COMPARACIÓN DE LA EFECTIVIDAD DE LA ANALGESIA MULTIMODAL VERSUS ANALGESIA ESTÁNDAR PARA EL MANEJO DE DOLOR POST- OPERATORIO EN PACIENTES SOMETIDOS A CIRUGÍA DE TRAUMA Y ORTOPEDIA EN EL CENTRO MÉDICO LIC. ADOLFO LÓPEZ MATEOS.

El manejo de dolor post-operatorio es fundamental para facilitar la recuperación, disminuir la estancia hospitalaria y ofrecer una atención de calidad a los pacientes. Para ello, la analgesia multimodal promete mejores resultados. Comparando la efectividad de la analgesia multimodal versus analgesia estándar para el manejo de dolor post-operatorio en pacientes sometidosa cirugía de trauma y ortopedia en el Centro Médico Lic. Adolfo López Mateos.UAEM-La autora

0307 Role of vascular mineralocorticoid receptor in renal injury induced by ischemia/reperfusion

IntroductionAcute kidney injury (AKI) is defined as an abrupt decrease (48h) in kidney function. One of the main causes of AKI is ischemia/reperfusion (I/R). AKI is related with high mortality, chronic kidney disease development and cardiac alterations like heart failure and arrhythmias. Mineralocorticoid receptor (MR) antagonism with spironolactone (Sp) prevents tubular injury and renal dysfunction induced by I/R in the rat. Although there is information supporting a role for aldosterone and MR in kidney injury, it remains unexplored the specific role of the MR expressed in the vasculature in mediating the deleterious effects of aldosterone during renal I/R.ObjectiveTo study the effect of inducing I/R in mice lacking the MR specifically in the endothelial cells or in the vascular smooth muscle cells.MethodsTo test if Sp is also able to prevent renal injury induced by I/R in the mice with the C57BL/6 background (same as MR KO mice) we included three groups of mice: 1) Sham, 2) I/R 20 min and 3) I/R 20 min + Sp pre-treatment. We analyzed the presence of renal dysfunction and inflammatory cytokines. In the MR KO mice, we will analyze the effect of MR deficiency after renal I/R in an acute phase (24h) and in chronic kidney disease development (after 4 weeks). In the acute studies the mechanisms that will be explored include: polarization of macrophages, endothelial injury and oxidative stress. In the chronic studies we will test if the wild type or MR knockout mice develop CKD as a consequence of renal I/R.ResultsMice underwent renal I/R developed injury characterized by increased serum creatinine and urea levels, urinary Hsp72 and elevation in the mRNA of TNF-alpha and MCP-1 pro-inflammatory cytokines. These alterations were prevented by the Sp pre-treatment.ConclusionThe protective effect of Sp against renal I/R that was previously reported in the rat is also observed in the C57BL/6 mice and supports the study of the MR KO mice in the renal I/R setting

Gene Expression Analysis Reveals the Cell Cycle and Kinetochore Genes Participating in Ischemia Reperfusion Injury and Early Development in Kidney

The molecular mechanisms that mediate the ischemia-reperfusion (I/R) injury in kidney are not completely understood. It is also largely unknown whether such mechanisms overlap with those governing the early development of kidney.We performed gene expression analysis to investigate the transcriptome changes during regeneration after I/R injury in the rat (0 hr, 6 hr, 24 hr, and 120 hr after reperfusion) and early development of mouse kidney (embryonic day 16 p.c. and postnatal 1 and 7 day). Pathway analysis revealed a wide spectrum of molecular functions that may participate in the regeneration and developmental processes of kidney as well as the functional association between them. While the genes associated with cell cycle, immunity, inflammation, and apoptosis were globally activated during the regeneration after I/R injury, the genes encoding various transporters and metabolic enzymes were down-regulated. We also observed that these injury-associated molecular functions largely overlap with those of early kidney development. In particular, the up-regulation of kinases and kinesins with roles in cell division was common during regeneration and early developmental kidney as validated by real-time PCR and immunohistochemistry.In addition to the candidate genes whose up-regulation constitutes an overlapping expression signature between kidney regeneration and development, this study lays a foundation for studying the functional relationship between two biological processes

