Search PubMed⌕ Search

Biomedical subjects

P Netter

Publications and source records attributed to P Netter.

At least 127 records · Page 7Linked to original sources
PubMed1994

Extraversion as a modifying factor in catecholamine and behavioral responses to ethanol.

Individual differences in catecholamine response to stress and ethanol were tested in extraverts and introverts on the basis of Eysenck's drug postulate claiming that introverts would be less susceptible to sedative drugs like ethanol. Forty-four healthy males received either 0.8 g/kg ethanol mixed into a drink of caffeine-free cola or a respective placebo and were tested with a stressful mental arithmetic task before and 40 min after the intake of the drink. Plasma catecholamines were determined from blood samples drawn at five defined intervals from an indwelling cannula and self-ratings on deactivation, relaxation, and anxiety were obtained as well as quality and quantity of performance in the arithmetic task. Results showed that there was no difference in catecholamine stress responses between introverts (Ex -) and extraverts (Ex +) before the drink, but that the intake of the fluid (both ethanol and placebo) resulted in higher norepinephrine (NE) increases in Ex - than in Ex +. The combined effects of ethanol and stress yielded larger responses of longer durations in Ex - than in Ex +. The concomitant psychological changes showed larger reductions in anxiety and increases in relaxation as well as larger decrements in quality of performance (% errors) in introverts in spite of their higher catecholamine increases. Thus, the predictions on the basis of arousal theory could not be verified experimentally and the drug postulate has to be modified in the sense that introverts probably have a higher depletion of NE in the central nervous system under physical but not under mental stress which is reflected by higher levels in the plasma and respective decreases in performance and activation.

Adult↗
PubMed1994

Characterization of zymosan-induced arthritis in the rat: effects on joint inflammation and cartilage metabolism.

A single intra-articular (ia) injection of 2 mg zymosan on D0 led to the production of acute periarticular edema followed by subacute erosive synovitis. The development of the zymosan-induced arthritis was associated with an initial loss of running activity and with an initial decrease of proteoglycan synthesis. Febrile response was present only on D1. In addition, on D20 synovial pannus led to a marked depletion of the proteoglycan content in the articular cartilage. When injected ia, IL1 beta (1 microgram) provoked similar fever and similar changes in cartilage anabolism, but did not affect cartilage proteoglycan content (D20). These results suggest that zymosan-induced synovitis in the rat combines early prostaglandin-dependent processes (edema, pain, fever) with IL1-related effects on cartilage metabolism, thus allowing evaluation of chondroprotective drugs.

Animals↗
PubMed1994

Representation of affinity in the case of co-operativity in protein-ligand binding.

We have already proposed a "Global Association Function" to represent the global affinity of proteins to a drug; it was first applied in the case of independent binding sites. In this paper, we show that this same function can also be used to assess interactions between sites by varying the number of interacting sites and their co-operativity level. The resulting curves in two application cases are given together with the corresponding Scatchard plot: i) in a system with one single class of identical and interacting sites, ii) in a system with two classes of sites in which either primary or secondary are interacting; unexpectedly, in this latter case we also observed that sometimes positive co-operativity occasionally resulted in a concave-up Scatchard plot which is unusually admitted. In addition, as described in one example, our function is assumption free; this might be an advantage over usual methods, such as discrete parameter methods, because they require additional and empirical hypotheses on their related binding model.

Binding Sites↗
PubMed1994

Binding sites of fluorescent probes on human serum albumin.

Human serum albumin is known to have two major and selective drug binding sites, termed sites I and II. The fluorescent probes, dansylamide and dansylsarcosine selectively interact with sites I and II, respectively. However, the binding site of the fluorescent probe dansylglycine on human serum albumin is not clear from the literature. This study investigated whether dansylglycine interacts tightly with site I or II. Spectrofluorimetric titrations (quenching and complex) and circular dichroism measurements were performed to determine the binding characteristics of dansylglycine to human serum albumin. Modification in probe fluorescence was described by fluorescence titrations to be a result of competitive displacement by ligands. The pattern of displacement of this probe by several ligands whose primary binding sites are exactly known, enabled the identification of its specific binding site. The fluorescence of dansylglycine is only extensively changed when ligands of site II are added, suggesting that it strongly interacts with the benzodiazepine/indole binding site on human serum albumin.

Binding Sites↗
PubMed1994

Experimental articular toxicity of aluminum compounds in vivo.

