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Biomedical subjects

C Jacquot

Publications and source records attributed to C Jacquot.

At least 55 records · Page 3Linked to original sources

Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid.

OBJECTIVE: To evaluate the effects of preoperative intentional hemodilution with 4% albumin solution on the extravasation rate of intravascular albumin and fluid in surgical patients. DESIGN: A prospective, randomized, clinical study. SETTING: University teaching hospital. PATIENTS: Two groups (control group [group 1] and hemodiluted group [group 2]) of 13 healthy patients were studied during a long-term (>4 hrs) surgical procedure. INTERVENTIONS: Autologous technetium-99m (99mTc)-labeled red blood cells and indium-oxine ((111)In)-labeled human serum albumin were injected intravenously during anesthesia at T = 0 min in the two groups for the determination of total blood volume and albumin diffusion space, respectively. In addition, body tetrapolar electrical impedance was used to assess extracellular fluid volume. In the hemodiluted group (group 2), 15 mL/kg of blood was withdrawn over 30 mins (T = 20 mins to T = 50 mins) and simultaneously replaced by an equal volume of 4% albumin solution (0.6 g/kg). MEASUREMENTS AND MAIN RESULTS: The albumin diffusion space, the colloid oncotic pressure, the plasma albumin concentration and the electrical impedance were measured before (T = 10 mins) and after (T = 60, 120, and 240 mins) hemodilution. Urine was collected from T = 10 mins to T = 240 mins. The total blood volume was calculated at T = 10 mins. No differences in the initial values were found between the two groups. In group 2, hemodilution (hematocrit 30 +/- 3%) resulted in a steeper increase in the albumin diffusion space (p < .05) and a progressive decrease in the body electrical impedance (p < .05). The extravasation rate of albumin was 0.052 +/- 0.007 mL/kg/min in group 2 vs. 0.038 +/- 0.020 mL/kg/min in group 1 (p < .05). The value of calculated plasma volume at T = 0 min did not shown any difference between the two groups. This value was then lower than expected in group 2, corresponding to a loss of plasma volume of >3 mL/kg. Urine output was significantly lower in group 2 than in group 1 (0.7 +/- 0.4 vs. 1.4 +/- 1.0 mL/min, respectively; p < .05). A comparable decrease in colloid oncotic pressure and in plasma albumin concentration was observed in both groups. CONCLUSIONS: These results suggest that preoperative hemodilution using 4% albumin on a 1:1 volume basis for blood substitution during a prolonged surgical procedure with reduced blood losses enhances the extravasation rate of albumin and fluid to the interstitial tissues, impeding the maintenance of isovolemia. These findings support the use of a volume of infused colloid solution higher than that of withdrawn blood during preoperative hemodilution.

Adolescent↗

Presence of norepinephrine and other biogenic amines in stonefish venom.

Although fish venoms exert a cardiovascular effect, the presence of adrenergic substances was not previously demonstrated. Chromatographic analysis with electrochemical detection showed the presence of substances co-migrating with norepinephrine, dopamine and tryptophan. Serotonin, which was thought to be implicated in the intense pain following fish envenomation, was not detected. Norepinephrine was identified as a component of the stonefish Synanceia verrucosa venom by gas chromatography-mass spectrometry.

Adrenergic alpha-Agonists↗

Microdialysis monitoring of variations in extracellular levels of serotonin, GABA and excitatory amino acids in the frontal cortex of awake rats in response to a single peripheral or central administration of dexfenfluramine.