Factores pedagógicos y la disciplina escolar en los estudiantes de secundaria de la I.E. "Dos de Mayo" de la región Callao, 2009

El presente estudio examinó la relación entre los factores pedagógicos y la disciplina escolar en los estudiantes de secundaria de la I.E. “Dos de Mayo” de la Región Callao, teniendo por objetivo determinar la relación entre los factores pedagógicos y la disciplina escolar en los estudiantes de secundaria de la I.E. “Dos de Mayo” de la Región Callao. La metodología aplicada es de tipo hipotético deductivo, siendo el diseño no experimental de tipo transversal y correlacional. El tamaño de la muestra se estimó por procedimientos probabilísticos de tipo estratificado y comprende a 262 sujetos. Se utilizaron dos instrumentos de evaluación: La encuesta de factores pedagógicos y la encuesta de disciplina escolar. Los resultados evidencian que existe una relación altamente significativa entre ambas variables, además se halló que la dimensión evasión y agresividad (de la encuesta de disciplina escolar) se relaciona de manera altamente significativa y negativa con el control de los factores pedagógicos; así como también, las normas de convivencia tienen una relación altamente significativa positiva con el control de los factores pedagógicos. Finalmente, se concluye que los docentes al tener un mayor control de los factores pedagógicos contribuyen a que exista un mayor nivel de disciplina escolar

Role of KLHL3 and dietary K⁺ in regulating KS-WNK1 expression

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this recordThe physiological role of the shorter isoform of WNK1 that is exclusively expressed in the kidney (KS-WNK1), with particular abundance in the distal convoluted tubule, remains elusive. KS-WNK1 despite lacking the kinase domain, is nevertheless capable of stimulating the NaCl cotransporter (NCC), apparently through activation of WNK4. It has recently been shown that a less severe form of the Familial Hyperkalemic Hypertension featuring only hyperkalemia is caused by missense mutations in the WNK1 acidic domain that preferentially affect CUL3-KLHL3 E3-induced degradation of KS-WNK1, rather than that of the full-length WNK1 (L-WNK1). Here we show that L-WNK1 is indeed less impacted by the CUL3-KLHL3 E3 ligase complex compared to KS-WNK1. We demonstrate that the unique 30 amino acid amino N-terminal fragment of KS-WNK1 is essential for its activating effect on NCC and recognition by KLHL3. We identify specific amino acid residues in this region critical for the functional effect of KS-WNK1 and KLHL3 sensitivity. To further explore this, we generated KLHL3-R528H knock-in mice that mimic human mutations causing Familial Hyperkalemic Hypertension. These mice revealed that the KLHL3 mutation specifically increased expression of KS-WNK1 in the kidney. We also observed that in wild type mice, expression of KS-WNK1 is only detectable after exposure to low potassium diet. These findings provide new insights into the regulation and function of KS-WNK1 by the CUL3-KLHL3 complex in DCT and indicate that this pathway is regulated by dietary K+ levels.National Institutes of Health (NIH)Conacyt MexicoPAPIIT UNAML'OréalMedical Research Council (MRC

Morbidade e mortalidade por doença da membrana hialina no Hospital Geral Dr. Agostinho Neto, Guantánamo 2016-2018

