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Andrea Flex

Publications and source records attributed to Andrea Flex.

17 recordsLinked to original sources
PubMed2006

Analysis of functional polymorphisms of metalloproteinase genes in persons with vascular dementia and Alzheimer's disease.

BACKGROUND: Vascular dementia (VAD) and Alzheimer's disease (AD) may share common neuropathological mechanisms. Matrix metalloproteinases (MMPs) may induce destruction of the extracellular matrix, neuronal dysfunction, and death. Increased expression of these molecules has been found in a number of neurological diseases, including cerebral ischemia and AD. Expression and activity of MMPs may be genetically influenced by common polymorphisms in the promoter regions of the corresponding genes. The purpose of this study was to evaluate whether functional polymorphisms of MMP genes are associated with dementia. METHODS: This is a cross-sectional study including a total of 599 individuals: 193 with VAD, 183 with AD, and 223 controls. Polymorphisms of the MMP-1, MMP-3, and MMP-9 genes were studied. RESULTS: MMP-1 2G2G, MMP-1 1G2G, MMP-3 5A5A, and MMP-9 TT genotypes were significantly and independently associated with VAD (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.4-4.4, OR = 1.7, 95% CI, 1.0-2.7, OR = 2.9, 95% CI, 1.5-5.9, and OR = 6.8, 95% CI, 1.3-35.1, respectively). MMP-1 2G2G and MMP-3 5A5A genotypes were associated with increased risk of AD only in persons who carry the apolipoprotein E (APOE) epsilon4 allele (OR = 6.0, 95% CI, 2.3-15.5, and OR = 14.3, 95% CI, 3.2-63.0, respectively). Interestingly, the odds of VAD and AD was further increased in persons concomitantly carrying more than one MMP gene variation, compared to individuals that only had one high-risk genotype. CONCLUSIONS: Our study suggests that MMP gene polymorphisms are associated with VAD and AD, although these results need to be treated with caution until replicated. MMP genotypes may influence the risk of dementia and merit further investigation as potential genetic markers of disease.

Aged↗
PubMed2005

Responsiveness to cholinesterase inhibitors in Alzheimer's disease: a possible role for the 192 Q/R polymorphism of the PON-1 gene.

Cholinesterase inhibitors (ChEIs) are the most established treatment strategy in Alzheimer's disease (AD). However, the responsiveness to these drugs is widely heterogeneous and the majority of AD subjects do not respond to treatment. Paraoxonase-1 (PON-1) is a potent endogenous ChEI and has been widely studied for its ability to hydrolyze environmental neurotoxins. Serum levels and biological activity of PON-1 display wide inter-individual variability and are strongly influenced by a common polymorphism at position 192 of the PON-1 gene. Here, we evaluated whether this gene variation is associated with differences in the ability of AD subjects to respond to therapy with ChEIs. We found that individuals that respond to ChEIs had a significantly higher frequency of the R allele, compared to non-responders (P<0.05). This study indicates that the 192 Q/R polymorphism of the PON-1 gene might influence responsiveness to ChEIs, with potentially important implications for the treatment of AD. Mutations of genes encoding for endogenous modulators of the cholinergic system should merit further investigation as prognostic indicators of individual response to treatment in AD subjects.

Aged↗
PubMed2005

Deep venous thrombosis and pulmonary embolism after knee arthroscopy in athletes carrying the thrombophilic factor lupus anticoagulant.

In patients undergoing arthroscopic knee surgery, deep venous thrombosis and pulmonary embolism are rare and there is not clear indication as to the necessity of thromboprophylactic treatment in these patients. However, the role of coagulation disorders in thrombotic events following arthroscopy is unknown. We report 2 cases of massive deep venous thrombosis and pulmonary embolism after knee arthroscopy in athletes carrying the thrombophilic factor lupus anticoagulant, but with no personal or familial history of thrombotic diseases. A few days after the arthroscopic intervention, both patients presented with deep venous thrombosis and 1 developed a severe pulmonary embolism. Blood examination showed that both athletes were lupus anticoagulant-positive. This is the first description of an association between venous thromboembolism, knee arthroscopy, and a prothrombotic condition. This report suggests that screening for hypercoagulability might be useful in athletes undergoing even minimally invasive orthopaedic surgery and that in cases of venous thromboembolism after knee arthroscopy, a prothrombotic disorder should be suspected.

Adult↗
PubMed2004

Proinflammatory genetic profiles in subjects with history of ischemic stroke.

