Neurotransmitter, opiodergic system, steroid-hormone interaction and involvement in the replacement therapy of sexual disorders

Dopamine (DA) and serotonin (5-HT) are the neurotransmitters most directly involved in sexual activity. DA plays a stimulatory role while 5-HT has an inhibitory effect. The two monoaminergic systems modulate the secretion of many hormones (GnRH, LH, testosterone, prolactin and endorphins) involved in sexual functional capacity. Furthermore, hormones influence synthesis and storage of brain neurotransmitters. Impotence can often be associated to clinical depression and altered neurotransmitter function. Moreover, stress represents an unbalance between various neurotransmitter systems and can induce impotence especially when disorders of the endorphinic system are present. Replacement therapy is based upon the understanding of these basic concepts. Impotence due to an underlying depressive illness must be treated with dopaminergic antidepressant drugs; while in stressful conditions a good response to the naloxone test is the preliminary criterion to subsequent naltrexone treatment. When a hormonal deficiency has been proved, the hormone replacement therapy is of course highly effective (gonadotropins in hypogonadotropic syndromes, testosterone in aging, etc.). Finally, idiopathic impotence could be treated by DA agonist and/or 5-HT antagonist drugs either alone or better yet in association with psychotherapy.     

Effects of recombinant human gamma interferon on intracellular survival of Bordetella pertussis in human phagocytic cells

Abstract Several studies have demonstrated that Bordetella pertussis has the ability to enter and survive intracellularly within human polymorphonuclear leukocytes (PMNL) and human monocytes/macrophages. The effects of human recombinant gamma interferon (IFN-γ) on the survival of B. pertussis in PMNL and human monocytes, and on the oxidative burst activity of PMNL and human monocytes in response to B. pertussis were assessed in this study. IFN-γ partially increased intracellular killing of phagocytosed B. pertussis in human monocytes, as determined by an orange acridine-crystal violet assay. In contrast, IFN-γ did not enhance intracellular killing of B. pertussis in PMNL. No significant increase of superoxide production was noted in human monocytes in response to B. pertussis when stimulated with various concentrations of IFN-γ. The partial increase of B. pertussis killing by IFN-γ within monocytes, together with poor production of superoxide may explain how B. pertussis can survive within human phagocytic cells, and thus cause a more prolonged course of the disease.     

Glioblastoma therapy by direct intralesional administration of I-131 radioiodine labeled antitenascin antibodies

Cell Biochemistry and Biophysics - Thirty patients with recurrent glioblastomas (29 brain, 1 spinal cord) received intralesional radioimmunotherapy aiming to control the progression of the tumor...     

Heritability of adult body height: a comparative study of twin cohorts in eight countries.

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.     

Anatomical studies of branchlet abscission related to crown modification in Quercus cerris L.

The basic anatomy of lateral twig insertion onto the main branch in both healthy and damaged Quercus cerris L. trees was studied. An abscission zone is always present: in healthy trees it is formed by a smaller number of cell layers than in damaged ones, where it is more evident with many layers of cells. Cells of the abscission zone are roundish, with many intercellular spaces between them; cell walls are thin, non-lignified and without secondary walls. No starch was found in cells of the abscission zone, where, instead, a few scattered calcium oxalate druses are seen.     

Distribution of15N fertilizer in field-lysimeters sown with garlic (Allium sativum) and foxtail millet (Setaria italica)

We examined the distribution of residual¹⁵N and its uptake by a foxtail millet crop grown in field lysimeters following at previous garlic crops fertilized with either¹⁵N-urea or¹⁵N-ammonium sulphate. Garlic apprently removed more N from the lysimeters treated with urea-N than from those treated with (NH₄)₂SO₄. Fertilizer-N in the lysmeters was similar (ca. 32% of original) following millet harvest. About 16 per cent of both fertilizers in the lysimeters was removed by the millet.     

