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Biomedical subjects

A Tozzi

Publications and source records attributed to A Tozzi.

At least 19 recordsLinked to original sources

Management and outcomes of hepatic cirrhosis: Findings from the RING study.

BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital admission (OA). The RING study collected hospital discharge files (HDF) from Italian hospital gastroenterology units (IGU). This caselist provides a broad picture of the patients admitted for this pathology. MATERIAL/METHODS: More than 50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS: Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2), HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for all the other pathologies in the same wards. Child-Pugh is a useful prognostic tool, higher classes implying a greater risk of death. HRS and bleeding varices were the complications with most influence on in-hospital mortality.

Journal Article↗

Pyramid sensor for segmented mirror alignment.

We report what is to our knowledge the first laboratory experiment that shows the use of a pyramid wavefront sensor to cophase and align segmented mirrors having three degrees of freedom per segment, i.e., piston, tip, and tilt. In the laboratory the iterative alignment procedure reached a wavefront residual error of about 10 nm. The residual error was equally distributed between piston, tip, and tilt. These results demonstrate that the pyramid can successfully simultaneously sense the piston, tip, and tilt of a segmented mirror. This last feature makes this technique very attractive in phasing and aligning astronomical segmented telescopes such as extremely large telescopes currently under extensive studies.

Journal Article↗

Reversible alopecia universalis during treatment with PEG-interferon and ribavirin for chronic hepatitis C.

The combination of PEG-interferon and ribavirin is currently recommended for the treatment of chronic hepatitis C, which is a common cause of morbidity and mortality worldwide. Hair disorders have often been described during interferon therapy, which include reversible hair discoloration, hypertricosis and alopecia. Ribavirin is reported to cause photoallergic reactions. We report two cases of alopecia universalis, with complete hair loss extended to the whole body, secondary to PEG-interferon and ribavirin combination therapy for chronic hepatitis C virus infection. Both female patients were infected by genotype 1 and presented alopecia during the second half of a 48-week therapy, concurrently with low levels of ferritin and thyroid dysfunction (patient 1) or depression (patient 2). Patient 1 withdrew from the therapy on week 26 and, due to the occurrence of maculo-erythematous cutaneous eczema, underwent corticosteroid therapy with complete hair regrowth. Patient 2 completed the scheduled therapy and showed a spontaneous complete hair regrowth. It should be noted that in spite of an early (within 4 weeks of therapy) virological response, patient 1 had a disease relapse after therapy withdrawal and corticosteroid therapy, while patient 2 maintained a sustained virological response. In conclusion, interferon therapy may trigger reversible alopecia universalis in susceptible patients. However, given the benign and reversible nature of this side effect, patients who achieve a virological response should be strongly advised to complete the treatment in order to prevent disease relapse.

Adult↗

Depression of mGluR-mediated IPSCs by 5-HT in dopamine neurons of the rat substantia nigra pars compacta.

Dopamine neurons of the substantia nigra pars compacta receive a prominent serotonin (5-HT) projection from the dorsal raphe nucleus and important functional interactions between the serotonergic and the dopaminergic system have been postulated. In the present report we examined the role of 5-HT in the modulation of the metabotropic glutamate receptor-mediated inhibitory postsynaptic current (mGluR-IPSC) in midbrain dopamine neurons, and we found a reversible depression of this synaptic response at concentrations of 5-HT ranging from 100 nm to 30 microm (EC50 1.06 microm). This resulted in a shift towards excitation of the overall dopamine neuron response to glutamatergic synaptic input. This effect was not because of a direct modulation of the Ca2+-sensitive K+ conductances underlying the mGluR-IPSC, but was associated with a decrease in the intracellular calcium signal triggered by mGluR stimulation. Similar results were obtained with alpha-methyl-5-hydroxytryptamine and 5-methoxytryptamine, but not with 5-carboxamidotryptamine or 1-(3-chlorophenyl) piperazine. No significant depression of the mGluR-IPSC by 5-HT was observed in the presence of the 5-HT2 antagonist cinanserin or the 5-HT4 receptor antagonist RS 23597-190, whereas the 5-HT2C antagonist RS 102221 was ineffective. Our results demonstrate a powerful inhibition of the mGluR-IPSC by 5-HT in midbrain dopamine neurons, most probably through stimulation of 5-HT2A and 5-HT4 receptors.

Animals↗

Group I mGluRs coupled to G proteins are regulated by tyrosine kinase in dopamine neurons of the rat midbrain.

