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1.
beta-Arteether (AE) is an endoperoxide sesquiterpene lactone derivative currently being developed for the treatment of severe, complicated malaria caused by multidrug-resistant Plasmodium falciparum. Studies were undertaken to determine which form(s) of human cytochrome P-450 catalyze the conversion of beta-arteether to its deethylated metabolite, dihydroqinghaosu (DQHS), itself a potent antimalarial compound. In human liver microsomes, AE was metabolized to DQHS with a Km of 53.7 +/- 29.5 microM and a Vmax of 1.64 +/- 1. 78 nmol DQHS/min/mg protein. AE biotransformation to DQHS was inhibited by ketoconazole and troleandomycin. Ketoconazole was a competitive inhibitor, with an apparent Ki of 0.33 +/- 0.11 microM. Because AE is being developed for patients who fail primary treatment, it is possible that AE may be involved in life-threatening drug-drug interactions, such as the associated cardiotoxicity of mefloquine and quinidine. Coincubation of AE with other antimalarials showed mefloquine and quinidine to be competitive inhibitors with a mean Ki of 41 and 111 microM, respectively. Metabolism of AE using human recombinant P450s provided evidence that cytochrome P450s 2B6, 3A4, and 3A5 were the primary isozymes responsible for its deethylation. CYP3A4 metabolized AE to dihydroqinghaosu at a rate approximately 10 times that of CYP2B6 and approximately 4.5-fold greater than that of CYP3A5. These results demonstrate that CYP3A4 is the primary isozyme involved in the metabolism of AE to its active metabolite, DQHS, with secondary contributions by CYP2B6 and -3A5.  相似文献   

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Nutritional husbandry of captive wild ruminants often requires feeding these animals a supplemental diet to enhance their health, reproductive performance, and productivity. Although supplemental diets for wild ruminants are commercially available, few have been evaluated in controlled intake and digestion trials. Voluntary intake, digestive efficiency, nitrogen retention, and gross energy utilization of pronghorn (Antilocapra americana), mule deer (Odocoileus hemionus), mountain sheep (Ovis canadensis), mountain goats (Oreamnos americanus), and wapiti (Cervus elaphus) consuming a high-energy, high-protein pelleted supplement were compared. Voluntary intake of dry matter, energy, and nitrogen were similar (P > 0.34) between mountain goats and mountain sheep and consistently lower (P < 0.03) for these species than for pronghorn, mule deer, and wapiti. Differences in digestive efficiency among species were inversely related to dry matter intake rates. Apparent digestibility of dry matter, organic matter, and neutral-detergent fiber was 10-20% higher for mountain goats and mountain sheep than for the other species (P < 0.04). Although these findings suggest a superior digestive efficiency for mountain goats and mountain sheep, species comparisons are inconclusive because of the confounding effects of season and ambient temperature on voluntary intake and digestion. Under the conditions of this experiment, the diet tested was safe, nutritious, and highly palatable. Protein and energy concentrations appear to be sufficient to meet or exceed known nutritional requirements of captive wild ruminants.  相似文献   

4.
The authors report 10 cases of cysticercosis registered by the National Reference Laboratory for tissue helminthiasis. Six Czech citizens and four foreigners contracted the disease. Four of 6 Czech citizens were contaminated abroad. Six patients suffered from nervous manifestations of cysticercosis, 2 from muscular or subcutaneous cysticercosis and 2 patients had an asymptomatic course of the infection. The prerequisite of successful treatment with new anthelmintics is early diagnostics.  相似文献   

5.
In recognition of the importance of environmental specimen banking (ESB) as an important component of the described ongoing real-time environmental and health-related monitoring programmes, a proposal for a planned ESB pilot study in the Czech Republic is presented. Selection of biomonitors, analytes, sampling techniques and sites is discussed, especially with regard to the possible harmonization with ESB already operational abroad. Availability of validated analytical techniques for determination of up to 30 elements using nuclear and spectroscopic techniques, including speciation of several metals, and of the most important organic pollutants employing various chromatographic techniques in biological and environmental samples is demonstrated.  相似文献   

6.
Increasing complexity in ambulatory care settings requires nurse managers who can function at higher levels. Little agreement currently exists regarding the role expectations and academic preparation needed for nurse managers in ambulatory care settings. The majority of surveyed ambulatory care nurse managers (40%) have an AD or diploma as their highest level of academic preparation, and have thus acquired the majority of their management skills in the practice setting. The authors express concern that there are pressures to employ non-nurses as managers in ambulatory health care settings and that ambulatory nurse managers are often seen as not needing advanced academic preparation. A wide variety of settings including university and community hospitals, outpatient departments, physician group practices and HMOs, currently employ nurse managers in their multidisciplinary ambulatory care sites. The majority of ambulatory care nurse managers describe their model of care as either the medical model or the functional model.  相似文献   

