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I Rossodivita

Publications and source records attributed to I Rossodivita.

17 recordsLinked to original sources

Age-related changes of sulphide-silver staining in the rat hippocampus.

The influence of ageing on sulphide-silver positive zinc stores was assessed in the stratum radiatum of the CA1-CA3 sub fields of the rat hippocampus and in the molecular layer of the dentate gyrus using a silver amplification histochemical technique associated with microdensitometry. The volume of areas examined for microdensitometry was evaluated as well by quantitative image analysis. Male Sprague-Dawley rats aged 3 months (considered to be young), 12 months (considered to be adult) and 24 months (considered to be old) were used. Microdensitometric analysis of values of sulphide-silver staining corrected for the volume of hippocampal areas investigated revealed no age-dependent changes of staining in the CA1 sub field of the hippocampus. In the CA2 sub field a decrease of sulphide-silver staining was noticeable in aged rats in comparison with younger cohorts. A progressive reduction in the intensity of sulphide-silver staining was observed in the CA3 sub field of the hippocampus. In the molecular layer of the dentate gyrus, the intensity of staining was decreased in adult and old rats in comparison with young animals. These findings indicate a different sensitivity to ageing of histochemically detectable zinc stores of rat hippocampus. The possibility of a specific sensitivity to senescence of different zinc-containing pathways of the hippocampus is discussed.

Aging↗

Use of [3H]-clozapine as a ligand of the dopamine D4 receptor subtype in peripheral tissues.

1. Molecular biology studies have documented the presence of peripheral dopamine D4 receptors. This site has not been characterized yet with classical radioligand binding assay techniques because of the lack of selective radioligands. 2. The atypical neuroleptic clozapine labelled with tritium ([3H]-clozapine) has been proposed and sold as a radioligand for brain dopamine D4 receptors. However, the selectivity of [3H]-clozapine for D4 receptor subtypes, and its specificity for brain dopamine receptors, have been questioned. 3. In this study dopamine D4 receptors were assayed in peripheral organs known to express them, such as rat atria and kidney, by using a radioligand binding assay technique with [3H]-clozapine as the radioligand. Parallel experiments were performed using Chinese hamster ovary (CHO) cells transfected with the D4 receptor clone (variant D4.2). 4. [3H]-Clozapine was bound to sections of rat atria and kidney. After appropriate blockade of sites other than dopamine receptors to which it can bind (i.e. muscarinic cholinergic, serotonergic and alpha-adrenergic receptors), the radioligand was bound to a site displaying a pharmacological profile similar to that expressed by CHO cells transfected with the D4 receptor. 5. The above findings indicate that with appropriate protocols, [3H]-clozapine may represent a radioligand for peripheral dopamine D4 receptors.

Animals↗

Autoradiographic localization of dopamine D2-like receptors in the rabbit pulmonary vascular tree.

In the present study, the pharmacological characteristics and the anatomical localization of dopamine D2-like receptor sites in the extraparenchymal and in the intraparenchymal portion of the rabbit pulmonary artery were investigated using combined radioligand binding and light microscope autoradiography with [3H]-spiroperidol (spiperone) as a ligand. The ligand was bound to sections of the pulmonary artery in a manner consistent with the labelling of dopamine D2-like receptors with an equilibrium dissociation constant (Kd) of about 2.4 +/- 0.07 nmol/l and a maximum density of binding sites of 65 +/- 4.5 fmol/mg tissue. In contrast, binding experiments made with sections of rabbit lung did not allow the evaluation of specific binding. Light microscope autoradiography showed the development of specific silver grains within the tunica adventitia of extraparenchymal branches of rabbit pulmonary artery and of large and, to a lesser extent, of medium-sized intraparenchymal branches of the pulmonary artery. No silver grains were found within small branches of the pulmonary artery or of the pulmonary vein. Development of adventitial silver grains was inhibited by compounds active at dopamine receptors. The greater sensitivity to displacement by domperidone, haloperidol, (-)-sulpiride and bromocriptine than to displacement by N-propyl-norapomorphine, quinpirole or clozapine suggests that the [3H]-spiroperidol binding sites observed in extraparenchymal, large and medium-sized branches of the pulmonary artery belong, probably, to the dopamine D2 receptor subtype. The possible pre-junctional localization of these sites is discussed.