Introduction: hyaline membrane disease is a health problem in the neonatal stage.Objective: to characterize the newborns admitted to the neonatal intensive care unit of the General Teaching Hospital “Dr. Agostinho Neto” due to hyaline membrane disease during the years 2016-2018.Method: an observational, descriptive, prospective and longitudinal study of 163 newborns who entered the unit was made.Results: 16.4% of the infants admitted to this unit had this disease and the lethality was 11.0%. The largest proportion of these were male (55.8%), were between 31.0 and 33.6 weeks of gestational age at birth (28.2%), weighed between 1500.9 and 1999.9 g (27.0 %), had an Apgar after 5 minutes of birth between 8 and 10 points (58.9%) and were in the unit for 7 to 14 days (40.4%). 93.3% were treated with pulmonary maturation inducing drugs and 100.0% with surfactant and conventional mechanical ventilation (100.0%). 84.7% presented complications and 55.6% died from intracranial hemorrhage (55.6%). It was common for mothers to be between 19 and 35 years old (76.6%), to be ceased (65.0%) and had pregnancy-related complications (82.2%).Conclusion: lethality was higher as the gestational age and birth weight decreased, in those who were not treated with pulmonary maturation inducing drugs and who presented meningoencephalitis.Introducción: la enfermedad de la membrana hialina es un problema de salud en la etapa neonatal.Objetivo: caracterizar a los recién nacidos ingresados en la unidad de cuidados intensivos neonatales del Hospital General Docente “Dr. Agostinho Neto” por enfermedad de la membrana hialina durante los años 2016-2018.Método: se hizo un estudio observacional, descriptivo, prospectivo y longitudinal de 163 recién nacidos que ingresaron en la unidad.Resultados: el 16,4 % de los neonatos ingresados en dicha unidad tenían esta enfermedad y la letalidad fue de 11,0 %. La mayor proporción de éstos eran varones (55,8 %), tenían entre 31,0 y 33,6 semanas de edad gestacional al nacer (28,2 %), pesaron entre 1500,9 y 1999,9 g (27,0 %), tuvieron un Apgar a los 5 minutos de nacidos entre 8 y 10 puntos (58,9 %) y estuvieron en la unidad de 7 a 14 días (40,4 %). El 93,3 % se trató con fármacos inductores de maduración pulmonar y 100,0 % con surfactante y ventilación mecánica convencional (100,0 %). El 84,7 % presentó complicaciones y el 55,6 % falleció por hemorragia intracraneal (55,6 %). Fue común que las madres tuvieran edad entre 19 y 35 años (76,6 %), fueran cesareadas (65,0 %) y presentaron complicaciones relacionadas con el embarazo (82,2 %).Conclusión: la letalidad fue superior en la medida que disminuye la edad gestacional y el peso al nacer, en los que no fueron tratados con fármacos inductores de maduración pulmonar y que presentaron meningoencefalitis.Introdução: a doença da membrana hialina é um problema de saúde no estágio neonatal.Objetivo: caracterizar os recém-nascidos internados na unidade de terapia intensiva neonatal do Hospital Geral de Ensino “Dr. Agostinho Neto” por doença da membrana hialina durante os anos de 2016 a 2018.Método: estudo observacional, descritivo, prospectivo e longitudinal de 163 recém-nascidos que ingressaram na unidade.Resultados: 16,4% dos lactentes internados nessa unidade apresentavam essa doença e a letalidade era de 11,0%. A maior proporção deles era do sexo masculino (55,8%), tinha entre 31,0 e 33,6 semanas de idade gestacional ao nascer (28,2%), pesava entre 1500,9 e 1999,9 g (27,0 %), apresentou Apgar após 5 minutos de nascimento entre 8 e 10 pontos (58,9%) e permaneceu na unidade por 7 a 14 dias (40,4%). 93,3% foram tratados com fármacos indutores de maturação pulmonar e 100,0% com surfactante e ventilação mecânica convencional (100,0%). 84,7% apresentaram complicações e 55,6% morreram de hemorragia intracraniana (55,6%). Era comum as mães ter entre 19 e 35 anos (76,6%), cessar (65,0%) e apresentar complicações relacionadas à gravidez (82,2%).Conclusão: a letalidade foi maior com a diminuição da idade gestacional e do peso ao nascer naqueles que não foram tratados com fármacos indutores da maturação pulmonar e que apresentaram meningoencefalite

The calcium-sensing receptor increases activity of the renal NCC through the WNK4-SPAK pathway

Background Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle’s loop controls Ca2+ excretion and NaCl reabsorption in response to extracellular Ca2+. However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. Methods We used a combination of in vitro and in vivo models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well. Results Thiazide-sensitive 22Na+ uptake assays in Xenopus laevis oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd3+. In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC. Conclusions Activation of CaSR can increase NCC activity via the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca2+ in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca2+ reabsorption, further promoting hypercalciuria