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Biomedical subjects

R Pola

Publications and source records attributed to R Pola.

At least 19 recordsLinked to original sources
PubMed2006

Vascular endothelial growth factor (VEGF) expression in noise-induced hearing loss.

Noise-induced hearing loss has been associated with alterations in cochlear blood flow. Our study analyzed the expression of Vascular Endothelial Growth Factor (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic agent, with multiple functions on vascular biology, ranging from vascular permeability to endothelial cell migration, proliferation, differentiation, and survival. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 min. Auditory function was evaluated by electrocochleographic recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes were studied by immunohistochemistry and scanning electron microscopy. The expression of VEGF and its receptors was examined by immunohistochemistry and western blotting analysis. The hearing threshold shift reached a level of 60 dB SPL on day 1 after trauma and underwent a partial recovery over time, reaching a value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the area located 14-16 mm from the apex. Increased cochlear VEGF expression was observed in noise-exposed animals, in particular at the level of stria vascularis, spiral ligament, and spiral ganglion cells. No changes were observed in the expression of VEGF-receptors. Our data suggest a role for VEGF in the regulation of the vascular network in the inner ear after acoustic trauma and during auditory recovery, with potentially important clinical and therapeutic implications.

Action Potentials↗
PubMed2005

Interleukin-6 gene polymorphism and risk of osteoarthritis of the hip: a case-control study.

OBJECTIVES: Osteoarthritis (OA) is considered a polygenic disease controlled by the expression of genetic factors. Genes encoding for cytokines have been associated with susceptibility for joint OA and interleukin (IL)-6 gene is also supposed to be involved in the cartilage degradation process. In this case-control study, we evaluated for the first time whether the risk of hip OA might be influenced by the -174 IL-6 gene polymorphism. METHODS: The distribution of IL-6 genotypes was evaluated in 75 patients affected by hip OA and in 107 age- and sex-matched controls. RESULTS: The distribution of IL-6 genotypes in (1) patients with hip OA: 33 GG, 30 GC, 12 CC and (2) control subjects: 34 GG, 40 GC, 33 CC. The frequency of the CC genotype was significantly higher in control patients (P=0.02). Logistic regression analysis indicated that the presence of the CC genotype is independently associated with a decreased risk of OA (odds ratio 0.4 [95% confidence interval 0.1-0.9], P=0.04). CONCLUSIONS: Primary OA of the hip has an important genetic component and variations of genes encoding for inflammatory cytokines, such as IL-6, may play an important role in the series of events responsible for the pathophysiology of OA.

Aged↗
PubMed2005

Stress proteins in Alzheimer's disease.

Environmental and genetic conditions can cause proteins to misfold or to accumulate abnormally due to impaired clearance. The chaperones which include heat shock proteins, aid survival by preventing protein mis-folding and the formation of cytotoxic protein aggregates. An increasing number of studies point to important roles for molecular chaperones in the biology of neurodegenerative diseases. Heat shock proteins can suppress neurotoxicity in animal models of Parkinson's and polyglutamine diseases, suggesting potential new therapeutic approaches in neurodegenerative disorders associated with abnormal protein folding and toxicity. Recent findings suggest that heat shock proteins can also be neuroprotective in Alzheimer's disease, but this area of research remains largely unexplored. This paper will review the literature related to the role of heat shock proteins in Alzheimer's disease.

Alzheimer Disease↗
PubMed2004

Prevalence of the K469E polymorphism of intercellular adhesion molecule 1 gene in Italian patients with inflammatory bowel disease.

