RESUMEN

Fatty and hydroxycarboxylic acids are one of the main intermediates of energy metabolism in ruminants and critical in the milk production of cattle. High production demands on a dairy farm can induce nutritional imbalances and metabolism disorders, which have been widely associated with the onset of sterile inflammatory processes and increased susceptibility to infections. The literature suggests that short-chain fatty acids (SCFA), long-chain fatty acids (LCFA) and hydroxycarboxylic acids are relevant modulators of the host innate inflammatory response. For instance, increased SCFA and lactate levels are associated with subacute ruminal acidosis (SARA) and the activation of pro-inflammatory processes mediated by diverse leukocyte and vascular endothelial cells. As such, free LCFA and the ketone body ß-hydroxybutyrate are significantly increased in the plasma 1-2 weeks postpartum, coinciding with the time period in which cows are more susceptible to acquiring infectious diseases that the host innate immune system should actively oppose. Today, many of these pro-inflammatory responses can be related to the activation of specific G protein-coupled receptors, including GPR41/FFA3 and GPR43/FFA2 for SCFA; GPR40/FFA1 and GPR120/FFA4 for LCFA, GPR109A/HCA2 for ketone body ß-hydroxybutyrate, and GPR81/HCA1 for lactate, all expressed in different bovine tissues. The activation of these receptors modulates the release of intracellular granules [e.g., metalloproteinase-9 (MMP-9) and lactoferrin], radical oxygen species (ROS) production, chemotaxis, and the production of relevant pro-inflammatory mediators. The article aimed to review the role of natural ligands and receptors and the resulting impact on the host innate immune reaction of cattle and, further, to address the most recent evidence supporting a potential connection to metabolic disorders.

Asunto(s)

Acidosis/veterinaria , Ácidos Grasos no Esterificados/inmunología , Inmunidad Innata , Enfermedades Metabólicas/veterinaria , Receptores Acoplados a Proteínas G/inmunología , Acidosis/metabolismo , Animales , Bovinos/inmunología , Bovinos/metabolismo , Metabolismo Energético , Ácidos Grasos Volátiles/inmunología , Femenino , Inflamación , Lactatos/metabolismo , Enfermedades Metabólicas/inmunología , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Cytoplasmic pH homeostasis is required for an appropriate response in polymorphonuclear neutrophils (PMNs). In these cells, chemotaxis and reactive oxygen species (ROS) production are reduced by the use of Na+/H+ exchanger (NHE-1) inhibitors, but these results are mainly obtained using amiloride, a non-selective NHE-1 inhibitor. In bovine PMNs, the role of NHE-1 in functional responses has not been confirmed yet. The aim of this study was to determine the role of NHE-1 using amiloride and zoniporide in pH regulation, ROS production, matrix metalloproteinase 9 (MMP-9) release and calcium flux in bovine PMNs induced by the platelet activation factor (PAF), additionally we evaluated the presence of NHE-1 and NHE-2 mRNA Our data show the presence only of NHE-1 but not NHE-2 in bovine PMNs. Amiloride or zoniporide inhibited the intracellular alkalization induced by PAF without affecting calcium flux. Amiloride diminished ROS production and MMP-9 release, while zoniporide enhanced ROS production without change the MMP-9 release induced by PAF. Our work led us to conclude that changes in intracellular pH induced by PAF are regulated by NHE-1 in bovine neutrophils, but the effects of amiloride on ROS production and MMP-9 release induced by PAF are not NHE-1 dependent.

Asunto(s)

Amilorida/farmacología , Metaloproteinasa 9 de la Matriz/metabolismo , Neutrófilos/efectos de los fármacos , Factor de Activación Plaquetaria/antagonistas & inhibidores , Estallido Respiratorio/efectos de los fármacos , Intercambiador 1 de Sodio-Hidrógeno/antagonistas & inhibidores , Animales , Calcio/metabolismo , Bovinos , Femenino , Guanidinas/farmacología , Neutrófilos/enzimología , Neutrófilos/metabolismo , Factor de Activación Plaquetaria/farmacología , Reacción en Cadena de la Polimerasa/veterinaria , Pirazoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Intercambiador 1 de Sodio-Hidrógeno/metabolismo