The effects of a single dexfenfluramine (D-fen) administration on the release of endogenous serotonin (5-hydroxytryptamine, 5-HT), excitatory (glutamate, Glu, aspartate, Asp) and inhibitory (gamma-aminobutyric acid, GABA) amino acids from the frontal cortex were studied by using in vivo microdialysis in freely-moving rats. Extracellular levels of these neurotransmitters were measured with HPLC coupled to electrochemical detection or with capillary electrophoresis coupled to laser-induced fluoresence detection (CE-LIFD). In a first study, single intraperitoneal administration of D-fen (0.5, 1.3, 5 and 10 mg/kg) increased extracellular 5-HT levels in a dose-dependent manner (maximal increase by 982% over baseline for the highest dose) while changes in Glu, Asp or GABA never reached statistical significance. In a second study, 73 nM of D-fen applied locally through the frontocortical dialysis probe, at a flow rate of 1.5 microliters/min in 30 microliters of perfusion fluid for 20 min, increased extracellular 5-HT and Asp levels [the maximal increases were to 1804% and 280% of the respective basal values (100%)] without altering extracellular levels of Glu and GABA. Thus, the order of magnitude of the changes induced by systemic administration or local infusion of D-fen on frontocortical extracellular levels of several neurotransmitters (5-HT > > Asp > GABA = Glu) demonstrate that D-fen, an indirect serotoninergic agonist, mainly increases 5-HT release while producing slight (Asp) or no (Glu, GABA) short-term in vivo variations in amino acid extracellular levels in the rat frontal cortex.

Animals↗

Regional differences in the effect of the combined treatment of WAY 100635 and fluoxetine: an in vivo microdialysis study.

We studied the changes in extracellular serotonin (5-HT) levels in the frontal cortex (FC) and ventral hippocampus (vHi) in conscious rats, induced by the combined administration of a highly selective 5-HT1A receptor antagonist, WAY 100635 (0.1 mg/kg, i.v.), and fluoxetine (1 mg/kg, i.p.), a selective 5-HT reuptake inhibitor (SSRI). In the two brain areas studied, no change in extracellular 5-HT concentrations was observed following fluoxetine administration over the 210 min post-injection period. However, in animals co-administered with [WAY 100635 + fluoxetine], the maximal increase in 5-HT levels in the FC was to 215% of the respective basal value (100%), while no significant change in 5-HT was observed in dialysates from the vHi. Furthermore, the [norfluoxetine]-to-[fluoxetine] ratio in the FC was significantly higher than in the hippocampus as measured in homogenates of animals treated with either fluoxetine alone or a prior administration of WAY 100635. Thus, WAY 100635 made the fluoxetine short-lasting effect apparent in the FC, but not by interfering with pharmacokinetic parameters of fluoxetine. Taken together, our data suggest the possibility, that either 5-HT1A autoreceptor sensitivity or uptake carrier density or higher [metabolite]-to-[parent drug] ratios in the FC than in the hippocampus may be involved in regional specific responses to SSRIs.

Animals↗

Severe head injuries: an outcome prediction and survival analysis.

OBJECTIVE: To identify the predictors determined early after admission and associated with unfavorable outcome or early (within 48 h) death after severe head injury. DESIGN: Prospective cohort study. SETTING: A neurosurgical intensive care unit in a university hospital. PATIENTS: 198 consecutive comatose patients hospitalized from 1989 to 1992. RESULTS: Logistic regression showed that a combination of age, best motor response score from the Glasgow Coma Scale, and hypoxia provided a good prediction model of unfavorable outcome (sensitivity = 0.93). The length of participation of survivors was 6 to 61 months (median 27.1). The Cox model demonstrated age, motor score less than 3, mydriasis, and hypoxia as poor prognosis factors. CONCLUSIONS: Clinicians can determine the odds of a good outcome from the combination of three easily measurable factors using a simple diagram constructed from logistic regression. Survival analysis showed that motor score adjusted values greater than 3 had the same prognosis.

Adult↗

Role of 5-HT1A autoreceptors in the mechanism of action of serotoninergic antidepressant drugs: recent findings from in vivo microdialysis studies.

