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Biomedical subjects

A Morelli

Publications and source records attributed to A Morelli.

At least 253 records · Page 14Linked to original sources

Chromatic perception in relation to an hypothesized cerebral dominance.

On the basis of the cerebral dominance, we have hypothesized an asymmetry (for saturation or brightness) between the two eyes in perception of chromatic stimuli. 51 subjects were tested on chromatic perception (green, red, yellow, blue). For each subject also an ocular-dominance score was obtained. The results substantially confirmed the hypothesis of cerebral dominance in color perception. Subjects with high ocular-dominance scores (right- or left-dominant subjects) showed for the green stimulus asymmetric behavior, while subjects with low ocular-dominance scores showed a tendency toward symmetry in perception.

Adult↗

Transition from nutcracker esophagus to diffuse esophageal spasm.

The nutcracker esophagus is a newly defined subset of primary esophageal motility disorders that can be responsible for dysphagia and/or chest pain. Any possible relationship between this entity and diffuse esophageal spasm is poorly understood. Herein we report a case of nutcracker esophagus that showed a transition to classical diffuse esophageal spasm during 1 year follow-up. This transition supports the hypothesis that nutcracker esophagus and diffuse esophageal spasm may be related disorders.

Deglutition Disorders↗

Nifedipine reduces the colonic motor response to eating in patients with the irritable colon syndrome.

Patients with the irritable colon syndrome have an exaggerated and/or prolonged colonic motor response to eating. This is believed to be the cause of their postprandial complaints. Since the flux of calcium ions across cell membranes plays a major role in the contractions of the gastrointestinal smooth muscle, we investigated the effect of nifedipine, a calcium channel blocker, on the gastrocolonic response in nine patients with the irritable colon syndrome. Colonic myoelectric and contractile activity was recorded during fasting and after a 1000-cal mixed meal, either with or without nifedipine (20 mg sublingually) administration. Nifedipine reduced the postprandial increase of both spike potential activity and motility index. This effect of acute administration of the drug provides rational support to test nifedipine in clinical trials as a possible means for treating the irritable colon syndrome.

Action Potentials↗

Prominent role of DT-diaphorase as a cellular mechanism reducing chromium(VI) and reverting its mutagenicity.

Rat liver postmitochondrial (S-12) fractions accounted for the bulk of the activity of whole cell homogenates in reducing chromium(VI) and accordingly in decreasing its mutagenicity. Both cytosolic (S-105) and microsomal fractions concurred to this process, which in all subcellular preparations tested was selectively induced by phenobarbital and especially by Aroclor 1254, but not by 3-methylcholanthrene. Cytosolic fractions were markedly more efficient in reducing chromium(VI) than microsomal fractions recovered from the same amount of tissue (liver or lung), although the latter preparations had a higher specific activity. The microsomal activity was exclusively NADPH dependent. A minor part of the cytosolic reduction was determined by nonenzymatic components, notably by some electron donors and chiefly by reduced glutathione, which proved to reduce chromium(VI) at physiological concentrations. However, also in cytosolic fractions, the most important contribution to chromium reduction was enzyme catalyzed, as shown by the following properties: thermolability; requirement for exogenous NADH or NADPH [supplied as such or in the form of a NADPH-generating system (S-9 mix)]; and saturation by chromium(VI). The likely involvement of DT-diaphorase in this metabolic process is supported by several findings, including its sharp pH dependence and its partial suppression by known inhibitors of this enzyme protein, such as p-chloromercuribenzoate, L-thyroxine, and dicumarol (which conversely did not counteract the metabolic deactivation of the other direct-acting mutagens 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine 2HCl and epichlorohydrin). Similarly, cytosolic reduction of chromium(VI) was partially inhibited by selective metabolic depletors of both coenzymes of DT-diaphorase, i.e., NADPH and NADH. Pretreatment of rats with enzyme inducers (phenobarbital and 3-methylcholanthrene) stimulated the activity of DT-diaphorase in liver cytosolic fractions. A dramatic stimulation (35 to 40 times over untreated controls) was produced by Aroclor 1254, which also coinduced the liver cytosolic activity of enzymes involved in the glucose 6-phosphate-dependent pathway of both nicotinamide-adenine-dinucleotide phosphate and glutathione reduction (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase). In the lung cytosol, a slight yet significant stimulation of some of these enzyme activities was determined by the daily intratracheal instillations of high doses of chromium(VI) itself for 4 weeks, a condition which has been found to enhance the pulmonary metabolism of this metal ion.

