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Biomedical subjects

E Riva

Publications and source records attributed to E Riva.

At least 19 recordsLinked to original sources

Impaired 2',3'-dideoxy-3'-thiacytidine accumulation in T-lymphoblastoid cells as a mechanism of acquired resistance independent of multidrug resistant protein 4 with a possible role for ATP-binding cassette C11.

Cellular factors may contribute to the decreased efficacy of chemotherapy in HIV infection. Indeed, prolonged treatment with nucleoside analogues, such as azidothymidine (AZT), 2',3'-deoxycytidine or 9-(2-phosphonylmethoxyethyl)adenine, induces cellular resistance. We have developed a human T lymphoblastoid cell line (CEM 3TC) that is selectively resistant to the antiproliferative effect of 2',3'-dideoxy-3'-thiacytidine (3TC) because the CEM 3TC cells were equally sensitive to AZT, as well as the antimitotic agent, vinblastine. The anti-retroviral activity of 3TC against HIV-1 was also severely impaired in the CEM 3TC cells. Despite similar deoxycytidine kinase activity and unchanged uptake of nucleosides such as AZT and 2'-deoxycytidine, CEM 3TC had profoundly impaired 3TC accumulation. Further studies indicated that CEM 3TC retained much less 3TC. However, despite a small overexpression of multidrug resistance protein (MRP) 4, additional studies with cells specifically engineered to overexpress MRP4 demonstrated there was no impact on either 3TC accumulation or efflux. Finally, an increased expression of the MRP5 homologue, ATP-binding cassette C11 (ABCC11) was observed in the CEM 3TC cells. We speculate that the decreased 3TC accumulation in the CEM 3TC might be due to the upregulation of ABCC11.

ATP-Binding Cassette Transporters↗

Phenylalanine hydroxylase mutations and phenylalanine-tyrosine metabolism in heterozygotes for phenylalanine hydroxylase deficiency.

UNLABELLED: The aim of this study was to determine whether any relationship exists between the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and semifasting conditions among heterozygotes in a matched case-control study. Parents of patients affected by PAH deficiency (n = 25) detected through the Italian Neonatal Screening Program and referred from January 1994 to June 2000, and parents of healthy children were investigated. In total, 68 subjects without any disease, 34 hyperphenylalaninaemia (HPA) heterozygous parents and 34 age- and gender-matched controls, were recruited. Plasma concentrations of Phe and Tyr in fasting and semifasting (1600 mg Phe oral load) conditions were the main outcome measures. DNA analysis for PAH mutations was performed in all 68 subjects. Compared with controls, heterozygotes showed higher fasting and semifasting Phe concentrations (p < 0.0001), lower semifasting Tyr concentrations (p = 0.015), lower Tyr variations (p = 0.003) and a higher Phe/Tyr ratio (p < 0.0001) in switching from fasting to semifasting conditions. Heterozygotes carrying a severe mutation showed semifasting plasma Tyr concentrations lower than controls (p = 0.019) but not significantly different from Tyr levels found in non-severe carriers (p = 0.197). The Tyr variations were minor in severe carriers than controls (p < 0.001) and non-severe carriers too, although with lower significance (p = 0.089). In six carriers of A403V mutation, parents of mild hyperphenylalaninaemics on an unrestricted diet, significant differences in variations from fasting to semifasting conditions were found compared with parents of patients on a diet. CONCLUSION: Although the great heterogeneity of PAH mutations limits any general conclusion, the results suggest that monitoring plasma Tyr variations may be more sensitive than plasma Phe in assessing the severity of PAH mutations in HPA heterozygotes.

Adult↗

Decay of HIV type 1 DNA and development of drug-resistant mutants in patients with primary HIV type 1 infection receiving highly active antiretroviral therapy.

The present study was aimed at describing the effect of highly active antiretroviral therapy (HAART) in 10 patients with primary HIV infection (PHI). Clearance rates of HIV RNA and HIV DNA in peripheral blood as well as the preexistence and the emergence of drug-resistant strains of HIV were determined over 52 weeks of treatment. The data indicate that HAART is able to induce a suppression of plasma viral load together with a significant decrease, but not a suppression, of peripheral blood mononuclear cell-associated proviral DNA in PHI subjects. Analysis of drug-resistant strains revealed that three PHI patients, showing a complete virologic response, developed mutations in the pol gene, thus suggesting that a persistent residual virus replication exists despite a sustained suppression of plasma viremia.

Adolescent↗

Sonographic findings in type I glycogen storage disease.

