RESUMEN
Quantum phases of electrons in the filling factor range 2≤ν≤3 are probed by the weak optical emission from the partially populated second Landau level and spin wave measurements. Observations of optical emission include a multiplet of sharp peaks that exhibit a strong filling factor dependence. Spin wave measurements by resonant inelastic light scattering probe breaking of spin rotational invariance and are used to link this optical emission with collective phases of electrons. A remarkably rapid interplay between emission peak intensities manifests phase competition in the second Landau level.
RESUMEN
Chiral pumping from optical electric fields oscillating at terahertz frequencies is observed in the Weyl material TaAs with electric and magnetic fields aligned along both the a and c axes. Free-carrier spectral weight enhancement is measured directly, confirming theoretical expectations of chiral pumping. A departure from linear field dependence of the Drude weight is observed at the highest fields in the quantum limit, providing evidence of field-dependent Fermi velocity of the chiral Landau level. Implications for the chiral magnetic effect in Weyl semimetals from the optical f -sum rule are discussed.
RESUMEN
The serum concentration of all subclasses of IgG (gamma(2)A, gamma(2)B, and gamma(1)) as well as IgA and IgM were reduced in normal and low pathogen mice receiving hydrocortisone acetate. Turnover studies using (131)I-labeled gamma(2)A subclass of IgG demonstrated that high dose corticosteroids cause a significantly shortened survival (increased catabolic rate) which contributes to the observed hypogammaglobulinemia. This increase in fractional catabolism is not due to excess loss in the urine or stool but reflects an increase in endogenous catabolism.
Asunto(s)
Hidrocortisona/farmacología , gammaglobulinas/metabolismo , Agammaglobulinemia , Animales , Depresión Química , Hemorragia Gastrointestinal/metabolismo , Inmunoglobulina G/metabolismo , Inmunoglobulina M/metabolismo , Inmunoglobulinas/análisis , Inmunoglobulinas/metabolismo , Radioisótopos de Yodo , Isótopos de Hierro , Ratones , Volumen Plasmático , ProteinuriaRESUMEN
The Wiskott-Aldrich syndrome is an immune deficiency disorder with an impairment of both humoral and cellular immune responses. Metabolic turnover studies of IgG, IgA, IgM, and albumin were conducted in seven patients with the Wiskott-Aldrich syndrome using purified radioiodinated proteins. The survival of each of the proteins studied was significantly shortened with a half-time of 7.5 days for IgG (normal 22.9 +/-4 SD), 3.0 days for IgA (normal 5.8 +/-1), 5.0 days for IgM (normal 10.1 +/-2.1), and 8.6 days for albumin (normal 17, range 13-20); the fractional catabolic rates were correspondingly elevated and the distribution of protein among the body compartments was normal. For three of the four proteins. IgG, IgA, and albumin, the steady-state synthetic rates were generally elevated leading to normal or even elevated serum proteins levels. Thus, in the case of IgA, the synthetic rate averaged five times normal while the fractional degradative rate was twice normal. The resulting serum concentration was, therefore, significantly elevated, IgM represented an exception to this pattern in that the increased rate of degradation was not counterbalanced by an increased synthetic rate and, therefore, the serum levels were low. Albumin clearance studies using albumin-(51)Cr showed gastrointestinal protein loss in these patients to be slightly greater than normal, but this could account for only a small fraction of the hypercatabolism observed. There was no proteinuria or abnormalities of thyroid, adrenal, renal, or liver function. Thus, none of the previously recognized causes of increased serum protein catabolism were present. Patients with the Wiskott-Aldrich syndrome, therefore, have a unique disorder of serum protein metabolism characterized by endogenous hypercatabolism of at least four major serum proteins. This phenomenon may be related to reticuloendothelial hyperfunction since the Wiskott-Aldrich syndrome is associated with reticuloendothelial hyperplasia and accelerated clearance of colloidal materials from the plasma.
