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Biomedical subjects

R Ceravolo

Publications and source records attributed to R Ceravolo.

At least 37 records · Page 2Linked to original sources

Mitochondrial DNA rearrangements in young onset parkinsonism: two case reports.

Parkinson's disease is a nosological entity of unknown origin for which, in some cases, a possible pathogenetic role for mitochondrial dysfunction has been postulated. Two young onset parkinsonian patients with mitochondrial DNA (mtDNA) deletions in skeletal muscle are reported on. Patient 1 also presented with increased blood creatine kinase and lactate concentrations and a family history which included a wide range of phenotypes affecting multiple systems. Patient 2 presented with multiple symmetric lipomatosis. Histopathological investigation showed ragged red fibres and COX negative fibres in muscle biopsies from both patients. The data support the hypothesis that mitochondrial DNA mutations may occur in some cases of parkinsonism, suggesting that a diagnosis of a mitochondrial disorder should be considered in the presence of consistent family history and clinical symptoms.

Adult↗

Relationship between angiotensin-converting enzyme gene polymorphism and insulin resistance in never-treated hypertensive patients.

The association between angiotensin-converting enzyme (ACE) gene polymorphism and insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we evaluated the possible association between IR and ACE gene polymorphism in a group of hypertensive, never-treated patients compared with that in a normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/- 4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr) normotensive subjects. A double PCR assay was used to identify ACE genotypes. We determined fasting glucose and insulin by the glucose oxidase method and using a standard RIA technique. IR was estimated using the homeostasis model assessment (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P < 0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in hypertensive patients than in the normotensive control group. When we subdivided hypertensive patients according to ACE genotype, we observed that fasting insulin and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1 and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the II group (P < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. In conclusion, we extended previous data regarding the relationship of hypertension and IR by demonstrating a dependence of this relationship upon the ACE gene polymorphism.

Adult↗

Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C.

Endothelial dysfunction has been reported in obese subjects, but its mechanism has not been elucidated. We have therefore investigated 1) the possible relationship among BMI, waist-to-hip ratio (WHR), and endothelium-dependent vasodilation and 2) whether oxidative stress participates in endothelial dysfunction. We recruited 76 healthy subjects (50 men and 26 women aged 21-45 years) and measured their BMI (kg/m2), WHR, and insulin resistance (IR) estimated by the homeostasis model assessment (HOMA). Endothelium-dependent and -independent vasodilation were assessed by increasing doses of acetylcholine (ACh) (7.5, 15, and 30 pg x ml(-1) x min(-1)) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)) during saline and vitamin C coinfusion (24 mg/min). The effects of cyclooxygenase activity were evaluated by a dose-response curve to intrabrachial coinfusion of ACh and indomethacin (500 microg/min). Three different groups have been identified according to their BMI: group A (BMI <25), consisting of 10 men and 5 women; group B (BMI between 25 and 29), consisting of 16 men and 8 women; and group C (BMI > or =30), consisting of 24 men and 13 women. Obese subjects had significantly lower forearm blood flow (FBF) during ACh infusions (means +/- SD): 19.8 +/- 2.8, 10.8 +/- 2.7, and 6.5 +/- 1.8 ml x 100 ml(-1) tissue x min(-1) (P < 0.0001) for groups A, B, and C, respectively. SNP caused comparable increments in FBF in all groups. Regression analysis revealed a significant negative correlation between BMI (r = -0.676, P < 0.0001), WHR (r = -0.631, P < 0.0001), fasting insulin (r = -0.695, P < 0.0001), HOMA-IR (r = -0.633, P < 0.0001), and percent peak increase in FBF during ACh infusion. In obese subjects, both vitamin C and indomethacin increased the impaired vasodilating response to ACh, whereas the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated vasodilation is blunted, and the increase in FBF is inversely related to BMI, WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity.

Acetylcholine↗

Paroxetine in Parkinson's disease: effects on motor and depressive symptoms.

