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C Bernard

Publications and source records attributed to C Bernard.

At least 109 records · Page 6Linked to original sources
PubMed1998

Resistance to endotoxin shock in spontaneously hypertensive rats.

Septic shock involves systemic vasodilation mediated by proinflammatory cytokines. In essential hypertension, vascular and immune dysfunctions are closely associated. The response of hypertensive animals compared with normotensive controls to endotoxin (lipopolysaccharide; LPS) challenge is not known. Age-matched (12 weeks) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were exposed to intravenous injection of 10 mg/kg LPS. Survival rate at 24 hours was markedly higher in SHR than in WKY (12 of 15 and 3 of 15, respectively; P<0.01). Survival of LPS-injected SHR was not related to their hypertension because hydralazine-treated SHR with normalized pressure had similar survival rates, and WKY made hypertensive by clipping of one renal artery showed fatality similar to that of normotensive WKY. Continuous arterial pressure and sequential plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured in LPS-treated SHR and WKY. Both the duration of the delayed hypotensive phase and the systemic release of IL-6 were much lower in SHR than WKY, whereas both acute hypotension and plasma TNF peak were equivalent. We further explored in vitro the inflammatory response and showed that LPS-activated whole blood from SHR produced less TNF and IL-6 than WKY LPS-activated whole blood. Our results indicate that SHR have a greater ability to resist endotoxic shock than WKY. This is not related to their hypertension but is associated with an attenuated inflammatory response to LPS.

Animals↗
PubMed1998

Regulation of cholecystokinin secretion by peptones and peptidomimetic antibiotics in STC-1 cells.

Peptones are potent stimulants of cholecystokinin (CCK) release in rats, both in vivo and ex vivo in a model of isolated vascularly perfused duodeno-jejunum preparation and in vitro in the intestinal CCK-producing cell line STC-1. The underlying mechanisms were here investigated with this cell line. Protein hydrolysates from various origins (meat, casein, soybean, and ovalbumin; 0.5-1%, wt/vol) dose dependently increased CCK release. Cephalosporin antibiotics, which mimic tripeptides, also stimulated the release of CCK over the concentration range 1-20 mM. The study of concentration dependence of cephalosporin uptake indicated a passive diffusion process at either pH 7.4 or pH 6.0, thus arguing against the involvement of a peptide transporter in CCK secretion. After pertussis toxin treatment (200 ng/ml; 5 h), the peptone- and cephalexin-induced CCK secretion was significantly reduced, suggesting the involvement of pertussis toxin-sensitive heterotrimeric G protein(s) in the secretory activity of STC-1 cells. Consistent with this was the identification by Western blot of G(i2)alpha, G(i3)alpha, and G(o)alpha immunoreactivities in STC-1 cell extracts. Additionally, peptones and cephalexin increased the cellular content in inositol phosphates, whereas a mild increase in cAMP content was restricted to peptone-treated cells. Protein kinase A or C inhibition did not modify peptone- or antibiotic drug-evoked CCK release. The extracellular Ca2+ chelator EGTA (500 microM) and the intracellular Ca2+ chelator BAPTA-AM [1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester; 20 microM] abolished the peptone- and antibiotic drug-induced CCK release. Nifedipine and verapamil (10 microM) reduced by about 50% the CCK secretion evoked by these two secretagogues. In conclusion, peptones and some cephalosporins are potent stimulants of CCK release in the STC-1 cell line. The cellular mechanisms involve pertussis toxin-sensitive G protein(s) and are dependent on Ca2+ availability. We suggest that the STC-1 cell line is a useful model to study the molecular basis of peptone-induced CCK secretion.

Animals↗
PubMed1998

Sternocostoclavicular hyperostosis in children: a report of eight cases.