Asunto(s)
Inmunoglobulinas/metabolismo , Síndromes de Inmunodeficiencia/metabolismo , Albúmina Sérica/metabolismo , Síndrome de Wiskott-Aldrich/metabolismo , Adolescente , Niño , Preescolar , Isótopos de Cromo , Humanos , Inmunoglobulina A/metabolismo , Inmunoglobulina G/metabolismo , Lactante , Enfermedades Linfáticas/complicaciones , Masculino , Tasa de Depuración Metabólica , Sistema Mononuclear Fagocítico/metabolismo , Enteropatías Perdedoras de Proteínas , Síndrome de Wiskott-Aldrich/complicacionesRESUMEN
The maximal activities of the key glycolytic enzymes hexokinase and 6-phosphofructokinase, were reduced in brown adipose tissue in db/db mice compared to their lean littermates. Treatment of db/db mice with the thermogenic beta-adrenoceptor agonist, BRL 26830, restored normoglycaemia. The only significant increase in activity of hexokinase and 6-phosphofructokinase in the BRL 26830-treated db/db mice occurred in brown adipose tissue where the total tissue activity increased 10- and 11-fold respectively. These changes together with increased 2-deoxyglucose uptake in vivo suggest that brown adipose tissue can play a quantitatively important role in the removal of glucose from the blood.
Asunto(s)
Tejido Adiposo Pardo/enzimología , Diabetes Mellitus Experimental/metabolismo , Etanolaminas/farmacología , Glucólisis/efectos de los fármacos , Obesidad/metabolismo , Agonistas Adrenérgicos beta/farmacología , Animales , Desoxiglucosa/metabolismo , Femenino , Hexoquinasa/metabolismo , Complejo Cetoglutarato Deshidrogenasa/metabolismo , Hígado/enzimología , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Músculos/enzimología , Fosfofructoquinasa-1/metabolismoRESUMEN
Zucker fa/fa rats exhibit glucose intolerance in comparison with lean Fa/? littermates. A single acute dose of BRL 26830 (2.9 mg/kg p.o.) improved glucose tolerance in Fa/? littermates but exacerbated glucose intolerance in the fa/fa rats. This latter effect occurred in spite of an increase in the plasma insulin concentration. Chronic treatment of Zucker fa/fa rats with BRL 26830 (2.9 mg/kg) for 24 days or more produced a significant reduction in the area under the glucose tolerance curve. In addition, the glucose decay rate (k%) following the administration of insulin intravenously was significantly increased in the BRL 26830-treated rats suggesting that tissue insulin sensitivity was increased. Glucose turnover measurements show that chronic treatment of Zucker fa/fa rats with BRL 26830 produced a significant increase in the rate of glucose utilization integrated over a 3 hr period, but this increase was, in part, off-set by an increase in the endogenous rate of glucose production. The ultimate fate of the extra glucose that is metabolized is not known but it is suggested that it might be used to support the thermogenic response that is also activated by BRL 26830.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Etanolaminas/farmacología , Glucosa/metabolismo , Resistencia a la Insulina , Animales , Glucemia/análisis , Prueba de Tolerancia a la Glucosa , Insulina/metabolismo , Secreción de Insulina , Masculino , Ratas , Ratas ZuckerRESUMEN
BRL 26830, (R*,R*)-(+/-)-methyl 4-[2-[(2-hydroxy-2-phenylethyl)amino] propyl] benzoate, is a new orally active anti-hyperglycaemic agent. In 24 hr-fasted rats and mice, BRL 26830 decreased the blood glucose concentration following the administration of a subcutaneous glucose load. It also improved oral and intravenous glucose tolerance in 24 hr-fasted rats and decreased the post-prandial blood glucose concentration following the consumption of the complete, milk-based, meal "Nutrament". BRL 26830 produced a dose-related increase in the plasma insulin concentration and since it was inactive in lowering blood glucose in streptozotocin-diabetic rats, it is likely that its acute action on glucose tolerance was through the stimulation of insulin secretion. In contrast to the sulphonylurea, glibenclamide, BRL 26830 had no effect on the blood glucose concentration in 5 hr-fasted rats and only produced a transient reduction in 24 hr-fasted rats. BRL 26830 did not improve glucose tolerance when given acutely to hyperinsulinaemic C57BL/6 ob/ob mice. However, chronic treatment of these mice with BRL 26830 for 14-43 days resulted in a significant improvement in glucose tolerance.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Etanolaminas/farmacología , Hipoglucemiantes , Animales , Diabetes Mellitus Experimental/sangre , Ayuno , Femenino , Alimentos , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/farmacología , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos/sangre , Ratas , Ratas Endogámicas , Compuestos de Sulfonilurea/farmacologíaRESUMEN
