Early impact of hormone replacement therapy on vascular hemodynamics detected via ocular colour Doppler analysis

Objective: To determine the effects of hormone replacement therapy (HRT) on ocular blood flow.

Study design: In a prospective controlled study, 40 healthy women who presented to the menopause clinic between December 2000 and December 2001 were randomly assigned into the study. The HRT-receiving group was administered estradiol 17-valerate 2 mg the first 11 days, and estradiol 17-valerate 2 mg plus ciproterone acetate 1 mg the next 10 days of the monthly cycle for 6 months. The control group did not receive any HRT for 6 months. The ocular colour Doppler analysis were performed at baseline and after 3 and 6 months. The ocular Doppler analysis was performed in the first half of the cycle in the HRT-receiving group.

Results: Central retinal artery and ophthalmic artery basal Doppler index (peak systolic velocity, end-diastolic velocity, resistive index and pulsatility index) values of the two groups at the beginning of the study did not show any statistically significant difference. Both the right and the left central retinal artery pulsatility index (PI) values of the study group, who received HRT at the end of the third and sixth months, showed a statistically significant decline (paired-samples test, P < 0.05), while the decrease in the resistive indexes was not significant.

Conclusion: These results suggest that 6 months of combined hormone replacement therapy with estradiol 17-valerate 2 mg plus ciproterone acetate 1 mg improves ocular vascular Doppler indices which may be a reflection of cerebral vascular status.     

Mutations causing gaucher disease

Glucocerebrosidase is a lysosomal enzyme responsible for hydrolysis of glucosylceramide to ceramide and glucose. Mutations disrupting the function of this enzyme cause autosomal recessive Gaucher disease. This disease is very heterogeneous. The clinical heterogeneity is due to a large number of mutations within the gene encoding glucocerebrosidase. To date 36 mutations have been described in Gaucher disease. In this part we present the mutations and review the more common ones. We also review the glucocerebrosidase natural activator, designated saposin C and mutations in its gene, associated with Gaucher disease. © 1994 Wiley-Liss, Inc.     

Ethical considerations for enzyme replacement therapy in neuronopathic Gaucher disease

Elstein D, Abrahamov A, Zimran A. Ethical considerations for enzyme replacement therapy in neuronopathic Gaucher disease. Clin Genet 1998: 54: 179–184. 0 Munksgaard, 1998
Enzyme replacement therapy for Gaucher diseases, the most prevalent lysosmal storage disease, was originally approved by the FDA for type I patients and has proven to be both safe and effective in reducing hepatosplenomegaly and improving the hematological parameters. However, the use of enzyme treatment in both neuronopathic forms has heretofore been on an investigational or trial basis, with reports of progression of neurological deterioration even at very high doses. To date, there are no guidelines for clinicians with regard to enzyme replacement therapy in the neuronopathic forms of metabolic diseases. Herein, we discuss strategies derived from the literature ub-his treatment of very premature babies and from the Jewish Halachic point of view. In conclusion, we describe recommendations for the ethical treatment and/or withdrawal of treatment. as well as practical guidelines for dosage regimens, in children with neuronopathic Gaucher disease.     

Platelet responses and coagulation activation on polylactide and heparin-polycaprolactone-L-lactide-coated polylactide stent struts

Despite modern stent technology and effective antiplatelet therapy, metallic stents carry the risk of (sub)acute thrombosis. Our aim was to examine short-term differences in platelet deposition and coagulation activation between biodegradable polylactide (PLA), heparin-polycaprolactone-L-lactide-coated polylactide (hepa-P(CL95/L-LA5)-PLA), and stainless steel (SS) stent struts. Gel-filtered platelets (GFP) and platelet-rich plasma (PRP) were labeled with 10 nM (3)H-serotonin. Platelet deposition was measured after incubation of the stent struts in human serum albumin-coated wells at 37 degrees C in either GFP or PRP. Platelet morphology was studied by scanning electron microscopy (SEM). For coagulation activation, the stent struts were incubated in either PRP or platelet-poor plasma (PPP), anticoagulated with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), followed by measurement of fibrinogen, thrombin time (TT), prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex (TAT). SS showed adherence of larger amounts of GFPs than did PLA at a platelet density of 300 x 10(6)/mL (p < 0.05). Furthermore, representative SEM studies showed more platelet spreading on SS than on PLA stent struts. Between PLA and SS, coagulation activity did not differ at any assessment. Based on prolonged TT values in plasma, the heparin coating strongly inhibited coagulation (p < 0.05). The values of soluble TAT and F1+2 for PLA were similar to those of controls, i.e., to incubated suspensions without a stent strut. In conclusion, when compared with stainless steel, both PLA and hepa-P(CL95/L-LA5)-PLA appear hemocompatible as intravascular stent materials.     

Gene dosage and down's syndrome: Metabolic and enzymatic changes in PC12 cells overexpressing transfected human liver-type phosphofructokinase

Down's syndrome (DS) is a human genetic disease caused by triplication of the distal third of chromosome 21 and overexpression of an unknown number of genes residing in it. The gene for the liver-type subunit of phosphofructokinase (PFKL), a key glycolytic enzyme, maps to this region and the product is overproduced in DS erythrocytes and fibroblasts. These facts, together with abnormalities which occur in DS glycolysis, make PFKL overexpression a candidate for causing some aspects of the DS phenotype. A cellular model for examining the consequences of PFKL overexpression in DS was constructed by transfecting rat PC12 cells with the human PFKL cDNA. Phosphofructokinase (PFK) isolated from PFKL-overexpressing clones was more inhibited by ATP and citrate and less activated by fructose-6-phosphate than control PFK; similar results were obtained when PFK preparations from DS and control fibroblasts were compared. In vivo NMR measurements determined that cells overexpressing PFKL performed glycolysis 40% faster than controls. These results show that overexpression of PFKL is the cause for altered biochemical regulatory characteristics of PFK in DS fibroblasts and can result in enhancement of glycolysis rates. It is also shown that increased gene dosage can exert its influence not merely by enhancing the amounts of gene products but also by altering their biochemical nature.     

Smoking, alcohol use, and physical activity: a 13-year longitudinal study ranging from adolescence into adulthood.

PURPOSE: To assess the associations among smoking, alcohol use, and physical activity, and to assess how the health behaviors predict changes in other health behaviors from adolescence to adulthood. METHODS: Subjects were the participants of the North Karelia Youth Project study from six schools in Eastern Finland. At the baseline in 1978 they were 13-year-olds (n = 903) and in the last of the six surveys in 1993 they were 28-year-olds. This study uses the data from three surveys in which the participants were 15-, 21-, and 28-year olds. The response rate was 71% in the last survey. Data were analysed by SPSS software. RESULTS: Smoking prevalence was highest at the age of 21 years and alcohol use at the age of 28 years. The prevalence of leisure-time physical activity did not change much over time. Smoking and alcohol use correlated positively for each survey. Smoking correlated negatively with leisure-time physical activity. The best predictors for each health behavior were the same behaviors measured before, but smoking had the strongest level of continuity. In addition, alcohol use at the age of 15 years predicted smoking at the ages of 21 years and 28 years, but smoking in adolescence did not predict alcohol use in adulthood. CONCLUSIONS: Smoking was associated with both alcohol use and physical activity and therefore has a central role among health behaviors. Smoking and alcohol use were particularly clearly related from adolescence to adulthood. Smoking behavior was the most constant behavior.