OBJECTIVE: The aim of this paper is to clarify the clinical and radiologic features of sternocostoclavicular hyperostosis by reviewing eight previously unpublished cases in children, identifying its similarities to chronic recurrent multifocal osteomyelitis and the differences between the pediatric and adult population affected with sternocostoclavicular hyperostosis. Appropriate imaging workup will obviate unnecessary diagnostic and therapeutic procedures. MATERIALS AND METHODS: We investigated the clinical and imaging features of sternocostoclavicular hyperostosis in eight children (seven girls and one boy) and compared those features with the characteristic features of chronic recurrent multifocal osteomyelitis and sclerosing Garré's osteomyelitis to determine if sternocostoclavicular hyperostosis can justifiably be classified as a separate entity. All patients underwent one or more bone biopsies to determine the cause of the bone lesion(s). RESULTS: Seven of the eight patients had involvement of the clavicle. Five of the eight patients had associated distant involvement in the pelvis, femur, tibia, fibula, talus, or sacroiliac joints. Except for predominant localization in the anterior chest wall, the symptoms, the clinical and imaging features, and the results of biopsy and histopathologic examination resemble those of chronic recurrent nonspecific sclerosing osteomyelitis. No skin lesion and no causative organism was found in any of the cases. CONCLUSION: Sternocostoclavicular hyperostosis is a descriptive term used to designate a form of chronic sclerosing osteomyelitis. Its only distinctive feature is localization on one or more sites of the anterior chest wall.

Adolescent↗
PubMed1998

Peptones stimulate both the secretion of the incretin hormone glucagon-like peptide 1 and the transcription of the proglucagon gene.

Truncated glucagon-like peptide (GLP)-1 is a potent incretin. Its synthesis and secretion are modulated by food, but the influence of individual nutrients remains to be established. The hypothesis that protein hydrolysates (peptones) can directly regulate both GLP-1 secretion and proglucagon (PG) gene transcription was tested in this study, ex vivo in the isolated vascularly perfused rat intestine and in vitro in the murine enteroendocrine cell line STC-1. Peptones were albumin egg hydrolysate (AEH) and meat hydrolysate (MH). We demonstrate in these two models that peptones dose-dependently stimulate GLP-1 release, whereas isocaloric quantities of bovine serum albumin or of an amino acid mixture had no stimulatory effect. A strong and rapid increase of PG RNA level was observed in STC-1 cells treated with peptones (14-fold and 7-fold increase after 4 h of incubation with 3% wt/vol MH and AEH, respectively). Peptones also increased the PG RNA level in the colonic PG-expressing cell line GLUTag. In contrast, peptones did not modify the PG RNA level in two pancreatic glucagon-producing cell lines, namely, the RINm5F and INR1G9 cells. The peptone effect in STC-1 cells was completely abolished by blocking transcription before MH treatment. The stability of proglugacon transcripts was not modified by MH treatment, but nascent transcripts were more abundant in STC-1 cells preincubated with MH. Finally, MH treatment strongly stimulated (15-fold stimulation) the transcriptional activity of two PG gene promoter fragments (-1100 and -350 base pair) linked to the CAT reporter gene transiently transfected in STC-1 cells. Overall, peptones evoke an as yet undescribed release of GLP-1 when brought into contact with native intestinal L-cells or with STC-1 enteroendocrine cells. The increased transcription of the glucagon gene in the latter system suggests an important role of protein hydrolysates in the control of not only the secretion but also the synthesis of the incretin hormone.

Animals↗
PubMed1998

Pancreatic beta-cell regeneration after 48-h glucose infusion in mildly diabetic rats is not correlated with functional improvement.

We investigated the effect of glucose infusion on beta-cell regeneration in rats made mildly diabetic by a single injection of low dosage (35 mg/kg) streptozotocin (STZ). Nondiabetic (ND) and STZ rats were submitted to a 48-h glucose infusion (hyperglycemia approximately 22 mmol/l in both groups: ND and STZ hyperglycemic-hyperinsulinemic [ND HG-HI and STZ HG-HI rats]). Before infusion, beta-cell mass was 65% lower in STZ rats than in ND rats (2.0 +/- 0.02 vs. 5.5 +/- 0.6 mg), 1.6-fold increased in ND HG-HI rats (8.7 +/- 1.7 mg), and 2.7-fold increased in STZ HG-HI rats (5.4 +/- 0.9 mg). In ND HG-HI rats, beta-cell enlargement was related to an increase in beta-cell responsiveness to nutrient secretagogues both in vivo and in vitro, whereas in STZ HG-HI rats, no significant improvement in insulin secretion could be noticed. To determine the respective role of hyperglycemia and hyperinsulinemia on beta-cell area changes, ND and STZ rats were submitted to a 48-h hyperinsulinemic-euglycemic clamp. No modification of beta-cell mass was detected in either group. In conclusion, 48-h superimposed hyperglycemia was enough to restore beta-cell mass previously reduced by STZ injection. This effect seemed to be due to hyperglycemia rather than hyperinsulinemia alone. The data stress the dissociation between beta-cell regeneration and improvement in islet function in diabetic rats. Our model seems suitable for studying factors that can improve the plasticity and function of the pancreas in NIDDM.

