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G Tran

Publications and source records attributed to G Tran.

At least 19 recordsLinked to original sources
PubMed2001

Il-4 therapy prevents the development of proteinuria in active Heymann nephritis by inhibition of Tc1 cells.

The role of IL-4, a key Th2 cytokine, in promoting or inhibiting active Heymann nephritis (HN) was examined. HN is induced by immunization with Fx1A in CFA, and proteinuria in HN is associated with subepithelial IgG and C3 deposition and infiltration of CD8(+) T-cytotoxic 1 (Tc1) cells and macrophages into glomeruli, as well as induction of Abs to Crry. Treatment with rIL-4 from the time of Fx1A/CFA immunization stimulated an earlier IgG1 response to Fx1A, induced anti-Crry Abs, and up-regulated IL-4 mRNA in lymphoid tissue, but did not alter proteinuria. Treatment with MRCOx-81, an IL-4-blocking mAb, resulted in greater proteinuria, which suggests endogenous IL-4 regulated the autoimmune response. Delay of rIL-4 treatment until 4 wk post-Fx1A/CFA immunization and just before the onset of proteinuria prevented the development of proteinuria and reduced Tc1 cell infiltrate in glomeruli. Delayed treatment with IL-4 had no effect on titer or isotype of Abs to Fx1A or on Ig, C3, and C9 accumulation in glomeruli. Treatment with rIL-13, a cytokine that alters macrophage function such as rIL-4, but has no direct effect on T or B cell function, reduced glomerular macrophage infiltrate, but did not prevent proteinuria or CD8+ T cell infiltrate. Anti-Crry Abs were paradoxically only induced with rIL-4 therapy, not in HN controls with proteinuria. It was concluded that the rIL-4 effect was probably by inhibition of Tc1 cells, which normally mediate the glomerular injury that results in proteinuria.

Animals↗
PubMed1999

Preoperative nutritional evaluation of elderly patients: the Mini Nutritional Assessment as a practical tool.

BACKGROUND AND GOAL: Age and malnutrition are each surgical risk factors. Because the Mini Nutritional Assessment (MNA) has been specifically designed for assessing the nutritional status of elderly patients, it can be used for preoperative nutritional evaluation. Therefore, the MNA was included in the preoperative clinical evaluation of patients over 60 years of age to describe their nutritional status. METHODS: Every patient over 60 years of age, scheduled for elective surgery, was seen in anaesthesiology consultation and was submitted to the MNA. The MNA is a clinical score consisting of four additive items: 'Anthropometric assessment' based on BMI, mid-arm and calf circumferences, weight loss; global evaluation; dietetic assessment, and subjective assessment - these last three items being obtained through a specific questionnaire. It requires no biological marker. Awarding to the obtained score, the MNA stratifies patients in the following categories: well-nourished (24 </= MNA </= 30), at risk of malnutrition (17 </= MNA < 23.5), and undernutrition (MNA < 17). Also recorded were: age, gender, type of scheduled operation, and the American Society of Anesthesiologists (ASA) physical status score. Results are given as median (extremes). RESULTS: Four hundred and nineteen patients (50.4% women) were seen between January and October 1996. The mean age was 72 years (range, 60-98 years); BMI: 25.2 (12.8-40.4) kg m(-2). The MNA score was recorded in 408 patients, ranging from 1.5 to 30 (median: 26). According to the score, the patients were stratified in: well-nourished, 276 patients (67.6%), at risk, 104 patients (25. 5%) and suffering from overt malnutrition, 28 patients (6.9%). According to the ASA score, 290 patients were found to be at low or mild risk for anaesthesia and surgery (ASA 1 and 2), and 72 patients (24.8%) were stratified as being at least at risk of malnutrition. One hundred and eighteen other patients were found to be at a higher risk (ASA 3 and 4), and 58 (49.2%) were not well-nourished (MNA < 24). CONCLUSION: The MNA was found to be well-suited for the preoperative assessment during anaesthesia consultation because it required no biological marker. It showed that approximately one-third of all the examined patients, and half of the ASA 3-4 patients, were not well-nourished. The ASA score could not predict poor nutritional status. The results suggested that nutritional assessment should be routinely performed in ASA 3-4 patients over 60 years of age.

