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排序方式: 共有490条查询结果,搜索用时 15 毫秒
81.
Mei-Ling Chen Vinod P. Shah Derek Ganes Kamal K. Midha James Caro Prabu Nambiar Mario L. Rocci Jr. Avinash G. Thombre Bertil Abrahamsson Dale Conner Barbara Davit Paul Fackler Colm Farrell Suneel Gupta Russell Katz Mehul Mehta Sheldon H. Preskorn Gerard Sanderink Salomon Stavchansky Robert Temple Yaning Wang Helen Winkle Lawrence Yu 《The AAPS journal》2010,12(3):371-377
Modified release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current industry practices and regulatory expectations for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products. 相似文献
82.
BACKGROUND: Automated blood culture systems are not FDA-approved for sterility testing of human cells, tissues, or cellular- or tissue-based products. It was previously demonstrated that BacT/ALERT (bioMérieux) and Bactec (Becton Dickinson) were superior to the manual CFR method described in the general biologics regulations, in rates of detection and time to detection of organisms seeded into mock mononuclear cell products with a variety of background media and antibiotics. In this study, the two automated systems were compared to the CFR method for sterility testing of actual cell therapy products manufactured in our facility. STUDY DESIGN AND METHODS: Over a 36-month period, in-process and final product samples from all cell therapy products manufactured in our facility were tested for sterility both by the CFR method and by either BacT/ALERT or Bactec. Products were categorized according to collection and processing variables for analysis of results. RESULTS: For 1617 samples of a broad range of cell therapy products, rates of true-positive tests were comparable for the automated and CFR methods (2.3% vs. 2.1%), but the CFR method had higher rates of false-positive results (7.3% vs. 0.2%). For automated systems, time to detection of organisms was equivalent to, or faster than, the CFR method. CONCLUSION: Compared to the CFR method, both BacT/ALERT and Bactec are more sensitive, faster in time to detection, less prone to false-positive results, and less labor-intensive. Both of these automated systems are suitable for sterility testing of cell therapy products after site-specific validation has been performed. 相似文献
83.
Rajender S Thangaraj K Gupta NJ Leelavathy N Rani DS Nambiar RG Kalavathy V Santhiya ST Rajangam S Gopinath PM Chakravarty B Singh L 《The Journal of clinical endocrinology and metabolism》2006,91(10):4028-4036
CONTEXT: The molecular basis for about 70-80% of 46,XY sex-reversed females remains unexplained, because they carry normal copies of the genes (SRY, SOX9, DAX1, DMRT, SF1, WT1) involved in sex determination pathway. OBJECTIVE: The objective of this study is to map the chromosomal locus responsible for an unexplained sex-reversed phenotype. DESIGN: The study implemented a genome-wide scan using families with multiple sex-reversed individuals. SETTING: The patients, along with the family members, were selected from different hospitals/reproductive centers. PARTICIPANTS: Sex-reversed individuals and their siblings and parents participated in the study. MAIN OUTCOME MEASURES: Identification of the chromosomal locus responsible for sex reversal in these families and sequence analysis of candidate genes were the main outcome measures. RESULTS: Parametric linkage analysis revealed a maximum two-point LOD score of 5.70 with marker DXS991 (Xp11.21) and 4.57 with marker DXS1039 (Xp11.23-Xp11.22), and a multipoint LOD score of 5.77 with marker DXS991 and 5.22 with marker DXS1039. The two markers (DXS991 and DXS1039) with highest LOD score span approximately 3.41 cM (75.79-79.2 cM) on the short arm of the X-chromosome. CONCLUSION: Our findings provide evidence for a major susceptibility locus for sex reversal/gonadal dysgenesis on the short arm of the X-chromosome (Xp11.21-11.23). Furthermore, molecular exploration of the expression of candidate genes in the embryonic gonad/gonadal ridge will help in the identification of the underlying gene for sex reversal. 相似文献
84.