PURPOSE: The aim of this study was to document the sonographic appearance and dimensions of the liver and spleen in patients affected by type I glycogen storage disease and to correlate those findings with laboratory data to evaluate the potential role of sonography in diagnosing that disease. METHODS: Fourteen patients (age range, 3-26 years; 10 patients younger than 18 years) with type I glycogen storage disease proved by liver biopsy were studied prospectively with gray-scale sonography, color Doppler sonography, and spectral analysis. The liver, kidneys, spleen, portal system, hepatic veins, and hepatic arteries were evaluated. Laboratory data were correlated with sonographic findings. RESULTS: In 13 (93%), of 14 patients, the liver was enlarged, and in 11 patients (79%), hepatic echogenicity was increased. In 9 patients (64%), both kidneys were enlarged, and in 6 cases (43%), the spleen was enlarged. In all patients, flow in the portal, splenic, and superior mesenteric veins was hepatopetal, and flow in the hepatic veins was triphasic. In 5 patients (36%), both triglyceride and total cholesterol levels were higher than normal. No focal hepatic lesions were identified. Analysis found no significant association between sonographic findings and laboratory data. CONCLUSIONS: The most frequent sonographic findings in patients with type I glycogen storage disease were hepatomegaly, increased hepatic echogenicity, and enlarged kidneys. Sonography may help in the diagnosis of type I glycogen storage disease, but a liver biopsy is required for a definitive diagnosis.

Adolescent↗

Prolonged breast-feeding (six months or more) and milk fat content at six months are associated with higher developmental scores at one year of age within a breast-fed population.

Since dietary fats may affect brain composition and function in early life, we evaluated developmental indices at 1 year of age in relation to the duration of breast-feeding and the milk fat composition in a breast-fed population. A blinded monitor administered the Bayley test (2nd edition) to 1-year-old subjects born at term and exclusively breast-fed for at least 3 months. Weaning foods were introduced from the 5th month onward. Mothers' milk lipid composition (fat [wt/dL], fatty acid [wt/dL], FA% [% of total fatty acids]) was determined at 0, 1, 3, 6, 9, and 12 months. Statistics used were Student's t-test, Pearson's r, and multiple regression. Forty-four infants out of 95 recruited at birth met inclusion criteria. There was a progressive reduction of the number of breast-fed babies to 29 (6 mo), 17 (9 mo), and 10 (12 mo). Breast-feeding for 6 months or longer gave a 6.6-point advantage (95% confidence interval, -0.6, 13.8; P = 0.07 for the Bayley psychomotor developmental index (PDI) and 2.0 for the Bayley mental developmental index (MDI) (95% confidence interval, -3.2, 7.3; NS) compared with the 15 subjects breast-fed for fewer than 6 months. Among the milk lipid factors, the fat weight (mg/dL) at 6 months showed the highest association with the MDI (r = 0.55, P = 0.002). Thus, prolonged breast-feeding during the weaning process may result in a better developmental performance at 12 months, possibly due to the supply of fats contributing energy and/or affecting brain composition.

Aging↗

Long-chain polyunsaturated fatty acid concentrations in human hindmilk are constant throughout twelve months of lactation.

We assessed the total fat content and fatty acid concentrations in colostrum and throughout a nursing period of 12 months in a group of mothers recruited after delivery of full-term infants. Pooled human milk (hindmilk) was collected from all feedings over 24 hours at the following times: 1st day of nursing (colostrum), and at 1, 3, 6, 9, and 12 months. Total fat was quantified by a microgravimetric method. Fatty acids were analyzed by means of capillary gas chromatography. Comparisons were made with analysis of variance for repeated measures. Ten mothers completed the follow-up 12-month nursing period. We found that the total lipid content of hindmilk (mg/dL) rises more than 3-fold from the colostrum up to the 3rd month, and then more slowly up to the 12th month. Total saturated fatty acids progressively increase and total monounsaturated FA progressively decrease. Among long-chain polyunsaturated fatty acids, we found that the concentrations (mg/dL) of C20:4 and C22:6 remain stable from colostrum up to the 12th month of nursing, while their percentage levels are highest in colostrum and decrease afterwards in association with the increase in total fats. The C18:2n6 and C18:3n3 amounts progressively increase, following the trend of total fats. These data indicate that the secretion of arachidonic acid and docosahexaenoic acid during lactation remains constant, in spite of changes in total fat and in the linoleic acid and alpha-linolenic acid contents of milk.

Arachidonic Acid↗

Epidemiology of breast-feeding in Italy.

