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BACKGROUND: Preservation of organ function and viability is a crucial factor for survival in cardiogenic shock (CS) patients. There is not information enough on cytoprotective substances that may delay organs damage in CS. We hypothesize that cytidine-5-diphosphocholine (CDP-choline) can act as a cytoprotective pharmacological measure that diminishes the target organ damage. So, we aimed to perform a review of works carried out in our institution to evaluate the effect of therapeutic cytoprotection of the CDP-choline. SUMMARY: CDP-choline is an intermediate metabolite in the synthesis of phosphatidylcholine. It is also a useful drug for the treatment of acute ischaemic stroke, traumatic brain injury, and neurodegenerative diseases and has shown an excellent pharmacological safety profile as well. We review our institution's work and described the cytoprotective effects of CDP-choline in experimental models of heart, liver, and kidney acute damage, where this compound was shown to diminish reperfusion-induced ventricular arrhythmias, oxidative stress, apoptotic cell death, inflammation, lactic acid levels and to preserve mitochondrial function. KEY MESSAGES: We propose that additional research is needed to evaluate the impact of cytoprotective therapy adjuvant to mitigate target organ damage in patients with CS.
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Citidina Difosfato Colina , Citoproteção , Estresse Oxidativo , Choque Cardiogênico , Citidina Difosfato Colina/farmacologia , Citidina Difosfato Colina/uso terapêutico , Humanos , Animais , Choque Cardiogênico/tratamento farmacológico , Choque Cardiogênico/metabolismo , Choque Cardiogênico/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologiaRESUMO
Background/Objective: Amyloid beta (ß) -40 levels increase with age and inflammation states and appear to be associated with clinical manifestations of acute coronary syndrome (ACS). We investigated the correlation of Aß peptides with myocardial injury and inflammation biomarkers in patients with or without ST elevation myocardial infarction (STEMI, NSTEMI). Methods: This singe-center, cross-sectional, observational, and correlation study included 65 patients with ACS (n = 34 STEMI, 29 males, age = 58 ± 12 years; n = 31 NSTEMI, 22 males, age = 60 ± 12 years) who were enrolled in the coronary care unit within 12 h after symptom onset from February 2022 to May 2023. Aß peptide levels and biochemical parameters were assessed. Results: NSTEMI patients had a higher prevalence of hypertension (p = 0.039), diabetes (p = 0.043), smoking (p = 0.003), and prior myocardial infarction (p = 0.010) compared to STEMI patients. We observed a higher level of Aß-42 in NSTEMI (p = 0.001) but no difference in Aß-40 levels. We also found a correlation between age and NT-proBNP with both Aß peptides (Aß-40, Aß-42) (p = 0.001, p = 0.002 respectively). Conclusions: Our results show that patients with NSTEMI had a higher prevalence of cardiovascular risk factors (hypertension, diabetes, smoking, and prior myocardial infarction). Considering these results, we propose that Aß-42 can add value to risk stratification in NSTEMI patients.
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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. .
