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Biomedical subjects

E Riva

Publications and source records attributed to E Riva.

At least 145 records · Page 8Linked to original sources

Age-dependent changes in myocardial susceptibility to ischemic injury.

We studied the relation between age and the heart's ability to tolerate ischemia. Groups of 5-7 isolated Langendorff perfused hearts from neonatal (5 days old), immature (11-44 days old), and adult (54 days old) rats, were subjected to 60 minutes of global ischemia and 60 minutes of reperfusion at 37 degrees C. Pre-ischemic left ventricular developed pressure was 54 +/- 1, 56 +/- 2, 59 +/- 4, 80 +/- 3, 91 +/- 9, 91 +/- 8, 94 +/- 3, 101 +/- 10, 107 +/- 8 and 132 +/- 4 mmHg in the 5, 11, 14, 18, 23, 26, 33, 40, 44, and 54 day old groups, respectively. Left ventricular developed pressure recovered to 65 +/- 13, 69 +/- 4, 103 +/- 14, 84 +/- 10, 81 +/- 3, 59 +/- 11, 42 +/- 10, 34 +/- 6, 34 +/- 6 and 25 +/- 7% respectively. Ischemia-induced contracture was greater in adult hearts and the time-to-onset and the time-to-peak contracture decreased with increasing age. Leakage of creatine kinase after ischemia correlated poorly with the recovery of contraction. Left ventricular end-diastolic pressure, at the end of 60 minutes of reperfusion, increased in an age-dependent manner from a pre-ischemic value which was set at 2-8 mmHg to 14 +/- 4, 22 +/- 2, 21 +/- 5, 27 +/- 3, 47 +/- 16, 52 +/- 7, 71 +/- 7, 81 +/- 9, 73 +/- 5, and 82 +/- 8 mmHg in the 5, 11, 14, 18, 23, 26, 33, 40, 44, and 54 day old groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Alternative splicing of mutant LDL-receptor mRNA in an Italian patient with familial hypercholesterolemia due to a partial deletion of LDL-receptor gene (FHPotenza).

An analysis of LDL-receptor gene was performed on an Italian patient with heterozygous familial hypercholesterolemia. Restriction enzyme analysis showed that the proband was heterozygous for a deletion of 4.5 kb spanning the 5' end of exon 13 (45 nucleotide residues) to intron 15. Amplification of genomic DNA, using polymerase chain reaction (PCR), followed by direct sequencing, showed that this deletion was identical to the one reported by Lehrman et al. (1986. Proc. Natl. Acad. Sci. 83: 3679-3683). As only the normal LDL-receptor mRNA was detectable in proband fibroblasts by Northern blot, we used reverse transcription-PCR to amplify the mutant mRNA using primers complementary to exon 6 (sense) and exon 18 (antisense). The amplification of control cDNA resulted in a single fragment of 1725 nucleotides containing the normal sequence. The amplification of cDNA from the proband produced the 1725-nucleotide fragment (as in the control) and three additional fragments (F1, F2, and F3) of smaller size. The direct sequence showed that in the F1 fragment exon 12 was joined to exon 16; in the F2 fragment exon 12 was joined to exon 17; and in the F3 fragment exon 11 was joined to exon 16. Thus, the deletion-bearing allele generated three mRNAs, two of which resulted from alternative splicings leading to the skipping of exons 16 and 12, respectively. It is expected that the translation of these mutant mRNAs will generate three aberrant proteins, the synthesis of which should be negligible in view of the very low content of the corresponding mRNAs.

Alternative Splicing↗

In vitro selection of human immunodeficiency virus type 1 resistant to 3'-azido-3'-deoxythymidine.

3'-Azido-3'-deoxythymidine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) was obtained by growing HTLV-IIIB in C8166 cell cultures in the presence of inhibitory concentrations of AZT. The AZT-resistant HIV-1 was capable of replicating, as measured by infectious virus yield, and inducing cytopathic effect in the presence of AZT concentrations able to completely suppress the replication of parental HTLV-IIIB. Cloning of the AZT-resistant HIV-1 revealed that a number of different variants of HIV-1 with various degrees of sensitivity to AZT emerged during propagation of HTLV-IIIB in C8166 cells in the presence of the drug. PCR experiments performed on DNA extracted from C8166 cells infected with a resistant strain revealed that viral DNA was produced in the presence of inhibitory concentrations of AZT, while viral DNA in C8166 cells infected with the parental virus was drastically inhibited. Reverse transcriptase isolated from the AZT-resistant HIV-1 variant failed to show resistance to AZT 5'-triphosphate.

