Niveles de IGF-1 en la plastía de ligamento cruzado anterior de rodilla empleando aloinjerto vs autoinjerto en pacientes del Hospital Central Militar / IGF-1 levels in anterior cruciate ligament reconstruction using allograft vs autograft in patients at Central Military Hospital

Resumen: Antecedentes: El tratamiento para la lesión del ligamento cruzado anterior (LCA) es la reconstrucción quirúrgica. Se desconoce si el resultado mejora, pues depende del tipo de injerto empleado. El factor de crecimiento semejante a la insulina tipo 1(IGF-1) es un potente estimulante de matriz extracelular y del crecimiento de condrocitos. Material y métodos: Estudio experimental, analítico, prospectivo, longitudinal en pacientes con reconstrucción del LCA en un período comprendido entre los años 2016 y 2017. Se determinó la concentración de IGF-1 en el líquido sinovial de estos pacientes operados con aloinjerto y autoinjerto además de determinar su asociación con la evolución postoperatoria. Para el análisis estadístico, se utilizó ANOVA de dos vías post hoc con la prueba U de Mann-Whitney. Resultados: Dentro del grupo de aloinjerto, se identificó un aumento significativo de IGF-1 a los 90 días del postoperatorio. En el grupo de autoinjerto, se observó un aumento significativo de IGF-1 desde los 30 días de postoperatorio. Se encontró además que el grupo de autoinjerto presentó niveles significativamente más altos de IGF-1 (3.27 ± 0.09 ng/ml) en comparación con el grupo de aloinjerto (2.80 ± 0.11 ng/ml; p < 0.001) a los 90 días después de la colocación del injerto. Discusión: Los niveles de IGF-1 fueron más altos en pacientes con injerto autólogo; la funcionalidad de la rodilla fue clínicamente similar en ambos grupos a los 30 y 90 días.

Abstract: Background: Treatment of ACL injury is surgical reconstruction. It is not known whether the result is better depending on the type of graft used. Insulin-like growth factor type 1(IGF-1) is a powerful stimulant of extracellular matrix and chondrocyte growth. Material and methods: Experimental, analytical, prospective, longitudinal study in patients with ACL reconstruction in a period from 2016 to 2017. The concentration of IGF-1 in synovial fluid of these patients operated with allograft and autograft was determined, its association with postoperative evolution was determined. For statistical analysis, two-way ANOVA with Mann-Whitney post-hoc U was used. Results: A significant increase in IGF-1 was identified in the allograft group at 90 days of postopertory. In the autograft group, a significant increase in IGF-1 was observed from 30 days of postoperative. The autograft group was found to have significantly higher levels of IGF-1 (3.27 ± 0.09 ng/ml) compared to the allograft group (2.80 ± 0.11 ng/ml; p < 0.001) at 90 days after graft placement. Discussion: IGF-1 levels were higher in patients with autologous graft, knee functionality was clinically similar in both groups at 30 and 90 days.

[IGF-1 levels in anterior cruciate ligament reconstruction using allograft vs autograft in patients at Central Military Hospital]. / Niveles de IGF-1 en la plastía de ligamento cruzado anterior de rodilla empleando aloinjerto vs autoinjerto en pacientes del Hospital Central Militar.

BACKGROUND: Treatment of ACL injury is surgical reconstruction. It is not known whether the result is better depending on the type of graft used. Insulin-like growth factor type 1(IGF-1) is a powerful stimulant of extracellular matrix and chondrocyte growth. MATERIAL AND METHODS: Experimental, analytical, prospective, longitudinal study in patients with ACL reconstruction in a period from 2016 to 2017. The concentration of IGF-1 in synovial fluid of these patients operated with allograft and autograft was determined, its association with postoperative evolution was determined. For statistical analysis, two-way ANOVA with Mann-Whitney post-hoc U was used. RESULTS: A significant increase in IGF-1 was identified in the allograft group at 90 days of postopertory. In the autograft group, a significant increase in IGF-1 was observed from 30 days of postoperative. The autograft group was found to have significantly higher levels of IGF-1 (3.27 ± 0.09 ng/ml) compared to the allograft group (2.80 ± 0.11 ng/ml; p 0.001) at 90 days after graft placement. DISCUSSION: IGF-1 levels were higher in patients with autologous graft, knee functionality was clinically similar in both groups at 30 and 90 days.