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BACKGROUND: The objective of this study was to evaluate the prevalence of osteoporosis and osteopenia in Czech women and men aged 50 to 75 years. METHODS AND RESULTS: Bone mineral density was assessed in an age-stratified random sample of 713 women and 429 men from two cities (Prague and Litom?rice) in the lumbar spine, proximal femur and total body by dual X-ray absorptiometry and in the distal forearm by single X-ray absorptiometry. The proportion of women and men in each age group with bone density below specified levels at any of these skeletal sites was projected to the population structure of the Czech Republic. With advancing age, in women at 55 years and in men at 65 years of age the population with normal bone mineral density becomes smaller, and a greater proportion has osteopenia or osteoporosis. Overall, an estimated 428,000 women and 195,000 men over age 50 have osteoporosis and another 680,000 women and 435,000 men have osteopenia. CONCLUSIONS: The results of this first population-based cross sectional study in the Czech Republic document a high prevalence of osteoporosis and osteopenia which is comparable with that published for the Netherlands and the United States. The results offer a basis for economical considerations in diagnosis, treatment and consequences of osteoporosis.  相似文献   

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In order to develop a methodology for measuring the occurrence and circumstances of sudden unexpected adult deaths due to cardiac and to unidentified causes throughout England, a stratified random pilot sample of 12 of the 133 coroner's jurisdictions in England was invited to survey prospectively a quota sample of 78 consecutive white Caucasians, aged from 16 to 64 years, with no history of ischaemic heart disease, who were last seen alive within 12 h of being found dead, and for whom a coroner's post-mortem examination found either a cardiac or no identifiable cause of death. Eleven (92%) coroners participated. In a median of 105 days (range 21-169), 65 cases (83% of the quota) were ascertained (54 (83%) males). Of the ascertained cases, registration forms were received on 62 (95%), tissue specimens on 63 (97%), and post-mortem reports on 58 (89%). Death was witnessed in 58%, of which 35% were 'instantaneous'. The median time from symptom onset to death was 40 min. In unwitnessed deaths, the median time since last being seen alive was 90 min. Sixty-eight per cent of all deaths were attended--by a relative in 34%, passer-by (8%), ambulance crew (32%), nurse (11%), doctor (38%), and police (9%). Cardio-pulmonary resuscitation was attempted in 38 of the 42 attended deaths. Sixty-seven per cent were taken ill at home, 12% at work, 12% in a public place, and 10% elsewhere. The certified cause of death was ischaemic heart disease in 89%, in whom coronary thrombosis and/or myocardial damage was absent in 6 cases (9%). In the remainder, the certified cause was hypertensive heart disease (5%), hypertrophic obstructive cardiomyopathy (3%), 'cardiomegaly' (1.5%) and 'sudden cardiac arrhythmia' alone (1.5%). A retrospective audit of coroner's records revealed the median case ascertainment rate was 75%. This approach to surveying sudden unexpected adult death nationally resulted in a high response rate (92%) from coroners, consultant pathologists and their staff, the identification of a large proportion of eligible cases, and complete information in most of the identified cases. In from 2% to 15% of cases, death may have been either purely dysrhythmic or due to a sudden adult death syndrome.  相似文献   

