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Biomedical subjects

P Giraud

Publications and source records attributed to P Giraud.

At least 91 records · Page 5Linked to original sources
PubMed1993

Comparative thermodynamics of opioid receptor ligand interaction in the bovine adrenal medulla membranes--evidence of opioid site heterogeneity.

1. A marked dependence on temperature of agonist binding delta, mu and kappa 1-3 opioid sites in the bovine adrenal medulla was observed, at the range of 0 to 37 degrees C. These changes concern kinetic (k1) and equilibrium constants (Kd), but not binding capacities (Bmax). 2. These dependences are different for each ligand and each opioid receptor, suggesting their molecular heterogeneity. 3. The comparative thermodynamics indicates that the interaction of opioid agonists with their receptor is exergonic (delta G degree < 0) and entropy driven (delta S degree > 0). 4. The comparison of Van't Hoff and Arrhenius plots indicates a discrete mechanism in the binding of each opioid receptor.

Adrenal Medulla↗
PubMed1993

Substance P-like immunoreactivity and analgesic effects of vibratory stimulation on patients suffering from chronic pain.

By applying vibratory stimulation to patients suffering from pain, it is possible to set up an inhibitory control on the pain pathways which is based on the activation of large-sized afferent fibres. The exact mechanisms responsible for these analgesic effects still remain to be determined, however. For this purpose, we investigated in the present study whether or not the analgesic effects were accompanied by a decrease in the CSF substance P-like immunoreactivity levels (SPLI) of seven patients suffering from chronic pain, who were fitted with a ventriculo-peritoneal drain. The SPLI levels were determined before and after 30-min vibratory stimulation sessions. The results show that the SPLI levels decreased as the result of the vibration, but this decrease seems to be too slight to account for the pain relief obtained.

Adult↗
PubMed1993

N-methyl-D-aspartic acid/glycine interactions on the control of 5-hydroxytryptamine release in raphe primary cultures.

Glutamic acid and glycine were quantified in cells and medium of cultured rostral rhombencephalic neurons derived from fetal rats. In the presence of 1 mM Mg2+, NMDA (50 microM) significantly stimulated (by 69%) release of newly synthesized 5-[3H]hydroxytryptamine ([3H]5-HT). D-2-Amino-5-phosphonopentanoate (AP-5; 50 microM) blocked the stimulatory effect of NMDA. AP-5 by itself inhibited [3H]5-HT release (by 25%), suggesting a tonic control of 5-HT by glutamate. In the absence of Mg2+, basal [3H]5-HT release was 60% higher as compared with release with Mg2+. AP-5 blocked the increased [3H]5-HT release observed without Mg2+, suggesting that this effect was due to the stimulation of NMDA receptors by endogenous glutamate. Glycine (100 microM) inhibited [3H]5-HT release in the absence of Mg2+. Strychnine (50 microM) blocked the inhibitory effect of glycine, indicating an action through strychnine-sensitive inhibitory glycine receptors. The [3H]5-HT release stimulated by NMDA was unaffected by glycine. In contrast, when tested in the presence of strychnine, glycine increased NMDA-evoked [3H]5-HT release (by 22%), and this effect was prevented by a selective antagonist of the NMDA-associated glycine receptor, 7-chlorokynurenate (100 microM). 7-Chlorokynurenate by itself induced a drastic decrease in [3H]5-HT release, indicating that under basal conditions these sites were stimulated by endogenous glycine. These results indicate that NMDA stimulated [3H]5-HT release in both the presence or absence of Mg2+. Use of selective antagonists allowed differentiation of a strychnine-sensitive glycine response (inhibition of [3H]5-HT release) from a 7-chlorokynurenate-sensitive response (potentiation of NMDA-evoked [3H]5-HT release).

Animals↗
PubMed1993

Neostigmine stimulates growth hormone-releasing hormone release into hypophysial portal blood of conscious sheep.

GH secretion is stimulated by the administration of cholinesterase inhibitors (such as pyridostigmine and neostigmine) in several species, including man. On the basis of indirect experiments, it has been postulated that this action is mediated by a decrease in hypothalamic somatostatin release. We have investigated the effect of neostigmine in sheep, since it is possible to collect hypophysial portal blood for GH-releasing hormone (GHRH) and somatostatin determination in this species under a conscious unstressed state. First, after i.v. injection of neostigmine (1 mg), a significant increase in plasma GH levels and an unequivocal potentiation of the GH response to GHRH were observed. Then, we observed that i.v. injection of neostigmine (1 mg) induced an immediate, short-lasting (30 min), and marked increase in GHRH (126.1 +/- 17 vs. 14.5 +/- 2.1 pg/ml; P < 0.01) levels in hypophysial portal blood of rams chronically implanted with perihypophysial cannulae. No change in somatostatin secretion was recorded during the same period. These data suggest that the stimulating effect of cholinergic drugs on GH secretion is mediated by stimulation of GHRH release. A direct effect of neostigmine at the level of pituitary gland is possible and may explain the potentiation of GHRH-induced GH release.

