Laura Gerardino

The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with Alzheimer's disease in an Italian population [corrected].

Interleukin-6 (IL-6) is a multifunctional cytokine playing a crucial role in inflammation and tissue injury. A role for this molecule in neurodegeneration and Alzheimers disease (AD) has been proposed. The aim of this study was to evaluate the association between a common polymorphism of the IL-6 gene promoter and AD in the Italian population. We found that the frequency of the GG genotype was significantly higher in AD patients than controls on both univariate ( rho< 0.0001) and multivariate analysis ( rho< 0.0001). In contrast, the CC genotype seems to be associated with a reduced risk of disease ( rho< 0.0001). Our data indicate that the IL-6 gene polymorphism is associated with AD in Italians and confirm that IL-6 is crucial in the pathophysiology of neurodegenerative disorders.

Hemodynamic and functional consequences of radial artery removal for coronary artery bypass grafting.

Five years after surgery the echo-Doppler characteristics of the forearm circulation and the transcutaneous oxygen and carbon dioxide pressures of the operated and control arm were determined at rest and under conditions of hand exercise in 34 patients who received a radial artery graft for myocardial revascularization. Doppler measurements showed the ulnar compensation to radial artery removal, and transcutaneous measurements demonstrated a moderate degree of exercise-induced hand ischemia on the operated site.

−174 G/C interleukin-6 gene polymorphism and increased risk of multi-infarct dementia: a case-control study

The aim of this study was to evaluate the association between the -174 G/C polymorphism of interleukin-6 (IL-6) gene promoter and multi-infarct dementia (MID). We studied a group of 122 patients affected by MID and 134 age- and sex-matched controls and evaluated classical risk factors for MID, as well as the distribution of IL-6 alleles and genotypes by polymerase chain reaction and restriction enzyme analysis. The distribution of IL-6 genotypes was 63 GG, 47 GC, 12 CC in patients with MID and 29 GG, 58 GC, 47 CC in control subjects. The GG genotype was significantly more common in the MID group (P<0.0001), while the CC genotype was more common in control patients (P<0.0001). Logistic regression analysis indicated that the presence of GG genotype significantly increases the risk of MID (odds ratio 9.1 [3.1-26.1], P<0.0001). This study indicates a strong association between the -174 G/C polymorphism of the IL-6 gene and MID. Our data support the hypothesis that IL-6 and inflammatory mechanisms are important in the pathophysiology of the vascular changes responsible for cognitive deterioration.

Lack of association between Alzheimer's disease and Gln-Arg 192 Q/R polymorphism of the PON-1 gene in an Italian population.

Alzheimer’s disease (AD) is characterized by deposition of oxidized low-density lipoprotein (LDL) forming the senile plaque and by structural changes and cell death in acetylcholine-producing neurons. Paraoxonase-1 (PON-1) is a secreted protein primarily associated with high-density lipoproteins (HDL) and participates in the prevention of LDL oxidation. PON-1 is also an arylesterase that hydrolyzes paraoxon, an active toxic metabolite of parathion, thus providing protection against organophosphate poisoning and metabolization of environmental neurotoxins that might be responsible for neurodegeneration with aging. Serum levels of PON-1 are genetically determined and strongly influenced by a common polymorphism on the position 192 of the PON-1 gene. The aim of this study was to evaluate whether the polymorphism of the PON-1 gene is associated with AD. We studied 124 Italian subjects affected by probable AD and 135 age- and sex-matched controls. The distribution of PON-1 genotypes was 64 QQ, 46 QR, 14 RR in the AD patients and 57 QQ, 59 QR, 19 RR in the control subjects. No statistically significant difference was found between the two groups in our population (p = 0.130 for homozygous QQ, p = 0.279 for heterozygous QR, and p = 0.502 for homozygous RR). These results suggest that the human Gln-Arg 192 Q/R polymorphism of the PON-1 gene is not associated with AD in an Italian population.

Long saphenous vein stripping reduces local level of reactive oxygen metabolites in patients with varicose disease of the lower limbs.

