[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.

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.

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.

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.

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.

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.

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.

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.

A two-layered classifier based on the radial basis function for the screening of thalassaemia.

The thalassaemias are blood disorders with hereditary transmission. Their distribution is global, with particular incidence in areas affected by malaria. Their diagnosis is mainly based on haematologic and genetic analyses. The aim of this study was to differentiate between persons with the thalassaemia trait and normal subjects by inspecting characteristics of haemochromocytometric data. The paper proposes an original method that is useful in screening activity for thalassaemia classification. A complete working system with a friendly graphical user interface is presented. A unique feature of the presented work is the adoption of a two-layered classification system based on Radial basis function, which improves the performance of the system.

Doxorubicin release is not a prerequisite for the in vitro cytotoxicity of HPMA-based pharmaceuticals: in vitro effect of extra drug-free GlyPheLeuGly sequences.

A systematic study was designed to elucidate differences in cytostatic activity in vitro between HPMA-based doxorubicin conjugates synthesized using different polymerization techniques and differing in peptidyl side chain. A polymer-drug conjugate containing doxorubicin (DOX) bound to HPMA copolymer backbone through the enzymaticaly non-cleavable sequence GlyGly shows low but significant cytotoxicity in vitro in seven cancer cell lines of mouse (EL4, 38C13, 3T3, BCL1) and human (SW620, Raji, Jurkat) origin. The low cytotoxicity can be considerably increased by the presence of additional drug-free GlyPheLeuGly side chains. P1 conjugate, i.e. non-targeted HPMA copolymer bearing doxorubicin bound via a biodegradable GlyPheLeuGly sequence, synthesized by direct copolymerization of HPMA with monomeric doxorubicin and thus without additional drug-free GlyPheLeuGly sequences is less effective compared to PK1 synthesized by polymer analogous reaction and thus containing extra drug-free GlyPheLeuGly sequences. Significant activity-enhancing effect was not seen with other amino acid/oligopeptide sequences (e.g., Gly or GlyGly). The activity-enhancing effect of GlyPheLeuGly sequences is more obvious in the conjugate containing doxorubicin bound to HPMA through GlyGly sequence. Derivatization of the terminal carboxyl group of the extra GlyPheLeuGly side chains (amide, N-substituted amide, free carboxyl) does not significantly influence the cytotoxicity of the conjugates. The presence of the GlyPheLeuGly sequence in the conjugate structure increases its rate of intracellular accumulation. Normal cells (Balb/c splenocytes) accumulate less polymer-doxorubicin conjugate compared to cancer cells (T cell lymphoma EL4, B cell lymphoma Raji and T cell leukemia JURKAT).

Serum macrophage migration inhibitory factor (MIF) in the intercritical phase of hereditary periodic fevers and its relationship with the MIF-173G/C polymorphism.

OBJECTIVES: To examine the association of the -173 single-nucleotide G/C polymorphism of the macrophage migration inhibitory factor gene (MIF) and serum macrophage migration inhibitory factor (MIF) concentrations in a group of Italian patients with hereditary periodic fevers (HPF), tested during a symptom-free phase of their disease. METHODS: Genomic DNA for MIF and serum MIF were evaluated in 22 patients with HPF and compared with healthy controls of the same ethnic group. The MIF-173G/C polymorphism was genotyped using polymerase chain reaction (PCR) and visualized by ethidium bromide staining. Serum MIF levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: MIF-173*C allele frequency and MIF serum concentrations were significantly higher in patients with HPF than in controls, with no statistically significant difference between familial Mediterranean fever (FMF) and hyperimmunoglobulinaemia D/periodic fever syndrome (HIDS) and no correlation with specific MIF genotypes. CONCLUSIONS: The MIF-173*C allele was found more frequently in patients with HPF than in controls and MIF serum concentrations were considerably elevated in attack-free phases, suggesting a persistent state of subclinical cytokine activation with MIF involvement in the autoinflammatory cascade.

Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia.

OBJECTIVES: Single nucleotide polymorphisms in genes encoding inflammatory molecules may determine genetic profiles associated with increased risk of development and progression of cardiovascular diseases. In this study, we evaluated distribution and reciprocal interaction of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in subjects with peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI). We also investigated whether synergistic interactions between these pro-inflammatory gene polymorphisms influence the risk of PAOD and CLI. DESIGN, SUBJECTS AND METHODS: In a genetic association study that included 157 PAOD patients and 206 controls, the following gene polymorphisms were analysed: C-reactive protein (CRP) 1059 G/C, interleukin-6 (IL-6)-174 G/C, macrophage migration inhibitory factor (MIF)-173 G/C, monocyte chemoattractant protein (MCP-1) - 2518 A/G, E-selectin (E-Sel) Ser128Arg, intercellular adhesion molecule-1 (ICAM-1) 469 E/K, matrix metalloproteinase (MMP)-1 -1607 1G/2G, MMP-3-1171 5A/6A and MMP-9-1563 C/T. RESULTS: We found that IL-6, E-sel, ICAM-1, MCP-1, MMP-1 and MMP-3 gene polymorphisms were significantly and independently associated with PAOD. We also found that these pro-inflammatory polymorphisms determine genetic profiles that are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes concomitantly carried by a given individual. CONCLUSIONS: Pro-inflammatory genetic profiles are significantly more common in subjects with PAOD. Synergistic effects between pro-inflammatory genotypes might be potential markers for the presence and severity of atherosclerotic disorders.

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.

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.

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.

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.

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.

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.