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Biomedical subjects

L Rossi

Publications and source records attributed to L Rossi.

At least 163 records · Page 9Linked to original sources

Analysis of poly(ADP-ribose) glycohydrolase activity in nuclear extracts from mammalian cells.

We have analysed poly(ADP-ribose) glycohydrolase, the enzyme responsible for in vivo degradation of ADP-ribose polymers, by means of a biochemical assay based on the capacity of the enzyme to use a synthetic 32P-labelled polymer as a substrate. The visualization of the reaction has been achieved by separation of poly and mono(ADP-ribose) by thin-layer chromatography followed by autoradiography, whereas polymer hydrolysis has been quantified by counting the spots corresponding to poly and mono(ADP-ribose). By addition of the enzyme inhibitor ethacridine to the reaction mixture, we have confirmed the specificity of the procedure we have developed. The protocol has been applied to study the specific activity of glycohydrolase in nuclear extracts from different mammalian cell lines and to an apoptotic experimental system, namely HL60 cells treated with etoposide. We have observed the activation of the enzyme after a two-hour drug treatment, that is concomitant with the activation of poly(ADP-ribose) polymerase, the enzyme which synthesizes the polymer. These data suggest a precise regulation of ADP-ribosylation process during cell death by apoptosis.

Adenosine Diphosphate Ribose↗

Phenotype expression of human bone cells cultured on implant substrates.

Bone cells derived from the human jaw were cultured on titanium, titanium coated with hydroxyapatite (THA) or with plasma spray (TPS) to study the behaviour of the cells anchored to implant substrates. Bone cells were cultured in MEM with the addition of [3H]-thymidine to evaluate cellular proliferation, and [3H]-glucosamine to evaluate GAG synthesis and accumulation in the extra-cellular matrix (ECM). Moreover, to study the degradation of GAG bone cells were cultured in the presence of NH4Cl, an amine known to inhibit lysosomal activity. Our results show that TPS is the substrate that favours both cellular proliferation and the accumulation of GAG in the ECM.

Ammonium Chloride↗

Targeting antiviral nucleotide analogues to macrophages.

Macrophages are important target cells for human immunodeficiency virus type 1 (HIV-1) infection. We have developed a drug targeting system for the selective delivery of phosphorylated nucleoside analogues to these phagocytosing cells. This system is based on the possibility of encapsulating the phosphorylated drugs into autologous erythrocytes and on the subsequent selective modification of their membranes to promote macrophage recognition and phagocytosis. Targeted delivery of phosphorylated nucleoside analogues to human, feline, and murine macrophages inhibits the infectivity of HIV-1, feline immunodeficiency virus, and LP-BM5 viruses more efficiently than the administration of the corresponding nucleoside analogues. In vivo administration of 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) encapsulated into autologous erythrocytes to LP-BM5-infected mice was found to reduce infectivity and disease progression. Furthermore, the simultaneous administration of AZT or ddC produced additive antiviral effects. The possibility of using red cells as drug targeting systems was useful for the design, synthesis, and delivery of new antiviral nucleoside analogues. As a prototype of these new drugs, di-(thymidine-3'-azido-2',3'-dideoxy-D-riboside)-5'-5'-p1-p2-pyrophospha te (AZTp2AZT) was prepared. Although this drug in solution has the same antiviral activity as AZT, when administered encapsulated into erythrocytes it was several times more efficient in inhibiting the infectivity of human, feline, and murine immunodeficiency viruses. Thus, the availability of a drug targeting system for the selective delivery of antivirals to macrophages offers an additional possibility for the development of new drugs and of new combination antiviral therapies.

Animals↗

Significance of the DNA synthesis in hypertrophic cardiomyopathies.

DNA content and proliferating cell nuclear antigen (PCNA) expression were investigated in normal hearts, in hypertrophic from hemodynamic overload hearts and in hypertrophic cardiomyopathy (HCM). The aim of this study was mainly to determine whether the hyperdiploid myocardial cells in all cases are in dynamic or static phase. The percentage of PCNA positive cells only in the HCM group was significantly higher (mean value = 25.4%) than the percentage of hyperdiploid cells (mean value = 9.3%). Therefore, the DNA replication occurs through a different process from that of normal cell cycle which lead to an increase in ploidy and eventually mitosis. These data should be interpreted not only as the result of a periodic amitotic DNA renewal and not even as the result of an increased apoptosis, but especially as a repair process of the DNA molecules affected by a various types of damages in HCMs.

