Functionalized hydrogel microparticles prepared by microfluidics and their interaction with tumour marker carbonic anhydrase IX.

Microfluidics allows precise control of the synthesis of microparticles for specific applications, where size and morphology play an important role. In this work, we have introduced microfluidic chip design with dedicated extraction and gelation sections allowing to prepare hydrogel particles in the size range of a red blood cell. The influence of the extractive channel size, alginate concentration and type of storage media on the final size of the prepared alginate microparticles has been discussed. The second part of the work is dedicated to the surface modification of prepared particles using chitosan, pHPMA and the monoclonal antibody molecule, IgG M75. The specific interaction of the antibody molecule with an antigen domain of carbonic anhydrase IX, the transmembrane tumour protein associated with several types of cancer, is demonstrated by fluorescence imaging and compared to an isotypic antibody molecule.

Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury.

The Hedgehog (Hh) pathway is a crucial regulator of muscle development during embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh) regulates postnatal myogenesis in the adult skeletal muscle both directly, by acting on muscle satellite cells, and indirectly, by promoting the production of growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, progression of the dystrophic pathology corresponds to progressive inhibition of the Hh signaling pathway in the skeletal muscle. We also show that the upregulation of the Hh pathway in response to injury and during regeneration is significantly impaired in mdx muscle. Shh treatment increases the proliferative potential of satellite cells isolated from the muscles of mdx mice. This treatment also increases the production of proregenerative factors, such as insulin-like growth factor-1 and vascular endothelial growth factor, from fibroblasts isolated from the muscle of mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the human Shh gene promotes successful regeneration after injury in terms of increased number of proliferating myogenic cells and newly formed myofibers, as well as enhanced vascularization and decreased fibrosis.

[Letournel ilioinguinal approach in the management of acetabular fractures]. / Abordaje ilioinguinal de Letournel en el manejo de fracturas de acetábulo.

The ilioinguinal approach described by Emile Letournel in 1961 allows an extensive exposure of the anterior elements of the pelvis and acetabular fractures involving the anterior wall and/or column, pubic symphysis, and sacroiliac joint. It also facilitates a rapid recovery of muscle function and leaves a cosmetic scar.

El abordaje ilioinguinal descrito por Emile Letournel en 1961 permite una extensa exposición de los elementos anteriores de la pelvis y de las fracturas acetabulares que involucran la pared o columna anterior, sínfisis del pubis y articulación sacroilíaca. Facilita una rápida recuperación de la función muscular y deja una cicatriz cosmética.

Direct anterior approach complications for total hip arthroplasty.

The direct anterior approach (DAA) for total hip arthroplasty has been popularized in the last decade as a minimally invasive approach used by many surgeons, including the authors, to preserve the integrity of muscle groups and their insertions and the dynamic hip stability resulting in less surgical trauma and faster recovery process with decreased postoperative pain. This surgical approach is not without a variety of complications and pitfalls. This review aims to identify any potential drawbacks and challenges associated with the DAA in THA and guide surgeons on minimizing and avoiding them.

El abordaje anterior directo (AAD) en artroplastía total de cadera se ha popularizado en la última década como un abordaje de mínima invasión utilizado por varios cirujanos, incluyendo a los autores, con la ventaja de preservar la integridad de los grupos musculares de la cadera y sus inserciones, así como la estabilidad dinámica de la articulación, resultando en menor trauma quirúrgico y una recuperación más rápida con menos dolor postoperatorio, a pesar de esto, el abordaje quirúrgico no está exento de complicaciones. El propósito de esta revisión es describir los riesgos y complicaciones potenciales relacionados al abordaje anterior directo en cirugía de artroplastía total de cadera y presentar una guía de cómo minimizarlas o evitarlas.

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.

Bilateral mirror hand: 2-year follow-up and literature review.

