Search for Non-Protein Protease Inhibitors Constituted with an Indole and Acetylene Core.

A possible inhibitor of proteases, which contains an indole core and an aromatic polar acetylene, was designed and synthesized. This indole derivative has a molecular architecture kindred to biologically relevant species and was obtained through five synthetic steps with an overall yield of 37% from the 2,2'-(phenylazanediyl)di(ethan-1-ol). The indole derivative was evaluated through docking assays using the main protease (SARS-CoV-2-Mpro) as a molecular target, which plays a key role in the replication process of this virus. Additionally, the indole derivative was evaluated as an inhibitor of the enzyme kallikrein 5 (KLK5), which is a serine protease that can be considered as an anticancer drug target.

Quadratic Non-Linear Optical Properties of the poly(2,5-bis(but-2-ynyloxy) Benzoate Containing the 2-(ethyl(4-((4-nitrophenyl)buta-1,3-diynyl)phenyl)amino)ethanol) Chromophore.

Excellent quadratic non-linear optical (ONL-2) properties of the poly(2,5-bis(but-2-ynyloxy) benzoate, containing a polar diacetylene as a chromophore, were found. According with the Maker fringes method, oriented polymer films showing an order parameter of ∼0.23 can display outstanding and stable Second Harmonic Generation (SHG) effects under off-resonant conditions (SHG-532 nm). Also, the macroscopic non-linear optical (NLO)-coefficients were evaluated under the rod-like molecular approximation, obtaining: χzzz(2) and χzxx(2) in the order of 280 ± 10 and 100 ± 10 pm V-1, respectively. The mechanical and chemical properties, in addition to the large ONL-2 coefficients exhibited by this polymer, make it a promising organic material in the development of optoelectronic/photonic devices.

Asociación entre bajo peso al nacer y parto pretermino en gestantes con signos de enfermedad periodontal atendidas en una institución del nivel primario de salud del valle del cauca-colombia / Association between low birth weight and preterm delivery in pregnant women with signs of periodontal disease treated at a primary health institution in the valle del cauca-colombia

RESUMEN INTRODUCCIÓN: El parto pretérmino (PPT) y el Bajo Peso al Nacer (BPN) y su consecuente morbilidad y mortalidad neonatal son problemas prevalentes de salud. Se ha planteado que las bacterias que participan en el desarrollo de la enfermedad periodontal (EP) estimulan la liberación de prostaglandinas, que, a su vez, estimulan el trabajo de parto, sin embargo, esta relación no ha sido claramente demostrada. OBJETIVO: Determinar la asociación entre BPN y PPT en gestantes con signos de EP en una Institución Pública de Salud. MATERIALES Y MÉTODOS: Estudio de casos y controles con relación 1:1. Los casos fueron gestantes con Recién Nacidos (RN) pretérmino (PT) <37 semanas y BPN <2.500 gr, los controles gestantes con parto a término y RN con peso >2.500 gr. Se excluyeron gestantes sin historia clínica odontológica o cuyos RN presentaron restricción del crecimiento intrauterino. Para determinar la asociación se estimaron OR con su respectivos IC al 95%, siendo estadísticamente significativo cuando el valor de P de chi2 fue menor de 0.05. RESULTADOS: El PPT/BPN supone una posible asociación con el antecedente familiar de hipertensión o diabetes OR: 2,76 IC: (0,87 - 9,26); (p=0,051), y hubo una asociación estadísticamente significativa con bajo peso materno (IMC<18.5) en el primer control prenatal OR: 2,85 IC: (0,96 - 8,66); (p=0,033), gingivitis OR: 4,03 IC: (1,04 - 18,83); (p=0,021), retracciones gingivales OR: 8,1 IC: (0,98 - 68) (p=0,027) y sangrado gingival OR 6,8 IC: (1,98 - 26,45); (p=0,000). CONCLUSIONES: Los resultados de este estudio sugieren que la enfermedad periodontal puede estar asociada al PPT/BPN.

