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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 343 records · Page 19Linked to original sources
PubMed1988

Does immunodeficiency in uremic patients promote dialysis-related amyloidosis?

The present study was undertaken to evaluate the immune function of 5 hemodialysis patients with dialysis-related amyloidosis as compared to 6 without, both groups having a dialytic age from 7 to 21 years, and 5 healthy controls. We investigated serum levels of immunoglobulins (IgG, IgA, IgM), made skin tests and measured peripheral lymphocyte subsets using monoclonal antibodies. 1) The absolute numbers of T3, T4 and T8 cells were significantly lower in hemodialysis patients than controls and T3, T4 cells were lower in patients with amyloidosis than in those without: T3 (m +/- SD/microliter), 387 +/- 253 vs 744 +/- 207 (p = 0.03); T4, 262 +/- 115 vs 589 +/- 297 (p = 0.04). 2) Serum levels of IgG and IgM were significantly lower in patients with amyloidosis than in the others: IgG (m +/- SD, g/l), 10.2 +/- 1.4 vs 15.4 +/- 3.2 (p less than 0.001); IgM, 0.65 +/- 0.28 vs 1.65 +/- 0.37 (p less than 0.001). 3) Delayed hypersensitivity studied by skin tests showed less than 3 positive antigens in 4/5 patients with amyloidosis against 1/6 patients without. These data suggest there is a marked defect of T-cell help in uremic patients with dialysis-related amyloidosis.

Adult↗
PubMed1988

Effects of imipramine-like drugs and serotonin uptake blockers on delay of reward in rats. Possible implication in the behavioral mechanism of action of antidepressants.

This study investigated in rats the action of a variety of antidepressants in two behavioral models. In model 1, animals trained in a T-maze were allowed to choose between 2 magnitudes of reward: immediate but small reward (2 pellets) vs. a 25-sec delayed but large reward (10 pellets). Under this alternative, vehicle-injected rats selected the large-but-delayed reward in less than 40% of the trials. Desipramine 8 mg/kg, clomipramine 8 mg/kg, maprotiline 8 mg/kg, indalpine 2 to 4 mg/kg, zimelidine 8 to 16 mg/kg, nialamide 16 to 32 mg/kg and clenbuterol 0.03 to 0.06 mg/kg significantly increased the number of choices of the large-but-delayed reward. In model 2, rats were subjected to a fixed ratio 48 schedule of food reinforcement; after completion of a series of exactly 48 presses a food pellet was delivered, and if no further press occurred, a sequence of free pellets was initiated according to fixed, increasing intervals (from 5-80 sec). Pressing during the sequence stopped it and required the rat to complete again the fixed ratio 48 to be reinforced and to reintiate the sequence. Waiting for free reward was significantly lengthened by desipramine 8, clomipramine 16, indalpine 8, zimelidine 8 to 16, nialamide 32 and clenbuterol 0.007 to 0.06 mg/kg. These results suggest that, possibly through noradrenergic and serotonergic mechanisms, antidepressants markedly enhanced rats' ability to wait for food reward, an affect which might reflect the ability of these drugs to improve impulse control. The relevance of such a property in the therapeutic action of antidepressants remains to be delineated.

Animals↗
PubMed1987

Tumor-specific genetically engineered murine/human chimeric monoclonal antibody.

Murine variable and human constant region exons were fused to produce "chimeric" immunoglobulin gamma and kappa genes. These constructs were cotransfected into murine myeloma cells which then produced and secreted intact, functional antibody. Cells secreting the chimeric antibody were introduced into mice. The engineered immunoglobulin was subsequently harvested from ascites fluid and was purified by affinity chromatography. Its immunological properties were compared to those of the parental murine monoclonal (B6.2), which exhibits specificity for human breast, lung, and colon carcinoma cells. Competitive binding, immunofluorescent cell staining, and analysis of immunoprecipitated antigen gave similar results for the chimeric and murine B6.2. The biodistribution of chimeric and murine B6.2 after injection into mice bearing human tumors was found to be identical. These results suggest that murine/human chimeric antibodies may be viable clinical replacements for murine monoclonals with the potential for better immunological tolerance and pharmacological efficacy.

