Preliminary insights into RNA in CSF of pediatric SMA patients after 6 months of nusinersen.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare autosomal-recessive neurodegenerative disorder caused by mutations in survival motor neuron 1 (SMN1) gene, and consequent loss of function of SMN protein, which results in progressive loss of lower motor neurons, and muscular wasting. Antisense oligonucleotide (ASO) nusinersen (Spinraza®) modulates the pre-mRNA splicing of the SMN2 gene, allowing rebalance of biologically active SMN. It is administered intrathecally via lumbar puncture after removing an equal amount of cerebrospinal fluid (CSF). Its effect was proven beneficial and approved since 2017 for SMA treatment. Given the direct effect of nusinersen on RNA metabolism, the aim of this project was to evaluate cell-free RNA (cfRNA) in CSF of SMA patients under ASOs treatment for biomarker discovery. METHODS: By RNA-sequencing approach, RNA obtained from CSF of pediatric SMA type 2 and 3 patients was processed after 6 months of nusinersen treatment, at fifth intrathecal injection (T6), and compared to baseline (T0). RESULTS: We observed the deregulation of cfRNAs in patients at T6 and we were able to classify these RNAs into disease specific, treatment specific and treatment dependent. Moreover, we subdivided patients into "homogeneous" and "heterogeneous" according to their gene expression pattern. The "heterogeneous" group showed peculiar activation of genes coding for ribosomal components, meaning that in these patients a different molecular effect of nusinersen is observable, even if this specific molecular response was not referable to a clinical pattern. CONCLUSIONS: This study provides preliminary insights into modulation of gene expression dependent on nusinersen treatment and lays the foundation for biomarkers discovery.

New CACNA1A deletions are associated to migraine phenotypes.

BACKGROUND: Familial hemiplegic migraine type 1 (FHM1) is a form of migraine with aura caused by heterozygous mutations in 4 genes: CACNA1A, ATP1A2, SNC1A and PRRT2, but further heterogeneity is expected. Here have been described clinical and molecular features in patients suffering from migraine with Aura (MA), without (MO) and hemiplegic migraine attacks. Next Generation Sequencing by TruSeq Custom Amplicon for CACNA1A and ATP1A2 gene has been performed. All genetic variants have been confirmed by Sanger sequencing and all samples were also analyzed with MLPA assay for ATP1A2-CACNA1A genes to detect duplication or deletion. All MLPA data were verified by Real Time PCR. RESULTS: Sequencing analysis showed 3 point mutations, two novel variants and one already described in literature. Moreover, MLPA analysis showed 3 deletions in 9 sporadic hemiplegic migraine (18%), in 3 patients with non-hemiplegic migraine (4.1%) and in 3 patients affected by episodic ataxia (20%). Two sporadic patients showed a deletion in exons 41-43, while the rest of HM patients (5) showed a deletion in the terminal part of the CACNA1A gene. About episodic ataxia, we have identified deletions in exon 12-15 and in exon 47. Finally, in migraine patients, we have found different subjects affected by different phenotypes deleted in exon 47. CONCLUSION: This work highlights the importance to complement analysis as direct sequencing with quantitative analysis (MLPA). In fact, intragenic CACNA1A rearrangements have been detected. Our work demonstrated that deletions in CACNA1A gene may be associated also to different migraine phenotypes.

Rosiglitazone reverses increased duodenal inhibitory response in spontaneously hypertensive rats.

