Evaluación in vivo e in vitro del tratamiento con plasma rico en plaquetas en osteoartrosis de rodilla.

Mario Alberto Simental Mendía Fecha de Graduación: Agosto, 2016 Universidad Autónoma de Nuevo León Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina Título de la Tesis: Evaluación in vivo e in vitro del tratamiento con plasma rico en plaquetas en osteoartrosis de rodilla. Número de páginas: Área de Estudio: Terapia Celular. Introducción. La osteoartrosis (OA) de rodilla es una enfermedad degenerativa y progresiva del cartílago articular y se caracteriza por presentar un estado catabólico en el cartílago inducido por citocinas pro-inflamatorias. La infiltración de plasma rico en plaquetas (PRP) autólogo se ha propuesto como una alternativa terapéutica, debido a su contenido de citocinas biológicamente activas. Además, el PRP ha mostrado tener propiedades anti-inflamatorias y regenerativas en cartílago articular dañado. Los mejores resultados del uso de esta terapia se han obtenido en cartílago con un menor grado de lesión y de OA. Objetivos. 1) Comparar la respuesta clínica a la infiltración con PRP y al tratamiento convencional en pacientes con OA leve, y 2) determinar el efecto in vitro del PRP sobre la expresión de marcadores genéticos específicos y sobre la matriz extracelular del cartílago. Materiales y Métodos. Se analizó un total de 65 pacientes con diagnóstico clínico y radiográfico de OA grado I y II. Los pacientes se aleatorizaron en dos grupos: a 32 se les trató con paracetamol (500 mg/8 h) por 6 semanas, y 33 recibieron 3 infiltraciones intra-articulares de PRP (una cada dos semanas). Todos los pacientes fueron evaluados con la Escala Visual Análoga (EVA), el índice de OA de Western Ontario and McMaster Universities (WOMAC) y la encuesta de salud SF-12 al inicio del tratamiento y 6, 12 y 24 semanas después. Se obtuvieron explantes de cartílago y PRP de 10 donadores que fueron sometidos a cirugía de reemplazo articular de rodilla. Los explantes se cultivaron en frascos spinner por hasta 28 días, en agitación constante y en presencia de interleucina-1β (IL-1β), PRP o PRP/IL-1β. Se cuantificó la expresión de genes asociados a inflamación y degradación de la matriz del cartílago (MMP-13, ADAMTS5, IL-1β) y de aquellos involucrados en la restauración de la matriz extracelular (colágeno tipo II, agrecano y SOX9). Se realizó un análisis histológico de acuerdo a la escala de Mankin modificada y a la cuantificación del marcaje por inmunohistoquímica de colágeno tipo II y tipo I. Resultados. Comparación de la respuesta clínica a la infiltración con PRP y del tratamiento convencional. Ambos tratamientos mostraron una disminución significativa en la EVA desde la semana 6. La disminución en el nivel de dolor de EVA fue mayor en el grupo tratado con PRP. Los pacientes tratados con PRP tuvieron una mejoría sostenida en la funcionalidad de la rodilla, al menos hasta las 24 semanas. Los resultados de SF-12 indican una mejoría en la calidad de vida sólo en el grupo tratado con PRP a las 6, 12 y 24 semanas. Evaluación del efecto in vitro del PRP sobre la expresión de marcadores genéticos específicos y sobre la matriz extracelular del cartílago. La expresión de los genes catabólicos y el valor de la escala de Mankin xiii fueron menores en los explantes tratados con PRP y PRP/IL-1β que en los tratados con IL-1β. Se observó una mayor expresión de los genes involucrados en la síntesis de matriz extracelular en los explantes tratados con PRP y PRP/IL-1β en comparación con el explantes tratados con IL-1β. Los explantes tratados con PRP y PRP/IL-1β mostraron una mayor presencia de proteoglicanos y colágeno tipo II, así como una menor presencia de colágeno tipo I; estos explantes también tuvieron una mejor integridad de la superficie y un incremento significativo en el número de condrocitos al compararlos con los explantes tratados con IL-1β. Conclusiones. El tratamiento con PRP presentó un mejor resultado clínico que el tratamiento convencional con paracetamol, con una disminución sostenida en los puntajes de las escalas EVA y WOMAC y una mejor calidad de vida de los pacientes. Además, el PRP favoreció la restauración de la matriz extracelular en explantes de cartílago con OA leve y disminuyó el efecto pro-inflamatorio de la IL-1β. El uso del PRP es una terapia prometedora para el cartílago dañado en OA temprana, ya que promueve la reparación de la matriz extracelular, disminuye la inflamación y retrasa la degeneración del cartílago. ____________________________________ Dra. C. Herminia Guadalupe Martínez Rodríguez Directora de Tesi