OBJECTIVE: Decreased cerebral blood flow (CBF) and cerebral ischemia occurring immediately after subarachnoid hemorrhage (SAH) may be caused by acute microvascular constriction. However, CBF can also be influenced by changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP). The goal of these experiments was to assess the significance of acute vasoconstriction after SAH and its relationship to changes in CBF, ICP, CPP, and extracellular glutamate concentrations. METHODS: Three experiments were performed using the endovascular filament technique to produce SAH. In the first experiment, CBF, ICP, and CPP were measured for 60 minutes after SAH (n = 21) and were correlated with the 24-hour mortality rate. In the second experiment, rats undergoing SAH (n = 23) or a sham procedure (n = 7) were perfused 60 minutes after SAH for measurement of the circumference and wall thickness of the internal carotid and anterior cerebral arteries and correlation with CBF, ICP, and CPP. In the third experiment (n = 11), extracellular glutamate concentrations determined by hippocampal and cortical microdialysis and high performance liquid chromatography were correlated with physiological changes. RESULTS: CBF reductions to less than 40% of baseline for 60 minutes after SAH predicted 24-hour mortality with 100% accuracy and were used to define "lethal" SAH. In contrast, ICP and CPP 60 minutes after SAH were not correlated with the mortality rate. The vascular circumference was significantly smaller in lethal than in sublethal SAH or sham-operated rats (P < 0.001). Vessel measurements were correlated with both CBF and hemorrhage size (P < 0.01). Extracellular glutamate concentration increased to 600% of baseline after lethal SAH in both hippocampus and cortex and was inversely correlated with CBF (r = 0.9, P < 0.001) but did not increase after sublethal SAH. CONCLUSION: Acute vasoconstriction after SAH occurs independently of changes in ICP and CPP and is associated with decreased CBF, larger hemorrhage size, persistent elevations of extracellular glutamate, and poor outcome. Acute vasoconstriction seems to contribute directly to ischemic brain injury after SAH. Further evaluations of pharmacological agents with the potential to reverse acute vasoconstriction may increase CBF and improve outcome.
Asunto(s)
Hemorragia Subaracnoidea/fisiopatología , Vasoconstricción/fisiología , Animales , Presión Sanguínea/fisiología , Vasos Sanguíneos/patología , Circulación Cerebrovascular/fisiología , Espacio Extracelular/metabolismo , Predicción , Ácido Glutámico/metabolismo , Hematoma/patología , Presión Intracraneal/fisiología , Masculino , Ratas , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/mortalidad , Hemorragia Subaracnoidea/patología , Factores de TiempoRESUMEN
A statistically significant difference was found between the mean baseline carboxyhemoglobin of non-smoking firemen (COHb 2.53, sd = 1.05, n = 32) and smoking firemen (COHb 5.54, sd = 2.61, n = 26). A consistent increase in mean COHb levels after exposure to smoke was seen in both non-smoking (4.41 sd = 2.95, n = 7) and smoking men (8.74, sd = 5.66, n = 11), but the mean increase in these two groups was statistically significant only at the 90 percent level (t = 1.85, df = 16, p less than 0.1).
Asunto(s)
Intoxicación por Monóxido de Carbono/epidemiología , Carboxihemoglobina/análisis , Incendios , Hemoglobinas/análisis , Enfermedades Profesionales/epidemiología , Humo , Fumar , Adulto , Exposición a Riesgos Ambientales , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Various non-immunochemical approaches to the quantitation of albumin in serum are reviewed. Salt fractionation techniques are unreliable, with substantial errors in estimating hypoalbuminemic states. Electrophoresis displays biases owing to irregular dye-binding or to densitometric scanning of irregular globulin bands. Currently, the most reliable colorimetric procedure for albumin quantitation is the rapid reaction with bromcresol green. By measuring final absorbance within fifteen seconds of mixing serum with reagent, the interference of globulins is eliminated. A microscale (5 microliter serum) rapid reaction for albumin assay has been developed; it can be readily automated on kinetic or centrifugal analyzers.