BACKGROUND: Thiazolidinediones (TZDs) including rosiglitazone (ROSI) are insulin sensitizing agents with beneficial gastrointestinal effects. However, no studies are available on TZDs effect in gastrointestinal motility. We evaluated the effects of ROSI on gastrointestinal inhibitory neurotransmission focusing on the modulatory roles of nitric oxide synthase/nitric oxide (NOS/NO) and heme oxygenase/carbon monoxide (HO/CO) pathways. METHODS: Spontaneously hypertensive rats (SHR) were used as model of insulin resistance. Duodenal strips were obtained from vehicle-treated SHR, ROSI-treated SHR (5 mg kg(-1) by gavage daily per 6 weeks), and Wistar Kyoto (WKY). Inhibitory responses to electrical field stimulation (EFS) were evaluated in the presence of HO inhibitor zinc protoporphyrin IX (ZnPPIX, 10 µmol L(-1)) or NOS inhibitor N(G)-nitro-L-arginine (L-NNA, 100 µmol L(-1)), alone and in combination. Protein levels of HO and NOS isoforms were evaluated by immunohistochemistry and western blot analysis. KEY RESULTS: Basal responses to EFS were significantly increased in duodenum strips from vehicle-treated SHR vs WKY. This effect was reversed in ROSI-treated SHR. The EFS-mediated relaxation was comparably reduced by ZnPPIX in WKY and SHR, but not in ROSI-treated SHR animals. The L-NNA reduced EFS response to a similar extent in WKY and ROSI -treated SHR, but its effect was significantly higher in vehicle-treated SHR. Expression of HO-1 protein was significantly lower, whereas HO-2 protein levels were unchanged in ROSI-treated SHR with respect to vehicle-treated SHR. Finally, increased levels of nNOS in vehicle-treated SHR were reduced in ROSI-treated SHR. CONCLUSIONS & INFERENCES: Chronic ROSI treatment reverses increased SHR duodenal inhibitory response acting on CO and NO components.

Effect of the 50 bp deletion polymorphism in the SOD1 promoter on SOD1 mRNA levels in Italian ALS patients.

The genetic association between homozygosity for a 50 bp deletion polymorphism in the SOD1 promoter, 1684 bp upstream of the ATG, and an increased age of symptom onset was observed in various populations of ALS patients. Moreover, it has been demonstrated that this deletion reduces SOD1 expression in vitro. The objective of the present study was to test whether the observed association is replicated in patients from an Italian population and to check whether the deletion correlates with reduced SOD1 mRNA expression in vivo. Genomic DNA from 235 Italian SALS cases and 245 age- and sex-matched donors from the same ethnic background was screened for the 50 bp SOD1 promoter deletion by real time PCR assays. No differences were observed between ALS patients and controls for the frequency of both the alleles (D=deleted, N=non-deleted; p=0.95) and genotypes (p=0.90). Furthermore, stratification of the ALS samples showed that this variation was not associated with increased age of onset in ND and DD patients in comparison to NN patients (p=0.48). Finally, we performed real-time RT-PCR to quantify SOD1 mRNA levels in 48 patients and we did not find a relevant difference among the three sub-groups of genotypes (p=0.30). Our data suggest that the studied polymorphism does not modulate SOD1 mRNA level and disease phenotype in an Italian population.

Evaluation in vitro of synthetic curcumins as agents promoting monocytic gene expression related to ß-amyloid clearance.

Accumulation of amyloid-beta (Aß) is one of the hallmarks of Alzheimer's disease (AD), and efficient clearance of Aß by cells of the innate immune system may be an important mechanism for controlling or preventing disease onset. It was reported that peripheral blood mononuclear cells (PBMCs) of most AD patients are defective in the phagocytosis of soluble Aß. Natural curcumins were shown to restore Aß phagocytosis by AD PBMCs and to up-regulate the expression of key genes including MGAT3 and those encoding Toll-like receptors (TLRs). Bisdemethoxycurcumin (BDC), a minor component of natural curcumin, was shown to have the greatest potency for stimulating AD PBMCs. Because natural curcumins have inherent limitations with regard to physicochemical properties, synthetic curcumin analogues were developed that showed improved solubility, stability, and bioavailability. An in vitro system using human monocytic cell lines (U-937, THP-1) was used to evaluate analogues for the potency of innate immune cell stimulation. These cell lines showed responses to curcuminoids and to 1α,25-dihydroxyvitamin D3 (VD3) resembling those seen in human PBMCs. From more than 45 curcuminoids analyzed, the most potent compounds possessing enhanced pharmaceutical properties were identified. The most promising candidates included prodrug versions containing water solubility-enhancing amino acids and stability-increasing modifications near the central diketone. In vivo studies showed compound (5) substantially increased bioavailability by combining several promising structural modifications. Studies examining ex vivo phagocytosis of Aß and bead particles in mouse microglia showed that BDC and several water-soluble analogues were quite effective compared to curcumin or an unnatural analogue. In vitro studies using monocytic cell lines reported herein complement those using human PBMCs and represent a routinely accessible and uniform cellular resource allowing direct comparisons between compounds.