Antiviral Agents↗

Cholesterol and lipoprotein levels in Milanese children: relation to nutritional and familial factors.

Dyslipidemia is a major risk factor for atherosclerosis in adults and children. This study investigated the levels of lipoproteins in a northern Italian pediatric population, in relation to nutritional and familial factors. We studied 650 children on the basis of a 3-day dietary record; 361 of these children had their lipid levels [total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides] measured by a dry, multilayer method and apoprotein A-I and B by an immunonephelometric method. Familial history of cardiovascular disease and dyslipidemia was recorded. Anthropometric variables were taken for each child. Mean TC and low-density lipoprotein cholesterol (LDL-C) were high compared with southern Italian data, but similar to those of other Western countries. Family history of cardiovascular disease could not identify children with higher levels of atherogenic lipoprotein. Nutritional factors affected lipoprotein levels. The most important finding was a higher TC/HDL-C ratio in the lower quartile of polyunsaturated fatty acid intake. Obese children had higher levels of ApoB, triglycerides, TC and LDL-C, and lower levels of HDL-C; figures were higher for obese boys than for obese girls. Our study confirms a high prevalence of elevated levels of atherogenic lipoproteins among the northern Italian pediatric population and an association with nutritional factors and weight.

Anthropometry↗

Resistance of HIV-1 to AZT might also involve the cellular expression of multidrug resistance P-glycoprotein.

Resistance of tumor cells to the antigrowth activity of several cytotoxic compounds has been associated with the expression of the so-called multidrug resistance protein or P-glycoprotein. This article addresses the question whether the expression of such protein could also affect the sensitivity of HIV to AZT. Our data indicate that this possibility does exist. In fact, multidrug-resistant CEM VBL100 cells, which express high levels of P-glycoprotein, are less sensitive to both the antiproliferative activity and the antiviral action of AZT. Additionally, our data suggest that this phenomenon is specifically mediated by P-glycoprotein since trifluoroperazine, which is known to circumvent multidrug resistance due to the action on P-glycoprotein, increases the intracellular accumulation of AZT and affects the sensitivity of HIV to AZT. Although the biological and clinical significance of these observations has still to be established, this study suggests that cellular factors, other than virus itself, should be taken into account to address the phenomenon of drug resistance of HIV.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effect of lisinopril and isosorbide-5-mononitrate on hemodynamics and mortality in rats with permanent coronary artery occlusion.

We studied the hemodynamic effects of lisinopril and isosorbide-5-mononitrate in rats with permanent coronary occlusion. Rats (n = 35) underwent left coronary occlusion, and ECGs were recorded before and after occlusion. Ventricular arrhythmias were observed in 57% (20 of 35) of animals. Treatment was given immediately after coronary occlusion and for 2 subsequent days. The control group received 100 mg/kg lactose (i.e., 80% vehicle for isosorbide-5-mononitrate). Lisinopril (100 mg/kg body weight) and isosorbide-5-mononitrate (400 mg/kg body weight) reduced systolic blood pressure (SBP) from 134 +/- 9 to 115 +/- 9 mm Hg (p less than 0.05) and from 137 +/- 9 to 126 +/- 9 mm Hg, respectively; the hypotensive effect lasted 2-3 days. No effect on BP was noted in the control group. Overall mortality was 23%; 8 of 35 animals died within 10-15 min of coronary occlusion. Survival after 4 weeks was similar in each group (approximately 80%). Left ventricular pressure (LVP) was measured 4 weeks after coronary artery occlusion and was similar in each group. However, dP/dt was lower in hearts with infarction than in hearts with none (12,608 +/- 906 vs. 8,992 +/- 1,242 mm Hg/s). The extent of the infarction was the same in groups with coronary artery occlusion. Lisinopril is more effective than isosorbide-5-mononitrate in reducing BP after acute myocardial infarction (AMI). Medium-term survival (4 weeks) is not jeopardized by effective treatment with angiotensin-converting enzyme (ACE) inhibitors or long-acting nitrates.

Angiotensin-Converting Enzyme Inhibitors↗

Familial history of cardiovascular disease and blood lipid pattern in newborn infants.