Asunto(s)
Albúmina Sérica/análisis , Verde de Bromocresol , Colorimetría/métodos , Humanos , Microquímica/métodosRESUMEN
The nitrogen-specific detector for gas chromatography consists of a non-volatile rubidium silicate bead, around which nitrogen-containing compounds are pyrolyzed. Speed, sensitivity, specificity, accuracy, small sample size and minumum sample handling are characteristics of the nitrogen detector that render it superior to conventional gas chromatographic detectors. The detector has been utilized to effect a simple and rapid quantitation of allobarbital, amobarbital, butabarbital, heptabarbital, pentabarbital, phenobarbital and secobarbital, plus the anticonvulsants diphenylhydantoin and primidone. Extraction of the drugs from acidified serum into organic solvent containing internal standard is followed by oncolumn methylation with methanolic trimethylphenyl ammonium hydroxide. The drugs, separated on a column of 3 percent OV-101 on Gas-Chrom Q, 100-120 mesh are readily quantitated by simple calculations based on peak-height ratios. Therapeutic drug monitoring is discussed in relation to recent concepts of drug-protein binding, drug-drug interactions, drug biotransformation and problems of multiple drug therapy.
Asunto(s)
Barbitúricos/sangre , Cromatografía de Gases/métodos , Fenitoína/sangre , Primidona/sangre , Amobarbital/sangre , Humanos , Nitrógeno , Pentobarbital , Fenobarbital/sangre , Secobarbital/sangreRESUMEN
The authors report the case of a 58-year-old male patient with clinical and electromyographic features of myasthenia. Muscle biopsy with histochemistry and electronic microscopy made it possible to diagnose a myopathy associated with tubular aggregates. Attention is called to the fact that the anatomical pathologic alterations which were found may be present in a heterogenous group of patients showing a great variety of symptoms. Thus, there is no reason to consider the existence of a myopathy associated with tubular aggregates, since the anatomical and pathologic findings are inespecific and do not characterize any specific disease.
Asunto(s)
Músculos/ultraestructura , Miastenia Gravis/patología , Biopsia , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana EdadRESUMEN
We compared two techniques for separating and evaluating serum creatine kinase isoenzymes--fluorometric agarose electrophoresis and Sephadex chromatography--in 50 patients, 25 of whom had confirmed acute myocardial infarction. In every case isoenzyme MB (heart isoenzyme) was detected with equal sensitivity by either procedure. Evidently, only the presence or absence of MB is clinically significant; none of the 25 patients without infarction had detectable MB activity in their serum. Columns connected to a continuous-flow sample line for analyses of the eluting stream without further modification produced satisfactory results.
Asunto(s)
Creatina Quinasa/sangre , Isoenzimas/sangre , Cromatografía en Gel/métodos , Creatina Quinasa/aislamiento & purificación , Electroforesis en Gel de Agar/métodos , Estudios de Evaluación como Asunto , Humanos , Isoenzimas/aislamiento & purificación , Infarto del Miocardio/enzimología , Miocardio/enzimologíaRESUMEN
BACKGROUND: Acute lymphocytic leukemia can be associated with an occlusive microvascular retinopathy. There is a potential for worsening of this occlusive microvascular retinopathy by radiation damage to the retinal vasculature (radiation retinopathy) and by the toxic effects of chemotherapy. METHODS: An 18-year-old woman with T-cell acute lymphocytic leukemia received low-dose irradiation to the brain and subsequent chemotherapy, which included cytosine arabinoside. RESULTS: During the chemotherapy, she developed severe bilateral occlusive microvascular retinopathy that progressed despite extensive panretinal photocoagulation to bilateral optic disc and retinal neovascularization and eventual traction retinal detachment involving the macula. CONCLUSION: The toxic effect of a chemotherapeutic agent such as cytosine arabinoside when combined with radiation retinopathy may be additive, leading to a much more severe ischemic retinal vasculopathy than one would encounter with acute lymphocytic leukemia alone. This must be kept in mind when planning combined radiation and chemotherapy for T-cell acute lymphocytic leukemia.