Animals↗
PubMed1998

Comparison of the kinetics of pancreatic secretion and gut regulatory peptides in the plasma of preruminant calves fed milk or soybean protein.

Exocrine secretion from the pancreas and concentrations of cholecystokinin, gastrin, secretin, and somatostatin in plasma were measured in relation to feeding in 70- to 120-d-old preruminant calves fed either a milk diet or a soybean diet. Pancreatic fluid was continuously collected, measured, and reintroduced in catheterized calves. Blood samples were withdrawn for measurements of gut regulatory peptide concentrations in plasma. A slight increase in outflow of pancreatic fluid was observed 30 min before the milk diet was introduced but not before the soybean diet was fed. In contrast, concentrations and outflows of protein and trypsin immediately after feeding were higher when calves were fed the soybean diet. Overall, during the first 5 h postfeeding, the outflow of pancreatic fluid was 40% higher when the milk diet was fed than when the soybean diet was fed. No difference in outflow of protein was observed, but that of trypsin was 82% higher when the soybean diet was fed. This enhanced enzyme secretion could have been related to the increased plasma concentrations of gastrin and cholecystokinin after the soybean diet was fed. Secretin release was less in calves fed the milk diet that in calves fed the soybean diet during the first 2 h postfeeding, suggesting that this gut peptide along with gastrin and cholecystokinin, contributed to the stimulation of enzyme secretion. Plasma gut regulatory peptides could be influenced by the soybean diet, which does not coagulate in the stomach, inducing faster gastric emptying of protein and fat, and by the chemical form of protein from the soybean diet and the lower susceptibility of these proteins to protease compared with casein. However, the resulting enhancement of pancreatic trypsin secretion and activity seemed to be insufficient to increase the digestibility of soybean protein up to a level similar to that of milk.

Animal Feed↗
PubMed1998

Effects of simulated gastroesophageal reflux on the untraumatized rabbit larynx.

OBJECTIVE: Gastroesophageal reflux (GER) has been shown, clinically and experimentally, to cause inflammation of traumatized laryngeal mucosa. This study was performed to determine if GER causes inflammation of untraumatized laryngeal mucosa. METHOD: Sixteen adult New Zealand white rabbits underwent tube pharyngostomy under general anaesthesia without endotracheal intubation. After 7 days recovery, 1 mL/kg of normal saline or HCl (pH 1.5) with pepsin (0.3 mg/mL) was infused into the piriform sinus while the rabbit was under mild sedation: once, twice, or three times per day, for 14 consecutive days. RESULTS: Rabbits that received HCl and pepsin exhibited various degrees of apnea and coughing. Eventually, most developed biphasic stridor on exertion. Histologically, the degree of laryngeal inflammation was greatest when GER was simulated three times per day. Glottic inflammation was greatest in one rabbit, which responded to GER simulation with paroxysmal coughing. CONCLUSION: The mechanism of injury in GER laryngitis is postulated to be a combination of chemical trauma (due to HCl and pepsin) and mechanical trauma (due to an individually variable laryngeal chemoreflex). Further study of GER laryngitis in this new animal model is warranted.

Animals↗
PubMed1998

Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome.

