RESUMEN
In the search of new cymantrenyl- and ferrocenyl-sulfonamides as potencial inhibitors of human carbonic anhydrases (hCAs), four compounds based on N-ethyl or N-methyl benzenesulfonamide units have been obtained. These cymantrenyl (1a-b) and ferrocenyl (2a-b) derivatives were prepared by the reaction between aminobenzene sulfonamides ([NH2-(CH2)n-(C6H4)-SO2-NH2)], where n = 1, 2) with cymantrenyl sulfonyl chloride (P1) or ferrocenyl sulfonyl chloride (P2), respectively. All compounds were characterized by conventional spectroscopic techniques and cyclic voltammetry. In the solid state, the molecular structures of compounds 1a, 1b, and 2b were determined by single-crystal X-ray diffraction. Biological evaluation as carbonic anhydrases inhibitors were carried out and showed derivatives 1b y 2b present a higher inhibition than the drug control for the Human Carbonic Anhydrase (hCA) II and IX isoforms (KI = 7.3 nM and 5.8 nM, respectively) and behave as selective inhibition for hCA II isoform. Finally, the docking studies confirmed they share the same binding site and interactions as the known inhibitors acetazolamide (AAZ) and agree with biological studies.
Asunto(s)
Inhibidores de Anhidrasa Carbónica , Anhidrasas Carbónicas , Simulación del Acoplamiento Molecular , Sulfonamidas , Humanos , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Anhidrasas Carbónicas/metabolismo , Anhidrasas Carbónicas/química , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/metabolismo , Anhidrasa Carbónica II/química , Anhidrasa Carbónica IX/antagonistas & inhibidores , Anhidrasa Carbónica IX/metabolismo , Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/química , Anhidrasa Carbónica I/antagonistas & inhibidores , Anhidrasa Carbónica I/metabolismo , Bencenosulfonamidas , Compuestos Organometálicos/química , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/farmacología , Cristalografía por Rayos XRESUMEN
Kidney-specific with-no-lysine kinase 1 (KS-WNK1) is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies have suggested that it could play a role in regulating potassium renal excretion by modulating the activity of the Na+-Cl- cotransporter (NCC). However, changes in the potassium diet from normal to high failed to reveal a role for KS-WNK1, but under a normal-potassium diet, the expression of KS-WNK1 is negligible. It is only detectable when mice are exposed to a low-potassium diet. In this study, we investigated the role of KS-WNK1 in regulating potassium excretion under extreme changes in potassium intake. After following a zero-potassium diet (0KD) for 10 days, KS-WNK1-/- mice had lower plasma levels of K+ and Cl- while exhibiting higher urinary excretion of Na+, Cl-, and K+ compared with KS-WNK1+/+ mice. After 10 days of 0KD or normal-potassium diet (NKD), all mice were challenged with a high-potassium diet (HKD). Plasma K+ levels markedly increased after the HKD challenge only in mice previously fed with 0KD, regardless of genotype. KSWNK1+/+ mice adapt better to HKD challenge than KS-WNK1-/- mice after a potassium-retaining state. The difference in the phosphorylated NCC-to-NCC ratio between KS-WNK1+/+ and KS-WNK1-/- mice after 0KD and HKD indicates a role for KS-WNK1 in both NCC phosphorylation and dephosphorylation. These observations show that KS-WNK1 helps the distal convoluted tubule to respond to extreme changes in potassium intake, such as those occurring in wildlife.NEW & NOTEWORTHY The findings of this study demonstrate that kidney-specific with-no-lysine kinase 1 plays a role in regulating urinary electrolyte excretion during extreme changes in potassium intake, such as those occurring in wildlife. .