Aged↗
PubMed1999

Pharmacokinetics, metabolism and bioavailability of the new anti-allergic drug BM 113. Part I: Pharmacokinetics and tissular distribution in Sprague-Dawley rats.

A new anti-allergic drug, BM 113 (1-(benzhydryloxyethyl)piperidino-4-ethylacetate, CAS 115313-90-1; BM 113 maleate: CAS 115313-91-2) with a piperidinic structure, showing antihistaminic properties was studied in male and female Sprague-Dawley rats after i.v. or p.o. administrations of 0.750 mg/kg 3H-BM 113. This product presented a rapid faecal elimination after i.v. and oral administration. The total recovery of the dose was obtained after 144 h. Biliary elimination was very fast: 54% of the intravenous dose were biliarily eliminated within 2 h, essentially as a conjugated form. For both i.v. and p.o. routes, the blood kinetics were biexponential. Intravenous administration led to elimination half-lives of 1.36 h and 0.75 h for the first phase and 38.6 h and 56.5 h for the second one for males and females, respectively. After oral administration, rebounds corresponding to the presence of enterohepatic cycle or metabolites were observed. Thus, the determination of half-lives was not possible. Slight but significant differences of some pharmacokinetic parameters were observed between genders. The results obtained during the protein binding study corresponded to the BM 113 metabolite known as BM 212. The free fraction corresponded to 55.5%. Tissular concentrations showed a rapid distribution of 3H-BM 113 followed by a slow elimination. In most of the tissues, the decrease was biexponential. The organs containing most of the radioactivity were those of the intestinal tract and the liver. Other tissues presented concentrations close to those of plasma. Lipidic tissues, showing low BM 113 concentrations, presented a slower elimination, probably related to the high lipophilicity of molecule.

Administration, Oral↗
PubMed1999

Pharmacokinetics, metabolism and bioavailability of the new anti-allergic drug BM 113. Part II: Pharmacokinetics in primates after repeated oral or single intravenous administration.

The pharmacokinetics of BM 113 (1-(benzhydryloxyethyl)piperidino-4-ethylacetate, CAS 115313-90-1; BM 113 maleate: CAS 115313-91-2) was studied using 3H-BM 113 in the Cynomolgus primate. Oral repeated administration of 0.75 mg/kg was performed on 8 days. 40 days after the oral treatment, a single intravenous administration of 0.4 mg/kg was done. Whatever the administration route, the radioactivity excretion was essentially urinary (about 60%) and most of the radioactivity was excreted within the first 24 h. The faecal elimination was low, about 10% of the administered dose. 40 days after the treatment, some radioactivity was already present in the urine. For this reason, the excretion balance ranged from 70 to 83% of the dose. The elimination half-life of 3H-BM 113 was long, about 80 h.

Administration, Oral↗
PubMed1999

Pharmacokinetics, metabolism and bioavailability of the new anti-allergic drug BM 113. Part III: Pharmacokinetics, metabolism, dose dependency and gender effect after single or repeated administration to human healthy volunteers.

A new anti-allergic drug, BM 113 (1-(benzhydryloxyethyl)piperidino-4- ethylacetate, CAS 115313-90-1; BM 113 maleate: CAS 115313-91-2), with a piperidinic structure, showing anti-histaminic properties was studied after administration to healthy human volunteers. The focus was on the pharmacokinetics, the metabolism, the dose dependency and gender differences of the pharmacokinetic parameters of BM 113 and its main desacetylated metabolite, BM 212. Unchanged BM 113 was not recovered in plasma or in urine. The elimination of the radioactivity was essentially urinary with about 81% recovered within 24 h. The elimination was completed with 97% of the administered dose recovered after 120 h. HPLC dosage of BM 212, using a specific method, showed that BM 212 represented 62% of the urine radioactivity. The plasma profile of radioactivity was characterized by two decreasing phases with respective half-lives of 3.71 +/- 0.66 h and 24.67 +/- 25.01 h. A dose dependency study realised with 20, 40, 60 and 80 mg oral doses administered to 8 healthy volunteers has proven the linearity of the pharmacokinetics of BM 212 in the studied range. BM 212 disposition after single and repeated BM 113 oral doses in a 14-day study did not vary and permitted to conclude that no auto-induction or auto-inhibition phenomenon was involved. No significant difference between men and women was observed. The concentration profile was mono or biexponential, depending on the subject but whatever the gender. An inter-individual variability appeared for both sexes and caused some variations in the pharmacokinetic parameters.