Calcium changes in immune complex-stimulated human neutrophils. Simultaneous measurement of receptor occupancy and activation reveals full population stimulus binding but subpopulation activation

Immune complexes (ICs) induce an initial transient increase in cytosolic intracellular calcium [( Ca2+]in) levels in human neutrophils (PMN). Changes in PMN [Ca2+]in were measured with the fluorescent calcium indicator Indo-1 ( [1-[2-amino-5-(6-carboxylindol-2-yl]-phenoxyl]-2-(2'-amino-5 '- methylphenoxy]ethane-N,N,N'N'-tetraacetic acid), at the level of individual cells by flow cytometry. Two kinds of immune complexes (ICs) were used in this study: an insoluble (IIC) and a more soluble less valent immune complex (SIC) with fewer available Fc receptor binding ends per molecule of SIC than IIC. Simultaneous binding and activation studies performed on the flow cytometer with fluoresceinated IIC or SIC demonstrated that a majority of the cells bound each stimulus uniformly. However, only an IC dose-dependent proportion of those IC-bound cells responded with an increase in [Ca2+]in. Analysis of Indo-1 fluorescence signals from neutrophils exposed to IIC, corrected for the contribution of the nonresponding population, indicated that every dose of IIC elicited a similar maximum [Ca+2]in within the responding population. In contrast, the magnitude of the increase in [Ca2+]in elicited by low doses of SIC did become dependent on dose. Cells treated with pertussis toxin and exposed to IIC exhibited a normal [Ca2+]in response both in magnitude and expression. Therefore, [Ca2+]in responses induced by immune complexes are expressed by subpopulations of PMN, in a response which is dependent on the valency of the stimulus. In addition, pertussis toxin sensitive G protein(s) appear not to have a major role in IIC-induced [Ca2+]in changes, membrane potential changes, production of superoxide anions, and elastase release.     

Neutrophil hyperpolarization in response to a chemotactic peptide

The chemotactic peptide formylmethionyl-leucyl-phenylalanine (fMLP), at concentrations below 10(-9) M, elicits a sustained increase in the human neutrophil's membrane potential within 10 s of its addition. This hyperpolarization, detected with the fluorescent cationic potentiometric probes, 3,3'-dipentyloxacarbocyanine (diO-C5-(3)), and 1,1'-dipropyl-3,3,3',3'-tetramethylindocarbocyanine iodide (diI-C3-(3)), and with the anionic probe bis-(1,3-diethylthiobarbituric)trimethine oxonol (bis-oxonol), is immediately followed by a large depolarization when [fMLP] greater than 10(-9) M. By extracellular substitution of sodium ions with potassium ions or choline or by pretreatment of the cells with ionophores, we report here that the hyperpolarization is primarily dependent on an intact potassium ion gradient and is accompanied by a concurrent acidification of the cytoplasm (approximately 0.05 pH unit) Although the latter occurs simultaneously with a large, transient increase in cytosolic Ca2+ at [fMLP] greater than 10(-10) M, it occurs without a detectable increase in cytosolic Ca2+ at [fMLP] less than 10(-10) M. The hyperpolarization is neither affected nor initiated by the chemotactic peptide antagonist tert-butyloxycarbonyl-methionyl-leucyl-phenylalanine, whereas the depolarization is completely inhibited. Neutrophils isolated from patients with X-linked chronic granulomatous disease exhibit normal hyperpolarizations and cytosolic Ca2+ increases in response to chemotactic peptides but exhibit no depolarization or oxidative burst. The hyperpolarization appears earlier in the ontogeny of differentiating myeloid precursor cells than either the rise in cytosolic Ca2+ or the depolarization response. Together, these findings indicate that an increase in transmembrane potential is one of the earliest events in the neutrophil response to chemotactic peptides, coinciding temporally with increases in cytoplasmic Ca2+ and H+ concentrations but preceding detectable oxidative burst activity.     

Specific antibodies to bovine choline acetyltransferase raised in mice immunised with small amounts of partially purified enzyme

Choline acetyltransferase was purified approximately 18,000-fold from 300 g of bovine caudate nuclei to a specific activity of 21 μmol min mg protein. The overall procedure used was: extraction of the enzyme by high salt concentration, chromatography on carboxy-methyl-Sephadex, precipitation by ammonium sulphate, affinity chromatography on Blue-Sepharose and, finally absorption on hydroxylapatite. When the enzyme absorbed on hydroxylapatite was injected into mice, it provoked reproducibly a transient production of ‘inhibitory’ antibodies, followed by higher antibody titres mainly of ‘non-inhibitory’ type. These responses were elicited by injecting less than a total of 20 μg of immunogen. The highest antibody titre was obtained less than 2 months following the initial immunisation. Species cross reactivity was investigated. This procedure should prove to be of value in the production of monoclonal antibodies to choline acetyltransferase.