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Biomedical subjects

P Turrini

Publications and source records attributed to P Turrini.

At least 19 recordsLinked to original sources
PubMed2006

Development of humanized mice for the study of hepatitis C virus infection.

The development of a small animal model for hepatitis C virus (HCV) infection is a critical issue for the development of novel anti-HCV drugs. To this aim, we have tried many different approaches for generating mice carrying humanized liver. Main efforts were focused on the transplantation of human hepatocytes into immunocompromised mice (SCID-/-, Bg-/-) carrying a genetic lethal liver disease (Alb-uPA). Survival of homozygotic animals should largely depend on early transplantation with healthy hepatocytes. In parallel to establishing a colony of Alb-uPA/SCID/Bg mice, we developed a microsurgical procedure for intrasplenic xenotransplantation of healthy hepatocytes in 1-week-old mice. So far, we generated several chimeras by xenotransplanting human hepatocytes in Alb-uPA+/+/SCID-/-/Bg-/- mice at 1 week after birth. In a first step, identification of successfully engrafted animals is possible by quantification of human serum albumin and human alpha 1 antitrypsin in mouse sera. Additional preliminary histomorphological analysis of liver sections from chimeric animals was also carried out. One of the mice was transiently infected with HCV, reaching viremia levels of approximately 10(5) genomes/mL. However, the efficiency of this system to generate chimeric mice is still very limited. We are currently exploring the use of more robust models of hepatic disease. Moreover, we have been also exploring novel strategies for the generation of chimeric mice by xenotransplanting human adult stem cells, instead of human hepatocytes, at preimmune stages of development.

Animals↗
PubMed2001

Dispersion of ventricular depolarization-repolarization: a noninvasive marker for risk stratification in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: We retrospectively investigated the value of clinical and ECG findings as well as QT-QRS dispersion in predicting the risk of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: Duration and interlead variability of the QT interval and QRS complex were measured manually from standard ECGs in 20 sudden death victims with ARVC diagnosed at autopsy (group I), in 20 living ARVC patients with sustained ventricular tachycardia (group II), in 20 living ARVC patients with </=3 consecutive premature ventricular beats (group III), and in 20 control subjects (group IV). QT and QRS dispersions were greater in group I (77.5+/-10.6 ms for QT and 45.7+/-8.1 ms for QRS) compared with group II (64.5+/-13.9 ms for QT [P=0.001] and 33.5+/-8.7 ms for QRS [P=0.0004]) and in group II compared with group III (48+/-8.9 ms for QT [P<0.0001] and 28+/-5.2 ms for QRS [P<0.0001]) and group IV (33.5+/-4.8 ms for QT [P<0.0001] and 18.5+/-3.6 ms for QRS [P<0.0001]). Negative T wave beyond V(1) and syncope were statistically more frequent in group I (P=0.02 and P=0.007, respectively). On multivariate analysis, QRS dispersion remained an independent predictor of sudden death (P<0.0001), followed by syncope (P=0.09). In assessing risk of sudden death, QRS dispersion >/=40 ms had a sensitivity and specificity of 90% and 77%, respectively; QT dispersion >65 ms, 85% and 75%, respectively; negative T wave beyond V(1), 85% and 42%, respectively; and syncope, 40% and 90%, respectively. CONCLUSIONS: QRS dispersion (>/=40 ms) was the strongest independent predictor of sudden death in ARVC. Syncope, QT dispersion >65 ms, and negative T wave beyond V(1) refined arrhythmic risk stratification in these patients.

Adolescent↗
PubMed2001

Cholinergic nerve terminals establish classical synapses in the rat cerebral cortex: synaptic pattern and age-related atrophy.

