Incidence of Surgical Site Infection in Patients who Underwent Surgery at Hospital Pasteur (Montevideo), July-August 2017

Martina Bañales: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Diego Castro: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Sabrina Della Mea: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Isabel Larre Borges: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Josefina Mora: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Manuel Soneira: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República, Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Alejandra Liz: Docente supervisor. Clínica Quirúrgica 1, Hospital Pasteur, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Contacto: [email protected] infecciones del sitio quirúrgico (ISQ) son una complicación frecuente en cirugía general. Generan múltiples problemas para el paciente y aumentan los costos en salud. Existe una carencia de datos a nivel nacional sobre dicha patología. El objetivo general del estudio fue determinar la incidencia de infecciones tipo I y II de la clasificación del Centers for Disease Control and Prevention en pacientes postoperatorios de cirugía abdominal y vascular periférica internados en el Hospital Pasteur, entre julio y agosto de 2017. Los objetivos específicos fueron identificar los factores de riesgo, determinar los gérmenes más prevalentes, frecuencia de tratamiento con drenaje o antibioticoterapia y el tiempo medio entre la cirugía y el diagnóstico de ISQ. Se realizó un estudio observacional longitudinal prospectivo que incluyó a 99 pacientes. Se analizaron los datos utilizando regresión logística simple y múltiple mediante el software “R project”. La incidencia de infecciones fue de 11,11%. Diabetes mellitus (D.M.), estadía en CTI e institucionalización fueron factores de riesgo. La cirugía sucia se vinculó en forma liminal con la aparición de ISQ; la cirugía laparoscópica fue un factor protector. El microorganismo predominante fue E. Coli (42,85%), seguido de cultivos polimicrobianos (28,57%), Klebsiella Pneumoniae (14,28%) y Bacilos Gram Negativos no especificados (14,28%). En 36,6% de los pacientes infectados se administraron antibióticos, mientras que el 81,81% requirió drenaje. El tiempo medio entre la cirugía y la infección fue de 15,45 días. Se concluye que estos resultados deben ser considerados para la realización de investigaciones más exhaustivas y elaboración de protocolos pre y perioperatorios.Surgical site infections (SSI) are a common postoperative complication in general surgery, aff ecting patients prognosis and increasing health care costs. There is a lack of national data about this compli cation. The aim of this study was to determine the incidence of type I and II infections according to the Centers for Disease Control and Prevention classifi cation, in patients admitted in Hospital Pasteur who underwent abdominal or peripheral vascular surgery between July and August 2017. The specific objectives were to identify risk factors, determine most prevalent germs, treatment strategies applied (drainage or antibiotics) and delay between surgery and diagnosis of infection. A longitudinal, ob servational and prospective study was performed including 99 patients. Multiple and simple logistic regression models were used to analyze the data with R Project software. The incidence of surgical site infections was 11,11%. Diabetes Mellitus, ICU stay and institutionalization were significant risk factors. Dirty surgical wounds showed a liminal association with SSI. Laparoscopic surgery was a protective factor. E. Coli was the main germ found (42,85%), followed by polymicrobial isolation (28,57%), Klebsiella Pneumoniae (14,28%) and Gram-Negative Bacilli (14,28%). Antibiotics were administered in 36,36% of infected patients, while drainage was required in 81,81%. The mean time between surgery and infection diagnosis was 15,45 days. It is concluded that the results may provide orientation for further investigation and elaboration of pre and perioperative protocols

Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line

Triple-negative breast cancer represents about 15% of all cases of breast cancer, and still represents a therapeutic challenge. 3′-Azido-3′-deoxythymidine (AZT) is a nucleoside reverse transcriptase inhibitor with antitumor activity. Chalcogenides compounds, such as selenium, are very important intermediates applied in organic synthesis. Our objective was to investigate the effect and the underlying cell death mechanisms of AZT and its derivatives, in human breast cancer cell lines. The inhibitory effect of AZT and derivatives (1072, 1073, and 1079) was determined by MTT assay (0.1, 1, 10, 50, and 100 μM for concentrations and times 4, 24, 48, and 72 h) and Live/Dead in tumor cell lines MCF-7, MDA-MB 231 and also in non-tumor cell line CHO. Gene expression profiles related to apoptosis were investigated by qRT-PCR and induction of apoptosis was investigated by flow cytometry. MTT and Live/Dead assays showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 50 and 100 μM in tumor cell lines MCF-7 and MDA-MB 231 while the commercial AZT presented a low antitumoral potential in all strains tested. In flow cytometry analysis we demonstrated that derivatives of AZT induced apoptosis, with an increase in both initial and late stages in both tumor cell lines evaluated, especially in MDA-MB 231. Our data show that the AZT derivative 1072 increased the expression of transcripts of the genes caspase 3 and 8 in MDA-MB 231 cell line when compared to control, suggesting that the extrinsic pathway of apoptosis was activated. In conclusion, derivatives of AZT, especially 1072, induce cytotoxicity in vitro in the triple negative breast cancer cell line through activation of the extrinsic pathway of apoptosis. These compounds containing selenium in its formulation are potential therapeutic agents for breast cancer

Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma

PURPOSE: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. METHODS: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. RESULTS: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. CONCLUSION: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736

Anales del III Congreso Internacional de Vivienda y Ciudad "Debate en torno a la nueva agenda urbana"