Animals↗
PubMed1987

Polymorphic DNA marker on X chromosome and manic depression.

Heredity is an important factor in vulnerability to manic depression. A genetic linkage has been demonstrated between manic depression and coagulation factor IX at Xq27 with a TaqI polymorphism at the F9 locus in DNA samples from peripheral leucocytes of manic depressive probands and relatives in 10 informative families. Statistical analysis of the pedigrees gave a maximum lod score of 3.10 at a recombination fraction of 0.11, demonstrating a linkage between a manic depressive locus and the F9 locus in the Xq27 region.

Bipolar Disorder↗
PubMed1987

Triiodothyroacetic acid-induced reversal of learned helplessness in rats.

Triiodothyronine (T3), successfully used as therapeutic agent in euthyroid depressive states, has been found to exert an antidepressant-like effect in various psychopharmacological tests in rodents. Therefore the possible antidepressant-like activity of triiodothyroacetic acid (TA3), a natural metabolite of T3, was investigated in rats subjected to helplessness training. The animals were first exposed to inescapable shock pretreatment (60 shocks, 15 s duration, 0.8 mA every min +/- 15 s) and 48 h later, shuttle-box training (30 trials/day, ITI: 30 s) was performed on 3 consecutive days in order to assess escape deficits. As compared to control rats (no shock pretreatment), the rats exposed to inescapable shocks exhibited escape deficits when tested for subsequent responding in the shuttle-box. Daily i.p. injections of TA3 (0.5 mg/kg) prevented escape deficits as did daily injections of tricyclic antidepressants. These data are in agreement with previous results bearing on the similarity of action of TA3 and tricyclic antidepressants and extend to the thyroid axis the neuroendocrine systems that can be affected by exposure to uncontrollable stressors.

Animals↗
PubMed1987

Effects of neuroleptic drugs, clonidine and lithium on the expression of conditioned behavioral excitation in rats.

Rats with a history of daily (21 days) amphetamine (2.5 mg/kg) treatment showed enhanced activity when under placebo in their amphetamine-associated environment. We found that this conditioned effect was reduced by haloperidol (0.06; 0.125; 0.25 mg/kg), pimozide (0.25; 0.5 mg/kg) and sulpiride (8; 16; 32 mg/kg) but only at doses similar to or, in the case of pimozide, higher than those required to antagonize the unconditioned stimulant effects of amphetamine (2.5 mg/kg). Conversely, we observed that clonidine (7; 15; 30; 60 micrograms/kg) or lithium regimen (between days 15 and 21) leading to lithium plasma levels of 1.3 +/- 0.1 mEq/l, abolished amphetamine-conditioned hyperactivity but did not affect the unconditioned stimulation of amphetamine or locomotor activity in control rats. Moreover, we found that hyperactivity induced by the daily anticipation of food delivery shared identical pharmacological sensitivity with the behavioural excitation produced by a conditioning history with amphetamine. In light of the antimanic properties of lithium and clonidine and the ability of this latter drug to reduce noradrenergic transmission, our findings raise the possibility that incentive activity may model noradrenergic-dependent aspects of mania.

Animals↗
PubMed1987

Comparing benzodiazepines using the staircase test in mice.

Eleven benzodiazepines were evaluated in the staircase test in mice. The behavioural parameters measured were the number of steps climbed and the number of rears during a 3-min test. Climbing and to a lesser extent rears were enhanced at low doses, whereas both parameters, particularly rearing, were reduced at higher doses. The differential effects of the drugs on the two parameters were used to determine indices of anxiolytic efficacy for each drug where increases in climbing were taken to indicate the onset of anxiolytic activity and decreases in rearing the onset of sedative activity. The compounds could be ranked according to these indices in a manner which appears to reflect their therapeutic profile in man.