The levels of atherogenic lipid fractions are higher in children with a family history of ischemic cardiovascular disease (CD). This study was designed to examine this relationship in neonates. A total of 1276 newborns were investigated; 400 cord blood samples were collected for measurement of triglycerides (TG), total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C); on day 4, 1200 capillary samples were taken for TC and TG measurements. Male newborns with a positive history of CD had higher concentrations of cord blood TC (P less than 0.04) and LDL-C (P less than 0.02). On day 4 this difference in TC was no longer detectable (LDL-C not determined). A coronary heart disease (CHD) risk factor family history is sensitive (0.87) in predicting high cord blood concentrations of LDL-C, the specificity being 0.46 and the positive predicting value 0.08.

Cardiovascular Diseases↗

Prevention of exercise-induced bronchoconstriction by a new leukotriene antagonist (SK&F 104353). A double-blind study versus disodium cromoglycate and placebo.

The effects of 800 micrograms of inhaled SK&F 104353, a peptidoleukotriene receptor antagonist, and of 20 mg disodium cromoglycate (DSCG) on exercise-induced bronchoconstriction were compared in 18 asthmatic patients. The study was conducted according to a double-blind, crossover, randomized, placebo-controlled design. Two baseline exercise tests were carried out, and pulmonary function tests were done before and at 1, 5, 10, 15, 20, and 30 min after completion of the exercise. Patients showing a 20% or greater decrease in FEV1 in both exercise challenges entered the blinded portion of the study. When placebo was administered before exercise, FEV1 fell to the same extent as during the baseline phase. After SK&F 104353 and DSCG, the bronchoconstriction was attenuated. The mean maximal percentage fall in FEV1 after exercise was 29% after placebo and 20% after SK&F 104353 and DSCG. The differences between the two active treatments did not reach the 5% level of statistical significance, though at 20 min SK&F 104353 showed a more pronounced effect than DSCG. The protective effect suggests an important role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

Adult↗

Combined zidovudine and interferon-alpha 2a therapy in children with acquired immune deficiency syndrome.

A study was carried out in five children with acquired immune deficiency syndrome to assess the effect of combined zidovudine/interferon-alpha 2a therapy with that of zidovudine given alone on immunological profiles and plasma zidovudine concentrations. Immunoglobulins A, G and M, total and absolute CD4 lymphocyte counts, and p24 antigen concentrations did not differ significantly when children were treated with 300 mg/m2 zidovudine given orally once every 12 h, or with 150 mg/m2 zidovudine plus 1.5 or 3 MIU interferon-alpha 2a given intramuscularly three times weekly. Peak plasma zidovudine concentrations were significantly (P less than 0.05) lower when combined treatment with 150 mg/m2 zidovudine/1.5 MIU interferon-alpha 2a was administered compared with 300 mg/m2 zidovudine alone, or combined 150 mg/m2 zidovudine/3 MIU interferon-alpha 2a. The results suggest that combination zidovudine/interferon-alpha 2a therapy may be more efficacious than zidovudine alone and that the normal zidovudine dose may be reduced if interferon-alpha 2a is given in addition, thus reducing the side-effects associated with zidovudine.

Acquired Immunodeficiency Syndrome↗

Vegetable foods in weaning.

Vegetable foods (cereals, non-starchy vegetables, legumes) make a unique nutritional and metabolic contribution during weaning. They provide proteins that are of low biological value individually but whose value can be raised by consuming appropriate combinations: minimal amounts of lipids, mostly essential polyunsaturated fats; complex carbohydrates; and soluble fibre, which are fermented by colonic flora to short-chain fatty acids that have beneficial effects. Insoluble fibre, minerals, trace elements and vitamins are also nutritionally important components of vegetable foods. Vegetable foods lower the calorific density of meals, modulate nutrient and antigen absorption, and promote a physiological copropoiesis. Recent nutritional surveys have shown that 12-month old children eat an excessive amount of animal proteins. Whole cereals and non-starchy vegetables, including whole legumes, should be routinely eaten during weaning to improve nutritional balance and to make children accustom to eating fibre, which has prophylactic properties. The daily intake of fibre should be progressively increased to 5 g during the first year of life.

Humans↗

[Ibopamine in the treatment of congestive heart failure. Multicenter follow-up study].