Acta de congresoEl III Congreso Internacional de Vivienda y Ciudad “Debates en torno a la NUEVa Agenda Urbana”, ha sido una apuesta de alto compromiso por acercar los debates centrales y urgentes que tensionan el pleno ejercicio del derecho a la ciudad. Para ello las instituciones organizadoras (INVIHAB –Instituto de Investigación de Vivienda y Hábitat y MGyDH-Maestría en Gestión y Desarrollo Habitacional-1), hemos convidado un espacio que se concretó con potencia en un debate transdisciplinario. Convocó a intelectuales de prestigio internacional, investigadores, académicos y gestores estatales, y en una metodología de innovación articuló las voces académicas con las de las organizaciones sociales y/o barriales en el Foro de las Organizaciones Sociales que tuvo su espacio propio para dar voz a quienes están trabajando en los desafíos para garantizar los derechos a la vivienda y los bienes urbanos en nuestras ciudades del Siglo XXI

Src-independent ERK signaling through the rat α3 isoform of Na/K-ATPase

The Na/K-ATPase α1 polypeptide supports both ion-pumping and signaling functions. The Na/K-ATPase α3 polypeptide differs from α1 in both its primary structure and its tissue distribution. The expression of α3 seems particularly important in neurons, and recent clinical evidence supports a unique role of this isoform in normal brain function. The nature of this specific role of α3 has remained elusive, because the ubiquitous presence of α1 has hindered efforts to characterize α3-specific functions in mammalian cell systems. Using Na/K-ATPase α1 knockdown pig kidney cells (PY-17), we generated the first stable mammalian cell line expressing a ouabain-resistant form of rat Na/K-ATPase α3 in the absence of endogenous pig α1 detectable by Western blotting. In these cells, Na/K-ATPase α3 formed a functional ion-pumping enzyme and rescued the expression of Na/K-ATPase β1 and caveolin-1 to levels comparable with those observed in PY-17 cells rescued with a rat Na/K-ATPase α1 (AAC-19). The α3-containing enzymes had lower Na+ affinity and lower ouabain-sensitive transport activity than their α1-containing counterparts under basal conditions, but showed a greater capacity to be activated when intracellular Na+ was increased. In contrast to Na/K-ATPase α1, α3 could not regulate Src. Upon exposure to ouabain, Src activation did not occur, yet ERK was activated through Src-independent pathways involving PI3K and PKC. Hence, α3 expression confers signaling and pumping properties that are clearly distinct from that of cells expressing Na/K-ATPase α1

Ouabain Modulates the Distribution of Connexin 43 in Epithelial Cells

Background/Aims: The fact that ouabain has been identified as an endogenous substance, led us to inquire its physiological role in epithelial cells. Based on previous observations, we hypothesized that it influences processes related to cell contacts. Previously we have shown that nanomolar concentrations of ouabain up-regulate tight junctions, accelerate ciliogenesis, and increase gap junctional intercellular communication (GJIC). Given that silencing assays indicated that connexin 43 (Cnx43) is involved in the GJIC response, in the present work we study whether ouabain affects Cnx43 expression and distribution. Methods: We seeded confluent monolayers of epithelial renal MDCK cells and incubated them with 10 nM ouabain during 1 h. Then we measured, by densitometric analysis of Western blot assays, the amount of Cnx43 in cells and in fractions enriched of plasma membrane. We also studied its localization with immunofluorescence and confocal microscopy. Results: Cnx43 is remarkably displayed, outlining the borders of cells gathered in clusters, randomly scattered throughout the monolayer. Ouabain increases the density of such clusters, as well as the average number of cells per cluster, without inducing the synthesis of new Cnx43. It also promotes relocation towards the membrane, of subunits already available. The fact that such changes are inhibited by PP2 and PD98059 indicates that a signaling pathway, that includes c-Src and ERK1/2, is involved in this response. Conclusion: Ouabain induces the translocation of Cnx43 from the cytoplasm to the plasma membrane. These findings support our hypothesis that one of the physiological roles of ouabain is the modulation of physiological processes that depend on cell to cell contacts

Na+,K+-ATPase is the putative membrane receptor of hormone ouabain

At 10 nM, ouabain elicits changes in cell contacts, which are independent and usually in opposite direction to effects occurring at µM levels, suggesting that these depend on entirely different mechanisms.1 However, this does not discard the possibility that in both instances ouabain would act on the same receptor. We demonstrate that such is the case by comparing the response of wild and ouabain-resistant MDCK cells on a very special type of cell contact, the tight junction (TJ)

Ouabain Increases Gap Junctional Communication in Epithelial Cells

Background/Aims: The finding that endogenous ouabain acts as a hormone prompted efforts to elucidate its physiological function. In previous studies, we have shown that 10 nM ouabain (i.e., a concentration within the physiological range) modulates cell-cell contacts such as tight junctions and apical/basolateral polarity. In this study, we examined whether 10 nM ouabain affects another important cell-cell feature: gap junction communication (GJC). Methods: We employed two different approaches: 1) analysis of the cell-to-cell diffusion of neurobiotin injected into a particular MDCK cell (epithelial cells from dog kidneys) in a confluent monolayer by counting the number of neighboring cells reached by the probe and 2) measurement of the electrical capacitance. Results: We found that 10 nM ouabain increase GJC by 475% within 1 hour. The Na+-K+-ATPase acts as a receptor of ouabain. In previous works we have shown that ouabain activates c-Src and ERK1/2 in 1 hour; in the present study we show that the inhibition of these proteins block the effect of ouabain on GJC. This increase in GJC does not require synthesis of new protein components, because the inhibitors cycloheximide and actinomycin D did not affect this phenomenon. Using silencing assays we also demonstrate that this ouabain-induced enhancement of GJC involves connexins 32 and 43. Conclusion: Ouabain 10 nM increases GJC in MDCK cells