BACKGROUND: Intercellular adhesion molecule 1 plays an important role in the recruitment of leucocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene has been identified. AIM: To assess the potential association of this polymorphism with inflammatory bowel disease. PATIENTS: A total of 165 inflammatory bowel disease patients, 75 with Crohn's disease and 90 with ulcerative colitis, and 187 controls were studied. METHODS: The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by chi2-test. RESULTS: In inflammatory bowel disease, the distribution of intercellular adhesion molecule 1 genotypes was 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls, 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly higher in inflammatory bowel disease (Crohn's disease and ulcerative colitis) patients than in controls. Subgroup analysis showed that the frequency of the E469 allele was significantly increased only in Crohn's disease patients with ileocolonic location of disease and penetrating behaviour compared with controls. CONCLUSIONS: We found an association of inflammatory bowel disease with the E/E genotype of intercellular adhesion molecule 1 gene, while allele E469 was associated with a subgroup of Crohn's disease patients with more extensive location of disease and penetrating behaviour. However, further studies are needed to confirm our findings.

Adolescent↗
PubMed2004

Comparative analysis of the in vivo angiogenic properties of stable prostacyclin analogs: a possible role for peroxisome proliferator-activated receptors.

OBJECTIVE: Until recently, prostacyclin (PGI2) biological activities were thought to be exclusively mediated by cell surface receptors named IP. Recent studies have instead identified a novel pathway of PGI2 signaling, occurring through activation of peroxisome proliferator-activated receptors (PPARs) located in the nucleus. The availability of stable PGI2 analogs with different affinity for IP receptors and PPARs provides the possibility to test the importance and function of this dual pathway in vitro and in vivo. In this study, the in vivo angiogenic properties of different PGI2 analogs and the potential relationship between PPAR-mediated pathways, vascular endothelial growth factor (VEGF), and angiogenesis were investigated. METHODS AND RESULTS: By using the murine corneal model of angiogenesis, we found that PGI2 analogs able to act on nuclear PPARs, such as iloprost and carbaprostacyclin (cPGI), induce angiogenesis in vivo. In contrast, cicaprost, a PGI2 analog that only acts on IP receptors, has no in vivo angiogenic activity. Interestingly, angiogenesis induced by iloprost and cPGI does not differ in extent and morphology from that induced by VEGF and is associated with local increment of VEGF mRNA expression and protein levels. Finally, iloprost-induced angiogenesis is significantly decreased by systemic inhibition of VEGF activity, obtained by gene transfer of a soluble form of the VEGF receptor Flt-1. CONCLUSIONS: These data demonstrate that stable PGI2 analogs may have angiogenic properties in vivo, depending on their ability to act on PPARs. The resulting angiogenic process appears to be mediated by VEGF. These findings indicate that important physiological activities in the cardiovascular system, such as angiogenesis and VEGF induction, may be modulated by PGI2 through specific activation of the PPAR signaling pathway in vivo, with potentially important fundamental and clinical implications.

Animals↗
PubMed2004

Efficient bone formation by gene transfer of human LIM mineralization protein-3.

LIM mineralization protein (LMP) is a novel positive regulator of the osteoblast differentiation program. In humans, three different LMP splice variants have been identified: LMP-1, LMP-2, and LMP-3. Gene transfer of human LMP-1 (hLMP-1) induces expression of genes involved in bone formation, including certain bone morphogenetic proteins (BMPs), promotes bone nodule formation in vitro, ectopic bone formation in vivo, and is therapeutic in animal models of posterior thoracic and lumbar spine fusion. To examine the osteoinductive properties of the LMP-3 in vitro and in vivo, we have generated plasmid and adenoviral vectors expressing codon-optimized hLMP-3. Here we demonstrate that gene transfer of hLMP-3 induces expression of the bone-specific genes osteocalcin, osteopontin, and bone sialoprotein and induced bone mineralization in preosteoblastic and fibroblastic cells. We also demonstrate that hLMP-3 is able to induce bone mineralization and the expression of the bone-specific genes, BMP-2, OSX, RunX2, and alkaline phosphatase in human mesenchymal stem cells in a dose-dependent manner. Finally, we demonstrate that direct gene transfer of hLMP-3 into murine skeletal muscle results in ectopic bone formation more efficiently than BMP-2. These results demonstrate that hLMP-3 gene transfer can be used to promote bone formation in cell culture and in vivo as or more efficiently than BMP-2, thus establishing feasibility and efficacy of direct gene delivery of hLMP-3 to produce bone in vivo. These results suggest that gene transfer of hLMP-3 could be developed as a bone-inductive therapeutic agent for clinical applications.

