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1.
RW Li  JB Wong 《Canadian Metallurgical Quarterly》1997,337(7):499-500; author reply 501
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Our model of the human m1 muscarinic receptor has been refined on the basis of the recently published projection map of bovine rhodopsin. The refined model has a slightly different helix arrangement, which reveals the presence of an extra hydrophobic pocket located between helices 3, 4 and 5. The interaction of series of agonists and antagonists with the m1 muscarinic receptor has been studied experimentally by site-directed mutagenesis. In order to account for the observed results, three-dimensional models of m1 ligands docked in the target receptor are proposed. Qualitatively, the obtained models are in good agreement with the experimental observations. Agonists and partial agonists have a relatively small size. They can bind to the same region of the receptor using, however, different anchoring receptor residues. Antagonists are usually larger molecules, filling almost completely the same pocket as agonists. They can usually produce much stronger interactions with aromatic residues. Experimental data combined with molecular modelling studies highlight how subtle and diverse receptor-ligand interactions could be.  相似文献   

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Wen's technique of electro-acupuncture was used successfully for treatment of withdrawal symptoms of 19 drug abusers. The drug common to all was opium (eating as well as smoking). Other drugs were amphetamine, methaqualone (mandrax) and barbiturates by mouth and cannabis (charas) smoking. The sample of the study is too small to draw statistical conclusions, but it is worth stating that all the cases showed a definite response to electro-acupuncture and that their withdrawal symptoms, especially those of opium, were controlled within 30 minutes of the application. The need for subsequent treatment varied, but all patients were symptom free and chemical free on the 6th-8th day of treatment. Thus, the period of active treatment was much shorter than that with codeine substitution therapy. It appears obvious that electro-acupuncture is an effective, simple and more economical method for the detoxification of opiate dependents.  相似文献   

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In the female mouse, dapsone (50-500 mg kg-1, p.o.) caused a dose-related methaemoglobinaemia which peaked at 0.5-1 h with recovery to baseline values occurring by 4 h. Cimetidine (100 mg kg-1, p.o.), a known inhibitor of several hepatic P450 isozymes administered 1 h before dapsone, prevented the methaemoglobinaemia. In-vitro, dapsone required activation by mouse hepatic microsomes to cause methaemoglobin formation in mouse erythrocytes and cytotoxicity to human mononuclear leucocytes. In both instances, the toxic effects were markedly reduced by cimetidine. Daily dosing of mice with dapsone (50 mg kg-1, p.o.) for 3 weeks induced a blood dyscrasia, characterized by a fall of platelet and white blood cell counts, which was inhibited by cimetidine (100 mg kg-1, p.o. daily). It is concluded that an active metabolite of dapsone arising from a P450-dependent pathway is involved in the genesis not only of the methaemoglobinaemia but also the blood dyscrasia arising from repeated administration of the drug in this species.  相似文献   

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During August 1988 to January 1990, the immunogenicity and safety of purified chick embryo cell rabies vaccine (PCEC) given by the conventional and abbreviated regimens in 82 vaccinees moderately to severely exposed to laboratory proven rabid animals were studied. The 16 vaccinees received PCEC six doses as conventional schedule on days 0, 3, 7, 14, 28 and 90, the 11 vaccinees received six doses of PCEC plus human rabies immune globulin (HRIG) on day 0. The 29 vaccinees received an abbreviated schedule of PCEC as two doses on day 0, one dose each on days 7 and 21 and the 26 cases received PCEC abbreviated schedule plus HRIG on day 0. The kinetics of the neutralizing antibodies on days 0, 7, 14, 28, 56, 180 and 365 were studied for comparative purpose. All vaccinees had high antibody levels from day 14 which last longer than a year and were safe after one year follow up. The adverse reactions of the vaccine were mild and self-limited.  相似文献   

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Psychiatric services in Pakistan have undergone considerable changes since independence 50 years ago. There has been an increased awareness of psychiatric illness on both public and professional levels and great emphasis has been laid on the education and training of medical and related professions in recent years. Although old traditional methods still prevail, it is becoming increasingly common to seek professional psychiatric advice. Like any developing country, however, much remains to be done especially on a government level in order to meet the basic mental health needs of the nation.  相似文献   

