RESUMEN
Skeletal muscle, as a producer of glutamine, is important for lymphocytes, monocytes and macrophages. Exercise-induced muscle damage could burden the immune system by concurrently eliciting a local inflammatory response and decreasing glutamine availability. The aim of this study was to determine whether blood leukocyte and glutamine concentrations were affected in individuals with high serum creatine kinase (CK) activity (indirect indication of muscle damage) compared to those with no change in CK. Twelve females performed maximal eccentric resistance exercise using one arm and one leg. Blood leukocyte subsets and glutamine were measured at 24 and 0 h pre-exercise, and post-exercise at intervals up to 9 d post-exercise. Eleven subjects were placed in High (n = 6) and Low CK (n = 5) groups. Lymphocytes, (total, natural killer, and T), monocytes, and granulocytes did not change significantly in either group, at any time. Whole blood glutamine concentration decreased (p < 0.05) from 437 microM pre-exercise to 332 microM 3 d post-exercise in both groups. The decrease in glutamine suggests that the metabolism of the muscle may be affected by this exercise, however, the occurrence of this decrease in both groups suggests that this change was not a response to muscle damage.
Asunto(s)
Ejercicio Físico/fisiología , Glutamina/sangre , Leucocitos/fisiología , Músculo Esquelético/lesiones , Adulto , Creatina Quinasa/metabolismo , Femenino , Humanos , Inflamación , Músculo Esquelético/fisiología , Soporte de PesoRESUMEN
Little is known about the role of the kidney in plasma glucose regulation during hyperglycemia. We studied 12 overnight-fasted conscious dogs after either intrarenal (IR, n = 6) or peripheral (PH, n = 6) dextrose infusion to maintain hyperglycemia without glycosuria. Systemic and renal glucose kinetics were measured with [6-3H]glucose, lactate balance was measured by arteriovenous difference, and glycogen content was assayed in the kidneys. Plasma glucose (approximately 5.5 vs. approximately 6.3 mM), insulin (approximately 70 vs. approximately 110 pM), and glucose appearance (approximately 14 vs. approximately 16 mumol.kg-1.min-1 increased comparably in both groups (P < 0.05). In IR, fractional extraction of glucose (FEGlc) increased from 4.1 +/- 0.2 to 16.1 +/- 0.5% (P < 0.001) and lactate balance reversed to renal output (+1.3 +/- 0.2 vs. -0.9 +/- 0.2 mumol.kg-1.min-1, P < 0.01). Glycogen content was twofold higher in the left (127 +/- 33 micrograms/g tissue) than in the right kidney (56 +/- 11 micrograms/g tissue, P < 0.01). In PH, FEGlc decreased from 4.9 +/- 0.6 to 2.2 +/- 0.3% (P < 0.05), renal glucose utilization did not change (approximately 1.3 mumol.kg-1.min-1); and glycogen content was equal in both kidneys (approximately 45 micrograms/g tissue). We conclude that, although the kidney plays a minor role in plasma glucose disposal in physiological hyperglycemia, increased glucose uptake, glycogen storage, and lactate formation precede glycosuria and may represent important mechanisms by which the kidney contributes to normalization of plasma glucose in diabetes.
Asunto(s)
Glucemia/metabolismo , Hiperglucemia/sangre , Riñón/fisiología , Animales , Arterias , Perros , Glucosa/metabolismo , Glucógeno/metabolismo , Hiperglucemia/inducido químicamente , Riñón/metabolismo , Ácido Láctico/sangre , Masculino , Circulación RenalRESUMEN
The endogenous opiate alkaloid content in tissues from fed, 24 h and 48 h fasted rats was determined. Plasma morphine and codeine concentrations did not change in response to fasting. Morphine levels in the spleen increased 3-fold after 24 h of fasting and were lower than fed rats by 48 h of fasting; no change was detected in spleen codeine levels. Brain morphine levels were elevated 5-fold after 24 h of fasting and were two-fold higher than those of fed rats after 48 h of fasting. Brain codeine levels did not change with fasting. These results indicate that opiate alkaloids are endogenously produced in rodent tissues, particularly in the spleen, liver, and adrenals. The synthesis of morphine, in the spleen and brain, is maximally stimulated after 24 h of fasting, without alterations in tissue codeine synthesis. These suggest differential regulation of the endogenous synthetic pathways of morphine and codeine in response to the stress of fasting.
