Biomedical subjects

Alessandra Bitto

Publications and source records attributed to Alessandra Bitto.

29 records · Page 2Linked to original sources

PubMed2004

Platelet-activating factor acetylhydrolase is not associated with carotid intima-media thickness in hypercholesterolemic Sicilian individuals.

BACKGROUND: Atherosclerosis is a complex, chronic disease that usually arises from the converging action of several pathogenic processes, including hypertension, hyperlipidemia, obesity, and the accumulation of oxidized LDL. Platelet-activating factor acetylhydrolase (PAF-AH) is a LDL- and HDL-bound enzyme that hydrolyzes and inactivates PAF and prevents LDL-cholesterol oxidation, thus delaying the onset of atherosclerotic disease. METHODS: We evaluated the relationship between variants of the PAF-AH gene polymorphisms Arg92His, Ile198Thr, and Ala379Val and the presence of carotid atherosclerosis in 190 hypercholesterolemic Sicilian individuals. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The participants were classified according to having normal (< or =1 mm) or abnormal (> or =1 mm) IMT and were also investigated for physical characteristics and biochemical indices, including PAF-AH activity. RESULTS: PAF-AH activity and LDL concentrations were significantly correlated in hypercholesterolemic patients, but plasma PAF-AH activity and HDL were not significantly correlated in either IMT group. No significant differences were detected among the PAF-AH gene polymorphisms in both groups after correction for age, sex, body mass index, plasma glucose and lipid concentrations, PAF-AH activity, blood pressure, and smoking habits. The analysis of PAF-AH genotype distribution showed no significant differences in percentage of 92, 198, and 379 genotypes in both IMT groups. CONCLUSION: Our data provided no evidence that PAF-AH polymorphisms influence PAF-AH activity and atherosclerosis in hypercholesterolemic Sicilian patients.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2004

Raxofelast, a hydrophilic vitamin E-like antioxidant, reduces testicular ischemia-reperfusion injury.

Testis torsion is a surgical emergency that lead to permanent gonad damage. The damage has been ascribed to mechanisms of ischemia-reperfusion similar to other tissues. The mechanisms involved are different, but the lipid peroxidation of plasma membrane, caused by reactive oxygen species (ROS), generated particularly during reperfusion, is one of the most accredited. In the present study, we aimed to evaluate the effects of raxofelast, a vitamin E-like antioxidant with potent action and no systemic toxicity, on lipid peroxidation and histopathology in both testes after unilateral testicular torsion and detorsion. Adult male Wistar rats were subjected to total occlusion (3 h) of the left testis followed by 4 hours of reperfusion (TI/R). Sham testicular ischemia-reperfusion rats (SHAM TI/R) were used as controls. The animals were then randomized to receive either vehicle (1 ml/kg/i.p. of a dimetylsulphoxide/NaCl 0.9% 1:10 v/v solution, injected either 15 min before detorsion and 15 min after detorsion) or raxofelast (20 mg/kg i.p. 15 min before detorsion and 15 min after detorsion). Conjugated dienes (CD) levels, an index of lipid peroxidation, and testis histopathology were evaluated. Testicular ischemia reperfusion (TI/R) in untreated rats produced high testicular levels of CD (3.6+/-0.3 DeltaABS/g protein on the left side and 2.5+/-0.2 DeltaABS/g protein on the right side). Furthermore, histological examination revealed marked damage to the testis interstitium with severe haemorrhage and edema. The administration of raxofelast lowered CD levels (2.8+/-0.2 DeltaABS/g protein on the left side and 1.9+/-0.1 DeltaABS/g protein in the right side) and significantly reduced histological damage. These data suggest that the hydrophilic vitamin E-like antioxidants are good candidates for designing a novel therapeutic strategy to halt the oxidative stress that follows acute testis torsion.

Animals↗

PubMed2004

The paraoxonase promoter polymorphism (-107)T>C is not associated with carotid intima-media thickness in Sicilian hypercholesterolemic patients.