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OBJECTIVES: This study assessed the rabies exposure and treatment that at least 665 persons in Concord, NH, received as a result of one proven rabid pet-store kitten in October 1994. METHODS: All treatment recipients were interviewed by person or phone. RESULTS: The median age of the treatment recipients was 14 years; 58% were female. The most common exposures were low risk (e.g., picking up, petting, nuzzling, or being scratched by a potentially rabid kitten). Local reactions to vaccine or immune globulin were reported by 76.5% of recipients, while 48.8% reported at least one systemic reaction. Cost for the biologicals was estimated at more than $1.1 million. CONCLUSIONS: Because of the inadequacy of pet store records, the inconsistent application of treatment guidelines, and other factors, many people received postexposure treatment as a result of contacts that were unlikely to transmit rabies. The rates of local and systemic adverse reactions experienced were consistent with previous reports.  相似文献   

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We describe a rabies epizootic in northwest Alaska (USA) during 1989 and 1990 which resulted in mortality to several different wolf (Canis lupus) packs. Four radio-collared wolves were confirmed to have rabies while evidence for seven others was strongly suggestive but not confirmed. The wolf population declined during the rabies epizootic; thus rabies may have been a significant limiting factor.  相似文献   

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Glucocorticoids are potent osteopenic agents, producing negative calcium and bone balance via actions at many sites. The most significant adverse effects of glucocorticoid drugs on the skeleton are probably a direct inhibition of matrix synthesis by the osteoblast, reductions in calcium absorption in both the gut and the renal tubule, and the production of hypogonadism, particularly in men. Reductions in bone density of 10-40% result, the loss being more marked in trabecular bone and in patients receiving a high cumulative dose of the steroid. Fractures occur in about 30% of individuals who take these drugs for an average of 5 years. Bone loss is reversible when glucocorticoid treatment is withdrawn. Bone density can also be increased by sex hormone replacement in those with demonstrable deficiency, by bisphosphonates, and possibly by vitamin D metabolites. All patients treated with glucocorticoids for more than 6 months should be considered for bone densitometry and be offered appropriate drug treatment if values are towards the lower end of the young normal range or if there is already evidence of fractures occurring after minimal trauma. With this approach, the significant morbidity associated with steroid osteoporosis might be substantially avoided.  相似文献   

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The background from which psychology is emerging in Pakistan as a separate discipline, its major trends as a continuation of the traditions of Indian psychology are discussed, and lines of research and problems currently being faced by Pakistan psychologists are also indicated. Major sections are: Background of Pakistan Psychology, Current Trends (Psychology Laboratory in Pakistan, Professional Organization, Professional Journals, Recent Trends), and Future Prospects. "With the present rate of growth of psychology, coupled with an unusual enthusiasm among the younger generation of psychologists, there is great hope that Pakistan psychology will soon catch up with the current developments in other countries." (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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OBJECTIVE: The present study was designed to generate population-based data on the prevalence and causes of hearing loss in rural Pakistani children. A community screening programme was utilized to identify and evaluate the hearing impaired. METHODS: The study was performed in conjunction with the Ministry of Population Welfare in Sialkot District, Punjab Province. School-aged children between the ages of 5 and 15 years were screened and examined for hearing impairment according to World Health Organization (WHO) protocols. Case-control analysis of audiometric, physical examination, and risk factors for hearing loss were performed, followed by chi-square analyses. RESULTS: A total of 607 children comprised the study population, with an overall point prevalence of hearing impairment of 7.9%. Fifty percent of all hearing loss was conductive in nature, amenable to either medical or surgical therapy. The risk factors most associated with conductive hearing loss were otorrhea and multiple ear infections greater than 5. In cases of severe hearing loss, 70% were the result of consanguinous marriages. Almost no cases of hearing loss were attributable to measles, mumps, rubella, and the TORCH infections. CONCLUSION: This study has generated some badly needed population-based data on the magnitude of the problem of hearing loss in rural Pakistan. It is hoped that the results of this work will stress the importance of hearing health in Pakistan and to encourage other professionals to pursue similar projects.  相似文献   

