Effect of dipyridamole on glomerular mesangial cell ecto-5′-nucleotidase expression

Although dipyridamole has been extensively studied as an anti-aggregating agent, its mechanism of action has not been elucidated. Cultured mesangial cells were treated with dipyridamole 1–100 M from 6–72 h. Ecto-5-nucleotidase activity approximately doubled (from 115±11 to 226±14 nmol/min/mg) after treatment with 100 M dipyridamole for 72 h. This effect was concentration- and time-dependent. Cycloheximide, an inhibitor of protein synthesis, did not alter basal 5-nucleotidase activity. However, it prevented stimulation by 5 M dipyridamole. Adenosine availability at the receptor sites was increased by dipyridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI), which inhibit adenosine uptake into the cell. Addition of dipyridamole or NBTI to the adenosine-treated mesagial cells produced an additive increase in ecto-5-nucleotidase activity. Dipyridamole, through its effect on extracellular adenosine and ecto-5-nucleotidase, may have an influence upon regulation of the glomerular microcirculation.     

Zur Frage der glomerulären Permeation höhermolekularer Proteine

Summary Haptoglobin and isoagglutinin were found in the urine of diabetic patients, and their renal excretion was higher in patients with diabetic angiopathy. It is concluded from these results (the biological activity of the two polypeptides in urine was intact) that the mechanism of proteinuria can perhaps be explained only by an extension of pores of the renal glomerular filter.     

The COMT inhibitor tolcapone potentiates the anticataleptic effect of Madopar in MPP+-lesioned mice

Orally administered Madopar (levodopa/benserazide 41) dose-dependently antagonized haloperidol-induced (1 mg/kg s.c.) catalepsy in MPP⁺-lesioned mice. Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy. The ability of tolcapone to increase the Madopar effect was significantly attenuated by high doses of 3-O-methyldopa (3-OMD) (800 mg/kg i.p.). This might suggest a competitive blockade of the active transport of levodopa through the blood-brain barrier. In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD.     

A2 adenosine receptors in human glomerular mesangial cells

A₂ adenosine receptors were characterized in human glomerular mesangial cells using [³H] 5-N-ethylcarboxamidoadenosine (NECA) as a tracer. There was a single group of receptor sites with a K_D of 184 nM, and a number of sites of 317 fmol/mg of cell protein. Adenosine agonists increased 5-nucleotidase activity via A₂ receptor stimulation. The specific A₂ agonist-NECA, at 0.1 and 1 m, was a potent inhibitor of DNA synthesis.     

Cyclophosphamide-impaired regulation of hepatic heme metabolism

Summary Im male rats hepatic cytochromes b₅ and P-450 were reduced at different times after treatment with cyclophosphamide (CP) (200 mg/kg i.p. for 3 days). In contrast, microsomal heme did not change until 48 h after the last dose of CP, leading to accumulation of heme in a non-cytochromal form. Parallel to the above changes the heme metabolism showed derangement: -aminolaevulinate synthase, the rate-limiting enzyme in heme synthesis, was depressed and heme oxygenase, the enzyme which catalyzes the oxidative degradation of heme, was increased.     

Effect of 723-1723-1723-1on ethanol withdrawal in mice

Summary ⁹ (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when ⁹ was administered chronically during the exposure to ethanol.     

Effect of desipramine on the contents of some free amino acids of mouse brain

Summary I.p. injections of desipramine-HCL (100 mg/kg) produced decreases in the contents of several amino acids of mouse brain after 1 h. Using a 10–100 mg/kg range of doses, these effects appeared to be dose-dependent for -alanine and aspartate. These changes may be due, in part, to a decrease in cerebral oxidative metabolism (Krebs cycle activity) which occurs secondarily to desipramine-induced hypothermia.This study was supported by Centro Ramón y Cajal and Fundacion Juan March.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Summary Low i.v. doses of cadmium chloride (15 g Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed.It is suggested that the renal changes following the i. v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

Monoaminoguanidine prevents sorbitol accumulation, nonenzymatic protein glycosylation and development of kidney lesions in diabetic rats

Monoaminoguanidine administration (25 mg/kg b.wt, i.p. for 14 weeks) to alloxan diabetic rats (blood glucose greater than or equal to 250 mg/dl) decreased the nonenzymatic protein glycosylation and sorbitol levels. It prevented development of Armanni-Ebstein tubular lesions, pathological changes in the glomerular capillary tufts and glomerular basement membrane thickening in the kidney.     

Comparative dominant lethal studies with phenylbutazone,thio-TEPA and MMS in the mouse

Zusammenfassung Im Gegensatz zu Thio-TEPA (N, N, N-Triaethylen-thiophosphoramid) und MMS (Methansulfonsäuremethylester) führten i.p. Dosen von Phenylbutazon (50 und 100 mg/kg) bei der Maus, unter Berücksichtigung von post- und prae-implantativen Gestationsstadien, zu keinen genetischen Effekten im Sinne der Induktion von dominanten Letalfaktoren.     

