RESUMEN
Mild hyperbaric oxygen therapy (mHBOT) is an adjuvant therapy used in conditions where tissue oxygenation is reduced and is implemented using pressures less than 1.5 ATA and 100% O2 (instead of the classical HBOT at 1.9-3 ATA) which results in cheaper, easier to implement, and equally effective. mHBOT is offered for wellness and beauty and as an anti-aging strategy, in spite of the absence of studies on the cardiovascular system. Consequently, we investigated the impact of mHBOT on the cardiovascular system. Mechanical and energetic parameters of isolated heart submitted to ischemia/reperfusion injury and arterial contractile response from mHBOT-exposed rats were evaluated. In the heart, mHBOT increased pre-ischemic velocity of contraction and ischemic end-diastolic pressure and developed pressure and contractile economy during reperfusion. mHBOT decreased infarct size and increased the plasma nitrite levels. In the artery, mHBOT increased acetylcholine sensitivity. mHBOT protects the heart during ischemia/reperfusion and affects vascular relaxation.
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Oxigenoterapia Hiperbárica , Daño por Reperfusión Miocárdica , Ratas Wistar , Vasodilatación , Animales , Oxigenoterapia Hiperbárica/métodos , Ratas , Masculino , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Corazón/fisiología , Corazón/fisiopatología , Contracción MiocárdicaRESUMEN
Since damage induced by ischemia-reperfusion (I/R) involves alterations in Ca2+ homeostasis and is reduced by ischemic postconditioning (IP) and that CoCl2 can trigger changes resembling the response to a hypoxic event in normoxia and its blockade on Ca2+ current in heart muscle, our aim was to evaluate CoCl2 as an IP therapeutic tool. Mechanic and energetic parameters of isolated and arterially perfused male Wistar rat heart ventricles were simultaneously analyzed in a model of I/R in which 0.23 mmol/L CoCl2 was introduced upon reperfusion and kept or withdrawn after 20 min or introduced after 20 min of reperfusion. The presence of CoCl2 did not affect diastolic pressure but increased post-ischemic contractile recovery, which peaked at 20 min and decreased at the end of reperfusion. This decrease was prevented when CoCl2 was removed at 20 min of reperfusion. Total heat release increased throughout reperfusion, while economy increased between 15 and 25 min. No effect was observed when CoCl2 was introduced at 20 min of reperfusion. In addition, both the area under the contracture curve evoked by 10 mmol/L caffeine-36 mmol/L Na+ and the contracture tension relaxation rate were higher with CoCl2.Furthermore, CoCl2 decreased the number of arrhythmias during reperfusion and the ventricular damaged area. The presence of CoCl2 in reperfusion induces cardioprotection consistent with the improvement in cellular calcium handling. The use of CoCl2 constitutes a potential cardioprotective tool of clinical relevance.
Asunto(s)
Contractura , Enfermedad de la Arteria Coronaria , Poscondicionamiento Isquémico , Daño por Reperfusión Miocárdica , Animales , Cobalto , Isquemia , Masculino , Reperfusión Miocárdica , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Ratas , Ratas WistarRESUMEN
Environmental hexachlorobenzene (HCB) increases blood pressure (BP) in female rats, causing alterations in arterial structure and function. Here we study the role of Angiotensin II receptor type 1 (AT1) in HCB-induced hypertension through the use of AT1 antagonist losartan. HCB-treated male rats showed a 22.7% increase in BP which was prevented by losartan. Losartan blocked HCB-induced changes in arterial morphology (decreased aorta cell number and increased wall thickness). Losartan also prevented HCB-induced alterations in artery relaxation by acetylcholine and nitroprusside but not the reduction in the maximum contraction by phenylephrine. Losartan rescued arterial molecular alterations caused by HCB (i.e. an increase in TGF-ß1 and AT1 expression and a decrease in eNOS expression and nitrite levels) and reduced hydrogen sulfide plasma concentration. In conclusion: in this work we demonstrate that AT1 activity is involved in HCB effects on the vascular system leading to hypertension.