ABSTRACT INTRODUCTION: Preterm birth (PB) and Low Birth Weight (LBW), and their consequent neonatal morbidity and mortality, are prevalent health problems. It has been suggested that bacteria responsible for the development of periodontal disease stimulate the release of prostaglandin, which in turn, stimulates labor. However, this relationship has not been clearly demonstrated. OBJECTIVE: To determine the association between low birth weight and premature delivery in pregnant women with signs of periodontal disease in the population of pregnant women in a public health institution. MATERIALS AND METHODS: Case-control study with a 1: 1 ratio. For our subjects we included pregnant women who gave birth prematurely (PT) <37 weeks to babies with a LBW <2,500 gr and as controls, pregnant women who delivered at term with newborns weighing more than 2,500 gr. Pregnant women without a dental history were excluded as were those whose NB presented an intrauterine growth restriction. To determine the association, we used the OR with its respective 95% confidence interval, it was statistically significant when the p values of chi test was less than 0.05. RESULTS: PB / LBW indicates a possible association with the family history of hypertension or diabetes OR: 2.76 CI: (0.87 - 9.26); (p = 0.051), and there was a statistically significant association with low maternal weight (BMI <18.5) in the first prenatal control OR: 2.85 IC: (0.96 - 8.66); (p = 0.033), gingivitis OR: 4.03 IC: (1.04 - 18.83); (p = 0.021), gingival retractions OR: 8.1 IC: (0.98 - 68) (p = 0.027) and gingival bleeding OR 6.8 CI: (1.98-26.45); (p = 0.000). CONCLUSIONS: The results of this study suggest an association between signs of periodontal disease and PB / LBW.

In vitro determination of the short-chain synthetic peptide RP13 antimicrobial activity.

BACKGROUND: The proliferation of antibiotic-resistant microorganisms, along with the lack of new drugs against them, has elicited the interest of the scientific community on the study and development of endogenous synthetic compounds with bacteriostatic or bactericidal activity. In recent years, several short-chain, low molecular weight peptides isolated from natural sources such as plants and animals have demonstrated an array of antimicrobial activities. Despite having structural characteristics similar to microbicidal peptides isolated from human platelets, peptide RP11 does not exhibit antimicrobial activity. OBJECTIVE: In vitro determination of the antimicrobial activity of the synthetic peptide RP13. MATERIAL AND METHODS: Peptide RP13 was prepared modifying the original amino acids sequence of peptide RP11, reversing the position of the amino acids lysine and tyrosine in order to modify the conformation of the original peptide. These amino acids are localized close to the N-terminus of the peptidic chain. Peptide RP13 was prepared in solution using conventional methods for peptide synthesis. The antimicrobial activity of RP13 was assessed against the microorganisms S. aureus, E. faecalis and E. coli in a test solution and later evaluated by cultivation of plates during the first 2 h after inoculation of bacteria. RP13 activity antimicrobial was compared against tetracycline, a broad-spectrum antibiotic. RESULTS: The new peptide RP13, resulting form the structural modification of the amino acid sequence of peptide RP11, displayed antimicrobial activity. RP13 demonstrated to be more efficient inhibiting the growth of gram-positive than gramnegative bacteria. CONCLUSIONS: The structural modification of peptide RP11, obtained from human platelets, resulted in a new peptide with improved antimicrobial activity. These results clearly demonstrate that peptides of natural origin, as well as their synthetic analogs, represent an attractive alternative against pathogenic agents.

Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children.

OBJECTIVE: To examine vitamin D, parathyroid hormone, and serum calcium-phosphorus levels relationships to biomarkers of oxidative/nitrosative stress, inflammation, and endothelial activation, potential contributors for vascular complications in obese children. STUDY DESIGN: Cross-sectional clinical study of 66 obese Caucasian children aged 7 to 14 years. Cardiovascular risk factors were assessed. Malondialdehyde and myeloperoxidase as measures of oxidative stress, and plasma nitrite+nitrate, urinary nitrate, and 3-nitrotyrosine as markers of nitrosative stress were measured. Adipocytokines, inflammatory molecules (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α), endothelial activation molecules (soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule 1 [sVCAM-1]), E-selectin, and vascular endothelial growth factor were also investigated. Serum 25-hydroxy-cholecalciferol [25(OH)D], intact parathormone, and calcium-phosphorus levels were determined in these children and in a comparison group of 39 non-obese children. RESULTS: Obese children had a significantly lower 25(OH)D level (P = .002) and a higher intact parathormone (P = .011) than non-obese children. Phosphorus and the calcium-phosphorus product were also significantly higher (P < .0001). Insufficient serum concentrations of 25(OH)D (<20 ng/mL) were detected in 5% of normal children and in 30% of the obese children. In the obese children with vitamin D insufficiency, malondialdehyde, myeloperoxidase, 3-nitrotyrosine, interleukin-6, and sVCAM-1 were substantially elevated. A partial correlation analysis showed an inverse relationship of 25(OH)D levels with 3-nitrotyrosine (r = -0.424, P = .001), and sVCAM-1 (r = -0.272, P = .032). CONCLUSIONS: Insufficient 25(OH)D levels were detected in severely obese children with increased markers of oxidative/nitrosative stress, inflammation, and endothelial activation.