Adult↗

Clinical subtypes of bipolar mixed states: validating a broader European definition in 143 cases.

OBJECTIVE: To validate and clinically characterize mixed bipolar states derived from the concepts of Kraepelin and the Vienna School and defined as sustained instability of affective manifestations of opposite polarity--that usually fluctuate independently of one another--in the setting of marked emotional perplexity. METHOD: Our criteria for mixed states represent a modified "user-friendly" operationalization of these classical concepts. We compared 143 mixed state patients, so defined, with 118 DSM III-R manic patients, systematically evaluated with the Semistructured Interview for Depression (SID) in our in-patient and day-hospital facilities. RESULTS: The two groups were comparable from demographic and familial standpoints (including family history for bipolar disorder). Mixed states were predominant in the past history of index mixed patients who were more likely to have experienced stressors and to have attempted suicide; manic and hypomanic episodes were more common in the past history of the index manic patients who, in addition, had more episodes and hospitalizations. Although rates of chronicity and rapid cycling were not significantly different in the two groups, the modal episodes in the mixed states were 3-6 months, and in mania they were less than 3 months. Two thirds of both groups arose from a dysregulated baseline temperamental dysregulation, which in manics, was largely hyperthymic, and in mixed patients, was both hyperthymic and depressive. Of our 143 mixed states, only 54% met the DSM III-R criteria for mixed states (which conformed to "dysphoric mixed mania"); of the remaining, 17.5% could be described as "mixed agitated psychotic depressive states" with irritable mood and flight of ideas, and 26% as "unproductive-inhibited manic" with fatigue and indecisiveness. The family history and course of these "non-DSM III-R" mixed states were essentially similar to DSM III-R mixed states. LIMITATION: Family history could not be obtained blind to clinical status in patients with severe psychotic mood states. CLINICAL RELEVANCE: These data favor the classical European approach to mixed states over the grossly under-inclusive current official diagnostic systems. CONCLUSION: The phenomenology of mixed states is more than the mere superposition of opposite affective symptoms and, in many instances, it represents an expansive-excited phase intruding into a depressive temperament, and a melancholic episode intruding into a hyperthymic temperament.

Adolescent↗

Purification of a fully metal-depleted Cu, Zn superoxide dismutase from copper-deficient rat liver.

A copper-deprived form of the enzyme Cu, Zn superoxide dismutase was identified in the liver of rats made copper-deficient by dietary restriction. In homogenates of such livers Cu, Zn superoxide dismutase presents a dis-homogeneous electrophoretic profile with respect to the native enzyme. When rat liver extracts were treated with exogenous copper an electrophoretic pattern resembling the native one was observed. Enzyme purified by chromatography on DE-52 resin shows two major components, one corresponding to genuine, native enzyme and another one, eluting at higher ionic strength. The latter protein (Fraction II) consists of several isoforms which show the same characteristics of the native superoxide dismutase as far as immunoreactivity and molecular weight are concerned, but with decreased contents of copper and zinc. Its catalytic constant, referring to copper content, was 15 times lower than that obtained for the native enzyme. Moreover, the catalytic power of purified Fraction II was not regained upon incubation with copper. The occurrence of a superoxide dismutase void of metals confirms the hypothesis that this protein plays a dual physiological role: in metal metabolism and in superoxide anion dismutation.

Animals↗

Postischemic hyperemia in subjects with lower limbs obstructive arteriopathy: role of PGI2 and endothelin.

