The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that Cmax and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.
The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.
The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey. 相似文献
The decoction of Sclerocarya birroea Hochst. shows hypoglycaemic effects, an increase in plasma IRI in normal rats and an incremented oral-glucose tolerance. The decoction is also active against diet-induced hypercholesterolaemia. 相似文献
An oral live attenuated Shigella flexneri vaccine candidate strain was constructed by making it auxotrophic and dependent on aromatic metabolites not available in mammalian tissues. An aroD gene of Escherichia coli K12 strain NK 5131, inactivated by insertion in it of the Tn 10 transposon, was transduced using phage P1 into a virulent S. flexneri serotype Y strain (Sfl 1) isolated from a patient with bacillary dysentery. One of the transductant strains Sfl 114 was found to invade HeLa cells in vitro, to cause plaque formation in HeLa monolayers (i.e. maintain intracellular multiplication in vitro), but to be unable to cause keratoconjunctivitis in guinea-pig eyes. When the strain was fed to Macacca fascicularis monkeys it was well tolerated, excreted for 1-4 days, and found to elicit a local intestinal sIgA and serum IgA, IgM and IgG responses. Monkeys challenged with 100 ID50 dose (1 X 10(11) bacteria) of the virulent parent Sfl 1 strain were completely protected from development of diarrhoea. Coloscopy of the monkeys and the sampling of intestinal biopsies showed that the vaccine protected against the surface epithelial erosions and ulcerations seen in unimmunized monkeys. Killing of invading virulent shigellae apparently took place intracellularly in the mucosa suggesting that cellular immune mechanisms played a role in the elicited host defence. The constructed S. flexneri Sfl 114 strain has the properties of a promising shigella vaccine and will next be the subject of studies with human volunteers. 相似文献
Eight-eight female weanling Sprague-Dawley rats were fed diets containing either 650 or 150 mg magnesium/kg diet and 7.0 or 3.5 mg pyridoxine-HCl/kg diet, in a 2 x 2 factorial arrangement, during growth, gestation, and lactation. The objective of the study was to determine whether concurrent dietary deficiencies of magnesium and pyridoxine were synergistic, additive, or antagonistic with regards to effects on reproductive performance, growth, and development of offspring, and tissue content of magnesium and calcium. Body weight of dams and pups was not different between groups until day 9 of lactation, at which point those animals in either low magnesium group weighed less than the other. Litter size and birth weight were not different. Development, as measured by timing of unfolding of the external ear, opening of both eyes, and clinical emergence of incisors, was delayed in pups from litters in the low magnesium groups. A synergistic effect on delay of onset of ear unfolding by deficiency of both magnesium and pyridoxine was observed. Calcium content of heart and kidney from dams was increased in the low magnesium groups. Renal calcium was not further increased by the level of pyridoxine deficiency in this study. The calcium to magnesium ratio in heart from pups was higher in those from litters in the low magnesium and pyridoxine group than in the others. Results indicate that simultaneous deficiencies of magnesium and pyridoxine may impair function synergistically. Because these two nutrients are often reported to be presented in inadequate amounts in diets of women in their reproductive years, the potential exists for impaired reproductive success. 相似文献
Harmful psychological and physical consequences may result when elderly people fall. I summarize the epidemiology of falls among elderly people and focus on three potentially remediable causes of falls: reduced peripheral neurosensation, the use of psychoactive medication, and environmental hazards. From 1960 to 1980, death rates from falls among white persons 75 years of age and older have decreased by more than 50%. Fall rates among community-dwelling elderly people increase with age and are greater for women than men. The death rates from falls, however, are now greater for men than women. Reduced peripheral neurosensation in the lower extremities may be a significant cause of falls among the elderly. Recreational walking or physical therapy may improve these deficits and lead to fewer falls. The use of psychoactive medications, most commonly benzodiazepine sedatives, is possibly associated with an increased risk of falls and hip fractures; greater caution in the use of these medications is warranted. The elimination or redesign of steps and curbs and the provision of hand railings and walking aids may be the most effective environmental approaches to preventing falls. These conclusions need further study in community-dwelling elderly populations. 相似文献
In the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man, single exponential disappearance curves for 2H2O and H2(18)O in body water are used; the precision with which the slopes and intercepts of the curves are estimated determines the precision of the estimate of carbon dioxide production rate. In studies with infants, and in computer simulations, the effect of different experimental regimes on the overall precision of the carbon dioxide production estimate was investigated. When the number of data points used was progressively reduced by shortening the total observation period from 7 d (about 3 biological half-lives for the isotopes) to 1 d there was a deleterious effect on precision and in the infants there was an upward bias in the values for carbon dioxide production. When the number of data points was reduced by removing points from the middle of the exponential curves with the maintenance of the 7-d experimental period, precision was also reduced but by less than in the former procedure and there were no consistent trends in the average values for carbon dioxide production. 相似文献
Herpes zoster probably occurs more often than generally thought. Since it produces a radicular distribution of pain, it should be included in the differential diagnosis of radiculopathy. A case is presented in which evaluating the radicular low back pain before the characteristic rash appears was misleading. Careful history-taking concerning the exact nature of the pain and sensory changes is needed to differentiate between zoster and radiculopathy, if no rash is evident. 相似文献
Eledoisin has been tried as a possible treatment for dry eye based on the hypothesis that it pharmacologically stimulates tear secretion when topically applied to the eye. To determine if topically applied eledoisin pharmacologically stimulates orbital lacrimal secretion, the orbital lacrimal gland excretory duct of normal rabbits was cannulated, and eledoisin was applied topically with and without prior administration of proparacaine. To determine if topically applied eledoisin stimulated accessory lacrimal gland secretion, isotonic buffer with and without eledoisin was tested in a rabbit model with only accessory lacrimal tissue remaining after the administration of proparacaine. Topically applied eledoisin did not pharmacologically stimulate lacrimal secretion but rather increased lacrimal gland secretion only in non-anesthetized eyes through a sensory reflex mechanism that is blocked by proparacaine. 相似文献