This study addresses the issue of whether cholinergic varicosities in the cerebral cortex establish 'classical synapses' or whether they communicate with their targets non-synaptically by 'volume transmission'. Most recent studies in the neocortex have suggested that acetylcholine acts non-synaptically, however in the present study we provide ultrastructural evidence that suggests synaptic mechanisms prevail. This conclusion is based upon our ultrastructural observations that cholinergic boutons--as revealed by immunoreactivity for the specific cholinergic market, vesicular acetylcholine transporter--establish a high percentage of classical synapses in layer V of the rat parietal cortex. Furthermore, the combination of this approach with the intracellular labeling of large pyramidal neurons on slice preparations revealed significant incidences of cholinergic contacts abutting preferentially on dendritic shafts. Finally, we have gathered information suggesting that cholinergic boutons undergo atrophy with aging which could be related to the well-known cholinergic and cognitive decline. These results illustrate that the cholinergic terminations in the neocortex establish proper synaptic connections and that they experience important age-dependent atrophy.

Acetylcholine↗
PubMed2001

Presence and possible functional role of nerve growth factor in the thymus.

We have previously reported that the nerve growth factor (NGF), a polypeptide known for its neurotrophic activities, is also involved in proliferation, growth and survival of cells of the immune system. Working with animal models, we found that NGF and NGF-receptors (NGF-r) are present in the cells of the medullary layer of the thymus, a lymphoid gland involved in the production and differentiation of T-lymphocytes. Using immunohistochemical and biochemical approaches, we also showed that the expression of NGF in the thymus is high during late prenatal life and decreases later in postnatal life. A significant alteration of NGF levels was also found during pregnancy and aging, two events characterized by thymic involution. The aim of this study is to investigate whether NGF and NGF-r expression in the thymus are influenced by immuno- and neuro-pathological events. These observations will be presented and discussed.

Animals↗
PubMed2000

Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome.

The neurotrophin nerve growth factor (NGF) is a major regulator of peripheral and central nervous system development. Serum NGF was measured in normally developing control children (n=26) and in individuals affected by congenital syndromes associated with learning disability: either Williams syndrome (WS; n=12) or Down syndrome (DS; n=21). Participants were assessed at three distinct developmental stages: early childhood (2 to 6 years), childhood (8 to 12 years), and adolescence (14 to 20 years). A sample was taken only once from each individual. Serum NGF levels were markedly higher in participants with WS, than DS and control participants. In addition, different developmental profiles emerged in the three groups: while in normally developing individuals NGF levels were higher in early childhood than later on, children with WS showed constantly elevated NGF levels. When compared to control participants, those with DS showed lower NGF levels only during early childhood. Neuropsychological assessment confirmed previously reported differences among the three groups in the development of linguistic/cognitive abilities. Some features of individuals with WS, such as hyperacusis and hypertension, could be related to high-circulating NGF levels.

Adolescent↗
PubMed2000

Signal-averaged electrocardiogram in patients with arrhythmogenic right ventricular cardiomyopathy and ventricular arrhythmias.

OBJECTIVE: The aim of the study was to assess the prevalence, sensitivity, specificity and predictive value of the signal-averaged ECG in patients with arrhythmogenic right ventricular cardiomyopathy and different forms of ventricular arrhythmias. METHODS: The signal averaged ECG in 138 patients and 146 healthy subjects (control group), using a three bandpass filter system (25-250, 40-250, 80-250 Hz), was considered abnormal when at least two parameters were abnormal at each filter setting. Patients were divided into three groups according to the extent of the right ventricular enlargement (mild, moderate, extensive), and into five groups according to the type of ventricular arrhythmia. RESULTS: The signal averaged ECG was abnormal in 57% of the patients and in 4% of the healthy subjects. The sensitivity was 57%, specificity 95% and positive predictive value 92%. The signal averaged ECG was abnormal in 94.4% of patients with the extensive form of the disease, in 77.7% of patients with the moderate form and in 31.8% of patients with the minor form, demonstrating good correlation with the extent of the disease. According to the type of ventricular arrhythmia, a higher correlation was found between signal averaged ECG abnormality and sustained ventricular tachycardia with superior axis (94.4%, P<0. 02); the correlation for the other arrhythmias varied from 16.6% to 55.8%. CONCLUSION: There is a closer correlation between the signal averaged ECG and extent of disease than with the presence of ventricular arrhythmias. The signal averaged ECG is not helpful in diagnosing minor forms of the disease, but since it is a non-invasive method, it may be useful in evaluating progression of the disease.