Saul Maayani Nayana D. Patel Barbara D. Craddock-Royal Todd E. Schwarz Thomas M. Tagliente 《Platelets》2013,24(2):89-102
This study tested the hypothesis that aggregation mediated by activation of a single G q -coupled receptor can be studied quantitatively if four concurrent but distinct components of the observed platelet response, autocrine stimulation, shape change (SC), aggregation and deaggregation, are separately measured. Responses mediated by two G q -coupled receptors, the TXA 2 and the P2Y 1 , were assayed by a novel, kinetics-based turbidimetric approach. Blocking the autocrine stimulation with a cocktail of receptor antagonists revealed rapid and sustained SC that largely masked the aggregation. Mathematical removal of the SC contribution from the changes in optical density indicated that selective activation of either the TXA 2 or the P2Y 1 receptor was sufficient to induce a small aggregation ( j OD = 0.1-0.2) that was reversed rapidly by a concurrent deaggregation. Model-derived rate constants of SC, aggregation and deaggregation described the observed complex time course of their concurrency well. Laser light scattering aggregometry confirmed the rapid deaggregation of platelet aggregates following TXA 2 or P2Y 1 receptor-mediated formation. Saturable concentration response curves of net aggregation were elicited at EC 50 values 6-15 higher than those of SC. The utility of this approach was further demonstrated by the separation of the four components of the response mediated by concurrent 5-HT 2A and f 2A -adrenoceptor activation, as well as the P2Y 1 and f 2A -adrenoceptor, and the autocrine stimulation and SC mediated by the 5-HT 2A receptor. We propose that the novel approach described here is necessary to study the receptor pharmacology and the kinetics of concurrent platelet responses in vitro as demonstrated by platelet aggregation elicited by selective activation of the TXA 2 or the P2Y 1 receptors. 相似文献
85.
86.
Sushil Chawla M. Nakra S. Mohan B.C. Nambiar Raju Agarwal A. Marwaha 《Medical Journal Armed Forces India》2013
Background
Pregnant women are at risk to develop complications due to illness related to pregnancy or due to aggravation of pre-existing disease. These patients also require critical care and ICU admissions in some cases. To determine the current spectrum of diseases in an obstetric population resulting in admission to the intensive care unit (ICU) at a tertiary care hospital.Methods
A retrospective case series study and analysis of data from obstetric patients admitted for critical care management.Results
0.26% of the total obstetric patients admitted to the hospital required ICU admissions. 46% of patients were admitted to ICU for ventilator support. Pre-eclampsia and obstetrical hemorrhage were the common diagnosis for these patients.Conclusion
Critically ill obstetric patients require a team approach of the obstetrician, anesthesiologist and intensive care specialist for the optimal care of these patients. 相似文献87.
Filipe S. Duarte Marcelo Duzzioni Alexandre A. Hoeller Nayana M. Silva Andy L. Ern Tetsade C. Piermartiri Carla I. Tasca Elaine C. Gavioli Tadeu Lemos Antonio P. Carobrez Thereza C. M. De Lima 《Psychopharmacology》2013,227(2):209-219
Rationale
There is extensive evidence indicating the influence of seizures on emotional responses observed in human and animals, but so far few studies are focusing on the behavioral profile of animals that do not have seizures despite being treated with convulsant agents.Objectives
We aimed to establish the behavioral profile, biochemical, and electrographic features of rats submitted to the pilocarpine model of temporal lobe epilepsyMethods
Rats treated with pilocarpine (20 to 350 mg/kg, i.p.) that did not develop status epilepticus or spontaneous recurrent seizures were evaluated 1 month later in the elevated plus maze (EPM), T-maze (ETM), open-field (OF), and step-down avoidance tests. Electroencephalographic (EEG), glutamate uptake, and hippocampal neuronal death assays were also performedResults
Pilocarpine (150 or 350 mg/kg) promoted anxiogenic-like effects in rats evaluated in the EPM, ETM, and OF tests, whereas only the highest dose evoked spike–wave discharges during EEG recordings. Hippocampal theta rhythm was increased by pilocarpine 150 or 350 mg/kg and only the highest dose reduced the l-[3H]-glutamate uptake and cell viability on hippocampal slices.Conclusions
Subconvulsant doses of pilocarpine promote long-lasting alterations on neural circuitry, reflected by an increased theta activity in the hippocampus and an anxiety-like profile of rats evaluated 1 month after the treatment which is independent of seizure occurrence and is not related to changes in glutamate uptake or hippocampal damage. These results prompt us to suggest that a systemic administration of subconvulsant doses of pilocarpine could be useful as a new tool to model trait anxiety in rats. 相似文献88.
