PubMed Health⌕ Search

Biomedical subjects

L Ferrara

Publications and source records attributed to L Ferrara.

At least 19 recordsLinked to original sources
PubMed2005

Gene therapy progress and prospects: targeted gene repair.

The capacity to correct a mutant gene within the context of the chromosome holds great promise as a therapy for inherited disorders but fulfilling this promise has proven to be challenging. However, steady progress is being made and the development of gene repair as a viable and robust approach is underway. Here, we present some of the recent advances that are helping to shape our thinking about the feasibility and the limitations of this technique. For the most part, these advances center on understanding the regulation of the reaction and validating its application in animal models.

DNA Repair↗
PubMed2003

The accumulation of alpha-Tocopherol and Retinol in the milk of water buffalo is correlated with the plasma levels of triiodothyronine.

Milk is the most important source of Retinol and alpha-Tocopherol for calves. These antioxidants save the food quality and prevent lipid oxidation in the mammary gland and the calf growing tissues. In Bubalus bubalis, seasonal changes for the plasma levels of both antioxidants were not found. The levels of Retinol and alpha-Tocopherol in the milk were 2 and 1.7 times higher in winter than in summer, respectively. These levels were correlated with the plasma level of triiodothyronine, and markedly increased in cows injected with triiodothyronine in summer. The cytosol from alveolar epithelial cells of mammary glands was incubated with alpha-Tocopherol and 3H-Retinol and, after gel filtration chromatography, both antioxidants were found associated with proteins migrating as a single peak of 33 kD. The amount of alpha-Tocopherol and Retinol binding proteins was 1.5 and 2.3 times higher in winter than in summer respectively. The Retinol binding proteins migrated as two bands (33 and 16 kD) by electrophoresis in denaturing and reducing conditions. Our data suggest that triiodothyronine enhances the transport of both liposoluble antioxidants through the blood-mammary barrier, and demonstrate that proteins of the mammary epithelial cells are involved in such a transport.

Animals↗
PubMed2003

Effects of different dairy products on postprandial lipemia.

BACKGROUND AND AIM: To evaluate the effects on postprandial lipemia (PPL), of three fat rich meals, with similar composition but different physical structure (liquid, semisolid and solid). METHODS AND RESULTS: Eight type 2 diabetic patients of both genders (6M/2F), age 51+/-9 yrs (M+/-SD), BMI 29+/-3 kg/m2, with fasting plasma glucose levels 145+/-24 mg/dL, cholesterol 200+/-38 mg/dL and triglyceride 110+/-45 mg/dL. Participants consumed in the morning, after a 12-hour fast and at 1-week intervals, three test meals with similar volume and composition [protein 36 g, lipid 30 g, carbohydrate 115 g, energy 3556 kJ (850 Kcal)] but with the main source of fat represented by foods with different physical structure (milk, mozzarella-cheese, butter). Each patient underwent gastric emptying measurements by echography; plasma FFA, triglycerides, glucose and insulin were evaluated at baseline and every hour for six hours after each meal. Fasting plasma glucose, cholesterol and triglyceride concentrations were similar at the baseline of the three test meals. Average increases in postprandial plasma triglyceride levels after butter (88+/-8 mg/dL) and mozzarella-cheese (104+/-56 mg/dL) were not different than after milk (98+/-53 mg/dL). The plasma triglyceride peak was also similar after the three test meals but peak time after butter (315+/-42 min; p<0.01) and mozzarella-cheese (277+/-31 min; p<0.02) was significantly delayed compared to milk (225+/-28 min). Gastric emptying rate was similar after butter and milk (14+/-2, 13+/-6 mL/h) and significantly faster after mozzarella-cheese (18+/-5 mL/h; p<0.03). CONCLUSIONS: While the physical structure of fat-rich foods has no major effect on postprandial plasma triglyceride concentrations, it is able to influence the timing of triglyceride peak; gastric emptying time does not play a major role in modulating the postprandial response of triglycerides and glucose.

Animals↗
PubMed2001

Bovine cytosolic 5'-nucleotidase acts through the formation of an aspartate 52-phosphoenzyme intermediate.