RESUMEN

Increased short-chain fatty acid (SCFA) production is associated with subacute ruminal acidosis (SARA) and activation of inflammatory processes. In humans and rodents, SCFAs modulate inflammatory responses in the gut via free fatty acid receptor 2 (FFA2). In bovines, butyric acid is one of the most potent FFA2 agonists. Its expression in bovine neutrophils has recently been demonstrated, suggesting a role in innate immune response in cattle. This study aimed to evaluate if butyric acid modulates oxidative and non-oxidative functions or if it can potentiate other inflammatory mediators in bovine neutrophils. Our results showed that butyric acid can activate bovine neutrophils, inducing calcium (Ca(2+)) influx and mitogen-activated protein kinase (MAPK) phosphorylation, two second messengers involved in FFA2 activation. Ca(2+) influx induced by butyric acid was dependent on the extracellular and intracellular Ca(2+) source and phospholipase C (PLC) activation. Butyric acid alone had no significant effect on reactive oxygen species (ROS) production and chemotaxis; however, a priming effect on platelet-activating factor (PAF), a potent inflammatory mediator, was observed. Butyric acid increased CD63 expression and induced the release of neutrophil granule markers matrix metalloproteinase-9 (MMP-9) and lactoferrin. Finally, we observed that butyric acid induced neutrophil extracellular trap (NET) formation without affecting cellular viability. These findings suggest that butyric acid, a component of the ruminal fermentative process, can modulate the innate immune response of ruminants.

Asunto(s)

Ácido Butírico/farmacología , Bovinos/inmunología , Neutrófilos/efectos de los fármacos , Factor de Activación Plaquetaria/farmacología , Animales , Calcio/metabolismo , Quimiotaxis de Leucocito , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Trampas Extracelulares/efectos de los fármacos , Ácidos Grasos no Esterificados/metabolismo , Neutrófilos/inmunología , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo

RESUMEN

AIM: The impetus of our study was to investigate the effects of a nutritional supplement Delphinol®, an extract of maqui berries (Aristotelia chilensis) standardised to ≥25% delphinidins and ≥35% total anthocyanins, on postprandial blood glucose and insulin levels and identify the physiologic mechanism involved. METHODS: Postprandial blood glucose and insulin were investigated in double-blind, placebo-controlled, cross-over fashion in ten volunteers with moderate glucose intolerance. Longer term effects on blood sugar levels were investigated in streptozotocin-diabetic rats over a four months period. Effects of maqui berry delphinidins on sodium-glucose symport were examined in rodent jejenum of the small intestine. RESULTS: Delphinol® intake prior to rice consumption statistical significantly lowered post prandial blood glucose and insulin as compared to placebo. We identified an inhibition of Na+-dependant glucose transport by delphinidin, the principal polyphenol to which Delphinol® is standardised. In a diabetic rat model the daily oral application of Delphinol® over a period of four months significantly lowered fasting blood glucose levels and reached values indistinguishable from healthy non-diabetic rats. CONCLUSION: Our results suggest a potential use of Delphinol® for naturally controlling post-prandial blood glucose owed to inhibition of sodium glucose co-transporter in small intestine.

Asunto(s)

Glucemia/efectos de los fármacos , Elaeocarpaceae , Intolerancia a la Glucosa/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Yeyuno/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Proteínas de Transporte de Sodio-Glucosa/antagonistas & inhibidores , Animales , Antocianinas/análisis , Antocianinas/uso terapéutico , Biomarcadores/sangre , Glucemia/metabolismo , Chile , Estudios Cruzados , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/diagnóstico , Diabetes Mellitus Experimental/tratamiento farmacológico , Método Doble Ciego , Elaeocarpaceae/química , Femenino , Frutas , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/diagnóstico , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/química , Insulina/sangre , Yeyuno/metabolismo , Masculino , Ratones Endogámicos C57BL , Fitoterapia , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Plantas Medicinales , Periodo Posprandial , Ratas , Ratas Sprague-Dawley , Proteínas de Transporte de Sodio-Glucosa/metabolismo , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

