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Blood lead levels were assayed in 261 children (133 males and 128 females) living in Campania, 137 (63 females and 74 males) in urban areas and 124 (65 females and 59 males) in rural zones, aged between 0.197 and 16.863 years. Blood lead determination was carried out by electrothermal atomic absorption spectroscopy. All children were interviewed about common risk factors for lead exposure. PbB (median +/- SD) were significantly higher in the urban than in the rural population (6.0 +/- 0.31 vs 3.75 +/- 0.25 micrograms/100 ml; p0.001). The frequency of blood lead level above 10 micrograms/100 ml was 4.21% in our tested group, i.e., significantly lower than in previous studies. A significant direct correlation between blood lead levels and age was found (r = 0.47; p0.001). In agreement with the literature on this subject, our findings show a significant reduction with time, of blood lead levels of children and adolescents in our region. Time of exposure more than total dose seems to be important for the increase of blood lead level.

In order to assess the possible effects of proteinuria on statural growth, we studied 14 children with various glomerulopathies and proteinuria persistently above 30 mg/kg/day which were followed-up for 1.5-4.3 years. They had received only short-term steroid therapy or no steroids at all. During the follow-up, 3 patients lost 1-2.1 height standard deviation scores. These patients had proteinuria above 100 mg/kg/day with associated glycosuria, and they went into chronic renal failure. The other patients had minor variations of the growth curve. In our experience heavy proteinuria represents a risk factor for growth delay when it is associated with glycosuria and chronic renal failure.

Histological examination of renal biopsies in 64 Neapolitan children aged 13 months to 14 years who presented with nephrotic syndrome or persistent hematuria and/or proteinuria revealed membranous glomerulopathy (M.G.) in 14. Hepatitis B surface antigen (HBsAg) was found in the serum of 9/14 children with M.G. and in 1/14 children in an age and sex matched control group. The prevalence of HBsAg positivity in the M.G. children suggests a relationship between HBV infection and the disease. The high prevalence of males in HBsAg positive M.G. children suggests that males have an increased risk of contracting M.G. The absence of chronic liver disease in 8/9 HBsAg positive M.G. patients, and the lack of correlation between the clinical manifestations of kidney disease and the rate of HBV replication indicate that different mechanisms underlie the hepatic and renal pathologies.

Cocaine- and amphetamine-regulated transcript (CART) inhibits feeding and induces the expression of c-Fos in hypothalamic areas implicated in appetite regulation. Furthermore, the CART peptide is found in neurons regulating sympathetic outflow, which in turn play an integral role in regulating body temperature and energy expenditure. The CART gene was screened by single-strand conformation polymorphism and automatic sequencing in 130 (72 girls) unrelated obese Italian children and adolescents. Their Z-scores (mean +/- SD) of relative to BMI percentiles was 3.9 +/- 1.8, and the average age at obesity onset was 4.7 +/- 2.6 years. Two previously described silent polymorphisms were found in the 3' untranslated region: an adenine deletion at position 1457 in 9 patients (allele frequency 0.035) and an A/G substitution at position 1475 in 11 patients (allele frequency 0.042). We found no difference between the obese patients heterozygous for one of these polymorphisms and those patients homozygous for the wild allele with respect to their age of obesity onset, BMI Z-scores, and leptin levels. A missense mutation of G729C resulting in the substitution of Leu with Phe at codon 34, within the NH2-terminal CART region, has been detected in the heterozygous state in a 10-year-old obese boy who has been obese since the age of 2 years. The patient belongs to a large family of obese subjects. The mutation cosegregated with the severe obesity phenotype over three generations and was not found in the control population. Resting metabolic rates were lower than expected in the propositus (-14%) and his mother (-16%), who carried the mutation. Leucine at codon 34, conserved in this position in the human and in the rat sequences, immediately precedes a couple of lysine residues that may well represent a dibasic processing site. The Leu34Phe mutation might alter the susceptibility to proteolysis of this potential processing site, likely altering the CART effect on thermogenesis and energy expenditure.

The synthesis, characterization, and functional in vitro assays in cardiac tissues and smooth muscle (vascular and nonvascular) of a number of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines are reported. The binding properties for the novel compounds have been investigated and the interaction with the binding site common to other aryl-dihydropyridines has been demonstrated. Interestingly, the novel 4-aryl-dihydropyridines are L-type calcium channel blockers with a peculiar pharmacological behavior. Indeed, the imidazo[2,1-b]thiazole system is found to confer to the dihydropyridine scaffold an inotropic and/or chronotropic cardiovascular activity with a high selectivity toward the nonvascular tissue. Finally, molecular modeling studies were undertaken for the most representative compounds with the aim of describing the binding properties of the new ligands at molecular level and to rationalize the found structure-activity relationship data. Due to the observed pharmacological behavior of our compounds, they might be promising agents for the treatment of specific cardiovascular pathologies such as cardiac hypertrophy and ischemia. © 2008 American Chemical Society.