To evaluate the prevalence of breast-feeding in Italy and to describe the social and environmental factors associated with its practice, 1601 mothers were systematically recruited as representative of deliveries across all regions of Italy during November 1995. They were interviewed in March, June, and September of 1996. Interviews were conducted by telephone using a standardized questionnaire designed for computer scanning. The results indicated that 85% of mothers breast-fed their infants. The rates of breast-feeding at 3, 6, and 9 months were, respectively, 51%, 32%, and 19%. Among the 830 lactating mothers at 3 months, 72% practiced breast-feeding "on demand." Pediatricians, midwives, and gynecologists were the main sources of information about breast-feeding, but 43% of the mothers did not receive any information. Media (radio, TV) were mentioned as sources of information by only 2% of the mothers. Maternal factors significantly associated with breast-feeding and its duration were: a) having been breast-fed as infants, b) being nonsmokers, and c) being given information about lactation at the time of discharge from their hospital ward. Maternal characteristics (age, weight, and height), parental socioeconomic indicators (profession and education), and neonatal care (rooming-in practice) were not significantly associated with breast-feeding. Our results show that in Italy a fairly high percentage of mothers start breast-feeding and that both maternal factors (history and habits) and good information may support its duration.

Breast Feeding↗

Breastfeeding duration, milk fat composition and developmental indices at 1 year of life among breastfed infants.

The associations of breastfeeding duration and milk fat composition with the developmental outcome at 1 year of age were measured within 44 infants exclusively breastfed for 3 months, out of 95 recruited at birth. Pooled breast milk (hindmilk) of the mothers was analysed at colostrum, 1, 3, 6, 9, and 12 months for total fat and fatty acid content. Infants were examined at 12 months by means of the Bayley test. There was a progressive reduction of the number of breastfed babies after the introduction of solids to 29 (6 months), 17 (9 months) and 10 (12 months). After adjusting for major confounders, infants breastfed for 6 months or longer showed a trend to have an advantage at the Bayley psychomotor developmental index compared to those breastfed >3 and <6 months (95% CI for difference: - 0.6, 13.8; P= 0.07) while the Bayley mental developmental index (MDI) was just 2.1 points higher. Among the milk fat components considered for each time-point, the total fat content at 6 months showed the strongest association with the MDI at 12 months (r=0.59, P=0.001). Prolonging breastfeeding during the weaning process may result in a better developmental performance at 12 months, possibly due to the supply of fats affecting brain composition.

Breast Feeding↗

Biochemical effects of supplemented long-chain polyunsaturated fatty acids in hyperphenylalaninemia.

Hyperphenylalaninemic (HPA) children display low levels of long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), in circulating lipids and erythrocytes. We have investigated the effects on the blood fatty acid status and lipid picture of a balanced supplementation with LCPUFA in HPA children through a double-blind, placebo-controlled trial. A total of 20 well-controlled HPA, school-age children were randomized to receive through a 12-month trial fat capsules supplying either 26% fatty acid as LCPUFA (including 4.6%gamma -linolenic acid, 7.4% arachidonic acid, AA, 5.5% eicosapentaenoic acid and 8% DHA) or placebo (olive oil). The study supplementation was administered in order to provide 0.3-0.5% of the individual daily energy requirements as LCPUFA. Reference data were obtained from healthy children of comparable age. Among HPA children (whose DHA status was poor at baseline), those supplemented with LCPUFA showed an increase of around 100% in the baseline DHA levels in plasma phospholipids and erythrocytes. No changes of AA levels were observed. Blood lipid levels did not significantly change. A balanced supplementation with LCPUFA in treated HPA children may improve the DHA status without adversely affecting the AA status.

Adolescent↗

Recovery of hematopoietic activity in bone marrow from human immunodeficiency virus type 1-infected patients during highly active antiretroviral therapy.

The mechanisms responsible for the hematopoietic failure in human immunodeficiency virus type 1 (HIV-1)-infected patients are still unknown. Several findings indicate that the in vitro proliferative potential of precursor cells from AIDS patients is reduced. The changes seen in bone marrow (BM) morphology and the defective BM functions associated with cytopenias have both been proposed as potential explanations. In patients treated with highly active antiretroviral therapy (HAART) an immune reconstitution associated with increased whole blood cell counts has been described. We have investigated the effects of HAART on the number of colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs), using long-term BM cell cultures (LTBMC) in a group of subjects with HIV-1 infection enrolled in an open study to evaluate the mechanisms of immune reconstitution during HAART. In each patient, the increase in colony growth was homogeneous, regardless of the type of hematopoietic progenitor cells assayed; in four subjects an increase in the most primitive progenitor cells (LTC-ICs) was observed. These findings were associated with the in vivo data showing increased numbers of BM mononuclear cells (BMMCs) after HAART and with a rise in peripheral CD4(+) T cell counts and decreased levels of plasma HIV-1 RNA. A decreased number of hematopoietic progenitor cells and/or a defective modulation of progenitor cell growth might be the cause of the hematological abnormalities in AIDS patients. Controlling HIV-1 replication by HAART could determine a restoration of stem cell activity, probably because of the suppression of factors that inhibit normal hematopoiesis.