INTRODUCTION: Mirror hand syndrome is a very rare congenital deformity, also called cubital dimelia, characterized by the absence of the thumb, as well as the duplication of the fingers in a symmetrical image and, in some cases, with a duplication of the bones of the forearm. METHODS: The current treatment consists of a thumb reconstruction through thumb pollicization, although there are alternatives such as rotating osteotomy, syndactylization or conservative treatment. In this article we present the case of a girl with a non-classic bilateral mirror hand, the clinical and radiological findings, the bilateral surgical technique in two surgical times with six months of difference and two years follow-up. RESULTS: Complete mobility arches, as well as a good hand holding function were achieved with metacarpophalangeal thumb flexion 0-40o, interphalangeal 5-45o and abduction-adduction 0-50o. We achieved a complete opposition of the new thumb with respect to the other fingers. The strength of the clamp between the fingers was 75.2% of the normal force for her given age, while the strength of the lateral clamp of 66.3% and that of the grip of the fist was 69.1%. CONCLUSION: The surgical technique in the present case (pollicization of the thumb) is an excellent option, achieving objectives of fine and gross motor skills, and good cosmetic results.

INTRODUCCIÓN: Mano en espejo es una deformidad congénita muy rara, en ocasiones conocida como dimelia cubital, caracterizada por la ausencia del dedo pulgar, así como la duplicación de los dedos en imagen simétrica y, de forma clásica, también de los huesos del antebrazo. MÉTODOS: El tratamiento actual consiste en una reconstrucción del pulgar mediante pulgarización, aunque existen alternativas como osteotomía rotadora, sindactilización o el tratamiento conservador. En este artículo se presenta el caso de una niña con mano en espejo no clásica bilateral, los hallazgos clínicos, radiológicos, la reconstrucción quirúrgica de ambas manos consistente en pulgarización tipo Buck-Gramcko bilateral en dos tiempos quirúrgicos con seis meses de diferencia y el seguimiento a corto plazo. RESULTADOS: Presentó arcos de movilidad completos, así como una buena función de sujeción de la mano, se lograron con la flexión del pulgar metacarpofalángica 0-40o, interfalángica 5-45o y abducción-aducción 0-50o. Logramos una oposición del nuevo pulgar con respecto a los otros dedos. La fuerza de la pinza entre los dedos fue del 75.2% de la fuerza normal para la edad, mientras que la fuerza de la pinza lateral fue de 66.3% y la de la empuñadura fue de 69.1%. CONCLUSIÓN: La técnica quirúrgica utilizada en el presente caso demuestra una excelente opción, logrando objetivos de pinza gruesa, pinza fina y agarres, así como un buen resultado cosmético.

Abordaje ilioinguinal de Letournel en el manejo de fracturas de acetábulo / Letournel ilioinguinal approach in the management of acetabular fractures

Resumen: El abordaje ilioinguinal descrito por Emile Letournel en 1961 permite una extensa exposición de los elementos anteriores de la pelvis y de las fracturas acetabulares que involucran la pared o columna anterior, sínfisis del pubis y articulación sacroilíaca. Facilita una rápida recuperación de la función muscular y deja una cicatriz cosmética.

Abstract: The ilioinguinal approach described by Emile Letournel in 1961 allows an extensive exposure of the anterior elements of the pelvis and acetabular fractures involving the anterior wall and/or column, pubic symphysis, and sacroiliac joint. It also facilitates a rapid recovery of muscle function and leaves a cosmetic scar.

Cell-penetrating peptides: a useful tool for the delivery of various cargoes into cells.

Cell-penetrating compounds are substances that enhance the cellular uptake of various molecular cargoes that do not easily cross the cellular membrane. The majority of cell-penetrating compounds described in the literature are cell-penetrating peptides (CPPs). This review summarizes the various structural types of cell-penetrating compounds, with the main focus on CPPs. The authors present a brief overview of the history of CPPs, discuss the various types of conjugation of CPPs to biologically active cargoes intended for cell internalization, examine the cell-entry mechanisms of CPPs, and report on the applications of CPPs in research and in preclinical and clinical studies.

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.

Coagulation factor XIII Val34Leu gene polymorphism and Alzheimer's disease.

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 Alzheimer's 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.

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.

Peptide-targeted polymer cancerostatics.