RESUMEN
The prevalence of coronary intimal thickening (IT) was assessed in fetuses and pediatric population. We studied the coronary arteries of 63 hearts obtained from fetuses, infants, children, and adolescents, deceased from noncardiac disease or trauma. Histomorphometric analysis, planimetry, and immunohistochemical studies were conducted. Intimal thickening consisted of proliferation of smooth muscle cells and scarce monocytes embedded in amorphous deposits within the internal elastic membrane (IEM). Intermingled lesions of intimal hyperplasia and parietal nonstenotic plaques were also observed. Intimal thickening was found in 10% of 20 fetuses, in 33.3% of 18 infants, 73.3% of 15 children, and 100% of 10 adolescents. A significant correlation (r = 0.671, P < 0.001) was found between the extent of IT and age. The IEM was duplicated or interrupted in 43% of patients, showing a positive correlation with the degree of IT (P = 0.01). Intimal thickening was predominantly found near bifurcation sites in the left anterior descending coronary artery (55.6%) and in zones free of bifurcation in the right coronary artery (75%). In conclusion, the prevalence and extension of IT lesions are higher at older ages within a young population. Intimal thickening may be regarded as the first event occurring in coronary preatherosclerosis, preceding lipid deposition.
Asunto(s)
Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/patología , Corazón Fetal/patología , Neointima , Placa Aterosclerótica , Túnica Íntima/patología , Adolescente , Factores de Edad , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Edad Gestacional , Humanos , Hiperplasia , Lactante , Recién Nacido , MasculinoAsunto(s)
Hipertensión , Preeclampsia , Femenino , Humanos , Embarazo , Embarazo de Alto Riesgo , Cordón UmbilicalRESUMEN
El uso indebido de drogas se ha convertido en un grave problema a nivel mundial. En los últimos años, en nuestro país se ha incrementado en más del 200% el consumo de pasta base de cocaína (paco). A pesar de que el paco es un producto intermedio en la obtención de cocaína, y que muchos de sus efectos son atribuibles al contenido de esa droga, su consumo produce un cuadro clínico claramente distinto al observado en los consumidores de clorhidrato de cocaína, lo cual puede estar relacionado con su impureza. Sin perjuicio del gran impacto social producido por el consumo de paco, poco se sabe sobre su composición química y menos aún sobre sus efectos crónicos en los distintos órganos ni sobre su fisiopatología. Si bien existe material de autopsia de adictos al paco, los hallazgos están contaminados por la coexistencia en un mismo paciente de múltiples tóxicos. Urge la formación de grupos multidisciplinarios, con moderna tecnología para enfrentar este gravísimo flagelo. (AU)
Drug abuse has become a serious problem worldwide. In recent years, in our country the consumption of cocaine base paste (Paco) has increased by more than 200%. Despite of the fact that Paco is an intermediate product in the manufacture of cocaine, and that many of its effects are attributable to its content, its consumption produces a clearly different clinical picture than that observed in cocaine hydrochloride users, which It may be related to the impurity of this drug. Without prejudice to the great social impact produced by the consumption of this drug, little is known about its chemical composition and even less about its chronic effects on the different organs or its pathophysiology. Although there is an autopsy material for drug addicts, the findings are contaminated by the coexistence of multiple toxins in the same patient. The formation of multidisciplinary groups is urgent, with modern technology to face this very serious scourge. (AU)
Asunto(s)
Humanos , Animales , Cocaína/análogos & derivados , Trastornos Relacionados con Sustancias/complicaciones , Argentina , Cardiopatías/inducido químicamente , Enfermedades Pulmonares/inducido químicamenteRESUMEN