10.
OBJECTIVE: To examine the impact of workplace smoking bans on smoking behavior of employees. PARTICIPANTS: A total of 1469 current or former smokers (intervention group) employed in smoke-free hospitals and 920 current or former smokers (comparison group) employed in non-smoke-free workplaces were surveyed to determine smoking behavior. DESIGN: This cross-sectional study is part of a larger, ongoing prospective study. The study design was quasi-experimental. We randomly selected sites consisting of a hospital and a corresponding community. Furthermore, we randomly selected subjects from hospitals and their corresponding communities. MAIN OUTCOME MEASURES: Postban quit ratio and progression along the stages-of-change continuum. METHODS: The Cox proportional hazards model was used to compare the postban quit ratio between the intervention and comparison groups. The Cochran-Mantel-Haenszel analysis of variance statistic was used to compare groups on the stages-of-change variables. RESULTS: Beginning with the smoking ban and continuing for 5 years after implementation, statistically significant differences in the postban quit ratio were observed between employees of smoke-free hospitals who were smokers and counterparts in the community (P<.001). Despite preban differences in smoking intensity, the overall difference in postban quit ratios remained significant even after multivariate adjustment for socioeconomic, demographic, and smoking intensity variables. For those sites that were 5 years postban, the quit ratio was 0.506 in smoke-free workplaces compared with 0.377 in workplaces where smoking was permitted. In all but 1 category, the intervention group was further along the stages-of-change continuum toward quitting smoking than the comparison group (P<.001). CONCLUSION: American hospitals' experiences with smoking bans, which directly affect more than 5 million workers, should be examined by other industries as a method of improving employee health. Workplace smoking bans could also be effective in saving lives, reducing health care costs, addressing safety concerns, and decreasing operating and maintenance expenses of employers.  相似文献   

11.
The arcuate nucleus of the hypothalamus, a highly sexually dimorphic brain region, has been called the bed nucleus for endogenous opioids. The potential contribution of opioids in this nucleus to modulate control of ventilation in male and female rats has not been investigated. The purpose of the present study is to determine the effect of microinjecting naloxone, an opioid receptor antagonist, into the arcuate nucleus of awake male and female rats on ventilation, oxygen consumption, heart rate, and blood pressure. Results of this study demonstrate that naloxone at doses of 1.5 and 3.0 nmol relative to vehicle caused a depression of ventilation due to a decrease of both frequency of breathing and tidal volume in male rats and a decreased response to a hypercapnic challenge in female rats. Although there were gender differences noted in oxygen consumption, heart rate, blood pressure, and ventilatory response to a hypoxic challenge, only oxygen consumption was significantly affected by naloxone. Potential mechanisms whereby naloxone may act to depressing ventilation are discussed.  相似文献   

12.
A retrospective analysis of 160 cases of bladder tumors in females revealed that in 9 of these cases cancer in the bladder arose 1 to 22 years after radiation for uterine and breast cancer. This secondary tumor manifested in 2 females as dysuria, in one of them transition cell cancer of the bladder followed Brunno's cystitis 2 years after the cystitis diagnosis. The other patients had macrohematuria. Being a frequent complication of radiotherapy of pelvic cancer, dysuria and macrohematuria should not be considered as a sign of radiation-induced cystitis. Such patients should be carefully followed up with annual microscopic and cytological examinations of residual urine and cystoscopic control.  相似文献   

13.
An enzyme linked immunosorbent assay, specific for prothymosin alpha (ProT alpha) was developed using an antibody against the synthetic C-terminal peptide ProT alpha[101-109] and isolated bovine ProT alpha for the preparation of standard solutions and immunoplates. Due to the antibody used, the ELISA developed was capable of fully discriminating between ProT alpha, the naturally occuring and partially homologous peptide parathymosin alpha (ParaT alpha) and the peptide thymosin alpha1 (T alpha1), whose sequence is identical to the [1-28] sequence of ProT alpha, and its in vivo occurrence is under question. Moreover, due to its improved sensitivity, the ELISA was capable of directly determining ProT alpha concentration in human serum and tissue extracts, without any pretreatment of the samples. ProT alpha levels were directly measured in sera obtained from 48 apparently healthy individuals and 27 patients with diagnosed breast cancer and found to range from 0.67 to 2.34 microg/ml (mean value 1.27 +/- 0.49 microg/ml) and from 0.47 to 1.74 microg/ml (mean value 1.02 +/- 0.29 microg/ml), respectively. ProT alpha levels were also measured in four breast tumor and adjacent normal breast tissue extracts and found to be elevated in the tumor extracts.  相似文献   

14.
1. In 1994 were 81 haemodialysis centers in the Czech Republic (including 12 private ones, i.e. 7.7 p.m.p.). 2. The capacity of dialysis centres enabled an outstanding number of new patients to be accepted--120 p.m.p. (the European average was half that number). Majority of the new patients were from higher age groups and diabetics. The number of patients, who were not followed prior to renal replacement therapy, still remains one third of the newly accepted ones. 3. In 1994 there were 3592 patients on dialysis treatment--342 p.m.p. (the maximum number so far), but by December 31st 1994 there were 2691 patients--256 p.m.p. surviving on dialysis treatment. We have achieved higher number dialysed patients p.m.p. than any other country of the former Eastern bloc, including the GDR. Mortality was 14%. 4. Hepatitis B as well as C remains a major problem, although there has been a slight decline of HBsAg positive patients. 5. The technical facilities for dialysis treatment are not optimal. 6. A favourable trend continued in the development of peritoneal dialysis programme.  相似文献   