Curcumins promote monocytic gene expression related to ß-amyloid and superoxide dismutase clearance.

Neurodegenerative diseases are associated with accumulation of modified proteins or peptides including amyloid-ß (Aß) in Alzheimer's disease (AD), and misfolded superoxide dismutase-1 (SOD-1) in amyotrophic lateral sclerosis (ALS). Clearance of Aß or SOD-1 by the innate immune system may be important for controlling or preventing disease onset. Curcumins restore Aß phagocytosis by peripheral blood mononuclear cells (PBMCs) from AD patients and Aß clearance with upregulation of key genes including MGAT3, vitamin D receptor (VDR) and Toll-like receptors (TLRs). Certain curcumins inhibit inflammatory processes of PBMCs from ALS patients. We developed an in vitro system using human monocytes from patients and monocytic cell lines (i.e. U-937, THP-1) for evaluating curcuminoid potency of innate immune cell stimulation. Bisdemethoxycurcumin and certain analogs potentiated MGAT3,VDR and TLR gene expression 3- to 300-fold in U-937 cells. The effect of curcumins on inflammation in monocytes from patients with ALS was examined. Recursive medicinal chemistry was applied to identify compounds that stimulate the innate immune system for use in the clearance of Aß in AD and the reversal of neuroinflammation and defective SOD-1 accumulation in ALS.

Cardiovascular complications in diabetes: lessons from animal models.

Micro- and macro-vascular complications are the leading causes of morbidity and mortality in type 1 and type 2 diabetic patients. Despite the vast clinical experience linking diabetic metabolic abnormalities to cardiovascular lesions, the molecular basis of individual susceptibility to diabetic cardiovascular injury is still largely unknown. Significant advances in this area may come from studies on suitable animal models. Although no animal model can accurately reproduce the human disease, experimental studies in animals have the great advantage to eliminate factors such as ethnicity, economic and geographic variables, drug interactions, diet, gender and age differences that importantly limit clinical studies. Indeed, appropriate animal models have provided important information on genetic and environmental risks of diabetes, and helped to dissect molecular mechanisms underlying the development, progression and therapeutic control of this disease. Unfortunately, none of the diabetic models presently available fully mimics the human syndrome. Therefore, the current knowledge on the pathogenesis of cardiovascular complications relies on the evaluation of distinct phenotypes from various diabetic models. In addition to strains prone to diabetes, this disease can be induced by surgical, pharmacological or genetic manipulation in several animal species. Rodents are the most used, although some studies are still performed in larger animals as rabbits, cats, pigs or monkeys. Far from being exhaustive, this work should serve as a general overview of the most relevant clues provided by major species and models for the overall comprehension of cardiovascular complications in type 1 and type 2 diabetes.

Platinum-gold nanoclusters as catalyst for direct methanol fuel cells.

Nanosized platinum-gold alloys clusters have been deposited on gas diffusion electrode by sputter deposition. The deposits were characterized by FE-SEM, TEM and XPS in order to verify the formation of alloy nanoparticles and to study the influence of deposition technique on the nanomorphology. The deposition by sputtering process allowed a uniform distribution of metal particles on porous surface of carbon supports. Typical island growth mode was observed with the formation of a dispersed metal nanoclusters (mean size about 5 nm). Cyclic voltammetry was used to determine the electrochemical active surface and the electrocatalytic performance of the PtAu electrocatalysts for methanol oxidation reaction. The data were re-calculated in the form of mass specific activity (MSA). The sputter-catalyzed electrodes showed higher performance and stability compared to commercial catalysts.

Electrocatalysts for methanol oxidation based on platinum/carbon nanofibers nanocomposite.