RESUMEN Introducción: En estudios previos, se determinó para una población con agravamiento de la diabetes tipo 2 con obesidad (DBT+Ob) que sufría estrés una prevalencia del polimorfismo de nucleótido único (SNP) rs4704963 (T > C) del gen Early B-Cell Factor 1 (EBF1) del 16,5%. Objetivos: Determinar la prevalencia de este SNP en pacientes con DBT+ Ob que acuden al Hospital Ramos Mejía de la Ciudad Autónoma de Buenos .Aires y establecer si dicho polimorfismo se asocia con el estrés o la ocurrencia de eventos coronarios agudos. Material y métodos: Se llevó a cabo un estudio observacional, prospectivo, sobre prevalencia del polimorfismo en 53 pacientes con DBT+Ob e índice de masa corporal (IMC) entre 28 y 41, atendidos en el citado hospital en un período de 15 meses. A cada paciente se le computó una escala de estrés percibido, además de evaluarlo mediante la escala de acontecimientos vitales estresantes. Para el análisis estadístico, se realizaron las pruebas de Chi cuadrado y se calcularon los odds ratio (OR). Resultados: La población evaluada (53 pacientes) tuvo una media de edad de 60,2 ±9,77 años; 47,2% fueron hombres. De ellos, 8 individuos (15,1%) presentaron el SNP y todos fueron heterocigotas. Quince sujetos (28,3%) tuvieron síndrome isquémico agudo (SIA) y de estos solo uno (6,6%) tenía el SNP No se halló relación estadísticamente significativa entre la presencia del SNP y la aparición de SIA (p = 0,282). Catorce pacientes (26,4%) presentaron estrés crónico moderado o grave, y no hubo relación entre este hallazgo y la presencia del SNP (p = 0,979). Conclusiones: La prevalencia del SNP rs4704963 (T > C) del gen EBF1 en la población de DBT+Ob estudiada fue del 15,1% y no se halló relación estadísticamente significativa del SNP con el estrés ni con el SIA.
ABSTRACT Background: Previous studies established that in a population with exacerbation of type 2 diabetes with obesity (DBT+Ob) suffering from stress, the prevalence of early B-Cell Factor 1 (EBF1) gene rs4704963 single nucleotide polymorphism (SNP) (T>C) is 16.5%. Objectives: The aim of this study was to determine the prevalence of this SNP in patients with DBT+Ob attending Hospital Ramos Mejía of the Autonomous City of Buenos Aires and to ascertain whether this polymorphism is associated with stress or acute coronary events. Methods: An observational, prospective study on the prevalence of rs4704963 SNP was performed in 53 patients with DBT+Ob and body mass index between 28 and 41, seen in Hospital Ramos Mejía for a period of 15 months. Each patient was evaluated with a stressful life events scale and a perceived stress scale. The chisquare test and odds ratio (OR) were used for statistical analysis. Results: A total of 53 patients were included in the study. Mean population age was 60.2±9.77 years and 47.2% were men. Among these patients, 8 (15.1%) presented SNP and all were heterozygous. Fifteen patients (28.3%) had acute ischemic syndrome (AIS), and among these, only one (6.6%) had SNP No statistically significant relationship was found between the presence of SNP and AIS (p=0.282). Fourteen patients (26.4%) presented moderate or severe chronic stress, and there was no relationship between this finding and the presence of SNP (p=0.979). Conclusions: The prevalence of EBF1 gene rs4704963 SNP (T>C) in the DBT+Ob population was 15.1%. No statistically significant association was found between SNP and stress or AIS.
RESUMEN
Perinatal Asphyxia (PA) represents an important cause of severe neurological deficits including delayed mental and motor development, epilepsy, major cognitive deficits and blindness. The interaction between neurons, astrocytes and endothelial cells plays a central role coupling energy supply with changes in neuronal activity. Traditionally, experimental research focused on neurons, whereas astrocytes have been more related to the damage mechanisms of PA. Astrocytes carry out a number of functions that are critical to normal nervous system function, including uptake of neurotransmitters, regulation of pH and ion concentrations, and metabolic support for neurons. In this work, we aim to review metabolic neuron-astrocyte interactions with the purpose of encourage further research in this area in the context of PA, which is highly complex and its mechanisms and pathways have not been fully elucidated to this day.