Asunto(s)
Ratones Noqueados , Potasio en la Dieta , Proteína Quinasa Deficiente en Lisina WNK 1 , Animales , Masculino , Ratones , Riñón/metabolismo , Túbulos Renales Distales/metabolismo , Ratones Endogámicos C57BL , Fosforilación , Potasio/orina , Potasio/metabolismo , Potasio/sangre , Potasio en la Dieta/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Eliminación Renal , Miembro 3 de la Familia de Transportadores de Soluto 12/metabolismo , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , Proteína Quinasa Deficiente en Lisina WNK 1/metabolismo , Proteína Quinasa Deficiente en Lisina WNK 1/genética , FemeninoRESUMEN
A series of new ferrocenyl nitroheterocyclic sulfonylhydrazones (1a-4a and 1b-2b) were prepared by the reaction between formyl (R = H) or acetyl (R = CH3) nitroheterocyclic precursors [4/5-NO2(C5H2XCOR), where X = O, S)] and ferrocenyl tosyl hydrazine [(η5-C5H5)Fe(η5-C5H4SO2-NH-NH2)]. All compounds were characterized by conventional spectroscopic techniques. In the solid state, the molecular structures of compounds 1a, 2b, and 3a were determined by single-crystal X-ray diffraction. The compounds showed an E-configuration around the C=N moiety. Evaluation of trypanocidal activity, measured in vitro against the Trypanosoma cruzi and Trypanosoma brucei strains, indicated that all organometallic tosyl hydrazones displayed activity against both parasite species with a higher level of potency toward T. brucei than T. cruzi. Moreover, the biological evaluation showed that the 5-nitroheterocyclic derivatives were more efficient trypanocidal agents than their 4-nitroheterocyclic counterparts.
Asunto(s)
Enfermedad de Chagas , Tripanocidas , Trypanosoma cruzi , Humanos , Metalocenos , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitologíaRESUMEN
Independent predictors of mortality for COVID-19 patients have been identified upon hospital admission; however, how they behave after hospitalization remains unknown. The aim of this study is to identify clinical and laboratory parameters from admission to discharge or death that distinguish survivors and non-survivors of COVID-19, including those with independent ability to predict mortality. In a cohort of 266 adult patients, clinical and laboratory data were analyzed from admission and throughout hospital stay until discharge or death. Upon admission, non-survivors had significantly increased C reactive protein (CRP), neutrophil count, neutrophil to lymphocyte ratio (NLR) (p < 0.0001, each), ferritin (p < 0.001), and AST (aspartate transaminase) (p = 0.009) compared to survivors. During the hospital stay, deceased patients maintained elevated CRP (21.7 mg/dL [admission] vs. 19.3 [hospitalization], p = 0.060), ferritin, neutrophil count and NLR. Conversely, survivors showed significant reductions in CRP (15.8 mg/dL [admission] vs. 9.3 [hospitalization], p < 0.0001], ferritin, neutrophil count and NLR during hospital stay. Upon admission, elevated CRP, ferritin, and diabetes were independent predictors of mortality, as were persistently high CRP, neutrophilia, and the requirement of invasive mechanical ventilation during hospital stay. Inflammatory and clinical parameters distinguishing survivors from non-survivors upon admission changed significantly during hospital stay. These markers warrant close evaluation to monitor and predict patients' outcome once hospitalized.
RESUMEN
The healthy newborn (NB) experiences physiological weight loss in her/his first days of life. Identi fying normal weight loss in this period is relevant since it allows the clinician to make decisions in relation to the need to supplement breastfeeding. OBJECTIVES: To determine the curves that graph the weight loss experienced by healthy newborns exclusively breastfed during the first 48 hours after birth. PATIENTS AND METHOD: Retrospective and analytical descriptive study in healthy full-term NBs during their stay in the nursery, exclusively breastfed, and with mixed feeding. Weights were recor ded at birth and on the first and second day of life. A quadratic polynomial was used to model the relative weights. The percentiles of the variations in weight loss were estimated. RESULTS: The sample consists of 4331 NBs with an average gestational age of 38.84 weeks. Of these, 56.45% were vaginal deliveries and 43.55% cesarean sections. The distribution by sex was 49.37% male and 50.63% fema le. Regarding adequacy, 82.96% were adequate for gestational age, 6.33% were small for gestational age, and 10.71% were large for gestational age. The greatest weight loss was observed in the first 12 hours of life. CONCLUSIONS: A weight loss graph is obtained for the first 48 hours of life, representing the weight loss per hour for healthy term NB exclusively breastfed. These curves can be used as a decision-making tool to categorize the weight loss of the NB and help in decision making regarding the indication to add artificial feeding.