Selective serotonin reuptake inhibitors have been used in the treatment of depression in patients with PD. Conflicting data as to whether selective serotonin reuptake inhibitors worsen parkinsonian motor symptomatology have been reported. In this study, the additional 6 months therapy with paroxetine 20 mg/d in a group of depressed patients with PD did not modify parkinsonian motor function (Unified Parkinson's Disease Rating Scale scores); however, in one patient, fully reversible worsening of tremor was observed. Depression, as evaluated by Beck Depression Inventory and Hamilton Depression Rating Scale, improved from baseline to final visit (p < 0.05 by analysis of variance).

Aged↗

Effects of atorvastatin and vitamin C on endothelial function of hypercholesterolemic patients.

We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged 20-46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20-45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 microg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 microg/min) and L-NMMA (2, 4, 8 micromol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 microg/min), FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1) respectively (P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1). min(-1) (P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.

Acetylcholine↗

Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts.

Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinson's disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement-related activation of frontal cortical areas in 4 PD patients using H2 15O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F-dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinson's Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F-dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD.

Adult↗

Relationship between left ventricular mass and endothelium-dependent vasodilation in never-treated hypertensive patients.

BACKGROUND: Hypertensive patients are characterized by development of both left ventricular hypertrophy (LVH) and endothelial dysfunction METHODS AND RESULTS: We enrolled 65 never-treated hypertensive patients (36 men and 29 women aged 45.6+/-6.0 years) to assess the possible relationship between echocardiographic left ventricular mass (LVM) and endothelium-dependent vasodilation. Left ventricular measurements were performed at end diastole and end systole according to the recommendations of the American Society of Echocardiography and the Penn Convention. LVM was calculated with the Devereux formula and indexed by body surface area and height raised to the 2.7th power. The endothelial function was tested as responses of forearm vasculature to acetylcholine (ACh), an endothelium-dependent vasodilator (7.5, 15, and 30 microg. mL-1. min-1, each for 5 minutes), and sodium nitroprusside (SNP), an endothelium-independent vasodilator (0.8, 1.6, and 3.2 microg. mL-1. min-1, each for 5 minutes). Drugs were infused into the brachial artery, and forearm blood flow (FBF) was measured by strain-gauge plethysmography. A negative significant relationship between indexed LVM and peak of increase in FBF was found during ACh infusions (r=-0. 554; P<0.0001). In addition, hypertrophic patients had a significantly lower responsive to ACh than patients without LVH (the peak increase in FBF was 9.9+/-3.7 versus 16.1+/-8.1 mL per 100 mL of tissue per minute; P<0.0001). No significant correlation was observed between LVM and FBF during SNP infusion. CONCLUSIONS: Our data provide the first evidence that echocardiographic LVM in hypertensive patients is inversely related to FBF responses to the endothelium-dependent vasodilating agent ACh, but it is likely that both endothelium and LVM are damaged by hypertension.

Acetylcholine↗

The role of inheritance in sporadic Parkinson's disease: evidence from a longitudinal study of dopaminergic function in twins.

Despite the major finding of a genetic defect being responsible for the Parkinson's disease (PD) phenotype in some kindreds with dominantly transmitted PD, the role of inheritance in the cause of the more widespread sporadic form of the disease is still unclear. Twin studies are a classic tool for assessing the influence of hereditary factors in diseases; however, the application of this approach to late-onset illnesses, like PD, poses some problems because of the identification of subclinical cases. In the present longitudinal study we have used [18F]dopa and positron emission tomography to study dopaminergic function in twin pairs at baseline clinically discordant for PD. At baseline, the concordance for subclinical striatal dopaminergic dysfunction was found to be significantly higher in 18 monozygotic than in 16 dizygotic twin pairs (55% vs 18%, respectively). The asymptomatic monozygotic cotwins all showed progressive loss of dopaminergic function over 7 years and 4 developed clinical PD. None of the dizygotic twin pairs became clinically concordant. At follow-up, the combined concordance levels for subclinical dopaminergic dysfunction and clinical PD were 75% in the 12 monozygotic and 22% in the 9 dizygotic twin pairs evaluated twice. Our findings suggest a substantial role for inheritance in sporadic PD.

Aged↗

Acute and chronic effects of clozapine in essential tremor.

