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1.
Studies were conducted to examine the absorption and disposition kinetics of insulin in dogs following intravenous (IV) and subcutaneous (SC) administration of commercial preparations. After IV and SC dosing, the plasma levels were described by models which considered basal insulin level contributions. Intersubject variation in the disposition kinetics was small with half-lives of 0.52 +/- 0.05 h and total body clearances of 16.21 +/- 2.08 ml min-1 kg-1. Calculated insulin plasma secretion rates in the canines were 14.4 +/- 3.3 mUh-1 kg-1. Following SC injection of regular insulin, the rate and extent of absorption were noted to be quite variable. The absorption process appeared first-order with half-life values of 2.3 +/- 1.3 h and extents of absorption of 78 +/- 15 per cent with a range of 55-101 per cent. Insulin absorption from SC NPH preparations was evaluated as being composed of two zero-order release phases, a rapid and a slow release phase. With a dose of 1.65 U kg-1, the rapid release phase had an average duration of 1.5 h and a rate of 580 +/- 269 mUh-1 (4.2 per cent of dose) while the slow phase had a zero-order rate of 237 +/- 92 mU h-1 which continued beyond 12 h. The extent of absorption from the NPH preparation was 23.6 +/- 5.1 per cent and was significantly lower than that for the regular injection. 相似文献
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Rickey L. Williams Catherine A. Schaefer Catherine M. Shisslak Virginia H. Gronwaldt George D. Comerci 《The International journal of eating disorders》1986,5(5):879-894
The prevalence of eating disorders has increased in teenage and young adult women. Since early treatment of eating disorders is thought to lead to improved outcomes, the development of an effective self-report screening device for eating disorders in adolescents could help reduce morbidity from these illnesses. In order to examine the feasibility of developing such an instrument, eating attitudes and behaviors were studied in a sample of 72 female adolescents, using the Eating Attitudes Test (EAT), the Eating Disorder Inventory (EDI), and blinded structured clinical interviews focused on eating disorders. Scores on the EAT and EDI were similar to scores of older normal female comparison groups in other studies. Based upon interview information, 54 subjects were classified as normal, 9 as dieters, 8 as suspected bulimics, and 1 as bulimic. Subjects, on average, accurately reported their actual weight and height. The results of the interviews indicated that 25% of the 72 subjects were currently dieting, 60% regularly skipped meals, 35% said they were overweight or very overweight, 22% were binge eaters, 8% vomited after eating, and 4% used drugs to lose weight. Linear discriminant analysis was used to compare the results of the questionnaires with that of the interviews in order to identify a composite set of questionnaire items to be used as a screening device for individuals with clinical eating disorders and for those at high risk of developing such disorders. A preliminary equation was obtained that correctly classified 86% of subjects into categories of normal, dieter, or suspected bulimic that were determined from the interviews. These preliminary data suggest that adolescents' scores on the EAT and the EDI are similar to young adult women's scores, and also that further refinement of a discriminant equation might lead to the development of an effective screening device for eating disorders in adolescents. 相似文献
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Guarna A Machetti F Occhiato EG Scarpi D Comerci A Danza G Mancina R Serio M Hardy K 《Journal of medicinal chemistry》2000,43(20):3718-3735