Metabotropic glutamate receptors (mGluRs) modulate neuronal function via different transduction mechanisms that are either dependent or independent on G-protein function. Here we investigated, using whole cell patch-clamp recordings in combination with fluorimetric measurements of intracellular calcium concentration ([Ca(2+)](i)), the metabolic pathways involved in the responses induced by group I mGluRs in dopamine neurons of the rat midbrain. The inward current and the [Ca(2+)](i) increase caused by the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG, 100 microM) were permanently activated and subsequently abolished in cells loaded with the nonhydrolizable GTP-analogue GTP-gamma-S (600 microM). In addition, when GDP-beta-S (600 microM) was dialyzed into the cells to produce the blockade of the G proteins, the DHPG-dependent responses were reduced. When the tissue was bathed with the phospholipase C inhibitor 1-[6[[(17 beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]exyl]-1H-pyrrole-2,5-dione (10 microM), the DHPG-induced calcium transients slightly diminished but the associated inward currents were not affected. Interestingly, a substantial depression of the DHPG-induced inward current and transient increase of [Ca(2+)](i) was caused by the protein tyrosine kinase inhibitors tyrphostin B52 (40 microM) and 4',5,7-trihydroxyisoflavone (genistein; 40 microM), whereas genistein's inactive analogue 4',5,7-trihydroxyisoflavone-7-glucoside (40 microM) was ineffective. The blockade of the Src family of tyrosine kinase by 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (20 microM), mitogen-activated protein kinase by 2'-amino-3' methoxyflavone (50 microM), and protein kinase C by staurosporine (1 microM) had no effect on the cellular responses caused by DHPG. The mGluR5-selective antagonist 2-methyl-6-(phenylethynyl)-pyridine (10--100 microM) did not affect the actions of DHPG. Thus our results indicate that the responses, mainly mediated by mGluRs1 in dopamine neurons, are activated by intracellular mechanisms coupled to G proteins and regulated by tyrosine kinases.

Animals↗

The EUVAC-NET project: creation and operation of a surveillance community network for vaccine preventable infectious diseases.

The EUVAC-NET network is in charge of the epidemiological surveillance and control of vaccine preventable diseases. It is coordinated by the SSI in Denmark, in collaboration with the ISS in Italy. The two main diseases targeted by the network are measles and pertussis. A collaboration is planned with the PHLS for the monitoring of Haemophilus influenzae b. EUVAC-NET includes the Member States of the European Union, and Iceland, Norway and Switzerland.

European Union↗

Effect of the dietary fiber glucomannan on chronic constipation in neurologically impaired children.

OBJECTIVE: Inadequate dietary fiber intake is a widely accepted explanation for chronic constipation in children with severe brain damage. The aim of our study was to evaluate the efficacy of glucomannan, a soluble fiber, as a treatment for chronic constipation in these children. STUDY DESIGN: Twenty children with severe brain damage and chronic constipation were randomly assigned to double-blind treatment with either glucomannan (n = 10) or placebo (n = 10) for 12 weeks. Stool habits, total and segmental gastrointestinal transit times, and anorectal motility were evaluated in all children before and after the treatment period. RESULTS: Glucomannan significantly increased (P <.01) stool frequency, whereas the effect of placebo was not significant. Laxative or suppository use was significantly reduced (P <.01) by glucomannan but was not affected by placebo. Clinical scores of stool consistency were significantly improved and episodes of painful defecation per week were significantly reduced by glucomannan (P <.01) but not by placebo. However, neither glucomannan nor placebo had a measurable effect on total and segmental transit times. CONCLUSIONS: In neurologically impaired children, glucomannan improves stool frequency but has no effect on colonic motility.

Administration, Rectal↗

Persistence of abnormal gastrointestinal motility after operation for Hirschsprung's disease.

