Acute paternal alcohol exposure impairs fertility and fetal outcome.

An acute injection of an intoxicating dose of alcohol to male rats 24 hours prior to breeding with drug-naive females produced no discernible effect on copulatory activity, as reflected in vaginal plugs, but resulted in markedly (> 50%) reduced pregnancy rates. Fetal outcome was also markedly affected in offspring sired by alcohol-treated males: litter sizes were appreciably smaller (30%) and fetal mortality was more than 2 times higher than in controls. These results suggest that paternal alcohol use, like maternal alcohol abuse, may adversely affect fertility and fetal outcome.

Acute alcohol exposure markedly influences male fertility and fetal outcome in the male rat.

Although it is recognized that drugs ingested by pregnant females produce marked cognitive and physiological deficits in their offspring, the possibility that paternal exposure to drugs prior to mating may have adverse effects on fertility and fetal outcome has not received much attention. The purpose of the present studies was to examine whether a single, acute exposure to alcohol influences the subsequent ability of adult male rats to mate and produce healthy and viable litters. Our results showed that a relatively large dose of alcohol 24 hours prior to breeding had little effect on the mating behavior of male rats, but there were markedly fewer pregnancies in females mated with alcohol-exposed male rats than in controls. Of equal importance, we found that, even when conception occurred and live births were produced, there were striking differences in fetal outcome. Alcohol-treated males sired many fewer pups than control males and there was a markedly enhanced mortality rate in their offspring. Collectively, these data suggest that acute paternal alcohol administration 24 hours prior to breeding does not affect mating behavior, but results in a greatly diminished fertility rate and fewer and less viable offspring. These studies suggest that paternal alcohol use may be as important as maternal alcohol abuse as a negative variable in pregnancy and fetal outcome.

[Localization of nonpalpable breast lesions in intraoperative rapid-section diagnosis using a new procedure]. / Lokalisation nicht-tastbarer Mammaveränderungen zur intraoperativen Schnellschnittdiagnostik mit einem neuen Verfahren.

The author describes a simplified method for the radiological demonstration of non-palpable breast lesions in operative specimens. The specimen is x-rayed with a wire grid let into the lid of a small plexiglass box. The box with the tissue is then sent to the pathologist. By comparing the radiograph with the specimen, the pathologist is able to orientate himself and to examine the area in question.

[The value of radiographic examinations of the thorax in acute myocardial infarction (author's transl)]. / Zum Stellenwert der Röntgenaufnahme der Thoraxorgane bei akutem Myokardinfarkt.

The degree of pulmonary congestion seen on chest radiographs taken in the intensive care unit was compared with the end-diastolic pulmonary artery pressure in 65 patients with recent transmural myocardial infarcts without cardiogenic shock. There was good correlation between the radiographic appearances and the end-diatrolic pulmonary artery pressure, so that the severity of left heart insufficiency could be diagnosed radiologically at an early stage. Errors were due to the time interval which must pass before the radiographic appearances approximate the haemodynamic changes. This resulted in a diagnostic "phase lag" (following a rise in end-diastolic pulmonary artery pressure) or in a post-therapeutic "phase lag" (after a fall in end-diastolic pulmonary artery pressure). Repeated examinations allow one to recognize changes in the haemodynamics. One should pay particular attention to the features of pulmonary venous and pulmonary arterial hy

Effects of nitric oxide-related agents on alcohol narcosis.

To examine whether nitric oxide (NO) affects alcohol (ethanol) narcosis, adult male rats were pretreated with a NO synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester (NAME); a NOS substrate, l-arginine methyl ester (AME); or a NO donor, isosorbide dinitrate (ISDN); then treated with anesthetic doses (3-5 g/kg, ip) of alcohol. Pretreatment with NAME (30-100 mg/kg, sc) 40 min before alcohol treatment delayed the onset of alcohol-induced loss of the righting reflex (LORR) and increased the duration of the LORR. NAME (100 mg/kg) pretreatment combined with high doses of alcohol (4-5 g/kg) exerted significant lethal effects, even though treatment with either agent alone or NAME combined with lower doses of alcohol (3-3.5 g/kg) was not lethal. Simultaneous treatment with the NOS substrate AME (100 mg/kg, subcutaneous) blocked the effects of NAME on LORR duration times, but did not alter LORR onset times. The NO donor ISDN (30 mg/kg) given by oral gavage 2 hr before alcohol decreased LORR duration times without affecting the onset of LORR. In addition, ISDN dose-dependently inhibited NAME-induced LORR duration increases during alcohol narcosis without significantly altering LORR onset times. Neither ISDN nor NAME significantly altered blood alcohol concentrations. These results suggest that NOS inhibition and subsequent decreases in NO production enhance alcohol-induced narcosis and that increases in NO concentrations inhibit alcohol narcosis, supporting the hypothesis that inhibition of arginine-NOS-NO systems mediates part of the sedative-hypnotic effect of alcohol.

Opioid-induced suppression of rat testicular function.