Animals↗

Interactions between endothelin and the dihydropyridine-type calcium antagonist nicardipine in the human renal artery: a radioligand and autoradiographic study.

The interactions between dihydropyridine Ca2+ channels and endothelin were analysed using combined radioligand binding and autoradiographic techniques. Endothelin is a potent constrictor peptide of arterial smooth muscle. Endothelin-induced vasoconstriction is attenuated by dihydropyridine-type Ca2+ antagonists such as nicardipine. However, the molecular mechanisms of this effect are not yet understood. Sections of the human renal artery bound [3H]-nicardipine in a manner consistent with the labelling of dihydropyridine-type Ca2+ channels. The highest density of [3H]-nicardipine binding sites occurred within the tunica media of the renal artery, probably over smooth muscle. A lower density of [3H]-nicardipine binding sites was noticeable in the tunica adventitia, whereas no specific binding occurred in the tunica intima. Endothelin-1, from a concentration of 1 pM l-1, reduced [3H]-nicardipine binding as a function of concentration. A 10 nM endothelin concentration reduced [3H]-nicardipine binding by about 85%. The isoform, endothelin-3, had little effect on [3H]-nicardipine binding. The above findings suggest the occurrence of an interaction, probably at the receptor level, between [3H]-nicardipine binding and endothelin-1. This interaction probably accounts for the attenuation of endothelin-1-elicited vasoconstriction induced by nicardipine.

Aged↗

Influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats.

The present study was designed to assess the influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats (SHR). Twelve week male SHR were used in this study. One group was treated with a daily dose of 5 mg/Kg of darodipine, while the control group of SHR was treated with placebo. Age-matched normotensive Wistar Kyoto (WKY) rats were used as a reference group. After 12 weeks of treatment the rats were sacrificed. The brains and the hearts were removed, embedded in resin, cut and used for light microscope analysis. Darodipine treatment reduced blood pressure in SHR. Morphometric analysis of different sized pial and coronary arteries revealed decreased arterial lumen in SHR in comparison with WKY rats. The area occupied by the tunica media and the media-to-lumen ratio were increased in SHR in comparison with WKY rats. In darodipine-treated rats the area occupied by the arterial lumen was increased in comparison with control SHR, whereas the area occupied by the tunica media and the media-to-lumen ratio were decreased. Pial arteries were more sensitive than coronary arteries to darodipine treatment. Medium and small sized pial and coronary arteries were most sensitive to darodipine treatment. Large-sized coronary artery branches were unaffected by pharmacological treatment. The above results suggest that treatment of SHR with darodipine is able to reduce high blood pressure and to counter the development of structural changes of pial and coronary arteries noticeable in SHR. The higher sensitivity of the cerebral vasculature to darodipine treatment is discussed.

Animals↗

Changes in glutathione content and localization in rat heart as a function of age.

The influence of aging on glutathione levels and distribution in the heart was studied in male Sprague-Dawley rats of 3 (young), 12 (adult) and 24 (old) months of age using biochemical and histofluorescence techniques, respectively. Biochemical assays of reduced glutathione (GSH) in the right and left ventricles and in the septum showed a significant decrease in GSH levels in adult in comparison with young animals. No further changes were noticeable between adult and old rats. GSH histofluorescence revealed a rather homogeneous distribution of the product of histochemical reaction within both right and left atria in 3-month-old rats. In 12-month-old rats a reduction of GSH histofluorescence in comparison with younger animals was noticeable. The loss is more consistent in the epicardial portion of the right atrium and in the endocardial region of the left atrium. In the atria of 24-month-old rats GSH reactivity was homogeneously distributed throughout the atrial wall and was significantly lower than in young or adult rats. In 3-month-old rats GSH histofluorescence was slightly lower in the epicardial than in the endocardial portions of both ventricles. In adult rats a significant decrease of GSH histofluorescence was noticeable in comparison with 3-month-old rats. The loss is particularly pronounced within the endocardial region of the left ventricle. In 24-month-old rats GSH histofluorescence showed no significant differences between adult rats. However, GSH was more homogeneously distributed throughout the ventricular wall than in adult animals. The significance of these data is discussed in relation to the role that GSH plays in protecting the myocytes against free radical damage.