The aim of this study was to perform a multivariate analysis including clinical and biological prognostic factors on glial tumor outcome. Seventy-nine patients were analyzed (48 men and 31 women; mean age = 56 years, range = 16-77 years): 7 had a benign glial tumor (grades 1 and 2), 21 had an anaplastic glial tumor (grade 3), and 51 had a glioblastoma (grade 4). Median follow-up was 17.9 months for patients who survived (50 patients died). Biopsies were obtained at time of diagnosis (complete tumor resection in 62 patients and stereotaxic biopsies in 17 patients). Epidermal growth factor receptor (EGFR) was measured by a binding assay, and labeling index (LI) was measured by tritiated thymidine incorporation. EGFR varied from 4 to 73,110 fmol/mg protein (mean = 3912 fmol/mg protein; median = 374 fmol/mg protein; n = 79). LI varied between 0.1 and 16.5% (mean = 6.2%; median = 5.2%; n = 40). Log10 EGFR was significantly and positively correlated with patient age. LI was significantly different according to tumor histology. Univariate Cox analysis (end point was cancer death) showed that age (P = 0.027), log10 EGFR (P = 0.025), and LI (P = 0.0019) were significant continuous variables, the survival being shortened when the covariable increased; tumor resection (P = 0.015, relative risk = 0.45) and histology (P = 0.0009) were significant categorical factors. A multivariate Cox analysis (forward selection) including age, histology, tumor resection, log10 EGFR, and LI revealed that log10 EGFR, LI, and tumor resection were the only independent significant predictors of survival. This multivariate approach reveals that the clinical prognostic factors of glial tumors, namely age and tumor histology, disappear, to the benefit of intrinsic characteristics of the tumor, i.e., EGFR expression and LI, suggesting that coupled EGFR and LI determination could be a useful tool for better evaluation of glial tumor outcome.

Adolescent↗
PubMed1997

Operative GABAergic inhibition in hippocampal CA1 pyramidal neurons in experimental epilepsy.

Patch-clamp recordings of CA1 interneurons and pyramidal cells were performed in hippocampal slices from kainate- or pilocarpine-treated rat models of temporal lobe epilepsy. We report that gamma-aminobutyric acid (GABA)ergic inhibition in pyramidal neurons is still functional in temporal lobe epilepsy because: (i) the frequency of spontaneous GABAergic currents is similar to that of control and (ii) focal electrical stimulation of interneurons evokes a hyperpolarization that prevents the generation of action potentials. In paired recordings of interneurons and pyramidal cells, synchronous interictal activities were recorded. Furthermore, large network-driven GABAergic inhibitory postsynaptic currents were present in pyramidal cells during interictal discharges. The duration of these interictal discharges was increased by the GABA type A antagonist bicuculline. We conclude that GABAergic inhibition is still present and functional in these experimental models and that the principal defect of inhibition does not lie in a complete disconnection of GABAergic interneurons from their glutamatergic inputs.

Action Potentials↗
PubMed1997

Regulation of the expression of cyclooxygenase-2 by nitric oxide in rat peritoneal macrophages.

Activation of rat peritoneal macrophages by LPS resulted in time-dependent production of nitric oxide and enhancement of cyclooxygenase (Cox) activity. This stimulation was accompanied by increased expression of inducible enzymes, NO synthase, and Cox-2, contrasting with no variation in constitutive Cox-1. Inhibition of NO production in LPS-treated macrophages by either the L-arginine analogue N(G)-monomethyl-L-arginine (L-NMMA) or aminoguanidine was accompanied by an additional enhancement of Cox activity parallel to the expression of Cox-2 protein analyzed by Western blot. Addition of NO donors (3-morpholinosydnonimine (Sin-1), sodium nitroprusside, or S-nitrosoglutathione) reversed the effects of L-NMMA, confirming the role of NO on Cox-2 expression. Specific immunoprecipitation of Cox-2 showed a pattern of protein expression similar to that observed in intact cells. Enzyme activity tested on the immunoprecipitates was correlated with the enzyme mass. In contrast, there was no variation in immunoprecipitated Cox-1 protein or in activity. Levels of mRNA for Cox-2 were increased in macrophages stimulated by LPS in the presence of L-NMMA compared with LPS alone. Metabolic labeling using [35S]methionine showed that inhibition of NO formation resulted in enhanced de novo synthesis of the 35S-labeled Cox-2. The amount of Cox-2 protein induced in the presence or absence of L-NMMA did not change for at least 6 h, suggesting that NO does not modify the t1/2 of the enzyme. These results provide evidence that NO participates in PG production by negative regulation of Cox-2 expression.

Animals↗
PubMed1997

Model of spatio-temporal propagation of action potentials in the Schaffer collateral pathway of the CA1 area of the rat hippocampus.