OBJECTIVE: To assess safety and efficacy of ibopamine, 200 mg TID, added to conventional treatment of congestive heart failure. DESIGN: A prospective, longterm, open study over two years (1986-88). A multicenter trial. SETTING: Outpatients of Departments of Internal Medicine of S. Francisco Xavier Hospital and Sta. Maria Hospital, and Departments of Cardiology of Sta. Cruz Hospital and Hospital Militar Principal, Lisbon. PATIENTS AND METHODOLOGY: 63 patients, 49 males from 34 to 80 years (m = 55.6 +/- 11.36) and 14 females from 41 to 80 years (m = 63 +/- 10.2), with congestive heart failure, NYHA class II in 52 patients (82.5%) and NYHA class III in 11 patients (17.5%) with a mean disease duration of 47.9 months entered into the study. Digoxin, diuretics, nitrates and antiarrhythmic drugs were allowed as concomitant therapy. Patients carried out clinical examination, ECG and laboratory tests monthly and X-Ray at the beginning and at the end of each year of the study. RESULTS: 42 patients completed one year of treatment and 20/42 continued for an additional year, 17 patients completed this second year of follow-up. From the 42 patients who completed the first year period, the NYHA class changed from II to I in 17/38 from II to III in 2/38 patients from III to II in 3/4 patients, and from III to IV in one patient. Twenty patients dropped during the first year of treatment. Six for non-compliance (less than 80% of the treatment). Two were submitted to cardiac valve surgery. Seven had cardiovascular clinical events: one ventricular tachycardia, one atrial fibrillation, one pulmonary edema, one patient had no therapeutic effect, two patients had anxiety and fatigue and one patient died suddenly. One diabetic patient had uncontrolled hyperglycemia. One patient had gastric ulcer. Two had nausea and vomiting. Dysrhythmia and nausea and vomiting were the only clinical events, considered, respectively, possibly related and related, to ibopamine. During the second year of treatment 9/11 patients were stabilized in NYHA class I and 6/9 in NYHA class II, one patient changed from class II to class I, and one patient changed from class I to class II of the NYHA. Three patients did not complete the second year of treatment; one due to abnormal creatininemia; one for probable pulmonary embolism with CHF worsening; the third died suddenly. None of these events was considered related to ibopamine. Heart rate, arterial pressure, laboratory values and cardiothoracic index did not vary over the two years of the study. CONCLUSIONS: This has been the first study with data from patients treated with 200 mg TID of ibopamine during two years. Ibopamine has been shown to be a safe and useful drug added to conventional treatment of cardiac heart failure. Clinical events were few and well controlled after ibopamine interruption.

Adult↗

[Acquired immunodeficiency virus (HIV-1). Biological aspects and virological diagnosis].

The etiologic agent of the acquired immunodeficiency syndrome is a retrovirus included in the subclass of lentiviruses in view of certain characteristics common to these viruses. Their similarity is mainly represented by the extreme slowness of disease manifestation and by the fact that HIV, like other lentiviruses, spreads within the organism in spite of an immune reaction. The mechanism of replication is not dissimilar to that of other retroviruses except for the expression of a particularly large number of regulating genes the most important of which are called tat, rev, and nef. Further genes with a probable regulating function are nef, vpr, and vpx. In the field of diagnostic virology, together with normal isolation tests, a technique that has become particularly important is PCR (polymerase chain reaction) which allows to obtain a relevant amount of specific viral DNA sequences by the use of a DNA polymerase and specific primers.

AIDS Serodiagnosis↗

Metabolic needs, utilization and dietary sources of fatty acids in childhood.

Fatty acids are molecules that differ in the length of their carbon chain and the number of double bonds within them. Each of the resulting "families" has its own peculiarities as regards energy, structure and metabolism. Passing from the short, saturated chains to the very long polyunsaturated ones produces an increasing degree of specialization in metabolic and structural functions important for the body's development and general homeostasis. The fetus and neonate (especially if preterm), the breast-fed and weaning baby all need fatty acids in the right amounts and ratios to achieve full expression of their genetic growth potential, especially of nerve tissues. Intake in these age groups depends on dietary factors such as the mother's diet during pregnancy, the type of milk (human or artificial), and the weaning schedule. Later in childhood and in adolescence not only must the body's somatic growth needs be covered, but intake must be adequate to lay the basis for prevention of chronic-degenerative pathologies. Dietary recommendations are therefore based on encouraging a normocaloric feeding pattern, with a controlled total and saturated lipid proportion and balanced intake of unsaturated fatty acids.

