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81.
A preliminary, clinical pharmacological assessment of L-659,066, a novel alpha 2-adrenoceptor antagonist. 下载免费PDF全文
R F Schafers H L Elliott C A Howie J L Reid 《British journal of clinical pharmacology》1992,34(6):521-526
1. The alpha 2-adrenoceptor antagonist activity of L-659,066 has been investigated in studies of healthy normotensive males to whom doses of up to 8 mg were administered by short intravenous infusion. 2. L-659,066 had no effect on basal levels of glucose or insulin and no significant effect on the plasma glucose and plasma insulin time profiles following an intravenous glucose load. 3. There was a non-significant trend for plasma noradrenaline concentrations to be higher after L-659,066. 4. L-659,066 had no significant effects on mood changes or on physical symptom scores. 5. There were no significant effects on supine blood pressure but there were consistent increases in heart rate both supine (non-significant) and erect (P < 0.01). 6. Ex vivo platelet aggregation studies confirmed alpha 2-adrenoceptor antagonist activity with L-659,066 but with an approximately 9-fold lesser potency than yohimbine. 7. While L-659,066 has alpha 2-adrenoceptor antagonist activity these results suggest that it is unlikely to present a new therapeutic approach for improving insulin release. 相似文献
82.
Anti-peptide antibodies to cathepsins B, L and D and type IV collagenase. Specific recognition and inhibition of the enzymes. 总被引:1,自引:0,他引:1
T H Coetzer E Elliott P H Fortgens R N Pike C Dennison 《Journal of immunological methods》1991,136(2):199-210
Anti-peptide antibodies were raised against synthetic peptides selected from the sequences of human cathepsins B and L, porcine cathepsin D and human type IV collagenase. Sequences were selected from the active site clefts of the cathepsins in the expectation that these would elicit immunoinhibitory antibodies. In the case of type IV collagenase a sequence unique to this metalloproteinase subclass and suitable for immunoaffinity purification, was chosen. Antibodies against the chosen cathepsin B sequence were able to recognize the peptide but were apparently unable to recognise the whole enzyme. Antibodies against the chosen cathepsin L sequence were found to recognise and inhibit the native enzyme and were also able to discriminate between denatured cathepsins L and B on Western blots. Antibodies against the chosen cathepsin D sequence recognised native cathepsin D in a competition ELISA, but did not inhibit the enzyme. Native type IV collagenase was purified from human leukocytes by immuno-affinity purification with the corresponding anti-peptide antibodies. 相似文献
83.
84.
Proper timing of surgery for gallstone pancreatitis 总被引:23,自引:0,他引:23
85.
Trehalose dimycolate enhances resistance to infection in neutropenic animals. 总被引:2,自引:0,他引:2 下载免费PDF全文
G S Madonna G D Ledney T B Elliott I Brook J T Ulrich K R Myers M L Patchen R I Walker 《Infection and immunity》1989,57(8):2495-2501
Bacterial infections are lethal complications of neutropenia, and antibiotics alone are inadequate therapy for these infections. Irradiated mice become severely neutropenic and remain susceptible to infection for 2 to 3 weeks, depending on the dose and quality of radiation. Some bacterial cell wall derivatives stimulate nonspecific host defense mechanisms against a variety of microbes which might cause postirradiation infection. In this study we determined if the cell wall glycolipid trehalose dimycolate (TDM), derived from Mycobacterium phlei, or a synthetic preparation of TDM was able to (i) enhance survival in mice when given before or after lethal doses of 60Co radiation and (ii) increase nonspecific resistance to postirradiation infection. Treatment with TDM oil-in-water emulsions and with synthetic TDM significantly enhanced survival before and after lethal doses of 60Co irradiation. This result correlated with the ability of TDM to reduce the translocation of intestinal bacteria and to stimulate hematopoiesis. With respect to nonspecific resistance to infection, TDM injected 1 h after sublethal irradiation increased resistance to a lethal Klebsiella pneumoniae challenge (10 50% lethal doses of K. pneumoniae in 30 days [LD50/30]) 4 or 14 days later. Increasing the dose of K. pneumoniae to 5,000 LD50/30 on day 4 overwhelmed the ability of TDM-treated mice to overcome infection. However, TDM treatment 1 h postirradiation combined with ceftriaxone antibiotic therapy (days 5 through 14) enhanced survival, even when the higher dose of bacteria (5,000 LD50/30) was used. These results indicate that in irradiated mice, TDM can be used to enhance survival and, as a potent stimulant of nonspecific resistance to infection in neutropenic mice, can act synergistically with antibiotic therapy to reduce sepsis and mortality. 相似文献
86.
M D Brewer M N Burgess R J Dorgan R L Elliott P Mamalis B R Manger R A Webster 《Journal of medicinal chemistry》1989,32(9):2058-2062
A series of 1,2,3,4,6,7,8,12b-octahydropyrazino[2,1-alpha][2] benzazepine derivatives was prepared and the cestocidal activity of the compounds evaluated in an in vitro Taenia crassiceps screen. Many of these derivatives proved to be highly active, and 2-(cyclohexylcarbonyl)-4-oxo-1,2,3,4,6,7,8,12b- octahydropyrazino[2,1-alpha][2]benzazepine, epsiprantel (BAN) (22), was selected for further development. The structure-activity relationships are discussed. 相似文献
87.
88.
Motor loss and swallowing difficulty after stroke: frequency, recovery, and prognosis. 总被引:8,自引:0,他引:8
Data relating to motor loss and swallowing difficulties in a community sample of 976 patients who suffered an acute stroke have been analysed. About 17% of patients seen within one week had no paralysis; at 6 months 48% of survivors had no paralysis and 9% had severe paralysis. The Motricity Index used to study motor loss related to functional loss and walking ability; it seems to be a simple valid measure of motor loss. Severe paralysis was associated with a high fatality rate, and only 6%-10% of survivors of an initially severe paralysis made a full recovery by 6 months. If severe persisted at 3 weeks, full recovery was not observed. Loss of sitting balance was associated with a poor outcome. Of conscious patients seen within one week, 14% choked on attempting to swallow and a further 28% had abnormal swallowing: this 42% of patients had a high fatality rate. 相似文献
89.
From a review of 131 children with arthrogryposis, we studied 18 patients with hip dislocations. Fourteen patients (10 unilateral, four bilateral) were treated by open reduction. Mean age at surgery was 9.7 months, and follow-up ranged from 9 to 245 months. Range of motion of patients treated by open reduction following the medial approach was greater than in those treated by anterolateral incision and greater than in bilateral cases treated by closed reduction. Acetabular development was satisfactory following the medial approach and there were no re-dislocations, but one hip developed avascular necrosis. 相似文献
90.
Behavioural studies showed that administration of alpha-methyl-p-tyramine (AMT; 10 mg/kg i.p.) to rats 24 hr before treatment with d-amphetamine (AMPHET; 4 mg/kg i.p.) resulted in augmentation of AMPHET-induced stereotype activity. Parallel experiments involving electro-chemical estimation of dopamine metabolites in the striatum showed that the decrease in the concentration of homovanillic acid (HVA) produced by AMPHET (4 mg/kg) was enhanced in AMT (10 mg/kg) pretreated animals. These findings suggest that AMT derived from previous doses of AMPHET may play a role in the phenomena of behavioural augmentation observed after chronic administration of AMPHET. 相似文献