Asunto(s)
Encéfalo/metabolismo , Ayuno , Péptidos Opioides/biosíntesis , Glándulas Suprarrenales/metabolismo , Animales , Peso Corporal , Codeína/sangre , Codeína/metabolismo , Hígado/metabolismo , Masculino , Morfina/sangre , Morfina/metabolismo , Especificidad de Órganos , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Timo/metabolismo , Factores de TiempoRESUMEN
In all patients and volunteers, the levels of immunoreactive SP measured in saliva were about 100 times higher than the levels measured in plasma. SP per mg protein was consistently lower in both plasma and saliva of chronic pain patients than in healthy volunteers. These findings suggest that a simple noninvasive objective method of determining SP in saliva may become useful in the evaluation and treatment of chronic pain.
Asunto(s)
Biomarcadores/análisis , Dolor de la Región Lumbar/metabolismo , Saliva/química , Sustancia P/análisis , Adulto , Biomarcadores/sangre , Proteínas Sanguíneas/análisis , Enfermedad Crónica , Humanos , Dolor de la Región Lumbar/sangre , Persona de Mediana Edad , Proteínas y Péptidos Salivales/análisis , Sustancia P/sangreRESUMEN
The influence of cimetidine on the pharmacokinetic and pharmacodynamic response to the insecticide carbaryl has been investigated in isolated human erythrocytes (red blood cells; RBC) and after oral administration of 1 mg/kg carbaryl to four normal subjects in the absence or presence of cimetidine (300 mg, 8/hr for 3 days). Carbaryl induced a concentration-dependent reduction of isolated RBC acetylcholinesterase activity requiring 1 microgram/ml to achieve 20% inhibition. Cimetidine also induced a dose-dependent inhibition of RBC acetylcholinesterase activity, but at 40-fold higher concentrations. At high concentrations, cimetidine was additive to carbaryl-induced inhibition of RBC acetylcholinesterase, but exhibited no effect at the therapeutically relevant concentrations (10 micrograms/ml). After oral carbaryl administration to normal subjects, plasma concentrations rapidly rose to a peak, then declined with a half-life of 0.79 +/- 0.47 hr. Oral carbaryl clearance was 5.4 +/- 2.0 l/min. Peak plasma carbaryl concentrations were associated with 27% inhibition of RBC acetylcholinesterase activity, and the concentration associated with a reduction of RBC acetylcholinesterase activity of 20% was 0.02 microgram/ml. The terminal half-life for the dynamic response was 2.6 +/- 1.5 hr. After pretreatment with cimetidine, peak plasma carbaryl concentrations doubled and clearance was reduced (to 2.5 +/- 1.5 l/min) (P less than .05). However, half-life remained unchanged. Despite increased carbaryl levels, the maximum inhibition of RBC acetylcholinesterase activity was significantly reduced, and the concentration of carbaryl required to achieve 20% inhibition of RBC acetylcholinesterase activity was increased to approximately 0.5 microgram/ml. These results are consistent with the hypothesis that carbaryl is metabolized by drug-metabolizing enzymes that can be inhibited by cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Carbaril/farmacocinética , Cimetidina/farmacología , Acetilcolinesterasa/sangre , Acetilcolinesterasa/metabolismo , Administración Oral , Adulto , Carbaril/metabolismo , Carbaril/farmacología , Interacciones Farmacológicas , Semivida , Humanos , Masculino , Tasa de Depuración MetabólicaRESUMEN