A tumor-targeting drug delivery system consists of a tumor recognition moiety and a directly linked cytotoxic agent or an agent attached to a water-soluble synthetic polymer carrier through a suitable linker. Conjugation of a drug with a polymer carrier can change its solubility, toxicity, biodistribution, blood clearance and therapeutic specificity. Increased therapeutic specificity of a polymer drug can be achieved by the attachment of a targeting moiety (e.g. a lectin, protein, antibody, or peptide) that specifically interacts with receptors on the target cells. A large number of tumor-specific peptides were described in recent years. After a short introduction, some important examples of peptide-targeted conjugates will be described and discussed.

The pH-dependent and enzymatic release of cytarabine from hydrophilic polymer conjugates.

Cytarabine is one of the most efficient drugs in the treatment of hematological malignancies. In this work, we describe the synthesis and characterization of two different polymer conjugates of cytarabine that were designed for the controlled release of cytarabine within the leukemia cells. Reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 3-(3-methacrylamidopropa-noyl)thiazolidine-2-thione) or 3-(Nmethacryloylglycyl-phenylalanylleucylglycyl)thiazolidine-2-thione were used in the study as reactive polymer precursors for reaction with cytarabine. The enzymatic release of cytarabine from the conjugate containing a GFLG spacer utilizing cathepsin B was verified. In addition to enzymolysis, the pH-dependent hydrolysis of cytarabine from both copolymers was also confirmed. Approximately 40 % and 20 % of the drug was released by spontaneous hydrolysis at pH 7.4 within 72 h from the polymer conjugates with the GFLG and beta-Ala spacers, respectively. At pH 6.0, the spontaneous hydrolysis slowed down, and less than 10 % of the drug was liberated within 72 h. The results of the cytotoxicity evaluation of the polymer conjugates in vitro against various cell lines showed that the cytotoxicity of the polymer conjugates is approximately three times lower in comparison to free cytarabine.

Micelle-forming HPMA copolymer conjugates of ritonavir bound via a pH-sensitive spacer with improved cellular uptake designed for enhanced tumor accumulation.

We describe design, synthesis, physico-chemical characterization and preliminary biological evaluation of micelle-forming polymer drug conjugates with controlled drug release intended for tumor treatment. The structure of the conjugates was designed to enable tumor tissue- and cell-specific drug release and micelle disassembly to avoid side effects accompanying classic chemotherapy and guarantee safe elimination of the drug-free carrier from the organisms. The amphiphilic polymer conjugates consisted of a hydrophobic hexaleucine block and a hydrophilic block based on the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer with an antiviral and cytostatic drug, ritonavir, bound through a pH-sensitive spacer. Diblock copolymers with low dispersity (D∼ 1.1) were prepared via reversible addition-fragmentation chain transfer (RAFT) copolymerization using a hexaleucine derivative as a chain transfer agent. The associative properties of the copolymers depend on the hydrophilic polymer block length and the hydrophobic ritonavir content. The micelles dissociated under mild acidic conditions mimicking the environment inside tumor tissue/cells, because of the decrease in polymer hydrophobicity after the rapid release of the hydrophobic drug from the polymer carrier. Unexpectedly, the polymer-ritonavir conjugates internalized into HeLa cells significantly more than the polymers without ritonavir. The enhanced cell penetration and pH-triggered micelle disassembly predetermine the polymer-ritonavir conjugates to become promising tumor-targeted drug carriers.

Impact of integrated home care services on hospital use.

OBJECTIVE: To examine the effect of a home care program based on comprehensive geriatric assessment and case management on hospital use and costs among frail older individuals. DESIGN: Quasi-experimental study with a 6-month follow-up. SETTING: Vittorio Veneto, a town in northern Italy. PARTICIPANTS: One hundred fifteen frail older people who applied for integrated home care services. INTERVENTION: Each patient was assessed with the Minimum Data Set for Home Care, and, subsequently, a case manager and a multidisciplinary team delivered social and health care services as indicated. MAIN OUTCOME MEASURES: We determined the hospital admissions and days spent in the hospital for all subjects during the first 6 months after the implementation of the home care program and compared them with the rate of hospitalization that the same patients had experienced in the 6 months preceding the implementation of the program. RESULTS: After the implementation of the integrated home care program, there was a significant reduction in the number of hospitalizations compared with pre-implementation (56% vs 46%, respectively; P < .001), associated with a reduction in the number of hospital days, both at the individual patient level (28+/-23 days vs 18+/-15 days, respectively; P < .01) and for each admission (16+/-12 days vs 12+/-8 days, respectively; P < .01). This resulted in a 29% cost reduction with an estimated savings of $1260 per patient. CONCLUSIONS: The implementation of an integrated home care program based on the use of a comprehensive geriatric assessment instrument guided by a case manager has a significant impact on hospitalization and is cost-effective.