Although a new generation of selective serotonin reuptake inhibitors (SSRIs) has been introduced in therapeutics as antidepressant drugs, a two to four week lag period still occurs between starting treatment with SSRIs and the onset of therapeutic effects in man. In vivo cerebral microdialysis can be used to measure extracellular concentrations of serotonin (5-hydroxytryptamine, 5-HT), which reflect intrasynaptic events. With the coupling of this new experimental method to very sensitive analytical assays such as liquid chromatography with electrochemical detection, it has recently been possible to obtain two major arguments supporting the hypothesis that somatodendritic 5-HT1A autoreceptors situated in the raphe nuclei play an important role in the mechanism of action of SSRIs. First, in the rat, single administration of SSRIs at low doses comparable to those used therapeutically increases extracellular 5-HT concentrations in the vicinity of the cell body and the dendrites of serotoninergic neurones of the raphe nuclei. This effect is more marked than that observed in regions rich in nerve endings (frontal cortex). The magnitude of the activation of the serotoninergic neurotransmission depends on the brain area studied and the dose of the SSRIs administered to rats. This could be explained by simultaneous activation of somatodendritic 5-HT1A autoreceptors by endogenous 5-HT in the raphe nuclei, thereby limiting the corticofrontal effects of the antidepressant. Second, SSRIs cause a larger increase in extracellular 5-HT concentrations in the nerve endings when administered chronically: 5-HT autoreceptors may have gradually desensitized during the 2-4 weeks of treatment with SSRIs. Preliminary studies of patients with depression appear to confirm these experimental results, as co-administration of a 5-HT1A autoreceptor antagonist and a SSRI accelerated the onset of the antidepressant effect (< 1 week).

Animals↗

[Traumatic rupture of the bladder. Apropos of 26 cases].

26 patients were seen with ruptured bladders at Grenoble Hospital during the last 15 years. Pelvic fractures were present in 95% of the cases. Bladder injuries were extraperitoneal (58%), intraperitoneal (27%), intraperitoneal and extraperitoneal (15%). Patients were hospitalised in Urological Department (40%) or General Surgical and Intensive Care (60%). All patients with intraperitoneal bladder injury, 61% with extraperitoneal ruptures were treated by surgical repair. 4 patients died, secondary to visceral associated injuries.

Adult↗

Effects of acute fluoxetine on extracellular serotonin levels in the raphe: an in vivo microdialysis study.

Acute administration of fluoxetine (1, 10 and 20 mg/kg i.p.) increased extracellular levels of serotonin (5-hydroxytryptamine, 5-HT) in the frontal cortex, ventral hippocampus and raphe nuclei as measured by in vivo microdialysis in anaesthetized rats. In the frontal cortex, fluoxetine showed a marked dose-response effect whereas in the ventral hippocampus and raphe nuclei the fluoxetine-induced effect was maximum at 10 mg/kg. However, the maximal increase in 5-HT was observed in the cell body-containing area, the raphe nuclei. The order of changes in extracellular 5-HT was raphe nuclei > ventral hippocampus > frontal cortex. Our results add further arguments in favour of the key role played by raphe nuclei in the mechanism of action of serotoninergic antidepressant drugs.

Animals↗

Lesions of the afferent catecholaminergic pathways inhibit the temporal activation of the CRH and POMC gene expression and ACTH release induced by human interleukin-1beta in the male rat.