BACKGROUND AND OBJECTIVES: Increased plasma low-density lipoprotein-cholesterol (LDL-C) levels in hypercholesterolemic subjects are associated with enhanced LDL oxidation that represents an additional risk for atherosclerotic disease. Human serum paraoxonase (PON1), a high-density lipoprotein (HDL) associated enzyme, has been shown to protect LDL from oxidation, thus playing an important role in reducing the risk of atherosclerosis. PON1 gene polymorphisms have been found to be associated with the variations in serum PON1 levels and activities, and with the risk for coronary artery disease (CAD). This study was performed to evaluate the contribution of the PON1 promoter (-107)T>C and the coding region Gln 192 Arg (Q192R) and Leu 55 Met (L55M) polymorphisms to the presence of carotid atherosclerosis in 208 Sicilian subjects with primary hypercholesterolemia. METHODS: Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The subjects were classified according to whether they have a normal ( 1 mm) IMT. Subjects were also investigated for physical and biochemical parameters, including PON1 activity. RESULTS: No significant differences were detected among the PON1 genotypes with respect to age, sex, BMI, plasma lipids, systolic blood pressure in both groups of patients. There were significant differences between PON1 genotypes with respect to PON1 activity. The 192QQ, 55MM and (-107)TT genotypes showed lower PON1 activity compared to the RR, LL and CC genotypes. The PON1 (-107)T>C genotype distribution in both IMT groups showed no significant differences in percentage of TT, CT and CC genotypes. Similar results were obtained analyzing the Q192R and L55M genotype frequencies. Stepwise forward logistic regression analysis confirmed the lack of association between PON1 genotypes and carotid abnormalities. CONCLUSIONS: In conclusion, our data provided no evidence of a significant association between either PON1 promoter (-107)T>C or coding region, Q192R and L55M, polymorphisms and early carotid atherosclerosis in Sicilian hypercholesterolemic subjects.

Aryldialkylphosphatase↗

PubMed2004

Association between serum paraoxonase (PON1) gene promoter T(-107)C polymorphism, PON1 activity and HDL levels in healthy Sicilian octogenarians.

Age is associated with an enhanced low density lipoprotein (LDL) oxidation and atherosclerosis, thus, subjects over 80 years without cardiovascular disease provide a model to investigate the protective factors against atherosclerosis. Serum paraoxonase (PON1), an high density lipoprotein (HDL)-bound enzyme, prevents LDL oxidation. The aim of the present study was to evaluate the contribution of the PON1 promoter T(-107)C and coding region Gln192Arg (Q192R) and Leu55Met (L55M) polymorphisms to the resistance to develop cardiovascular events in Sicilian healthy octogenarians. Distribution of PON1 genotypes and activity, and biochemical parameters, were compared between 100 octogenarians and 200 adults. Individuals in the elderly group displayed significant higher levels of HDL-C (P < 0.001) and PON1 activity (P < 0.001). The analysis of PON1 genotypes distribution showed an higher percentage of (-107)CC among octogenarians compared with controls. A significant difference among T(-107)C genotypes respect to PON1 activity and HDL-C levels occurred in both groups. The CC genotype was associated with higher PON1 activity and HDL levels compared to the TT genotypes. In conclusion, our results provide a strong evidence that in healthy Sicilians ageing may be characterized by a low frequency of PON1 (-107)T 'risk' allele and by an high frequency of favourable genotypes such as (-107)CC, influencing PON1 activity and HDL-C levels.

Adult↗

PubMed2004

Modulation of IL-1 beta gene expression by lipid peroxidation inhibition after kainic acid-induced rat brain injury.

Brain injury was induced by intraperitoneal administration of kainic acid (KA, 10 mg/kg). Animals were randomized to receive either IRFI 042 (20 mg/kg i.p.), a lipid peroxidation inhibitor, or its vehicle (NaCl 0.9% DMSO 10% 1 ml/kg i.p.) 30 min before KA administration. A first set of animals was sacrificed 6 h after KA injection to measure malondialdehyde (MDA) content, glutathione-reduced (GSH) levels and the mRNA for interleukin-1beta (IL-1beta) in the cortex and in the hippocampus. A second set of animals was sacrificed 48 h after KA administration for histological analysis. All animals were observed for monitoring the behavioral sequelae and for evaluating latency of convulsions. Sham brain injury rats were used as controls. Intraperitoneal administration of IRFI 042 significantly decreased brain MDA (cortex: KA + vehicle = 0.285 +/- 0.04 nmol/mg protein; KA + IRFI 042 = 0.156 +/- 0.02 nmol/mg protein, P < 0.005; hippocampus: KA + vehicle = 0.350 +/- 0.03 nmol/mg protein; KA + IRFI 042 = 0.17 +/- 0.04 nmol/mg protein, P < 0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 7.81 +/- 1 micromol/g protein; KA + IRFI 042 = 12.1 +/- 1 micromol/g protein; P < 0.005) and hippocampus (KA + vehicle = 5 +/- 0.8 micromol/g protein; KA + IRFI 042 = 9.4 +/- 1.8 micromol/g protein; P < 0.005), reduced both brain IL-1beta mRNA expression and oedema, and increased latency of convulsions. Histological analysis showed a reduction of cell damage in IRFI 042-treated samples. The present data indicate that lipid peroxidation inhibition reduces IL-1beta gene expression and protects against kainic acid-induced brain damage.