Animals↗
PubMed1987

Lesions of the serotonergic system impair the facilitation of but not the tolerance to the effects of chronic clenbuterol administration.

Acute clenbuterol, a beta-adrenergic stimulant, decreases motility and antagonizes reserpine-induced hypothermia in mice. After repeated treatment with clenbuterol, the hypomotility disappears (tolerance) but the antagonism of reserpine-induced hypothermia increases (facilitation). To investigate the function of serotonin in tolerance and facilitation, lesions of the serotonergic system were performed by intracerebroventricular administration of the neurotoxin 5,7 dihydroxytryptamine (5,7-DHT). After lesions of the serotonergic system, the tolerance to clenbuterol-induced hypomotility persists, but the facilitation of the antagonism by clenbuterol of reserpine-induced hypothermia disappears. Thus, the serotonergic nerve terminals must be intact for the latter but not the former response to occur. Since the reversal of reserpine-induced hypothermia in animals is predictive of antidepressant effects in man, it is suggested that the therapeutic action of clenbuterol in depressed patients may be mediated through the serotonergic system.

5,7-Dihydroxytryptamine↗
PubMed1987

Differential effect of N-acetylcysteine on excretion of the metals Hg, Cd, Pb and Au.

Male Wistar rats were subacutely treated with sublethal doses of HgCl2, CdCl2, Pb(NO3)2, or Na-aurothiomalate. The metal preparations contained trace doses of radioactive nuclide. Based on the doses given and on the radioactivity excretion in urine and faeces the body burden was determined. After the metal treatment periods, some of the animals received N-acetylcysteine (up to 100 mg/kg daily, on 6 consecutive days, i.p.), and the effect of this potential chelator on metal excretion was monitored. The excretion of Hg (after dosing with HgCl2) was not influenced by N-acetylcysteine. The elimination of Cd in urine (after dosing with CdCl2) was increased by a factor of four. Also, the elimination of Pb [after dosing with Pb(NO3)2] was gradually increased (in faeces and urine) by increasing doses of N-acetylcysteine. After dosing with Na-aurothiomalate, the excretion of Au in urine was increased to about 30%. The data suggest some activity of N-acetylcysteine in facilitating excretion of Pb, Cd or Au, but not of Hg.

Acetylcysteine↗
PubMed1987

Pharmacokinetics of desferrioxamine and of its iron and aluminium chelates in patients on haemodialysis.

We have used a new analytical micromethod to study the pharmacokinetics of desferrioxamine and its aluminium chelates in patients with chronic renal failure on haemodialysis. Desferrioxamine (Desferal, CIBA, Basle) was given by 1-h infusion just after the haemodialysis at 20, 40, 80 mg/kg body wt. and during the first and the last hour of the haemodialysis at 40 mg/kg. The concentrations of desferrioxamine during infusions showed a linear increase with increasing doses. The maximum concentrations and the AUC obtained when desferrioxamine was infused during the haemodialysis were not statistically different but slightly lower than those obtained in post dialysis administration. This result indicates that the loss of desferrioxamine by transfer in the dialysate is quite moderate within 1 h. During the interdialysis period, there was a decrease of plasma desferrioxamine concentrations with a mean half-life of 18.7 +/- 5.2 h and an increase in plasma concentrations of aluminium desferrioxamine chelate. In vitro studies show that a lengthy contact between desferrioxamine and plasma is necessary for complete chelation of A1 already present in plasma. During the following dialysis session, there was an important decrease of desferrioxamine and of its iron and aluminium chelates in blood plasma representing their transfer to the dialysis fluid.

Adult↗
PubMed1987

Noradrenergic rather than GABAergic processes as the common mediation of the antidepressant profile of GABA agonists and imipramine-like drugs in animals.

