007Tetsuya Nakamura Abstract Background:,Candida sp are frequently isolated from the ascitic fluid of patients with perforated ulcers. The present study was performed to examine whether Candida infection may be involved in the process of ulcer perforation. Methods:, Male Wistar rats were divided into a saline group (n = 15) and a Candida group (n = 17). Cysteamine-HCl (Sigma; 31 mg/100 g) was administered thrice on day 1 to both groups of animals. Candida albicans at a density of 108 in 0.5 mL of saline was administered 1 h before, and 12 h and 24 h after the first administration of cysteamine in the Candida group. Results:, Perforated duodenal ulcers were observed in 94.1% of the rats in the Candida group, but only 26.7% of the rats in the saline group (P < 0.01). The area of the duodenal ulcers in the Candida group was 40.89 ± 33.07 mm2, whereas that in the saline group was 16.53 ± 20.4 mm2 (P < 0.05). The mortality rate was significantly higher in the Candida group than in the saline group. In the Candida group, colonization by C. albicans was recognized at the ulcer base, surrounded by marked granulocytic infiltration. The number of eosinophils infiltrating the ulcer base was also significantly greater in the Candida group than in the saline group. Immunohistochemical analysis revealed the expression of secretory aspartyl protease (SAP) in the region of the ulcer showing colonization by C. albicans in the Candida group. Conclusion:,Candida albicans aggravates duodenal ulcer perforation in the experimental model of cysteamine-induced duodenal ulcer perforation. The present findings suggest that SAP and host,parasite relationships, including granulocyte-dependent mechanisms, may be involved in the aggravation of ulcer perforation by C. albicans. [source] The pharmacokinetics and safety of porfimer after repeated administration 30,45 days apart to patients undergoing photodynamic therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010S. P. Pereira Summary Background, Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus. Aim, To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30,45 days apart in patients undergoing photodynamic therapy. Methods, Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3,5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations. Results, Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related. Conclusion, Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days. [source] Can Politicians Control Bureaucrats?LATIN AMERICAN POLITICS AND SOCIETY, Issue 4 2003Applying Theories of Political Control to Argentina's Democracy ABSTRACT In the United States, an important literature shows that legislators use interest groups, courts, and budgets to assert political control over bureaucrats. Similar theories can be applied to study the scores of new democracies that have emerged in recent decades. In Argentina, politicians in the first administration of Carlos Menem (1989-95) rewrote administrative procedures and relied on both "police patrol" and "fire alarm" oversight to realign the behavior of tax bureaucrats in conformance with their own policy preferences. Whereas U.S. legislators generally prefer complex administrative procedures, different electoral incentives led their Argentine counterparts to support reforms that significantly streamlined those procedures. This finding challenges theories that attribute legislators' bureaucratic preferences to the separation or fusion of powers between the executive and legislative branches. [source] Association of body rolling, leg rolling, and rhythmic feet movements in a young adult: A video-polysomnographic study performed before and after one night of clonazepamMOVEMENT DISORDERS, Issue 4 2008Giovanni Merlino MD Abstract We report clinical and polysomnographic data of a young adult affected by several forms of rhythmic movement disorder (RMD), present in the same night, including a new kind of it, known as rhythmic feet movements. The patient was monitored by means of three consecutive video-polysomnographic recordings, the first two performed to confirm the presence of the sleep disorder and the last one to observe the acute effectiveness of clonazepam on rhythmic movements. We discuss the characteristics of the RMD and the response to the first administration of pharmacological treatment, observed in our patient. © 2007 Movement Disorder Society [source] Morbidity and mortality in rheumatoid arthritis patients with prolonged therapy-induced lymphopenia: Twelve-year outcomesARTHRITIS & RHEUMATISM, Issue 2 2008Alice R. Lorenzi Objective To assess immunologically relevant outcomes in a cohort of rheumatoid arthritis (RA) patients with prolonged therapy-induced lymphopenia. Methods Morbidity (infection or malignancy) and mortality were assessed in 53 RA patients who were treated with the lymphocytotoxic monoclonal antibody alemtuzumab between 1991 and 1994. Data were obtained by interview, medical record review, and Office for National Statistics mortality monitoring. Lymphocyte subsets were enumerated by flow cytometry. A retrospective, matched-cohort study of mortality was performed with 102 control subjects selected from the European League Against Rheumatism database of patients with rheumatic disorders. Results Lymphopenia persisted in the patients: median CD3+CD4+, CD3+CD8+, CD19+, and CD56+ lymphocyte counts measured at a median followup of 11.8 years from the first administration of alemtuzumab were 0.50 × 109/liter, 0.26 × 109/liter, 0.11 × 109/liter, and 0.09 × 109/liter, respectively. Twenty-seven of 51 cases and 46 of 101 controls with available data had died, yielding a mortality rate ratio of 1.20 (95% confidence interval 0.72,1.98). Causes of death were similar to those that would be expected in a hospital-based RA cohort. No opportunistic infections were noted, and only 3 infections were documented following 36 elective orthopedic procedures. Conclusion Despite continued lymphopenia 11.8 years after therapy, our patient cohort did not exhibit excess mortality or unusual infection-related morbidity, and surgery was well tolerated. These data should be reassuring for clinicians and patients who are considering lymphocytotoxic or other immunomodulatory therapy for RA. [source] Co-Administration of Dextromethorphan and Morphine: Reduction of Post-Operative Pain and Lack of Influence on Morphine MetabolismBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Maciej Suski In a double-blind study, 60 patients with ASA physical status I,II were randomised into two groups. Group dextromethorphan (n = 30; age: 15.9 ± 2.4 years) was given oral dextromethorphan 30 or 45 mg 1 hr before surgery and 8, 20 and 32 hr after operation. Group placebo (n = 30; age: 16.5 ± 2.7 years) received placebo at identical times. Post-operative analgesic requirements were assessed using nurse-controlled analgesia system. Pain was assessed using numeric rating scale before first administration of morphine and at 2, 3, 4, 6, 24 and 48 hr after operation. Blood samples were taken 20 min. after the first use of morphine (within 1 hr after operation). The total use of analgesics during surgery was lower in the dextromethorphan group. The dose of morphine providing relief immediately after surgery, as well as total analgesic requirements in the first and second day after surgery did not differ between groups. Subjectively evaluated pain intensity score (numeric rating scale) was lower for the dextromethorphan patients in the first 4 hr, but not later after surgery. Plasma levels of morphine, morphine-6-glucuronide and morphine-3-glucuronide did not differ between groups. Dextromethorphan did not influence morphine glucuronidation, in terms of promotion of formation of any morphine glucuronides. In conclusion, in young patients subjected to spine surgery, addition of dextromethorphan to morphine reduced pain only in early post-operative period. In such patients, co-analgesic action of dextromethorphan was not associated with significant changes in plasma levels of morphine metabolites. [source] | |||||||||||||||||||