Commercial sources for neuropeptide radioimmunoassays have made this sensitive tool available to clinical investigators for monitoring the potential involvement of neuropeptides in pain modulation. We measured substance P-like immunoreactivity in the plasma, saliva, and pericardial fluid of subjects with and without pain (chronic and acute) to determine if substance P levels are altered. Some recent studies have suggested that substance P in various body fluids may be a correlate of chronic pain. To test this correlation it is important to ensure that the assay is measuring what it was designed to measure. Therefore, the influence of three tachykinins on the analysis of substance P concentrations was assessed with a commercially available radioimmunoassay kit. A small (approximately 2 to 6%), apparently nonspecific elevation in measured substance P was found when alpha-neurokinin, beta-neurokinin, or eledoisin was incubated with substance P and its antibody. Our results also indicate an apparent specific affinity of the substance P antibody for alpha-neurokinin (above 1,000 pg/ml) and beta-neurokinin (above 5,000 pg/ml). Substance P levels in the body fluids we tested ranged from 0.47 to 62.88 pg/mg protein (47.4 to 230.8 pg/ml). Levels of the tested tachykinins have not been determined in body fluids. If alpha-neurokinin or beta-neurokinin is found to be present in high concentrations in these fluids, this commercially available substance P kit may overestimate substance P levels. The concentrations of tachykinins necessary to interfere specifically with the assay are 10- to 100-fold higher than substance P in body fluids.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Eledoisina/química , Neuroquinina A/química , Neuroquinina B/química , Sustancia P/análisis , Angina de Pecho/metabolismo , Dolor de Espalda/sangre , Dolor de Espalda/metabolismo , Tumor Carcinoide/sangre , Humanos , Derrame Pericárdico/metabolismo , Unión Proteica , Saliva/química , Especificidad de la Especie , Sustancia P/sangreRESUMEN
The in vitro effects of two metabolites of inhalational anaesthetics, fluoride and bromide, on pseudocholinesterase (PCHE) and acetylcholinesterase (ACHE) activities in the blood samples of seven healthy patients were studied. The PCHE and ACHE activities were determined by kinetic spectrophotometric methods. Fluoride at the levels achieved with clinical concentrations of enflurane and sevoflurane (25-75 microM.L-1) inhibited PCHE activity by 28-65 per cent (P less than 0.01) and ACHE activity by less than five per cent (P greater than 0.05). Bromide at the levels achieved with clinical concentrations of inhalational anaesthetics had no significant effect on either PCHE or ACHE activity. We recommend caution when succinylcholine and/or ester type local anaesthetics are used in the immediate postoperative period following enflurane or sevoflurane anaesthesia. We also recommend that blood drawing for PCHE activity be delayed at least until 24 hr following enflurane or sevoflurane anaesthesia.
Asunto(s)
Acetilcolinesterasa/sangre , Bromuros/farmacología , Butirilcolinesterasa/sangre , Fluoruros/farmacología , Acetilcolinesterasa/metabolismo , Adulto , Análisis de Varianza , Anestesia por Inhalación , Anestésicos/farmacología , Bromuros/administración & dosificación , Butirilcolinesterasa/metabolismo , Calorimetría , Femenino , Fluoruros/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , EspectrofotometríaRESUMEN
Substance P, a neuropeptide associated with pain perception, is widely distributed in the central nervous system and is decreased in the cerebrospinal fluid of chronic pain patients as compared with that of healthy human volunteers. In this study, we have demonstrated the presence of immunoreactive substance P in saliva and further, that both saliva and plasma levels of immunoreactive substance P are lower in patients with chronic low back pain than in healthy human volunteers. To our knowledge, this is the first time that substance P has been identified in human saliva. These findings, together with the noninvasive nature of saliva collection, suggest that substance P in saliva may be useful as an alternative neurochemical correlate of chronic low back pain when collection of cerebrospinal fluid and plasma samples for substance P analysis is unacceptable or inappropriate.