Asunto(s)
Lactancia Materna , Leche Humana , Embarazo , Femenino , Humanos , Recién Nacido , Masculino , Niño , Lactante , Estudios Retrospectivos , Pérdida de Peso/fisiología , Parto ObstétricoAsunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Distribución por Edad , Factores de Edad , COVID-19 , Niño , Chile/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Humanos , Pandemias , Pediatría , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2Asunto(s)
Humanos , Niño , Neumonía Viral/epidemiología , Infecciones por Coronavirus/epidemiología , Betacoronavirus/aislamiento & purificación , Pediatría , Neumonía Viral/transmisión , Neumonía Viral/virología , Chile/epidemiología , Factores de Edad , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Distribución por Edad , PandemiasRESUMEN
A new ruthenium complex, [Ru(bpy)2(dbe-ppl)](PF6)2 (bpy=2,2'-bipyridine and dbe-ppl=dimethyl 4,4'-(pyrazino[2,3-f][1,10]phenanthroline-2,3-diyl)dibenzoate, has been synthesized and characterized by (1)H NMR spectroscopy, UV-Vis, IR, and cyclic voltammetry. Irradiation on the MLCT band results in photoluminescence in both protic and aprotic solvents. The photoluminescence in water is pH dependent, it shows a behavior which can be described by the Henderson-Hasselbalch assuming the protonation/deprotonation of the excited state with a pKa of 2.40±0.01.
Asunto(s)
Mediciones Luminiscentes , Fenantrolinas/química , Rutenio/química , Concentración de Iones de HidrógenoRESUMEN
Se realizó un estudio descriptivo y transversal para evaluar la satisfacción de prestadores de salud y pacientes con el funcionamiento del Sistema Integrado de Urgencias Médicas en el municipio de Guantánamo, perteneciente a la provincia del mismo nombre, durante el primer cuatrimestre de 2010. Para ello, por medio de un muestreo intencional fueron escogidos 8 médicos, 126 paramédicos encargados del servicio y 350 pacientes, a partir del criterio de los autores. Un grupo de expertos, en unión de estos últimos, elaboró los criterios, indicadores, estándares e instrumentos que se utilizaron para la evaluación. Los resultados mostraron amplias desviaciones de los valores obtenidos en relación con los establecidos, puesto que en 70 por ciento fueron inadecuados por insatisfacción de los que ofrecían y recibían la atención sanitaria, respectivamente(AU)
A descriptive and cross-sectional study was carried out during the first four-month period in the year 2010 in order to evaluate the health workers´and patients´satisfaction with the functioning of the Integrated Medical Emergency System in Guantánamo municipality, which belongs to the province under the same name. For this reason, 8 doctors, 126 paramedics in charge of that service, and 350 patients were chosen using an intentional sampling starting from the author's criterion. An expert group, along with the aforementioned group, devised the criteria, indicators, standards, and tools used for the assessment. Results showed large deviations of the obtained values in relation to those established, since 70 per cent of them were inadequate due to the dissatisfaction for both, those who received the health care and those who offered it, respectively(AU)
Asunto(s)
Humanos , Masculino , Femenino , Urgencias Médicas , Calidad de la Atención de Salud , Satisfacción del Paciente , Competencia Profesional , Satisfacción en el Trabajo , Servicios Médicos de Urgencia , Epidemiología Descriptiva , Estudios TransversalesRESUMEN
Se realizó un estudio descriptivo y transversal para evaluar la satisfacción de prestadores de salud y pacientes con el funcionamiento del Sistema Integrado de Urgencias Médicas en el municipio de Guantánamo, perteneciente a la provincia del mismo nombre, durante el primer cuatrimestre de 2010. Para ello, por medio de un muestreo intencional fueron escogidos 8 médicos, 126 paramédicos encargados del servicio y 350 pacientes, a partir del criterio de los autores. Un grupo de expertos, en unión de estos últimos, elaboró los criterios, indicadores, estándares e instrumentos que se utilizaron para la evaluación. Los resultados mostraron amplias desviaciones de los valores obtenidos en relación con los establecidos, puesto que en 70 por ciento fueron inadecuados por insatisfacción de los que ofrecían y recibían la atención sanitaria, respectivamente.