3T3 Cells↗
PubMed2004

Enhanced oxidative stress in workers with a standing occupation.

BACKGROUND: Several epidemiological studies have shown a statistically significant association between standing work and chronic venous insufficiency of lower limbs. This condition has been associated with an enhanced oxidative stress that, according to the literature, could represent a risk factor for cardiovascular and other systemic diseases. AIMS AND METHODS: To evaluate venous pressure of the lower limbs and reactive oxygen species (ROS) before and after work in 62 workers with a standing occupation (surgery room nurses) and 65 outpatient department nurses who can walk during their working time. RESULTS: After work, a statistically significant increase of venous pressure of the lower limbs levels was observed in both the study group and controls. Standing workers showed significantly higher mean levels of ROS after work.

Adult↗
PubMed2002

The -174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population.

Several studies have proposed a relationship between blood pressure and inflammation. Interleukin-6 (IL-6) is a multifunctional cytokine involved in inflammation and tissue injury and potentially influencing blood pressure. Recently, a common polymorphism of the IL-6 gene, associated with differences in the transcription rate of the protein, has been described. The aim of this study was to investigate a possible association between genetic variations of the -174GC polymorphism of the IL-6 gene promoter and hypertension in humans. IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 210 elderly Italian patients affected by essential hypertension (EH) and 177 age- and sex-matched controls. The distribution of IL-6 genotypes was 85 GG, 88 GC, 37 CC in the hypertensive patients and 65 GG, 73 GC, 39 CC in the control subjects. In this elderly cohort, no statistically significant association was found between the two groups (P = 0.45 for GG homozygous, P = 0.89 for GC heterozygous and P = 0.27 for CC homozygous). In conclusion the -174 GC polymorphism of the IL-6 gene promoter is not a marker for EH in this sample of elderly Italians.

Aged↗
PubMed2002

The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with peripheral artery occlusive disease.

OBJECTIVE AND DESIGN: high plasma levels of Interleukin-6 (IL-6) are found in patients with atherosclerotic disorders. Recently, a common polymorphism of the IL-6 gene promoter, influencing the transcription rate of the gene, has been described and associated with atherosclerosis of carotid and coronary arteries. The objective of this study was to test whether IL-6 gene promoter polymorphism is associated with peripheral artery occlusive disease (PAOD) in a case-control study. METHODS: IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 84 patients affected by PAOD and 183 controls. RESULTS: the distribution of IL-6 genotypes was: patients with PAOD: 44 GG, 30 GC, 10 CC; control subjects: 53 GG, 80 GC, 50 CC. The GG genotype was significantly more common in the PAOD group (p<0.0001), while the CC genotype was significantly more common in control patients (p=0.005). CONCLUSIONS: this study indicates a strong association between IL-6 gene polymorphism and PAOD and support the hypothesis that IL-6 and IL-6 gene polymorphism are important in the pathophysiology and evolution of ischaemic diseases of the lower limbs.

Aged↗
PubMed2002

The K469E polymorphism of the ICAM-1 gene is a risk factor for peripheral arterial occlusive disease.

Intercellular adhesion molecule-1 (ICAM-1) plays a crucial role in lymphocyte migration and activation, and is considered important in the pathogenesis of atherosclerosis. K469E is a common polymorphism of the ICAM-1 gene with potential functional significance. The aim of the present case-control study was to evaluate the association between this polymorphism and peripheral arterial occlusive disease (PAOD). ICAM-1 gene polymorphism was examined by polymerase chain reaction and restriction enzyme analysis in 75 Italian subjects affected by PAOD and 227 controls. The distribution of ICAM-1 genotypes in patients affected by PAOD was 32.1% EE, 50.6% EK, and 17.3% KK. The distribution of ICAM-1 genotypes in control subjects was 17.2% EE, 55.1% EK, and 27.7% KK. The EE genotype was significantly more common in patients than controls (P = 0.006). Logistic regression analysis indicated that the presence of the EE genotype significantly increases the risk of PAOD (odds ratio, 3.5; 95% confidence interval, 1.5-8.4; P = 0.004). This is the first study documenting a role of the ICAM-1 gene polymorphism in the pathogenesis of a cardiovascular disease, such as PAOD. Our data support the hypothesis that inflammatory mechanisms are important in the pathophysiology of vascular diseases with an atherosclerotic basis.

