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Biomedical subjects

Francesco Chiarelli

Publications and source records attributed to Francesco Chiarelli.

At least 19 recordsLinked to original sources
PubMed2006

Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in type 2 diabetes.

OBJECTIVE: Receptor for advanced glycation end products (AGEs) (RAGE) plays a central role in the process of plaque rupture in diabetic patients. Recently, it has been reported that RAGE may be downregulated by improving glycemic control. In contrast, despite being well known that RAGE may be induced in human vessels in a glucose-independent fashion, also by myeloperoxidase (MPO)-dependent AGE generation, no data exist regarding the possibility of a pharmacological modulation of glucose-independent RAGE generation. Thus, the aim of this study was to characterize the effect of simvastatin on the expression of RAGE and RAGE-dependent plaque-destabilizing genes in human atherosclerotic plaques. METHODS AND RESULTS: Seventy type 2 diabetic patients with asymptomatic carotid artery stenosis (>70%) were randomized to American Heart Association (AHA) step 1 diet plus simvastatin (40 mg/d) or AHA step 1 diet alone for 4 months before endarterectomy. Plaque expression of MPO, AGEs, RAGE, NF-kappaB, COX-2, mPGES-1, matrix metalloproteinase (MMP)-2 and MMP-9, lipid and oxidized LDL (oxLDL) content, procollagen 1, and interstitial collagen was analyzed by immunohistochemistry and Western blot; zymography was used to detect MMP activity. Plaques from the simvastatin group had less (P<0.0001) immunoreactivity for MPO, AGEs, RAGE, p65, COX-2, mPGES-1, MMP-2, and MMP-9, lipids and oxLDL; reduced (P<0.0001) gelatinolytic activity; increased (P<0.0001) procollagen 1 and collagen content; and fewer (P<0.0001) macrophages, T-lymphocytes, and HLA-DR+ cells. Of interest, RAGE inhibition by simvastatin, observed not only in plaque sections but also in plaque-derived macrophages, was reverted by addition of AGEs in vitro. CONCLUSIONS: This study supports the hypothesis that simvastatin inhibits plaque RAGE expression by decreasing MPO-dependent AGE generation. This effect in turn might contribute to plaque stabilization by inhibiting the biosynthesis of PGE2-dependent MMPs, responsible for plaque rupture.

Aged↗
PubMed2006

Oral clonidine provocative test in the diagnosis of growth hormone deficiency in childhood: should we make the timing uniform?

INTRODUCTION: Oral clonidine is one of the most frequent drugs used for the diagnosis of growth hormone deficiency (GHD), but the duration of the test, depending on which European centres use it, is not uniform and can vary from 120 to 150 min or even 180 min. SUBJECTS AND METHODS: To standardize this test, evaluating the possibility to shorten it to 90 min, we investigated the response of GH to the oral clonidine test in 291 children evaluated for short stature (height <-2 SD). Of these, 164 were diagnosed as idiopathic short stature (ISS) and 127 as GHD. In these patients, we calculated: (1) the frequency distribution of the GH peaks to clonidine in GHD and in ISS at various times; (2) the percentage of GH peaks to clonidine before and after 90 min in all and in ISS children; (3) the percentage of the first GH value >or=10 ng/ml before 90 min and after 90 min in ISS. RESULTS: GH peak distribution varied between 30 and 180 min, even though the vast majority of peaks occurred between 30 and 60 min. There was no significant difference (p > 0.05) in the peak distribution between ISS and GHD children. The percentages of GH peaks within 90 min were 92.1% in all children and 95.7% in ISS. If considering the first value of GH >or=10 ng/ml this last percentage reaches 96.3%. CONCLUSION: Our study suggests that the oral clonidine test can be administered for only 90 min without significantly changing its validity. This test should be standardized at 90 min in European protocols just as in those currently used in the USA in order to reduce the discomfort of patients and the cost of this diagnostic procedure.

Child↗
PubMed2006

Parent and health professional perspectives in the management of adolescents with diabetes: development of assessment instruments for international studies.

OBJECTIVE: Assessment of quality of life (QOL) in adolescents with diabetes requires patient, parent and health professional input. Psychometrically robust instruments to assess parent and professional perspectives are required. RESEARCH DESIGN AND METHODS: Questionnaires concerning adolescent QOL were developed for completion by parents and health professionals. In an international study assessing QOL in 2,101 adolescents with diabetes (median age 14 years, range 10-18; from 17 countries including Europe, Japan and North America), parents and health professionals completed their respective questionnaires between March and August 1998. RESULTS: Feasibility and acceptability of the new questionnaires were indicated by high questionnaire completion rates (adolescents 92%; parents 89%; health professionals 94%). Internal consistency was confirmed (Cronbach's alpha coefficients 0.80 parent; 0.86 health professional). Correlations of Diabetes Quality of Life Questionnaire for Youths (DQOLY) scores with parent and health professional global QOL ratings were generally low (r ranging from 0.12 to 0.36). Parent-rated burden decreased incrementally across adolescence, particularly for girls. Professional-rated burden followed a similar profile but only after age 15 years. Until then, burden was rated as uniformly high. Clinically relevant discrepancies in parent and professional burden scores were noted for one-parent families and families where adolescents had been referred for psychological help. In both cases, health professionals but not one-parent families perceived these as high burden situations. The clinical significance of this relates to the significantly poorer metabolic control recorded for adolescents in both situations. CONCLUSIONS: Parent and health professional questionnaires were found to have adequate internal consistency, and convergent and discriminant validity in relation to key clinical and QOL outcomes. The questionnaires are brief, easy to administer and score. They may also enable comparisons across countries and languages to facilitate development of international health outcome parameters. The inclusion of the parent and health professional perspectives completes a comprehensive assessment of adolescent QOL relevant to diabetes.