Cytosolic 5'-nucleotidase/phosphotransferase (cN-II), specific for purine monophosphates and their deoxyderivatives, acts through the formation of a phosphoenzyme intermediate. Phosphate may either be released leading to 5'-mononucleotide hydrolysis or be transferred to an appropriate nucleoside acceptor, giving rise to a mononucleotide interconversion. Chemical reagents specifically modifying aspartate and glutamate residues inhibit the enzyme, and this inhibition is partially prevented by cN-II substrates and physiological inhibitors. Peptide mapping experiments with the phosphoenzyme previously treated with tritiated borohydride allowed isolation of a radiolabeled peptide. Sequence analysis demonstrated that radioactivity was associated with a hydroxymethyl derivative that resulted from reduction of the Asp-52-phosphate intermediate. Site-directed mutagenesis experiments confirmed the essential role of Asp-52 in the catalytic machinery of the enzyme and suggested also that Asp-54 assists in the formation of the acyl phosphate species. From sequence alignments we conclude that cytosolic 5'-nucleotidase, along with other nucleotidases, belong to a large superfamily of hydrolases with different substrate specificities and functional roles.

5'-Nucleotidase↗
PubMed2001

Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura.

Recent reports have suggested an association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP). The prevalence of H pylori infection and the effect of its eradication in a series of 30 ITP patients were investigated. H pylori infection has been documented in 13 patients (43.33%) by 13C urea breath test and confirmed by histologic examination. Bacterium eradication with antibiotics, obtained in 12 of 13 infected patients (92.3%), led to a complete response in 4 (33.33%) and to a partial response (platelets 90 x 10(9)/L-120 x 10(9)/L) in 2 (16.66%). The response was maintained for a median of 8.33 months, but 1 patient relapsed 7 months after eradication. Search for H pylori infection seems appropriate in ITP patients at diagnosis. Bacterium eradication provides a new good option for a nonimmunosuppressive treatment in some ITP patients.

Adolescent↗
PubMed2001

Purification, cloning and characterisation of odorant- and pheromone-binding proteins from pig nasal epithelium.

Two distinct classes of lipocalin isoforms (OBP-IIs and OBP-IIIs) were purified and identified from porcine nasal mucosa of male and female individuals. Using primers designed on their N-terminal sequence, the complete primary structures of the mature polypeptides were determined. Mass spectrometry analysis confirmed the identity of the cDNA-derived sequences and provided information regarding their post-translational modifications. These species strongly resemble a lipocalin expressed by von Ebner's gland and salivary lipocalins carrying sex-specific pheromones secreted only by the boar's submaxillary glands. Both OBP-IIs and OBP-IIIs present two cysteines paired in a disulphide bond; the remaining residues occur in a reduced form. In addition, OBP-IIIs are heavily glycosylated and markedly different in their glycan moiety from the salivary lipocalins. A three-dimensional model is proposed based on protein species with known structure. Like salivary lipocalins, OBP-IIIs bind a number of odorant molecules, with highest affinity for the specific pheromone 5alpha-androst-16-en-3-one. The high similarity between OBPs from the nasal area and lipocalins from secretory glands suggests a common function in binding the same pheromonal ligands, the latter carrying chemical messages into the environment the former delivering them to specific receptors.

Amino Acid Sequence↗
PubMed2001

Dilated cardiomyopathy in dialysis patients--beneficial effects of carvedilol: a double-blind, placebo-controlled trial.

OBJECTIVES: The aim of this study was to investigate in dialysis patients with symptomatic heart failure New York Heart Association (NYHA) functional class II or III whether the addition of carvedilol to conventional therapy is associated with beneficial effects on cardiac architecture, function and clinical status. BACKGROUND: Congestive heart failure (CHF) in chronic hemodialyzed patients, particularly when associated with dilated cardiomyopathy, represents an ominous complication and is an independent risk factor for cardiac mortality. METHODS: We enrolled 114 dialysis patients with dilated cardiomyopathy. All patients were treated with carvedilol for 12 months in a double-blind, placebo-controlled, randomized trial. The patients underwent M-mode and two-dimensional echocardiography at baseline, 1, 6 and 12 months after the randomization. Each patient's clinical status was assessed using an NYHA functional classification that was determined after 6 and 12 months of treatment. RESULTS: Carvedilol treatment improved left ventricular (LV) function. In the active-treatment group, the increase in LV ejection fraction (from 26.3% to 34.8%, p < 0.05 vs. basal and placebo group) and the reduction of both LV end-diastolic volume (from 100 ml/m2 to 94 ml/m2, p < 0.05 vs. basal and placebo group) and end-systolic volume (from 74 ml/m2 to 62 ml/m2, p < 0.05 vs. basal and placebo group) reached statistical significance after six months of therapy, compared with baseline and corresponding placebo values, and they remained constant at one year of treatment (p < 0.05 vs. basal and placebo group). The clinical status of patients, assessed by NYHA functional classification, improved during the treatment period. Moreover, at the end of the trial, there were no patients in NYHA functional class IV in the carvedilol group, compared with 5.9% of the patients in the placebo arm. CONCLUSIONS: One year of therapy with carvedilol in dialysis patients with CHF and dilated cardiomyopathy reduces LV volumes and improves LV function and clinical status.