The synthesis and biological evaluation of a series of novel, selective inhibitors of isoenzyme 1 of human 5alpha-reductase (5alphaR) (EC 1.3.99.5) are reported. The inhibitors are 4aH- (19-29) or 1H-tetrahydrobenzo[c]quinolizin-3-ones (35-47) bearing at positions 1, 4, 5, and 6 a methyl group and at position 8 a hydrogen, methyl group, or chlorine atom. All these compounds were tested toward 5alphaR-1 and 5alphaR-2 expressed in CHO cells (CHO 1827 and CHO 1829, respectively) resulting in selective inhibitors of the type 1 isoenzyme, with inhibitory potencies (IC(50)) ranging from 7.6 to 9100 nM. The inhibitors of the 4aH-series, having a double bond at position 1,2, were generally less active than the corresponding inhibitors of the 1H-series having the double bond at position 4,4a on the A ring. The presence of a methyl group at position 4 (as in compounds 39-40 and 45-47), associated with a substituent at position 8, determined the highest inhibition potency (IC(50) from 7.6 to 20 nM). Compounds 39 and 40, having K(i) values of 5.8+/-1.8 and 2.7+/-0.6 nM, respectively, toward 5alphaR-1 expressed in CHO cells, were also tested toward native 5alphaR-1 in human scalp and 5alphaR-2 in human prostate homogenates, in comparison with finasteride and the known 5alphaR-1-selective inhibitor LY191704, and their mechanism of inhibition was determined. They both inhibited the enzyme through a reversible competitive mechanism and again were selective inhibitors of 5alphaR-1 with IC(50) values of 41 nM. These specific features make these inhibitors suitable candidates for further development as drugs in the treatment of DHT-dependent disorders such as acne and androgenic alopecia in men and hirsutism in women. 相似文献
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Natali R Lotrionte M Marchese N Di Giannuario G Brugaletta S Pisanello C Comerci G Savino M Lombardo A Forni F Vigna C Loperfido F 《Minerva cardioangiologica》2008,56(3):277-285
AIM: The aim of this study was to determine if low-dose dobutamine stress echocardiography (LD-DSE) is associated with functional capacity in unselected elderly patients with chronic heart failure. METHODS: This was a prospective trial.Thirty five consecutive patients were included, with age >65 years and left ventricular dysfunction (12 ischemic), by blindly assessed LD-DSE and cardiopulmonary exercise testing (CPT). Contractile reserve was defined as a change (D) in wall motion score index (WMSI) = or <0.2 at peak dose dobutamine. At CPT treadmill exercise time, peak VO2, %Vo2 and VE/VCO2 slope were determined. Preserved functional capacity was defined as percent of maximal predicted O2 consumption (%VO2) >80%. Baseline NT-proBNP plasma levels were assessed. RESULTS: CPT variables were not related to clinical and baseline echocardiography characteristics but were related to DWMSI (exercise time, P=0.004; peak VO2, P=0.008; %VO2, P<0.001; VE/Vco2, P<0.001). Contractile reserve was present in 16 of 17 patients with preserved functional capacity (sensitivity=94%) and in 2 of 13 patients without (specificity=85%). Baseline NT-proBNP levels were lower in patients with contractile reserve (476+/-365 pg/mL) than in those without (1 345+/-1 219 pg/mL) (P=0.019), but were mildly related to CPT variables (P=0.049 and 0.027 with exercise time and %VO2, respectively). CONCLUSION: Contractile reserve elicited at LD-DSE is associated with functional capacity in unselected elderly patients with chronic heart failure. 相似文献
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Vector Development for the Expression of Foreign Proteins in the Vaccine Strain Brucella abortus S19 总被引:4,自引:0,他引:4
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Diego J. Comerci Guido D. Pollevick Ana M. Vigliocco Alberto C. C. Frasch Rodolfo A. Ugalde 《Infection and immunity》1998,66(8):3862-3866
A vector for the expression of foreign antigens in the vaccine strain Brucella abortus S19 was developed by using a DNA fragment containing the regulatory sequences and the signal peptide of the Brucella bcsp31 gene. This fragment was cloned in broad-host-range plasmid pBBR4MCS, resulting in plasmid pBEV. As a reporter protein, a repetitive antigen of Trypanosoma cruzi was used. The recombinant fusion protein is stably expressed and secreted into the Brucella periplasmic space, inducing a good antibody response against the T. cruzi antigen. The expression of the repetitive antigen in Brucella neither altered its growth pattern nor generated a toxic or lethal effect during experimental infection. The application of this strategy for the generation of live recombinant vaccines and the tagging of B. abortus S19 vaccine is discussed. This is the first time that a recombinant protein has been expressed in the periplasm of brucellae. 相似文献