Insulin dose-response characteristics for suppression of glycerol release and conversion to glucose in humans

To compare the dose-response characteristics for suppression of lipolysis and suppression of glucose production by insulin, 13 normal nonobese individuals were infused with insulin at rates of 0.1, 0.2, 0.4, 0.8, and 1.6 mU X kg-1 X min-1 while normoglycemia was maintained with the glucose clamp technique. Glucose appearance and glycerol appearance (taken as index of lipolysis) were measured isotopically with simultaneous infusions of 3-[3H]glucose and U-[14C]glycerol. Baseline glucose and glycerol rates of appearance were 14 +/- 0.5 and 1.7 +/- 0.2 mumol X kg-1 X min-1, respectively. Approximately 3% of plasma glucose originated from glycerol, and this accounted for approximately 50% of glycerol disposal. During the insulin infusions, arterial insulin (basal, 9.8 +/- 0.6 microU/ml) increased to 14 +/- 0.5, 20 +/- 0.5, 31 +/- 1, 58 +/- 2, and 104 +/- 6 microU/ml; calculated portal venous insulin (basal, 24 +/- 2 microU/ml) increased to 26 +/- 1, 32 +/- 3, 70 +/- 4, and 115 +/- 6 microU/ml. The rate of glucose appearance was suppressed 100%, whereas the rate of appearance of glycerol was maximally suppressed only 85%. Nevertheless, the insulin concentration that produced half-maximal suppression of glucose appearance was twice as great as that required for half-maximal suppression of glycerol appearance (26 +/- 2 vs. 13 +/- 2 microU/ml, P less than .001). Insulin decreased both the absolute rate of glycerol conversion to plasma glucose and the percent of glycerol disposal appearing in plasma glucose (both P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

Quality of object relations versus interpersonal functioning as predictors of therapeutic alliance and psychotherapy outcome

The purpose of the study was to compare an interview measure of quality of object relations to questionnaire and interview measures of recent interpersonal functioning with respect to the prediction of therapeutic alliance and psychotherapy outcome. The sample consisted of 64 patients who had received approximately 20 sessions of short-term individual psychotherapy within a controlled, clinical-trial investigation. Ratings of therapeutic alliance were provided independently by the patient and the therapist after each session. Outcome measures, which were provided by three sources (patient, therapist, and independent assessor), covered the areas of interpersonal functioning, psychiatric symptomatology, self-esteem, and life satisfaction. Quality of object relations, which characterizes the patient's lifelong pattern of relationships, was the best predictor. It was significantly related to patient-rated and therapist-rated therapeutic alliance and to patient improvement of both general symptomatology and specific target problems. The study also replicated previous studies that have reported significant relationships between therapeutic alliance and therapy outcome. The advantages of pretherapy predictors of therapy outcome, such as quality of object relations, are discussed.     

Renal function and the disposition of antidepressants and their metabolites.

Reports of plasma concentrations of antidepressants and their metabolites in patients with reduced renal function have been reviewed. The consequences of alteration of various pharmacokinetic factors on drug and metabolite concentrations have been compared with the observed data. Concentrations of drugs that are more than 95 percent metabolized are not altered by decreased renal function. Concentrations of drugs that are mostly excreted unchanged in urine are greatly increased in patients with reduced renal function. Concentrations of metabolites that account for 10 percent or more of the dose of a parent drug in urine are usually increased. In general, the observations can be explained without hypothesizing an effect of reduced renal function on clearance by metabolism.     

Spectrophotometric determination of isonaphthazarin impurity in 1,4-dioxo-2,2,3,3-tetrahydroxy-1,2,3,4-terahydronaphthalene (tetraxolin)

A quantitative spectrophotometric method has been developed for determining the impurity of isonaphthazarin in samples of tetraxolin. The relative error of determination is about 1.0% at a confidence probability of P = 0.95%. The procedure is recommended for the quantitative control of the possible impurity of isonaphthazarin in the parent substance of tetraxolin. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 1, pp. 38–40, January, 2007.     

Quantitative ESI-MS analysis of antiarrhythmic drugs in blood plasma without chromatographic separation

A highly sensitive method for the quantitative determination of a potential antiarrhythmic drug (OF-7976) in the blood plasma has been developed. The method is based on the electron spray ionization/mass spectrometry (ESI-MS) technique without preliminary chromatographic separation and makes use of nibentan as the internal standard. A linear relationship between drug concentration and the peak intensity of ions of the analyzed substance (m/z = 398) and the internal standard (m/z = 382) is established. The detection limit is 3 ng/(0.5 ml plasma). The method is linear from 3 to 25 ng/(0.5 ml plasma) with a correlation coefficient of 0.98. The coefficient of variation was less than 7 %. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 3, pp. 45–48, March, 2007.