Aging↗

Dopamine receptors mediating inhibition of the cyclic adenosine monophosphate generating system in the rat renal cortex.

1. In vitro addition of dopamine (DA) or of DA-1 receptor agonists increases 3'- 5'-cyclic adenosine monophosphate (cAMP) levels through the stimulation of DA-1 receptors. 2. Although receptor binding studies suggest the existence of DA-2 receptors in the renal cortex, the presence of DA receptors negatively coupled to cAMP generation (DA-2 effect) has not been so far characterized. 3. In this study we have shown that the addition of DA plus the selective DA-1 receptor antagonist SCH 23390 to membrane fractions of rat renal cortex decreased cAMP concentration below basal levels. 4. DA-2 receptor responses were also elicited with the DA-2 receptor agonists bromocriptine and quinpirole in the absence of SCH 23390. These inhibitory effects on cAMP generation were abolished by the DA-2 receptor antagonist 1-sulpiride. 5. The above findings are indicative of the existence in the rat renal cortex of DA-2 receptors showing an effect upon cAMP generation similar to that found in the brain and in several peripheral tissues.

Animals↗

Vasoactive intestinal polypeptide receptors in rat cerebral vessels: an autoradiographic study.

1. Localization and pharmacological properties of the vasoactive intestinal polypeptide (VIP) receptors in rat circle of Willis arteries and in the arteries of pial-arachnoid membrane were studied using light microscope autoradiography combined with radioreceptor binding techniques. 2. [125I]-VIP was specifically bound to sections of rat cerebral arteries with a dissociation constant value of 0.5 nM and a binding site density of 80 fmol mg protein-1. Radioreceptor binding experiments revealed that the binding characteristics of [125I]-VIP were consistent with the labelling of specific VIP receptors. The rank order of potency of various substances tested to inhibit [125I]-VIP binding was the following: VIP greater than peptide histidine methionine greater than secretin greater than glucagon. 3. Light microscope autoradiography revealed the localization of [125I]-VIP binding sites in the medial layer of circle of Willis and pial arteries. Quantitative determination of [125I]-VIP binding site density in the different circle of Willis arteries demonstrated a higher accumulation of silver grains in the anterior than in the posterior cerebral arteries. Pial arteries are richer in VIP receptor sites than circle of Willis arteries. 4. These results suggest that the physiological neurogenic vasodilation elicited by VIP on cerebral arteries is mediated by the interaction with specific receptor sites located primarily within cerebral vessels structures involved in the control of cerebrovascular resistances.

Animals↗

In situ hybridization and immunocytochemistry of alpha1-adrenoceptors in human peripheral blood lymphocytes.

1 alpha1-Adrenoceptor subtypes were investigated in cytospin centrifuged preparations of human peripheral blood lymphocytes by in situ hybridization and immunocytochemistry. 2 In situ hybridization cytochemistry revealed alpha1A-, alpha1B-, and alpha1D-receptor mRNA in human peripheral blood lymphocytes. Lymphocytes hybridized for alpha1A receptor subtype represented approximately 30% of total lymphocytes, those hybridized for alpha1Beta- and alpha1D-receptor subtypes averaged 42 and 25% of total lymphocytes, respectively. 3 Cytospin centrifuged lymphocytes exposed to anti-alpha1A-, alpha1Beta- or alpha1D-receptor protein antibodies, developed specific immunostaining. Approximately 27% of total lymphocytes were immunoreactive for alpha1A-receptor protein, 40% displayed alpha1B-receptor protein immunoreactivity and 22% alpha1D-receptor protein immunoreactivity. Analysis of percentages as well as of lymphocyte morphology of in situ hybridized and immunolabelled lymphocytes suggests the co-expression of mRNA receptor signal and protein receptor immunostaining in the same lymphocyte. 4 The demonstration of both alpha1-adrenoceptor mRNA and receptor protein subtypes suggests that alpha1-adrenoceptors may have a role in regulating lymphocyte function. 5 The possibility of demonstrating receptor protein immunoreactivity in a small amount of blood, such as that required for preparing cytospin-centrifuged lymphocytes, may stimulate research to evaluate the role of these receptors in lymphocytes and to establish if assessment of lymphocyte alpha1-adrenoceptors may represent a marker of their status in health and disease.

Adult↗

The dopaminergic system in hypertension.