Short-chain fatty acids (SCFA) are produced by bacterial fermentation in the rumen of cattle and are the primary energy source in ruminants. Propionate is one of the main SCFA and it can exert multiple effects on the inflammatory process and neutrophil function via calcium (Ca(2+)) release, reactive oxygen species, and intracellular pH changes. However, currently no evidence has shown whether propionate can induce granule release from bovine neutrophils. The purpose of this study was to analyze the effect of propionate on granule release and to evaluate the expression of two G-protein coupled receptors-GPR41 and GPR43-that are activated by propionate. Neutrophil degranulation was assessed by quantifying the release of the neutrophil enzymes myeloperoxidase (MPO), lactoferrin, and matrix metalloprotease-9 (MMP-9) as markers of azurophil, specific granules, and gelatinase granules, respectively. Isolated bovine neutrophils were treated with millimolar concentrations of propionate (0.3, 3 and 30mM), and the cell-free supernatants were recovered. The stimulation of neutrophils with 0.3mM propionate induced the release of lactoferrin and MMP-9 as revealed by ELISA and gelatin zymography, respectively. Propionate at 30mM induced the release of MPO as demonstrated using an enzymatic assay. The role of intracellular Ca(2+) influx and the signaling pathways that may regulate the propionate effect on granules release were also determined. Reverse transcription (RT)-PCR and real-time PCR were performed to analyze the expression of GPR41 and GPR43 mRNA in bovine neutrophils. Both mRNA were detected, whereas the expression of GPR43 was higher than that of GPR41, and the synthetic agonists for this receptor, phenylacetamides 1 and 2, caused an increase in intracellular Ca(2+), lactoferrin, and MMP-9 release. These results support that propionate-induced granule release is mediated by intracellular Ca(2+) influx and activation of extracellular signal-regulated kinase ERK 1/2. We also propose a potential role of GPR43 in propionate-induced granule release from bovine neutrophils that may be involved in regulatory effects of propionate in the innate immune response in cattle.

Asunto(s)

Bovinos/inmunología , Bovinos/fisiología , Degranulación de la Célula/efectos de los fármacos , Neutrófilos/fisiología , Propionatos/farmacología , Animales , Calcio/sangre , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Expresión Génica/efectos de los fármacos , Lactoferrina/sangre , Metaloproteinasa 9 de la Matriz/sangre , Neutrófilos/química , Peroxidasa/sangre , ARN Mensajero/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Receptores Acoplados a Proteínas G/efectos de los fármacos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/fisiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología

RESUMEN

2-Aminoethoxydiphenyl borate (2-APB) interferes with the Ca(2+) influx and reduces the ROS production, gelatinase secretion and CD11b expression in bovine neutrophils. Moreover, it has been suggested that inhibition of the Ca(2+) channel involved in the store operated Ca(2+) entry (SOCE) is a potential target for the development of new anti-inflammatory drugs in cattle, however it is unknown whether 2-APB affects neutrophil functions associated with the innate immune response. This study describes the effect of 2-APB, a putative SOCE inhibitor, on alkaline phosphatase activity a marker of secretory vesicles, CD63 a marker for azurophil granules, F-actin polymerization and in vitro chemotaxis in bovine neutrophils stimulated with platelet-activating factor (PAF). Also, we evaluated the effect of 2-APB in the phagocytic activity against Escherichia coli and Staphylococcus aureus bioparticles. We observed that doses of 2-APB ≥10 µM significantly reduced alkaline phosphatase activity and in vitro chemotaxis, whereas concentrations of 2-APB ≥50 µM reduced CD63 expression and F-actin polymerization. Finally, we observed that 2-APB did not affect the phagocytic activity in neutrophils incubated with E. coli and S. aureus bioparticles. We concluded that inhibition of Ca(2+) influx could be a useful strategy to reduce inflammatory process in cattle.