BACKGROUND AND PURPOSE: Proinflammatory genetic profiles, resulting from the combination of single nucleotide polymorphisms in genes encoding inflammatory molecules, may contribute to the development and progression of cardiovascular diseases. We evaluated the association between history of ischemic stroke and genetic profiles determined by the synergistic effects of polymorphisms in genes encoding prototypical inflammatory proteins. METHODS: The study included 237 individuals with history of ischemic stroke and 223 age-matched and gender-matched controls. The polymorphisms of the C-reactive protein (CRP), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin (E-sel), and matrix metalloproteinase-3 (MMP-3) genes were studied. RESULTS: IL-6 GG, IL-6 GC, MCP-1 GG, ICAM-1 EE, E-sel AA, and MMP-3 5A5A genotypes were significantly and independently associated with stroke history. The odds of stroke increased with the number of high-risk genotypes: carrying 1 proinflammatory gene variant conferred a risk of 3.3 (1.6 to 6.9), whereas individuals concomitantly carrying 2 and 3 proinflammatory gene variants had adjusted odds ratios of 21.0 (7.6 to 57.5) and 50.3 (10.2 to 248.1), respectively. CONCLUSIONS: Proinflammatory genetic profiles are significantly more common in subjects with stroke history. Synergistic effects between proinflammatory genotypes might be potential markers for cerebrovascular diseases.

Aged↗
PubMed2004

Polymorphisms of the macrophage inhibitory factor and C-reactive protein genes in subjects with Alzheimer's dementia.

Neuroinflammation is a central feature of Alzheimer's disease (AD). C-reactive protein (CRP) is a key molecule of the acute phase of inflammation that has been localized in the two characteristic lesions of AD brain, senile plaque and neurofibrillary tangles. On the other hand, the macrophage migration inhibitory factor (MIF) is a cytokine with multiple biological activities, including the ability to act as potent amyloid beta (A-beta)-binding protein. Two common polymorphisms have been recently detected in the genes encoding for CRP and MIF and have been associated with significant modifications of plasma levels and activity of the corresponding proteins. Following these observations, we hypothesized that CRP and MIF gene polymorphisms might contribute to the development and progression of neurodegenerative disorders and evaluated their association with AD. CRP and MIF gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis in 116 Italian subjects affected by probable AD and 184 age- and sex-matched controls. We did not find a statistically significant difference in the distribution of CRP and MIF genotypes and alleles between AD subjects and controls. Although these data need further confirmation, they indicate that CRP and MIF gene polymorphisms are not associated with AD.

Acute Disease↗
PubMed2004

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer's disease in Italians.

Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer's disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position -2518 of the MCP-1 gene promoter. A recent study has investigated the possible association between this gene polymorphism and AD in a Spanish population, with negative results. Here, we performed a case-control study to test whether the risk for AD might be influenced by the -2518 A/G polymorphism of the MCP-1 gene in an ethnically homogeneous Italian population. The GG genotype and the G allele of the MCP-1 gene polymorphism were significantly more common in the AD group than in control individuals (P<0.0001) A logistic regression analysis indicated that the GG genotype was an independent risk factor for AD in our population. This effect was not influenced by the presence of the APOE 4 high-risk allele, nor by the presence of other gene variations associated with a pro-inflammatory phenotype. These findings indicate that the -2518 A/G polymorphism of the MCP-1 gene is associated with AD in Italians and confirm that inflammatory gene variations may be important contributors in the development and progression of neurodegenerative disorders.

Aged↗
PubMed2003

Synergistic effect of -174 G/C polymorphism of the interleukin-6 gene promoter and 469 E/K polymorphism of the intercellular adhesion molecule-1 gene in Italian patients with history of ischemic stroke.

BACKGROUND AND PURPOSE: Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) are involved in the pathogenetic mechanisms responsible for several ischemic cardiovascular disorders, including cerebral ischemia. IL-6 and ICAM-1 plasma levels and/or function may be genetically influenced. We sought to evaluate distribution and reciprocal interaction of IL-6 G/C gene promoter polymorphism and ICAM-1 E/K gene polymorphism in Italian patients with history of ischemic stroke. METHODS: One hundred nineteen patients with history of ischemic stroke and 133 age- and sex-matched controls were studied. IL-6 and ICAM-1 genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis. RESULTS: The GG genotype of -174 IL-6 G/C gene polymorphism was significantly associated with history of ischemic stroke at both univariate (P<0.0001) and multivariate analysis (odds ratio [OR], 8.6; P<0.0001). Additionally, the EE genotype of ICAM-1 E/K gene polymorphism was significantly more common in the group of patients with history of ischemic stroke (P=0.003) and was an independent variable associated with stroke history (OR, 4.0; P=0.002). Interestingly, a further increased risk of stroke was found in subjects who concomitantly carry the IL-6 GG and ICAM-1 EE genotypes (IL-6 GG/ICAM-1 EE double-homozygous subjects) (OR, 10.1; P=0.004). CONCLUSIONS: There is a synergistic effect of IL-6 G/C and ICAM-1 E/K gene polymorphisms in patients with stroke history. Reciprocal interactions between genotypes may contribute in determining the risk profile for cardiovascular diseases and may merit further investigation as potential therapeutic targets.

Aged↗
PubMed2003

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.

Adult↗
PubMed2003

Peripheral nerve ischemia: apolipoprotein E deficiency results in impaired functional recovery and reduction of associated intraneural angiogenic response.