The effects of opioids on testicular function were assessed in the rat through measurements of serum testosterone levels, testicular interstitial fluid (TIF) formation and TIF testosterone levels after morphine and opioid antagonist (naloxone, naltrexone) treatment. Serum and TIF levels of testosterone were significantly decreased 1 to 6 h after morphine (10 mg/kg) injection, and TIF volumes were decreased 2-3 h after injection morphine. Each of these decreases was dose-related. In contrast to the effects of morphine, the opioid antagonist naloxone increased TIF testosterone but did not alter TIF volumes. Moreover, the opioid antagonist naltrexone totally blocked morphine's effects on both testosterone secretion and TIF volume, suggesting that morphine's testicular effects were mediated by naltrexone-sensitive opioid receptors in the testes. The possible role of morphine-induced reductions in gonadotropin secretion in morphine's testicular effects was also examined. Morphine suppressed testosterone secretion and TIF volumes after pretreatment with human chorionic gonadotropin, which reverses morphine's suppression of luteinizing hormone (LH). Our results, therefore, indicate that morphine exerts effects on testicular function that are independent of its effects on LH. They furthermore support the hypothesis that both endogenous and exogenous opioids disrupt two major aspects of testicular function: Testosterone secretion and TIF formation. Because of the role of TIF in maintaining testicular function, our results suggest that opioid-induced changes in testosterone secretion into TIF and TIF formation may, at least in part, explain the well-established effects of opioids on reproductive endocrinology and function in the male.

Nitric oxide-related agents alter alcohol withdrawal in male rats.

Evidence has been reported supporting the hypothesis that nitric oxide (NO) partially mediates the expression of morphine dependence. To examine whether NO-related agents also affect the expression of alcohol dependence, adult male rats were treated chronically with alcohol. Upon withdrawal of alcohol administration, abstinence signs were observed after treatment with a NO synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (NAME), or a NO donor, isosorbide dinitrate (ISDN). Withdrawal severity was based primarily on the presence and intensity of tremors, rigidity, hyperactivity, and spontaneous and audiogenic convulsions. The NOS inhibitor, NAME (10-100 mg/kg), injected during alcohol withdrawal significantly inhibited withdrawal severity decreasing the intensity of signs of hyperactivity, tremors, and rigidity, but not affecting the occurrence of convulsions. The NO donor, ISDN (30 mg/kg), administered during alcohol withdrawal significantly increased the severity of most withdrawal signs. These results suggest that NO mediates some aspects of the expression of alcohol dependence.

Effects of nitric oxide-related agents on rat testicular function.

The effects of nitric oxide (NO)-related agents on testicular function were examined in male rats with measurements of serum luteinizing hormone, serum testosterone, testicular interstitial fluid (TIF) testosterone, and TIF volumes. Serum and TIF testosterone levels and luteinizing hormone secretion were significantly decreased by the NO donor, isosorbide dinitrate (ISDN), and the NO synthase (NOS) substrate, L-arginine methyl ester, a source for the endogenous production of NO. The effects of ISDN on TIF volumes were inconsistent, but L-arginine methyl ester decreased TIF formation in a dose-dependent manner. In addition, ISDN dose dependently suppressed testosterone secretion stimulated by human chorionic gonadotropin treatment, suggesting that the effects on testosterone secretion were independent of changes in secretion of the endogenous gonadotropin luteinizing hormone. ISDN, L-arginine methyl ester, and the endogenous NOS substrate L-arginine completely blocked testosterone secretion stimulated by the NOS inhibitor NG-nitro-L-arginine methyl ester (NAME), whereas the relatively inactive NOS substrate, D-arginine, only partially blocked NAME-stimulated testosterone secretion. Hydralazine and nicardipine, two vasodilators that do not exhibit prominent NO-related effects, also blocked basal testosterone secretion and testosterone secretion stimulated by the vasoconstrictor NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Antagonism of alcohol-induced suppression of rat testosterone secretion by an inhibitor of nitric oxide synthase.

To examine whether nitric oxide (NO) mediates the suppression of testosterone secretion by alcohol (ethanol), adult male rats were pretreated with a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (NAME), then treated with alcohol. Serum and testicular interstitial fluid (TIF) testosterone concentrations, serum luteinizing hormone (LH) concentrations, blood alcohol concentrations (BAC), and TIF volumes were measured 2 hr after alcohol treatment at a time of peak effects of alcohol and NAME on testosterone secretion. Pretreatment with NAME (30 or 100 mg/kg, subcutaneous) 30 min before alcohol treatment (0.5-3 g/kg, intraperitoneal) completely blocked the alcohol-induced suppression of testosterone secretion into the general circulation and into TIF without significantly altering blood alcohol concentrations (BAC) or TIF volumes. These results support the hypotheses that NO synthase inhibitors can antagonize alcohol-induced suppression of testicular steroidogenesis, that alcohol interacts with arginine-NO synthase systems that regulate testicular steroidogenesis, and that NO is involved in mediating alcohol's testicular and reproductive effects.