We investigated serum leptin levels in 103 mother-newborn-pairs; Cord leptin was significantly higher than mother's leptin (5.7 ± 5.5 vs. 22.1 ± 19.9 ng/ml; p

We evaluated the effect of one year of supplementation with iron plus zinc (12 mg/day of Fe+++ and 12.5 mg/day of Zn++), zinc alone (12.5 mg/day of Zn++) and placebo on growth and on the iron, zinc, copper and selenium tissue contents in 30 well-selected children of short stature (16 M and 14 F; 4-11 years old). Before and after supplementation, we measured the concentrations of iron, transferrin, ferritin, zinc and copper in serum, of zinc in erythrocytes and leukocytes, and of zinc, copper and selenium in hair, as well as glutathione peroxidase activity in erythrocytes. Before supplementation, ferritin and serum, erythrocyte and hair zinc contents were significantly lower than in age-matched controls, while the other measured indices were in the normal range. Iron plus zinc supplementation caused an improvement in growth rate in all subjects, i.e., the median Z-score increased from -2.22 +/- 0.45 to -0.64 +/- 0.55; (p < 0.01). In the zinc-supplemented group, only the subjects whose ferritin levels were higher than 20 ng/L before supplementation showed a similar improvement of growth rate. Iron plus zinc supplementation could be a reasonable treatment in short, prepubertal children affected by marginal zinc and iron deficiency.

We studied circulating levels of endothelin-1, catecholamines and nitric oxide after a mental arithmetic test in 14 patients with early ischemic lesions of the extremities due to systemic sclerosis and slightly impaired peripheral vascular flow. The test induced an increase (P < 0.01) in blood pressure, heart rate, endothelin-1 and catecholamine levels, whereas it did not change the low basal levels of nitric oxide. In healthy subjects (n = 20) the test significantly (P < 0.01) decreased endothelin-1 without affecting nitric oxide. The low basal levels of nitric oxide and the high plasma concentration of endothelin-1 after psychological stress cannot be explained by an impaired release from the limited ischemic lesions alone. This suggests a diffuse microvascular derangement that aggravates the course of peripheral microvascular ischemic lesions.

The repressor element-1 (RE-1) silencing transcription factor (REST) interacts with an RE-1 cis element and represses the transcription of neuron-specific genes in neuronal progenitors but is down-regulated in post-mitotic neurons. We report that REST expression is modified, in a time-dependent manner, in SH-SY5Y neuroblastoma cells exposed to insulin-like growth factor I (IGF-I), a polypeptide hormone affecting various aspects of neuronal induction and maturation. REST is increased in cells treated with IGF-I for 2 days and then declines in 5-day-treated cells concomitant with a progressive neurite extension. To investigate any role played by REST in neurodifferentiation by IGF-I, we employed an antisense oligonucleotide (AS-ODN) complementary to REST mRNA. In AS-ODN-treated cells, the effects elicited by IGF-I on cell proliferation are not influenced whereas a marked decrease of REST significantly increases neurite elongation without any gross perturbation of neurogenesis. Synapsin I and betaIII-tubulin gene promoters contain an RE-1 motif and their transcription is repressed by REST; both of them are increased in cells exposed to IGF-I for 5 days and further elevated by AS-ODN treatment. A parallel increase of growth cone-associated protein 43, a protein chosen as a neuronal marker not directly regulated by REST, is also observed. Therefore, REST is elevated during early steps of neural induction by IGF-I and could contribute to down-regulate genes not yet required by the differentiation program while it declines later for the acquisition of neural phenotypes. These results suggest a model in which differentiating neuroblastoma cells determine their extent of neurite outgrowth on the basis of REST disappearance.