New carbon nanomaterials, i.e., carbon nanotubes and nanofibers, with special physico-chemical properties, are recently studied as support for methanol oxidation reaction electrocatalysts replacing the most widely used carbon black. Particularly, carbon fibrous structures with high surface area and available open edges are thought to be promising. Platelet type carbon nanofibers, which have the graphene layers oriented perpendicularly to the fiber axis, exhibit a high ratio of edge to basal atoms. Different types of carbon nanofibers (tubular and platelet) were grown by plasma enhanced chemical vapour deposition on carbon paper substrates. The process was controlled and optimised in term of growth pressure and temperature. Carbon nanofibers were characterised by high resolution scanning electron microscopy and X-ray photoelectron spectroscopy to assess the morphological properties. Then carbon nanofibers of both morphologies were used as substrates for Pt electrodeposition. High resolution scanning electron microscopy images showed that the Pt nanoparticles distribution was well controlled and the particles size went down to few nanometers. Pt/carbon nanofibers nanocomposites were tested as electrocatalysts for methanol oxidation reaction. Cyclic voltammetry in H2SO4 revealed a catalyst with a high surface area. Cyclic voltammetry in presence of methanol indicated a high electrochemical activity for methanol oxidation reaction and a good long time stability compared to a carbon black supported Pt catalyst.

Validación de una versión argentina del Health Assessment Questionnaire-II (HAQ-II) / Validation of an Argentine version of the Health Assessment Questionnaire-II (HAQ-II)

La versión argentina de Health Assessment Questionnaire (HAQ-A) es un instrumento útil para documentar el estado clínico, la evolución y el pronóstico funcional de nuestros pacientes con Artritis Reumatoidea (AR). Sin embargo, presenta algunas limitaciones. Esto dio lugar a una versión más simple: el HAQ-II, el cual consta de 10 preguntas. Nuestro objetivo fue determinar la reproducibilidad y validez de una versión argentina del HAQ-II en pacientes con AR. Material y métodos: Se incluyeron pacientes consecutivos con diagnóstico de AR (ACR ‘87) de 4 centros reumatológicos de Argentina. La versión original del HAQ-II fue traducida por 3 reumatólogos argentinos y retraducida al inglés por un individuo bilingüe no relacionado. La reproducibilidad del cuestionario fue evaluada en el 30% de los pacientes con un segundo cuestionario completado dentro de los 3 a 7 días de la primera visita. La validez constructiva fue evaluada comparando el HAQ-II con parámetros clásicos de actividad de la enfermedad, capacidad funcional y compromiso radiológico (medido por el método de Sharp van der Heijde). Se evaluó también el tiempo y dificultad para realizarlo, así como la confiabilidad y correlación con HAQ-A. Resultados: 97 pacientes fueron incluidos, de los cuales el 82% eran mujeres, 95% seropositivas para factor reumatoideo, 87% erosivas y 22% nodulares. La reproducibilidad del HAQ-II fue buena (r=0,94). En la correlación intraítem se halló una única redundancia (entre la pregunta 8 y 9 (r=0,92)), por este motivo la pregunta 8 fue reemplazada manteniendo excelente correlación con la versión original (r=0,99). El HAQ-II tuvo buena correlación con EVA (escala visual análoga) para dolor, EVA para actividad y articulaciones dolorosas; regular correlación con recuento de articulaciones inflamadas, menor nivel educativo y eritrosedimentación (ERS). No se observó correlación con daño radiológico.

Pregnancy modulates precursor cell proliferation in a murine model of focal demyelination.

In mice, pregnancy has been shown to have a beneficial effect on the endogenous repair of focal lysolecithin-induced CNS demyelinative lesions, enhancing the genesis of new oligodendrocytes and the degree of remyelination. To identify local cells undergoing mitosis in response to such lesions, we examined the time course of phospho-histone H3 (PH3) and myelin basic protein (MBP) expression by immunohistochemistry. After lysolecithin injection into the corpus callosum of virgin female mice, the number of dividing cells peaked about 48 h after injection and declined gradually to baseline by day 7; in pregnant mice, this initial peak was unchanged, but a new delayed peak on day 4 was induced. Colocalization data using PH3 and NG2 proteoglycan, or bromodeoxyuridine (BrdU) and oligodendrocyte transcription factor 1 (Olig1), suggested that about 75% of the proliferating cells on day 2, and about 40% of the cells on day 4, were likely of oligodendrocyte lineage; these differential percentages were of the same magnitude in both virgin and pregnant animals. Notably, the heightened proliferative response to focal lysolecithin injection during pregnancy was specific to gestational stage (early, but not late) and to lesion location (in the corpus callosum of the periventricular forebrain, but not in the caudal cerebellar peduncle of the hindbrain).

