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91.
Ted Van Noord D. Scott Wright Be-Sheng Kuo 《Journal of pharmaceutical and biomedical analysis》1996,14(12):1709-1716
CAM 4515 and CAM 4750 are new nonpeptide tachykinin NK1 receptor antagonists with different lipophilicities. Two separate, simple, and sensitive HPLC methods for the quantitation of these two compounds in plasma and the evaluation of their oral bioavailability in rats were developed and validated. Extraction of CAM 4515 from plasma involved protein precipitation with acetonitrile, while that for CAM 4750 involved a one-step liquid-liquid extraction with methylene chloride. The analytes in extracts were chromatographed on a C18 column using two different separation buffers, 47% 0.02 M sodium citrate (pH 3.5)-53% acetonitrile for CAM 4515 and 59% 0.02 M potassium phosphate dibasic (pH 7.0)-41% acetonitrile for CAM 4750, and both compounds were detected by fluorescence (excitation 278 nm; emission 342 nm). Stability profiles of both drugs at −20°C or room temperature in plasma and in reconstituted buffers were good. The limit of quantitation for both drugs was 5 ng ml−1 with good linearity from 5 to 1000 ng ml−1 using 100–200 μl of plasma. Excellent precision (relative standard deviation < 8.3%) and accuracy (relative error ± 9.2%) were observed for both CAM 4515 and CAM 4750. Oral bioavailability studies were conducted for each compound in rats receiving a p.o. dose of 20 mg kg−1 and an i.v. dose of 5 mg kg−1. The absolute oral bioavailability of CAM 4750 (80%) was estimated to be 40-fold greater than that of CAM 4515 (2%). The experimental results suggest that incorporation of a pyridine group into the structural backbone may greatly improve bioavailability. 相似文献
92.
A series of 5-alkyl-5-phenylbarbituric acid analogues were shown to be potent hypolipidemic agents in rats and mice at 20 mg/kg/day. This dose is lower than that required for hypolipidemic activity for clofibrate and nicotinic acid derivatives in rodents and man. These new derivatives reduced both serum cholesterol and triglyceride levels in rodents by either the oral or intraperitoneal route of administration. Previous studies have demonstrated that similar heterocyclic compounds, i.e. cyclic imides, glutarimides and hydantoins are potent hypolipidemic agents in rodents. The barbituric acid derivatives probably interfered with de novo synthesis of cholesterol and fatty acids in the early steps since the agents inhibit the activities of ATP-dependent citrate lyase and acetyl-CoA synthetase. Triglyceride synthesis may be blocked since the agents inhibited the rate limiting enzyme, sn-glycerol-3-phosphate-acyl-transferase. Rat tissue lipids especially cholesterol and triglycerides were reduced after 14 days treatment. Fecal lipids were increased in cholesterol and phospholipid content by selected compounds. The rat serum lipoprotein after 14 days drug administration showed reduced VLDL-cholesterol and HDL-triglyceride contents. The modulation of the lipid content of the serum lipoproteins by the barbituric acids suggest that these agents may be helpful in treating clinical hyperlipidemic disease states. 相似文献
93.
James K. Hartsfield Bryan D. Hall Arthur W. Grix Boris G. Kousseff Jose F. Salazar Scott M. W. Haufe 《American journal of medical genetics. Part A》1993,45(5):552-557
We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin-Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These “;new”; clinical manifestations expand the phenotype of Coffin-Lowry syndrome and constitute an additional indication of pleiotropy. © 1993 Wiley-Liss, Inc. 相似文献
94.
95.
Amrik Sahota Min Yang Sujuan Gao Siu L. Hui Olusegun Baiyewu Oyewusi Gureje Steven Oluwole Adesola Ogunniyi Kathleen S. Hall Hugh C. Hendrie 《Annals of neurology》1997,42(4):659-661
As a part of our ongoing study on Alzheimer's disease (AD) in elderly African Americans, we obtained clinical assessment and apolipoprotein E (ApoE) genotype data on 288 individuals (including 60 with AD). The ApoE σ4 allele frequency was significantly increased in AD patients compared with controls. The age-adjusted odds ratio (OR) for AD in σ4 homozygotes was 4.83 (95% confidence interval [CI], 1.71–13.64) compared with the σ3/σ3 genotype, but the OR for AD with the σ3/σ4 genotype did not reach significance (1.20; 95% CI, 0.58–2.45). These findings suggest that the association between ApoE σ4 and AD is weaker in African Americans than in whites. 相似文献
96.
Vivian E. von Gruenigen M.D. Joseph T. Santoso M.D. Robert L. Coleman M.D. Carolyn Y. Muller M.D. David Scott Miller M.D. J.Michael Mathis Ph.D. 《Gynecologic oncology》1998,69(3):197-204
Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD100dose of 1 × 107cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 108pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 108pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy. 相似文献
97.
Treatment of dyskeratosis congenita with Granulocyte Colony-Stimulating Factor and Erythropoietin 总被引:1,自引:0,他引:1
Blanche P. Alter Frank H. Gardner & Robert E. Hall 《British journal of haematology》1997,97(2):309-311
Aplastic anaemia is both frequent and difficult to manage in patients with dyskeratosis congenita (DC). We recently treated a 23-year-old male for a year with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Ep), with an excellent neutrophil response, and a transient effect on haemoglobin levels. G-CSF alone or combined with other cytokines may provide at least a partial effect in pancytopenic patients with DC. 相似文献
98.
Megakaryocytic Progenitors Can Be Generated Ex Vivo and Safely Administered to Autologous Peripheral Blood Progenitor Cell Transplant Recipients 总被引:9,自引:1,他引:8
99.
Urinary tract injuries during obstetric intervention 总被引:11,自引:0,他引:11
Dhanasekaran Rajasekar Supervisory Senior House Officer Marion Hall Consultant 《BJOG : an international journal of obstetrics and gynaecology》1997,104(6):731-734
A retrospective case record review of obstetric urinary tract injury in the Grampian region from 1976 to 1993 identified 16 cases of bladder injury (0.1 per 1000 deliveries, 1.4 per 1000 caesarean sections and four cases of ureteric injury (0.03 per 1000 deliveries, 0.27 per 1000 caesarean sections). Diagnosis of bladder injury was immediate, but of ureteric injury often delayed. Although the injury rates are lower than previously reported and previously reported risk factors not confirmed, this audit has resulted in guidelines for junior staff, compliance with which will be monitored, and every case of urinary tract injury will be reviewed. 相似文献
100.
OXA-14, another extended-spectrum variant of OXA-10 (PSE-2) beta-lactamase from Pseudomonas aeruginosa. 下载免费PDF全文
Pseudomonas aeruginosa 455, isolated in Ankara, Turkey, produced a pI 6.2 beta-lactamase determined by plasmid pMLH53 and resisted all beta-lactams except carbapenems. This beta-lactamase, named OXA-14, corresponded to OXA-10 (PSE-2) except that aspartate replaced glycine at position 157 and thus is intermediate between OXA-10 and OXA-11, which has aspartate at position 157 and a further substitution at position 143. 相似文献