Adult↗
PubMed2001

Insulin, renin-aldosterone system and blood pressure in obese people.

OBJECTIVE: To evaluate the relationship between insulin, the renin-aldosterone system and blood pressure in obese subjects. DESIGN AND METHODS: A cross sectional study of a group of severely obese normotensive subjects who were surgical candidates (n=39; mean BMI: 47.8+/-1.4) and a group of hypertensive patients (n=57; mean BMI: 28.0+/-0.7) twenty-nine of whom had BMI>27. All subjects were studied after 15 days on a balanced diet. Insulin, plasma renin activity and aldosterone were measured. RESULTS: Fasting insulin, plasma renin activity and aldosterone were higher in severely obese normotensive subjects than in hypertensive subjects (respectively 32.3+/-3.0 vs 13.1+/-1.0 mU/l, P=0.0001; 1.34+/-0.22 vs 0.88+/-0.12 ng/ml/h, P=0.04; 137.2+/-16.2 vs 87.9+/-12.1 pg/ml, P=0.015). Insulin was related to BMI and to aldosterone both in normotensive and in hypertensive patients. CONCLUSION: Hyperinsulinemia itself does not determine hypertension; in some people it could play a vasodilator role in opposition to the renin-aldosterone system.

Adult↗
PubMed2001

Bacterial expression and conformational analysis of a chemosensory protein from Schistocerca gregaria.

Chemosensory proteins (CSPs) are a class of small, soluble proteins present at high concentrations in chemosensory organs of different insect species. Several pieces of evidence suggest their involvement in carrying chemical messages from the environment to chemosensory receptors. However, a structural description of the mechanism of delivery has not been reported. In order to provide the first detailed conformational characterization of these molecules, we cloned a specific isoform (CSP-sg4) from Schistocerca gregaria and expressed it in Escherichia coli. The product was obtained with yields of more than 20 mg per L of culture, all in its soluble form. The recombinant protein was identical to the native one with respect to pairing of the disulfide bridges, aggregative state and secondary structure elements. Structural investigations revealed a significantly stable polypeptide with respect to variations in temperature and acidity. CD analysis, preliminary NMR data and secondary structure prediction pointed to a correctly folded structure where helical regions and loops are alternated in a similar fashion as that observed for other classes of odorant- and pheromone-binding proteins presenting no sequence similarity to CSPs.

Amino Acid Sequence↗
PubMed2000

Cloning, post-translational modifications, heterologous expression and ligand-binding of boar salivary lipocalin.

Boar submaxillary glands produce the sex-specific salivary lipocalin (SAL), which binds steroidal sex pheromones as endogenous ligands. The cDNA encoding SAL was cloned and sequenced. From a single individual, two protein isoforms, differing in three amino acid residues, were purified and structurally characterized by a combined Edman degradation/MS approach. These experiments ascertained that the mature polypeptide is composed of 168 amino acid residues, that one of the three putative glycosylation sites is post-translationally modified and the structure of the bound glycosidic moieties. Two of the cysteine residues are paired together in a disulphide bridge, whereas the remaining two occur as free thiols. SAL bears sequence similarity to other lipocalins; on this basis, a three-dimensional model of the protein has been built. A SAL isoform was expressed in Escherichia coli in good yields. Protein chemistry and CD experiments verified that the recombinant product shows the same redox state at the cysteine residues and that the same conformation is observed as in the natural protein, thus suggesting similar folding. Binding experiments on natural and recombinant SAL were performed with the fluorescent probe 1-aminoanthracene, which was efficiently displaced by the steroidal sex pheromone, as well as by several odorants.

Amino Acid Sequence↗
PubMed2000

Ventricular tachyarrhythmias following coronary surgery: predisposing factors.