The physiological basis of postischemic hyperemia is not yet fully understood. The present study investigated the effects of pharmacologic manipulation of the prostaglandin system on local hemodynamics. Strain-gauge plethysmography was used to study 8 normal subjects and 9 patients with obliterating arterial disease of the lower limbs. Hemodynamic evaluations were performed before treatment, after seven days of low-dose acetylsalicylic acid (100 mg/day) to inhibit platelet thromboxane synthesis, and after acute infusion of 1 g of acetylsalicylic acid to inhibit endothelial prostacyclin synthesis. In patients with arterial disease, the hemodynamic study was also carried out after infusion of iloprost, a synthetic prostacyclin analogue. Acute infusion of acetylsalicylic acid significantly reduced basal blood flow in normal subjects, but not in patients with arterial disease. In the latter group, iloprost affected neither basal nor maximal postischemic flow. The study also evaluated the role of endothelin in musculocutaneous hemodynamic regulation, both in physiological conditions and in atherosclerosis. This part of the study addressed the possibility that the hemodynamic effects of vasodilator prostanoids like prostacyclin might affect endothelin release in vivo. During reactive hyperemia, plasma endothelin was reduced in normal subjects (-1.02 pg/mL, 95% CI: -2.23, 0.08), but not in patients with atherosclerosis (-0.35 pg/mL, 95% CI: -1.45, 0.75). In both groups, plasma endothelin was not affected by aspirin. These findings confirm the role of prostacyclin in local hemodynamic regulation. In the normal subject, musculocutaneous blood flow seems to depend at least in part on the action of vasodilator prostanoids and endothelin. This is not the case in patients with arterial disease, in whom plasma endothelin does not seem to be affected by postischemic changes in blood flow. A possible explanation for this difference could be alteration of the endothelial function in patients with arterial disease, related to the functional and structural characteristics of the artery wall in atherosclerosis.

Aged↗

Haemonchosis in Spanish ibex.

Two cases of haemonchosis occurred in the Spanish ibex (Capra pyrenaica) population of the National Hunting Reserve of Tortosa and Beseit, northeastern Spain, in July 1992 and May 1993. The animals were cachectic and recumbent and had an acute hemorrhagic, macrocytic and hypochromic anemia; which was related to a high infection of 2,016 and 1,863 Haemonchus contortus, respectively, in the abomasum of the animals.

Abomasum↗

Laparoscopic groin hernia surgery: the TAPP procedure. Transabdominal preperitoneal hernia repair.

OBJECTIVE: To describe the technique and results of laparoscopic transabdominal preperitoneal (TAPP) hernia repair. DESIGN: A case series, with a detailed description of the operative technique. SETTING: A university affiliated hospital. PATIENTS: A consecutive series of 554 patients (494 male, 60 female) who underwent laparoscopic hernia repair in a single institution. The mean follow-up was 14 months. INTERVENTIONS: Laparoscopic TAPP hernia repair was performed in almost all patients. Simple closure was performed in a patient with a strangulated hernia, and a mesh-based repair was used in a patient with bilateral obturator hernias. MAIN OUTCOME MEASURES: Complications and recurrence. RESULTS: The laparoscopic TAPP repair was successful in 550 of the 554 patients who underwent 632 hernia repairs. conversion was necessary in 4 patients. Complications were infrequent and there were no recurrences. Only 3.4% of patients were lost to follow-up. The most frequent complications were urinary retention (27) and hematoma and seroma (38) in the early postoperative period. Neuralgia (11) and hydrocele (10) also occurred. Mesh infection occurred in only 1 patient and port-site hernias in 3 patients. there was 1 death from an acute myocardial infarction. CONCLUSION: Laparoscopic TAPP hernia repair is associated with an exceedingly low recurrence rate and an acceptable complication rate.

Adolescent↗

Functional uncertainty, aging and memory processes during sleep.

Disorganized sleep patterns, can be found both during normal development and in pathological conditions. Aging could also be accompanied by a disorganization of the night sleep episode; sleep could be interrupted by spontaneous awakening, sleep cycle could be shortened or incomplete, sleep states modified. These patterns suggest an inability to sustain a stable condition, i.e. a condition of functional uncertainty. Biological and cognitive implications of functional uncertainty conditions are discussed. In particular, the hypothesis has been put forward that disturbances of sleep could have a detrimental role on memory. Recent results obtained in our lab support this hypothesis: recall is correlated with NREM-REM cycles proportion. Future research should ascertain the role of the functional uncertainty with respect to the kind of memory being involved during sleep, and establish how much and for which cognitive processes (including those involved in dream production) the inability to sustain a steady condition impairs the functioning during sleep. The duration of the functional uncertainty condition is also important. The long-term study of the link between functional uncertainty and cognitive resources, could be important for the understanding of the night life and for an adequate treatment of patients.

Adult↗

Sudden death in young people with apparently isolated mitral valve prolapse.