A number of recent studies have suggested that interleukin-1beta (IL-1beta) is a major mediator contributing to the recruitment of the hypothalamo-pituitary-adrenal (HPA) axis following infectious aggressions. Central catecholamines modulate the response of the HPA axis. To investigate the importance of the afferent catecholaminergic pathways in a pathophysiological situation, we used the intraperitoneal (i.p.) IL-1beta injection (mimicking peripheral infections) and we investigated the effects on the HPA responses to IL-1beta of bilateral neurotoxic (6-OHDA) deletion of the ventral noradrenergic ascending bundle (VNAB-X). The VNAB is an essential stimulating pathway linking the brainstem and the paraventricular nucleus (PVN). We determined the time courses of a number of HPA variables up to 240 min after i.p. injection of IL-1beta. We followed: plasma ACTH and corticosterone (CORT) concentrations, AP POMC nuclear primary RNA transcripts, AP POMC nuclear intermediate transcript RNA, AP POMC cytoplasmic mRNA, and hypothalamus (HT) CRH cytoplasmic mRNA. Compared to sham-lesioned male rats, VNAB-X animals displayed: (1) a reduced increase in plasma ACTH, and to a lesser extent in CORT throughout the experimental period with a 85% inhibition at the peak (90 min); (2) an increase in AP POMC primary nuclear transcript and in AP POMC nuclear intermediate transcript RNAs which last 60 min, instead of sustained significantly higher levels up to 240 min; (3) a similar, although reduced inhibition in the corresponding POMC cytoplasmic mRNA; (4) an almost complete abolishment of the marked biphasic rise in HT CRH mRNA. In conclusion, activation of the HPA axis by peritoneal IL-1beta challenge involves CRH-producing neurons, and afferent catecholaminergic innervation of the PVN plays a crucial role in the signaling machinery linking the peritoneal aggression to the HPA axis.

Adrenocorticotropic Hormone↗

Pharmacokinetic study of the low-molecular-weight heparin fraxiparin in patients with nephrotic syndrome.

We studied the pharmacokinetics of the low-molecular-weight heparin (LMWH) Fraxiparin in 6 patients with the nephrotic syndrome. Maximal plasma anti-Xa activity was obtained 5 h after a subcutaneous injection of 60 IU anti-Xa/kg. Anti-Xa activity was no longer detectable 24 h postinjection. These results are similar to those obtained with the same dosage in other clinical settings. The biological response to a daily subcutaneous injection of 60 IU anti-Xa/kg was studied for 8 days. No cumulative effect was observed. All the patients had an abnormal activation state of hemostasis mechanisms before treatment, as shown by high prothrombin fragment 1 + 2 and D-dimer levels, which were not decreased by Fraxiparin. It remains to be determined whether a higher dosage of LMWH might attenuate the hypercoagulability in these patients.

Adult↗

8-OH-DPAT attenuates the dexfenfluramine-induced increase in extracellular serotonin: an in vivo dialysis study.

Rats with frontocortical microdialysis probes were treated with dexfenfluramine or dexfenfluramine with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) pretreatment. Dexfenfluramine (10 mg/kg i.p.) increased extracellular serotonin (5-hydroxytryptamine, 5-HT) (calculated area under the curve (AUC) for the 0 to 105-min period after dexfenfluramine treatment = 8.22 +/- 2.66 pmol 5-HT). Systemic (0.025 mg/kg i.p.) or local (0.01 microM into the dorsal raphe nucleus) 8-OH-DPAT pretreatement decreased the dexfenfluramine response (AUC: 1.03 +/- 0.07 and 0.44 +/- 0.04 pmol 5-HT, respectively). This result might be explained by the decrease in 5-HT neuronal discharge caused by somatodendritic 5-HT1A autoreceptor activation, and suggests that the 5-HT releasing effect of dexfenfluramine in vivo depends on nerve terminal depolarization.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effects of a primary immune response to T-cell dependent antigen on serotonin metabolism in frontal cortex: in vivo microdialysis study in freely moving Fischer 344 rat.

Antigenic challenge is known to influence brain catecholamine turnover, e.g. hypothalamic norepinephrine activity, but little is known about effects on the activity of serotoninergic neurons, i.e. the release of the neurotransmitter at nerve terminals. In the present study, we first investigated the changes of central serotonin (5-HT) metabolism in Fischer 344 male rats at 2, 3, 4 and 5 days following i.v. immunization with sheep red blood cell (SRBC). Major decreases in 5-HT levels were evident in the hypothalamus (Hy) and cortex (Cx) at a time which corresponded to the late phase of the production of specific antibodies to SRBC measured with a plaque-forming cell assay (PFC). A pretreatment with an immunosuppressive drug, cyclosporin A (CsA; 12.5 mg/kg by gavage for 7 days) prevented the decreases in cortical 5-HT levels. Concomitantly, a 2-fold increase in the basal 5-HT release at frontocortical nerve terminals was observed by using in vivo microdialysis in awake rats on Day 3 following SRBC inoculation. This effect was totally suppressed by CsA. Our data suggest that the decrease in brain 5-HT levels that occurs after antigen administration may reflect a specific short-lasting CsA-dependent-release of 5-HT at frontocortical nerve terminals at a time (Day 3 or 4) when the splenic immune response is maximal.

