Effect of acetylsalicylic acid on renal function in systemic lupus erythematosus

Summary Glomerular filtration rate (GFR;⁵¹Cr-EDTA clearance), serum creatinine concentration and urinary excretion of prostaglandins were measured in 8 patients with systemic lupus erythematosus (SLE) before and after 2 weeks of treatment with acetylsalicylic acid (ASA). ASA 65 mg/kg or up to 4 g/daily was given as a sustained release preparation. The serum salicylate concentration ranged from 0.3 to 1.6 mmol/l. Serum creatinine after 1 and 2 weeks and GFR after 2 weeks of ASA treatment showed no significant changes. There was a clearcut decrease in urinary excretion of prostaglandins PGE₂ and PGF₂, by 44% and 50%, respectively. It is concluded that therapeutic doses of ASA do not cause deterioration of GFR in patients with SLE and normal or moderately reduced renal function.     

Effects of L-ascorbic acid supplementation on dieldrin toxicity in rats

Chronic dieldrin administration to rats (5 mg/kg/day) produced pathological changes in liver and kidney tissues. Dieldrin treated rats showed high levels of liver ascorbic acid and increased activities of inorganic pyrophosphatase in brain and glucose-6-phosphatase in liver. The activities of Mg²⁺-ATPase in liver and acetylcholinesterase in brain were decreased under toxic doses of dieldrin. L-Ascorbic acid supplements in treated animals could partially prevent the pathological alterations, as observed histologically in liver and kidney tissues. Administration of this vitamin could also prevent alterations in some enzyme activities produced by toxic dieldrin doses.     

Huntington's Disease — Imbalance of free amino acids in the cerebrospinal fluid of patients and offspring at-risk

Summary A total of 27 different amino acids were determined in the fasting, morning lumbar CSF of 12 patients with Huntington's Disease (HD), 8 at-risk offspring and 16 non-choreic control patients. A significant (P<0.001) decrease was observed for asparagine, isoleucine, leucine, phenylalanine, histidine, arginine, -aminoadipic acid and homocarnosine in patients with HD compared to the non-choreic controls. Only tyrosine was increased in HD. These alterations were to an extent more pronounced in 5 neurophysiologically conspicuous offspring. The alterations suggest that amino acid imbalance is an early metabolic disturbance in HD.

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Zusammenfassung Bei 12 Patienten mit manifester Huntingtonscher Krankheit (HD), 8 nicht erkrankten Nachkommen und 16 nicht choreatischen Kontrollpatienten wurden 27 verschiedene Aminosäuren im Liquor cerebrospinalis (nüchterner Lumballiquor) untersucht. Asparagin, Isoleucin, Leucin, Phenylalanin, Histidin, Arginin, -Aminoadipinsäure und Homocarnosin waren signifikant (P<0.001) erniedrigt bei Patienten gegenüber den Kontrollen. Diese Veränderungen waren bei 5 neurophysiologisch auffälligen Nachkommen teilweise ausgeprägter, was für eine frühzeitige metabolische Störung spricht. Tyrosin war als einzige Aminosäure erhöht. Die Veränderungen sprechen für eine Aminosäurenimbalanz bei Huntingtonscher Krankheit, deren Bedeutung besprochen wird.

     

Glutamic acid concentration in human semen--its origin and significance

Glutamic acid content of semen was determined photometrically in over 400 semen specimens. Glutamatic acid content was found to increase proportionately to temperature in the first few hours post ejaculation. The glutamate estimation should therefore be performed on semen at 30 min. after ejaculation. The frequency distribution of glutamic acid concentration with 400 unselected specimens, 50 "normozoospermias" as well as 42 azoospermias is shown. The mean value of normozoospermias was 10.6 mg% (+/- 4.6 mg%) that of azoospermias 7.7 mg% (+/- 4.7 mg%). There was no correlation found between glutamic acid content and pH value. A correlation however, was demonstrated between glutamic acid and following: sperm count, citrate concentration, gamma-GT and carnitine. No correlation to fructose content was detectable. That suggests that glutamate gets to the ejaculate with the secretions from the prostate gland and epididymis whereas the seminal vesicles do not play a role in the level in the total semen.     

Cerebrospinal fluid cyclic AMP and acid monoamine metabolites following probenecid: Studies in psychiatric patients

At probenecid levels greater than 10 g/ml, CSF cAMP was independent of CSF probenecid concentration. At these levels of probenecid, cAMP transport out of CSF is probably maximally blocked and cAMP levels reflect cAMP release into CSF. CSF cAMP was significantly higher in RDC-diagnosed schizophrenics than in other psychotics or depressives. A significant decrease in CSF cAMP was found in psychotic patients treated with chlorpromazine. No changes in CSF cAMP were observed in patients treated with tricyclic antidepressants or lithium.     