There is a sharp contrast between the profuse in vivo axonal arborization of CA3 pyramidal cells in the CA1 area and the low probability of finding pairs of connected CA3-CA1 pyramidal cells in vitro. These anatomical differences contribute to a connectivity argument for discrepancies between electrophysiological data recorded in vitro and in vivo. In order to investigate this issue, we have developed a realistic computer model of the Schaffer collateral pathway of the hippocampus and analyzed the spatio-temporal distribution of action potentials along this pathway following three different types of electrical test stimulus. Direct activation of mossy fibers, CA3 pyramidal cells and focal stimulation of CA1 stratum radiatum were investigated. The parameters of the model were selected from available biological data. Spikes in Schaffer collaterals were followed from their onset in the CA3 pyramidal cell initial segment to the last order branches of their axonal tree in two types of configuration: the whole hippocampus and the slice configuration. The anatomical and electropysiological characteristics of the mossy fibre and Schaffer collateral pathways were found to impose strong constraints on the spatio-temporal distribution of action potentials in the CA1 area. Specific projection zones are determined by the spatial localization of the emitting CA3 pyramidal cells. Their position also defines precise time windows during which some CA1 projection zones receive a large number of correlated signals. Moreover, the variability of the delay at the mossy fibre/CA3 pyramidal cell synapse seems to provide the CA1 projection zones with a background level of excitation. Finally, we show how the patterns of activation obtained in the whole hippocampus are different from those obtained in the slice.

Action Potentials↗
PubMed1997

Hemispheric asymmetries of visual evoked potentials in relation to spatial frequency, handedness and familial left-handedness.

The effects of handedness and of familial left-handedness on the asymmetry of the cerebral hemispheres were investigated by means of visual evoked potentials. Square gratings of different spatial frequencies were presented, at 1 Hz in ON-OFF mode to 60 subjects: 30 right-handers and 30 left-handers, 15 with familial handedness and 15 without in each group. The results show that the patterns of hemispheric asymmetry differ in right- and left-handers. They also show that in left-handers these patterns depend on the presence or absence of familial left-handedness, whereas in right-handers the role of this genetic factor is less evident.

Adolescent↗
PubMed1997

Kinetics of pancreatic exocrine secretion and plasma gut regulatory peptide release in response to feeding in preruminant and ruminant calves.

Pancreatic exocrine secretion and plasma cholecystokinin, gastrin, secretin, and somatostatin concentrations were examined in relation to feeding in 70- to 120-day-old preruminant and ruminant calves. The apparatus used was designed to immediately re-infuse the animal's own pancreatic juice and to carry out accurate measurements of the juice flow in real time and to take samples. In the preruminants, pancreatic juice, protein, and trypsin flows increased from 45 min before and until 15 min after the meal and decreased sharply thereafter over a period of 30 min. while protein and trypsin concentrations peaked after feeding. A significant increase in plasma gastrin and cholecystokinin (CCK), a fall in secretin and no change in somatostatin were observed after milk ingestion. By contrast, in the ruminants, feeding had no effect on the pancreatic secretion and on the plasma concentrations of these peptides. Similar and simultaneous patterns of juice flow and secretin, as well as of protein and trypsin concentrations, CCK and gastrin, could support the hypothesis that these gut regulatory peptides play a significant role in the regulation of the pancreatic function. In preruminant calves, the existence of cephalic, gastric and intestinal phases is discussed. In the ruminants, that of the ruminal phase is questionable.

Animals↗
PubMed1997

Epileptiform activity but not synaptic plasticity is blocked by oxidation of NMDA receptors in a chronic model of temporal lobe epilepsy.