Asunto(s)

Actinas/efectos de los fármacos , Fosfatasa Alcalina/antagonistas & inhibidores , Compuestos de Boro/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Quimiotaxis/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Tetraspanina 30/biosíntesis , Actinas/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Calcio/metabolismo , Bovinos , Quimiotaxis/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Citometría de Flujo/veterinaria , Neutrófilos/enzimología , Neutrófilos/metabolismo , Neutrófilos/fisiología , Fagocitosis/fisiología , Factor de Activación Plaquetaria/farmacología , Polimerizacion/efectos de los fármacos

RESUMEN

This study describes the effect of 2-aminoethoxydiphenyl borate (2-APB), a putative store-operated calcium (Ca(2+)) entry (SOCE) inhibitor, on reactive oxygen species (ROS) production, matrix metalloproteinase 9 (MMP-9) release, CD11b and l-selectin (CD62L) expression, size changes and apoptosis in bovine neutrophils stimulated with platelet-activating factor (PAF). It was observed that doses ⩾1µM 2-APB significantly reduced ROS production, whereas 50 and 100µM 2-APB reduced MMP-9 release induced by PAF. Moreover, concentrations ⩾10µM 2-APB reduced CD11b expression and increased l-selectin shedding. PAF induced size changes in neutrophils, and this effect was inhibited by 2-APB. From this work it is possible to conclude that 2-APB at concentrations that inhibit SOCE responses was able to inhibit ROS and MMP-9 release and CD11b expression, and increase l-selectin shedding, suggesting that the Ca(2+) channel involved in SOCE is a potential target for the development of new anti-inflammatory drugs in cattle.

Asunto(s)

Compuestos de Boro/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Bovinos/metabolismo , Neutrófilos/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Compuestos de Boro/administración & dosificación , Antígeno CD11b/metabolismo , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/administración & dosificación , Señalización del Calcio/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida/veterinaria , Citometría de Flujo/veterinaria , Selectina L/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Neutrófilos/metabolismo , Factor de Activación Plaquetaria/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estallido Respiratorio/efectos de los fármacos

RESUMEN

D-lactic acidosis occurs in ruminants, such as cattle, with acute ruminal acidosis caused by ingestion of excessive amounts of highly fermentable carbohydrates. Affected animals show clinical signs similar to those of septic shock, as well as acute laminitis and liver abscesses. It has been proposed that the inflammatory response and susceptibility to infection could both be caused by the inhibition of phagocytic mechanisms. To determine the effects of d-lactic acid on bovine neutrophil functions, we pretreated cells with different concentrations of D-lactic acid and measured intracellular pH using 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and calcium flux using FLUO-3 AM-loaded neutrophils. Reactive oxygen species (ROS) production was measured using a luminol chemiluminescence assay, and MMP-9/gelatinase-B granule release was measured by zymography. CD11b and CD62L/l-selectin expression, changes in cell shape, superoxide anion production, phagocytosis of Escherichia coli-Texas red bioparticles, and apoptosis were all measured using flow cytometry. Our results demonstrated that D-lactic acid reduced ROS production, CD11b upregulation and MMP-9 release in bovine neutrophils treated with 100 nM platelet-activating factor (PAF). D-lactic acid induced MMP-9 release and, at higher concentrations, upregulated CD11b expression, decrease L-selectin expression, and induces late apoptosis. We concluded that D-lactic acid can interfere with neutrophil functions induced by PAF, leading to reduced innate immune responses during bacterial infections. Moreover, the increase of MMP-9 release and CD11b expression induced by 10mM D-lactic acid could promote an nonspecific neutrophil-dependent inflammatory reaction in cattle with acute ruminal acidosis.

Asunto(s)

Ácido Láctico/farmacología , Neutrófilos/efectos de los fármacos , Factor de Activación Plaquetaria/antagonistas & inhibidores , Acidosis Láctica/metabolismo , Acidosis Láctica/veterinaria , Animales , Antígeno CD11b/análisis , Calcio/análisis , Bovinos , Enfermedades de los Bovinos/metabolismo , Femenino , Citometría de Flujo/veterinaria , Concentración de Iones de Hidrógeno , Selectina L/análisis , Mediciones Luminiscentes/veterinaria , Metaloproteinasa 9 de la Matriz/metabolismo , Neutrófilos/química , Fagocitosis/efectos de los fármacos , Factor de Activación Plaquetaria/farmacología , Especies Reactivas de Oxígeno/análisis

