Miglustat has no apparent effect on spermatogenesis in normal men.

BACKGROUND: In mice, administration of the glycosphingolipid biosynthesis inhibitor miglustat results in reversible infertility, characterized by impaired sperm motility and markedly abnormal sperm morphology. This observation suggested that miglustat might have utility for fertility control in man. To ascertain the impact of miglustat on human spermatogenesis, we conducted a pilot study of miglustat administration in normal men. METHODS: After a 2-week baseline period, seven normal men were administered miglustat 100 mg, orally, twice daily for 6 weeks. During treatment, subjects had frequent seminal fluid analyses to assess the impact of treatment on sperm concentration, motility and morphology and the ability to undergo the acrosome reaction by in vitro assays. RESULTS: Five subjects completed all aspects of the study. In these subjects, there was no apparent effect of miglustat on sperm concentration, motility or sperm morphology after 6 weeks of therapy. In addition, no changes in acrosome structure or function were observed with treatment, despite therapeutic concentrations of miglustat in the serum and seminal plasma. All subjects experienced gastrointestinal upset, diarrhoea and mild weight loss during treatment. No other abnormalities in blood counts, serum chemistries, vision or overall health were observed. CONCLUSION: In contrast to the observations in mice, the oral administration of miglustat does not appear to affect human spermatogenesis. Further elucidation of the mechanism underlying the species specificity of miglustat may improve our understanding of the role of glycosphingolipids in spermatogenesis and result in alternative approaches to male fertility control.

Detection of donor-reactive alloantibody in the early posttransplant period. Elimination of therapeutic ALG as a complicating factor.

We have developed an immunoabsorbent reagent that can differentially remove ALG from human serum samples in vitro--i.e., goat antihorse IgG covalently linked to Sepharose beads. When used according to protocol, this immunoabsorbent can effectively remove up to 0.78 mg/ml of ALG from human serum mixtures. To demonstrate that immunoabsorption is selective, an HLA-B7-specific alloserum was mixed with a known amount of ALG and absorbed with antibody-conjugated Sepharose beads. The addition of ALG to the serum sample caused high degrees of nonspecific lympholysis in standard microcytotoxicity assays. When this serum/ALG mixture was immunoabsorbed detectable ALG activity was lost but the original HLA alloantibody titer (1:2) against specific target lymphocytes was retained.

[Changes in the heart beat of puppies in the first twelve weeks of life]. / Anderungen der Herzschlagzahlen beim Hundewelpen in den ersten zwölf Lebenswochen.

In 37 healthy pups and seven pups with congenital pulmonic stenosis ECG were recorded and the heart rate determined. Between the first week of life in healthy pups (mean = 230/min) and the twelfth week of life the heart rate in both groups at six weeks was 195/min and 180/min. At the end of the investigation the averaged heart rate was 167/min or 166/min respectively. In single weeks during the investigation a slightly increased heart rate occurred in a few dogs between the fourth and sixth week of life owing to an increased restlessness during this time span. The heart rate of newborn pups at the first day (mean = 215/min) was a little lower than the average in the first week of life.