Simultaneous extracellular recordings were performed in stratum radiatum and stratum pyramidale of hippocampal slices 7 days following unilateral intracerebroventricular injections of kainic acid. In this ex vivo experimental model of human temporal lobe epilepsy, stimulation of the surviving commissural fibres in stratum radiatum produced graded epileptiform activity in the CA1 area. The oxidizing reagent 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) acting at NMDA receptors redox sites decreases NMDA receptor-mediated responses by half and suppresses evoked epileptiform discharges. We have examined the effect of DTNB on NMDA-dependent bidirectional synaptic plasticity and EPSP/spike coupling. DTNB treatment did not prevent either long-term potentiation induced by tetanic stimulation or long-term depression induced by low frequency stimulation of field EPSPs. Application of DTNB alone did not induce EPSP/spike dissociation. However, both high and low frequency stimulations induced EPSP/spike potentiation indicating that neurons had a high probability to discharge in synchrony. These results suggest that oxidizing reagents may provide novel antiepileptic treatments since they decrease NMDA-dependent evoked epileptiform activity but do not interfere with either NMDA-dependent synaptic plasticity or the probability of synchronous discharge.

Animals↗
PubMed1997

Overexpression of p53 mRNA in colorectal cancer and its relationship to p53 gene mutation.

We analysed the frequency of p53 mRNA overexpression in a series of 109 primary colorectal carcinomas and its association with p53 gene mutation, which has been correlated with short survival. Sixty-nine of the 109 cases (63%) demonstrated p53 mRNA overexpression, without any correlation with stage or site of disease. Comparison with p53 gene mutation indicated that, besides cases in which p53 gene mutation and p53 mRNA overexpression were either both present (40 cases) or both absent (36 cases), there were also cases in which p53 mRNA was overexpressed in the absence of any mutation (29 cases) and those with a mutant gene in which the mRNA was not overexpressed (four cases). Moreover, the mutant p53 tumours exhibited an increase of p53 mRNA expression, which was significantly higher in tumours expressing the mutated allele alone than in tumours expressing both wild- and mutated-type alleles. These data (1) show that p53 mRNA overexpression is a frequent event in colorectal tumours and is not predictive of the status of the gene, i.e. whether or not a mutation is present; (2) provide further evidence that p53 protein overexpression does not only result from an increase in the half-life of mutated p53 and suggest that inactivation of the p53 function in colorectal cancers involves at least two distinct mechanisms, including p53 overexpression and/or mutation; and (3) suggest that p53 mRNA overexpression is an early event, since it is not correlated with Dukes stage.

Colonic Neoplasms↗
PubMed1997

Indwelling silicone femoral catheters: experience of three haemodialysis centres.

The aim of this study is to describe the experience of three haemodialysis centres using indwelling femoral silicone catheter (model SSL 1220M, Medcomp, USA) in 55 patients, three with acute renal failure, one requiring plasmapheresis, and 51 with chronic renal failure but no other available vascular access. Sixty-four catheters were in place for a mean duration of 41.5 +/- 30 days. The rate of catheter-related complications, including mechanical problems, thromboses, and infections was low and they were never life-threatening. The results of the study suggest that femoral cannulation with modern flexible devices can be considered as a reliable temporary access, even for extended periods, with advantages exceeding those for subclavian and jugular routes.

Acute Kidney Injury↗
PubMed1997

Morphometric study of the equine navicular bone: comparisons between fore and rear limbs.

Navicular bones collected from the four limbs of 95 sound horses were studied. The anatomic bases have been laid down about morphometry of the navicular bones and their variations according to limbs, after corrections have been made for morphologic type, gender, weight, size and age. All the dimensions of the navicular bone (except for the thickness) were larger in the fore limb. This phenomenon probably reflects an attempt to compensate for the greater forces exerted upon the fore limbs during exercise and at rest. Navicular bones collected from the four limbs of 61 sound horses were studied and the anatomic bases were described for histomorphometry of the fore and rear navicular bones. Fore navicular bones possess less cortical bone at the level of the articular surface, as well as at the level of the flexor surface and proximal border, but larger amounts of cancellous bone. Articular and flexor surface cortical bone show a larger porosity in the fore navicular bones and a larger amount of mineralized cartilage. The mineralized portion for distal impar- and collateral sesamoidean ligaments are also larger for the fore navicular bones. Two distinct zones are observed for the flexor surface cortex that have never been reported in the literature before: an external zone, which is mainly composed of poorly remodelled lamellar bone, arranged in a disto-proximal oblique direction, and an internal zone, which is mainly composed of secondary bone, with a latero-medial direction of Haversian canals. Bone architecture is discussed with regard to the mechanic load, encountered by the bone during locomotion.

Animals↗