ABSTRACT
Gravity Probe B, launched 20 April 2004, is a space experiment testing two fundamental predictions of Einstein's theory of general relativity (GR), the geodetic and frame-dragging effects, by means of cryogenic gyroscopes in Earth orbit. Data collection started 28 August 2004 and ended 14 August 2005. Analysis of the data from all four gyroscopes results in a geodetic drift rate of -6601.8±18.3 mas/yr and a frame-dragging drift rate of -37.2±7.2 mas/yr, to be compared with the GR predictions of -6606.1 mas/yr and -39.2 mas/yr, respectively ("mas" is milliarcsecond; 1 mas=4.848×10(-9) rad).
ABSTRACT
GABA level and the activity of L-glutamate-1-decarboxylase (GAD) (EC 4.1.1.15) were studied in brains of mice treated with beta-vinyllactic acid, a new, selective and pyridoxal phosphate-independent GAD inhibitor. Valproate and diazepam protected mice against convulsions caused by beta-vinyllactic acid although both anti-epileptic drugs antagonized neither the decrease in GABA concentrations nor the inhibition of GAD observed after treatment with beta-vinyllactic acid alone. Assuming that the anticonvulsant effect measured with both antiepileptics is GABA mediated, these results support the hypothesis of a postsynaptic enhancement of GABAergic transmission by diazepam and valproate.
Subject(s)
Convulsants/antagonists & inhibitors , Diazepam/pharmacology , Lactates/antagonists & inhibitors , Seizures/chemically induced , Valproic Acid/pharmacology , Animals , Brain/drug effects , Convulsants/toxicity , Dose-Response Relationship, Drug , Glutamate Decarboxylase/antagonists & inhibitors , Lactates/toxicity , Male , Mice , Synaptic Transmission/drug effects , gamma-Aminobutyric Acid/metabolismABSTRACT
Racemic d,l-baclofen and l-baclofen depressed the patellar, flexor, linguo-mandibular (0.1--30 mg/kg i.v.) and the H-reflex (1--3 mg/kg i.v.) in a dose-dependent fashion. Racemic and l-baclofen partly antagonized electroshock-induced convulsions in mice (30--60 mg/kg p.o.) and depressed the firing rate of nigral cells when applied iontophoretically. d,l-Baclofen and l-baclofen (0.1--3.0 mg/kg i.v.) moderately reduced the blood pressure in cats. Dextrorotatory baclofen, at identical doses was inactive in all these tests. It is concluded that the biological activity of baclofen resides with the l-enantiomer.
Subject(s)
Aminobutyrates/pharmacology , Baclofen/pharmacology , Animals , Blood Pressure/drug effects , Cats , Dose-Response Relationship, Drug , Male , Mice , Reflex/drug effects , Seizures/drug therapy , Substantia Nigra/drug effects , Synaptic Transmission/drug effectsSubject(s)
Hypolipidemic Agents/pharmacology , Animals , Antioxidants/pharmacology , Benzoates/pharmacology , Clofibrate/analogs & derivatives , Clofibrate/pharmacology , Cyclization , Dietary Fats/metabolism , Estradiol Congeners/pharmacology , Humans , Intestinal Absorption/drug effects , Lipoproteins/blood , Metabolism/drug effectsSubject(s)
Amidines/chemical synthesis , Hypoglycemic Agents/chemical synthesis , Amidines/pharmacology , Aniline Compounds/analysis , Aniline Compounds/chemical synthesis , Animals , Benzazepines/analysis , Benzazepines/chemical synthesis , Blood Glucose/analysis , Butyrates/analysis , Butyrates/chemical synthesis , Chemical Phenomena , Chemistry , Female , Hypoglycemic Agents/analysis , Hypoglycemic Agents/pharmacology , Male , Models, Structural , Rats , Tolbutamide/pharmacologyABSTRACT
PIP: Despite the fact that the role of lipids and cholesterol in atherosclerosis has not been totally clarified to the clinician's satisfaction, medicinal chemistry has been very successful in this last decade in showing that a diverse group of compounds is capable of reducing blood lipid levels in many animal species and in humans. The pharmacological basis for the evaluation of many hypolipidemic agents is summarized. The prostaglandins are vasodepressor agents. They inhibit uterine contraction, yet, on the other hand, they increase cardiac output and induce contraction of intestinal smooth muscle. Prostaglandins exhibit marked antilipolytic activity. It has been shown that 0.2 mug/kg/min, of intravenous infusion of prostaglandin E1 produced an increase in serum-free fatty acide levels in the dog. At a 4 times higher rate of infusion, the plasma-free fatty acid concentration was lowered. The pharmacological activities of individual prostaglandins embrace a great variety of biological phenomena. In certain systems their effects are antagonistic. The rationale for the use of estrogens as hypolipidemics is the observation of the low incidence of atherosclerotic heart disease in Caucasian women of childbearing age.^ieng