Dopamine exerts cardiovascular and renal actions mediated through interaction with specific dopamine receptors. Dopamine receptors are cell surface receptors coupled to G-proteins and classified into two main super families based on biochemical, pharmacological and molecular characteristics. The dopamine D1-like receptor super family includes D1 and D5 receptors, known also in rodents as D1A and D1B sites. These receptors are linked to stimulation of adenylate cyclase. The dopamine D2-like receptor super family includes D2, D3 and D4 receptors. These receptors are linked to inhibition of adenylate cylase or not related with this enzyme activity. They also interfere with opening of Ca+2 channels and are linked to stimulation of K+ receptors. Dopamine receptor subtypes are expressed in brain as well as in extracerebral structures such as the heart, blood vessels, carotid body, kidney, adrenal gland, parathyroid gland and gastrointestinal tract. In the kidney, which represents the peripheral organ where dopamine receptors were more extensively investigated, dopamine receptors are involved in regulation of hemodynamic, electrolyte and water transport, as well as renin secretion. Hypertension-related dopamine receptor changes were also investigated primarily in the kidney. Defective renal dopamine production and/or dopamine receptor function have been reported in human primary hypertension as well as in genetic models of animal hypertension. There may be a primary defect in D1-like receptors and an altered signalling system in the proximal tubules that lead to reduced dopamine-mediated effects on renal sodium excretion in hypertension. Studies on the influence of hypertension on dopamine D2-like receptors are sparse Disruption of either D1A or D3 receptors at the gene level causes hypertension in mice. Using peripheral blood lymphocytes as possible markers of the status of dopamine receptors in essential hypertension, no changes of dopamine D1-like receptors were noticeable, whereas an increase of dopamine D2-like receptors likely representing an up-regulation mechanism was reported. Available information collectively indicates an involvement of peripheral dopaminergic system in hypertension consisting either in impaired receptor transduction mechanisms and/or in receptor loss. A better knowledge of molecular bases of these changes may contribute to the development of specific therapeutic approaches in the future.

Animals↗

Neurotrophins and neurotrophin receptors in human pulmonary arteries.

The localization of neurotrophins (NTs) and NT receptors was analyzed in sections of human extra- and intrapulmonary arteries by Western blot analysis and immunohistochemistry. In extrapulmonary branches of human pulmonary artery, NT and NT receptor immunoreactivity was located in the tunica intima, within endothelium, in the tunica media, within smooth muscle and in the tunica adventitia. In different sized intrapulmonary arteries, NT and NT receptor immunoreactivity was observed primarily in the tunica adventitia. A faint NT and NT receptor immunoreactivity was observed in the tunica media of large-sized branches of intrapulmonary arteries, but not within medium- or small-sized intrapulmonary vessels or in tunica intima of different sized intrapulmonary arteries. These findings suggest that NTs may have a role in the control of vascular responses in the pulmonary system acting as local paracrine or autocrine mediators. The possible relevance of the NT system in human pulmonary vasculature identified in this study is discussed.

Adolescent↗

[Angiodysplasia of the colon].

The Authors report their experience with a case of angiodysplasia of the colon. It is outlined how these lesions can be demonstrated by angiography and colonoscopy. The pathophysiology, diagnosis and management are discussed as well.

Aged↗

Autoradiographic localization of peripheral [3H]-hydergine binding sites.

The anatomical distribution of the ergot derivative [3H]-hydergine (co-dergocrine mesylate) was analyzed by the use of an in vitro autoradiographic technique on frozen sections of rat heart, mesenteric and renal arteries, adrenal gland and kidney. In the heart, [3H]-hydergine was bound by atria and by myocytes of ventricles. In the arterial wall, the drug was bound primarily by the adventitia, by the adventitia-media border and by the intimal layer. The density of adventitial and adventitial-medial binding sites has an inverse relation with the diameter of mesenteric or renal vessels. In the adrenal gland, [3H]-hydergine was bound primarily by the medulla and, in lesser amounts, by the zona glomerulosa. In the kidney, the drug was localized within the arterial tree as well as in cortical tubules and in medullary collecting tubules. The above findings suggest that [3H]-hydergine is bound by various structures involved in the regulation of cardiovascular homeostasis. Interaction with these sites probably accounts for the antihypertensive action of hydergine.

Adrenal Glands↗