Asunto(s)
Apolipoproteína B-100/biosíntesis , Enfermedad de la Arteria Coronaria/metabolismo , Receptor alfa de Estrógeno/biosíntesis , Cardiopatías Congénitas/metabolismo , Túnica Íntima/metabolismo , Niño , Preescolar , Enfermedad de la Arteria Coronaria/patología , Femenino , Regulación de la Expresión Génica , Cardiopatías Congénitas/patología , Humanos , Hiperplasia/metabolismo , Hiperplasia/patología , Lactante , Recién Nacido , Masculino , Túnica Íntima/patologíaRESUMEN
Cerebral hypoxia-ischemia damages synaptic proteins, resulting in cytoskeletal alterations, protein aggregation and neuronal death. In the previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia that leads to ubi-protein accumulation. Recently, we also showed that, changes in F-actin organization could be related to early alterations induced by hypoxia in the Central Nervous System. However, little is known about effective treatment to diminish the damage. The main aim of this work is to study the effects of birth hypothermia on the actin cytoskeleton of neostriatal post-synaptic densities (PSD) in 60 days olds rats by immunohistochemistry, photooxidation and western blot. We used 2 different protocols of hypothermia: (a) intrahypoxic hypothermia at 15°C and (b) post-hypoxia hypothermia at 32°C. Consistent with previous data at 30 days, staining with phalloidin-Alexa(488) followed by confocal microscopy analysis showed an increase of F-actin fluorescent staining in the neostriatum of hypoxic animals. Correlative photooxidation electron microscopy confirmed these observations showing an increment in the number of mushroom-shaped F-actin staining spines in neostriatal excitatory synapses in rats subjected to hypoxia. In addition, western blot revealed ß-actin increase in PSDs in hypoxic animals. The optic relative density measurement showed a significant difference between controls and hypoxic animals. When hypoxia was induced under hypothermic conditions, the changes observed in actin cytoskeleton were blocked. Post-hypoxic hypothermia showed similar answer but actin cytoskeleton modifications were not totally reverted as we observed at 15°C. These data suggest that the decrease of the body temperature decreases the actin modifications in dendritic spines preventing the neuronal death.
Asunto(s)
Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Asfixia Neonatal/metabolismo , Espinas Dendríticas/metabolismo , Hipotermia Inducida , Neostriado/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Neuronas GABAérgicas/patología , Densidad Postsináptica/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Congenital heart defects or the process of their repair leads to an increased risk for adult cardiovascular disease compared with the general population. Intimal hyperplasia is a preatherosclerotic lesion that may be produced as a consequence of transforming growth factor ß1 (TGF-ß1) pathway activation. We studied the presence of intimal hyperplasia in arteries from a pediatric population with congenital heart disease (CHD) and TGF-ß1 expression to enlighten its possible role in the genesis of these lesions. METHODS: Coronary arteries from 10 controls and 98 CHD patients (54% cyanotic type, 32% surgically repaired) were stained, and the presence and degree of intimal thickening were analyzed. The expression of TGF-ß1 was studied by immunohistochemistry. RESULTS: The difference between the presence of coronary intimal hyperplasia in patients with cyanotic (35; 66.1%) and noncyanotic CHD (29; 64.3%) was not significant. However, surgically repaired CHD presented a higher rate of coronary intimal hyperplasia (80%) than did the group without surgical intervention (47.3%), P = 0.0002. The immunostaining for TGF-ß1 analyzed in samples of patients with cyanotic and noncyanotic CHD showed no significant differences. However, TGF-ß1 expression was more intense on the intimal layer of patients with surgically repaired CHD than on that of those without surgery (intimal area positive for TGF-ß1, 50.43% vs 15.91%, respectively; Mann-Whitney U test P = 0.0005). CONCLUSION: The high incidence of intimal hyperplasia in patients with surgically repaired CHD is correlated with TGF-ß1 expression and may contribute to the development of atherosclerotic coronary artery disease in CHD patients.