RESUMEN

Neutrophils are the first line of defense against pathogens in bovines; however, they are also one of the most aggressive cells during the inflammatory process, causing injury in surrounding tissues. At present, anti-inflammatory drugs are limited in acute diseases, such as pneumonia, mastitis and endometritis, because neutrophils are mostly insensitive. One of the earliest events during neutrophil activation is the increase in intracellular calcium concentration. The calcium movement is attributed to the release from intracellular stores and influx through the calcium channels in the plasma membrane, a process called store operated calcium entry (SOCE). Recently, several calcium influx blockers have been shown to have strong effects on bovine neutrophils, and this suggests that the manipulation of this pathway can be useful in the control of neutrophil functions during acute inflammatory processes. In this paper, we will review the role of calcium influx as a potential anti-inflammatory target and summarize the most recent evidences for this in bovine neutrophils.

Asunto(s)

Señalización del Calcio/efectos de los fármacos , Enfermedades de los Bovinos/tratamiento farmacológico , Enfermedades de los Bovinos/metabolismo , Inflamación/veterinaria , Animales , Bovinos , Degranulación de la Célula/efectos de los fármacos , Femenino , Concentración de Iones de Hidrógeno , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Modelos Biológicos , Activación Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Estallido Respiratorio/efectos de los fármacos

RESUMEN

The importance of neutrophils in human disease such as rheumatoid arthritis, asthma, adult respiratory distress syndrome, and COPD has prompted the search for drugs capable to slow down neutrophil-dependent inflammation, without interference with innate immune responses. In this review, we summarize new potential drugs targets against neutrophils mediated inflammatory responses.

Asunto(s)

Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , Neutrófilos/efectos de los fármacos , Neutrófilos/patología , Animales , Humanos , Inmunidad Innata/efectos de los fármacos

RESUMEN

Propionate is a short-chain fatty acid produced under normal physiological conditions in the rumen of cattle. It is also involved in the inflammatory process and neutrophil function via calcium release, reactive oxygen species and intracellular pH (pH(i)) changes. This study examined the effect of propionate on the pH(i) of bovine neutrophils; specifically if pH(i) changes are controlled by calcium flux, and the mitogen-activated protein kinase (MAPK) pathway. Propionate caused rapid intracellular acidification and sustained alkalinization in bovine neutrophils loaded with 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM), a fluorescent indicator of pH(i). The acidification phase seems to be controlled by intracellular calcium release and p38 MAPK pathway. The pH recovery phenomenon was mediated by an amiloride-sensitive Na+/H+ exchanger and H+ channel, and was inhibited by UO126 (an ERK1/2 MAPK phosphorylation inhibitor), Gö6850 (a PKC inhibitor) and calcium chelating. Ionomycin, a calcium ionophore, induced intracellular acidification and sustained alkalinization. The intracellular acidification was strongly inhibited by BAPTA-AM (an intracellular calcium chelator) and SB203580 (a p38 MAPK inhibitor). In addition, the intracellular alkalinization was reduced by EGTA (a calcium chelator), UO126, LY294002 (a PI3K inhibitor) and Gö6850. Propionate did not increase superoxide production, however it reduced the superoxide production induced by platelet-activating factor (PAF), and increased the release of superoxide induced by ionomycin. Our results suggest that propionate-induced intracellular acidification is mediated by intracellular calcium release and p38 MAPK activation, and that pH recovery is controlled via ERK1/2 MAPK, PKC and calcium entry in bovine neutrophils.

Asunto(s)

Calcio/sangre , Bovinos/sangre , Quinasas MAP Reguladas por Señal Extracelular/sangre , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Propionatos/farmacología , Proteína Quinasa C/sangre , Animales , Butadienos/farmacología , Quelantes/farmacología , Cromonas/farmacología , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Femenino , Concentración de Iones de Hidrógeno , Imidazoles/farmacología , Indoles/farmacología , Ionomicina/farmacología , Maleimidas/farmacología , Morfolinas/farmacología , Neutrófilos/enzimología , Nitrilos/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Intercambiadores de Sodio-Hidrógeno/metabolismo , Espectrometría de Fluorescencia/veterinaria , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/sangre