Asunto(s)
Dolor de Espalda/metabolismo , Saliva/análisis , Sustancia P/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sustancia P/inmunología , Sustancia P/fisiologíaRESUMEN
Maternal smoking depressed the active uptake of amino acids by human placentae and lowered their levels in the placenta and umbilical vein. During starvation of cells for amino acids, more amino acid carriers are induced and incorporated into the plasma membrane. A question arises whether there could be similar changes due to maternal smoking in the placental amino acid uptake carrier systems. Therefore, the characteristics of (a) the uptake of 2-amino[I-14C]-isobutyric acid (AIB) by isolated placental villi, (b) gammaglutamyltranspeptidase (GGTP), a critical enzyme of the gammaglutamyl cycle (GGC) for the uptake of amino acids in human placenta, and (c) lipid structural parameters (reciprocal of fluidity), by steady state fluorescence polarization of plasma membrane vesicles of microvilli (MV) and microsomal membranes (MM) of umbilical and chorionic plate arteries of placentae of smoking and non-smoking mothers were investigated. The above investigations gave the following results: (a) Washed placental villi of smokers exhibited higher capacity for AIB uptake than those of non-smokers. The higher uptake capacity was mainly due to increase in Vmax for AIB uptake in smokers. Km increased for placental AIB uptake in smokers. (b) Maternal smoking lowered GGTP activity of MV by decreasing its Vmax. Therefore, maternal smoking decreases the formation of gammaglutamyl-amino acid (GGAA) on the surface of trophoblast which are absorbed by the trophoblast. The degree of absorption of GGAA is considered as an inverse environmental signal for the cell to regulate amino acid transport systems. Maternal smoking seems to decrease the formation and absorption of GGAA and thereby induce the formation of new carriers for AIB uptake. (c) Maternal smoking increased the values for lipid structural order parameters and microviscosity of MV and induced tolerance against fluidization by ethyl alcohol in MM of umbilical and chorionic arteries. The alterations could increase Km for AIB uptake system and decrease the sensitivity of umbilical and chorionic arteries to vasoconstrictive substances like 5-hydroxytryptamine and catecholamine which are released by nicotine. All these changes tend to overcome the deficits produced in placental amino acid transport and satisfy the demands of the growing fetus for amino acids.
Asunto(s)
Aminoácidos/metabolismo , Ácidos Aminoisobutíricos/metabolismo , Fluidez de la Membrana , Fumar/metabolismo , Trofoblastos/enzimología , gamma-Glutamiltransferasa/metabolismo , Femenino , Humanos , Lípidos de la Membrana/metabolismo , Microsomas/enzimología , Embarazo , Arterias Umbilicales/metabolismo , ViscosidadRESUMEN
A choline acetyltransferase (ChA) inhibitor with an optimum combination of properties of potency, stability and membrane permeability is required to study several functional aspects of acetylcholine in nervous and non-nervous tissues. Therefore, 2-(alpha-naphthoyl)ethyltrimethylammonium iodide (alpha-NETA), 2-(beta-naphthoyl)ethyltrimethylammonium iodide (beta-NETA), 2-(9'-anthroyl)ethyltrimethylammonium iodide (9'-AETA) and their corresponding tertiary dimethylamine hydrochloride analogs (alpha-NEDA, beta-NEDA, 9'-AEDA) were synthesized and tested for their ChA inhibitory activities. The quaternary ammonium compounds were more potent inhibitors (150 in microM: alpha-NETA, 9; beta-NETA, 76; 9'-AETA, 32) than the corresponding tertiary compounds (150 in microM: alpha-NEDA, 63; beta-NEDA, 1400; 9'-AEDA, 77). The alpha-naphthyl moiety was preferable to the beta-naphthyl- or 9'-anthryl moieties for alignment with the enzyme for inhibition. alpha-NETA and alpha-NEDA exhibited adequate ChA inhibitory potencies for further pharmacological studies and localization of membrane bound ChA. They exhibited fluorescent characteristics of the alpha-naphthyl moiety. Their ChA inhibition was not reversible by dialysis. They were considerably more potent for inhibiting ChA than cholinesterases and carnitine acetyltransferase.
Asunto(s)
Acetilcolina/análogos & derivados , Colina O-Acetiltransferasa/antagonistas & inhibidores , Naftalenos/farmacología , Compuestos de Amonio Cuaternario/farmacología , Carnitina O-Acetiltransferasa/antagonistas & inhibidores , Inhibidores de la Colinesterasa/farmacología , Humanos , Relación Estructura-ActividadRESUMEN
The in vitro effect of procainamide on plasma cholinesterase (PCHE) activity in the plasma of ten normal ASA physical status I patients was studied using a kinetic method. The mean plasma cholinesterase activity without procainamide (control) was 0.90 +/- 0.09 units.ml-1. The dibucaine numbers of all the samples were in the normal range of 78 to 86, indicating normal genotypes. The mean plasma cholinesterase activity, in the presence of procainamide in concentrations of 5.0, 10.0, 20.0 and 40.0 micrograms.ml-1, was reduced to 0.73 +/- 0.04, 0.61 +/- 0.03, 0.45 +/- 0.02, and 0.36 +/- 0.01 units.ml-1, respectively. At therapeutic concentrations of 4 to 12 micrograms.ml-1, procainamide inhibited cholinesterase activity 15 to 30 per cent. The authors also showed that the concentration of procainamide required to inhibit 50 per cent of plasma cholinesterase activity was 20 micrograms.ml-1 (I50). The authors conclude that procainamide when tested in vitro had a statistically significant depressant effect on plasma cholinesterase activity at all the concentrations studied.