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Twelve naive and nine test-vaccinated horses which developed clinical signs of rabies as a result of the required protocol of a vaccine trial were prospectively observed. Nineteen of the 21 cases were confirmed positive for rabies infection of the brain by fluorescent antibody test. The two horses with negative results had ganglioneuritis of the trigeminal ganglion or lymphocytic perivascular cuffing in the brain stem in addition to clinical signs. Average incubation period was 12.3 days and average morbidity was 5.5 days. Naive animals had significantly shorter incubation and morbidity periods (P < 0.05). Muzzle tremors were the most frequently observed (81%) and most common initial sign. Other common signs were pharyngeal spasm or pharyngeal paresis (71%), ataxia or paresis (71%), lethargy or somnolence (71%). The furious form was manifested in 43% of rabid horses and some of these furious animals initially manifested the dumb form. The paralytic form was not observed. Histopathology was characteristics for rabies. The results of this trial do not reflect on the efficacy of commercially licensed equine rabies vaccines.  相似文献   

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Isl-1 is a member of a family of Homeodomains containing proteins that possess an N-terminal pair of zinc binding LIM domains. The Isl-1 gene in rat codes for a protein that binds to the insulin gene enhancer and is also involved in regulation of amylin and proglucagon genes. A DNA sequence coding for 66 amino acid residues containing the C-terminal homeodomain fragment of Isl-1 was expressed as a soluble protein in Escherichia coli. Here, we describe a procedure which allows the rapid native purification of recombinant homeodomain protein fused to an N-terminal tag of six histidines. The purified homeodomain showed DNA-binding activity to its cognate DNA sequence. An enhanced binding activity is observed in the presence of a reducing agent in electrophoretic mobility shift assays. The DNA binding was further characterized by circular dichroism spectroscopy. Addition of DNA to the homeodomain did not change the overall secondary structure content, but the thermal and chemical denaturing profiles were altered. A stabilization of the secondary structure was observed upon DNA binding. The free energy of unfolding at 23 degrees C was 7 kJ mol(-1) in absence of DNA and 29 kJ mol(-1) in the presence of DNA.  相似文献   

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Effects of outcome-alone pretraining and posttraining exposure were investigated in conditioned suppression experiments conducted within a sensory preconditioning preparation with rats. Experiment 1 found that interference by outcome postexposure was stronger than that by outcome preexposure, suggesting a recency effect. Experiment 2 found that after a long retention interval, outcome preexposure produced more interference than outcome postexposure, suggesting a shift from recency to primacy with increasing retention interval. Experiment 3 showed that presentation of a priming stimulus that had been embedded within the earlier phase of treatment also caused a shift from recency to primacy. These results suggest that, at least in a sensory preconditioning paradigm, retrievability of outcome-alone exposure memory is an important determinant of any outcome-alone exposure effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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In the wake of recent breakthroughs in antiviral therapies and Centers for Disease Control and Prevention (CDC) recommendations advocating occupational postexposure prophylaxis (PEP), health care workers are increasingly receiving inquiries about PEP following exposures to the human immunodeficiency virus (HIV) through sex and injection drug use. The probability of HIV transmission by certain sexual or injection drug exposures is of the same order of magnitude as percutaneous occupational exposures for which the CDC recommends PEP. In such cases, if the exposure is sporadic, it seems appropriate to extrapolate from the data on occupational PEP and recommend prophylaxis. However, for individuals with continuing or low-risk exposures, we instead recommend referrals to state-of-the-art risk reduction programs. Clinicians, using local HIV seroprevalence data and their knowledge of transmission probabilities, can help exposed patients make an informed decision regarding PEP. Because of the large number of risky encounters that will not be treated prophylactically, even after significant outreach efforts, public health interventions that emphasize PEP as part of a comprehensive HIV prevention program should be confined to cities with highest HIV prevalences.  相似文献   

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