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101.
S. Sunano T. Shimada K. Moriyama K. Shimamura 《Clinical and experimental pharmacology & physiology》1990,17(6):413-425
1. The time courses of the relaxation, induced by removal of extracellular Ca2+, of K-depolarized mesenteric artery preparations from stroke prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) were compared. 2. The time course of the decline in extracellular Ca2+ was estimated from the time course of the relaxation and the concentration-response curve of K(+)-depolarized preparations to Ca2+. The time course of the decline in the intracellular free Ca2+ concentration was also estimated from the reported relation between Ca2+ concentration and the contraction of skinned vascular smooth muscle. 3. The time course of relaxation was exponential, the curve being made up of three components. The time course was slower in preparations from SHRSP, especially the first component of the relaxation curve. 4. The time courses of the decline in the intracellular and extracellular Ca2+ concentrations were also exponential, being made up of three components and were also slower in the preparation made from SHRSP. 5. The wall and muscle layer of the mesenteric arteries used in the present experiments were significantly thicker in the SHRSP preparations. 6. Calculation of the half relaxation time, based on the diffusion of Ca2+ across the blood vessel wall, suggested that the slower relaxation in preparations from SHRSP is due largely to the thicker muscle layer, although differences in Ca2+ sequestration by the smooth muscle cells may also be involved. 相似文献
102.
O. A. MIRGHANI† E. O. EL AMIN† M. E. S. ALI† H. S. OSMAN‡ B. HAMAD§ 《Medical education》1988,22(4):314-316
The community-based course presented is a longitudinal course running through four semesters in the Faculty of Medicine, University of Gezira, Sudan. Students combine their regular work in primary health care centres with attachments to a number of families in Wad Medani town. They continue to visit these families regularly throughout their entire medical course with the aim of studying them and helping them with some of their medical and psychosocial problems. 相似文献
103.
A comparison of 121 mature-age and 270 normal-age entrants who graduated from the University of Queensland Medical School between 1972 and 1987 shows that mature-age entrants are some 7 years older, are more likely to come from public (state) schools and less likely to have parents in professional/technical occupations. Otherwise, the two groups were similar in terms of gender, marital status, number of children, ethnic background and current practice location. The educational background of mature-age entrants prior to admission includes 44.6% with degrees in health-science areas and 31.4% with degrees in non-health areas. Reasons for delayed entry of mature-age entrants include late consideration of medicine as a career (34.7%), financial problems (31.4%), dissatisfaction with previous career (30.6%), poor academic results (19.8%), or a combination of the above factors. Motivations to study medicine include family influences (more so in normal-age entrants), altruistic reasons (more so in mature-age entrants) and a variety of personal/social factors such as intellectual satisfaction, prestige and financial security (similar for both groups) and parental expectations (more so in normal-age entrants). Mature-age entrants experienced greater stress throughout the medical course, especially with regard to financial difficulties, loneliness/isolation from the students and family problems (a greater proportion were married with children). While whole-course grades were similar in both groups, normal-age entrants tended to win more undergraduate honours/prizes and postgraduate diplomas/degrees, including specialist qualifications. Practice settings were similar in terms of group private practice, hospital/clinic practice or medical administration, but there was a greater proportion of mature-age entrants in solo private practice, and a smaller proportion in teaching/research. If given the time over, some two-thirds of both groups would choose medicine as a career. Reasons for job satisfaction include helping patients, intellectual stimulation and financial rewards. Reasons for dissatisfaction include pressure of work, red-tape/paperwork, 'doctor-bashing', long working hours, emotional strain, financial pressure, unfulfilled career expectations and irritation with trivial medical complaints. 相似文献
104.
Hilary Eadon Marlene Rose Richard O'Neill Neil Leaver Magdi Yacoub 《Transplant international》1995,8(1):35-40
Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, Cmax, Cmin and tmax) showed that there were no significant differences between the two formulations except for the tmax, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar.This work was carried out in partial fulfillment of the requirements for the Master of Science Degree in Clinical Pharmacy, University of London 相似文献
105.