Aged↗
PubMed2001

The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors.

Sonic hedgehog (Shh) is a prototypical morphogen known to regulate epithelial/mesenchymal interactions during embryonic development. We found that the hedgehog-signaling pathway is present in adult cardiovascular tissues and can be activated in vivo. Shh was able to induce robust angiogenesis, characterized by distinct large-diameter vessels. Shh also augmented blood-flow recovery and limb salvage following operatively induced hind-limb ischemia in aged mice. In vitro, Shh had no effect on endothelial-cell migration or proliferation; instead, it induced expression of two families of angiogenic cytokines, including all three vascular endothelial growth factor-1 isoforms and angiopoietins-1 and -2 from interstitial mesenchymal cells. These findings reveal a novel role for Shh as an indirect angiogenic factor regulating expression of multiple angiogenic cytokines and indicate that Shh might have potential therapeutic use for ischemic disorders.

Angiopoietin-1↗
PubMed2001

Abdominal aortic aneurysm in normotensive patients: association with angiotensin-converting enzyme gene polymorphism.

OBJECTIVE AND DESIGN: to assess if deletion of the angiotensin-converting enzyme (ACE) gene is a risk factor for abdominal aortic aneurysms (AAAs) in normotensive patients. MATERIALS AND METHODS: ACE gene polymorphism was examined by polymerase chain reaction in 124 subjects with AAA and in 112 control subjects. AAA normotensive patients (group A, n=56) were compared to normotensive control subjects (group B, n =112) and to AAA hypertensive patients (group C, n =68). All subjects enrolled in this study were Caucasian and from central and southern Italy. RESULTS: the distribution of ACE genotypes was: normotensive patients with AAAs (group A): 3 II, 14 ID, 39 DD; normotensive control subjects (group B): 36 II, 48 ID, 28 DD; hypertensive patients with AAAs (group C): 14 II, 32 ID, 22 DD. The DD genotype was more common in group A than in control groups (A vs B p<0.001; A vs C p <0.001). The ID genotype was more common in group A as well (A vs B p <0.05; A vs C p <0.005). CONCLUSIONS: our data suggest a role for ACE I/D gene polymorphism in the pathogenesis of AAA in normotensive patients.

Aged↗
PubMed2001

Acute abdominal symptoms in malignant hypertension: clinical presentation in five cases.

Malignant hypertension causes anatomical and functional damage in several target organs, in particular brain, retina, heart and kidneys. Although vascular lesions in the gastroenteric tract are known to occur in several instances, their clinical relevance is unknown. In this study five cases of malignant hypertension, presenting with acute abdominal symptoms, are reported. A history of essential arterial hypertension was present in three patients; while one patient had a previous diagnosis of renovascular hypertension and one patient had renoparenchymal hypertension. However, in all cases the antihypertensive treatment was discontinued and inadequate before the accelerated malignant phase. The acute abdominal symptoms at presentation were due to intestinal infarction in 3 patients and acute pancreatitis in 2 patients. One patient with intestinal infarction died of postoperative cardiogenic shock. Our data are in agreement with previous reports describing the possible intra-abdominal complications of malignant hypertension. The therapeutic approach in such conditions should always consider an effective antihypertensive treatment in conjunction with surgical options.

Acute Disease↗
PubMed2001

Reversal of experimental diabetic neuropathy by VEGF gene transfer.