A descriptive and cross-sectional study was carried out during the first four-month period in the year 2010 in order to evaluate the health workers´and patients´satisfaction with the functioning of the Integrated Medical Emergency System in Guantánamo municipality, which belongs to the province under the same name. For this reason, 8 doctors, 126 paramedics in charge of that service, and 350 patients were chosen using an intentional sampling starting from the author's criterion. An expert group, along with the aforementioned group, devised the criteria, indicators, standards, and tools used for the assessment. Results showed large deviations of the obtained values in relation to those established, since 70 per cent of them were inadequate due to the dissatisfaction for both, those who received the health care and those who offered it, respectively.
Asunto(s)
Humanos , Masculino , Femenino , Urgencias Médicas , Servicios Médicos de Urgencia , Satisfacción en el Trabajo , Satisfacción del Paciente , Competencia Profesional , Calidad de la Atención de Salud , Estudios Transversales , Epidemiología DescriptivaRESUMEN
Plagiarism is defined as the intellectual fraud in which an individual attempts to unduly appropriate, for his/her own benefit, the knowledge, ideas or discoveries of someone else. It is not uncommon in academic settings where research is conducted and a creative work is carried out. Due to the dismal consequences of plagiarism, cautionary measures and sanctions are required to avoid it. This paper is intended to warn and promote a discussion about plagiarism. The Faculty of Medicine of the University of Chile and its ethics committee believe that a fight against these type of actions will contribute to prevent their detrimental effects on the moral and intellectual patrimony of our society.
Asunto(s)
Códigos de Ética/legislación & jurisprudencia , Plagio , Mala Conducta Científica/ética , Chile , Comités de Ética en Investigación , Humanos , Mala Conducta Científica/legislación & jurisprudenciaRESUMEN
Plagiarism is defined as the intellectual fraud in which an individual attempts to unduly appropriate, for his/her own benefit, the knowledge, ideas or discoveries of someone else. It is not uncommon in academic settings where research is conducted and a creative work is carried out. Due to the dismal consequences of plagiarism, cautionary measures and sanctions are required to avoid it. This paper is intended to warn and promote a discussion about plagiarism. The Faculty of Medicine of the University of Chile and its ethics committee believe that a fight against these type of actions will contribute to prevent their detrimental effects on the moral and intellectual patrimony of our society.
Asunto(s)
Humanos , Códigos de Ética/legislación & jurisprudencia , Plagio , Mala Conducta Científica , Chile , Comités de Ética en Investigación , Mala Conducta Científica/legislación & jurisprudenciaRESUMEN
Se presenta un caso de adenoma paratiroideo de localización intratiroidea, situado en hemitiroides izquierda, el cual hizo su presentación en la clínica como un nódulo frío en la gammagrafía tiroidea. Los autores resaltan la rareza del caso presentado dentro de la literatura universal, de los cuales hay descritos previamente 7 casos. Por ello, se deberá tener en cuenta esta posibilidad en la clínica, especialmente si van asociados a sintomatología hiperparatiroidea
Asunto(s)
Adulto , Humanos , Femenino , Adenoma , Glándulas Paratiroides , Neoplasias de las Paratiroides , Adenoma/patología , Neoplasias de las Paratiroides/patologíaRESUMEN
Se presenta un caso de adenoma paratiroideo de localización intratiroidea, situado en hemitiroides izquierda, el cual hizo su presentación en la clínica como un nódulo frío en la gammagrafía tiroidea. Los autores resaltan la rareza del caso presentado dentro de la literatura universal, de los cuales hay descritos previamente 7 casos. Por ello, se deberá tener en cuenta esta posibilidad en la clínica, especialmente si van asociados a sintomatología hiperparatiroidea (AU)