Adolescent↗
PubMed2006

Pharmacotherapy of spasticity in children with cerebral palsy.

Spasticity is one of the most common symptoms presented by neurologic patients. Apart from surgical management, drug therapy is an important treatment of children suffering from spasticity. In this review, recent advances in the pharmacologic armamentarium are reported in detail. In particular, there are oral medications (benzodiazepines, baclofen, dantrolene sodium, alpha 2 adrenergic agonists) and parenteral medications (botulinum toxin type A and B, alcohol). Moreover, there is also baclofen that can be administered intrathecally. There are some reports supporting the use of intramuscular alcohol (45% and/or 5-7% phenol) to reduce spasticity without the loss of voluntary movement or loss of sensation. Among these drugs, intrathecal baclofen is one of the most effective substances that can reduce spasticity significantly in the upper and lower extremities. Finally, the effectiveness of therapy with botulinum toxin type A in the management of spasticity is analyzed. Botulinum toxin type A reduces hypertonia in the injected muscles for a period of 2 to 4 months without important side effects. The purpose of this article is to provide an overview of available oral and parenteral drugs for treatment of spasticity in cerebral palsy and to outline indications and contraindications.

Administration, Oral↗
PubMed2006

Ambulatory blood pressure monitoring in obese children: role of insulin resistance.

OBJECTIVES: To investigate the relationship between ambulatory blood pressure (ABPM) parameters and insulin resistance in obese children. METHODS: A population of 56 obese prepubertal children was recruited for the study. They underwent ABPM, an oral glucose tolerance test and complete physical examination, including adiposity indexes such as body mass index (BMI), skinfolds, waist-to-hip ratio (WHR) and fat mass. RESULTS: The standard deviation score for BMI was significantly correlated with 24-h systolic blood pressure (SBP) (r = 0.30; P = 0.02) and diastolic blood pressure (DBP) (r = 0.29; P = 0.03), daytime SBP and DBP (r = 0.28; P = 0.04 and r = 0.32; P = 0.02), night-time SBP and DBP (r = 0.32; P = 0.01 and r = 0.27; P = 0.04). Fat mass was correlated with 24-h SBP (r = 0.46; P = 0.005), daytime SBP (r = 0.40; P = 0.01) and night-time SBP (r = 0.49; P = 0.03). No correlations were found between ABPM parameters and WHR. Furthermore, significant correlations were found between insulin resistance indexes, such as the homeostasis model assessment of insulin resistance and quantitative insulin-sensitivity check index, and 24-h DBP (r = 0.34; P = 0.01 and r = -0.29; P = 0.03), daytime DBP (r = 0.35; P = 0.009 and r = -0.34; P = 0.01) and daytime SBP (r = 0.32; P = 0.02 and r = -0.27; P = 0.04). Only 24-h and daytime DBP remained correlated with insulin resistance after adjustment for obesity. The analysis of the circadian rhythm of blood pressure revealed that 24 out the 56 children were non-dippers. CONCLUSIONS: The results of the present study indicate that adiposity and insulin resistance have an important role in influencing blood pressure in obese children, and also show a high prevalence of non-dipping phenomenon. This is of particular relevance because blood pressure tracks from childhood into adulthood and an already early-life high blood pressure is associated with an increased cardiovascular risk.

Blood Pressure↗
PubMed2006

Retinal nerve fiber layer and macular thickness in adolescents with epilepsy treated with valproate and carbamazepine.

PURPOSE: To evaluate retinal nerve retinal nerve fiber layer (RNFL) and macular thickness by using optical coherence tomography (OCT) in epileptic adolescents before and during monotherapy with valproic acid (VPA) and carbamazepine (CBZ). METHODS: We examined prospectively 45 epilepsy patients with partial and generalized epilepsy. The patients were evaluated before the beginning of therapy and after 1 year of VPA or CBZ monotherapy. Forty-five untreated healthy controls were evaluated at baseline and after 1 year. RESULTS: At the beginning of the study, the two groups of patients showed RNFL and macular thickness measurements similar to control values. At the end of the follow-up, the data of the three groups were similar to baseline, showing no significant differences in the evaluated parameters. CONCLUSIONS: The present study demonstrates that no modification of RNFL and macular thickness parameters is found after 1 year of treatment with VPA and CBZ monotherapy.

