Identification of an anion-transport ATPase that catalyzes glutathione conjugate-dependent ATP hydrolysis in canalicular plasma membranes from normal rats and rats with conjugated hyperbilirubinemia (GY mutant).

Rat liver canalicular plasma membranes were found to contain a 37-kDa protein that is immunologically cross-reactive with the dinitrophenyl glutathione-stimulated ATPase previously identified in human tissues. The protein, which was partially purified by affinity chromatography, exhibited ATPase activity dependent on dinitrophenyl glutathione, bilirubin ditaurate, and other dianionic compounds. The localization of this protein in the canalicular membrane and its measured enzymatic activity indicate that it is involved in the transport of glutathione derivatives and other dianionic organic compounds. A rat mutant in which the above transport activities are impaired contained the protein in amounts similar to those in a normal control.     

Changes in histochemically detectable calcium and zinc during tolbutamide-induced degranulation and subsequent regranulation of rat pancreatic islets

Secretory granules of pancreatic B-cells contain high concentrations of zinc and calcium. The effect of gradual degranulation (induced by tolbutamide over a period of 3 days) and the subsequent regranulation (over a period of 4 days) on the histochemically detectable zinc (Zn) and calcium (Ca) content of B-cells was investigated. Zn was stained by dithizone, Ca by glyoxal-bis-(2-hydroxyanil), (GBHA), and B-granules by aldehyde fuchsin (AF). The staining intensities were determined cytophotometrically. A decrease of the granulation by 50% causes a comparable decrease of the Zn content. Almost complete degranulations, however, hardly further diminished the Zn content. Regranulation restores the Zn content parallel to the granulation. The presence of 40% of the initial Zn content in degranulated B-cells suggests the existence of a non-granular Zn fraction. The Zn content of B-cells may be partly involved in the storage of insulin as a Zn-insulin complex in the secretory vesicles. A-cells, however, contain even more (+ 30%) Zn than B-cells. Degranulation of B-cells is accompanied by a moderate decrease of the zinc content of the A-cells. The function of Zn in A-cells is completely unknown. Degranulation of B-cells causes the GBHA-Ca content to decrease to a very low level parallel to the AF-positive granulation. During regranulation the GBHA-Ca content restores parallel to the granulation and reaches after complete regranulation a slightly higher level than in untreated control rats. Almost complete disappearance of CBHA-Ca in the B-cells is accompanied by a decrease of the total islet calcium content of 33%. The results indicate that GBHA stains a Ca fraction which is mainly localized to the secretory granules. The stainability of granular Ca by GBHA is probably based on: a) the high Ca concentration in the granules, b) the presence of ionized Ca in the granules, due to the low intragranular pH, and c) on the properties of GBHA, which stains, under conditions used, only ionized (possibly also readily ionizable) Ca.     

Clinical signs,diagnostics and successful treatment of a myocarditis in an adult chimpanzee (Pan troglodytes)

A chimpanzee (Pan troglodytes) was presented with lethargic behaviour. Echocardiography and abnormal cardiac and inflammatory biomarkers revealed a myocarditis. The animal fully recovered after prolonged treatment with losartan and carvedilol. This is the first report of the diagnosis and successful treatment of myocarditis in this species.     

INHIBITION OF RAT BRAIN PHENOL SULPHOTRANSFERASE IN VITRO BY NORADRENALINE and DOPAMINE METABOLITES1

Abstract— Kinetic parameters of the sulphotransferase reaction in rat brain were investigated in vitro at pH 7.4. Evidence is presented that the enzyme phenol sulphotransferase (EC 2.8.2.1) can be assayed with 4-methylumbelliferone or 3-methoxy-4-hydroxyphenylethyleneglycol as the substrate. Both assays give identical V_max values, whereas K_m values are 0.026 mm and 0.039 mm , respectively. Normetanephrine, metanephrine and the catecholamines adrenaline and dopamine, having a positive charge on the side chain at pH 7.4, do not inhibit 4-methylumbelliferone and 3-methoxy-4-hydroxyphenylethy-leneglycol sulphotransferase at this pH. Their deaminated metabolites 3,4-dihydroxyphenylethyleneglycol, 3,4-dihydroxymandelic acid, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol, 3-methoxy-4-hydroxyphenethanol and 3-methoxy-4-hydroxyphenylacetic acid inhibit both the enzyme activities. The type of inhibition is noncompetitive with the exception of 3-methoxy-4-hydroxy-phenylethyleneglycol, which is a competitive inhibitor of 4-methylumbelliferone sulphation. 3-Methoxy-4-hydroxy-mandelic acid does not inhibit the enzyme activities. It is concluded that the catecholamines themselves are not sulphated by rat brain in vitro at pH 7.4.     

Parkinson's disease.

In Parkinson''s disease there is degeneration of neurons in the substantia nigra, with consequent depletion of the neurotransmitter dopamine. The triad of tremor, rigidity and bradykinesia is the clinical hallmark. Drugs currently used for palliative therapy fall into three categories: anticholinergic agents, dopamine precursors (levodopa combined with extracerebral decarboxylase inhibitors) and artificial dopamine agonists. It has been argued, on theoretical grounds, that some drugs slow the progress of Parkinson''s disease, although no firm evidence has supported this. Treatment must be individualized, and more than one type of drug can be given concurrently after a careful build-up in dosage. We review the adverse effects of various drugs and consider new developments such as slow-release preparations, selective D-1 and D-2 agonists and transplants of dopaminergic cells into the brain. The treatment of Parkinson''s disease can be demanding, rewarding and sometimes frustrating, but it remains a most challenging exercise in pharmacotherapy.     

Tc-99m-Labeling of Modified RNA

Abstract

The synthesis of Tc-99m-labeled, modified RNA is reported. This new class of radiopharmaceuticals is of potential interest as target specific imaging agents. The preparation of N₃S-RNA was achieved by coupling protected MAG₂-units to amino modified ON's. The N₃S-RNA was Tc-99m-labeled with 90–95% radiochemical yield and specific activities of 37MBq/nmol leading to 1:1-Tc-99m-N₃S-aptamers.