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1.
2.
Initially, there is a high incidence of CNS-depressant side-effects when the aromatase inhibitor, aminoglutethimide, is used in the treatment of patients with advanced breast cancer. Tolerance to these effects develops with continued dosing. This study examines the development of tolerance to various indices of CNS depression with the drug in mice. Single doses of aminoglutethimide induced a dose-dependent depression of spontaneous locomotor activity, rotarod performance, righting reflex and body temperature and a dose-related antileptazol activity. On repeated dosing with the drug, tolerance to these various activities occurred. The tolerance was found to be dose-dependent in the rotarod and righting reflex tests and time-dependent in the locomotor and body temperature tests. Although the results do not allow a determination of whether this clearly demonstrated phenomenon in the mouse is primarily functional or dispositional, the slow onset (14 days) for complete tolerance may be indicative of a functional mechanism. 相似文献
3.
Barry J. Nicholls MB ChB FFARCS Bruce F. Cullen MD 《Journal of clinical anesthesia》1988,1(2):115-129
Trauma is the leading cause of death for persons aged 1 to 38 years. Successful management is facilitated by prehospital endotracheal intubation, transport to regional trauma centers, rapid resuscitation by an on-site team of trained physicians, timely operative intervention, and provision of care by well-prepared anesthesiologists familiar with the potential complications typical of traumatized patients. No particular anesthetic agent or technique is ideal. Causes for intraoperative hypotension include hypovolemia, hemopneumothorax, pericardial tamponade, an intracranial mass, acidosis, and hypothermia. The anesthesiologist should play an active role in all phases of trauma management, including provision of postoperative intensive care and pain relief. 相似文献
4.
The release and uptake of excitatory amino acids 总被引:47,自引:0,他引:47
In this article, David Nicholls and David Attwell describe recent advances in our understanding of the mechanisms by which excitatory amino acids are released from cells, and of the way in which a low extracellular glutamate concentration is maintained. Glutamate can be released from cells by two mechanism: either by Ca2(+)-dependent vesicular release or, in pathological conditions, by reversal of the plasma membrane uptake carrier. The contrasting pharmacology and ionic dependence of the glutamate uptake carriers in the vesicle membrane and in the plasma membrane explain how glutamate (but probably not aspartate) can function as a neurotransmitter, and why the extracellular glutamate concentration rises to neurotoxic levels in brain anoxia. 相似文献
5.
1. The P1-purinoceptors mediating relaxation of the rat duodenum and inhibition of contraction of the rat urinary bladder were characterized by use of adenosine and its analogues 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclopentyladenosine (CPA) and 2-p-((carboxyethyl)phenethylamino)-5'- carboxamidoadenosine (CGS 21680), as well as the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The stable analogue of adenosine 5'-triphosphate (ATP), adenylyl 5'-(beta,gamma-methylene)diphosphonate (AMPPCP), was also used as previous work had indicated that it has a direct action on some P1 receptors in addition to its P2-purinoceptor activity. 2. In the rat duodenum, the order of potency of the adenosine agonists was NECA greater than or equal to CPA greater than AMPPCP = adenosine greater than CGS 21680, and DPCPX antagonized CPA and AMPPCP at a concentration of 1 nM whereas equivalent antagonism of NECA and adenosine required a concentration of 1 microM. This suggests the presence of a mixture of A1 and A2 receptors in this tissue, with CPA and AMPPCP acting on the A1 and NECA and adenosine acting on the A2 receptors. 3. In the rat bladder, the order of potency of the adenosine agonists for inhibition of carbachol-induced contractions was NECA much greater than adenosine greater than CPA = CGS 21680, and a concentration of DPCPX of 1 microM was required to antagonize responses to NECA and adenosine. This suggests the presence of A2 receptors in this tissue.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
M J Blackman I T Ling S C Nicholls A A Holder 《Molecular and biochemical parasitology》1991,49(1):29-33
The amino-terminal sequence has been obtained for 2 fragments of the Plasmodium falciparum T9/94 merozoite surface protein precursor (PfMSP1) and these have been compared with the sequence predicted from the gene. These data define the position of these fragments in the precursor and indicate that the C-terminal sequence which is carried into the red cell during invasion consists of 2 epidermal growth factor (EGF)-like domains. A homologous cleavage sequence and domain structure can be identified in the MSP1 molecules of other malarial species. In addition the results suggest that the smaller fragment is not N-glycosylated. 相似文献
7.
