1 The effect of short-term treatment of ganciclovir on male reproduction in adult rats was studied. The animals were treated subcutaneously with either a single dose of 60 mg/kg daily for 5 days (Gan5day) or with 100 mg/kg administered three times at 4 h- intervals (Gan1day). The effects were investigated every 2 weeks up to 8 weeks, followed by investigations 16 and 24 weeks after treatment to detect the potential of recovery. 2 Time to mating was significantly increased in Gan1day group. The pregnancy index and outcome were only decreased 8 weeks (Gan5day and Gan1day) or 16 weeks (Gan1day) after treatment. 3 The lowest values of sperm variables studied were registered 8 weeks after treatment: The number of spermatid was reduced up to 4% (Gan5day) or 2% (Gan1day) of control; the sperm number was 5% and 8% of control in Gan5day and Gan1day, respectively. Over 80% of sperm were abnormal in Gan5day group, and only few normal sperm was detected in Gan1day group. 4 Morphological investigation of testes revealed a clear- cut time-dependency effect. Four weeks after treat ment distinct alterations were located exclusively in the peripheral part of the tubuli which included fat inclusions, cell and pyknotic nuclear debris and swellings of Sertoli cells. The effect was reversible 24 weeks after treatment. 5 Ganciclovir induces testicular damage and affects sperm variables after short-term exposure. The in tensity and degree of the hazards varied in between the time of investigation after treatment.
Fetal sheep (n = 13) were chronically instrumented to measure temperatures in the maternal femoral artery (MAT), the amniotic fluid (AFT), the fetal brown adipose tissue (BFT) and the fetal arterial blood (DAT). Cooling loops were inserted into the amniotic cavity. In 4 fetuses osmotic minipumps delivering triiodothyronine (T3) were implanted subcutaneously. One to seven days after surgery the following results were obtained: 1) During control DAT was 0.59 +/- 0.2 degrees C (SD), BFT 0.60 +/- 0.24 degrees C and AFT 0.38 +/- 0.31 degrees C higher than MAT. T3 levels in treated fetuses were 3.4 +/- 1.5 micrograms/l. 2) Infusion of norepinephrine (NE) (5.2 +/- 0.9 micrograms/min per kg fetal body weight) with phentolamine (26.1 +/- 4.3 micrograms/min per kg) into a fetal vein did not change temperatures. 3) During cooling (-53 +/- 15 W) MAT decreased 0.45 +/- 0.3 degrees C, DAT 1.9 +/- 0.39 degrees C, BFT 1.61 +/- 0.52 degrees C and AFT 4.2 +/- 1.8 degrees C. 4) The amniotic fluid was cooled until steady state temperatures were achieved. Then propranolol (26.1 +/- 4.3 micrograms/min per kg) or suxamethonium (3 +/- 1 mg/kg) were introduced into the fetal vein. No consistent and significant changes of temperatures could be detected. It is concluded that 1) lowering the fetal core temperature by 1.6 - 1.9 degrees C and its ambient temperature (AFT) by 4.2 degrees C does not induce shivering or non-shivering thermogenesis suppressible by pharmacologic agents, 2) thermogenesis in fetal brown adipose tissue cannot be induced by NE (with or without supplemention of T3).(ABSTRACT TRUNCATED AT 250 WORDS)
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