Enlarged internal auditory canal and sudden deafness.

OBJECTIVES: We report a young man with bilateral enlarged internal auditory canals who developed sudden sensorineural hearing loss following weight-lifting exercise. METHODS: We present a detailed clinical history, including the patient's high resolution computed tomography and magnetic resonance imaging scans. RESULTS: The patient reported left-sided hearing loss immediately following weight-lifting exercise. He had no vestibular disturbance. He was treated with a combined regimen of steroids and an antiviral drug, but his profound hearing loss did not resolve. During another session of weight-lifting exercise, he suffered another episode of sudden hearing loss. CONCLUSIONS: To the best of our knowledge, this is the first report of a patient with patulous internal auditory canals, with no other anomalies, who developed bilateral sudden hearing loss after weight-lifting exercise. Although no definitive conclusions can be drawn, close surveillance and lifestyle warnings should be considered in such patients, even if they are clinically asymptomatic.

Determinantes de discapacidad funcional en pacientes con espondilitis anquilosante en Argentina / Risk factors for functional disability in patients with ankylosing spondylitis in Argentina

La espondilitis anquilosante (EA) es una enfermedad crónica que se caracteriza por dolor lumbar, rigidez, limitación de la movilidad espinal, fatiga y depresión que conducen a pérdida de la capacidad funcional. El objetivo de este estudio fue determinar las principales variables asociadas a discapacidad funcional en pacientes con EA. Pacientes y métodos: Se incluyeron pacientes con EA (criterios de NY modificados) mayores de 16 años. Se recolectaron datos demográficos, nivel educacional, demanda física diaria laboral, por medio de la escala de Jaime Pujol. La actividad de la enfermedad y la capacidad funcional fueron evaluadas por los cuestionarios BASDAI y BASFI, respectivamente. También se realizaron HAQ-A y HAQ-S. Todos los pacientes completaron además cuestionarios de calidad de vida (ASQoL), de depresión (CES-D) y escala de fatiga (FSS), los cuales fueron previamente validados al español en Argentina en nuestro centro. Para el análisis estadístico, correlación de Pearson de las principales variables. Las variables continuas fueron comparadas por test de Student y ANOVA. Las posibles variables asociadas a discapacidad funcional fueron analizadas por regresión lineal. Resultados: Se incluyeron 64 pacientes, 88% varones, con una edad mediana de 44 años (RIQ: 33,25-53) y un tiempo mediano de evolución de la enfermedad de 17 años (RIQ: 10,25-28). La mediana de BASFI fue 45,35 mm (RIQ: 16,8-64), la mediana de HAQ-A fue 0,5 (RIQ: 0,15-1) y HAQ-S fue 0,7 (RIQ: 0,32-1,2). El BASFI presentó una excelente correlación con HAQ-A (r: 0,77) y HAQ-S (r: 0,83), p <0,0001. El BASFI presentó muy buena correlación con las escalas de depresión (r: 0,47), fatiga (r: 0,53), calidad de vida (r: 0,77) (p <0,0001) y una correlación negativa con los años de educación (r: -3,41, p = 0,006). No hubo diferencias significativas en el BASFI entre pacientes con y sin compromiso periférico, como tampoco entre los pacientes con reemplazo articular...