ANTECEDENTES: El tratamiento para la lesión del ligamento cruzado anterior (LCA) es la reconstrucción quirúrgica. Se desconoce si el resultado mejora, pues depende del tipo de injerto empleado. El factor de crecimiento semejante a la insulina tipo 1(IGF-1) es un potente estimulante de matriz extracelular y del crecimiento de condrocitos. MATERIAL Y MÉTODOS: Estudio experimental, analítico, prospectivo, longitudinal en pacientes con reconstrucción del LCA en un período comprendido entre los años 2016 y 2017. Se determinó la concentración de IGF-1 en el líquido sinovial de estos pacientes operados con aloinjerto y autoinjerto además de determinar su asociación con la evolución postoperatoria. Para el análisis estadístico, se utilizó ANOVA de dos vías post hoc con la prueba U de Mann-Whitney. RESULTADOS: Dentro del grupo de aloinjerto, se identificó un aumento significativo de IGF-1 a los 90 días del postoperatorio. En el grupo de autoinjerto, se observó un aumento significativo de IGF-1 desde los 30 días de postoperatorio. Se encontró además que el grupo de autoinjerto presentó niveles significativamente más altos de IGF-1 (3.27 ± 0.09 ng/ml) en comparación con el grupo de aloinjerto (2.80 ± 0.11 ng/ml; p 0.001) a los 90 días después de la colocación del injerto. DISCUSIÓN: Los niveles de IGF-1 fueron más altos en pacientes con injerto autólogo; la funcionalidad de la rodilla fue clínicamente similar en ambos grupos a los 30 y 90 días.

Pregnancy-associated plasma protein-A (PAPP-A) as a possible biomarker in patients with coronary artery disease.

BACKGROUND: Cardiovascular disease is the leading cause of death in the Western world, and a major cause of this disease is atherosclerosis. Research has demonstrated that pregnancy-associated plasma protein A (PAPP-A) plays a role in cardiovascular disease, as evidenced by the association between PAPP-A and severity of heart damage. AIM: The aim of this work was to investigate the correlation between PAPP-A concentrations in coronary and peripheral blood and certain clinicopathological factors and antioxidant enzyme activities in patients diagnosed with coronary artery disease. METHODS: For 65 patients, arterial blood was obtained by puncturing the femoral or radial artery, and coronary blood was obtained via percutaneous coronary intervention. PAPP-A, catalase (CAT), superoxide dismutase-1 (SOD-1), and superoxide dismutase-2 (SOD-2) levels were measured using spectrometric methods. RESULTS: Coronary PAPP-A levels were slightly higher than peripheral PAPP-A levels (81.25 ± 2.34 and 62 ± 3 ng/mL, respectively, P < 0.0001); these levels were correlated with each other (r = 0.6629, P < 0.001) but not with clinicopathological factors (P > 0.05). Coronary PAPP-A levels were significantly elevated among patients at risk for cardiovascular disease (P < 0.05). Antioxidant enzyme activities were significantly higher in coronary samples than in peripheral samples from subjects with ischemic cardiopathy secondary to atherosclerosis (P < 0.001). Neither coronary nor peripheral PAPP-A levels were correlated with antioxidant enzyme activities in patients with cardiopathy secondary to atherosclerosis (P > 0.05). CONCLUSIONS: PAPP-A levels could be used as biomarkers to identify patients at risk of coronary artery disease.

Botulinum neurotoxin type A inhibits synaptic vesicle 2 expression in breast cancer cell lines.