OBJECTIVE: To investigate the articular toxicity of 2 aluminum derivatives, one insoluble (hydroxide) and/or the other soluble (lactate), after a single administration in rabbits and rats. METHODS: First, aluminum levels in plasma, urine, synovial tissue, liver and kidney were measured in saline treated rabbits and 1 to 2 days after an articular injection of 75 mg of aluminum compounds into their right knee. The methodology used was argon plasma emission spectrometry. Thereafter, the joint toxicity of aluminum lactate at the same dose regimen was evaluated for 2 days by a qualitative histological examination of synovial tissue and articular surfaces and a colorimetric assay (1,9-DMB) of patellar articular cartilage proteoglycan content. Secondly, the single injection of 50 mg of aluminum derivatives as an inducer of inflammation was studied in the rat subcutaneous air pouch, a model for a synovial-like space. Leukocytes and eicosanoids levels were measured in pouch washout fluids from 1 to 72 h after injection. RESULTS: After injection into rabbit knee, aluminum lactate largely distributed within the body while hydroxide remained locally. However, aluminum lactate resulted in perivascular edema, sparse infiltration of inflammatory cells in the synovium and a hemorrhagic effusion. Proliferation of the synovial cell layer coexisted with an apparent loss of proteoglycan in superficial zones of tibial and femoral cartilages when patellar proteoglycan content remained unchanged. Aluminum hydroxide did not affect joint structures. In the air pouch experiment, aluminum lactate increased prostaglandin E2 (PGE2) levels from 3 to 10 h after its injection and less intensively leukotriene B4 (LTB4) levels after 6 h, in the absence of leukocytes migration into the cavity. In contrast, aluminum hydroxide increased leukocytes count in pouch-washout fluid from 3 to 24 h after its injection when PGE2 and LTB4 levels were little modified. CONCLUSION: Although some differences attributable to dissimilarities in the experimental model used, aluminum compounds, even in a soluble form, may damage joint structures either directly or through stimulating the secretion of eicosanoids by synovial-like cells.

Aluminum Compounds↗
PubMed1993

Direct high-performance liquid chromatographic resolution of the enantiomers of tiaprofenic acid using immobilized human serum albumin.

Resolution of racemic tiaprofenic acid (TA) has been performed using immobilized human serum albumin as the stationary phase. The eluent was phosphate buffer-acetonitrile-n-octanoic acid (90:10:0.015, v/v). Detection was achieved at 305 nm. The pharmacokinetics of the enantiomers were studied following oral administration into humans and after subcutaneous injection in rats. Plasma concentrations of (+)-TA were much greater than those of (-)-TA. For the rat, the pharmacokinetic parameters between (-)-TA and (+)-TA were all statistically different (p < 0.005).

Administration, Oral↗
PubMed1993

Stereoselective protein binding of ketoprofen: effect of albumin concentration and of the biological system.

Equilibrium dialysis was used to study in vitro the enantioselective binding of R, S, and racemic ketoprofen at physiological pH and temperature in human serum albumin (HSA) (1, 20, and 40 g/liter) and in plasma. The binding of enantiomers in a racemic mixture was studied to see the effect of each isomer on the other's interaction with the protein. The free fractions were determined by high-performance liquid chromatography. The binding of ketoprofen enantiomers to albumin was enantioselective, depending on both drug and protein concentrations. Enantioselectivity was observed in plasma too but was the opposite of that in HSA at 40 g/liter. The percentage of each isomer unbound was higher in the racemic mixture than with the isomer alone. The displacement of probes specific for HSA sites I and II, studied by spectrofluorimetry, suggests that all three preparations of ketoprofen are bound mainly to site I and secondarily to site II.

Binding Sites↗
PubMed1993

Hyaluronidase degradation of hyaluronic acid from different sources: influence of the hydrolysis conditions on the production and the relative proportions of tetra- and hexasaccharide produced.

1. Hyaluronic acid (HA) can be digested with a Streptomyces hyaluronidase. 2. The rate of production and the ratio of tetrasaccharide (T) and hexasaccharide (H), studied by HPLC, varied with the temperature and duration of hydrolysis. 3. The rates of production and the respective amounts of the two oligosaccharides depended on the rheological properties of the HA from different sources. 4. A close relationship was found between the initial rate of hydrolysis and the intrinsic viscosity of the HA (eta i). 5. Our data suggest that enzymatic degradation at a given pH value, temperature, and duration of hydrolysis is dependent on the conformation of HA. 6. Moreover, under given conditions, the relative proportions of the two oligosaccharides depend on the eta i and may also reflect the degree of hydrolysis of the substrate.

Chromatography, High Pressure Liquid↗
PubMed1993

Pro- and anti-inflammatory properties of human recombinant IL-1 beta during experimental arthritis in rats: 2. Period-dependent effect.