Animals↗
PubMed1993

[Met-enkephalin and substance P. Comparison of CSF levels in patients with chronic pain based on a sampling procedure].

The purpose of this study was to evaluate the Met-enkephalin and the SP-like immunoreactivity levels in the CSF of 16 patients suffering from chronic sciatalgia and to compare them with those of 8 control subjects. Eight of the patients had a ventriculo-peritoneal shunt which made it possible to collect samples of CSF painlessly. For the others patients and controls, CSF samples were collected by lumbar puncture. The results showed that there was no difference in the Met-enkephalin and SP levels whatever the method of sample collection. On the other hand, SP-like immunoreactivity was lower in patients suffering from chronic pain.

Adult↗
PubMed1993

[Co-release of neuropeptides and catecholamines by adrenal medulla].

Different neuropeptides are costored together with catecholamines in the adrenal medulla. The concurrent release of these neuropeptides [neuropeptide Y (NPY), met-enkephalin (ME)] and catecholamines (adrenaline and noradrenaline) from the adrenal gland was examined in chloralose-anesthetized dogs after intravenous administration of dihydralazine (1 mg/kg) and insulin (0.3 U/kg). These results were compared to those obtained after the stimulation of the right splanchnic nerve at 1, 5 and 10 Hz frequencies. Baroreflex involvement or hypoglycemia induced a significant preferential increase in CA and ME versus basal values: around 16 fold for dihydralazine and 28 fold after insulin administration. In opposite, increase in NPY was only two times baseline. Splanchnic nerve stimulation induced a frequency-dependent increase in catecholamines and neuropeptides. At the lower frequencies (1 to 5 Hz), splanchnic nerve stimulation elicited a parallel increase in catecholamines and ME (13 to 17 fold basal values). By contrast, NPY increases 2 fold in the same conditions. At the higher frequencies (5 to 10 Hz), we observed a parallel (4 fold) increase in NA, ME and NPY adrenal plasma levels. In conclusion, the present data indicate that both adrenal ME and catecholamines (mainly NA) always exhibit a parallel fashion of corelease which is not the case for NPY and that different populations of chromaffin vesicles could be preferentially mobilized according to different physiological and pharmacological patterns.

Adrenal Medulla↗
PubMed1992

Ontogeny of prolyl endopeptidase, pyroglutamyl peptidase I, TRH, and its metabolites in rat pancreas.

We demonstrate that two enzymes, soluble unspecific pyroglutamyl peptidase I and prolyl endopeptidase, able to degrade thyrotropin-releasing hormone (TRH) in vitro were present in pancreas at the early stage of rat development. Specific particulate pyroglutamyl peptidase II remained undetectable during ontogenesis. Pyroglutamyl peptidase I specific activity increased until day 3 and decreased after day 5. Furthermore, prolyl endopeptidase specific activity rose slightly to a peak on postnatal day 20. A good correlation between immunoreactive TRH and deaminated TRH (TRH-OH) was found in the 1st wk after birth. However, His-Pro diketopiperazine (DKP) levels were stable and low during development. We show that hot acidic extraction conditions could artefactually generate His-Pro DKP. In vivo, active site-directed inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase enzymes do not show any TRH-deamidating and/or pyroglutamyl peptidase I pathways in neonatal rat pancreas. The data suggest that these two enzymes are not involved in intra- or extracellular control of TRH levels in neonatal rat pancreas and that pancreatic TRH content appears to be principally regulated by biosynthetic steps. Nevertheless, low levels of endogenous His-Pro DKP and TRH-OH identified in neonatal rat pancreas suggest that TRH or TRH-like peptides may be metabolized in this tissue in intact rats, albeit at low rates.

Aging↗
PubMed1992

Assignment of the beta-thyroid hormone receptor to 3,5,3'-triiodothyronine-dependent inhibition of transcription from the thyrotropin-releasing hormone promoter in chick hypothalamic neurons.

Thyroid hormone, T3, is essential to the normal development and metabolism of vertebrates. Fine tuning of circulating levels of T3 is critical and involves feedback inhibition of the TRH and TSH genes by T3 at the hypothalamic and hypophyseal levels. However, the molecular basis of T3 inhibition of TRH gene expression in the hypothalamus is not known. The actions of T3 on target gene expression are mediated through nuclear receptor proteins, TR alpha and TR beta. To examine their effects on T3-dependent transcription from the rat TRH promoter, we used a gene transfer technique to express TR alpha and TR beta in cultured embryonic chick hypothalamic cells. Transcription from the TRH promoter construct transfected into these cultures was depressed in the presence of 10(-9) M T3. Cotransfecting TR alpha or TR beta activated transcription from the TRH promoter. However, only TR beta-dependent TRH transcription was differentially modulated by T3. Physiological concentrations of T3 decreased TR beta-dependent TRH transcription 4-fold. Thus, when T3 levels increase, TR beta mediates inhibition of TRH expression, a key step in down-regulating the hypophyseal-thyroid axis. This study demonstrates for the first time a T3-dependent differential regulation of the TRH promoter by TR beta and not TR alpha. Thus, the negative regulation of the TRH promoter in transiently transfected primary embryonic chick hypothalamic neurons provides a useful system for studying the molecular actions of thyroid hormone receptors.