AIM: It is known that botulinum neurotoxin type A (BoNTA) improves some kinds of cancer (e.g. prostate) and that synaptic vesicle glycoprotein 2 (SV2) is the molecular target of this neurotoxin. Besides having potential therapeutic value, this glycoprotein has recently been proposed as a molecular marker for several types of cancer. Although the mechanisms of cancer development and the improvement found with botulinum treatment are not well understood, the formation of the botulinum-SV2 complex may influence the presence and distribution of SV2 and the function of vesicles. To date, there are no reports on the possible effect of botulinum on breast cancer of unknown causes, which have a great impact on women's health. Thus we determined the presence of SV2 in three breast cancer cell lines and the alterations found with botulinum application. MATERIALS AND METHODS: With and without adding 10 units of botulinum, SV2 protein expression was determined by optical densitometry in T47D, MDA-MB-231 and MDA-MB-453 cell lines and the distribution of SV2 was observed with immunochemistry (hematoxylin staining). RESULTS: The SV2 protein was abundant in the cancer cells herein tested, and maximally so in T47D. In all three cancer cell lines botulinum diminished SV2 expression, which was found mostly in the cell periphery. CONCLUSION: SV2 could be a molecular marker in breast cancer. Its expression and distribution is regulated by botulinum, suggesting an interesting control mechanism for SV2 expression and a possible alternative therapy. Further studies are needed in this sense.

Association of Histopathological Markers with Clinico- Pathological Factors in Mexican Women with Breast Cancer.

BACKGROUND: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors. MATERIALS AND METHODS: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied. RESULTS: On average, patients were 58±10.4 years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p <0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subtype was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02). CONCLUSIONS: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes.

RNA expression of cytochrome P450 in Mexican women with breast cancer.

Involvement of cytochrome P450 genes (CYPs) in breast cancer (BCa) may differ between populations, with expression patterns affected by tumorigenesis. This may have an important role in the metabolism of anticancer drugs and in the progression of cancer. The aim of this study was to determine the mRNA expression patterns of four cytochrome P450 genes (CYP2W1, 3A5, 4F11 and 8A1) in Mexican women with breast cancer. Real- time PCR analyses were conducted on 32 sets of human breast tumors and adjacent non-tumor tissues, as well as 20 normal breast tissues. Expression levels were tested for association with clinical and pathological data of patients. We found higher gene expression of CYP2W1, CYP3A5, CYP4F11 in BCa than in adjacent tissues and only low in normal mammary glands in our Mexican population while CYP8A1 was only expressed in BCa and adjacent tissues. We found that Ki67 protein expression was associated with clinicopathological features as well as with CYP2W1, CYP4F11 and CYP8A1 but not with CYP3A5. The results indicated that breast cancer tissues may be better able to metabolize carcinogens and other xenobiotics to active species than normal or adjacent non-tumor tissues.

CYP2W1, CYP4F11 and CYP8A1 polymorphisms and interaction of CYP2W1 genotypes with risk factors in Mexican women with breast cancer.

Breast cancer (BCa) is the leading type of cancer in Mexican women. Genetic factors, such as single nucleotide polymorphisms (SNP) of P450 system, have been reported in BCa. In this report, and for the first time in the literature, we analyzed the rs3735684 (7021 G>A), rs11553651 (15016 G>T) and rs56195291 (60020 C>G) polymorphisms in the CYP2W1, 4F11 and 8A1 genes in patients with BCa and in healthy Mexican women to identify a potential association between these polymorphisms and BCa risk. Patients and controls were used for polymorphism analysis using an allelic discrimination assay with TaqMan probes and confirmed by DNA sequencing. Links with clinic-pathological characteristics were also analyzed. Statistical analysis was performed using the standard χ2 or Fisher exact test statistic. No significant differences were observed in the distributions of CYP2W1 (OR 8.6, 95%CI 0.43-172.5 P>0.05; OR 2.0, 95%CI 0.76-5.4, P>0.05) and CYP4F11 (OR 0.3, 95%CI 0.01-8.4 P>0.05) genotypes between the patients and controls. Only the CYP8A1 CC genotype was detected in patients with BCa and the controls. All polymorphism frequencies were in Hardy-Weinberg Equilibrium (HWE) in the controls (P>0.05). We found a significant association between BCa risk and smoking, use of oral contraceptives or hormonal replacement therapy (HRT), obesity, hyperglycemia, chronic diseases, family history of cancer and menopausal status in the population studied (P<0.05). Tobacco, oral contraceptive or HRT, chronic diseases and obesity or overweight were strongly associated with almost eight, thirty-five, nine and five-fold increased risk for BCa. Tobaco, obesity and hyperglycemia significantly increased the risk of BCa in the patients carrying variant genotypes of CYP2W1 (P<0.05). These results indicate that the CYP2W1 rs3735684, CYP4F11 rs11553651 and CYP8A1 rs56195291 SNPs are not a key risk factor for BCa in Mexican women. This study did not detect an association between the CYP2W1, 4F11 and 8A1 genes polymorphisms and BCa risk in a Mexican population. However, some clinico-pathological risk factors interact with CYP2W1 genotypes and modifies susceptibility to BCa.