Patients with essential tremor (ET) may not respond to commonly used drugs. Clozapine, an atypical neuroleptic drug, has been reported to improve postural Parkinson's disease tremor clinically resembling ET. The effects of a single dose of 12.5 mg clozapine and placebo were evaluated in a randomized, double-blind, crossover study in 15 drug-resistant patients with ET. Patient responders with more than 50% improvement after a single dose of clozapine subsequently received the drug (39+/-9 mg up to 50 mg) unblinded for a period of 15.8+/-7.7 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients (p <0.01). Sedation was the only side effect reported during the clozapine test; however, the time course of sedation and of the antitremor effect were not coincident. A significant reduction of tremor was reported with chronic clozapine treatment (p <0.01) with no tolerance to drug antitremor effect, whereas sedation markedly decreased after 6-7 weeks of therapy. No clozapine-induced hematologic side effects were observed in our cohort of patients during long-term treatment. Our results suggest that in selected drug-resistant ET cases, clozapine should be considered before resorting to neurosurgical options.

Antipsychotic Agents↗

Calcium antagonist isradipine improves abnormal endothelium-dependent vasodilation in never treated hypertensive patients.

OBJECTIVE: To examine whether middle (two months) and long-term (six months) isradipine sustained-release treatment improves endothelium-dependent vasodilation in never treated hypertensive patients. METHODS: The responses of the forearm vasculature to acetylcholine (7.5, 15 and 30 micrograms/min) and sodium nitroprusside (0.8, 1.6, 3.2 micrograms/min) were evaluated in 12 normotensive controls (seven men and five women, aged 25 to 49 years), and in 12 hypertensives (eight men and four women, aged 20 to 47 years) at baseline and after two and six months of isradipine sustained-release treatment. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. RESULTS: At baseline, the response to acetylcholine was significantly lower in hypertensives vs controls: at the highest dose (30 micrograms/min), forearm blood flow was 28.6 +/- 2.4 ml/100 ml of tissue per min in the controls vs 8.9 +/- 1.0 ml/100 ml of tissue per min in hypertensive (p < 0.0001). Similarly, vascular resistance was significantly (p < 0.0001) higher in hypertensives: 4.8 +/- 0.5 units (controls) vs 15.1 +/- 1.7 units (hypertensives). After isradipine treatment, the forearm blood flow in hypertensive patients changed from 8.9 +/- 1.0 ml/100 ml of tissue per min to 16.0 +/- 1.2 ml/100 ml of tissue per min (two months; p < 0.0001) and 15.2 +/- 1.4 ml/100 ml of tissue per min (six months; p < 0.0001). Isradipine treatment did not modify the vasodilating effect of sodium nitroprusside. CONCLUSIONS: Our data demonstrate for the first time that the calcium antagonist isradipine improves acetylcholine-induced vasodilation in hypertensives.

Acetylcholine↗

Hypertensive left ventricular remodeling and ACE-gene polymorphism.

OBJECTIVE: To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives. METHODS: We enrolled 200 hypertensive outpatients that underwent clinical and ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45. RESULTS: The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different. CONCLUSIONS: The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.

Age Factors↗

Angiotensin-converting enzyme gene polymorphism is associated with endothelium-dependent vasodilation in never treated hypertensive patients.

The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 microg/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min, each for 5 minutes) was evaluated in 32 never-treated hypertensive outpatients (17 men and 15 women, aged 43+/-7 years) and in 24 normotensive control subjects (14 men and 10 women, aged 42+/-6 years). Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. In both hypertensive and normotensive groups, a deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene was determined by polymerase chain reaction. The response to acetylcholine was significantly reduced in hypertensive patients versus control subjects: at the highest dose (30 microg/min), forearm blood flow was 13.9+/-6.3 mL x 100 mL tissue(-1) x min(-1) in hypertensives versus 27.1+/-9.7 mL x 100 mL tissue(-1) x min(-1) in the controls (P<.001); similarly, vascular resistance was 10.6+/-5.6 U in hypertensive patients and 4.9+/-1.9 U in normotensive subjects. In the hypertensive group, the patients with DD genotype showed significantly less endothelium-dependent vasodilation compared with ID+II genotypes (at the highest dose of acetylcholine, forearm blood flow was 12.1+/-4.2 versus 17.0+/-4.1 mL x 100 mL tissue(-1) x min(-1)) (P<.005). The vasodilator effect of sodium nitroprusside infusions was not statistically different in DD and ID+II hypertensive patients. In conclusion, our data suggest that ACE polymorphism affects endothelium-dependent vasodilation in hypertensive patients and confirm that hypertensive patients had a blunted response to the endothelium-dependent agent acetylcholine.