We distinguished the scintigraphy pattern of congenital reflux nephropathy from that of acquired scarring in children with primary vesicoureteral reflux.We retrospectively evaluated the frequency and pattern of renal scintigraphy abnormalities in 41 patients with prenatally detected primary vesicoureteral reflux and in 322 with a mean age plus or minus standard deviation of 3.6 + or - 1 years in whom primary reflux was detected after urinary tract infection. Dimercapto-succinic acid scintigraphy was performed 4 to 6 and 1 to 4 months after reflux was diagnosed and/or the infection was cured in patients with urinary tract infection and prenatal detection, respectively.We identified 3 patterns of renal damage, including overall decreased uptake of renal radionuclide that was 20% to 40% of relative uptake, focal defects in uptake and shrunken kidney with relative uptake less than 20%. Scintigraphy revealed renal damage in 12 prenatally detected cases of vesicoureteral reflux, including overall decreased uptake in 58% and shrunken kidney in 42%, and in 111 cases of reflux detected at urinary tract infection, including overall decreased uptake in 50%, uptake focal defects in 37% and shrunken kidney in 13%. In the urinary tract infection group overall decreased uptake was present in 25 of 90 boys and in 40 of 232 girls (p = 0.05). Of these children 15% of the girls had uptake focal defects and 17% had overall decreased uptake. Overall decreased uptake and uptake focal defects were significantly more common in kidney-ureter units with reflux grade 4 or greater than in those with grade 3 or less (p = 0. 00001 and 0.027, respectively).When assuming that overall decreased radionuclide uptake indicates congenital reflux nephropathy and uptake focal defects indicate postnatal acquired scarring, congenital reflux nephropathy appears to be an important cause of renal damage in children with primary vesicoureteral reflux even beyond the neonatal age and even in girls. This finding is of interest because postnatally acquired scarring may but congenital reflux nephropathy may not be prevented.

We compared the accuracy of isotope cystography (IC) and fluoroscopic cystourethrography (FC) in detecting vesicoureteric reflux (VUR) in children. FC and IC were performed in 124 children, 56 boys and 68 girls, aged 1 month to 9.2 years (mean 2.1 years), admitted consecutively for suspected VUR over a 10-month period. VUR was diagnosed by one or both studies in 51 of 124 (41%) patients. The two methods were concordant for the detection of VUR in 84% of kidney-ureter units and in 93% for the detection or exclusion of severe VUR. IC detected VUR more accurately than FC, both when all grades of VUR were considered together (P=0.00001) and when only severe reflux was considered (P=0.004). VUR was missed by FC in 23 of 51 (45%) subjects. Of those 23, 12 had severe VUR detected on one side at least by IC. VUR was missed by IC in 3 subjects. IC is significantly more accurate than FC in the initial diagnosis of VUR, even of severe grade. IC is the method of choice for the first diagnosis of VUR. Boys with VUR diagnosed by IC also need FC to investigate for posterior urethral valves.

Calyceal microlithiasis (CM) is characterized by the sonographic finding of hyperechogenic spots less than 3 mm in diameter in renal calyces, and it may be the first step in calculus formation. From January 1992 to January 1998, we have observed 216 children with CM. The present report deals with 34 of them in whom renal sonography was negative at first observation and the diagnosis of CM was made only on repeated sonographic examinations. The presenting symptoms were recurrent abdominal pain, dysuria, and hematuria occuring alone or in combination. Half of the patients had hypercalciuria. A history of urolithiasis in at least one first- or second-degree relative was present in 85% of patients. Renal sonography was repeated after 6-22 months (mean 11) and showed unilateral CM in 16 subjects and bilateral in18. The finding of CM may be preceded by a period of time when symptoms and/or signs are present while microcalculi are not yet detectable. Repeated ultrasound examinations may be needed not only in patients with hypercalciuria but also in those with recurrent abdominal pain, dysuria, and/or hematuria not associated with hypercalciuria. Clin Pediatr. 1999;38:521-524

The aim of the present study is to evaluate blood levels (PbB) in a group of 500 (245 M, 255 F) children and adolescents of Campania (Italy) aged from 0.197 to 16.915 years, 269 (136 M, 133 F) of whom lived in urban zones and 231 (109 M, 122 F) in rural zones. PbB was assayed by electrothermal atomic absorption spectroscopy. The parents of the examined subjects children were interviewed about common risk factors for lead exposure using a standardized questionnaire. The PbB of children living in urban zones were significantly higher than the PbB of those living in rural zones (60.0 +/- 3.0 mg/L vs. 40.0 +/- 2.0 mg/L, p < 0.001). A PbB higher than 100 mg/L was found in 27 children (5.4%). We observed a significant correlation between age and PbB (p < 0.001, r = 0.529). Our data regarding children and adolescents demonstrate that the prevalence of PbB higher than 100 mg/L is greater in children living in urban areas (6.89%) than in subjects living in rural areas (3.89%). The findings can be explained by the higher presence of risk factors of Pb exposure in urban areas. Our data, if compared with those of previous studies concerning children of Campania, show a clear decrease of PbB. The correlation that we found between age and PbB indicates that long-term exposure at low doses more than a more intensive but short-term exposure seems to be important for the increase of blood lead levels.