The systemic effects of human recombinant Interleukin-1 beta (HrIL-1 beta) on hindpaw edema were determined in arthritis induced by human native type II collagen (CII) with muramyl dipeptide (MDP) both injected on day 0. Daily treatment with HrIL-1 beta (0.2 microgram sc) pretreatment, from D-1 (the day before MDP and CII were injected) to D3 significantly delayed the secondary inflammation in the uninjected left hindpaw, whereas the same treatment from D6 to D10 at the end of the "primary" inflammation, enhanced the volume of the left hindpaw. Treatment from D13 to D17 did not affect the "secondary" edema in the left hindpaw. Thus, HrIL 1 beta administration produces pro- or anti-inflammatory effects on a developing polyarthritis depending on when treatment is started and is most effective as an anti-inflammatory molecule when started at the peak of the the inflammatory reaction, as previously described. In view of these early findings, we have compared the effect of adding HrIL-1 beta along with MDP in the sensitization procedure on the time-course of CII-induced arthritis. No adjuvant effect of HrIL-1 beta was observed. On the contrary, HrIL-1 beta significantly decreased the signs of inflammation in the injected hindpaw during the secondary inflammation. In addition, the immune response to type II collagen was less in the group receiving HrIL-1 beta, maybe because of nonspecific increase of antigen clearance. On the other hand, the MDP sensitization procedure enhanced the incidence of CII arthritis and significantly worsened the clinical parameters in both primary and secondary inflammations.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Cortisol reaction in success and failure condition in endogenous depressed patients and controls.

The authors studied differences in cortisol response to controllable and uncontrollable stress and its relationship to Seligman's theory of learned helplessness in hospitalized unipolar depressed patients (11 nontreated, acutely depressed; 11 treated patients) and 11 age and sex matched controls hospitalized for traumatic surgery. Control and lack of control were achieved by induction of success and failure in a simple number addition test and applied in balanced order on 2 consecutive days. Saliva cortisol samples were collected before and after the test. No group differences in baseline cortisol levels were observed. Cortisol increased after uncontrollable and decreased after controllable stress in control patients, whereas cortisol decreased after both conditions in the acutely depressed group and less so in the treated group, although they were as emotionally upset after failure as controls. Thus, the normally observed ability of the neuroendocrine system to discriminate between controllable and uncontrollable stress deteriorates with increasing severity of depression.

Adaptation, Psychological↗
PubMed1993

Lowering of body core temperature by exposure to a cold environment and by a 5-HT1A agonist: effects on physiological and psychological variables and blood serotonin levels.

The present study was designed to compare the effects of a pharmacologically induced decrease in body core temperature to the effects observed with lowering of body temperature by exposure to a cold environment. Our special interest was the involvement of 5-HT in thermoregulatory responses. Sixty healthy male volunteers were randomly assigned to one of the following conditions: exposure to normal ambient temperature (28 degrees C) and placebo, exposure to cold ambient temperature (5 degrees C) and placebo, or normal ambient temperature and 10 mg of the partial 5-HT1A agonist ipsapirone. As indicators of physiological responses to lowering of body temperature, tympanic temperature, skin temperature, EMA, metabolic rate, and heart rate were monitored and saliva cortisol levels and peripheral 5-HT concentrations were determined. In addition, ratings on ambient temperature, thermal discomfort, and feelings of irritability were obtained. While lowering of body core temperature was associated with marked counterregulations (decrease of skin temperature, increase in EMA and metabolic rate) and feelings of discomfort, this was not observed with ipsapirone. An increase in cortisol levels was primarily observed in the ipsapirone group and was not reflected by respective changes in whole blood or platelet 5-HT indicating that brain and platelet 5-HT are not related.

Adult↗
PubMed1993

Immune cell and cortisol responses to physically and pharmacologically induced lowering of body core temperature.

In a placebo-controlled double-blind study described by Rammsayer and co-workers in this volume, we investigated the influence of decreased body core temperature (BCT) on responses of cortisol and the immune system. As described in the first paper, the decrease in BCT was achieved by: (a) exposure to ambient cold temperature of 5 degrees C for 20 min (CT group), or (b) application of a 5HT-1a agonist under normal temperature conditions (5HT group). A third group serving as control was exposed to normal temperature and placebo (NT group). The decrease of BCT seen in both CT and 5HT was accompanied by an increase in cortisol. This seemed to be due to stress experience in the CT group and to the pharmacological challenge in the 5HT group. The number of peripheral CD4+ cells was reduced in both experimental groups. This was not mediated by decreased BCT. In the CT group the reduction of CD4+ cells showed no relationship to changes in cortisol. However, in the 5HT group cortisol could be demonstrated to be the mediator of changes in peripheral CD4+ cells.

Adult↗