OBJECTIVE: Recent studies in patients with Hirschsprung's disease (HD) suggest that morphological abnormalities of the intramural intestinal plexuses are not restricted to the colon. In this report, symptoms and objective tests of gastrointestinal (GI) motor dysfunction were determined long after operative treatment to see whether evidence of a more widespread and relevant motility disturbance could be detected. METHODS: Twenty-one children were available for study an average of 6.6 yr after surgery for HD. All of these patients underwent evaluation of bowel frequency per week, total GI transit time (TGTT), and a scintigraphic gastric emptying test using solid food; anorectal manometry and segmental colonic transit times were performed in a subset of patients. Results were compared with findings in appropriately matched controls. RESULTS: Frequency of defecation per week in patients with HD after surgery was not different from that in control children, but TGTT was significantly longer (p < 0.01). Percentage retention of gastric isotope at 60 min exceeded the normal range in 12 of 21 (57.1%) patients, and colonic transit was abnormal in all six children studied. Symptoms persisted in two-thirds of patients postoperatively, and transit abnormalities were more common in the symptomatic subset (p = 0.026). CONCLUSIONS: Our data show that, in a subset of patients with HD, GI motor dysfunction persists long after surgical correction. The heterogeny of basic defects responsible for HD could provide the substrate for these motor abnormalities that, in turn, seem at least partially responsible for continuation of the symptomatic state.

Adolescent↗

Hypoxic and hypoglycaemic changes of intracellular pH in cerebral cortical pyramidal neurones.

Intracellular pH and membrane potential were measured during hypoxia and/or hypoglycaemia in cortical pyramidal neurones of a rat cortical slice preparation. Intracellular pH (pHi) was calculated from ratiometric microfluorometry of the pH-sensitive dye BCECF injected via sharp recording microelectrodes into the neurones. Transient (5 min) hypoxia induced a fall of pHi (7.12 +/- 0.03) of -0.72 +/- 0.11 pH units while transient (10 min) hypoglycaemia induced an increase of 0.37 +/- 0.09 pH units. Hypoglycaemia did not prevent the hypoxic acidification. Lowering extracellular Na+ induced a membrane hyperpolarization and alkalinization by 0.29 +/- 0.12 pH units but did not affect the development or recovery of the hypoxic acidification. The alkalinization during hypoglycaemia suggested that there is some anaerobic glycolysis under normoglycemic conditions. The hypoxic acidification, however, is unlikely to result from anaerobic glycolysis or reversal of Na(+)-dependent H+ extrusion.

Animals↗

Early sodium elevations induced by combined oxygen and glucose deprivation in pyramidal cortical neurons.

We investigated the effects of oxygen (O2)/glucose deprivation on intracellular sodium concentration ([Na+]i) of cortical pyramidal cells in a slice preparation of rat frontal cortex. Intracellular recordings were combined with microfluorometric measurements of [Na+]i using the Na+-sensitive dye sodium-binding benzofuran isophthalate (SBFI). Deprivation of O2/glucose caused an initial membrane hyperpolarization that was followed by a slowly developing large depolarization. Levels of [Na+]i started to increase significantly during the phase of membrane hyperpolarization. Neither tetrodotoxin, a combination of ionotropic and metabotropic glutamate receptor antagonists (D-amino-phosphonovalerate, 6-cyano-7-nitroquinoxaline-2,3-dione plus S-methyl-4-carboxyphenylglycine) nor bepridil, an inhibitor of the Na+/Ca2+-exchanger, affected these responses to O2/ glucose. The present results demonstrate that, in cortical neurons, O2/glucose deprivation induces an early rise in [Na+]i which cannot be ascribed to the activity of voltage gated Na+-channels, glutamate receptors or of the Na+/Ca2+-exchanger.

Animals↗

Diagnosis and treatment of constipation in children.

This review highlights the most significant progress in treatment of constipation occurring in the last year, underlying the advances in pathophysiology, clinical presentation, diagnosis, and treatment of both organic and functional constipation. Recent developments in the field of the pathophysiology of idiopathic chronic constipation and Hirschsprung's disease are discussed. Furthermore, a description of the new methods, which may have considerable diagnostic potential in children with functional and organic constipation, is presented. Finally, the recent therapeutic approaches to pediatric constipation and fecal incontinence are illustrated.

Child↗

L-type Ca2+ channel blockers attenuate electrical changes and Ca2+ rise induced by oxygen/glucose deprivation in cortical neurons.

