Effects of Ethanol on the Contractile Function of the Heart: A Review

Chronic ethanol consumption leads to a number of alterations in the contractile function of the heart and is a leading cause of cardiomyopathy. Ethanol also has an acute negative inotropic effect mediated by direct interaction with cardiac muscle cells, although this action is often masked by indirect actions resulting from enhanced release of catecholamines in vivo. This article reviews the effects of ethanol on the contractile function of the heart. The specific targets affected by ethanol in cardiac muscle cells are discussed in terms of potential mechanisms underlying the depressions of contractility resulting from both acute and chronic actions of ethanol.     

High-dose epirubicin in chemotherapy refractory non-seminomatous germ cell cancer: a phase II study. EORTC Genito-Urinary Tract Cancer Co-operative Group. EORTC Early Clinical Trials Group.

Eighteen patients with progressive disseminated, platinum-resistant germ cell tumors were treated with epirubicin 135 mg/m2, every 3 weeks. One patient had stable disease, 17 developed progression. Myelosuppression was dose-limiting. One patient died of neutropenic septicemia. High-dose epirubicin is not active against platinum-resistant germ cell cancer.     

Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA-AUT.

We developed a questionnaire to assess autonomic symptoms in patients with Parkinson's disease (PD) and evaluated its reliability and validity. Based on the results of a postal survey in 46 PD patients, 21 multiple system atrophy patients, and 8 movement disorders specialists, items were included according to their frequency, burden, and clinical relevance. The questionnaire was evaluated in 140 PD patients and 100 controls, and test-retest reliability was established in a sample of 55 PD patients. The SCOPA-AUT consists of 25 items assessing the following regions: gastrointestinal (7), urinary (6), cardiovascular (3), thermoregulatory (4), pupillomotor (1), and sexual (2 items for men and 2 items for women) dysfunction. Test-retest reliability was good. Autonomic problems increased significantly with increasing disease severity for all autonomic regions, except sexual dysfunction. We conclude that SCOPA-AUT is a reliable and valid questionnaire that evaluates autonomic dysfunction in PD.     

In-vivo studies on Haemaccel-fibronectin interaction in man

An enzyme-linked immunoassay has been recently set up for direct measurement of the binding capacity of plasma fibronectin to gelatin. This binding capacity could be completely inhibited in vitro by an eight-fold excess of gelatin, of Haemaccel, but not of Geloplasma. On the contrary, the levels of immunoreactive fibronectin measured by laser nephelometry did not change, in presence of 10 to 1000 micrograms ml-1 of gelatin, of Haemaccel or of Geloplasma. When infused into normal volunteers, Haemaccel provoked a strong and immediate inhibition of the plasma fibronectin binding capacity to gelatin. This inhibition was dose-dependent and maximal after infusion of 500 ml of Haemaccel. Twenty-four hours after this infusion, there was a progressive recovery of the gelatin-binding capacity, which was almost completely achieved 96 h later. The formation of complexes between Haemaccel and fibronectin was demonstrated by gel filtration chromatography and by affinity chromatography. Immunoreactive plasma fibronectin levels remained unchanged up to 24 h after infusion of 500 ml of Haemaccel. A transient decline to 50% of its initial value then occurred the second day after the infusion. Therefore, a delay existed between the formation of fibronectin-Haemaccel complexes and their elimination from the bloodstream. This delay decreased when smaller volumes of Haemaccel were infused, which strongly suggests that plasma fibronectin is cleared by means of Haemaccel and does not seem to play a role of opsonin in these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuronal projections to the medial preoptic area of the sheep,with special reference to monoaminergic afferents: Immunohistochemical and retrograde tract tracing studies

The preoptic area contains most of the luteinizing hormone releasing hormone immunoreactive neurons and numerous monoaminergic afferents whose cell origins are unknown in sheep. Using tract tracing methods with a specific retrograde fluorescent tracer, fluorogold, we examined the cells of origin of afferents to the medial preoptic area in sheep. Among the retrogradely labeled neurons, immunohistochemistry for tyrosine hydroxylase, dopamine-β-hydroxylase, phenylethanolamine N-methyltransferase, and serotonin was used to characterize catecholamine and serotonin fluorogold labeled neurons. Most of the afferents came from the ipsilateral side to the injection site. It was observed that the medial preoptic area received major inputs from the diagonal band of Broca, the lateral septum, the thalamic paraventricular nucleus, the lateral hypothalamus, the area dorsolateral to the third ventricle, the perimamillary area, the amygdala, and the ventral part of the hippocampus. Other numerous, scattered, retrogradely labeled neurons were observed in the ventral part of the preoptic area, the vascular organ of the lamina terminalis, the ventromedial part of the hypothalamus, the periventricular area, the area lateral to the interpeduncular nucleus, and the dorsal vagal complex. Noradrenergic afferents came from the complex of the locus coeruleus (A6/A7 groups) and from the ventro-lateral medulla (group A1). However, dopaminergic and adrenergic neuronal groups retrogradely labeled with fluorogold were not observed. Serotoninergic fluorogold labeled neurons belonged to the medial raphe nucleus (B8, B5) and to the serotoninergic group situated lateral to the interpeduncular nucleus (S4). In the light of these anatomical data we hypothesize that these afferents have a role in the regulation of several functions of the preoptic area, particularly those related to reproduction. Accordingly these afferents could be involved in the control of luteinizing hormone releasing hormone (LHRH) pulsatility or of preovulatory LHRH surge.     

Neural plasticity in vivo: opioid sensitivity of memory develops gradually after a septal lesion

Neuronal plasticity can manifest itself in alterations in the sensitivity of memory to the effects of drugs. After the production of a brain lesion, the memory processing of a passive-avoidance task in mice gradually becomes sensitive to the effect of morphine, i.e., an improvement in retention performance is seen after 6 weeks, but not after 1 or 2 weeks. The results presented demonstrate that, even if they lead to no discernible changes in behaviour, plastic processes can still be detected by means of behavioural tests.     

In vitro metabolism of ferroquine (SSR97193) in animal and human hepatic models and antimalarial activity of major metabolites on Plasmodium falciparum.

Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.     

Pilomatrixoma of the eyelid. Apropos of a case]

Primary adnexal tumors of the eyelids are quite uncommon. This diagnosis should be considered in the case of a sub-epidermal tumor. We report the case of a 25-year-old female patient presenting with a left eyelid nodular tumor, which appeared clinically as a whitish swelling of the lateral part of the eyelid, covered by normal epidermis. Ultrasonography showed a heterogeneous structure probably containing calcified areas. Complete surgical removal was performed under local anesthesia. Macroscopically, the tumor was encapsulated, with an irregular surface, and it appeared stony under section. Microscopically, it was characteristic of a pilomatrixoma, with sheets of mummified cells devoid of nuclei, either clear or basophilic, and partially calcified. Neither granulomatous reaction nor ossification were observed. This clinicopathological report recalls that pilomatrixoma may appear as a single nodular tumor of the eyelid.