A progressive decrease of dopamine and related enzyme activities and a decline in the dopaminergic receptor functions in the striatum and limbic system controlling behavior have been observed in senescent brain. These changes provide a neurochemical basis for some behavioral and mental disturbances of the aged and suggest the possibility of a substitution therapy of neurotransmitter deficiency of senile and presenile dementia. Previous reports on the effects of levodopa treatment of dementia in parkinsonism and aging have given conflicting results. A controlled double-blind study of 6 months' administration of levodopa plus decarboxylase inhibitor given at oral doses of 250 mg daily versus placebo in twelve patients aged 54--60 years showing initial signs of organic dementia was performed. Clinical rating of twelve parameters of organic brain syndrome and psychometric studies using three subtests of the HAWIE (digit span, coding B test and block design) indicate improvement in the overall scores of organic brain syndrome and in particular in the visuospatial functions, visual memory, and visual-motor coordination. In general, improvement increased with the duration of levodopa treatment. These preliminary data suggest some beneficial effect of levodopa treatment in early stages of presenile dementia and thus open new therapeutic aspects in neurogerontology.

Benserazide↗

PubMedDate not supplied

Stabilization and characterization of the dexamethasone-binding proteins in rat liver cytosol.

Conditions were worked out for maximal stabilization of dexamethasone binding activity of rat liver cytosol in the absence of the protective steroid ligand. Important stabilization factors are ionic strength, thiol-protecting agents, glycerol and pH. Maximal stability of the cytosol is observed in a buffer consisting of 20 mM Tris-HCl, pH 7.5, 50 mM KCl, 25 mM beta-mercaptoethanol and 20% glycerol. Chromatography of cytosol on DEAE-cellulose revealed the existence of three dexamethasone receptors, binder DE-1, present in the flow-through fraction and binders DE-2 and DE-3, eluting from the column with salt concentrations of 100 and 190 mM, respectively. Binders DE-2 and DE-3 are not adsorbed on phosphocellulose at pH 7.5, whereas binder DE-1 is. All three receptors are retained to varying degrees on DNA-cellulose columns: binder DE-1 is eluted with salt concentrations of 270 mM, whereas binders DE-2 and DE-3 are eluted between 180 and 200 mM NaCl. The dexamethasone receptors also bind natural glucocorticoids, but to varying degrees, the highest binding being observed to binder DE-2. The receptors obtained after chromatography on DEAE-cellulose, but not on phosphocellulose, cannot be to an appreciable extent charged with dexamethasone.

Animals↗

PubMedDate not supplied

[Acceleration of epiphyseolysis capitis femoris lenta as a complication of growth hormone therapy in hypophyseal insufficiency].

Slipped capital femoral epiphysis is a rare complication of growth hormone therapy. We report on a young man with pituitary insufficiency, diagnosed and treated with growth hormone at the age of 14 9/12. The patient withdrew from treatment after 6 months of growth hormone therapy without significant catch-up growth or complications. At the age of 21 8/12 years slipping of the left femoral capital epiphysis became apparent 2 1/2 months after treatment with growth hormone had been resumed in combination with low dose testosterone. Young adult patients with unfused epiphyses undergoing growth hormone substitution should be informed that pain in the lower extremities during therapy may be an important sign of a complication of growth hormone therapy. In this age group, patients complaining of pain in the limb should alert the physician to the possibility that a slipped capital femoral epiphysis may be present.

Adolescent↗

PubMedDate not supplied

Human fibroblasts in culture exhibit a low sensitivity against cyclosporin A treatment.

The nephrotoxicity of cyclosporin A (CSA) after chronic treatment is well known and includes in later stages tubular atrophy associated with interstitial fibrosis. In order to examine whether interstitial fibrosis due to CSA treatment in vivo is related to a hyperproliferative activity of fibroblasts, the effects of CSA on the growth characteristics of cultured human skin fibroblasts (HUSF) were investigated at CSA concentrations ranging from 10 ng/ml to 50 micrograms/ml. We found that CSA at concentrations higher than 7.5 micrograms/ml inhibited cell proliferation (p < 0.05 at concentrations above 5 micrograms/ml; n = 3) and cloning efficiency (p < 0.05 at concentrations above 5 micrograms/ml; n = 3) in a dose-dependent manner and caused a promotion of cell attachment at concentrations above 10 micrograms/ml (p < 0.05; n = 4), but did not influence cell spreading. At lower concentrations CSA-treated HUSF did not differ in their growth characteristics from the corresponding controls. A 50% inhibition of proliferation was calculated by extrapolation for a CSA concentration of 70 micrograms/ml for HUSF. The inhibition of HUSF proliferation was reversible even at the highest CSA concentration of 50 micrograms/ml. Under the same experimental conditions, a 50% inhibition of proliferation was observed for Madin-Darby canine kidney (MDCK) cells to be 5.5 micrograms/ml, e.g. at a 15-fold lower CSA concentration. Moreover, CSA caused a dose-dependent and reversible cell elongation of HUSF and a significant increase in the average cell diameter from 19.2 +/- 0.3 microns (control; mean +/- SEM, n = 4) to 22.2 +/- 0.2 microns for 50 micrograms/ml CSA (mean +/- SEM, n = 4) and in median cell volume from 4,210 +/- 160 fl (control; mean +/- SEM, n = 4) to 7,020 +/- 190 fl for 50 micrograms/ml CSA (mean +/- SEM; n = 4). These alterations described above were not correlated with a cytotoxic effect as checked by a fluorescent staining for cell vitality. Alterations in the organization of cytoskeletal components such as stress fibers, intermediate-sized filaments and microtubules directly due to CSA treatment were not observed. In contrast, the amount of fibronectin present on the cell surface was considerably increased by CSA. Although HUSF in culture do not respond to CSA treatment by an increased proliferative activity, they are much less affected by CSA than other cell types (i.e MDCK cells).(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Adhesion↗

PubMedDate not supplied

Peripheral and central thermosensitivity.

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Animals↗