Effects of endocrine disruptors on prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part III: Cyproterone acetate and vinclozolin as antiandrogens.

The effects of suspected endocrine disrupting chemicals on freshwater and marine prosobranch species were analysed in laboratory experiments. In this last of three publications, the responses of the fresh water snail Marisa cornuarietis and of two marine prosobranchs (Nucella lapillus, Nassarius (Hinia) reticulatus) to the antiandrogenic model compounds cyproterone acetate (CPA) and vinclozolin (VZ) are presented. The snails were exposed to nominal CPA concentrations of 1.25 mg/L alone and simultaneously to a potent synthetic estrogen (ethinylestradiol), androgen (methyltestosterone) or an indirectly acting xeno-androgen (tributyltin) in experiments with adult specimens and in a life cycle test for 12 months. Marisa and Nucella were furthermore exposed to nominal concentrations of 0.03-1.0 microgram VZ/L for up to 5 months. The antiandrogens induced a number of biological responses in all three species. The length of the penis and of accessory male sex organs (e.g., penis sheath, prostate) were significantly reduced. For Marisa, this effect occurred only in sexually immature specimens and was reversible as the males attained puberty. Typical androgen-mediated responses (imposex development, delayed spermatogenesis, tubulus necrosis of the testis with orchitis and Leydig cell hyperplasia) were partially or totally suppressed by a simultaneous administration of CPA. In the two marine species even adult, sexually mature males responded to antiandrogens with a reduction of the male sex organs and an advancement of the sexual repose phase. The results for CPA and VZ are compared with the effects of an exposure to xeno-estrogens (bisphenol A, octylphenol) and xeno-androgens (triphenyltin, tributyltin) in the same species. Each group of endocrine disruptors induces a characteristic set of toxicological effects in prosobranch snails which can be used as endpoints in an organismic invertebrate test for the identification of endocrine mimetic test compounds. Estrogens cause primarily an induction of superfemales resulting in an increased female mortality by the enhancement of spawning mass and egg production. The main effects of androgens are a virilization of females by imposex development and a marked decrease of the fecundity. Compared with estrogens and androgens, the antiandrogen responses seem to be less drastic and might have--in contrast to the two other disruptor classes--no biologically significant effects at the population level.

Simultaneous bilateral contrast transcranial doppler monitoring in patients with intracardiac and intrapulmonary shunts.

The prevalence of a right-to-left intracardiac shunt, demonstrated by echocardiography and transcranial Doppler sonography has been shown to be higher in stroke patients than in normal controls. The aim of this study was to assess the sensitivity and specificity of contrast transcranial Doppler sonography in comparison to transesophageal echocardiography in the detection and differentiation of intracardiac and intrapulmonary shunts and to correlate the transcranial Doppler findings with clinical outcome and morphological findings. Forty five consecutive stroke patients with suspected paradoxical embolism were entered into the study. In all 25 patients with middle cerebral artery stroke of the left (56%) or right (44%) territory and echocardiographic demonstrated patent foramen ovale (80%) or intrapulmonary shunt (20%), simultaneous bilateral transcranial Doppler sonography of the middle cerebral arteries was performed after contrast medium injection during rest and valsalva straining under standardized and optimized conditions. Overall sensitivity for the detection of a right-to-left shunt by contrast transcranial Doppler sonography was 97% and overall specificity was 70%. Bilateral appearance of microbubbles, microbubble count and time delay of microbubble appearance significantly increased after valsalva straining. In patients with intracardiac shunts, a significantly higher microbubble count (32 vs. 13 in patients with an intrapulmonary shunt) and a shorter time interval of microbubble appearance (11 vs. 14 s in patients with intrapulmonary shunts) was observed. There was no correlation between the side and numerical distribution of microbubble count and the location and severity of the current clinical symptoms, as well as between microbubble count and presence and hemispherical distribution of brain infarcts. Transcranial Doppler sonography is a highly sensitive method for the detection of right-to-left shunts, whether of cardiac or pulmonary location. However. no correlation was found between the side and number of microbubbles counted and the clinical symptomatology.

[Evaluation of vascular risk factors in patients with Parkinson syndrome]. / Evaluation vaskulärer Risikofaktoren bei Patienten mit Parkinson-Syndrom.

A vascular etiology of Parkinson's disease (PD) has been long debated. In order to search for an ischemic basis of PD we assessed the clinical symptomatology of a consecutive group of 60 PD patients and compared their frequency of cerebrovascular risk factors, carotid atherosclerosis and ischemic brain lesions with age-matched groups of stroke patients and normals. There were 16 (27%) subjects with PD who also had symptoms of cerebrovascular disease. The frequencies of carotid stenoses, ischemic brain lesions and most of cerebrovascular risk factors seen in the latter group was comparable with those of stroke patients and significantly higher than in the investigational subsets of patients with "pure" PD and normals. Only one (1.6%) individual with PD presented signs suggestive of an ischemic etiology of parkinsonism. These findings suggest that cerebrovascular disease occurs in approximately one fourth of patients with PD, but seldomly is causally related.

EEG, CT and neurosonographic findings in patients with postischemic seizures.

Seventy-two patients with postischemic seizures were evaluated with electroencephalography (EEG), computerized tomography (CT) and neurosonography. There were 24% early-onset and 76% late-onset initial seizures. Early-onset seizure was more likely to be simple partial (53%), whereas late-onset seizure was more likely to be primarily generalized (56%). 76% early-onset and 80% late-onset seizures were single. Status epilepticus was more frequent in early-onset that late-onset seizures (p = 0.023). The possibility of recurrence was greater in late-onset than early-onset seizures (p < 0.001). 88% patients had EEG abnormalities, and the most common finding was focal slowing. 75% patients had cerebral infarctions on CT scan, and the majority of them involved cortex. 89% postischemic seizures had carotid lesions which mostly were carotid plaques < 50%. We failed to find these data to be useful in predicting the time of onset of initial seizures after acute ischemic stroke and recurrence.

[Effect of head rotation on the vertebrobasilar system. A transcranial Doppler ultrasound contribution to the physiology]. / Einfluss der Halsdrehung auf das vertebrobasiläre System. Ein transkraniell-dopplersonographischer Beitrag zur Physiologie.

Examination of the vertebrobasilar system until a short time ago was possible only by invasive and therefore potentially harmful techniques. The results of these studies were also contradictory. The objective of the present study was to determine how blood flow velocity differed in the vertebral arteries during head rotation in normal subjects. The origin of cervical vertigo essentially involves three components that are difficult to distinguish. There are the sensory proprioceptive, vascular and sympathicotonic components. Use of transcranial Doppler sonography (TCD) has now made it possible to measure the flow velocity of the vertebral arteries. In 17 normal probands without vertigo or cervical nystagmus, the mean diameters of the vertebral arteries were measured by means of duplex scanning. TCD was used to determine the mean flow velocities of the vertebral arteries in a median position and after head rotations of 30 degrees and 60 degrees to the left and right. Blood flow velocities in both vertebral arteries were not altered by head rotation. This observation contrasted with that of other publications, which were mainly based on cadaver findings. The results of this study form the basis for further investigations on symptomatic patients with recurring cervical nystagmus and cervical vertigo.