Adolescent↗
PubMed2006

The treatment of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy is a common type of epilepsy with onset occurring during adolescence. This review provides a collection of evidence relating to the treatment of this type of epilepsy. Historically, the large majority of patients become seizure-free when treated with valproate. Over recent years, there has been a marked improvement in the pharmacological armamentarium by the physicians. Currently, administration of new antiepileptic drugs, such as levetiracetam, lamotrigine and topiramate, seems to have beneficial effects in the patients with poor response to valproate.

Anticonvulsants↗
PubMed2006

Recent advances on neural tube defects with special reference to Valproic Acid.

Epilepsy is a common medical problem and many studies have demonstrated that infants of women with epilepsy (WWE) have a two to threefold higher risk of congenital malformations compared with the background population. The majority of WWE have normal, healthy children. However, WWE have an increased risk of congenital malformations. Congenital malformations are twice as common in infants exposed to antiepileptic drugs in utero. A variety of congenital malformations have been reported, with a particular preponderance of orofacial clefts. Valproate is often associated with the development of neural tube defects. In this review, we analyse the problem of neural tube defects and report in detail the main pathogenetic theories about the onset of this type of congenital malformation. There is strong evidence for a protective effect of adequate folate consumption.

Adult↗
PubMed2006

Serum and urinary nitrites and nitrates and Doppler sonography in children with diabetes.

OBJECTIVE: The aim of the present study was to evaluate serum and urinary nitric oxide (NO) concentrations in children and adolescents with diabetes compared with age-matched healthy control subjects to find out whether Doppler ultrasonography could be used to detect changes in renal resistive indexes (RIs) in children with diabetes and to assess whether there are correlations between these parameters and NO excretion. RESEARCH DESIGN AND METHODS: We studied 42 children with type 1 diabetes and 41 matched healthy control subjects, both divided into prepubertal or pubertal children. Serum and urinary nitrite and nitrate (NO2-+NO3-) concentrations were evaluated as an index of NO production. Doppler ultrasonographic registration of intrarenal RI was performed. RESULTS: Compared with healthy control subjects, children with diabetes had significantly increased concentrations of serum (30.26 +/- 6.52 vs. 24.47 +/- 7.27 mmol/l, P = 0.001) and urinary NO2-+NO3- (345.07 +/- 151.35 vs. 245.86 +/- 80.25 mmol/l, P = 0.002); the same was true for Doppler RI values (0.64 +/- 0.03 vs. 0.60 +/- 0.04, P = 0.035). This occurs in both prepubertal and the pubertal children. A significant positive correlation was found between serum and urinary NO2-+NO3- levels (P = 0.002, r = 0.374). Serum NO2-+NO3- concentrations also correlated positively with Doppler RI (P = 0.032, r = 0.262) and HbA1c (A1C) (P = 0.004, r = 0.329); urinary NO2-+NO3- concentrations correlated positively with A1C (P = 0.001, r = 0.394). Doppler RI correlated positively with A1C (P = 0.000, r = 0.424). CONCLUSIONS: This study demonstrates that in children with diabetes, chronic hyperglycemia may act through a mechanism that involves increased NO production and/or action and contributes to generating intrarenal hemodynamic abnormalities, which are detectable by Doppler ultrasonography even in early diabetic nephropathy.

Blood Glucose↗
PubMed2006

Physical exercise and diabetes during childhood.

Active life and physical fitness may represent the most effective strategies to prevent chronic diseases and to improve growth and development for children, including those with diabetes. Observational studies have demonstrated the association between life style and prevention of chronic diseases in the general population. These studies have been showed a reduction of morbidity for vascular diseases in trained subjects who present adequate cardiovascular fitness and practise regular exercise. The exercise-related protective effects may be mediated in part through components of the metabolic syndrome: improved insulin sensitivity, decreased weight and visceral fat accumulation, reduced low density lipoprotein (LDL) and triglycerides, increased high density lipoprotein (HDL), decreased blood pressure. These effects are more significant in patients with type 1 diabetes (T1DM), because hyperglycemia-related morbidity and mortality are associated with chronic complications. In particular, improved insulin sensitivity may determine a better glucose profile which in turn may positively influence the diabetes-related microvascular complications. Furthermore, improved blood pressure and normalization of lipid profile may also contribute to the prevention of vascular complications. Nonetheless, physical activity can improve psychological well-being by increasing self-esteem and enhancing quality of life. Although patients with T1DM may participate in all kind of sports and physical activities, there are several potential adverse events, including hypoglycemic and hyperglycemic episodes, that can occur. Thus, patients and health professionals have to know in details the physiological effect of physical exercise and its metabolic events in order sport to be healthy and enjoyable for all children, adolescents and young adults with T1DM.

Adolescent↗
PubMed2005

Insulin analogues.

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Child, Preschool↗