Adult↗

The number of HIV DNA-infected mononuclear cells is reduced under HAART plus recombinant IL-2. IRHAN Study Group.

It is common opinion that, in addition to potent antiretroviral regimens which effectively reduce plasma viremia, new strategies should be developed to ensure the reduction of cell-associated HIV DNA load together with HIV RNA plasma levels. The present study explored whether the number of provirus-infected cells can be reduced by combined antiviral and immunomodulatory regimens. Thus, 14 naive patients (with CD4 > 400/microl and plasma HIV RNA copies > 5000/ml) were randomly assigned to receive highly active antiretroviral therapy (HAART) alone or HAART plus rIL-2. Plasma viremia (measured by a commercial RT-PCR assay) and the number of provirus-infected cells (measured by an endpoint cell dilution PCR assay) were monitored at the enrollment and after 12 weeks of treatment. The results indicate that while HAART and HAART plus rIL-2 are both able to significantly reduce plasma viremia after 12 weeks of treatment, a significant reduction of the number of provirus-infected cells can be achieved only by treatment with HAART plus rIL-2.

Anti-HIV Agents↗

Beef allergy in children.

Beef allergy was poorly known before the '90s. Since then, a number of papers appeared elucidating the nature, epidemiology, and symptoms of beef allergy in children allergic to cow's milk and children suffering from atopic dermatitis. It is now clear that beef allergy is not an infrequent occurrence, with an incidence between 3. 28% and 6.52% among children with atopic dermatitis, its incidence may be as much as 0.3% in the general population. A diagnosis of beef allergy must be supported by skin prick tests, RASTs, and challenges. The specificity and sensitivity according to type of test and the type of extract, however, remains to be evaluated. Despite the fact that other allergens can be sensitizing, the major beef allergen is bovine serum albumin (BSA). Beef-sensitive children are also sensitized to ovine serum albumin, as well as to other serum albumins; therefore, the use of alternative meats in beef-allergic children must be carefully evaluated on an individual basis. Because industrial heat processing is more efficient than domestic cooking in reducing reactivity in beef-sensitive children, freeze-drying and homogenization may support the introduction of processed beef into the diet of beef-allergic children.

Allergens↗

Adolescence: macronutrient needs.

Dietary needs during adolescence lack specific definitions, and most evidence is derived from indirect indications. The data on dietary needs for energy and proteins are mainly extrapolated from subjects in other age-classes. Lipids and carbohydrates are being progressively considered for preventive purposes since the qualitative distribution of saturated and unsaturated fats and slowly and rapidly absorbed carbohydrates, respectively, seems to be associated with metabolic index predictors of degenerative disorders in later stages of life. The recent results of multicentric autoptic studies in young people from the US indicate that the lipoprotein status of the second decade of life is associated with the first raised arterial lesions in the third decade. The evidence of these links needs further confirmation from ongoing surveys. We must recognize that adolescence is a critical period of life, and food fads may deeply change the dietary habits acquired within the familiar group. As nutritionists, we may suggest that all adolescents should be supplied with nutritional support in terms of education, maybe at school, to improve their knowledge of nutrition.

Adolescent↗

Early macronutrient intake and overweight at five years of age.

OBJECTIVE: To examine the influence of the macronutrient intake in early life on the development of overweight in children. DESIGN AND SUBJECTS: An ongoing longitudinal study including 147 randomized healthy children followed up from birth. MEASUREMENTS: Anthropometric parameters were measured at birth, 1 and 5 y of age. Dietary habits at the age of 1 and 5 were assessed by age-adjusted food-frequency questionnaires and 24 h recalls. Parents' body mass index (BMI) was also recorded. RESULTS: Parental overweight was observed for 51% children. The prevalence of overweight at the age of 5 y was higher in children with than without parental overweight (37.3% vs 8.3%, P<0.0001). Five-year old overweight children had a higher percentage intake of proteins at the age of 1 y than non overweight children (22% vs 20%, P=0.024) and lower intake of carbohydrates (44% vs 47%, P=0.031). Multiple logistic analysis confirmed that protein intake at 1 y of age was associated with overweight at 5 y (P=0.05). In children born from overweight mothers, prevalence of overweight at the age of 5 y tended to be higher in bottle-fed than in breast-fed ones (62.5% vs 23.3%, P=0.08). CONCLUSION: Parental overweight is a major risk factor for childhood overweight in the first years of life, but an early high protein intake may also influence the development of adiposity.

