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

The major molecular mechanisms mediating the renoprotective effects of SGLT2 inhibitors: An update

Abstract The incidence of diabetes mellitus, as well as its complications, is rapidly growing. Diabetic nephropathy is one of the most prevalent disorders induced by chronic uncontrolled hyperglycemia and is accompanied by a reduction in renal sufficiency with microstructural tissue damage in the kidneys. Many therapeutic protocols have been designed to address the treatment and prevention of diabetic nephropathy. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a newly introduced class of glucose-lowering agents that reduce blood glucose by inhibition of urinary glucose reabsorption in renal proximal tubules and so induce glycosuria. Also, these hypoglycemic agents may provide protective effects in different tissues such as cardiovascular, brain, and kidneys. In recent years, accumulating evidence has indicated that SGLT2i possess potent renal protective properties in the setting of diabetes. In the current study, we present the latest findings regarding the renoprotective effects of SGLT2 inhibition and discuss the molecular mechanisms involved

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

Effect of fenofibrate on plasma apolipoprotein C-III levels: a systematic review and meta-analysis of randomised placebo-controlled trials

OBJECTIVES: This meta-analysis of randomised placebo-controlled clinical trials aimed to assess the effect of fenofibrate on apolipoprotein C-III (apo C-III), a key regulator of triglyceride metabolism. ----- MATERIALS AND METHODS: Randomised placebo-controlled trials investigating the impact of fenofibrate treatment on apo C-III levels were searched in PubMed-Medline, Scopus, Web of Science and Google Scholar databases from inception to 18 August 2017. Quantitative data synthesis was determined by a random-effects model and generic inverse variance method. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate glycaemic parameter confounders. ----- RESULTS: Meta-analysis of 10 clinical trials involving 477 subjects showed fenofibrate therapy decreased apo C-III levels (weighted mean difference (WMD) -4.78 mg/dL, 95% CI -6.95 to -2.61, p200 mg/day (p=0.006), with no significant difference between the subgroups. ----- CONCLUSION: This meta-analysis found that fenofibrate therapy significantly decreases apo C-III levels, an effect evident with both short-term treatment and doses less than 200 mg/day

Inhibitory effects of Buddleja scordioides (salvilla) leaves on digestive enzymes and carbohydrate absorption in vivo

The effects of Buddleja scordioides (BsLI) leaf infusions on digestive enzymes and carbohydrate absorption were evaluated. The BsLI yield was 21.64 %. In addition, a chemical characterization was carried out identifying hydroxybenzoic acids, hydroxycinnamic acids, flavonols, flavanones and flavones. In vitro studies were performed to determine the inhibitory action of BsLI on lipase, α-amylase, and α-glucosidase. Then, in rats, oral starch tolerance tests (OSTT) were carried out using BsLI at a dose of 9.5 mg/kg body weight. Results showed moderate inhibition of lipase and α-glucosidase, but greater inhibition of α-amylase compared to positive controls. During the OSTT trial, the group receiving BsLI showed a significant reduction in glucose levels compared to the negative control group. Bioactive compounds, such as naringenin, luteolin, quercetin, and coumaric acid, were identified after BsLI administration. Furthermore, the consumption of BsLI was safe and showed antioxidant activity like Trolox. In conclusion, BsLI may have an enhanced effect on glucose metabolism by inhibiting carbohydrate absorption. DOI: https://doi.org/10.54167/tch.v17i2.122

The product of triglycerides and glucose as biomarker for screening simple steatosis and NASH in asymptomatic women

Introduction and aim. Given that early identification of non-alcoholic fatty liver disease (NAFLD) is an important issue for primary prevention of hepatic disease, the objectives of this study were to evaluate the efficacy of the product of triglyceride and glucose levels (TyG) for screening simple steatosis and non-alcoholic steatohepatitis (NASH) in asymptomatic women, and to compare its efficacy vs. other biomarkers for recognizing NAFLD.Material and methods. Asymptomatic women aged 20 to 65 years were enrolled into a cross-sectional study. The optimal values of TyG, for screening simple steatosis and NASH were established on a Receiver Operating Characteristic scatter plot; the sensitivity, specificity, and likelihood ratios of TyG index were estimated versus liver biopsy. According sensitivity and specificity, the efficacy of TyG was compared versus the well-known clinical biomarkers for recognizing NAFLD.Results. A total of 50 asymptomatic women were enrolled. The best cutoff point of TyG for screening simple steatosis was 4.58 (sensitivity 0.94, specificity 0.69); in addition, the best cutoff point of TyG index for screening NASH was 4.59 (sensitivity 0.87, specificity 0.69). The positive and negative likelihood ratios were 3.03 and 0.08 for simple steatosis, and 2.80 and 0.18 for NASH. As compared versus SteatoTest, NashTest, Fatty liver index, and Algorithm, the TyG showed to be the best test for screening.Conclusions. TyG has high sensitivity and low negative likelihood ratio; as compared with other clinical biomarkers, the TyG showed to be the best test for screening simple steatosis and NASH