Asunto(s)
Leucemia-Linfoma de Células T del Adulto/terapia , Disco Óptico/irrigación sanguínea , Enfermedades de la Retina/etiología , Neovascularización Retiniana/etiología , Adolescente , Terapia Combinada , Citarabina/efectos adversos , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/complicaciones , Disco Óptico/patología , Disco Óptico/efectos de la radiación , Radioterapia/efectos adversos , Oclusión de la Arteria Retiniana/etiología , Oclusión de la Arteria Retiniana/patología , Desprendimiento de Retina/etiología , Desprendimiento de Retina/patología , Neovascularización Retiniana/patología , Oclusión de la Vena Retiniana/etiología , Oclusión de la Vena Retiniana/patologíaRESUMEN
The administration of an oral glucose load to 24 h-starved lean (+/?) male C57BL/6 mice produced a rapid, 7-fold increase in the rate of hepatic glycogen synthesis and a sustained activation of glycogen synthase. In contrast, glucose produced only a small (4.5-fold), short-lived increase in hepatic glycogen synthesis in genetically obese (ob/ob) mice and no activation of glycogen synthase.
Asunto(s)
Glucosa/farmacología , Glucógeno Hepático/biosíntesis , Ratones Obesos/metabolismo , Animales , Activación Enzimática/efectos de los fármacos , Glucógeno Sintasa/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , RatonesRESUMEN
We have adapted the commercially available EMIT kit [Clin. Chem. 23, 1161 (1977)] to the Gilford System 3500 Analyzer. Sample volume is 10 microliter. We compare reagent blank-corrected absorbance changes at 340 nm between 15 and 55 s for samples and a series of calibrators, and calculate results with use of a logarithmic transformation. Within-run precision (CV) for a serum pool with 4.0 mg of added lidocaine per liter was 2.7% (n = 45); day-to-day precision was 3.3% (n = 15). Analytical recoveries of 2 to 6 mg of lidocaine per liter were 90-102% (average, 97.3%). Results correlated significantly with those by a gas-chromatographic technique. No clinically significant interferences by concomitantly administered medications were observed. The procedure is rapid (42 samples per hour) and is well suited to the fast response required in monitoring lidocaine therapy. Usefulness of the assay data in the management of arrhythmias in the coronary care unit is discussed.
Asunto(s)
Lidocaína/sangre , Autoanálisis , Reacciones Cruzadas , Humanos , Técnicas para Inmunoenzimas , Lidocaína/uso terapéuticoRESUMEN
We assayed serum and urine specimens for amylase activity by the nephelometric (I),dyed-starch (Amylochrome) (II), and mayloclastic (III) techniques. For serum, the correlation coefficients of the regression lines were: I vs. II, 0.978 (n = 106); I vs. III, 0.736 (n = 110); and II vs. III, 0.739 (n = 108). For urine, they were I vs. II, 0.938 (n = 49); and I vs. III, 0.752 (n = 46). Because calculation of the Kolmogorov-Smirnov statistic showed the distributions to be nongaussian, Spearman rank correlation coefficients were determined and showed that I and II correlated well but neither method correlated with III. The clinical data show that I and II gave above-normal activities in every case of pancreatitis, but III gave normal values in two of eight cases. In all cases, I and II were more sensitive, giving higher amylase activities (as compared with the upper limit of normal) than did III. The nephelometric procedure is most suitable for routine and emergency testing; the dyed-starch assay is equally sensitive and reliable, but less convenient. The amyloclastic procedure appears to be less reliable.
Asunto(s)
Amilasas/análisis , Adulto , Amilasas/sangre , Amilasas/orina , Colorantes , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Métodos , Nefelometría y Turbidimetría , Análisis de Regresión , AlmidónRESUMEN
To determine whether responses to exercise in children with sickle cell trait (AS) are different from those of normal children, we performed dynamic cycle ergometer stress testing in 48 children with AS, aged 4 to 21 years. We compared these data with those obtained from 184 healthy black children. No subject with AS demonstrated definite ischemia on the exercise ECG, but four (8.3%) had equivocal ischemia. Population statistics derived from Z score values showed that the subjects with AS had lower exercise values for heart rate and work load than the controls. The BP response to exercise was normal in subjects with AS. Since no ischemia or complications occurred, exercise in subjects with AS appears to be safe. Further studies are needed to define the mechanism for the impaired pulse rate and work load variables.