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Camundongos Knockout , Potássio na Dieta , Proteína Quinase 1 Deficiente de Lisina WNK , Animais , Masculino , Camundongos , Rim/metabolismo , Túbulos Renais Distais/metabolismo , Camundongos Endogâmicos C57BL , Fosforilação , Potássio/urina , Potássio/metabolismo , Potássio/sangue , Potássio na Dieta/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Eliminação Renal , Membro 3 da Família 12 de Carreador de Soluto/metabolismo , Membro 3 da Família 12 de Carreador de Soluto/genética , Proteína Quinase 1 Deficiente de Lisina WNK/metabolismo , Proteína Quinase 1 Deficiente de Lisina WNK/genética , FemininoRESUMO
BACKGROUND: Fresh frozen plasma (FFP) administration may increase the risk of nosocomial infections in parallel with the development of immune modulation. This could be driven by soluble mediators, possibly influencing the in vitro activation of human U937 monocyte cells, in a manner dependent on the age of the donors. METHODS: FFP donors were stratified into groups of 19-30 years, 31-40 years or 41-50 years, and U937 cells were cultured with FFP (alone or plus lipopolysaccharide-LPS) for 24 h. Both in FFP and supernatants, TNF, IL-1ß, IL-6, and IL-10 levels were measured by ELISA. Additionally, CD11B, TLR2, and CASP3 gene expression were measured by qtPCR in U937 cells. Total phagocytic activity was also assayed. RESULTS: Elevated IL-10, but low TNF and IL-1ß levels were measured in FFP from individuals aged 19-40 years, whereas in individuals aged 41-50 years FFP were characterized by equalized TNF and IL-10 levels. Elevated IL-6 levels were found in all FFP samples, especially in those from the oldest individuals. FFP stimulation was associated with striking modifications in cytokine production in an age-dependent way. Exposure to FFP attenuates the response to LPS. TLR2 and CD11B expression were enhanced regardless of the age of plasma donors, although CASP3 expression was increased only when FFP from individuals aged 19-40 years were tested. Phagocytosis decreased after exposure to FFP regardless of donor age. CONCLUSION: Our results suggest that soluble mediators in FFP may modulate the functioning of monocytes. Interestingly, this effect appears to be partially influenced by the age of donors.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Plasma/imunologia , Doadores de Sangue , Monócitos/imunologia , Citocinas/imunologia , Células U937/imunologia , Ensaio de Imunoadsorção Enzimática , Monócitos/fisiologia , Fatores Etários , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismoRESUMO
Objective: To describe the design of a protocol of intracoronary autologous transplant of bone marrow-derived stem cells for acute ST-elevation myocardial infarction (STEMI) and to report the safety of the procedure in the first patients included. Methods: The TRACIA study was implemented following predetermined inclusion and exclusion criteria. The protocol includes procedures such as randomization, bone marrow retrieval, stem cells processing, intracoronary infusion of stem cells in the infarct-related artery, pre-and-post MRI, pre-and-post SPECT with radioisotope ventriculography, and clinical follow-up at 6 months. Results: Eight patients with a diagnosis of acute STEMI and duration of symptoms of <24 hours that were perfused successfully through primary percutaneous coronary intervention (PPCI) with a LVEF of <45% were assigned randomly to two groups (n = 4 each). One group treated with stem cells and the other corresponded to the control group. Neither death, re-infarction, no need for revascularization or thrombosis of the stent were observed at follow-up. Conclusions: The initial experience at the Instituto Nacional de Cardiología Ignacio Chávez in the treatment of acute STEMI by means of autologous transplantation of bone marrow-derived stem cells is encouraging. Implementation was possible in the first eight patients with no complications.
Objetivo: Describir el diseño y la implementación de un protocolo de transplante autólogo intracoronario de células madre derivadas de médula ósea en infarto agudo al miocardio con elevación del ST y reportar la seguridad del procedimiento en los primeros pacientes incluidos. Métodos: El estudio TRACIA se implementó con base en criterios de inclusión y exclusión predeterminados. El protocolo incluye la aleatorización, obtención de médula ósea, procesamiento de células madre, infusión intracoronaria de células madre, RM basal y al seguimiento, SPECT con ventriculografía radioisotópica basal y post-procedimiento, y seguimiento clínico a seis meses. Resultados: Ocho pacientes con diagnóstico de infarto agudo del miocardio con elevación del ST y duración de síntomas <24 horas que fueron reperfundidos exitosamente con angioplastia primaria y con fracción de expulsión <45%, fueron aleatorizados a dos grupos; uno de ellos fue tratado con células madre y el otro grupo permaneció como control. No se observó muerte, re-infarto, necesidad de revascularización o trombosis del Stent durante el seguimiento. Conclusiones: La experiencia inicial en el Instituto Nacional de Cardiología Ignacio Chávez en el tratamiento del infarto agudo del miocardio con elevación del ST mediante trasplante autólogo de células madre derivadas de médula ósea, es alentadora. La implementación sin complicaciones fue posible en los primeros ocho pacientes.
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas/métodos , Infarto do Miocárdio/cirurgia , Células da Medula Óssea , Vasos Coronários , Método Simples-Cego , Transplante Autólogo/métodosRESUMO
Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, differents cellular lines such as cardiomyocites, sheletal myoblast, embryonic stem cells and adult mesenchymal stem cells has been used, resulting in an improvement in ventricular function and decrease in amount of infarted tissue. The first three cells line have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, prior to stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation metods in infarted myocardial tissue.
