The effect of intramuscular stanozolol on fibrinolysis and blood lipids

The effects of a single 50 mg intramuscular injection of the anabolic steroid stanozolol (Stromba) on fibrinolysis, blood coagulation and lipids was evaluated in 12 healthy male volunteers. Significantly increased plasminogen activator levels (p < 0.05) was noted 24 hours following the injection and these remained elevated for one week. Plasminogen levels increased significantly by day two (p < 0.01) and remained elevated for three weeks. HDL cholesterol fell (p < 0.01) and both total and LDL cholesterol increased (p < 0.05) when measured one month post injection. Stanozolol appears to have therapeutic potential as an activator of the fibrinolytic system when given by intramuscular injection.     

The proteolytic action of ancrod on human fibrinogen and its polypeptide chains

The digestion of human fibrinogen and fibrin by the coagulant enzyme ancrod (Arvin) was studied, and by use of polyacrylamide gel electrophoresis in sodium dodecyl sulphate (SDS) the molecular weights of subunit polypeptides and digestion products were estimated. Ancrod attacked only the α (A) chain of human fibrinogen to produce a polypeptide of molecular weight 39,000 which was bound within the clot, and also a free polypeptide of 31,000 which appeared in the supernatant and was further digested to fragments of 27,000, 25,000, 16,000 and about 10,000. Ancrod in higher concentrations also digested the α polymers of crosslinked fibrin producing fragments similar to those from the α (A) monomer but differing in their distribution between clot and supernatant. Digestion of the separated α (A), β (B) and γ chains of S-carboxymethyl fibrinogen by ancrod showed the α (A) chain to be the most susceptible to proteolysis and that the same digestion products were formed as from the intact fibrinogen molecule. Additionally, limited proteolytic digestion of the separated γ chain was observed.     

Effect of apolipoprotein E genotype on vitamin K status in healthy older adults from China and the UK

The vitamin K concentration in the circulation and the availability of vitamin K to bone may be affected by factors influencing lipoprotein metabolism, such as apoE genotype. The relationships between markers of vitamin K status, bone mineral content and apoE genotype were studied in healthy older men and women aged 60-83 years, 177 from Shenyang, China, and 132 from Cambridge, UK. Fasting plasma was analysed for vitamin K1, triacylglycerol, total osteocalcin, undercarboxylated osteocalcin (ucOC) and apoE genotype. Hip bone mineral content was measured using dual-energy X-ray absorptiometry. Subjects were grouped according to apoE genotype as E2/3, E3/3 and [E3/4+E4/4]. The mean plasma vitamin K1 concentration of the three genotype groups was significantly higher and the percentage ucOC was lower in the Chinese than in the British subjects (P<0.01). A higher vitamin K1 concentration was found in subjects with [E3/4+E4/4] than those with either E2/3 or E3/3 in Cambridge (32.2 (SE 14.6 ) %, P=0.03; 24.6 (SE 10.7 ) %, P=0.02). Similar trends were observed although were not statistically significant in Shenyang (26.5 (18.9) %, P=0.16; 23.1 (13.0) %, P=0.08). Subjects with [E3/4+E4/4] had a lower percentage ucOC (total osteocalcin adjusted) than did those with either E2/3 or E3/3 in Shenyang (65.1 (27.2) %, P=0.02; 49.6 (19.9) %, P=0.01 respectively) but not in Cambridge. This study demonstrates that a superior vitamin K status is associated with the apoE4 genotype in healthy older individuals from China and the UK.     

Effect of sulphinpyrazone and aspirin on latelet adhesion to activated charcoal and dialysis membranes in vitro.