The perioperative factors potentially associated with post-coronary artery bypass grafting (CABG) ventricular tachyarrhythmias (VT) onset have not been deeply investigated. Monomorphic or polymorphic ventricular tachycardia and ventricular fibrillation represent the most dreadful arrhythmic events that can complicate the postoperative course of CABG. As a consequence, the aim of our paper was to identify which perioperative variables might predict post-CABG VT occurrence. One hundred and fifty-two consecutive patients who underwent CABG surgery at our Institution were included in the study. Post-CABG VT occurred in 13 out of 152 patients (8.5%, six cases of monomorphic ventricular tachycardia and seven cases of ventricular fibrillation). At univariate analysis, VT patients were significantly younger (54.8+/-6.6 vs. 60.1+/-8.8, P=0.038), exhibited a more severe coronary artery disease (CAD) (number of diseased vessels 2.92+/-0.3 vs. 2.45+/-0.7, P=0.023, and percentage of patients with three-vessel CAD 91.7% vs. 57.3%, P=0.043) and received a greater number of CABGs than those remaining in sinus rhythm (SR) (percentage of patients receiving three or more CABGs 76. 9% vs. 38.8%, P1000 76.9% vs. 38%, Pnormal range 72.7% vs. 30.7%, P=0.014), electrolyte derangement (84.6% vs. 45.6%, P=0.017) and a severe haemodynamic impairment (need for IABP 23% vs. 2.9%, P1000, postoperative electrolyte imbalance, the need for three or more CABGs and of IABP all were independent correlates for VT. In conclusion, post-CABG VT seem to be related to the preexistence of a severe underlying coronary artery disease along with perioperative triggering factors such as acute ischemia, electrolytic disorders and a sudden haemodynamic impairment.

Causality↗
PubMed2000

Bone mineral density and body composition in underweight and normal elderly subjects.

The importance of malnutrition as a risk factor in osteoporosis is emphasized by the evidence that patients with fractures of the proximal femur are often undernourished. In this study, nutritional status, bone mineral mass and its association with body composition were investigated in underweight and normal weight elderly subjects. Moreover the hypothesis that malnutrition in elderly is associated with a higher risk of osteoporosis was tested. The participants were 111 elderly subjects divided into two groups according to body mass index (BMI): 51 patients were underweight (BMI < 22 kg/m2) while in 60 subjects BMI ranged from 22 to 30 kg/m2. In all patients anthropometric parameters and blood indices of malnutrition and of bone turnover were measured. Fat-free soft mass (FFSM), fat mass (FM), bone mineral content (BMC) and bone mineral density (BMD) 'total body' and at the hip were obtained by dual-energy X-ray densitometry. Dietary intake was evaluated with the diet history method, while resting energy expenditure (REE) was measured by indirect calorimetry. Underweight subjects had other signs of malnutrition, such as low visceral proteins, sarcopenia, and an inadequate energy intake. Moreover they showed a significant reduction of BMC and BMD compared with normal subjects. In men with BMI <22 kg/m2, T-score was below -2.5 (-3 at femoral neck and -2.7 at total hip) while men in the control group had normal bone mineral parameters. T-score at different sites was lower in underweight women than in underweight men, always showing values under -3.5, with clear osteoporosis and a high fracture risk. In healthy women the T-score values indicated the presence of mild osteoporosis. In underweight subjects, low levels of albumin (< 35 g/l) were associated with higher femoral bone loss. Using a partial correlation model, BMC, adjusted for age, bone area, knee height and albumin showed a significant association with FM in women (r = 0.48; p < 0.01) and with FFSM in men (r = 0.48; p < 0.05). Albumin, when adjusted for other variables, was significantly correlated (r = 0.52; p < 0.05) with femoral neck BMC only in women. In conclusion, the underweight state in the elderly is associated with malnutrition and osteoporosis; other factors occurring in malnutrition, besides body composition changes, such as protein deficiency, could be involved in the association between underweight and osteoporosis. Moreover bone mineral status seems to be related to fat-free soft mass tissue in men while in women it is much more closely associated with total body fat.

Aged↗
PubMed2000

Antibacterial and allelopathic activity of extract from Castanea sativa leaves.

Following the extraction of Castanea sativa with an aqueous solution of sulfuric acid (pH 3.0), the ethyl acetate soluble fraction was tested for its antibacterial and allelopathic activity. The extract was shown to have pronounced antibacterial effects against seven of the eight strains of Gram-positive and Gram-negative bacteria used (MIC in the range of 64-256 microg/ml and MBC in the range of 256-512 microg/ml). The active fraction was analyzed by TLC and HPLC showing the presence of rutin, hesperidin, quercetin, apigenin, morin, naringin, galangin and kaempferol. Standards of the identified flavonoids were tested against the same bacterial strains. The highest activity was shown by quercetin, rutin and apigenin. The allelopathic effect was tested against Raphanus sativus seed germination. The extract, quercetin, rutin and apigenin caused a decrease in the percentage of seed germination and root and epicotyl growth.

Anti-Bacterial Agents↗