Animals↗
PubMed1992

[Investigation of phosphorus calcium metabolism after oral phosphorus supplementation].

Effects of oral administration of phosphorus on phosphorus and calcium parameters and on bone metabolism hormones were investigated in two studies: in the first, 12 young female adults and 8 females over 50 years of age took a single oral load dose of 780 mg elemental phosphorus, whereas in the second study assays were performed 5 and 15 days after initiation of twice-daily phosphorus supplements in 19 young adults, 14 subjects above 50 years of age who were free of osteoporosis, and 12 patients with osteoporosis also over 50 years of age. The phosphorus load was associated with an increase in intact parathyroid hormone levels (iPTH 1-84), which was more marked in subjects above 50 years of age than in younger adults. On the 15th day of phosphorus supplementation, there was no significant increase in baseline iPTH and no change in baseline dihydroxyvitamin D or osteocalcin levels; during the Nordin tests, the fractional calcium excretion index (CaU/CrU) and the fractional hydroxyproline excretion index (OH Pro/CrU) remained unchanged. In contrast, the phosphorus load was followed by a decrease in the maximum phosphorus reabsorption threshold (TMP/DFG), which was more marked on the 5th day than on the 15th day; a slight fall in serum phosphorus levels was also seen on the 15th day. These findings suggest that phosphorus supplementation should be intermittent rather than continuous. Analysis of subjects aged 50 to 69 years failed to disclose any significant differences between patients with and without osteoporosis.

Administration, Oral↗
PubMed1992

[Initial stability and pelvic deformation in cemented and non-cemented acetabular components].

Periacetabular surface deformation of the pelvis and micromotion between implant and bone were measured in three cementless acetabular components. Pelvic deformation was greater in cementless implants than in cemented ones-independent of the stiffness of the implant. The results of micromotion measurements confirmed the function of certain of anchorage concepts, but they also illustrated the limitations of such measurements in single locations.

Acetabulum↗
PubMed1991

Evidence for pyroglutamyl peptidase I and prolyl endopeptidase activities in the rat insulinoma cell line RINm 5F: lack of relationship with TRH metabolism.

Thyrotropin-Releasing hormone (TRH)-degrading pyroglutamyl peptidase I (PGP I) and prolylendopeptidase (PE) activities have been demonstrated in rat insulinoma RINm 5F cell line. These two enzymes catalyze the conversion of TRH to Histydyl-Proline-Diketopiperazine and to acid TRH respectively. After cell fractionation, we found all the PGP I and PE activities in the cytosolic fraction. The membrane-bound PGP II activity is not detectable in the RINm 5F cells. Further investigations on these two cytosolic enzymes show that pyroglutamyl- and proline-containing peptides are inhibitors of each TRH-degrading enzyme. Gel filtration chromatography on Sephadex G100 shows that PGP I and PE activity have an apparent molecular mass of about 18 kDa and 57 kDa, respectively. Kinetic analysis with TRH as substrate, gives a Km of 44 microM and 235 microM, and a Vmax of 1.49 and 8.80 pmol/min/micrograms protein for PGP I and PE, respectively. Immunoreactive TRH, His-Pro-Diketopiperazine and acid TRH levels in the cell line extracts are 2.2 +/- 0.9, 22.5 +/- 11.1 and 28.7 +/- 14.6 pg/1O6 cells, respectively. When cells have been incubated for 2 to 72 hours with a P.E. inhibitor (Z-Gly-Pro-CHN2) at 5 x 10(-7) M, both cell PGP I and PE activities are inhibited. No change in the cellular content of immunoreactive TRH, His-Pro-Diketopiperazine and acid TRH have been observed in treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Islet Cell↗
PubMed1991

Striatal proenkephalin turnover and gene transcription are regulated by cyclic AMP and protein kinase C-related pathways.