Long saphenous vein (LSV) stripping is the most common surgical procedure in patients affected by varicose disease of the lower limbs. Reactive oxygen metabolites (ROM) generation plays a crucial role in chronic venous insufficiency (CVI). The aim of this study was to investigate whether ROM generation is increased in patients affected by varicose disease versus healthy controls and whether LSV stripping has a positive effect on the local production of ROM. The local production of ROM was assessed measuring hydroperoxides in the blood collected from the leg of 30 patients consecutively undergoing LSV stripping and 30 controls. In both the patient group and the control group, the test was repeated 30 days later. We found that ROM levels before surgery are higher in varicose vein patients than in controls (p < .0001) and that ROM are significantly reduced 30 days after LSV stripping (p < .0001). At that time point, no significant differences between patients and controls was found. We also found that sex and age do not affect ROM concentration in patients and controls, either before or after surgery. In conclusion, our data indicate that CVI is characterized by significant oxidative stress and that LSV stripping is able to normalize local production of ROM in patients with varicose disease of the lower limbs. We suggest that measurement of ROM might be useful to test the positive effects of LSV stripping in these patients.

Association between intercellular adhesion molecule-1 E/K gene polymorphism and probable vascular dementia in humans

Intercellular adhesion molecule-1 (ICAM-1) is implicated in the pathogenesis of ischemic cardiovascular disorders, including cerebral ischemia. A common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In this case-control study, we evaluated the association between this polymorphism and vascular dementia (VD) by studying 107 patients affected by probable VD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in VD patients than controls (P=0.009). Logistic regression analysis indicated that the presence of the EE genotype significantly increased the risk of VD (odds ratio 3.25, P=0.024). Our findings support the hypothesis that ICAM-1 plays a role in the physiopathology of ischemic cerebrovascular disorders and suggest that genetic polymorphisms of ICAM-1 might be clinically important in the development and progression of neurodegenerative diseases.

Probiotics: Which and When?

There is a natural feeling between our intestinal flora and the gut. These microorganisms, living in the various tracts of human intestine, may affect the host homeostasis. Some of these bacteria can perhaps be a source of infection and sepsis when the bowel barrier is physically or functionally breached. The term ‘probiotic’ dates from the beginning of the last century and in the last years a market for probiotics worldwide, estimated to be worth billions of pounds, has developed. Although there is persuasive advertising for probiotics and there have been methodological advances in the study of the intestinal microbiota, much remains unproven, e.g. how probiotics work, which strains are effective, what can be expected to be achieved, and what dosage is required for effectiveness. This review of the literature is an evidence-based guide through the developing microbial universe affecting our life.

New Prospects for the Treatment of Raynaud's Phenomenon Using A Serotoninergic S2 Receptor Antagonist (Ketanserin) and Stable Derivatives of Prostacyclin

The authors propose a promising new therapy for the treatment of Raynauds phenomenon, with parenteral prostacyclin (carbaprostacycline) and a serotonergic S2-receptor antagonist (ketanserin) given orally. They studied 31 patients, 22 treated with ketanserin and carbaprostacycline, 9 with carbaprostacycline alone. Both groups demonstrated successful results and a significant improvement in measurements performed by photoplethysmography and transcutaneous pulse oxymetry.

Coagulation factor XIII Val34Leu gene polymorphism and Alzheimer's disease

Abstract Blood coagulation factor XIII (FXIII) plays a role in inflammatory processes and a pathogenetic role of inflammation in neurodegenerative disorders has been proposed. FXIIIa subunit was immunohistochemically detected in a subpopulation of reactive microglia in Alzheimers disease (AD). Aim of the present study is to evaluate whether a common polymorphism of the FXIII gene is associated with sporadic AD. We examined 90 patients affected by sporadic AD and 139 age- and sex-matched controls to assess the distribution of V/L alleles and genotypes of the FXIIIa-subunit gene. The LL genotype showed a significantly higher frequency in AD patients (p<0.05) with a significantly increased risk of AD in the presence of LL genotype at the logistic regression analysis [odds ratio: 3.6 (1.36–9.44), p<0.01]. This study shows for the first time an association between FXIII Val34Leu polymorphism and AD.

Treatment of retinal vein thrombosis with defibrotide

Abstract The therapeutic effects of defibrotide, a polydesoxyribonucleotide derivative with antithrombotic, fibrinolytic, and anti-ischemic activity, were explored in 15 patients with occlusion of the central vein (5 cases) or peripheral branches of the retinal venous system (10 cases). Defibrotide was administered by slow intravenous infusion in doses of 2 gm daily for 21 days: at the start and end of the study, all patients underwent ophthalmologic examination with measurements of visual acuity and funduscopy by direct and indirect ophthalmoscopy. Visual acuity improved in 11 patients, while it remained unchanged in four cases; the difference between means was statistically significant ( P P P