Asunto(s)
Anemia de Células Falciformes/fisiopatología , Esfuerzo Físico , Rasgo Drepanocítico/fisiopatología , Adolescente , Adulto , Presión Sanguínea , Niño , Preescolar , Electrocardiografía , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Oximetría , Evaluación de Capacidad de TrabajoRESUMEN
BACKGROUND: If monotherapy with an intranasal corticosteroid can alleviate both nasal and ocular symptoms of allergic rhinitis, treatment may be simplified and costs may be reduced. OBJECTIVE: The purpose of this study was to evaluate the efficacy of once-daily fluticasone propionate (FP) aqueous nasal spray 200 microg compared with vehicle placebo and oral loratadine (LOR) 10 mg in reducing ocular symptoms associated with seasonal allergic rhinitis. METHODS: A total of 471 patients received vehicle placebo, LOR, or FP in this multi-centre, double-blind, double-dummy, randomized study. Patients were > or =12 years old with a history of seasonal allergic rhinitis and a positive skin test for a relevant allergen. During the baseline and treatment periods, patients rated the severity of eye itching, tearing, and redness via visual analogue scales that ranged from 0 (no symptoms) to 100 (most severe symptoms). The three ocular ratings were added to derive the total ocular symptom score (TOSS). Patients with a TOSS > or =120 on at least 4 of the 7 days before the randomization visit were enrolled. The primary outcome was the difference between FP and vehicle placebo in the mean change from baseline in the reflective TOSS overall (averaged over the 28-day treatment period). A difference between FP and vehicle placebo of 25.5 was considered clinically significant. RESULTS: The overall mean change from baseline in the TOSS was significantly greater in the FP group compared with vehicle placebo (clinically significant difference of 28.8; P<0.001) and compared with LOR (difference of 16.2; P=0.028). Overall mean (SEM) changes were -59.9 (5.4) for the placebo group, -72.5 (5.4) for the LOR group, and -88.7 (5.3) for the FP group. The FP treatment group also showed significantly greater overall mean changes in ocular itching, tearing, and redness compared with vehicle placebo (P<0.001) and compared with LOR (P< or =0.045). CONCLUSION: Patients treated with intranasal FP had clinically and statistically significant decreases in ocular symptom scores compared with vehicle placebo. Data also suggest that FP reduced ocular symptoms more than or comparable with oral LOR. Patients experiencing ocular symptoms associated with allergic rhinitis may benefit from monotherapy with intranasal FP.
Asunto(s)
Androstadienos/administración & dosificación , Glucocorticoides/administración & dosificación , Rinitis Alérgica Estacional/tratamiento farmacológico , Administración Tópica , Adulto , Aerosoles , Androstadienos/efectos adversos , Androstadienos/uso terapéutico , Método Doble Ciego , Femenino , Fluticasona , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Tamaño de la MuestraRESUMEN
BRL 26830A, (R*, R*)-(+/-)-methyl 4-[2-[(2-hydroxy-2-phenylethyl) amino] propyl]-benzoate, (E)-2-butenedioate (2:1) salt, is a new antihyperglycemic agent orally active in obese-hyperglycemic animal models. In C57Bl/6 ob/ob mice, BRL 26830A (1 mg/kg) given daily for periods of 14 d-6 weeks produced a marked improvement in glucose tolerance and a reduction in the fasting plasma insulin concentration. Adipocytes prepared from treated mice showed improved insulin responsiveness. In Zucker fa/fa rats, treatment with BRL 26830A (2.9 mg/kg/d for 23 d) produced improvements in both glucose tolerance and whole animal insulin sensitivity, as assessed by rate of fall of blood glucose in response to an intravenous dose of insulin. In C57Bl/KSJ db/db mice, BRL 26830A (admixed with food at 50 mg/kg diet) decreased blood glucose to values similar to those in lean mice. At the end of a 10-week treatment, BRL 26830A-treated mice had a higher plasma and pancreatic insulin content than the untreated db/db mice. In normoglycaemic rats and mice, BRL 26830A increases the plasma insulin concentration and increases glucose disposal. However, in most circumstances, there is a counteracting increase in endogenous glucose synthesis and, therefore, no change in blood glucose occurs. Improvements in glucose tolerance occur in 24-h fasted rats and mice. BRL 26830A has thermogenic activity and it is suggested that this might be linked to increased glucose utilization. Brown adipose tissue (BAT) of C57Bl/KSJ db/db mice has a reduced maximum glycolytic capacity relative to lean littermates. Treatment with BRL 26830A increased the glycolytic capacity 10-fold.