The pathogenetic basis for diabetic neuropathy has been enigmatic. Using two different animal models of diabetes, we have investigated the hypothesis that experimental diabetic neuropathy results from destruction of the vasa nervorum and can be reversed by administration of an angiogenic growth factor. Nerve blood flow, as measured by laser Doppler imaging or direct detection of a locally administered fluorescent lectin analogue, was markedly attenuated in rats with streptozotocin-induced diabetes, consistent with a profound reduction in the number of vessels observed. A severe peripheral neuropathy developed in parallel, characterized by significant slowing of motor and sensory nerve conduction velocities, compared with nondiabetic control animals. In contrast, 4 weeks after intramuscular gene transfer of plasmid DNA encoding VEGF-1 or VEGF-2, vascularity and blood flow in the nerves of treated animals were similar to those of nondiabetic control rats; constitutive overexpression of both transgenes resulted in restoration of large and small fiber peripheral nerve function. Similar experiments performed in a rabbit model of alloxan-induced diabetes produced comparable results. These findings support the notion that diabetic neuropathy results from microvascular ischemia involving the vasa nervorum and suggest the feasibility of a novel treatment strategy for patients in whom peripheral neuropathy constitutes a secondary complication of diabetes.

Animals↗
PubMed2000

Association between Helicobacter pylori cytotoxic type I CagA-positive strains and migraine with aura.

Recent studies have suggested an association between Helicobacter pylori infection and migraine. However, various strains of the bacterium are present, some endowed with greater pathogenicity. In particular, H. pylori type I CagA-positive strains induce a higher release of proinflammatory substances by the gastric mucosa that could trigger systemic vasospasms. The aim of the present study was to assess the prevalence of H. pylori CagA-positive strains in subjects with migraine. One hundred and seventy-five patients affected by migraine (49 with aura, 126 without aura) were consecutively enrolled and matched for sex, age, social background and geographical origin with 152 controls. Helicobacter pylori infection was assessed through 13C-urea breath test. Specific serological IgG against CagA were detected through ELISA. The prevalence of H. pylori infection was similar in migraine patients and in controls (40% vs. 39%, respectively). Among migraine patients, prevalence of infection was not related to presence or absence of aura (45% vs. 37%, respectively). However, among infected subjects, a significantly higher prevalence of CagA-positive strains was observed in patients affected by migraine with aura when compared with those affected by migraine without aura (41% vs. 19%, P < 0.01) and with controls (41% vs. 17%, P < 0.01). CagA-positive H. pylori strains were found to be strongly associated with migraine with aura. A higher inflammatory response of the gastric mucosa to more virulent strains could release substances that may act as triggers of vasospasm in peculiar cerebral arterial districts, probably implicated in the 'aura' phenomenon.

Adult↗
PubMed2000

Role of sucralfate in gastrointestinal diseases.

Sucralfate is a cytoprotective drug widely used in clinical practice to prevent or treat several gastrointestinal diseases such as gastro-esophageal reflux, gastritis, peptic ulcer, stress ulcer and dyspepsia. Sucralfate is a safe and well tolerated drug, as demonstrated by the quite complete lack of side effects and it is, for this reason, one of the most important therapeutic choices in the management of acid related diseases during pregnancy. Moreover, sucralfate has recently been shown to be useful in non-acid related gastrointestinal disease as well. In fact, sucralfate has also been administered topically in patients with radiation-induced mucosal procto-sigmoiditis or ulcerative colitis with surprising results. The drug is actually able to form a physical barrier between epithelium and damaging agents (-bile salts, drugs, refluxate...). Moreover, sucralfate increases the local levels of fibroblast growth factors and induces a rise in the mucosal concentration of prostaglandins which are considered important factors in mucosal healing. The aim of this paper is to describe the current and probably forthcoming uses of sucralfate in the field of gastrointestinal disorders. Moreover, we investigate the role of sucralfate as a reliable means to prevent the occurrence of reflux-like symptoms after Helicobacter pylori eradication and in the management of Helicobacter pylori negative patients affected by non-ulcer dyspepsia.

Anti-Ulcer Agents↗