Animals↗

Palliative surgery in irreparable lesions of the peroneal nerve.

The operation of transposition of tibialis posterior into tibialis anterior is indicated in irreparable lesions of the peroneal nerve. The authors present a critical review of 16 cases submitted to this operation during the last 5 years using the Barr technique. This is described in detail. Evaluation of the overall results shows this to be an excellent procedure in such cases.

Adolescent↗

Favism: a hemolytic disease associated with increased superoxide dismutase and decreased glutathione peroxidase activities in red blood cells.

Red blood cells of favism patients with acute hemolytic crisis have markedly more superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and less glutathione peroxidase (glutathione:hydrogenperoxide oxidoreductase, EC 1.11.1.9) than either normal controls, glucose-6-phosphate dehydrogenase-deficient subjects or favism patients outside hemolytic crisis. This altered value of the two enzyme activities is not due to increased reticulocyte content of blood. The electrophoretic triplet pattern of superoxide dismutase is also changed, with significant increase of the most positively charged band. Similar modifications of the two enzyme activities are observed after treatment of normal red blood cells with high concentrations of divicine and ascorbate, which are redox compounds that are contained in fava seeds. This treatment produces no hemolysis, but leads to hemolysis if the treated cells are resuspended in the homologous plasma. These results suggest a possible role of active oxygen species in the development of favism.

Ascorbic Acid↗

G6PD Cagliari: a new low activity glucose 6-phosphate dehydrogenase variant characterized by enhanced intracellular lability.

A new variant of human erythrocyte glucose 6-phosphate dehydrogenase (G6PD), designated G6PD Cagliari, has been characterized. It is associated with severe enzyme deficiency and can be placed in Class 2 of the usual tabulation of G6PD variants. The specific activity of this variant is near normal, while its decay within the circulating erythrocytes is very rapid compared with normals. Genetic analysis of the family of the propositus indicated that the two available females are heterozygotes characterized by extremely unbalanced mosaic phenotypes.

Adolescent↗

In vitro effects of N-acetylcysteine on the mutagenicity of direct-acting compounds and procarcinogens.

N-Acetylcysteine (NAC), reduced (GSH) and oxidized (GSSG) glutathione were negative in the Ames test with 7 Salmonella strains, while L-cysteine was activated by rat liver S-9 fractions to metabolites mutagenic to strains TA102, TA97 and TA100. The mutagenic response in S. typhimurium strains (TA1535, TA98, TA100, TA102) and the levels of enzyme activities, responsible for NADP+ or GSSG reduction and for the utilization of NADPH or GSH in rat liver S-9 fractions, were investigated following in vitro preincubation of NAC with four direct-acting mutagens and six procarcinogens. Treatment with this nucleophilic and reducing compound resulted in a dose-related decrease of the direct mutagenicity of epichlorohydrin, hydrogen peroxide and, sharply, of 4-nitroquinolino-N-oxide and sodium dichromate. The mutagenicity of these compounds, both in the absence and in the presence of NAC, was decreased by rat liver S-9 fractions and to some extent by lung S-9 fractions. A diphasic effect was observed in the case of procarcinogens (cyclophosphamide, 2-aminofluorene, cigarette smoke condensate, Trp-P-2, aflatoxin B1 and benzo[a]pyrene), i.e., an enhancement of S-9 requiring mutagenicity at intermediate NAC doses, which could be ascribed to metabolic factors acting in vitro, and a loss of mutagenicity at high NAC doses, which could be ascribed to trapping of electrophilic metabolites. Out of the five S-9 enzyme activities under study, i.e., glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme, GSH peroxidase and GSSG reductase, only the last one showed significant changes following mutagen and/or NAC treatment.

Acetylcysteine↗

Mediterranean glucose 6-phosphate dehydrogenase (G6PD) deficiency--near normal decay of the mutant enzyme protein in circulating erythrocytes.