Body Mass Index↗

Effects of long-chain polyunsaturated fatty acid supplementation on fatty acid status and visual function in treated children with hyperphenylalaninemia.

BACKGROUND: Children with phenylalanine-hydroxylase deficiency (type-I hyperphenylalaninemia, HPA) follow a low-phenylalanine diet, severely restricted in animal foods and long-chain polyunsaturated fatty acids (LCPUFA). Consequently, they have a poor LCPUFA status, particularly for docosahexaenoic acid (DHA). DHA is relevant to visual and neural development. OBJECTIVE: To investigate the effects of a 12-month supplementation with LCPUFA in a double-blind, placebo-controlled trial in treated children with HPA. STUDY DESIGN: Twenty children with well-controlled HPA were randomly allocated to receive either a fat supplement (supplying 26% as fatty acids including DHA, 8%) or a placebo. The fatty acid composition of erythrocyte lipids and the visual evoked potentials were measured at baseline and after 12 months of supplementation. Reference data were obtained from healthy children of comparable age. RESULTS: At baseline children with HPA had a poorer DHA status and prolonged P100 wave latencies than the reference group. At the end of the trial the LCPUFA group showed a significant increase in DHA levels of erythrocyte lipids. In the LCPUFA group P100 wave latency decreased and was negatively associated with the DHA changes. CONCLUSIONS: A balanced dietary supplementation with LCPUFA in children with HPA is associated with an increase of the DHA pool and improved visual function.

Child↗

Free amino acid content in standard infant formulas: comparison with human milk.

OBJECTIVE: To compare the concentration of non-protein nitrogen (NPN) and free amino acids (FAA) in powdered and liquid commercial formulas with that in human milk. METHODS: The non-protein nitrogen and FAAs in pooled breast milk was compared with that in 11 protein-modified starting infant formulas (seven powdered, four liquid whey-predominant formulas) and one powdered soy-formula. Human milk was collected at the end of each feeding (hindmilk) over 24 hours in a group of 40 healthy lactating women after delivery of full-term infants at age one month. RESULTS: In human milk glutamic acid plus glutamine and taurine were the prevalent amino acids, accounting for around 50% total FAA. In the analysed formulas the total FAA fraction was 10% or even less than in human milk, mostly represented by taurine, while methionine was high in soy formula. The sum of glutamic acid and glutamine in all the formulas was much lower than in human milk. CONCLUSIONS: Breastfed infants are supplied with FAA, mainly glutamic acid and glutamine, compared to formula-fed counterparts. The different FAA intake might be the origin of some functional differences at the enteral level between breast- and formula-fed infants.

Amino Acids↗

Fatty acid composition of plasma lipids in HIV-infected children. Comparison with seroreverters.

Children infected with the type-1 human immunodeficiency virus (HIV) are at risk of nutritional deficiencies leading to an impaired polyunsaturated fatty acid (PUFA) status. The aim of the present study was to compare the PUFA composition of plasma lipid classes (total lipids, phospholipids (PL), cholesteryl esters (CE) and triglycerides) in well-growing HIV-infected children with an age-matched group of HIV-seroreverter children born to infected mothers. Eighteen HIV children, of both sexes, mean age 4.6 y, most of whom under combined antiretroviral regimen, were compared with 18 seroreverters, mean age 5.4 y, comparable for demographic, anthropometric and dietary characteristics. All children had adequate growth parameters (weight and height > 3rd percentile). The plasma fatty acid content was similar in the two groups. HIV seropositive subjects showed lower linoleic acid (LA) levels in all the plasma lipid fractions, with higher 20:3n-9 and 20:5n-3 levels in PL and CE. The plasma PL triene/tetraene ratio (marker of relative LA deficiency) related positively to the viral load and negatively to the blood CD4+ lymphocyte count. Compared to age-matched seroreverter subjects, HIV-seropositive children show a lipid fatty acid status suggestive of relative LA deficiency and increased turnover of the PUFA series.

Child↗