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.

Insulin-dependent diabetes mellitus affects eradication rate of Helicobacter pylori infection.

BACKGROUND: Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; however, antibiotic absorption may be influenced by the disease. Helicobacter pylori, the most common gastric infection worldwide, is the main acquired factor in the pathogenesis of gastritis and peptic ulcer. The aim of the study was to compare the H. pylori eradication rate obtained with a standard 7-day antibiotic regimen in a group of IDDM H. pylori infected patients and in a control group of infected dyspeptic patients. METHODS: Thirty-one patients (18 male, 13 female, 39+/-12 years) affected by IDDM and H. pylori infection, and 50 dyspeptic infected patients (23 male, 17 female, 37+/-10 years) were evaluated. H. pylori infection was assessed through 13C-urea breath test. A triple therapy with amoxycillin (1 g b.i.d.), clarithromycin (250 mg t.i.d.) and pantoprazole (40 mg b.i.d.) was given to both groups at the time of diagnosis for 7 days. Cure was defined as the absence of H. pylori infection, assessed by 13C-urea breath test, 6 weeks after completing anti-microbial therapy. Effects of H. pylori eradication on gastrointestinal symptoms (pyrosis, epigastric pain, belching, bloating, halitosis and nausea) were also evaluated. RESULTS: All enrolled patients completed the study. When compared to dyspeptic patients, the eradication rate was significantly lower in IDDM patients: 92% (46/50) versus 65% (20/31), respectively (P < 0.002). IDDM patients infected by H. pylori showed a different prevalence of some of the gastrointestinal symptoms assessed when compared to the infected dyspeptic patients; in particular, pyrosis, epigastric pain and belching were significantly more prevalent in the infected dyspeptic group. After H. pylori eradication, both groups showed a significant reduction of the intensity of all the gastrointestinal symptoms evaluated, except for nausea. CONCLUSIONS: IDDM patients showed a significantly lower H. pylori eradication rate when compared to that observed in dyspeptic subjects. The dosage and/or the duration of a standard eradication regimen does not appear to be sufficient to eradicate the infection in IDDM patients. The impairment of the gastrointestinal mucosa microvasculature with a reduction of antibiotic absorption, or the frequent use of antibiotics for other infections with development of resistant strains, may be the mechanisms underlying the observation.

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.

Post-traumatic basilar artery thrombosis in a young man with atrial septum aneurysm and prothrombin gene G20210A polymorphism.

Prothrombin gene G20210A polymorphism has been recently identified as a cause of venous thrombosis. However the association between this mutation and arterial thrombosis remains uncertain. Some authors have suggested that the polymorphism in the 3' region of the prothrombin gene may precipitate cerebral arterial thrombosis in young patients with prothrombotic conditions. We report a case of post-traumatic basilar artery thrombosis in a young patient carrier of the prothrombin gene G20210A polymorphism. Thirty-six hours after sustaining a head injury in the occipital region, a young man developed vomiting, headache, dizziness and truncal ataxia, without signs of focal impairment. Magnetic resonance imaging and selective angiography carried out 2 days later showed an obstruction of the basilar artery, with infarction of the right cerebellar region. A transthoracic echocardiogram showed a patent foramen ovale with little left-to-right shunt and an aneurysm of the interatrial septum. Blood examination showed a heterozygous status for prothrombin gene G20210A polymorphism. We conclude that this prothrombin gene mutation and the coexisting particular head injury and interatrial septal aneurysm could have contributed simultaneously to the development of basilar artery occlusion and cerebellar infarction. We suggest that in selected cases of cerebellar ischemia a prothrombin gene G20210A polymorphism should be considered.

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.