Asunto(s)
Inhibidores de la Colinesterasa , Colinesterasas/sangre , Procainamida/farmacología , Adulto , Femenino , Humanos , Técnicas In Vitro , Cinética , Masculino , Procainamida/sangreRESUMEN
Carbon tetrachloride, chloroform, dimethylnitrosamine, thioacetamide or acetaminophen was each administered to rats in a single hepatotoxic dose. Nifedipine, verapamil or chlorpromazine was administered in association with the hepatotoxic agents to determine if calcium channel blocking agents would prevent an increase in liver cell calcium associated with hepatotoxicity and to determine if these agents would protect against the development of centrilobular necrosis. Following a latent period different for each toxic agent, a 4- to 18-fold increase in liver cell calcium content had occurred by 24 hr. The calcium increase and the centrilobular necrosis (mean histologic score) were correlated. A relatively high calcium to necrosis ratio was obtained with dimethylnitrosamine, thioacetamide and acetaminophen. A lesser calcium to necrosis ratio was obtained with chloroform and carbon tetrachloride, the two toxic agents that destroyed the intracellular calcium sequestration activity of the liver endoplasmic reticulum. Nifedipine or chlorpromazine, administered prior to and 7 hr after the toxic agent, completely prevented the centrilobular necrosis caused by thioacetamide, carbon tetrachloride and acetaminophen; almost completely prevented necrosis with dimethylnitrosamine; and provided partial protection against chloroform toxicity. Two doses of verapamil provided partial protection against necrosis when carbon tetrachloride was the toxic agent and provided almost complete protection with dimethylnitrosamine. A reduction in liver cell calcium was associated with the protective action of the three calcium channel blocking agents. These findings are compared with earlier studies of the protective effects of calcium channel blocking agents in cardiac ischemia.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Calcio/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hígado/efectos de los fármacos , Acetaminofén/antagonistas & inhibidores , Animales , Tetracloruro de Carbono/antagonistas & inhibidores , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cloroformo/antagonistas & inhibidores , Dimetilnitrosamina/antagonistas & inhibidores , Hígado/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Necrosis/inducido químicamente , Necrosis/prevención & control , Ratas , Ratas Endogámicas , Tioacetamida/antagonistas & inhibidoresRESUMEN
Membrane microviscosity was determined from the polarized fluorescence of diphenylhexatriene in plasma membranes and microsomes prepared from the liver of carbon tetrachloride treated rats. It was greatly depressed between 12 and 24 hr after the administration of the carbon tetrachloride. Depression of microviscosity was also seen in the liposomes which were prepared from these membranes. There were decreases in phospholipid content and phospholipid methyltransferase activity, but these changes did not appear to explain the decreased microviscosity. A large accumulation of calcium occurred in the liver cells between 12 and 24 hr after the administration of carbon tetrachloride. Chlorpromazine, verapamil and nifedipine, when administered prior to the carbon tetrachloride, partially reduced the later accumulation of calcium and reduced the degree of histological damage observed. When these agents were administered 12 hr after the administration of carbon tetrachloride, they did not reduce the subsequent accumulation of calcium. When administered prior to and 7 hr after carbon tetrachloride, they had a small but potentially significant effect on the microviscosity change. It is suggested that at low levels of microviscosity a critical threshold may exist below which entry of calcium into the cell is poorly controlled and that calcium channel blocking agents may be ineffective if administered at a time when membrane microviscosity is very low. Tissue calcium accumulation was associated with visible cell damage.