RESUMEN

PURPOSE: To evaluate selective effects of ultraviolet (UV) irradiation on spontaneous and induced apoptosis in freshly extracted mice thymocytes. MATERIALS AND METHODS: Cells were exposed to UV radiation with emission peaks of 365 nm (UVA) exposures of 1620-10200 J m(-2), of 312 nm (UVB) exposures of 34-1620 J m(-2) or of 254 nm (UVC) exposures of 1.5-1620 J m(-2), and incubated for 5.5 h with or without hydrocortisone, phorbol-12-myristate-13-acetate or anti-Fas antibody. Additionally, cells were irradiated with gamma-rays (5 Gy) before UVB exposure (408 J m(-2)) at different times. Apoptosis was quantified by DNA fragmentation. RESULTS: Up to an irradiation of 5000 J m(-2), UVA exposure did not show any effect on thymocyte apoptosis, while at 10200 J m(-2) irradiation, considerable DNA fragmentation was observed. In contrast, UVB and UVC irradiation clearly inhibited natural and cortisone-induced apoptosis. Moreover, UVB inhibited apoptosis triggered by phorbol-12-myristate-13-acetate and gamma-irradiation, but not by anti-Fas antibody. CONCLUSIONS: The response of mouse thymocytes in culture to UV irradiation strongly depends on the wavelength used. It is suggested that either a survival or an apoptotic pathway occurs depending on the physiological state of the cell, spectral composition of the UV light and cell type. The possible involvement of extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase in the apoptotic pathway is discussed.

Asunto(s)

Apoptosis/efectos de la radiación , Linfocitos T/citología , Linfocitos T/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Animales , Anticuerpos/farmacología , Apoptosis/efectos de los fármacos , Activación Enzimática/efectos de la radiación , Rayos gamma/efectos adversos , Hidrocortisona/farmacología , Técnicas In Vitro , Sistema de Señalización de MAP Quinasas/efectos de la radiación , Masculino , Ratones , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Receptor fas/metabolismo

Asunto(s)

Amiloidosis/complicaciones , Cardiomiopatías/complicaciones , Paraproteinemias/complicaciones , Amiloidosis/diagnóstico , Amiloidosis/patología , Proteína de Bence Jones/análisis , Cardiomiopatías/diagnóstico , Cardiomiopatías/patología , Electrocardiografía , Femenino , Humanos , Cadenas kappa de Inmunoglobulina/análisis , Persona de Mediana Edad

Asunto(s)

Bovinos , Acetato de Clormadinona/farmacología , Sincronización del Estro/efectos de los fármacos , Animales , Cruzamiento , Acetato de Clormadinona/administración & dosificación , Formas de Dosificación , Femenino , Lactancia , México , Inducción de la Ovulación , Embarazo , Estaciones del Año

RESUMEN

Severe hypoglycemia may be present in seriously ill patients; if it is not corrected opportunely a series of neuroendocrinal mechanisms take place aimed at correcting metabolic alterations. These mechanisms can produce hemodynamic alterations as well. Nine mongrel dogs were studied with continuous registration of: blood pressure, central venous pressure, cardiac frequency, respiratory frequency, electrocardiogram and first derivative (Dp/Dt). Six dogs received crystalline (fast acting) insuline intravenously (group 1). After hemodynamic changes were registered hypoglycemia was corrected with 50 per cent glucose solution. Complementary insuline doses were administered to three dogs (group 2); in this group hypoglycemia was not corrected. In group 1 during hypoglycemia there was an increase in blood pressure, central venous pressure, cardiac frequency, respiratory frequency and Dp/Dt, and changes in QT and T wave on the EKG; these changes were partially reversible after hypoglycemia was corrected. The above mentioned alterations persisted in group 2, breathing became irregular irregular and respiratory arrest supervened. It can be inferred that the hemodynamic response to hypoglycemia is predominantly adrenergic. The role of catecolamines, glucocorticoides, glucagon, insuline, cyclic AMP in metabolic and hemodynamic alterations consecutive to hypoglycemia are discussed.

Asunto(s)

Hipoglucemia/fisiopatología , Animales , Perros , Hemodinámica , Choque/etiología , Choque/fisiopatología