Apolipoprotein E-knockout (apoE KO) mice have peripheral sensory nerve defects, reduced and delayed response to noxious thermal stimuli, abnormal morphology of unmyelinated fibers, and impaired blood-nerve and blood-brain barriers. In this study, we show that, compared to wild-type mice, peripheral nerves of apoE KO mice have impaired ability to respond to ischemia, as demonstrated by measurement of motor and sensory conduction velocity. In addition, mice lacking apoE exhibit a deficit of reinnervation of ischemic epidermis, evaluated by immunofluorescent staining for the pan-neuronal marker PGP 9.5. Also regional nerve blood flow, measured by laser Doppler, and intraneural angiogenesis after ischemia are significantly compromised in apoE-deficient mice. Finally, upregulation of the angiogenic cytokine vascular endothelial growth factor (VEGF), which physiologically occurs after ischemia in the peripheral nerve of wild-type mice, is severely impaired in apoE KO mice. Among the several neural defects that have already been described in mice lacking apoE, this is the first demonstration that functional recovery to ischemia is impaired in the peripheral nerves of these animals. This deficit is mirrored by the inability of upregulating VEGF and mounting an appropriate intraneural angiogenic response following injury. These findings provide new evidence of possible interdependent relationships between VEGF, angiogenesis, and nerve function and regeneration and may provide new important information on the role of apoE in the nervous system.

Animals↗
PubMed2003

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.

Aged↗
PubMed2002

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 Alzheimer's 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.

Aged↗
PubMed2002

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.

Aged↗
PubMed2002

-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.

Aged↗
PubMed2002

Angiotensin-converting enzyme gene polymorphism may influence blood loss in a geriatric population undergoing total hip arthroplasty.

OBJECTIVES: To evaluate how angiotensin-converting enzyme (ACE) gene polymorphism is associated with perioperative blood loss in hip arthroplasty in a geriatric population. DESIGN: A case-control study of subjects consecutively undergoing total hip arthroplasty. SETTING: A department of orthopedic surgery in Italy. PARTICIPANTS: One hundred five patients, mean age +/- standard deviation 68.6 +/- 10.4, undergoing total hip arthroplasty. MEASUREMENTS: ACE gene polymorphism was analyzed using polymerase chain reaction. Decrement of hemoglobin (Hb) and hematocrit (Ht) was calculated as the difference between the preoperative and the lowest postoperative value, measured 1, 2, and 3 days after surgery. Total blood loss was calculated as the sum of intra- and postoperative blood loss. RESULTS: Patients carrying the deletion homozygous and insertion/deletion heterozygous genotypes of the ACE gene show a higher decrement of Hb (P <.01) and Ht (P <.01) and higher total blood loss (P <.007) after hip surgery than subjects carrying the insertion (II) homozygous. The role of ACE gene polymorphism seems hypertension independent. Logistic regression analysis showed that II genotype reduces total blood loss. CONCLUSIONS: This is the largest study evaluating the distribution of ACE gene genotypes in patients undergoing hip arthroplasty and the first investigating the association between bleeding and ACE gene polymorphism. Our data suggest that II genotype is associated with lower total blood loss.

Aged↗
PubMedDate not supplied

Age-dependent VEGF expression and intraneural neovascularization during regeneration of peripheral nerves.

The physiologic ability of peripheral nerves to regenerate after injury is impaired with aging. However, the mechanisms responsible for this phenomenon are still incompletely characterized. In this study, we investigated whether aging influences the intraneural angiogenic response that occurs after injury and during regeneration of peripheral nerves. We performed a crush injury of the sciatic nerve in old and senescence accelerated mice and found that the peripheral nerves of these animals are unable to locally upregulate vascular endothelial growth factor (VEGF), a prototypical angiogenic cytokine, after injury and have substantial deficits in mounting an appropriate intraneural angiogenic response during nerve regeneration. Our findings provide new evidence of possible interdependent relationships between aging, VEGF, angiogenesis, and nerve regeneration and suggest that vascular abnormalities might play a role in aging-associated neurological dysfunction, with potentially important fundamental and clinical implications.

Aging↗
PubMedDate not supplied

Intercellular adhesion molecule-1 K469E gene polymorphism and Alzheimer's disease.

Inflammatory processes are considered important in the pathogenesis of Alzheimer's disease (AD). Intercellular adhesion molecule-1 (ICAM-1) is an important mediator of inflammatory response and immune cell activation, is expressed on cerebrovascular endothelium and neuritic plaques in brain of AD patients, and seems to be implicated in the process of neuro-degeneration. A common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In this case-control study, we evaluated the distribution of E/K alleles and genotypes of the ICAM-1 gene in 98 patients affected by sporadic AD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in AD patients (P<0.01). Logistic regression analysis indicated that the presence of EE genotype significantly increased the risk of AD (odds ratio 3.01 [1.1-8.0], P<0.05). This study shows for the first time an association between ICAM-1 E/K gene polymorphism and AD, suggesting that polymorphisms of the ICAM-1 gene may be clinically important and confirming that inflammatory mechanisms may be crucial in the pathophysiology of neuro-degenerative diseases.

Aged↗