Animals↗

PubMed2004

Recombinant human erythropoietin stimulates angiogenesis and healing of ischemic skin wounds.

Wound healing in ischemic tissues such as flap margins due to inadequate blood supply is still a source of considerable morbidity in surgical practice. Adequate tissue perfusion is particularly important in wound healing. We investigated the effects of recombinant human erythropoietin (rHuEPO) on wound healing in an ischemic skin wound model. Sixty-three Sprague-Dawley rats were used. Normal incisional wound and H-shaped double flaps were used as the wound models. Animals were treated with rHuEPO (400 IU/kg) or its vehicle. Rats were killed on different days (3, 5, and 10 days after skin injury) and the wounded skin tissues were used for immunohistochemistry and for analysis of vascular endothelial growth factor content and collagen content. Tissue transglutaminase immunostaining of histological specimens was used as a vascular marker to determine the level of microvessel density. The results showed a higher level of vascular endothelial growth factor protein and an increased microvessel density in ischemic wounds with rHuEPO treatment than the normal incisional wounds and ischemic control wounds. Collagen content was higher in the incisional wounds and in the ischemic wounds with rHuEPO treatment compared with the ischemic control wounds. Our results suggest that erythropoietin may be an effective therapeutic approach in improving healing in ischemic skin wounds.

Animals↗

PubMed2004

Effects of the phytoestrogen genistein on the circulating soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin system in early postmenopausal women.

We investigated the serum levels of both receptor activator of nuclear factor kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) in postmenopausal healthy women after a 1-yr therapy with genistein, (n = 30; 54 mg/d), hormone replacement therapy (n = 30; 1 mg/d 17beta-estradiol combined with norethisterone acetate) and placebo (n = 30). By comparison with placebo, the soluble RANKL (sRANKL)/OPG ratio was lower in the genistein group (-69 +/- 7%; P < 0.01 vs. placebo 81 +/- 24%) and in hormone replacement therapy-treated women (-11 +/- 2%; P < 0.01 vs. placebo). A positive correlation (r = 0.63; P < 0.01) was found between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in urinary deoxypyridinoline, a bone resorption marker. A negative correlation was observed between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in femoral neck bone mineral density (r = -0.7; P < 0.01). Our findings suggest that the sRANKL-OPG system may mediate the beneficial effects of genistein on bone remodeling in postmenopausal women.

Amino Acids↗

PubMed2004

Cardiovascular effects of the phytoestrogen genistein.

Phytoestrogenic molecules have received a great deal of attention over the last few years because of their potentially preventive roles against a few of today's most prevalent chronic diseases, namely cardiovascular diseases, osteoporosis and hormone related cancers. Of the several phytoestrogens, genistein in particular has been shown to be the most efficacious in animal models and experimental studies. Genistein in vitro relaxes rat arteries by a nitric oxide dependent mechanism and enhances the dilator response to acetylcholine of atherosclerotic arteries. Genistein supplementation improves endothelial dysfunction induced by oophorectomy in rats and reduces infarct size in an experimental model of myocardial ischaemia-reperfusion injury. Furthermore, genistein in postmenopausal women increases plasma nitric oxide breakdown products, reduces endothelin-1 levels and improves endothelial dependent vasodilation in post-menopausal women. All these findings, taken together, would suggest that this molecule might represent an attractive alternative for cardiovascular protection.

Animals↗

PubMed2004

Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse.

