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The subcellular distribution of malate, 2-oxoglutarate, citrate, aspartate and glutamate and the mitochondrial and cytosolic pH values were determined in perfused livers from fed and fasted rats. The method of fractionation of the freeze-dried tissue in non-aqueous solvents was employed. The following results were obtained: 1) Di- and tricarboxylates are(More)
In 2000, regulation on orphan medicinal products was adopted in the European Union with the aim of benefiting patients who suffer from serious, rare conditions for which there is currently no satisfactory treatment. Since then, more than 850 orphan drug designations have been granted by the European Commission based on a positive opinion from the Committee(More)
The simultaneous determination of serum catecholamine (CA) and their receptors in blood cells offers the possibility of evaluating disturbances of the dopamine (DA) and noradrenaline (NA) neuronal systems in man. High-affinity binding sites for 3H-yohimbine in platelets, 3H-DHA in granulocytes, and 3H-spiperone in lymphocytes from healthy control persons,(More)
1. Isolated rat kidneys were perfused (single pass) with 4 to 40 microM soln. of 4-dimethylamino[14C]phenol (DMAP). 2. Nephrotoxicity was not detected at concn. of 14C-DMAP up to 18 microM; higher conc. resulted in irreversible loss of physiological functions with simultaneous five-fold increase in covalently bound 14C. 3. At all concn., 85% of the(More)
The specific binding of the dopamine antagonist 3H-spiperone to lymphocytes from a healthy control group (n = 40), a group of acute, unmedicated schizophrenic patients (n = 27), and a psychiatric control group (n = 16) was investigated. There were no differences in binding parameters between the healthy controls (Bmax 2.6 +/- 0.7 fmoles/10(6) cells; Kd 0.17(More)
The use of biomarkers within the procedures of the Committee of Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) is discussed herein. The applications for Orphan Medicinal Product designation in the EU are evaluated at two stages. At the time of orphan designation application, the file undergoes an assessment to establish whether the(More)
The intestinal first pass metabolism of amygdalin has been investigated in rat small intestine in vitro. The results show that amygdalin is hydrolyzed to prunasin, essentially in the wall of the proximal jejunum. This specific beta(1-6)hydrolytic cleavage of the terminal glucose residue is pH-dependent and can be inhibited by glucono-delta-lactone, a potent(More)