Plantar Fasciitis—A Comparison of Treatment with Intralesional Steroids versus Platelet-Rich Plasma

Background: Many treatment options for plantar fasciitis currently exist, some with great success in pain relief. The objective of our study was to compare the use of intralesional steroids with platelet-rich plasma (PRP), using pain scales and functional evaluation, in patients with plantar fasciitis who did not respond to conservative treatment. Methods: A controlled, randomized, blinded clinical assay was performed. Patients were assigned to one of the two groups by selecting a sealed envelope. The steroid treatment group received 8 mg of dexamethasone plus 2 mL of lidocaine as a local anesthetic. The PRP treatment group received 3 mL of PRP activated with 0.45 mL of 10% calcium gluconate. All of the patients were evaluated at the beginning of the study, and at 2, 4, 8, 12, and 16 weeks post-treatment with the Visual Analog Scale (VAS), Foot and Ankle Disability Index (FADI), and American Orthopedic Foot and Ankle Society (AOFAS) scale. Results: The right foot was the most frequently affected foot (63%). The average age of the patients was 44.8 years (range, 24–61 years). All scales used (VAS, FADI and AOFAS) showed that the difference was not statistically significant between the two groups. Conclusions: We can conclude that the use of PRP is an effective treatment method for patients with plantar fasciitis who do not respond to conservative treatment because PRP demonstrates an efficacy equal to that of steroids. However, the cost and the time for preparation the PRP are two of the disadvantages of this treatment. (J Am Podiatr Med Assoc 107(6): 490-496, 2017

Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials

Abstract Objective The aim of this meta-analysis of randomized placebo-controlled trials was to examine whether ursodeoxycholic acid treatment is an effective lipid-lowering agent. Methods PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched in order to find randomized controlled trials evaluating the effect of ursodeoxycholic acid on lipid profile. A random-effect model and the generic inverse variance weighting method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A random-effects meta-regression model was performed to explore the association between potential confounders and the estimated effect size on plasma lipid concentrations. Results Meta-analysis of 20 treatment arms revealed a significant reduction of total cholesterol following ursodeoxycholic acid treatment (WMD: − 13.85 mg/dL, 95% CI: -21.45, − 6.25, p < 0.001). Nonetheless, LDL-C (WMD: -6.66 mg/dL, 95% CI: -13.99, 0.67, p = 0.075), triglycerides (WMD: − 1.42 mg/dL, 95% CI: -7.51, 4.67, p = 0.648) and HDL-C (WMD: -0.18 mg/dL, 95% CI: -5.23, 4.87, p = 0.944) were not found to be significantly altered by ursodeoxycholic acid administration. In the subgroup of patients with primary biliary cirrhosis, ursodeoxycholic acid reduced total cholesterol (WMD: − 29.86 mg/dL, 95% CI: -47.39, − 12.33, p = 0.001) and LDL-C (WMD: -37.27 mg/dL, 95% CI: -54.16, − 20.38, p < 0.001) concentrations without affecting TG and HDL-C. Conclusion This meta-analysis suggests that ursodeoxycholic acid therapy might be associated with significant total cholesterol lowering particularly in patients with primary biliary cirrhosis

The matrix synthesis and anti-inflammatory effect of autologous leukocyte-poor platelet rich plasma in human cartilage explants

Objective. To determine the effects of autologous leukocyte-poor platelet-rich plasma (LPPRP) on the expression of markers involved in cartilageextracellular matrix production and inflammation in cartilage explants bearing osteoarthritis. Materials and Methods. Cartilage explants and LP-PRP were obtained from 10 patients who underwent total knee arthroplasty. The explants were cultured in spinner flasks for 28 days in the presence of interleukin (IL)-1β and/or LP-PRP. The gene expression of catabolic (MMP13, ADAMTS5, and IL1β) and anabolic factors (COL2A1, ACAN, and SOX9) was quantified. A histological assessment was performed according to a modified Mankin score, and quantification of type II and I collagen deposition. Results. The gene expression of catabolic factors and the Mankin score were lower in LP-PRP- and LP-PRP/IL1β- than in IL-1β-treated explants, suggesting less matrix degradation in explants cultured in the presence of LP-PRP. Higher expression of genes involved in cartilage matrix restoration was observed in LP-PRP and LP-PRP/IL-1β- when compared to IL-1β-treated explants. The explants treated with LP-PRP and LPPRP/IL-1β exhibited a higher deposition of type II collagen as well as a lower deposition of type I collagen and also better surface integrity and a significant increase in the number of chondrocytes. Conclusion. LPPRP treatment favored restoration in early osteoarthritic cartilage and reduced the pro-inflammatory effect of IL1β. LP-PRP is a promising therapy for early osteoarthritis, as it promotes extracellular matrix repair, reduces inflammation, and slows cartilage degeneration