El infarto del miocardio es la principal causa de falla cardiaca y muerte en países industrializados. A la fecha, la cardiomioplastia celular ha emergido como una alternativa en la regeneración de infartos miocárdicos. En modelos animales se han utilizado diferentes líneas celulares como cardiomiocitos fetales, mioblastos de músculo esquelético, células tallo embrionarias y células tallo mesenquimales del adulto, con mejoría en la función ventricular y disminución del área de tejido infartado. Las tres primeras líneas celulares tienen desventajas porque son alogénicas y difíciles de obtener. Las células tallo mesenquimales del adulto son autólogas y se pueden obtener de aspirados de médula ósea o de la circulación periférica previa estimulación con citocinas (G-CSF). La implantación de estas células en seres humanos con infartos del miocardio recientes y antiguos han mostrado mejorías similares a los reportes con modelos animales. Estos hallazgos alientan a continuar la investigación clínica y básica en busca de los mecanismos de diferenciación celular y selección de vías de implantación, en tejido miocárdico infartado.
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Animais , Humanos , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/cirurgia , Diferenciação Celular , Ensaios Clínicos como Assunto , Fator Estimulador de Colônias de Granulócitos/farmacologia , Substâncias de Crescimento/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Modelos Cardiovasculares , Infarto do Miocárdio/patologia , Miócitos Cardíacos/citologia , Células-Tronco/classificação , Transplante AutólogoRESUMO
The aim of this work was to determine whether there is a pre-established basal condition of the endothelial cells isolated from aortic abdominal aneurysm that might augment immune effector mechanisms and thus provide us an insight into the possible causes of aneurysm rupture. Endothelial cells isolated from saccular aortic aneurysm fragments were analyzed by cytofluorometry for the expression of different immune response-related molecules. Our results showed that there is a subpopulation of granule-rich, CD105 positive and von Willebrand antigen negative endothelial cells that have an enhanced basal expression of ICAM-1, and Fas antigen, but, interestingly, no apoptotic bodies were detected. Control endothelial cells derived from healthy areas of the same abdominal aortas did not show such enhanced expression. We conclude that in the endothelium that lines abdominal aorta aneurysms there is, at least, one endothelial cell subpopulation with an apparent inhibition of programmed cell death and in a proinflammatory activation status.
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Humanos , Aneurisma da Aorta Abdominal , Endotélio Vascular , Molécula 1 de Adesão Intercelular , Antígenos CD/imunologia , /imunologia , Antígenos/imunologia , Aorta Abdominal , Aneurisma da Aorta Abdominal , Apoptose , Células Cultivadas , Meios de Cultura , Endotélio Vascular , Citometria de Fluxo , Molécula 1 de Adesão Intercelular/imunologia , Fenótipo , Fator de von WillebrandRESUMO
La presente revisión menciona las características del factor de necrosis tumoral-a y el papel que esta citocina juega en el desarrollo de la lesión ateromatosa. Se describe, al detalle los efectos que tiene esta citocina sobre células endoteliales vasculares en condiciones normales así como de alto riesgo. Se propone que el TNF-a posee un papel central en el desarrollo inicial y en el progreso de la placa ateromatosa debido a que al afectarse los mecanismos de autorregulación de la célula endotelial la concentración de TNF-a se eleva de manera importante a nivel local generando, junto con la presencia local de diversos factores conocidos de riesgo, un microambiente autoperpetuable que favorece el desarrollo de la lesion ateromatosa.