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Vasos Coronarios/patología , Cardiopatías Congénitas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Túnica Íntima/patología , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Vasos Coronarios/metabolismo , Femenino , Cardiopatías Congénitas/cirugía , Humanos , Hiperplasia/etiología , Hiperplasia/metabolismo , Inmunohistoquímica , Lactante , Recién Nacido , Masculino , Prevalencia , Túnica Íntima/metabolismoRESUMEN
Long chain acyl CoA synthetase 4 (Acsl4) is a key enzyme in steroidogenesis. It participates in steroid synthesis through of arachidonic acid release and Steroidogenic Acute Regulatory protein (StAR) induction. Acsl4 prefers arachidonic acid as substrate and acts probably as a homodimer. In steroidogenic cells, it has been demonstrated that Acsl4 is a high turnover protein located mainly in mitochondrial-associated membrane fraction (MAM) bound to other proteins and that it is newly synthesized by hormone stimulation. The synthesis of Acsl4 constitutes an early step in steroidogenesis. In the steroid synthesis process, activation of kinases plays a very important role. For this reason, the aim of this work was to study Acsl4 as a possible phosphoprotein and try to elucidate the role of its phosphorylation. We have determined for the first time that Acsl4 is a phosphoprotein whose phosphorylation is hormone-dependent. We also demonstrated that Acsl4 acts effectively as a dimer and that phosphorylation occurs after dimer formation. Studies in vitro demonstrated that Acsl4 is a substrate of both PKA and PKC and its phosphorylation by these kinases regulates its activity.
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Coenzima A Ligasas/metabolismo , Hormonas Esteroides Gonadales/metabolismo , Mitocondrias/enzimología , Fosfoproteínas/metabolismo , Animales , Línea Celular Tumoral , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Hormonas Esteroides Gonadales/biosíntesis , Ratones , Fosforilación , Proteína Quinasa C/metabolismo , Especificidad por SustratoRESUMEN
The studies presented herein were designed to investigate the effect of mouse epidermal growth factor (mEGF) on arachidonic acid (AA) release in a clonal strain of cultured murine Leydig cells (designed MA-10). In MA-10 cells, mEGF promotes AA release and metabolism to lipoxygenated products to induce the steroidogenic acute regulatory (StAR) protein. However, the mechanism by which mEGF releases AA in these cells is not totally elucidated. We show that mEGF produces an increment in the mitochondrial AA content in a short-term incubation (30 min). This AA is released by the action of a mitochondrial acyl-CoA thioesterase (Acot2), as demonstrated in experiments in which Acot2 was down or overexpressed. This AA in turn regulates the StAR protein expression, indirect evidence of its metabolism to lipoxygenated products. We also show that mEGF induces the expression (mRNA and protein) of Acot2 and an acyl-CoA synthetase that provides the substrate, arachidonyl-CoA, to Acot2. This effect is also observed in another steroidogenic cell line, the adrenocortical Y1 cells. Taken together, our results show that: 1) mEGF can induce the generation of AA in a specific compartment of the cells, i.e. the mitochondria; 2) mEGF can up-regulate acyl-CoA synthetase and Acot2 mRNA and protein levels; and 3) mEGF-stimulated intramitochondrial AA release leads to StAR protein induction.
