Cryopreservation of human embryos obtained after gamete intra-Fallopian transfer and/or in-vitro fertilization

During a one-year period 636 excess embryos obtained after in-vitrofertilization and gamete intra-Fallopian transfer combined within-vitro fertilization were cryopreserved using two differentprotocols. For early stage embryos including the pronucleatestage, 1,2-propanediol was used as cryoprotectant (procedureA, adapted from Renard) and for later stage embryos dimethylsulphoxidewas used in protocol B, adapted from Trounson and Mohr. Afterthawing 288 embryos, half of them were of sufficient qualityto be replaced. After cryopreservation, procedure A gave thebest survival in embryos having 2 blastomeres; for later stageembryos best survival was obtained using the dimethylsulphoxideprotocol. Survival after cryopreservation was also clearly relatedto the quality of the embryos prior to freezing. Embryos werereplaced during endocrinologically monitored natural cyclesand were transferred in synchrony between endornetrial and embryonicage. After replacement of 126 embryos in 110 patients, 20 pregnanciesoccurred. So far six healthy children have been born, two patientsaborted and 12 pregnancies are ongoing. In this series no statisticaldifference was observed between the implantation rate of embryoscryopreserved by procedure A or B. Six pregnancies occurredin patients from the oocyte and embryo donation programme. Anadequate cryopreservation programme circumvents the difficultproblem of synchronizing the ovarian cycles of donor and acceptorpatients.     

Serum lipoprotein profiles in mice: effects of early over- and undernutrition

Effects of early over- and undernutrition on lipoprotein profiles of adult Swiss male mice reared in litters of different sizes were investigated. Lipoproteins were isolated by density gradient ultracentrifugation and defined by chemical composition. Protein moieties were defined by their changes. The lipoprotein lipase (LPL) activity in epididymal adipose tissue, heart and diaphragm was measured. Early feeding patterns induced permanent body weight differences in adult mice. Serum phospholipid content was significantly higher in obese than in control mice. Overfeeding led to significantly higher activity of LPL in adipose tissue; inversely, undernutrition induced a lower LPL activity. There was a trend toward variations of lipoprotein concentrations in relation to litter size, with significant differences being observed only between obese and undernourished mice for LDL-HDL1 (low density lipoprotein--high density lipoprotein) and HDL2 concentrations. Compared with normally fed mice the most notable alterations in plasma lipoprotein composition were, in LDL-HDL1, greater cholesteryl ester in obese and less phospholipid in undernourished mice. In contrast, tetramethylurea-soluble apolipoprotein distribution was unaffected by litter size. Although moderate differences were observed in lipoprotein compositions and levels in over- or undernourished mice, further investigations of lipoprotein metabolism and metabolic abnormalities in this animal model are required.     

Interaction of the human leukocyte proteinases elastase and cathepsin G with gold, silver and copper compounds

Gold thiomalate and the corresponding silver and copper derivatives were investigated as inhibitors of the human leukocyte proteinases elastase and cathepsin G. The kinetic inhibition mechanism for gold- and silver thiomalate is of the hyperbolic non-competitive type with both enzymes and the inhibitory efficiency of the metals increases in the order Cu less than Ag less than Au. On the contrary, D-penicillamine derivatives of the three metals do not influence at all the activity of the two proteinases. Although gold thiomalate is the most efficient of the investigated metal compounds (Ki = 33 microM and 25 microM for elastase and cathepsin G, respectively), the hyperbolic nature of the inhibition imposes a serious limit to its practical usefulness since the maximum inhibitory action on both enzymes is about 40%. We suggest that, in order to act as inhibitor, a copper, silver or gold compound must be able to easily transfer the metal to the enzyme.     

Effects of nifedipine and diltiazem on pharmacokinetics of cefpodoxime following its oral administration.

We compared the effects of nifedipine and diltiazem on the uptake of cefpodoxime proxetil (CP). The study was aimed at establishing the impact of increased mesenteric blood flow due to calcium channel blockers on passive transport. Twelve volunteers were given CP (200 mg) orally in a crossover design. The absorption, disposition, and elimination parameters of cefpodoxime were compared among the following three treatment groups: CP alone, CP following oral administration of diltiazem (60 mg), or CP following oral administration of nifedipine (20 mg). No statistically significant difference in pharmacokinetic parameters was observed between the three treatment groups.     

Comparative effects of alpha-methyldopa, propranolol and hydralazine therapy on cardiac adenylate cyclase activity in normal and spontaneously hypertensive rats

Normotensive (WKY) and spontaneously hypertensive (SHR) male rats were treated orally, one week after weaning and for 9 weeks, with alpha-methyldopa (100 mg/kg per day), propranolol (30 mg/kg per day) or hydralazine (10 mg/kg per day). Untreated WKY and SHR rats served as controls. The development of hypertension in SHR rats were attenuated by treatment but none of the drugs was able to restore the impairment in isoproterenol, secretin and glucagon responsiveness of cardiac adenylate cyclase activity which is characteristic of these animals. In heart membranes from both WKY and SHR rats, alpha-methyldopa treatment increased the number of beta-adrenoceptors by 20-32% and the maximal response of adenylate cyclase activity to isoproterenol and glucagon by 20-34%. By contrast, the beta-blocker propranolol was ineffective on these parameters. The results obtained are consistent with the hypothesis that the change in adenylate cyclase seen in SHR rats is genetic in origin and is not a consequence of hypertension.     

Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors.

We investigated the binding properties of the (R)- and (S)-enantiomers of the muscarinic antagonists trihexyphenidyl, procyclidine, hexahydro-difenidol, p-fluoro-hexahydro-difenidol, hexbutinol, p-fluoro-hexbutinol, and their corresponding methiodides at muscarinic M1, M2, M3 and M4 receptor subtypes. In addition, binding properties of the (R)- and (S)-enantiomers of oxyphencyclimine were studied. The (R)- enantiomers (eutomers) of all the compounds had a greater affinity than the (S)-isomers for the four muscarinic receptor subtypes. The binding patterns of the (R)- and (S)-enantiomers were generally different. We did not observe any general correlation between the potency of the high-affinity enantiomer and the affinity ratio (eudismic ratio) of the two enantiomers. The results are discussed in terms of a 'four subsites' binding model.     

Medico-economic assessment of neuroleptics in schizophrenia. Amisulpride versus haloperidol]

The aim of this study is to assess the economic impact of neuroleptic strategies in the long-term treatment of schizophrenic patients. In this respect a new neuroleptic strategy (amisulpride) was compared to a reference drug (haloperidol) using a cost minimization method. Clinical, demographic and economic (direct medical costs) data were obtained retrospectively from patients' charts. Patients (n = 160) were randomly selected according to diagnosis (schizophrenia, DSM III-R), treatment (outpatient, amisulpride or haloperidol) and follow up period (at least 6 months). The health insurance point of view was selected for the economic analysis. We found a significant reduction of the annual number of days of relapse when patients were treated with amisulpride compared to haloperidol. This reduction was associated with a significant reduction of direct costs mainly related to shorter length of hospitalization. This result was only partly explained by demographic and clinical variables such as the severity of the disease. The differences remained significant when populations were matched. This finding illustrates the validity of the concept of efficiency in psychiatry.