Adult↗
PubMed2000

Biventricular pacing and atrioventricular junction ablation as treatment of low output syndrome due to refractory congestive heart failure and chronic atrial fibrillation.

A 71-year-old male patient with end-stage heart failure, atrial fibrillation, congestive and low output symptoms, underwent biventricular pacing and atrioventricular junction ablation while anuric and hypotensive. Following atrioventricular junction ablation blood pressure increased by 20 mmHg during biventricular but not during right ventricular apical pacing. A rapid clinical improvement was observed and the patient was discharged from the hospital in NYHA functional class III.

Aged↗
PubMed1999

Cholecystokinin-8 protects central cholinergic neurons against fimbria-fornix lesion through the up-regulation of nerve growth factor synthesis.

In this study, we demonstrate that cholecystokinin-8 (CCK-8) induces an increase in both nerve growth factor (NGF) protein and NGF mRNA in mouse cortex and hippocampus when i.p. injected at physiological doses. By using fimbria-fornix-lesioned mice, we have also demonstrated that repeated CCK-8 i.p. injections result in recovery of lesion-induced NGF deficit in septum and restore the baseline NGF levels in hippocampus and cortex. Parallel to the effects on NGF, CCK-8 increases choline acetyltransferase (Chat) activity in forebrain when injected in unlesioned mice and counteract the septo-hippocampal Chat alterations in fimbria-fornix-lesioned mice. To assess the NGF involvement in the mechanism by which CCK-8 induces brain Chat, NGF antibody was administrated intracerebrally to saline- and CCK-8-injected mice. We observe that pretreatment with NGF antibody causes a marked reduction of NGF and Chat activity in septum and hippocampus of both saline- and CCK-8-injected mice. This evidence indicates that the CCK-8 effects on cholinergic cells are mediated through the synthesis and release of NGF. Taken together, our results suggest that peripheral administration of CCK-8 may represent a potential experimental model for investigating the effects of endogenous NGF up-regulation on diseases associated with altered brain cholinergic functions.

Animals↗
PubMed1999

Late potentials and ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

We studied 38 patients (mean age 32 +/- 14 years) with arrhythmogenic right ventricular cardiomyopathy (ARVC) to evaluate the clinical significance of histologic features on endomyocardial biopsy specimens as related to signal-averaged electrocardiography (SAECG), spontaneous ventricular arrhythmias, and hemodynamic features. Fifteen patients presented with ventricular tachycardia or fibrillation (sustained ventricular arrhythmias), 23 with other minor arrhythmias. SAECG variables and right ventricular ejection fraction (RVEF) were statistically correlated with the extent of myocardial fibrosis on biopsy in ARVC. An increased percentage of fibrous tissue (> or = 30%) was a significant univariate predictor of late potentials (p = 0.004) and reduced RVEF (p = 0.02). The 18 patients with late potentials had an increased percentage of fibrous tissue (p = 0.01), a reduced RVEF (p = 0.0004), and a higher risk for sustained ventricular arrhythmias (p = 0.05) than the 20 patients without late potentials. RVEF was the most powerful predictor of late potentials (p = 0.004) at multivariate analysis. Moreover, RVEF < or = 50% was associated with an increased risk for development of sustained ventricular arrhythmias (p = 0.02). A SAECG parameter, namely the root-mean-square voltage of the terminal 40 ms at 25 Hz, was an independent predictive factor for the occurrence of sustained ventricular arrhythmias (p = 0.02). Although fibrous tissue may contribute to delayed myocardial activation in ARVC, a reduced RVEF plays an essential role for spontaneous manifestation of sustained ventricular arrhythmias.