Adolescent↗

High-performance liquid chromatographic determination of rifapentine and its metabolite in human plasma by direct injection into a shielded hydrophobic phase column.

A simple high-performance liquid chromatographic method for determination of rifapentine, a cyclopentyl semisynthetic analogue of rifamycin belonging to the class of piperazinyl hydrazone derivatives of 3-formylrifamycin SV, and its metabolite, 25-desacetylrifapentine, in human plasma was developed using direct injection of the sample onto a Supelco LC HISEP column. The mean recovery was 100.3% for rifapentine and 99.7% for the metabolite and the precision of the assays was 3% and 7%, respectively. The limit of determination was 0.2 micrograms/ml and the method was validated for concentrations up to 64 micrograms/ml for rifapentine and 32 micrograms/ml for the metabolite. The results correlated well with those of the microbiological assay with Sarcina lutea as test organism.

Anti-Bacterial Agents↗

Molecular characterization of PKU allele prevalent in southern Europe and Ireland.

A novel substitution has been characterized in the phenylalanine hydroxylase (PAH) gene that is linked exclusively to mutant haplotype 6, which is prevalent in southern Europe but rare in northern and eastern Europe. It is a G-to-A transition in intron 10, 11 bases from exon 11. This substitution creates an additional AG dinucleotide, which may serve as a cryptic splice acceptor site. Individuals who bear this substitution in the homozygous state have a severe PKU phenotype with pretreatment serum phenylalanine levels over 1200 mumol/liter. The frequency and distribution of this substitution among European populations suggests two possible founding populations, one being Middle Eastern and the other Roman. The use of this substitution as a marker to identify PKU chromosomes will be an invaluable aid to carrier screening and prenatal diagnosis in populations where mutant haplotype 6 is prevalent.

Alleles↗

Isolated, perfused neonatal rat heart preparation for studies of calcium and functional stability.

We describe an isolated, perfused preparation for neonatal rat hearts to assess the relationship between extracellular calcium and (1) cardiac function and (2) contractile stability over 2 hours of perfusion. Neonatal (3 to 5 days old) rat hearts (n = 6 per group) were perfused for 30 minutes (Langendorff) with oxygenated buffer (37 degrees C) containing 1.4 mmol/L calcium (control period) and 90 minutes with buffer containing 0.5, 0.8, 1.0, 1.2, 1.4, 1.8, or 2.5 mmol/L calcium. Upon changing from 1.4 mumol/L to either a higher or low calcium concentration there were no significant changes in left ventricular developed pressure, heart rate, or coronary flow. However, left ventricular developed pressure progressively deteriorated in a time-dependent and calcium-dependent manner. Thus, after 90 minutes, developed pressure fell to 18% +/- 2%, 27% +/- 3%, 41% +/- 5%, 47% +/- 8%, 55% +/- 10%, 64% +/- 5% and 76% +/- 4% of its initial value with 0.5, 0.8, 1.0, 1.2, 1.4, 1.8, and 2.5 mmol/L calcium. In conclusion, in studies with the neonatal rat heart, extracellular calcium concentrations in the range of 1.8 to 2.5 mmol/L are recommended.

Animals↗

Phenylketonuria missense mutations in the Mediterranean.

Two missense mutations have been identified in the phenylalanine hydroxylase (PAH) genes of an Italian phenylketonuria (PKU) patient. Both mutations occurred in exon 7 of the PAH gene, resulting in the substitution of Trp for Arg at amino acid 252 (R252W) and of Leu for Pro (P281L) at amino acid 281 of the protein. Expression vectors containing either the normal human PAH cDNA or mutant cDNAs were constructed and transfected into cultured mammalian cells. Extracts from cells transfected with either mutant construct showed negligible enzyme activity and undetectable levels of immunoreactive PAH protein as compared to the normal construct. These results are compatible with the severe classical PKU phenotype observed in this patient. Population genetic studies in the Italian population revealed that both the R252W and the P281L mutations are in linkage disequilibrium with mutant restriction fragment length polymorphism (RFLP) haplotype 1, which is the most prevalent RFLP haplotype in this population. The R252W mutation is present in 10% and the P281L mutation is present in 20% of haplotype 1 mutant chromosomes. These mutations are both very rare among other European populations, suggesting a Mediterranean origin for these mutant chromosomes.

Base Sequence↗