Optimum level of combined adrenergic blockade for the experimental study of hemorrhagic shock

Zusammenfassung Die Kombination von 1,0 mg/kg -Blocker und 0,1 mg/kg Blocker ergibt im experimentellen hämorrhagischen Shock die geringste Reduktion des tolerierten Blutverlustes zusammen mit einer maximalen Hemmung seiner metabolischen Konsequenzen und erscheint daher als optimal.

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Work supported by Research Grant No. 4423 from the Swiss National Foundation for the Advancement of Scientific Research.     

Occurrence of mitochondrial monoamine oxidase in human semen

Summary Mitochondrial monoamine oxidase (MAO) was found in human semen, showing its K_m and V_max values of 91.7 M and 290 pmoles/mg of protein/60 min, respectively, with kynuramine as substrate. A major part of the activity was due to type A MAO.     

Interaction of chloramphenicol and 181-1181-1181-1in barbital-anesthetized mice

Résumé L'augmentation de l'anesthésie produite par le barbital chez la souris traitée au ¹-tétrahydrocannabinol ( ¹-THC) à 10 ou 20 mg/kg par voie i.p. est accentuée d'une manière significative par le traitement préalable au chloramphénicol (CHPC) à 100 mg/kg, mais non pas par 50 mg/kg de ce composé injecté par voie i.p. Le CHPC seul n'a aucun effet. Le CHPC étant un inhibiteur des systèmes enzymatiques des microsomes hépatiques, on en a conclu que l'effet du ¹-THC sur le prolongement de la durée du sommeil au barbital est dû au composé parent plutôt qu'à l'un des produits de transformation biologique.     

Tumor necrosis factor α in the pathogenesis of cerebral malaria

Physiologically in the brain, cytokines such as tumor necrosis factor-alpha (TN) are released by the immune system and can modulate neurological responses. Conversely, the central nervous system (CNS) is also able to modulate cytokine production. In the case of CNS disorders, cytokine release may be modified. Cerebral malaria (CM) is a complication of Plasmodium falciparum infection in humans and is characterized by a reversible encephalopathy with seizures and loss of consciousness. Central clinical signs are partly due to sequestration of parasitized red blood cells in the brain microvasculature due to interactions between parasite proteins and adhesion molecules. TNF is produced and released by host cells following exposure to various malarial antigens. The increase of TNF release is responsible for the overexpression of adhesion molecules. This article reviews the involvement of TNF in cerebral malaria and the relation with all the processes involved in this pathology. It shows that (i) TNF levels are increased in plasma and brain but with no clear correlation between TNF levels and occurrence and severity of CM; (ii) TNF is responsible for intercellular adhesion molecule-1 upregulation in CM, the relation being less clear for other adhesion molecules; (iii) TNF receptors are upregulated in CM, with TNF receptor 2 (TNFR2) showing a higher upregulation than TNFR1 in vivo; (iv) in murine CM, low doses of TNF seem to protect from CM, whereas excess TNF induces CM and anti-TNF therapies (antibodies, pentoxifylline) did not show any efficiency in protection from CM. Moreover, the involvement of lymphotoxin a, which shares with TNF the same receptors with similar affinity, appears to be an interesting target for further investigation.Received 4 December 2002; received after revision 7 February 2003; accepted 14 February 2003     

The effect of o,p′-DDD on the adrenal cortex in sheep

Summary The effect of o,p-DDD (200 mg/kg/day given p.o. for 100 consecutive days) on the sheep adrenal gland was studied. The results suggest that this ruminant species is highly resistant to the adrenocorticolytic activity of o,p-DDD when compared with dogs.This work was supported by a grant of Bristol Laboratories, Syracuse, New York 13201, USA.     

Rat mammary cancer inhibition by a prolactin suppressor, 2-bromo-α-ergokryptine (CB 154)

Zusammenfassung 2-Br--Ergokryptin (=CB 154) wurde täglich während 80–100 Tagen, beginnend mit der Carcinogenapplikation, DMBA - (5 mg i.v.)-behandelten weiblichen Ratten in der Dosis 6 mg/kg i.p. verabreicht. CB 154 bewirkte ein verzögertes Erscheinen und ein langsameres Wachsen der Mamma-Tumoren sowie eine verminderte Todesrate der carcinogenbehandelten Ratten.     

Physiological importance of ω-3/ω-6 polyunsaturated fatty acids in man. An overview of still unresolved and controversial questions

Summary The essentiality of (-6) and (-3) fatty acids in mammals is well known. Nevertheless, some important points remain unclear concerning their implication in physiology. After a short discussion about the definition of essential fatty acids deficiency, this brief overview deals with some of these points, pointing out some of the unresolved questions. Different subjects are approached concerning the (-6) and (-3) fatty acids metabolism: desaturases, eicosanoids, production, as well as some of their metabolic effects on cell membranes, intestinal function, glucose and lipid metabolism, haemorheology.     

Inhibition of food intake in the rat by cyproheptadine

Summary In a model of conditioned feeding behavior, oral administration of cyproheptadine (1–100 mg/kg), 30 min before presentation of food, produced a dose-dependent reduction of food intake in the rat (ED₅₀17 mg/kg during the 1st h of testing). This anorexic effect persisted for at least 24 h. These results provide further evidence that under certain conditions cyproheptadine, which is used as an orectic agent in man, can produce anorexia.