The present study was aimed at investigating in rats whether a common mechanism might underlie the reversal of depressive-like behaviors by classical antidepressants and by GABA agonists such as muscimol. Blockade of GABA transmission with picrotoxin (1 mg/kg IP) abolished the muscimol (0.5-1 mg/kg)-induced reduction of immobility in the swimming test and the reversal of escape failures in the learned helplessness paradigm. Conversely, picrotoxin was found not to reduce the efficacy of imipramine-like drugs in these same animal models. The combination of muscimol and tricyclics given at subeffective doses resulted in behavioral changes that can be accounted for by an additive interaction between these two classes of drugs. These data confirm the antidepressant-like profile of GABA agonists but suggest that it is unlikely that the primary antidepressant mechanism of conventional antidepressants involves GABA-A receptors. In the swimming test, prazosin (2 mg/kg), an alpha adrenoceptor blocker, antagonized the reduction of immobility produced by both muscimol and imipramine-like drugs. In the learned helplessness paradigm, penbutolol (0.25-0.5 mg/kg) and, though to a lesser extent prazosin, counter-acted the reversal of escape failures caused by muscimol and imipramine. On the basis of these data, it is tempting to speculate that increased transmitter outflow at noradrenergic receptors may be an essential component in the mechanism of action of imipramine-like drugs but also of GABA agonists.

Animals↗
PubMed1987

Reserpine-induced hypothermia: participation of beta 1 and beta 2 adrenergic receptors.

In mice, reserpine-induced hypothermia is partly antagonized by clenbuterol, a beta-adrenergic agonist specific for beta 2 receptors, and completely antagonized by dobutamine, a beta-adrenergic agonist specific for beta 1 receptors. In addition, the effects of dobutamine and of clenbuterol are impaired by betaxolol (1 and 4 mg/kg) and unchanged by ICI 118,551 (1 and 4 mg/kg) beta-blocking drugs respectively selective for beta 1 and beta 2 receptors. These results indicate that reserpine-induced hypothermia depends on the beta 1 receptors and lend support to an indirect effect of clenbuterol. After a chronic treatment, clenbuterol-induced antagonism of reserpine hypothermia is facilitated. This facilitation is impaired by ICI 118,551 and by betaxolol but, in this last case, with high doses only. So the facilitation involves beta 2 adrenergic receptors and implies an increase in the sensitivity of beta 1 receptors.

Animals↗
PubMed1987

Beta-adrenergic agonists reduce spontaneous motor activity through either beta 1 or beta 2 receptors.

In mice, the clenbuterol-induced decrease in spontaneous motor activity was antagonized by IPS-339 (beta 2 antagonist) but not by betaxolol (beta 1 antagonist), whereas the isoproterenol-induced decrease in spontaneous motor activity was completely antagonized by betaxolol and only partially by IPS-339. It can be concluded that the clenbuterol-induced decrease in spontaneous motor activity is of the beta 2-type, whereas that induced by isoproterenol is essentially of the beta 1 type. In addition, chronic treatment with clenbuterol induced a tachyphylaxis to the effect of clenbuterol but not of isoproterenol. After chronic administration of tricyclic antidepressants (imipramine and desipramine) the number of cortical beta 1 adrenergic receptors decreased without impairing the clenbuterol-induced decrease in spontaneous motor activity. We conclude that beta 2 adrenergic receptors mediate the clenbuterol-induced decrease in spontaneous motor activity and the tachyphylaxis to this effect after chronic treatment.

Adrenergic beta-Agonists↗
PubMed1987

Triiodothyronine potentiation of antidepressant-induced reversal of learned helplessness in rats.

Several clinical investigations have suggested that a special relationship exists between thyroid function and affective disorders and/or therapeutic response to antidepressants. The present report describes that the reversal by antidepressants (imipramine, desipramine, and nomifensine) of depressive-like behavior in rats (escape deficits produced by previous exposure to uncontrollable stress) was significantly hastened in animals given daily triiodothyronine (T3). The learned helplessness paradigm might be a useful model for approaching in animals the neurohormonal correlates of affective disorders and the neurobiochemical bases of the reported T3 enhancement of antidepressants.

Animals↗