TP Amadeu† AB Seabra‡ MG de Oliveira‡ AMA Costa† 《Journal of the European Academy of Dermatology and Venereology》2007,21(5):629-637
BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization. 相似文献
8.
The effect of environmental temperature on stroke occurrence in a subtropical climate was studied over a 1-year period by documenting the number of strokes (subdivided into cerebral infarct and intracerebral hemorrhage) admitted into a district hospital in Hong Kong at different temperatures. There was no significant correlation between the number of strokes (or its subtypes) per day per temperature category and the environmental minimum or maximum temperature. However, an association was present between the occurrence of cerebral infarcts and maximum temperature on the day of onset in elderly patients aged 70 years and above. Environmental temperature is not a strong risk factor for the occurrence of stroke in a subtropical climate. 相似文献
9.
J H Van der Walt B Nicholls M Bentley D P Tomkins 《Anaesthesia and intensive care》1987,15(2):151-157
Preoperative and postoperative sedation, postoperative analgesia and vomiting were assessed following four different oral premedications in 143 children aged 1-10 years, weighing 10-30 kg, and undergoing elective adenotonsillectomy or inguinal surgery. Diazepam, diazepam combined with droperidol, trimeprazine and trimeprazine combined with droperidol were compared in a double-blind trial in conjunction with a standardised inhalational anaesthetic technique employing an intraoperative narcotic. Trimeprazine produced significantly more preoperative sedation (P less than 0.001) and was associated with enhanced postoperative analgesia (P less than 0.01). The incidence of postoperative vomiting was significantly less in the group receiving trimeprazine (P less than 0.001). The addition of droperidol to diazepam and trimeprazine only marginally improved the performance of those drugs but significantly prolonged postoperative recovery times. This was more marked when droperidol was combined with trimeprazine. 相似文献
10.
A pharmacokinetic and pharmacodynamic comparison of plain and enteric-coated prednisolone tablets. 下载免费PDF全文
C G Adair O McCallion J C McElnay M G Scott B A Hamilton J P McCann C F Stanford D P Nicholls 《British journal of clinical pharmacology》1992,33(5):495-499
1. Eight healthy volunteers and eight patients suffering from chronic obstructive pulmonary disease (COPD) received 30 mg prednisolone as plain (P) and enteric-coated tablets (EP) in a randomised, cross-over manner. Plasma prednisolone and cortisol and blood glucose were measured over 24 h. 2. Although absorption of prednisolone was considerably slower when administered as the enteric-coated form, peak plasma drug concentrations and total AUC (0,24 h) were equivalent for the two formulations. Malabsorption of prednisolone was not observed. 3. The administration of EP was associated with significantly less adrenal suppression in volunteers than P as judged by measurement of AUC (0,24 h) values for endogenous cortisol. However, this difference did not reach statistical significance in the patient group. 4. Plasma cortisol concentrations declined more slowly following administration of the enteric-coated form to both groups. The difference in time taken (median and range) to maximum suppression of cortisol was statistically significant (P less than 0.05) between P (2.5 h; 2-4 h) and EP (4 h; 3-12 h) preparations administered to volunteers. There was a similar significant difference (P less than 0.05) between P (2.5 h; 1-4 h) and EP (7 h; 2-12 h) in the patients. 5. Plasma cortisol concentrations were significantly lower at 24 h in patients receiving the enteric-coated product in association with higher terminal prednisolone concentrations. 6. Blood glucose concentrations increased over an 8 h period in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献