Animals↗

6-Fluoro-serotonin as a substrate for the neuronal serotonin transporter.

6-Fluoro-serotonin (6F-5-HT) was previously identified in the rat brain after peripheral administration of 6-fluoro-DL-tryptophan, a serotonin (5-HT) synthesis inhibitor. These present studies, performed with rat brain synaptosomes show that: i-neuronal 6F-5-HT uptake partly involved the 5-HT transporter since it was inhibited by clomipramine, a 5-HT uptake inhibitor, ii-6F-5-HT blocked the synaptosomal uptake of 3H-5-HT, with an IC50 value of 98 +/- 13 nM, and iii- 6F-5-HT induced 3H-5-HT release from preloaded synaptosomes, with an EC50 value of 95 +/- 6 nM; this release was decreased in the presence of clomipramine, suggesting the involvement of the 5-HT transporter. This release was also reduced when using synaptosomes from reserpinized rats, suggesting that the vesicular pool also participates to the 3H-5-HT release induced by 6F-5-HT. So, 6F-5-HT behaved as a substrate for the 5-HT neuronal transporter.

Animals↗

Changes in dopamine metabolism in rat forebrain regions after cessation of long-term fluoxetine treatment: relationship with brain concentrations of fluoxetine and norfluoxetine.

We examined the effects of repeated administration of the selective serotonin uptake inhibitor (SSRI) fluoxetine (Flx) (5, 10, or 15 mg/kg i.p., twice daily for 21 days) on brain and plasma concentrations of the parent drug and its active desmethyl metabolite, norfluoxetine (NFlx), in rats during the 21-day regimen as well as after cessation of drug treatment. We also measured dopamine (DA) levels in 2 midbrain regions (the striatum, St and nucleus accumbens, NAc) in rats killed 1-14 days after the last dose. NFlx concentrations in plasma and brain were ten times higher than those of Flx during the period of drug treatment. Although Flx accumulated more markedly in the rat brain than NFlx, it disappeared completely from plasma and brain after treatment stopped, while NFlx persisted up to Day P7. Chronic Flx treatment caused a persistent decrease in brain DA levels of -60% to -70% in St and NAc; this lasted for 7-14 days after cessation of treatment, depending on the dose used. The levels of DA metabolites decreased by 20-40%, and, except for 3-MT, tended to overshoot during the recovery period. Our data suggest that the long-term inhibition of DA neurons after cessation of Flx treatment parallels the inhibition previously observed for 5-HT neurons. Thus, besides blocking 5-HT uptake, Flx is likely to also inhibit in vivo DA uptake in forebrain regions, following prolonged administration.

Animals↗

Primary bilateral B-cell renal lymphoma: a case report and review of the literature.

Renal lymphoma is commonly secondary to lymphomatous infiltration of the kidneys in disseminated lymphoma and advanced stage IV disease. We describe a 57-year-old white woman presenting with an acute renal failure due to a bilateral "primary" B-cell lymphoma infiltration of the kidneys. The diagnosis of the lymphoma was made by renal biopsy. The striking feature observed was a destructive infiltration of the kidney by a malignant B-cell lymphoma that left the renal capsule intact, without any sign of secondary localization on the hilar regions. Physical examination did not reveal any peripheral lymphadenopathy or hepatosplenomegaly. A bilateral infiltration of both kidneys was the only feature shown by computed tomography and renal angiography. This case raises the question of the occurrence of a primary B-cell lymphoma in a nonlymphoid organ, which was diagnosed by renal biopsy at a time when the development was exclusively renal in origin.

Female↗