Adolescent↗
PubMed1999

Overexpression of tumour necrosis factor alpha in the brain of transgenic mice differentially alters nerve growth factor levels and choline acetyltransferase activity.

Tumour necrosis factor alpha (TNF-alpha) is a pleiotrophic cytokine synthesized primarily by macrophages and monocytes, which exerts a variety of biological activities during inflammatory responses, immune reactions, and wound healing. Within the central nervous system (CNS), the basal levels of TNF-alpha are almost undetectable, but increase after neurological insults. Using transgenic mice expressing high levels of TNF-alpha in the CNS, we investigated the effect of this cytokine on the levels of brain nerve growth factor (NGF), a neurotrophin playing a crucial role in the development, maintenance and regeneration of basal forebrain cholinergic neurons. The immunoenzymatic assay and in situ hybridization revealed that the constitutive expression of NGF decreased in the hippocampus, increased in the hypothalamus, while remained unchanged in the cortex. Moreover, septal cholinergic neurons which receive trophic support from NGF produced in the hippocampus display loss of choline acetyltransferase immunoreactivity, suggesting that the reduced availability of NGF may influence negatively the synthesis of brain cholinergic neurons. These observations indicate that the basal level of brain NGF can be influenced negatively or positively by local expression of TNF-alpha and that this cytokine, through dose-dependent regulation of NGF synthesis and release, may be involved in neurodegenerative events associated with aging.

Age Factors↗
PubMed1999

Evidence that endogenous thymosin alpha-1 is present in the rat central nervous system.

We have previously reported that administration of Thymosin alpha 1 (T-alpha1) can enhance the level of the Nerve Growth Factor and the distribution of its receptor in the developing Central Nervous System (CNS) of rat. To further explore the role of T-alpha1 and verify its presence in cells of rat CNS, we carried out an immunohistochemical study using a polyclonal antibody against T-alpha1. T-alpha1 immunoreactivity was found mainly in neurons of the hippocampus and spinal cord and in several small cells, resembling glial cells, of specific regions of the brain. Moreover, to study whether cerebral cells were receptive to T-alpha1, we injected iodinated T-alpha1 (125I-T-alpha1) i.c.v.. 125I-T-alpha1 labelled neurons were observed in the hypothalamus and septal nuclei. Our results indicate that specific neuronal populations in the rat CNS are able to express and respond to T-alpha1.

Animals↗
PubMed1999

Accuracy of electrocardiographic and echocardiographic indices in predicting life threatening ventricular arrhythmias in patients operated for tetralogy of Fallot.

OBJECTIVE: To validate the accuracy of the prognostic significance of non-invasive clinical diagnostic indices as predictors of sustained ventricular tachycardia (sVT) or fibrillation (VF) in patients undergoing repair for tetralogy of Fallot. METHODS: One way analysis of variance and pairwise comparison of the values with the Bonferroni correction, logistic multivariate analysis, and ordinal logistic analysis were used to study quantitative electrocardiographic and echocardiographic variables in 66 patients who had undergone surgery for tetralogy of Fallot by ventriculotomy at a mean (SD) age of 11.8 (9.5) years. The mean (SD) period of follow up was 16.1 (5.7) years after surgery. RESULTS: Four groups of patients were identified by ECG and 24 hour Holter monitoring: 19 (28.7%) without ventricular arrhythmias, 34 (51.5%) with minor ventricular arrhythmias, seven (10.6%) with non-sustained ventricular tachycardia (nsVT), and six (9.0%) with sVT or VF. One way analysis indicated significant differences in QT dispersion (QTd) and end diastolic volume of the right ventricle (EDVRV) among the groups. Univariate logistic analysis showed EDVRV, QTd, and QRS duration to be significantly associated with sVT or VF. Stepwise multivariate analysis and ordinal logistic analysis showed QTd to be preferable to QRS duration as an indicator, because it was unrelated to EDVRV, and was capable of separating different probability curves for nsVT as opposed to sVT or VF. CONCLUSIONS: Stratification of patients undergoing corrective surgery for tetralogy of Fallot and at risk of life threatening arrhythmias is possible by simple and inexpensive means, which provide sensitive and specific indices.