Physical, Mechanical, and Biological Properties of Fibrin Scaffolds for Cartilage Repair

Articular cartilage is a highly organized tissue that provides remarkable load-bearing and low friction properties, allowing for smooth movement of diarthrodial joints; however, due to the avascular, aneural, and non-lymphatic characteristics of cartilage, joint cartilage has self-regeneration and repair limitations. Cartilage tissue engineering is a promising alternative for chondral defect repair. It proposes models that mimic natural tissue structure through the use of cells, scaffolds, and signaling factors to repair, replace, maintain, or improve the specific function of the tissue. In chondral tissue engineering, fibrin is a biocompatible biomaterial suitable for cell growth and differentiation with adequate properties to regenerate damaged cartilage. Additionally, its mechanical, biological, and physical properties can be enhanced by combining it with other materials or biological components. This review addresses the biological, physical, and mechanical properties of fibrin as a biomaterial for cartilage tissue engineering and as an element to enhance the regeneration or repair of chondral lesions

Repair of ovine peripheral nerve injuries with xenogeneic human acellular sciatic nerves prerecellularized with allogeneic Schwann-like cells—an innovative and promising approach

Introduction: The iatrogenic effects of repairing peripheral nerve injuries (PNIs) with autografts (AGTs) encouraged the present study to involve a new approach consisting of grafting xenogeneic prerecellularized allogeneic cells instead of AGTs. Methods: We compared sheep's AGT regenerative and functional capacity with decellularized human nerves prerecellularized with allogeneic Schwann-like cell xenografts (onwards called xenografts). Mesenchymal stem cells were isolated from ovine adipose tissue and induced in vitro to differentiate into Schwann-like cells (SLCs). Xenografts were grafted in ovine sciatic nerves. Left sciatic nerves (20 mm) were excised from 10 sheep. Then, five sheep were grafted with 20 mm xenografts, and five were reimplanted with their nerve segment rotated 180° (AGT). Results: All sheep treated with xenografts or AGT progressively recovered the strength, movement, and coordination of their intervened limb, which was still partial when the study was finished at sixth month postsurgery. At this time, numerous intrafascicular axons were observed in the distal and proximal graft extremes of both xenografts or AGTs, and submaximal nerve electrical conduction was observed. The xenografts and AGT-affected muscles appeared partially stunted. Conclusions: Xenografts and AGT were equally efficacious in starting PNI repair and justified further studies using longer observation times. The hallmarks from this study are that human xenogeneic acellular scaffolds were recellularized with allogenic SCL and were not rejected by the nonhuman receptors but were also as functional as AGT within a relatively short time postsurgery. Thus, this innovative approach promises to be more practical and accessible than AGT or allogenic allografts and safer than AGT for PNI repair

Prevalence of morphological variations associated with femoroacetabular impingement according to age and sex: a study of 1878 asymptomatic hips in nonprofessional athletes

Background: Radiographic findings related to the cam and pincer variants of femoroacetabular impingement (FAI) include measurements of the alpha angle and lateral center-edge angle (LCEA). The function of these radiographic findings has been put into question because of high heterogeneity in reported studies. Purpose: The aim of this study was 3-fold: (1) to determine the prevalence of cam and pincer variants according to sex and age on anteroposterior (AP) pelvic radiographs from an asymptomatic nonathletic population, (2) to identify the most common radiographic signs of cam- and pincer-type variants, and (3) to determine if there are variations in the prevalence of these radiographic signs according to sex and age. Study design: Cross-sectional study; Level of evidence, 3. Methods: There were 3 independent observers who retrospectively analyzed the 939 AP pelvic radiographs (1878 hips) of patients aged 18 to 50 years who did not have hip symptoms and who were not professional athletes. The prevalence of the cam and pincer variants according to the alpha angle and LCEA, respectively, and the presence of other radiographic signs commonly associated with these variables were determined in the overall population and by subgroup according to sex and age group (18-30, 31-40, and 41-50 years). Descriptive and inferential statistics were used to analyze the study sample. Results: The mean age of the included population was 31.0 ± 9.2 years, and 68.2% were male. The prevalence of the cam-type variant was 29.7% (558/1878), and that of the pincer-type variant was 24.3% (456/1878). The radiographic signs that were most associated with the cam and pincer variants were a pistol-grip deformity and the crossover sign, respectively. Significant differences (P < .001) in the prevalence of these variants were identified between men and women in both variants. No differences were observed in the alpha angle or LCEA according to sex or age. Conclusion: Radiographic findings suggestive of FAI had significant variations with respect to sex and age in this study sample. This study provides information to determine the prevalence of these anatomic variants in the general population