Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

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 C_max 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.     

Evolution of the sperm aster after microinjection of isolated human sperm centrosomes into meiotically mature human oocytes

This study examined the feasibility of isolating and transferringthe centrosome-containing region of spermatozoa to mature humanoocytes. The findings demonstrate that individual sperm centrosomescan be transferred and are capable of nucleating maternal tubulinto form a well-developed sperm aster in the recipient oocyte.The results are discussed with respect to centrosome functionin early human development and applications in clinical in-vitrofertilization in the treatment of certain forms of male factorinfertility.     

Use of algal fluorescence for determination of phytotoxicity of heavy metals and pesticides as environmental pollutants

The phytotoxicity of heavy metals and pesticides was studied by using the fluorescence induction from the alga Dunaliella tertiolecta. The complementary area calculated from the variable fluorescence induction was used as a direct parameter to estimate phytotoxicity. The value of this parameter was affected when algae were treated with different concentrations of mercury, copper, atrazine, DCMU, Dutox, and Soilgard. The toxic effect of these pollutants was estimated by monitoring the decrease in the complementary area, which reflects photosystem II photochemistry. Further, the authors have demonstrated the advantage of using the complementary area as a parameter of phytotoxicity over using variable fluorescence yield. The complementary area of algal fluorescence can be used as a simple and sensitive parameter in the estimation of the phytotoxicity of polluted water.     

Falls among the elderly: epidemiology and prevention

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.     

The Framingham Disability Study: physical disability among community-dwelling survivors of stroke

The relationship between stroke and physical disability was examined in a cohort of adult, Framingham, Massachusetts, residents who, between 1948 and 1951, were assembled for a longitudinal examination of cardiovascular disease. Multivariate analyses examined the amount of residual disability attributable to stroke among 2540 community-dwelling survivors, 27 years after their initial examination, after controlling for age, cardiovascular risk factors, other cardiovascular diseases, and eight general health conditions related to physical disability. Among men living in the community, a history of stroke explained 12% of the variance in physical disability. Suffering a stroke, however, was not as strongly related to physical disability among women living in the community, accounting for only 3% of the variance. Results suggest that although older men and women die from the same major causes, they may not be disabled by the same conditions.     

Factors affecting the toxicity of rotting carcasses containing Clostridium botulinum type E

Mice killed shortly after receiving c. 2000 spores of a type E strain of Clostridium botulinum per os were incubated at one of five chosen temperatures together with bottles of cooked meat medium seeded with a similar inoculum. After incubation the rotting carcasses were homogenized. Sterile membrane filtrates of the homogenates (10%, w/v) and pure cultures were then titrated for toxicity. Some of the main findings were confirmed with two further type E strains. Toxicity produced at 37 degrees C was poor in both carcasses and cultures (200-20,000 mouse intraperitoneal LD/g or ml). It was good in both systems at 30 and 23 degrees C, usually reaching 20,000-200,000 LD/g or ml, and in carcasses occasionally more; at 30 degrees C maximal toxicity was reached more quickly in carcasses than in cultures. Prolonged incubation (36-118 days) at 30 or 23 degrees C resulted in complete loss of toxicity in virtually all carcasses but not in cultures. At 16 degrees C the development of toxicity in carcasses was strikingly greater than in cultures. At 9 degrees C neither system produced more than slight toxicity after prolonged incubation. Trypsinization increased the toxicity of cultures but not usually of carcasses. Unfiltered carcass homogenate (10%, w/v) with maximal intraperitoneal toxicity was harmless for mice by mouth in doses of 0.25 ml. These findings differed in important respects from those made earlier with a type C strain.