Ankylosing Spondylitis (AS) is a chronic disease, characterized byinflammatory back pain, stiffness, limitation in spinal mobility fatigueand depression leading to loss in functional capacity. Objective:To identify main variables associated to functional disability in AS patients.Material and Methods: AS patients older than 16 years according to New York modified criteria were included. Demographic, socioeconomic and laboral characteristics were collected. Functional capacity was observed using the Bath Ankylosing SpondylitisFunctional Index (BASFI) and the Health Assessment Questionnairefor the Spondyloarthropathies (HAQ-S) and disease activity using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Quality of life, depression, and fatigue were respectively evaluated using ASQoL, CES-D, FSS Questionnaire which were previously validated into Spanish in our centre. Results: 64 patients were included, 88% male, median age 44 years (IQR: 33.25-53) and median disease duration 17 years (IQR: 10.25-28). Mean score for BASFI was 45.35 mm (IQR: 16.8-64). BASFI had a very good correlation with HAQ-S (r: 0.83), p <0.0001, depression (r: 0.47), fatigue (r: 0.53), and quality of life (r: 0.77) (p <0.0001) and negative correlation with education level (r: -3.41, p = 0.006). Noassociation was found between BASFI and peripheral joint involvement, or the degree of physical demand on job. In multivariate analysis disease activity was the only variable associated with BASFI. Conclusion: Disease activity is the main variable that impairs functional capacity in AS patients.

Determinantes de discapacidad funcional en pacientes con espondilitis anquilosante en Argentina / Risk factors for functional disability in patients with ankylosing spondylitis in Argentina

La espondilitis anquilosante (EA) es una enfermedad crónica que se caracteriza por dolor lumbar, rigidez, limitación de la movilidad espinal, fatiga y depresión que conducen a pérdida de la capacidad funcional. El objetivo de este estudio fue determinar las principales variables asociadas a discapacidad funcional en pacientes con EA. Pacientes y métodos: Se incluyeron pacientes con EA (criterios de NY modificados) mayores de 16 años. Se recolectaron datos demográficos, nivel educacional, demanda física diaria laboral, por medio de la escala de Jaime Pujol. La actividad de la enfermedad y la capacidad funcional fueron evaluadas por los cuestionarios BASDAI y BASFI, respectivamente. También se realizaron HAQ-A y HAQ-S. Todos los pacientes completaron además cuestionarios de calidad de vida (ASQoL), de depresión (CES-D) y escala de fatiga (FSS), los cuales fueron previamente validados al español en Argentina en nuestro centro. Para el análisis estadístico, correlación de Pearson de las principales variables. Las variables continuas fueron comparadas por test de Student y ANOVA. Las posibles variables asociadas a discapacidad funcional fueron analizadas por regresión lineal. Resultados: Se incluyeron 64 pacientes, 88% varones, con una edad mediana de 44 años (RIQ: 33,25-53) y un tiempo mediano de evolución de la enfermedad de 17 años (RIQ: 10,25-28). La mediana de BASFI fue 45,35 mm (RIQ: 16,8-64), la mediana de HAQ-A fue 0,5 (RIQ: 0,15-1) y HAQ-S fue 0,7 (RIQ: 0,32-1,2). El BASFI presentó una excelente correlación con HAQ-A (r: 0,77) y HAQ-S (r: 0,83), p <0,0001. El BASFI presentó muy buena correlación con las escalas de depresión (r: 0,47), fatiga (r: 0,53), calidad de vida (r: 0,77) (p <0,0001) y una correlación negativa con los años de educación (r: -3,41, p = 0,006). No hubo diferencias significativas en el BASFI entre pacientes con y sin compromiso periférico, como tampoco entre los pacientes con reemplazo articular...(AU)