Adult↗

Deletion polymorphism of angiotensin-converting enzyme gene and left ventricular hypertrophy in southern Italian patients.

OBJECTIVES: This study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI). BACKGROUND: The renin-angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy. METHODS: The study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/ deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient. RESULTS: Left ventricular mass index values (mean +/- SD) were 137 +/- 28 g/m2 in patients with the DD genotype, 125 +/- 27 g/m2 in those with the ID genotype and 115 +/- 27 g/m2 in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI] interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02). CONCLUSIONS: Our data show that the LVMI was significantly enhanced in patients with the DD genotype.

Adult↗

Clozapine in Parkinson's disease tremor. Effects of acute and chronic administration.

The effects of the acute administration of clozapine on parkinsonian mixed tremor (i.e., resting and postural tremors) were evaluated to establish clozapine's predictive value for long-term response and to determine if there is a difference in the pharmacologic responses of the two tremors. We also investigated the correlation between reduction of tremor and induction of sedation after acute and chronic administration of clozapine. Clozapine (12.5 mg) or placebo were administered po in a double-blind manner to 17 PD patients with mixed L-dopa-resistant tremors. Two patients did not reach 50% improvement and were considered nonresponders. The remaining 15 patients reported moderate to marked reduction of tremor. Responsive patients in the acute test moved on to a long-term, open clozapine add-on study receiving an average daily dose +/- SD of 45 +/- 9.6 mg for a period of 15.5 +/- 8.3 months. A significant reduction of both resting (p < 0.05) and postural (p < 0.05) tremors was observed under clozapine from the first week of treatment through the entire period of the study. There was no statistically significantly difference between the degree of improvement for resting and postural tremors after either single or chronic clozapine administration. Sedation was the only side effect reported after clozapine; however, the time courses of sedation and tremor reduction did not coincide in the acute or in the chronic experimental paradigm, where it decreased considerably in a few weeks in all patients. During long-term clozapine treatment, neither systemic side effects nor worsening of motor disability scores were noted. Thus we wish to propose an acute test or a therapeutic attempt, or both, with clozapine before defining a case of mixed parkinsonian tremor as resistant tremor and therefore resorting to a neurosurgical approach.

Aged↗

Electrophoretic pattern of physiological human nasal secretions.

Various proteins have been detected in human nasal mucus, but their electrophoretic pattern has not been extensively investigated. Therefore, we have studied this pattern in nasal mucus samples from a group of 40 healthy subjects (20 males and 20 females). The electrophoretic separations have been performed under both native and denaturing conditions. The electrophoretic pattern of nasal mucus obtained under denaturing conditions and stained with Coomassie brilliant blue R-250, reveals 17 distinguishable areas into which protein bands are divided, with no significant variations from one individual to another. Eight of these areas contain high concentrations of nasal mucus proteins, whereas lower concentrations are seen in the other nine areas. The electrophoretic patterns of nasal mucus differs from that of eye mucus. The method used for sampling is rapid, simple, requires no local anaesthetic, and supplies an adequate quantity of proteins for laboratory testing. Electrophoresis under denaturing conditions proves to be the better of the two techniques, since it permits good separation of proteins. Among the protein bands revealed in our study there are some already known proteins (i.a. pre-albumim, albumin, lysozymne), but the presence of other proteins which have yet to be identified cannot be excluded. Hence, a study is underway for the purification and identification, by amino-acid sequencing, of the various proteins which make up each band. A through definition of the protein pattern of nasal mucus might prove useful for detecting anomalies in its composition, for example, in cases of olfactory disorders.

Adult↗