The effects of recombinant human erythropoietin (rHuEPO) in diabetes-related healing defects were investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ-m(+/+)Lept(db) mice (db(+)/db(+)) and their normoglycemic littermates (db(+/+)m). Animals were treated with rHuEPO (400 units/kg in 100 microl s.c.) or its vehicle alone (100 microl). Mice were killed on different days (3, 6, and 12 days after skin injury) for measurement of vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, for monitoring angiogenesis by CD31 expression, and for evaluating histological changes. Furthermore, we evaluated wound-breaking strength at day 12. At day 6, rHuEPO injection in diabetic mice resulted in an increase in VEGF mRNA expression (vehicle = 0.33 +/- 0.1 relative amount of mRNA; rHuEPO = 0.9 +/- 0.09 relative amount of mRNA; P < 0.05) and protein wound content (vehicle = 23 +/- 5 pg/wound; rHuEPO = 92 +/- 12 pg/wound; P < 0.05) and caused a marked increase in CD31 gene expression (vehicle = 0.18 +/- 0.05 relative amount of mRNA; rHuEPO = 0.98 +/- 0.21 relative amount of mRNA; P < 0.05) and protein synthesis. Furthermore, rHuEPO injection improved the impaired wound healing and, at day 12, increased the wound-breaking strength in diabetic mice (vehicle = 12 +/- 2 g/mm; rHuEPO 21 +/- 5 g/mm; P < 0.05). Erythropoietin may have a potential application in diabetes-related wound disorders.

Animals↗

PubMed2003

Imbalance of serum cytokine network in sarcoid patients: index of sarcoidosis relapse?

BACKGROUND AND AIM OF THE WORK: The follow-up of sarcoidosis is usually performed by invasive tools such as thoracic biopsy, supported by Broncho-Alveolar Lavage (BAL), Gallium-scintigraphy and Gadolinium Magnetic Resonance Imaging (Gd-MRI) to evaluate the degree of disease. Its pathogenesis can be ascribed to an accumulation of cells due to the disregulation of the immune system which involves Th1/Th2 cells as well as the soluble factors they generate. We evaluated serum cytokine and membrane marker levels (cytokine network) in sarcoid patients in order to study the correlation with the disease activity, in particular with the occurrence of sarcoidosis relapses. PATIENTS AND METHODS: Seven sarcoid patients clinically stable without therapy, at different stages, were enrolled in our study. Cytokine and membrane marker serum values were measured monthly for 24 months, after a six-month period of run-in, by ELISA assay and MoAb indirect immunofluorescence, respectively. RESULTS: In some patients at the first and second stages of the disease we observed MCP-1 and inflammatory cytokine peaks and, moreover, MCP-1 values were increased before other cytokine values. After three subsequent increases of these parameters were observed, according to our personal experience, Gadolinium-MRI confirmed the presence of an increase of the lesion and therefore our hypothesis of sarcoidosis relapse. Only one patient at stage III showed constantly elevated values of fibro-angiogenic cytokines and membrane receptors of the TNF receptor family. CONCLUSIONS: Cytokine network monitoring could be a non-invasive means of following up the clinical course of sarcoidosis.

Adult↗

PubMedDate not supplied

Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study.

OBJECTIVE: We evaluated and compared the effects of the phytoestrogen genistein, estrogen-progestogen therapy (EPT), and placebo on hot flushes and endometrial thickness in postmenopausal women. DESIGN: Ninety healthy, postmenopausal women, 47 to 57 years of age, were randomly assigned to receive for 1 year continuous EPT (n = 30; 1 mg 17beta-estradiol combined with 0.5 mg norethisterone acetate), the phytoestrogen genistein (n = 30; 54 mg/day), or placebo (n = 30). Endometrial safety was evaluated by intravaginal ultrasounds at baseline, 6 and 12 months. RESULTS: By comparison with placebo, daily flushes reduced significantly by a mean of 22% (95% CI: -38 to -6.2; P < 0.01) after 3 months, by a mean of 29% (95% CI: -45 to -13; P < 0.001) after 6 months, and by a mean of 24% (95% CI: -43 to -5; P < 0.01) after 12 months of genistein treatment. Flush score decreased by a mean of 53% (95% CI: -79 to -26; P < 0.001) after 3 months, by a mean of 56% (95% CI: -83 to -28; P < 0.001) after 6 months, and by a mean of 54% (95% CI: -74 to -33; P < 0.001) after 12 months of EPT, as compared with placebo. No side effect was observed on the uterus of the participants. CONCLUSIONS: The present study confirms that genistein might have positive effects on hot flushes without a negative impact on endometrial thickness and suggests a future role of this phytoestrogen as a strategically therapeutic alternative in the management of postmenopausal symptoms.

Double-Blind Method↗