Body growth was studied in 32 subjects with vesicoureteric reflux (VUR), diagnosed following the prenatal finding of urinary tract dilatation, who had normal renal filtration function and who received antibacterial prophylaxis by the first few days of life. They were followed for 1-5 years (mean 2.3 years). Most had persistent VUR during the 1st year of life. Body growth performance was compared with that of 94 subjects with VUR diagnosed and treated by us after the neonatal period. During the follow-up period, none of the patients with prenatally detected VUR had a height Z score below -2, nor a weight-for-height index below 90%, and 1 had variations in height Z score >/=1. The difference in the percentage of patients with prenatally detected VUR (1/32) and those with VUR diagnosed and treated after the neonatal period (20/94) who had variations in height Z score >/=1 was significant (P=0.035). Patients with prenatally detected VUR and normal renal filtration function, given antibacterial prophylaxis by the first few days of life, have normal body growth, although VUR still persists.

Zinc content of serum, hair and erythrocytes, urinary zinc excretion, zinc clearance (CZn) and the ratio of CZn to creatinine clearance (CCr) (CZn/CCr) were measured in 32 children aged between 2.1 and 14.4 years suffering from idiopathic nephrotic syndrome (INS) without renal failure (CCr greater than 70 ml/min 1.73 m2 body surface area). Nineteen subjects had proteinuria and the remaining 13 were in remission. All children received calcium and vitamin D supplementation while on steroid therapy. There was high dietary zinc and protein intake. The results were compared with those obtained from 19 healthy subjects (aged 2-14 years). Zinc concentration in serum, erythrocytes and urine were measured by a colourimetric method. Proton induced X-ray emission was used to determine zinc content in hair. In patients both with and without proteinuria, the mean contents of serum, hair and erythrocytes were significantly lower than in the control group. The urinary zinc excretion, CZn and CZn/CCr in INS children were significantly higher than in the control group. A positive correlation was found between urinary zinc and protein excretion. In spite of high dietary zinc intake and normal intestinal absorption, children with INS had a zinc deficiency. This was probably caused by an increased urinary zinc loss.

Hair trace element (TE) (Cr, Mn, Fe, Zn, Cu, Br, Rb, Sr, Pb) levels from 336 healthy subjects were measured by the Proton-Induced X-ray Emission (PIXE) method. The subjects were divided in three groups: 157 full-term neonates (75 male and 82 female), 86 children (41 male and 45 female) ages 6 to 11 yr, and 93 adolescents (51 male and 42 female) 11 to 16 yr old. Cu, Zn, Cr, and Br show an increase from birth to 8 yr and then decrease. Fe, Mn, and Sr strongly decrease up to 8 yr and then remain almost stable. Sex differences are present in Fe, Zn, and Br of children and in Cu, Cr, and Br of adolescents.

Zinc and copper status was examined in 19 healthy and 43 atopic children (22 asthmatics and 21 eczematous) 2-14 years old. Dietary intakes for energy, protein, zinc and copper and some nutritional indices (height, weight, serum protein, albumin, ceruloplasmin) were similar in the allergic and in the control group. The proton-induced X-ray fluorescence technique was used to assess zinc and copper concentrations in serum and hair. No difference was detected in serum zinc concentration between allergic and healthy children. In contrast, mean hair zinc level was lower (p less than 0.05) in allergic than in healthy children (99 +/- 6 vs. 147 +/- 9 micrograms/g). Mean serum copper content was higher in asthmatic than in control children while mean hair copper was higher (p less than 0.05) in asthmatic and eczematous children than in the control group. These findings suggest a different zinc and copper nutritional status between allergic and healthy subjects. Allergic children, in particular, seem to be a risk of zinc deficiency.

Serum HBsAg positivity prevalence was studied on 98 children affected by various nephropathies or obstructive uropathies and on a control group of 71 children, consecutively admitted into the same clinical ward, suffering from other than hepatic or renal diseases. No significant difference was found between the group of children with non-glomeruiar nephropathies or obstructive uropathies and the control group. The prevalence of HBsAg positivity was significantly higher in male children with membranous glomerulopathy and in those with lipoid nephrosis than in the control group. All HBsAg positive children with glomerulopathies were chronic carriers of the hepatitis B virus. However, though left undemonstrated, there still lies a probable pathogenetic relationship between the hepatitis B virus infection and membranous glomerulopathy. The authors hypothesize that an impaired immune response in male children with lipoid nephrosis may account for both the hepatitis B virus infection and the development of the glomerular disease.