Ankylosing Spondylitis (AS) is a chronic disease, characterized byinflammatory back pain, stiffness, limitation in spinal mobility fatigueand depression leading to loss in functional capacity. Objective:To identify main variables associated to functional disability in AS patients.Material and Methods: AS patients older than 16 years according to New York modified criteria were included. Demographic, socioeconomic and laboral characteristics were collected. Functional capacity was observed using the Bath Ankylosing SpondylitisFunctional Index (BASFI) and the Health Assessment Questionnairefor the Spondyloarthropathies (HAQ-S) and disease activity using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Quality of life, depression, and fatigue were respectively evaluated using ASQoL, CES-D, FSS Questionnaire which were previously validated into Spanish in our centre. Results: 64 patients were included, 88% male, median age 44 years (IQR: 33.25-53) and median disease duration 17 years (IQR: 10.25-28). Mean score for BASFI was 45.35 mm (IQR: 16.8-64). BASFI had a very good correlation with HAQ-S (r: 0.83), p <0.0001, depression (r: 0.47), fatigue (r: 0.53), and quality of life (r: 0.77) (p <0.0001) and negative correlation with education level (r: -3.41, p = 0.006). Noassociation was found between BASFI and peripheral joint involvement, or the degree of physical demand on job. In multivariate analysis disease activity was the only variable associated with BASFI. Conclusion: Disease activity is the main variable that impairs functional capacity in AS patients.(AU)

Hernia repair with porcine small-intestinal submucosa.

PURPOSE: Although at present nonabsorbable meshes are the preferred material for tension-free hernioplasty, some problems with their use have yet to be addressed (i.e., chronic pain and infections). In order to address these disadvantages, a collagen-based material, the porcine small-intestinal submucosa mesh (Surgisis Inguinal Hernia Matrix, Cook Surgical, Bloomington, IN, USA), has recently been developed for hernia repair. METHODS: With the aim of investigating the clinical safety and effectiveness of Surgisis IHM inguinal hernia repair, we report our experience of 45 consecutive hernioplasties with a medium-term follow-up. The surgical technique for the use of this material in hernioplasty is described in detail. RESULTS: Although some local (i.e., seromas) and general (i.e., hyperpyrexia), complications appeared in the immediate postoperative period (all of them disappeared spontaneously), no rejection or infection was observed after operations. At the 2-year follow-up, a low degree of pain and discomfort and no recurrences were observed. CONCLUSIONS: We conclude that the Surgisis IHM hernioplasty is feasible with promising results and, from a clinical perspective, seems safe and effective.

Use of porcine dermal collagen graft (Permacol) for hernia repair in contaminated fields.

BACKGROUND: Complicated hernias often involve contaminating surgical procedures in which the use of polypropylene meshes can be hazardous. Prostheses made of porcine dermal collagen (PDC) have recently been proposed as a means to offset the disadvantages of polypropylene meshes and have since been used in humans for hernia repairs. The aim of our study was to evaluate the safety and efficacy of incisional hernia repair using PDC as a mesh in complicated cases involving contamination. METHODS: A prospective study of hernia repair of complicated incisional hernias with contamination using PDC grafts was carried out at the Department of General, Emergency and Transplant Surgery of St Orsola-Malpighi University Hospital. RESULTS: From January 2004 up to the writing of this article, seven patients were treated for complicated incisional hernias with a PDC prosthesis. In six out of seven patients a bowel resection was carried out. There were not surgical complications. Morbidity was 14.2%. No recurrences and wound infections were observed. CONCLUSIONS: Incisional hernioplasty using PDC grafts is a potentially safe and efficient approach in complicated cases with contamination.

Experimental evaluation of Surgisis as scaffold for neointestine regeneration in a rat model.

The aim of the study was to evaluate the use of Surgisis (Cook Biotech Inc.), a porcine derived extracellular matrix already used in tissue engineering, as a scaffold for neointestinal regeneration in a rat model. A 3-cm length of tubular Surgisis graft was interposed with bilateral anastomoses in the middle of an isolated ileal loop of Sprague Dawley rats with an ileostomy. The grafts were harvested and analyzed using histology and immunohistochemistry at 24 weeks after operation. Macroscopic examination revealed neither stenosis nor adhesions in the area surrounding the neointestine. The regenerated small bowel showed a mean shrinkage of 30.7% (range 20%-40%). Histologic and immunohistochemical evaluation showed a well-developed three layers of mucosa and smooth muscle and serosa in the regenerated bowel wall that were similar to those of the normal bowel with evident neovascularization. Also, the regeneration of smooth muscle fibers and innervation were evident. The preliminary results of this study showed that Surgisis allowed rapid regeneration of mucosa and smooth muscle and therefore may be a promising material for the creation of a neointestine.