[Evaluation of the expression of p22 phox subunit of NADPH oxidase (NOX) in prostate cancer and benign prostatic hyperplasia: a comparative study]. / Evaluación de la expresión de la subunidad p22 phox de la NADPH oxidasa (NOX) en cáncer de próstata e hiperplasia prostática benigna: estudio comparativo.

INTRODUCTION AND OBJECTIVE: Recent reports found that prostate cancer is the second most common cancer and second leading cause of cancer death in men. METHODS AND RESULTS: 62 samples were obtained (30 of patients with cancer and 32 of patients with hyperplasia) collected from January 2004 to december 2007. Was conducted a clinical, experimental, transversal, comparative and descriptive trial. Were followed the inclusion (cancer or hyperplasia diagnosis), exclusion (patients not authorized to participate in the study or not candidates for resection of prostate) and elimination (damage tissue) criteria. Was detected by immunohistochemistry the presence of p22 phox NADPH oxidase subunit in patients with prostate cancer and prostatic hyperplasia from the formation of avidin-biotin complex using diaminobenzidine as a dye contrast. The statistical analysis was determined with t test (Graph Prism 3.0 software) considering p<0.05 for statistical differences. The results of the immunoreactivity of p22 phox in the stroma and gland of the prostate showed an increase in prostate cancer (8.45+/-3.6 and 25.08+/-7.5% p<0.0001, respectively) in comparison with the results for prostatic hyperplasia (4.8+/-2.8 and 6.7+/-3.1% p<0.0001, respectively). CONCLUSIONS: The over-expression of the NADPH oxidase is involved in the prostate cancer. Moreover, we suggested that the NADPH oxidase, in combination with other classical markers, could be an indicator for the post-treatment monitoring of the patients diagnosed with hyperplasia and others minors pathologies of the prostate.

Evaluación de la expresión de la subunidad p22 phox de la NADPH oxidasa (NOX) en cáncer de próstata e hiperplasia prostática benigna: estudio comparativo / Evaluation of the expression of p22 phox subunit of NADPH oxidase (NOX) in prostate cancer and benign prostatic hyperplasia: A comparative study

Introducción y objetivo: Recientes reportes ubican que el cáncer de próstata es el segundo cáncer más común y la segunda causa principal de muerte por cáncer en los hombres. Métodos y resultados: Se obtuvieron 62 muestras (30 de pacientes con cáncer y 32 de pacientes con hiperplasia) colectadas desde enero de 2004 a diciembre de 2007. Se llevó a cabo un estudio clínico, experimental, transversal, comparativo y descriptivo. Se cumplieron los criterios de inclusión (diagnóstico de cáncer o hiperplasia), exclusión (pacientes que no autorizaron a participar en el estudio o no candidatos a la resección prostática) y de eliminación (tejidos dañados). Se detectó por inmunohistoquímica la presencia de la subunidad p22 phox de la NADPH oxidasa en pacientes con cáncer de próstata e hiperplasia prostática a partir de la formación del complejo avidina-biotina en presencia de diaminobenzidina como colorante de contraste. El análisis estadístico fue determinado con la prueba t de student (software Graph Prism 3.0) considerando una p<0,05 para diferencias estadísticas. Los resultados de la inmunorreactividad de p22 phox en estroma y glándula de la próstata mostraron un incremento en el cáncer de próstata (8,45±3,6 y 25,08±7,5% p<0,0001, respectivamente) en comparación con los resultados encontrados para hiperplasia prostática (4,8±2,8 y 6,7±3,1% p<0,0001, respectivamente). Conclusiones: La sobreexpresión de NADPH oxidasa se encuentra involucrada en el cáncer de próstata. Además, sugerimos que la NADPH oxidasa, en combinación con otros marcadores clásicos, podría funcionar como un indicador para el monitoreo postoperatorio de pacientes diagnosticados con hiperplasia u otras patologías menores de la próstata (AU)