Recidiva local en cirugía conservadora en el cáncer de mama / Local recurrence after conservative surgery in breast cancer

Objetivos: estudiar el rol de la edad, el tamaño tumoral,la colonización ganglionar axilar, el carcinoma ductal "in situ", el "índice histológico" y los márgenes de resección, en la ocurrencia de la recidiva locorregional luego de terapéutica conservadora mamaria. Material y método: Se reportan 156 pacientes con cáncer mamario en estadios I y II, tratadas con terapéutica conservadora mamaria, entre 1987 y 1995. Se comparó la ocurrencia o no de recidiva locorregional para cada una de las variables, mediante tablas de tabulación cruzada, chi cuadrado y test de Fisher. Resultados: el porcentaje de recidivas locorregionales fue 13,4 por ciento (21/156). En pacientes con carcinoma ductal "in situ" mayor de 25 por ciento ocurrieron 40,7 por ciento de recidivas (11/27) versus 7,7 por ciento (10/129) en pacientes con menos de 25 por ciento (p<0,00001, RR=8,18). En cinco pacientes menores de 35 años ocurrieron dos recidivas, en 34 pacientes entre 36-49 años, ocho recidivas (22,8 por ciento) y en 117 pacientes de 50 o más años, 11 recidivas (9,3 por ciento), (p <0,001). En pacientes con T1, hubo 8,3 por ciento de recidivas (8/96) vs 21,7 por ciento (13/60) con T2 (p<0,03, RR=3,04). Con margen de resección menores de 1 mm, hubo 25 por ciento de recidivas, descendiendo a 10,5 por ciento cuando el margen fue mayor de 1 mm(p<0,03, R=2,8). En tumores indiferenciados, con "indice histológico" de seis o más, hubo 18,6 por ciento recidivas, en comparación con los más diferenciados con un índice de tres a cinco con 5,9 por ciento de recidivas (p<0,003, RR= 3, 65). No hubo diferencias estadísticamente significativas, considerando el estado de colonización ganglionar axilar. Conclusiones: edades tempranas, carcinoma ductal "in situ" extensivo, T mayor de cm, "indice histológico" de seis o más, y márgenes de resección exiguos, se asociaron con incremento significativo de recidivas locorregionales. Se sugiere que para disminuir el fallo locorregional en terapéutica conservadora mamaria, deben tenerse en cuenta estas caracteristicas clásicas, sobre todo en nuestros países en desarrollo, sin acceso rutinariamente a factores más costosos y sofisticados

Recidiva local en cirugía conservadora en el cáncer de mama / Local recurrence after conservative surgery in breast cancer

Objetivos: estudiar el rol de la edad, el tamaño tumoral,la colonización ganglionar axilar, el carcinoma ductal in situ, el índice histológico y los márgenes de resección, en la ocurrencia de la recidiva locorregional luego de terapéutica conservadora mamaria. Material y método: Se reportan 156 pacientes con cáncer mamario en estadios I y II, tratadas con terapéutica conservadora mamaria, entre 1987 y 1995. Se comparó la ocurrencia o no de recidiva locorregional para cada una de las variables, mediante tablas de tabulación cruzada, chi cuadrado y test de Fisher. Resultados: el porcentaje de recidivas locorregionales fue 13,4 por ciento (21/156). En pacientes con carcinoma ductal in situ mayor de 25 por ciento ocurrieron 40,7 por ciento de recidivas (11/27) versus 7,7 por ciento (10/129) en pacientes con menos de 25 por ciento (p<0,00001, RR=8,18). En cinco pacientes menores de 35 años ocurrieron dos recidivas, en 34 pacientes entre 36-49 años, ocho recidivas (22,8 por ciento) y en 117 pacientes de 50 o más años, 11 recidivas (9,3 por ciento), (p <0,001). En pacientes con T1, hubo 8,3 por ciento de recidivas (8/96) vs 21,7 por ciento (13/60) con T2 (p<0,03, RR=3,04). Con margen de resección menores de 1 mm, hubo 25 por ciento de recidivas, descendiendo a 10,5 por ciento cuando el margen fue mayor de 1 mm(p<0,03, R=2,8). En tumores indiferenciados, con indice histológico de seis o más, hubo 18,6 por ciento recidivas, en comparación con los más diferenciados con un índice de tres a cinco con 5,9 por ciento de recidivas (p<0,003, RR= 3, 65). No hubo diferencias estadísticamente significativas, considerando el estado de colonización ganglionar axilar. Conclusiones: edades tempranas, carcinoma ductal in situ extensivo, T mayor de cm, indice histológico de seis o más, y márgenes de resección exiguos, se asociaron con incremento significativo de recidivas locorregionales. Se sugiere que para disminuir el fallo locorregional en terapéutica conservadora mamaria, deben tenerse en cuenta estas caracteristicas clásicas, sobre todo en nuestros países en desarrollo, sin acceso rutinariamente a factores más costosos y sofisticados(AU)