Sajid S. Qureshi Deepak Ramraj Girish Chinnaswamy Badira C. Parambil Maya Prasad Nayana Amin Subramaniam Ramanathan Nehal Khanna Siddharth Laskar 《Medicine》2021,100(35)
To describe the outcomes of elective cancer surgeries and adverse consequences on the patients and medical staff due to the surgical interventions in children during the Coronavirus Disease 2019 (COVID-19) pandemic.The study included children younger than 15 years who underwent elective cancer surgeries from March 4, 2020 and December 3, 2020.A total of 121 patients (62% male; median age, 3 years) underwent surgery. The surgical procedures included nephrectomies (n = 18), neuroblastoma (n = 26) and soft tissue tumor resections (n = 24) and complex surgical procedures like extended liver resections (n = 2), intra-atrial thrombectomy under cardiopulmonary bypass (n = 2), pancreatoduodenectomy (n = 1), and free microvascular flaps (n = 7). Clavien-Dindo Grade III complications were 5% (n = 6), and there were no postoperative deaths. Preoperative COVID-19 testing was performed in 82% of children, and only 2% showed severe acute respiratory syndrome coronavirus 2 positivity. Postoperatively, 26 children were tested because of specific symptoms and, 6 tested positive for severe acute respiratory syndrome coronavirus 2. Except for a median delay of 23 days in treatment, none of the patients with COVID-19 required critical hospital management. None of the surgical residents or faculty acquired COVID-19, while 4 each medical and support staff were tested positive in the study period.COVID-19 was not a deterrent for continued cancer care, and surgeries could be safely performed adopting universal preventive measures without any added morbidity from COVID-19. Caregivers and centers dealing with childhood cancers can be encouraged to sustain or seek early healthcare. 相似文献
89.
Erin C. Bridgeford James G. Fox Prashant R. Nambiar Arlin B. Rogers 《Journal of clinical microbiology》2008,46(5):1881-1884
Sentinel mouse seroconversion to infectious agents is critical for laboratory animal facility disease monitoring. We report spontaneous emergence of non-sex-linked agammaglobulinemia with B-cell deficiency and cutaneous Staphylococcus aureus granulomatosis (botryomycosis) in a cohort of related Swiss Webster sentinel mice. Our experience reinforces the importance of immunocompetency validation in surveillance programs.Immunocompetence of sentinel mice is an integral component of laboratory animal facility disease-monitoring programs. If immunity is compromised, surveillance mice may fail to detect infectious agents. This can have a serious impact on animal health and on the integrity of scientific data. Here we report the spontaneous emergence of non-sex-linked agammaglobulinemia with B-cell deficiency and frequent Staphylococcus aureus pyogranulomas (botryomycosis) in a cohort of sentinel Swiss Webster mice intended for disease surveillance or used as embryo transfer recipients in our transgenic facility. The condition first manifested as an unusual cluster of cutaneous botryomycosis over an 11-month period, prompting further investigation and the discovery of an underlying B-cell deficiency and agammaglobulinemia. Records indicated that all affected mice were descended from eight breeding pairs purchased from a single vendor. Depopulation and replacement with new sentinels eliminated the problem. Our experience underscores the importance of periodic validation of immunocompetence in surveillance animals, which we have incorporated into our standard operating procedures (5, 6). All protocols described in this report were in compliance with the U.S. Public Health Service Policy on Humane Care and Use of Laboratory Animals (14) and approved by the Massachusetts Institute of Technology Committee on Animal Care. 相似文献
90.
Jayatilaka NK Angela Montesano M Whitehead RD Schloth SJ Needham LL Barr DB 《Archives of environmental contamination and toxicology》2011,61(1):59-67
Acephate, methamidophos, o-methoate, and dimethoate are organophosphorus pesticides, and ethylenethiouria and propylenethiourea are two metabolites
from the bisdithiocarbamate fungicide family. They are some of the most widely used pesticides and fungicides in agriculture
both domestically and abroad. The existing high-performance liquid chromatography (HPLC)–tandem mass spectrometry (MS/MS)
method for the measurement of these compounds in human urine was improved by using a 96-well plate format sample preparation;
the use of HPLC-MS/MS was comparable with a concentration range of 0.125 to 50 ng/ml. Deuterium-labeled acephate, ethylenethiouria,
and methamidophos were used as internal standards. The sample preparation procedure, in the 96-well format with a 0.8-ml urine
sample size, uses lyophilization of samples, followed by extraction with dichloromethane. The analytes were chromatographed
on a Zorbax SB-C3 (4.6 × 150 mm, 5.0-μm) column with gradient elution by using 0.1% formic acid in aqueous solution (solvent
A) and 0.1% formic acid in methanol (solvent B) mobile phase at a flow rate of 1 ml/min. Quantitative analysis was performed
by atmospheric pressure chemical ionization source in positive ion mode using multiple-reaction monitoring of the precursor-to-product
ion pairs for the analytes on a TSQ Quantum Ultra HPLC-MS/MS. Repeated analyses of urine samples spiked with high (15 ng/ml),
medium (5 ng/ml), and low (1 ng/ml) concentrations of the analytes gave relative SDs of <13%. The limits of detection were
in the range of 0.004–0.01 ng/ml. The method also has high accuracy, high precision, and excellent extraction recovery. Furthermore,
the improved sample preparation method decreased the cost and labor required while effectively doubling the analytic throughput
with minimal matrix effect. 相似文献