Acid maltase deficiency in non-identical adult twins

Summary Acid maltase deficiency is described in non-identical adult twins. The onset of the disease can be traced into late infancy; the clinical picture is one of severe muscular dystrophy; respiratory insuficiency was the cause of death in one case. The autopsy showed the central nervous system, heart and liver to be spared. Glycogen filled vacuoles are found in skin, mesenchymal cells, small nerves and skeletal muscles. The light microscopic study of 9 different muscles showed extremely variable involvement ranging from normal appearance to overt vacuolization. A 6–20% residual acid -glucosidase activity was found in visceral organs, cultured fibroblasts and in some skeletal muscles. No satisfactory explanation can be given why this generalized acid -glucosidase deficiency produces a selective involvement of skeletal muscles. If compared with infantile AMD (Pompe's disease) our cases have a much higher residual acid -glucosidase activity and show the presence of an antigenically detectable protein.From our study and from a similar report in the literature (de Barsy et al., 1975), it appears that a combined approach of light microscopy, electron microscopy and biochemical analysis (determination of acid -glucosidase) is necessary to make a diagnosis of AMD in adults.Dr. Th. de Barsy is a Research Fellow of the Fonds National de la Recherche Scientifique.     

Pharmacokinetics of ascorbic acid in man

Summary The pharmacokinetic characteristics of ascorbic acid have been investigated in normal adult volunteers, using a two-compartment open model. After oral administration in a normal gelatine capsule the bioavailability of ascorbic acid was 69%. It was 98% when a sustained-release preparation was given in an identical capsule. During daily oral intake of ascorbic acid 1 g in the sustained-release form blood levels reached the equilibrium state within 3 days. Daily doses of ascorbic acid 1 g resulted in tissue saturation in 7 days, with a profound change in the pharmacokinetics of the vitamin. The binding of ascorbic acid to plasma proteins was low (24%). Its significance for the pharmacokinetic behaviour of the drug is discussed.     

Connective tissue growth factor: a novel player in tissue reorganization after brain injury?

Recent studies have suggested a role of connective tissue growth factor (CTGF) in repair processes of the skin as well as in various types of fibrotic disease. However, a function of this molecule in central nervous system (CNS) repair has not been demonstrated yet. In this study we analysed the temporal and spatial expression pattern of CTGF after unilateral kainic acid lesions of the hippocampal CA3 region in mice. We found a strong induction of CTGF mRNA and protein expression in neurons and glial cells of the lesioned hippocampus. Interestingly, increased expression of this mitogen was accompanied by elevated levels of the extracellular matrix molecule fibronectin, which is a known target of CTGF action. Therefore, our data indicate a novel function of CTGF in postlesional restructuring of the hippocampus, where it possibly participates in glial scar formation.     

Norepinephrine regulation of growth hormone release from goldfish pituitary cells. II. Intracellular sites of action

Previous results suggest that norepinephrine decreases growth hormone (GH) release in goldfish by means of alpha-2 adrenoceptor activation. The intracellular mechanisms by which norepinephrine inhibits GH release were examined in the present study using dispersed goldfish pituitary cells. In 2-h static incubation experiments, norepinephrine and the alpha-2 agonist clonidine decreased basal GH release and the GH responses to stimulation by the dopamine D1 agonist SKF38393 and two native gonadotropin-releasing hormones (GnRH). Norepinephrine also reduced GH responses to the adenylate cyclase activator forskolin, two protein kinase C (PKC) activators (phorbol ester and synthetic diacylglycerol), and two Ca2+ ionophores (ionomycin and A23187). Similarly, norepinephrine applied as a 1-h pulse in cell column perifusion experiments reduced basal GH release and abolished the GH response to a 5-min pulse of arachidonic acid. In goldfish, D1-stimulated GH release is mediated by AC-, arachidonic acid-and Ca2+-dependent pathways, whereas GnRH action is coupled to PKC-and Ca2+-dependent mechanisms. These results suggest that norepinephrine activation of alpha-2 receptors inhibits ligand-induced GH secretion by actions subsequent to activation of these second messenger cascades. To further characterize norepinephrine mechanisms of action on unstimulated hormone release, the ability of norepinephrine and an alpha-2 agonist to affect activation of two second messenger cascades under basal conditions was also investigated. Static incubation with clonidine reduced cAMP production in a time-and dose-dependent manner, suggesting that norepinephrine inhibitory action can also be expressed at the level of cAMP production. Resting intracellular free calcium levels in single, identified goldfish somatotropes was unaffected by norepinephrine. However, the inhibitory effects of norepinephrine on basal GH secretion was not observed in the presence of a voltage-sensitive Ca2+ channel agonist. Whether these channels are targets for norepinephrine action on unstimulated GH release requires further investigation.