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Factor de Crecimiento Epidérmico/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Animales , Ácido Araquidónico/metabolismo , Western Blotting , Línea Celular Tumoral , Células Cultivadas , Células Clonales , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Tumor de Células de Leydig/genética , Tumor de Células de Leydig/metabolismo , Tumor de Células de Leydig/patología , Células Intersticiales del Testículo/citología , Células Intersticiales del Testículo/metabolismo , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fosfoproteínas/metabolismo , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tioléster Hidrolasas/genética , Tioléster Hidrolasas/metabolismoRESUMEN
Recent studies demonstrated the importance of the mitochondrial ATP in the regulation of a novel long-chain fatty acid generation/export system in mitochondria of diabetic rat heart. In steroidogenic systems, mitochondrial ATP and intramitochondrial arachidonic acid (AA) generation are important for steroidogenesis. Here, we report that mitochondrial ATP is necessary for the generation and export of AA, steroid production and steroidogenic acute regulatory protein induction supported by cyclic 3'-5'-adenosine monophosphate in steroidogenic cells. These results demonstrate that ATP depletion affects AA export and provide new evidence of the existence of the fatty acid generation and export system involved in mitochondrial cholesterol transport.
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Ácido Araquidónico/metabolismo , Colesterol/metabolismo , Ácidos Grasos/metabolismo , Células Intersticiales del Testículo/metabolismo , Mitocondrias/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Transporte Biológico Activo/fisiología , AMP Cíclico/metabolismo , Células Intersticiales del Testículo/citología , Masculino , Miocardio/metabolismo , Fosfoproteínas/metabolismo , RatasRESUMEN
We have investigated the direct effect of arachidonic acid on cholesterol transport in intact cells or isolated mitochondria from steroidogenic cells and the effect of cyclic-AMP on the specific release of this fatty acid inside the mitochondria. We show for the first time that cyclic-AMP can regulate the release of arachidonic acid in a specialized compartment of MA-10 Leydig cells, e.g. the mitochondria, and that the fatty acid induces cholesterol transport through a mechanism different from the classical pathway. Arachidonic acid and arachidonoyl-CoA can stimulate cholesterol transport in isolated mitochondria from nonstimulated cells. The effect of arachidonoyl-CoA is inhibited by the reduction in the expression or in the activity of a mitochondrial thioesterase that uses arachidonoyl-CoA as a substrate to release arachidonic acid. cAMP-induced arachidonic acid accumulation into the mitochondria is also reduced when the mitochondrial thioesterase activity or expression is blocked. This new feature in the regulation of cholesterol transport by arachidonic acid and the release of arachidonic acid in specialized compartment of the cells could offer novel means for understanding the regulation of steroid synthesis but also would be important in other situations such as neuropathological disorders or oncology disorders, where cholesterol transport plays an important role.
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Ácido Araquidónico/metabolismo , Colesterol/metabolismo , AMP Cíclico/fisiología , Células Intersticiales del Testículo/metabolismo , Mitocondrias/metabolismo , Animales , Transporte Biológico , Ácidos Grasos/fisiología , Masculino , Ratones , Mitocondrias/fisiología , Orgánulos/metabolismo , Progesterona/biosíntesis , Transfección , Células Tumorales CultivadasRESUMEN
The activation of the rate-limiting step in steroid biosynthesis, that is the transport of cholesterol into the mitochondria, is dependent on PKA-mediated events triggered by hormones like ACTH and LH. Two of such events are the protein tyrosine dephosphorylation mediated by protein tyrosine phosphatases (PTPs) and the release of arachidonic acid (AA) mediated by two enzymes, ACS4 (acyl-CoA synthetase 4) and Acot2 (mitochondrial thioesterase). ACTH and LH regulate the activity of PTPs and Acot2 and promote the induction of ACS4. Here we analyzed the involvement of PTPs on the expression of ACS4. We found that two PTP inhibitors, acting through different mechanisms, are both able to abrogate the hormonal effect on ACS4 induction. PTP inhibitors also reduce the effect of cAMP on steroidogenesis and on the level of StAR protein, which facilitates the access of cholesterol into the mitochondria. Moreover, our results indicate that exogenous AA is able to overcome the inhibition produced by PTP inhibitors on StAR protein level and steroidogenesis. Then, here we describe a link between PTP activity and AA release, since ACS4 induction is under the control of PTP activity, being a key event for AA release, StAR induction and steroidogenesis.