Complete removal of leucocytes and platelets from erythrocytes and the development of a sensitized procedure for the assay of G6PD activity allowed the biochemical mechanisms of the Mediterranean variety of G6PD deficiency to be re-evaluated. Activity in the young erythrocytes from 9 G6PD-deficient subjects averaged 0.1% of the levels observed in the corresponding erythrocyte fraction from normal individuals: moreover, the decline of activity during aging of the G6PD-deficient erythrocytes was comparable with that observed for the normal enzyme. Mutant G6PD purified from granulocytes of a G6PD-deficient subject and entrapped within the corresponding erythrocytes was remarkably stable. Exposure of native erythrocytes to an oxidative stress (divicine plus ascorbate) resulted in a decrease of G6PD activity that was significantly more rapid and extensive in control than in G6PD-deficient cells. These results seem to exclude enhanced intracellular breakdown of the mutant protein within the circulating erythrocytes.

Ascorbic Acid↗

The production of activated oxygen species by an interaction of methemoglobin with ascorbate.

Ascorbate reacts with methemoglobin to produce reactive oxygen species, most probably hydroxyl radicals. The main features of this system are: a) disappearance of ascorbate; b) consumption of oxygen with an ascorbate/O2 stoichiometry of 2:1; c) requirement of unliganded heme iron; d) formation of H2O2. The proposed mechanism involves an ascorbate-mediated interconversion of methemoglobin and oxy-hemoglobin, resulting in the production of H2O2. This product is decomposed by hemoglobin to produce hydroxyl radicals according to a Fenton-like reaction in which ascorbate recycles methemoglobin to hemoglobin. Alternative pathways of formation and of decomposition of H2O2 in this system appear to play a minor role.

Ascorbic Acid↗

Oxidant damage of normal and glucose 6-phosphate dehydrogenase (G6PD)-deficient red blood cells is enhanced by iron-EDTA complex.

A combination of divicine (an aglycone from the fava bean beta-glucoside vicine) and ascorbate results in a marked production of ethylene from methional, as a probable indication of OH radical formation. Addition of iron-EDTA to this oxidising system enhances the ethylene production significantly. The enhancing effect of iron-EDTA is also observed when both normal and Glucose 6-phosphate dehydrogenase (G6PD)-deficient red cells are exposed to the divicine-ascorbate system. Moreover, iron-EDTA magnifies other consequences of oxidant damage afforded by divicine-ascorbate or by ascorbate alone on the target red cells, such as depletion of reduced glutathione, formation of methemoglobin, stimulation of hexose monophosphate shunt activity and lipid peroxidation. Although the biochemical changes induced by this oxidative system are not remarkably different in normal and in G6PD-deficient red cells, the extra-damaging effect of chelated iron might be important in the mechanism of hemolysis.

Ascorbic Acid↗

Structural variants of human glucose 6-phosphate dehydrogenase (G6PD): role of intracellular decay in the expression of deficiency.

The biochemical mechanisms of enzyme deficiency were investigated for two low activity G6PD variants, i.e. G6PD Mediterranean and G6PD Cagliari (a new variant). This study required the complete removal of leukocytes and platelets from blood samples and the use of sensitized procedures for assays of activity. G6PD Cagliari has a highly accelerated decay within circulating RBC and a near normal catalytic efficiency. The deficiency typical of G6PD Mediterranean (approx. 0.1% of the normal levels) is mediated by moderately reduced specific activity, while no clear decay was seen in mature RBC: however, the minute levels of activity that are observed in reticulocytes suggest that a strongly enhanced breakdown takes place during maturation of erythroid cells.

Erythrocyte Aging↗

Endoscopic retrograde cholangiopancreatography study in Alagille's syndrome: first report.

Endoscopic retrograde cholangiopancreatography revealed the association between intra- and extra-hepatic biliary tree hypoplasia in an 8-year-old boy affected by Alagille's syndrome. The patient, in whom chronic cholestasis had been present from birth, presented characteristic facies, retarded growth, hepatomegaly, and splenomegaly. Chromosome studies were normal. HIDA Tc 99m appeared late in the gallbladder and emptied into the bowel after 3 h. Endoscopic retrograde cholangiopancreatography showed marked and diffuse narrowing of the extrahepatic biliary ducts and uniform narrowing of the intrahepatic ducts with reduced arborization. Menghini needle biopsy revealed no interlobular ducts in the portal tracts. The last two techniques confirmed the clinical picture and made surgical diagnosis unnecessary. This is, as far as we know, the first time endoscopic retrograde cholangiopancreatography has been used in the diagnosis of Alagille's syndrome.

Bile Ducts↗