3-Methoxytyramine (3-MT) is a minor metabolite of dopamine which is suggested to reflect the turnover and utilization of dopamine. A novel, isocratic HPLC method has been developed which can be used to analyse 3-MT in homogenates of rat brain without the need for additional purification procedures. Furthermore, the coulometric electrochemical detection system is sensitive enough to measure 3 pg of 3-MT (equivalent to 0.6 ng/g tissue wet weight). 3-Methoxytyramine was measured in the striatum and n. accumbens after decapitation and rapid freezing, using 3-methoxy-4-hydroxybenzylamine as the internal standard. The effects of dopaminergic and other drugs on this metabolite were examined using this method. -Methyl-p-tyrosine (200 mg/kg i.v.) produced parallel linear decreases in dopamine and 3-MT in naive rats, but not those pretreated with tranylcypromine (5 mg/kg i.p.). Methamphetamine (0.3–10 mg/kg i.p.) and amphetamine (0.3–10 mg/kg i.p.) both dose-dependently increased 3-MT in naive and tranylcypromine-pretreated rats. In naive animals, 3-MT was not altered by intraperitoneal injection of the dopamine reuptake inhibitors, bupropion (10 mg/kg) and nomifensine (10 mg/kg) or by sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg) and zimeldine (10 mg/kg). 3-Methoxy-tyramine was decreased by apomorphine (5 mg/kg i.p.) and also by large doses of the selective D2 antagonist, BRL 34778 (5 mg/kg i.p.) or
-DOPA (50 mg/kg i.p.). The selective D1 antagonist, SCH 23390 (0.1 or 5 mg/kg i.p.) was without effect. In tranylcypromine-pretreated rats, 3-MT was dose-dependently reduced and increased by apomorphine (0.01–5 mg/kg i.p.) and BRL 34778 (0.1–5 mg/kg i.p.), respectively. The drug SCH 23390 (0.1–5 mg/kg i.p.) produced much smaller increases in 3-MT which were probably mediated through the striatonigral pathway. Overall, the data suggest that measurement of 3-MT, after inhibition of monoamine oxidase, is a useful index of the release and utilization of dopamine. However, after substantial and prolonged depletion of dopamine, levels of 3-MT in naive animals are a better index. Also, the formation of 3-MT in naive rats provides a sensitive method for distinguishing between dopamine releasing agents and reuptake inhibitors. 相似文献
106.
The optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for the production of a safe and potent whole cell pertussis vaccine were investigated. Two bacterial harvests from B. pertussis strain 10536 were treated with glutaraldehyde, each with 0.025, 0.05 and 0.1% concentrations of glutaraldehyde for 10, 60 and 120 min. The nine types of glutaraldehyde-inactivated pertussis vaccine (GIPV) and conventional heat-inactivated pertussis vaccine (HIPV) preparations made from two bacterial harvests were comparatively evaluated for the mouse weight gain test (MWGT), potency, and the histamine-sensitization (HS) and leucocytosis-promoting-factor (LPF) tests. The minimum period for killing the B. pertussis organisms with glutaraldehyde was>10 min for 0.025%, 10 min for 0.05% and 5 min for 0.1% concentration. The average loss in opacity varied from 5 to 10% for GIPV preparations and was 14% for HIPV preparations. The GIPV preparations except those inactivated with 0.025% glutaraldehyde for 10 min (GIPV-A) were much less toxic than the HIPV preparations in the MWGT. The GIPV-A preparations did not pass the MWGT. The GIPV preparations were also much less toxic in HS and LPF tests than the HIPV preparation. The potency of GIPV preparations inactivated with 0.05% glutaraldehyde for 10 min (GIPV-D) was similar to that of HIPV preparations. The prolonged treatments with glutaraldehyde reduced the potency. The GIPV-D preparation with good potency and less toxicity was found to be inactivated with glutaraldehyde under optimal conditions. All the preparations were innocuous in the abnormal toxicity test. 相似文献
107.
David L. Mattson Shanhong Lu Allen W Cowley Jr 《Clinical and experimental pharmacology & physiology》1997,24(8):587-590
1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure. 相似文献
108.
Thilo Klindert Isabel Stroetmann Gunther Seitz Georg Hfner Klaus Th. Wanner Gerlinde Frenzen Brigitta Eckhoff 《Archiv der Pharmazie》1997,330(6):163-168
A number of novel pyridazinomorphinans have been synthesized by the inverse electron demand Diels-Alder reaction of various 3,6-disubstituted 1,2,4,5-tetrazines with enamines derived from dihydrocodeinone and with codeinone. Reduction of some of the pyridazinomorphinans did not furnish the expected pyrroloepoxymorphinans; in all cases investigated reductive cleavage of the epoxybridge was observed to yield dihydropyridazino- or pyrrolomorphinans. The structures of all new compounds were assigned by the spectral data, that of the cycloadduct of codeinone was additionally verified by X-ray crystallography. Compounds 5a, 8, 11a , and 16 have been evaluated for their affinity at μ and κ opioid receptors in radioligand binding assays. Their ability to inhibit [3H]DAMGO binding at μ and [3H]U 69.593 binding at κ receptors, respectively as compared to codeine has been found to be lower. 相似文献
109.
Rolf W. Hartmann Martin Frotscher Dorothea Ledergerber Gerald A. Wchter Gertrud L. Grün Tom F. Sergejew 《Archiv der Pharmazie》1996,329(5):251-261
In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH3 derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests. 相似文献
110.
The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption. 相似文献