BACKGROUND AND PURPOSE: Experimental evidence supports a major role of increased intracellular calcium [Ca2+]i levels in the induction of neuronal damage during cerebral ischemia. However, the source of Ca2+ rise has not been fully elucidated. To clarify further the role and the origin of Ca2+ in cerebral ischemia, we have studied the effects of various pharmacological agents in an in vitro model of oxygen (O2)/glucose deprivation. METHODS: Pyramidal cortical neurons were intracellularly recorded from a slice preparation. Electrophysiological recordings and microfluorometric measurements of [Ca2+]i were performed simultaneously in slices perfused with a glucose-free physiological medium equilibrated with a 95% N2/5% CO2 gas mixture. RESULTS: Eight to twelve minutes of O2/glucose deprivation induced an initial membrane hyperpolarization, followed by a delayed, large but reversible membrane depolarization. The depolarization phase was accompanied by a transient increase in [Ca2+]i levels. When O2/glucose deprivation exceeded 13 to 15 minutes, both membrane depolarization and [Ca2+]i rise became irreversible. The dihydropyridines nifedipine and nimodipine significantly reduced either the membrane depolarization or the [Ca2+]i elevation. In contrast, tetrodotoxin had no effect on either of these parameters. Likewise, antagonists of ionotropic and group I and II metabotropic glutamate receptors failed to reduce the depolarization of the cell membrane and the [Ca2+]i accumulation. Finally, dantrolene, blocker of intracellular Ca2+ release, did not reduce both electrical and [Ca2+]i changes caused by O2/glucose depletion. CONCLUSIONS: This work supports a role of L-type Ca2+ channels both in the electrical and ionic changes occurring during the early phases of O2/glucose deprivation.

Animals↗

[Iatrogenic and non-iatrogenic factors as causes of progressive sensorineural hearing loss].

The aim of our study was to analyze factors such as noise, chemical drugs, industrial solvents and radiotherapy, which can cause cochlear lesions with progressive sensorineural hearing loss. Although an acute overstimulation by acoustic energy may induce an irreversible hearing loss, in most cases the noise-induced deafness is related to the duration of the exposure and to the level of the acoustic stimulation. A permanent hearing deficit occurs when the acoustic level exceeds 85 dBs. Also several classes of drugs are described as having ototoxic potential: aminoglycoside antibiotics, loop diuretics, antimalarial drugs such as quinine, salicylates, some chemotherapeutic antineoplastic agents. Their potential ototoxic effect seems to be related not only to the molecule, but also to individual predisposition, dose and route of administration. Regarding the benzene derivatives, there is a relationship between their ototoxicity and factors such as duration of exposure and concentration in the local environment. Finally, radiotherapy to areas near the temporal bone may produce a degenerative insult to the vascular stria and the hair cell causing a progressive sensorineural hearing loss.

Disease Progression↗

[Treatment of Hirschsprung's disease with the Soave-Coran technique: experience with newborns and children].

Authors report their experience with Soave endorectal pull-through (ERPT) procedure modified by Coran for Hirschsprung's disease. At the Santobono Children's Hospital of Naples 30 patients have been operated for Hirschsprung's disease; 21 of them (age 10 days-3 years and 7 months) have undergone a Coran's procedure: a single stage procedure was performed in 16, the other 5 underwent ERPT following colostomy. Four complications occurred: 2 intestinal obstruction and 2 anastomotic leaks. Excellent long-term results reported from literature and proved by Author's experience suggest that one stage Coran's procedure can be safely performed even in neonates avoiding colostomy complications and reducing total duration and costs of hospitalization.

Child, Preschool↗

The differences shown by C57BL/6 and DBA/2 inbred mice in detecting spatial novelty are subserved by a different hippocampal and parietal cortex interplay.

Inbred C57BL/6 (C57) and DBA/2 (DBA) mice with hippocampus, posterior parietal cortex or sham lesions were placed in an open-field containing five objects and their reactivity to the displacement (spatial novelty) or the substitution (object novelty) of some of these objects was examined. C57 mice reacted to spatial novelty by exploring more the displaced than the non-displaced objects while DBA mice did not show any consistent reaction. In the highly reactive C57 strain, the peak of exploratory responses directed towards the displaced objects was completely abolished by hippocampal and posterior parietal cortex lesions. In the non-reactive DBA strain, hippocampal lesions induced an aspecific decreased interest towards the two categories of objects while posterior parietal cortex lesions did not produce any behavioral modification. The high reactivity of C57 mice to spatial change appears to be subserved by the conjunctive participation of the hippocampus and the posterior parietal cortex. Conversely, the deficit shown by DBA mice in that situation seems to be related to: (i) a poorly functional hippocampus; and (ii) the non-involvement of the posterior parietal cortes. The present data suggest that the participation of the posterior parietal cortes to the detection of spatial novelty may depend on the degree of functionality of the hippocampus.

Animals↗