Ventricular electrical instability and sudden death in mitral valve prolapse (MVP) have been related to mitral valve regurgitation and left ventricular dysfunction, autonomic nervous system abnormalities, or underlying cardiomyopathy. The aim of the present study was to assess the frequency, nature and pathophysiologic significance of histologic myocardial abnormalities in young patients with apparently isolated MVP and sudden cardiac death. Among 163 cases of sudden cardiovascular death in young people, MVP was the only cardiac pathology found at postmortem gross examination in 17 (10%) (12 females and 5 males) aged 14 to 35 years, mean 24. In 12 cases sudden death occurred at rest (during pregnancy in 2). MVP was diagnosed during life in 8 patients, 6 of whom had experienced palpitations and/or syncope, and 3 had premature ventricular beats. In every case, postmortem gross examination revealed "floppy" mitral valve leaflets with marked myxoid degeneration, and no other cardiovascular pathology. Cardiomegaly with left chamber enlargement was observed in 5 cases (mild in 3 and moderate in 2). In 12 cases (70%), histopathologic study disclosed myocardial abnormalities which consisted of focal myocardial atrophy and fatty replacement of the right ventricular wall (mostly the outflow tract) in 9 cases, left ventricular myocardial disarray (without hypertrophy) in 2, and lymphocytic infiltrates in one. "Foetal" dispersion of specialized atrioventricular junction and fasciculoventricular Mahaim's fibers were found in 2 cases. In conclusion, apparently isolated MVP was found in nearly 10% of sudden cardiovascular fatalities in young people. Most young sudden death victims with MVP were asymptomatic females without significant mitral valve regurgitation. In more than two-thirds of the cases, histopathologic examination evidenced underlying silent but potentially arrhythmogenic myocardial substrates, mostly consisting of segmental right ventricular cardiomyopathic changes.

Adolescent↗

[Sudden cardiac death in non-professional athletes].

Sudden death during sports activities in non-professional athletes is a rare occurrence, however it is of great interest in clinical pathology and forensic medicine. We performed chemico-toxicologic and histopathologic investigations in three cases of sudden cardiac death in non-professional athletes, focusing in particular on the cardiac conduction system. Examination of conduction tissue was performed on sections seriated every 150 microns, stained alternately with hematoxylin-eosin and Heidenhain's trichrome (azan). In all three cases diagnostic evidence showed hyperacute myocardial infarction, due to spasm of coronaries with mild atherosclerosis, and myocardial lesions due to reperfusive necrosis. The pathogenesis of sudden death in young athletes is not related only to ischemic-coronary damage that is not exclusively mechanical, but also a dynamic event (spasm and reperfusion), but also to fatal arrhythmias related to abnormal findings in the conduction system. Such findings can therefore be considered the morphologic substrate of sudden cardiac death.

Adult↗

Nifedipine GITS versus diltiazem in chronic stable angina: a randomised multicentre study.

In order to compare the efficacy of nifedipine gastrointestinal therapeutic system (GITS) with diltiazem, 99 patients with chronic stable angina were studied in a parallel-group randomised trial. According to the results of the two exercise tolerance tests (ETTs) performed during the placebo run-in, patients were divided into a fixed threshold group if the variability in time to 1 mm ST-segment depression was 20%, or a variable threshold group if it was higher. Efficacy was assessed by comparing the time to 1 mm ST-depression on a bicycle ETT after 4 weeks of treatment, adjusting for the baseline value. The adjusted means were 7.44 min for nifedipine GITS and 7.68 min for diltiazem; the difference was -0.24 min, with a lower 90% confidence limit of -0.90, which is within the stated interval for equivalence. The same result was confirmed by the 'intention-to-treat' analysis, and comparable results were obtained both in fixed and in variable threshold groups. The incidence of side effects was 12% with nifedipine GITS and 8.2% with diltiazem. Nifedipine GITS and diltiazem were found to be equally effective in increasing exercise tolerance in chronic stable angina patients.

Angina Pectoris↗

Screening of gestational diabetes in Tuscany: results in 2000 cases.