Adolescent↗
PubMed1997

Angiographic and morphologic features of the left ventricle in Ebstein's malformation.

Quantitative and qualitative cineangiographic analysis of the left ventricle (LV) was performed in 26 patients with isolated Ebstein's malformation, having a mean age of 23 +/- 17 years. Nine autopsied hearts with isolated Ebstein's malformation were submitted to morphologic and morphometric analysis. In 4 of the cases, it was possible to make a direct correlation between the angiographic data obtained during life and the autopsy findings. On the basis of the LV end-diastolic volume we identified 3 groups of patients: 7 with volume <60 ml/m2, another 7 with volume between 60 and 80 ml/m2, and 12 with volume >80 ml/m2. The LV ejection fraction was reduced in 2 patients with normal LV end-diastolic volume and in 6 with increased LV end-diastolic volume. The ratio of ventricular mass to LV end-diastolic volume was always adequate, but a reduction of the ventricular contractive performance (end-systolic pressure to end-systolic volume ratio <3 mm Hg/ml/m2) was found only in patients with a dilated left ventricle. No correlation was demonstrated between the extent of the atrialized component of the right ventricle (mean value 67 +/- 31 cm2, range 13 to 133) and the LV dimensions. All but 2 patients showed a leftward diastolic displacement of the ventricular septum, but in only 1 did this produce an elongated shape of the left ventricle. Sixteen had anomalies of LV dynamics: 10 with hypokinesia (3 of the posterior wall, 4 of the apex, 1 of the inferior wall, 1 of the septum, and 1 global), 6 with dyskinesia (1 of the posterior wall, 2 of the apex, 1 of the posterior wall and apex, 1 of the superior part of the septum, and 1 of the anterior wall), and 8 with premature diastolic distension of the anterobasal wall. Morphometric analysis produced mean values for myocytes of 59 +/- 10%, for the interstitium of 21 +/- 4%, and for fibrous tissue of 20 +/- 9% (normal 4 +/- 1%). Five autopsied hearts had a prolapsing and/or dysplastic mitral valve.

Adolescent↗
PubMed1997

Presence of nerve growth factor in the thymus of prenatal, postnatal and pregnant rats.

The presence of Nerve Growth Factor (NGF) and the expression of low- and high-affinity NGF receptor were investigated in prenatal, postnatal and pregnant rats. Using ELISA and immunohistochemistry it was found that both NGF and its receptors are present in the medulla of the thymus and are more strongly expressed in pre- and early postnatal life and nearly absent in adult and ageing rats. It was also found that during pregnancy, which is characterised by an involution of the cortex and hypertrophy of the medulla, the level of NGF in the thymus increases. The present study showed not only that NGF is produced in a specific compartment of the thymus, the medulla, but that its synthesis declines with age, following thymus involution. These results suggest that NGF may be critically involved in the proliferation and differentiation of thymic cells.

Animals↗
PubMed1996

Familial cardiomyopathy underlies syndrome of right bundle branch block, ST segment elevation and sudden death.