Charcoal haemoperfusion is used in the treatment of severe drug overdosage, and is potentially useful in fulminant hepatic failure and chronic uraemia. Haemo-compatibility of early devices has improved, but platelet loss and occasional associated haemorrhage still occur. During a double blind cross-over study, in 8 healthy male volunteers, aspirin 600 mg/day, sulphinpyrazone 800 mg/day, or a combination of both or placebo were administered for 2 days at 14 day or longer intervals. The effects of these agents were measured with reference to 1) forearm bleeding times using a spring loaded device, 2) platelet adsorption during 2 hrs haemoperfusion of heparinized blood through 2% acrylic hydrogel coated or uncoated activated charcoal in vitro, and 3) platelet retention from citrated blood on PT₁₅₀ and PT₂₅₀ cuprophan dialysis membranes in vitro. Aspirin and aspirin in combination with sulphinpyrazone prolonged bleeding time, but sulphinpyrazone alone had no significant effect on bleeding time. Aspirin alone, sulphinpyrazone alone, and their combination reduced platelet adsorption on coated activated charcoal, and platelet retention on cuprophan membranes. Aspirin, and aspirin in combination with sulphinpyrazone, reduce platelet adsorption on uncoated charcoal, while sulphinpyrazone alone had no significant effect. The results indicate that 2 days treatment with sulphinpyrazone or aspirin produce significant antiplatelet action and that the effects of sulphinpyrazone on platelet function should be explored in relation to clinical haemoperfusion and haemodialysis.     

Early programming of adult diseases in resource poor countries.

Considerable evidence now exists to suggest that early exposure to nutritional deprivation can have long term consequences to health, with low birth weight now considered a risk factor for later health outcomes such as coronary heart disease, stroke, type 2 diabetes, and the metabolic syndrome. Of importance, such effects are most exaggerated when faced with over-nutrition in later life, forming the basis for the "thrifty phenotype" hypothesis. The evidence in support of these associations comes largely from retrospective cohort studies in which adult outcomes were correlated with birth weight records. Relatively little data is available from developing countries, where long term record keeping of birth weight data has not been a high priority. Arguably however, such countries are at the greatest risk from the mismatch of early nutritional deprivation and later nutritional affluence. This paper explores the importance of the "developmental origins of health and disease" hypothesis in resource poor countries.     

Maternal preconceptional weight and gestational length

Recent animal studies suggest that preconceptional undernutrition shortens gestation. We retested this idea among rural Gambian women who experience annual fluctuations in energy balance caused by the rains (with lowest weights in September to November) using records from 1918 infants. Pregnancies conceived in September to November were significantly shorter than those from better-fed months (38.6 vs 39.0 weeks; log-rank chi 2 = 17.4, P < .0001).     

Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's disease

BACKGROUND: Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response. METHODS: A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER). RESULTS: 43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4, 139) = 5.60, p < 0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p < 0.05 in each case). This effect could not be explained by age or by smoking status. CONCLUSION: Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome.     

Predicting the outcome of cholinesterase inhibitor treatment in Alzheimer's disease

OBJECTIVE: To investigate the possibility that response to cholinesterase inhibitor therapy could be predicted by easily measurable variables that are known to change as a result of treatment (such as the Mini Mental State Examination), measures of function (such as the instrumental activities of daily living and the social behaviour subscales of the Nurse's Observation Scale for Geriatric Patients), and measures of attention (such as the Digit Symbol Substitution Test; DSST), or that might influence response through structural (for example, age, cerebrovascular disease, medial temporal lobe (MTL) atrophy, hypertension) or chemical (for example, smoking) mechanisms. METHOD: This was a cohort study of 160 consecutive outpatients with probable Alzheimer's disease who commenced cholinesterase inhibitor treatment over a 3 year period in a semi-rural area of Scotland. RESULTS: The overall response rate was 42.1%. Stratification of response between good and poor responders was possible using baseline DSST and a measure of MTL thickness using CT. Among the patients, 60.4% of those above the cut off point for both DSST and MTL thickness (29/48 subjects) were classified as good responders, compared with 6.3% of subjects below the cut off point for both (1/16 subjects). Subjects above the cut off point for both measures were more likely to be classified as good responders than subjects with only one or no values above the respective cut off points (chi(2) = 10.61, df = 1, p = 0.001) CONCLUSIONS: The DSST and a measure of MTL thickness derived from CT scanning may be useful in improving the prediction of response to cholinesterase inhibitors in subjects with AD. Subjects with low DSST scores and more severe MTL atrophy are unlikely to respond to treatment. These preliminary data justify a prospective trial of the usefulness of our suggested predictive measures.