According to the guidelines of the "Third international workshop conference on GDM", we have examined 2000 pregnant women. The glucose challenge test (GCT) was positive in 408 cases (20.4%) and negative in 1592 (79.6%). The OGTT (Carpenter and Coustan's criteria) was performed in 647 pregnant women. GDM and IGGT prevalence was of 6.25% and 5.5% respectively and normal glucose tolerance (NGT) 88.25%. The GCT effectiveness for GDM and IGGT diagnosis is: sensibility 75.1%, specificity 44%, positive predictive value 46.4% and negative predictive value 74%. GDM and IGGT compared with NGT women were significantly older (p < 0.05) and prepregnancy BMI was higher (p < 0.01); the prevalence of previous macrosomia (p < 0.01), previous gestational diabetes (p < 0.01) and family history for diabetes mellitus (p < 0.05) was greater in GDM and IGCT. The prevalence of preterm delivery was higher in both GDM and IGCT (GDM 12.5% and IGGT 15.4% vs NGT 6%; p < 0.01), as well as the prevalence of cesarean sections (GDM 31.6% vs IGGT 23.5% and NGT 20.3%; p < 0.02), and the occurrence of macrosomia (GDM 27.6%, IGGT 16.6% and NGT 16.2%). In addition a higher prevalence (p < 0.01) of hyperbilirubinaemia, hypoglycemia and hypertrophy cardiomyopathy was observed in newborns from GDM women. Our data show that: GCT has a good specificity for GDM diagnosis, prevalence of GDM in our population is about 6%, GDM is still correlated to an elevated maternal and neonatal morbility.

Adult↗

[Evaluation by bioelectric impedance of body fluid compartments and body mass in cardiosurgical patients before and after total cardiopulmonary bypass].

BACKGROUND: To evaluate the influence of extracorporeal circulation (ECC) on fluid compartments and body mass using impedance measurements. METHODS: A prospective study was performed in 20 consecutive patients undergoing ECC during heart surgery at the Department of Heart Surgery of Verona Hospital. Resistance or reactance measurements at 1-5-10-50-100 KHz were performed in 20 patients undergoing heart surgery for valvular or coronary pathologies in class NYHA I or II, preoperatively and on day 1, 3 and 6 in order to evaluate total body water (TBW), intracellular water (ICW), extracellular water (ECW), thin and fat body mass. Weight, fluid-electrolytic balance and hematochemical parameters relating to electrochemical phenomena and the distribution of volumes in the various compartments, namely sodium, potassium and plasmatic osmolarity, were measured at the same times. Comparisons were made both between the data and during ECC. RESULTS: It was found that there was a mean postoperative weight gain of 2 kg in terms of total body water. Subsequently, this finding tended to decrease to basal values by day 6. Immediately after ECC, the water gain appeared to be predominantly extracellular, whereas the intracellular increase peaked on day 1. The change in total body water was correlated with the weight and fluid balance, but electrical measurements showed values above the corresponding weight gain. The duration of ECC was significantly correlated with bioelectric parameters, but not with absolute weight values. CONCLUSIONS: The method proved useful for the purpose, especially with regard to the overall population examined rather than individual patients. The dual-compartment electric model appears to be more suitable than the single-compartment model for exploring the different compartments. The trend of weight and total body water, which were correlated in pattern but not in absolute values, may be interpreted as a redistribution of fluids, also suggested by changes in electric parameters relating to compartmental distribution.

Aged↗

A survey of the gastro-intestinal nematodes of roe deer (Capreolus capreolus) in a mountain habitat.

Two hundred and twenty one roe deer from a xeric inner-alpine valley in Italy were investigated along four yearly cycles for the presence of gastro-intestinal nematodes. Road kills were the main source of this material. Spiculopteragia spiculoptera and Ostertagia leptospicularis, with their "minor" morphs S. mathevossiani and O. kolchida, were the dominant abomasal species, whereas Nematodirus europaeus was the only dominant species in the small intestine; therefore, species composition was typical of this ruminant host. Nematodes whose prime hosts are domestic and wild Bovids (Rupicapra rupicapra) were found occasionally. Abundances were low (407 nematodes in the abomasum, 209 in the small intestine, 6 in the large intestine) in spite of a high population density. Significant differences in worm counts were observed between seasons (abomasal worm counts peaked in late spring and summer whereas N. europaeus was more abundant in winter), years and between sex and age classes (higher abomasal counts in bucks vs does and in adult individuals vs fawns). Associations between worm counts and the condition of roe deer (five parameters taken into account) could not be demonstrated unambiguously. Based on data, the use of abomasal counts as a herd health index in the study area is not recommended.

Abomasum↗