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Arteriosclerose , Citocinas , Fator de Necrose Tumoral alfa , Moléculas de Adesão CelularRESUMO
La hipótesis de la reacción inmmunológica primaria reconoce que el daño inicial en la formación de la placa ateromatosa está mediado por linfocitos T reactivos dirigidos contra proteínas de choque térmico, lipoproteínas, bacterias, virus o antígenos del sistema principal de histocompatibilidad del donador. Una causa frecuente de falla de trasplante cardiaco es la formación de lesiones ateromatosas en los vasos arteriales del órgano trasplantado a pesar de la ausencia de dichas lesiones en el donador, lo cual sugiere que las lesiones obstructivas de novo son consecuencia de una respuesta inmune celular por parte del receptor. En este estudio determinamos el fenotipo y la reactividad de linfocitos T aislados de sangre periférica y de biopsias de endomiocardio y aterectomía de un paciente vivo e inmunosuprimido, sometido a trasplante cardiaco en 1989. Los linfocitos del paciente fueron enfrentados a un grupo de linfocitos B transformados por EBV con diferences alelos HLA. Los resultados demostraron un incremento notable en el porcentaje de linfoncitos CD4+ en la placa ateromatosa y en el endocardio, una importante cantidad de linfocitos T TCRd+ en la placa, y una considerable pérdida de alorreactividad a diferentes antígenos HLA. Estos re sultados sugieren que a pesar de que existen poblaciones linfocíticas adecuadas para generar una respuesta celular, existe un estado de energia a los antígenos HLA, que pudiera ser secundario al prolongado tratamiento inmunosupresor. Creemos que las lesiones obstructivas en este paciente no responden a alorreactividad a los antígenos HLA, sino más bien a un cambio en el tipo de respuesta inmune celular como consecuencia a una exposición crónica a algún antígeno del donador, explicando así la elevada proporción de linfocitos T TCRd+
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Humanos , /imunologia , Antígenos HLA/imunologia , Aterectomia , Aterosclerose/imunologia , Aterosclerose/patologia , Aterosclerose/cirurgia , Linfócitos B/imunologia , Biópsia , Células Cultivadas , Endocárdio/imunologia , Endocárdio/patologia , Imunofluorescência , Imunidade Celular/imunologia , Terapia de Imunossupressão , Miocárdio/imunologia , Miocárdio/patologia , Fenótipo , Linfócitos T/imunologia , Ativação Linfocitária , Transplante de CoraçãoRESUMO
In this study we compared natural vs induced Haemophilus influenzae type b (hib) anti-capsular polyribosylribitol phosphate (PRP) antibody response in a low socioeconomic population. One hundred twenty five 2-month-old children received the complete HbOC vaccine immunization scheme and a boster dose at 15 month of age. One hundred twenty five non-immunized children served as the control group. Serum Hib anti-PRP antibody titers were determuined by ELISA in all children. We found at the end of the primary immunization scheme an antibody concentration of 27.28 µg/ml in the immunized group vs. 7.48 µg/ml in the control group. The antibody response was mainly of the IgG1 class in both groups. After the booster dose the antibody concentration was 30.14 g/ml in the vaccinated group vs. 6.06 µg/ml in the control group (p<0.01). Ninety nine percent of immunized and non-immunized infants had titers greater than 1 µg/ml. These results confirm that immunization with the HbOC vaccine induces an important increase in anti-PRP specific antibody titer, but they also demonstrate that natural exposure induces responses higher than those referred as protective (1 µg/ml)
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Lactente , Humanos , Masculino , Feminino , Ensaio de Imunoadsorção Enzimática , Haemophilus influenzae/patogenicidade , Oligossacarídeos/imunologia , Fosfatos/imunologia , Sorologia , Vacinas Conjugadas/imunologia , Vacinas/imunologiaRESUMO
La producción de interleucina-2 así como la repuesta a la administración exógena de la misma linfocina fue valorada en células periféricas mononucleares de pacientes con tuberculosis pulmonar, antes de iniciar tratmiento y dos meses después de haberlo iniciado. El estudio incluyó a 5 pacientes del sexo femenino con tuberculosis avanzada. Los resultados obtenidos demuestran que las células periféricas mononucleares obtenidas de estas pacientes fueron incapaces de producir cantidades adecuadas de interleucina-2 además de presentar dificuldades para responder adecuadamente a la misma. En dos de los casos estudiados que mostraban mejoría al término de los dos meses de tratamiento se observó que las células periféricas mononucleares tenían tendencia a producir y responder de manera adecuada a la interleucina-2. Es posible que esta observación se relacione con un defecto funcional de las células mononucleares el cual presiste mientras la infección sea activa