Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine with subacute ischemic cardiomyopathy.

BACKGROUND: Growth hormone-releasing hormone agonists (GHRH-As) stimulate cardiac repair following myocardial infarction (MI) in rats through the activation of the GHRH signaling pathway within the heart. We tested the hypothesis that the administration of GHRH-As prevents ventricular remodeling in a swine subacute MI model. METHODS AND RESULTS: Twelve female Yorkshire swine (25 to 30 kg) underwent transient occlusion of the left anterior descending coronary artery (MI). Two weeks post MI, swine were randomized to receive injections of either 30 µg/kg GHRH-A (MR-409) (GHRH-A group; n=6) or vehicle (placebo group; n=6). Cardiac magnetic resonance imaging and pressure-volume loops were obtained at multiple time points. Infarct, border, and remote (noninfarcted) zones were assessed for GHRH receptor by immunohistochemistry. Four weeks of GHRH-A treatment resulted in reduced scar mass (GHRH-A: -21.9 ± 6.42%; P=0.02; placebo: 10.9 ± 5.88%; P=0.25; 2-way ANOVA; P=0.003), and scar size (percentage of left ventricular mass) (GHRH-A: -38.38 ± 4.63; P=0.0002; placebo: -14.56 ± 6.92; P=0.16; 2-way ANOVA; P=0.02). This was accompanied by improved diastolic strain. Unlike in rats, this reduced infarct size in swine was not accompanied by improved cardiac function as measured by serial hemodynamic pressure-volume analysis. GHRH receptors were abundant in cardiac tissue, with a greater density in the border zone of the GHRH-A group compared with the placebo group. CONCLUSIONS: Daily subcutaneous administration of GHRH-A is feasible and safe in a large animal model of subacute ischemic cardiomyopathy. Furthermore, GHRH-A therapy significantly reduced infarct size and improved diastolic strain, suggesting a local activation of the GHRH pathway leading to the reparative process.

Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation.

RATIONALE: The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes. OBJECTIVE: Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire. METHODS AND RESULTS: Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit(+) CSCs increased 20-fold in MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in GATA-4(+) CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit(+) CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I. CONCLUSIONS: MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.

Enfermedad de Creutzfeldt-Jakob en un paciente interpretado como encefalitis por herpes simple / Creutzfeldt-Jakob disease in a patient with possible herpes simplex encephalitis

Se presentó un paciente con una enfermedad de Creutzfeldt-Jakob, al cual se le realizó un diagnóstico presuntivo inicial de encefalitis por herpes simple, que comenzó con trastornos conductuales, agresividad, alucinaciones visuales y pérdida progresiva de la visión, empeoró de forma paulatina, aparecieron movimientos involuntarios inespecíficos y estado de postración, convulsiones técnico-clínicas del hemicuerpo izquierdo, paresia homolateral, poca respuesta al dolor con empobrecimiento de la mímica facial e imposibilidad para localizar el estímulo nociceptivo y discreta rigidez nucal. Se le realizaron estudios microbiológicos para pesquisaje virológico incluido herpes virus, bacterias y hongos, así como análisis citoquímico del líquido cefalorraquídeo y resultaron normales, en el electroencefalograma aparecieron alteraciones que señalaron actividad paroxística asimétrica. El paciente evolucionó tórpidamente y falleció, se presenta el resultado de los estudios anatomopatológicos de la microscopia óptica

This is the case of a patient presenting with Creutzfeldt-Jakob disease with an initial presumptive diagnosis of herpes-simplex encephalitis started with behavioral disorders, aggression, visual hallucinations and a progressive loss of vision, worsening in a gradual way, non-specific unintentional movements and prostration status, left hemi-body tonic-clonic convulsions, homolateral paresis, a low response to pain with a poor facial expression and inability to locate the nociceptive stimulus and a light nuchal stiffness. Microbiologic studies were conducted for a virology screening including herpesvirus, bacteria and fungi, as well as, cytochemistry of cerebrospinal fluid with normal results, in electroencephalogram appeared alterations related to an asymmetric paroxysmal activity. Patient evolved with torpidity and died. Anatomic-pathologic studies result of optical microscopy is showed

Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity.

The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC) remain highly controversial. Here we tested the hypothesis that MSCs regenerate chronically infarcted myocardium through mechanisms comprising long-term engraftment and trilineage differentiation. Twelve weeks after myocardial infarction, female swine received catheter-based transendocardial injections of either placebo (n = 4) or male allogeneic MSCs (200 million; n = 6). Animals underwent serial cardiac magnetic resonance imaging, and in vivo cell fate was determined by co-localization of Y-chromosome (Y(pos)) cells with markers of cardiac, vascular muscle, and endothelial lineages. MSCs engrafted in infarct and border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4, Nkx2.5, and alpha-sarcomeric actin. In addition, Y(pos) MSCs exhibited vascular smooth muscle and endothelial cell differentiation, contributing to large and small vessel formation. Infarct size was reduced from 19.3 +/- 1.7% to 13.9 +/- 2.0% (P < 0.001), and ejection fraction (EF) increased from 35.0 +/- 1.7% to 41.3 +/- 2.7% (P < 0.05) in MSC but not placebo pigs over 12 weeks. This was accompanied by increases in regional contractility and myocardial blood flow (MBF), particularly in the infarct border zone. Importantly, MSC engraftment correlated with functional recovery in contractility (R = 0.85, P < 0.05) and MBF (R = 0.76, P < 0.01). Together these findings demonstrate long-term MSC survival, engraftment, and trilineage differentiation following transplantation into chronically scarred myocardium. MSCs are an adult stem cell with the capacity for cardiomyogenesis and vasculogenesis which contribute, at least in part, to their ability to repair chronically scarred myocardium.

Algunas reflexiones sobre la nutrición en el paciente neurocrítico / Some reflections on the nutrition of the neurocritical patient

La calidad de la nutrición influye de manera activa en el quehacer cotidiano, en sus reacciones emocionales, en su afectividad así como en la génesis del substrato de los aspectos cognoscitivos. No existe a nuestro juicio un criterio uniforme acerca de la nutrición en el paciente neuroquirúrgico ni neurológico complejo. Se realiza un análisis reflexivo sobre aspectos novedosos relativos al cerebro como órgano metabólico y sus relaciones con sustancias neurotransmisoras de origen nutrimental. Se abre una perspectiva del empleo de la Alimentación y la Nutrición como herramientas para modular funciones nerviosas superiores

Carbapenémicos y monobactámicos / Carbapenemics and monobactemics

Se hace una revisión y actualización de los antibióticos del grupo de los carbapenémicos y monobactámicos, se hace énfasis en algunos aspectos como espectro antibacteriano, utilidad clínica, estructura química y otros. Se señalan las diferencias entre los diversos fármacos que conforman estos grupos

Penicilinas / Penicillines

En el presente artículo se aborda el tema de las penicilinas y se hace énfasis en la clasificación, mecanismo de acción, utilidad clínica y principales efectos adversos. Se particulariza en la asociación de penicilinas con inhibidores de las betalactamasas y se muestran las dosis de las penicilinas más usadas