OBJECTIVES: We sought to assess whether structural heart disease underlies the syndrome of right bundle branch block, persistent ST segment elevation and sudden death. BACKGROUND: Ventricular fibrillation and sudden death may occur in patients with a distinctive electrocardiographic (ECG) pattern of right bundle branch block and persistent ST segment elevation in the right precordial leads. METHODS: Sixteen members of a family affected by this syndrome underwent noninvasive cardiac evaluation, including electrocardiography, Holter ambulatory ECG monitoring, stress testing, echocardiography and signal-averaged electrocardiography; two patients had electrophysiologic and angiographic study. Endomyocardial biopsy was performed in one living patient, and postmortem examination, including study of the specialized conduction system, was performed in one victim of sudden death. RESULTS: Five years before a fatal cardiac arrest, the proband had been resuscitated from sudden cardiac arrest due to recorded ventricular fibrillation. Serial ECGs showed a prolonged PR interval, right bundle branch block, left-axis deviation and persistent ST segment elevation in the right precordial leads, in the absence of clinical heart disease. Postmortem investigation disclosed right ventricular dilation and myocardial atrophy with adipose replacement of the right ventricular free wall as well as sclerotic interruption of the right bundle branch. A variable degree of right bundle branch block and upsloping right precordial ST segment was observed in seven family members; four of the seven had structural right ventricular abnormalities on echocardiography and late potentials on signal-averaged electrocardiography. A sib of the proband also had a prolonged HV interval, inducible ventricular tachycardia and fibrofatty replacement on endomyocardial biopsy. CONCLUSIONS: An autosomal dominant familial cardiomyopathy, mainly involving the right ventricle and the conduction system, accounted for the ECG changes and the electrical instability of the syndrome.

Adolescent↗
PubMed1995

Signal-averaged electrocardiography in familial form of arrhythmogenic right ventricular cardiomyopathy.

This study was performed to establish whether signal-averaged electrocardiography can aid in the diagnosis of the familial form of arrhythmogenic right ventricular cardiomyopathy in order to determine the severity of the disease and to predict ventricular arrhythmias. In arrhythmogenic right ventricular cardiomyopathy there is a fatty fibrous substitution of myocardium, which is the substrate for delayed myocardial activation; this is responsible for the abnormalities seen on the signal-averaged electrocardiogram (SAECG). Seventy-five members of 11 families, both healthy and with various forms of the disease, were studied using a signal-averaged electrocardiographic technique. Forty-seven members, 16 with a severe and 31 with a minor form of the disease, were found to be affected. Forty-three subjects had abnormal results on the SAECG; of these, 39 had the disease (100% in patients with widespread disease and 74.1% in patients with a minor form), whereas the other 4 had no sign of the disease. Only 44.1% of the subjects with an abnormal SAECG had ventricular arrhythmias, whereas 76% of the subjects with ventricular arrhythmias had an abnormal SAECG. In contrast, 90.6% of patients with an abnormal SAECG had the disease, and only subjects with arrhythmogenic right ventricular cardiomyopathy had ventricular arrhythmias. The abnormality on the SAECG appears to be correlated with the severity of the disease. Signal-averaged electrocardiography does not seem useful in diagnosing the minor forms of the disease and it does not give precise information about electrical instability in these patients.

Adolescent↗
PubMed1995

The effects of sympathetic stimulation induced by mental stress on signal-averaged electrocardiogram.

We evaluated the influence of sympathetic stimulation, induced by mental stress test, on signal-averaged ECG in 30 healthy subjects and in 30 patients with previous myocardial infarction. Both patient and control groups underwent three consecutive signal-averaged ECG: under basal conditions, during a continuous mental stress test, and 5 min after the mental stress test. The signal-averaged ECG parameters, analyzed by mean of a bandpass filter of 25-250 and 40-250 Hz, were: the filtered QRS duration, the duration of the low-amplitude high frequency signals in the terminal portions of the QRS complex below 40 microV (HFLA), and the root mean square voltage in the last 40 ms of the filtered QRS (RMS). The mathematical stress test was considered effective when the heart rate increased by at least 15 beats/min, remaining stable for the total duration of the signal-averaged ECG acquisition. A significant reduction of the filtered QRS duration and HFLA with a simultaneous increase of RMS were found in control group, while no significant changes occurred in patient group. These results indicate that the sympathetic nervous system may affect the results of signal-averaged ECG, probably by influences on intraventricular conduction, in healthy subjects. On the contrary, myocardial alterations in ischemic heart disease induce modification of signal-averaged ECG not influenced by autonomic nervous system activity.

Adult↗