15.
The national reference Center for blood groups checked samples of reagents and devices used in France for a definitive verification of pretransfusion ABO tests performed at the patient's bedside, as defined by French health authority regulations. The results of an initial inquiry was published in 1991. The new study shows no significant improvement of the quality of reagents and devices. This is a major concern considering the importance of ABO incompatibility in severe hemolytic transfusion reactions.  相似文献   

16.
The aims of this study were to examine the development and structure of identity throughout adolescence, and the influence of parents and peers on identity development. A representative sample of Dutch adolescents, aged 12 to 14, completed the Utrecht-Groningen Identity Development Scale (U-GIDS). This instrument encompasses separate scales for commitment in exploration for relational, school, and occupational identity. The results show that relational identity becomes consistently stronger as adolescents grow older. Less consistent developmental trends were found for school identity, and no developmental trends for occupational identity. A different identity structure was found in different groups of adolescents. For girls the relational identity is much more important than school or occupational identity. The same difference was found in adolescents aged 21 to 24 vs. their younger peers. Identity development is mostly influenced by peers, with parents having only an additive positive influence.  相似文献   

17.
To improve the health outcome of adults with asthma, it is important to understand the current practice behaviors of physicians related to the prevention and treatment of asthma. A national survey was conducted to ascertain the practice behaviors of physicians in five specialty areas: internal medicine, pulmonary, allergy/immunology, occupational health, and family health. Similarities and differences in practice among the specialty areas are indicated. The data provide a basis for recommendations to improve the management of asthma by standardizing history taking, increasing the use of pulmonary function testing, and using effective counseling and patient education strategies.  相似文献   

18.
The United States end-stage renal disease (ESRD) population is growing progressively older. As a percentage of the overall ESRD population, the number of patients 65 years of age and older approached 40% by 1989. However, the percentage of ESRD patients with a functioning transplant was only 2.7% in this age group. Success of transplantation in geriatric ESRD patients over the last decade is due to improved patient selection as well as the use of cyclosporine A and lower doses of corticosteroids, with the achievement of 1-year patient and graft survival rates of 85% and 75%, respectively. For patients older than 60 or 65 years, the 5-year "functional" graft survival is 55% to 60%. Although overall results are excellent, the management of transplantation in the elderly requires an understanding of pharmacology, immunology, and physiology peculiar to this age group. Since the elderly have a degree of immune incompetence, they require less aggressive immunotherapy. Elderly patients have decreased hepatic enzyme activity, especially the P450 system, and therefore require a lower cyclosporine dose. Although elderly patients experience less rejection episodes than younger patients, graft loss in the elderly transplant recipient is due mainly to patient death. Most common causes of death in the elderly transplant recipient are cardiovascular disease and infection related to peaks of immunosuppression. Shortage of cadaver kidneys and limited life expectancy of the geriatric ESRD patient make allocation of cadaver kidneys to patients over 70 years (and even 65 years) a controversial issue and an ethical dilemma. Use of elderly cadaver donors (over 55 to 60 years) is associated with inferior success rates and is not an optimal solution to shortage of cadaver kidneys.  相似文献   

19.
To investigate the activity of cortical regions in the control of movement, we studied event-related desynchronization/synchronization (ERD/ERS), event-related coherence (ERC), and phase coherence in 29-channel EEGs from 9 subjects performing self-paced movements of the right index finger. Movement preparation and execution produced ERD over the sensorimotor areas at 10 Hz and 20 Hz, followed by ERS. ERD corresponded spatiotemporally to an increase in coherence over the frontocentral areas. For both frequency bands, ERD began over the left sensorimotor areas and became bilateral at the time of movement onset. The coherence increase with frontal areas began in the left central areas and became symmetrical after EMG onset. The ERD and coherence increase was longer at 10 Hz than at 20 Hz. Phase coherence at 10 Hz showed a lead of anterior regions to posterior regions throughout the time period, and at 20 Hz showed a tendency toward zero phase delay corresponding with the movement. EEG desynchronization parallels functional coupling over sensorimotor and frontal areas. Event-related coherence and phase coherence findings implicate the frontal lobes in control of movement planning and execution. The involvement of different frequency bands with different timings may represent parallel changes in the cortical network.  相似文献   

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