Preproenkephalin metabolism, in the rat, was studied in primary striatal neurons maintained in a chemically defined medium. Acute treatment (30 min) with forskolin (10(-5) M) or phorbol 12 myristate 13 acetate (10(-7) M) resulted, respectively, in a two- and seven-fold increase in methionine-enkephalin secretion. Chronic treatment with forskolin or phorbol 12 myristate 13 acetate (24 h) induced a 100% increase in methionine-enkephalin content (forskolin) and on the other hand a 50% decrease in methionine-enkephalin (phorbol 12 myristate 13 acetate). Both treatments increased preproenkephalin mRNA levels in a time-dependent manner, this augmentation being observable after 180 min by Northern blot analysis and in situ hybridization. These data indicate that under chronic stimulation, with either forskolin or phorbol 12 myristate 13 acetate, proenkephalin turnover is accelerated. However, after stimulation with phorbol 12 myristate 13 acetate, the more potent methionine-enkephalin secretagogue, increased peptide synthesis is not sufficient to replenish methionine-enkephalin intracellular stores. Preproenkephalin gene transcription was analysed by introducing the preproenkephalin gene promoter fused to the bacterial acetyl chloramphenicol transferase reporter gene into primary neurons. Chronic stimulation (48 h) by forskolin (10(-5) M) or phorbol 12 myristate 13 acetate (10(-7) M) of striatal neurons transfected with this fusion gene increased chloramphenicol acetyltransferase activity six-fold and the two effects were additive. These data suggest that the cyclic AMP and the protein kinase C pathways directly activate preproenkephalin gene transcription.

Animals↗
PubMed1991

Telematic transmission of computerized blood glucose profiles for IDDM patients.

OBJECTIVE: To improve the analysis of self-monitoring of blood glucose (SMBG) and its communication between patients and physicians by a telematic transmission of computerized SMBG and to study the consequences of its use on glucose control of insulin-dependent diabetic (IDDM) patients. RESEARCH DESIGN AND METHODS: A prospective randomized crossover trial with two 3-mo periods, one with SMBG recorded on traditional booklets (booklet period) and another with computerized SMBG transmitted to a central data base through a telematic network (telematic period), comprised the study. During the latter phase, patients could receive computerized SMBG analysis on individual terminals connected to the telephone network (Minitel system). Blood glucose recordings and HbA1c were measured at inclusion and end of each period. Eleven pairs of IDDM patients on intensified insulin therapy were randomized within each pair to start with the telematic period (group A) or the booklet period (group B). RESULTS: Telematic transmissions were successful (less than 1% failure rate). Although initial HbA1c was low (6.7%), it declined during the telematic period (delta = -0.41%) compared with the booklet period (delta = +0.37%, P = 0.05). The percentage of low (less than 3.3 mM) blood glucose values correlated with HbA1c changes during the telematic period (r = 0.714, P = 0.0014) but not the booklet period. The patients favored the telematic tool to analyze SMBG. CONCLUSIONS: Telematic transmission of SMBG is feasible. It can improve SMBG analysis and perhaps glucose control, therefore offering a new way of communication between diabetic patients and their physicians.

Blood Glucose↗
PubMed1991

[Role of beta thyroid hormone receptor in the modulation of the TRH transcription].

Two genes coding for thyroid hormone (T3) receptors (THR) have been identified: THR alpha and THR beta. To determine their transcriptional effects we transfected reporter genes expressing chloramphenicol acetyl transferase (CAT) alone or with vectors coding for THR alpha or THR beta in primary cultures of embryonic chick hypothalami. Transcription from a promotor containing a T3 Response Element (T3RE-CAT), was activated in the presence of tri-iodo thyronine (T3) and much reduced in the absence of the hormone. In contrast, in the absence of T3, transcription from the Thyrotropin releasing hormone (TRH) promoter (TRH-CAT) was much greater than in cultures grown with T3. In cotransfection experiments where THR alpha or THR beta was expressed with the TRH promoter construct, THR beta-dependent transcription, but not THR alpha-dependent transcription, was significantly reduced in the presence of T3.

Animals↗
PubMed1991

[A study of primary mooring and deformation of the peri-acetabular area under static load].

We propose a method to study the primary stability and the periacetabular deformation under static load, with and without cemented and cement-free acetabular implants, using a biomechanical model that stimulates the balance mechanism described by Pauwels. The biomechanical model uses whole pelvises of recently frozen corpses. We have imitated the gluteus medius and minimus muscles on the pelvis with cables and pulleys. The loading device comprises a metallic frame, on which a hydraulic press is set up for static testing, and a prototype femoral prosthesis made of two main parts: one on which the gluteal muscles are inserted, and another one on which the femoral head is attached. The pelvis is fixed to the metallic frame by a plate attached to the sacrum and allowing movements in all planes of space. The measurement method utilizes: for primary stability, four transducers, including three three-directional ones, in the three planes of space outside the pelvis, only one being located inside the pelvis with a 16 degrees orientation relative to the vertical; for deformation, a transducer located in three different places in the periacetabular region. We have used ten freshly frozen pelvises with six different implants (two with and four without cement) and eighteen implantations.

Acetabulum↗