Introduction and objective: Recent reports found that prostate cancer is the second most common cancer and second leading cause of cancer death in men. Methods and results: 62 samples were obtained (30 of patients with cancer and 32 of patients with hyperplasia) collected from January 2004 to december 2007. Was conducted a clinical, experimental, transversal, comparative and descriptive trial. Were followed the inclusion (cancer or hyperplasia diagnosis), exclusion (patients not authorized to participate in the study or not candidates for resection of prostate) and elimination (damage tissue) criteria. Was detected by immunohistochemistry the presence of p22 phox NADPH oxidase subunit in patients with prostate cancer and prostatic hyperplasia from the formation of avidin-biotin complex using diaminobenzidine as a dye contrast. The statistical analysis was determined with t test (Graph Prism 3.0 software) considering p<0.05 for statistical differences. The results of the immunoreactivity of p22 phox in the stroma and gland of the prostate showed an increase in prostate cancer (8.45±3.6 and 25.08±7.5% p<0.0001, respectively) in comparison with the results for prostatic hyperplasia (4.8±2.8 and 6.7±3.1% p<0.0001, respectively). Conclusions: The over-expression of the NADPH oxidase is involved in the prostate cancer. Moreover, we suggested that the NADPH oxidase, in combination with other classical markers, could be an indicator for the post-treatment monitoring of the patients diagnosed with hyperplasia and others minors pathologies of the prostate (AU)

DD3(PCA3) gene expression in cancer and prostatic hyperplasia.

PURPOSE: DD3(PCA3) is a novel gene with characteristics that indicate its potentially valuable role in early identification and diagnosis of malignancy and highly upregulated in transformed cells in PCa. The aim of this work was to validate and analyze, by real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR), the expression of the DD3(PCA3)gene in a Mexican population, both in intratumoral tissue with PCa and benign prostatic hyperplasia (BPH). METHODS: Human samples from patients with PCa (40 cases) and benign prostatic hyperplasia (40 cases) were analyzed for the mRNA expression of DD3(PCA3)by RT-PCR RESULTS: The GAPDH gene showed better stability with a Pearson correlation of 0.953 (P < 0.007) for the determination of housekeeping gene. DD3(PCA3)gene expression was 29.74 times higher in PCa tissue (P < 0.0001) than in BPH. The gene expression for the PCa and BPH was 1731+/-280 and 58.23+/-9.9 fold, respectively. CONCLUSIONS: Determination of DD3(PCA3)gene expression by RT-PCR could be a potentially tool for the early detection of PCa in clinical specimens.

Copper reduces striatal protein nitration and tyrosine hydroxylase inactivation induced by MPP+ in rats.

Striatal administration of 1-methyl-4-phenylpyridinium (MPP(+)), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes nigrostriatal dopaminergic pathway damage similar to that observed in Parkinson's disease. Copper acts as a prosthetic group of several antioxidant enzymes and recent data show that copper attenuated MPP(+)-evoked neurotoxicity. We evaluated the effect of copper (as a supplement) upon proteins nitration (60 kDa) and tyrosine hydroxylase (TH) inactivation induced by MPP(+) (10 microg/8 microL) injection into the rat striatum. Copper pretreatment (10 micromol/kg i.p.) prevented both MPP(+)-induced proteins nitration and TH inactivation. Copper treatment also prevented the dopamine-depleting effect of MPP(+) injection. Those results were accompanied by a significant reduction of enzymatic activity of the constitutive nitric oxide synthase (cNOS), whereas, the protein levels of the three isoforms of NOS remained unchanged. Results indicate that the effect of copper against MPP(+)-induced proteins nitration and TH inactivation in the striatum of rat may be mediated by a reduction of cNOS activity.