Adult↗
PubMed1998

Treatment with interleukin-4 prolongs allogeneic neonatal heart graft survival by inducing T helper 2 responses.

BACKGROUND: The T helper (Th) 2 cytokine interleukin (IL)-4 has been implicated as a major regulatory cytokine for the induction of transplant tolerance, but few studies have examined the capacity of IL-4 to induce tolerance. The effect of IL-4 therapy alone or with low doses of anti-CD4 monoclonal antibody (mAb) therapy on survival of fully allogeneic PVG neonatal heart graft in adult DA rats was examined. METHODS: Rat recombinant (r) IL-4 was given at 30 microg (10(4) U)/kg daily intraperitoneally for 10 days and MRC OX35 (anti-CD4, nondepleting) or MRC OX81 (anti-IL-4) was given intraperitoneally on days 0, 3, 7, and 10. Semiquantitative reverse transcriptase-polymerase chain reaction was used to assay mRNA for cytokine in the graft, regional node and spleen and fluorescence-activated cell sorting was used to assay alloantibody Ig isotypes. RESULTS: Grafts in rIL-4-treated rats survived a median period of 39 days (range, 28-52 days), significantly longer than in both untreated and nontransfected Chinese hamster ovary-K1 supernatant-treated controls (median, 14 days; range, 10-16 days, P=0.009). rIL-4 treatment with a suboptimal dose of anti-CD4 mAb prolonged median survival to 70 days (range, 63-80 days), which was longer than rIL-4 treatment alone or anti-CD4 mAb alone (median, 36 days; range, 30-55 days; P<0.0045). Combining MRC OX81 with MRC OX35 therapy led to earlier rejection at a median period of 26 days (range, 20-28 days); MRC OX81 alone had no effect on graft survival. Alloantibody titers, especially IgG1, were higher in rIL-4-treated animals and lower in anti-CD4 mAb-treated animals than in animals with normal rejection (P<0.05). IL-4 mRNA was increased in regional lymph nodes and spleen of the rIL-4-treated groups compared with all other groups, but there were no differences for IL-2, interferon-gamma, or IL-10. CONCLUSIONS: rIL-4 therapy markedly prolonged neonatal cardiac allograft survival, and, with anti-CD4 therapy, it further prolonged survival. It induced IL-4 mRNA in lymphoid tissues and enhanced alloantibody production, especially IgG1, which demonstrated enhanced Th2 responses, but did not affect Th1 cytokines.

Animals↗
PubMed1998

Effects of muscimol or homotaurine on sleep-wake states in alcohol-dependent rats during withdrawal.

Sleep-wake states were studied following withdrawal in 36 adult male wistar alcohol-dependent rats, after chronic administration of ethanol (10 g/kg/24 h) for 13 days. In the light phase of the withdrawal day, 12 alcohol-dependent rats received muscimol (0.25 mg/kg), 12 received homotaurine (140 mg/kg), and 12 received 0.9% physiological saline (10 ml/kg). The results have been compared with a control group of 36 rats that received water during the treatment phase of the experiment, and the 14th day received intraperitoneal muscimol or homotaurine. Muscimol significantly improves the alterations of sleep-wake states in alcohol-withdrawn rats, decreasing the percentage of active wakefulness and increasing the percentage of REMS, but without any action on the latency of appearance of REMS, which remains shortened. The effects of homotaurine are less important on the wakefulness, but it also increases the percentage of REMS without influencing its latency of appearance. The influence of these GABA(A) agonists is not identical during the whole period of survey in the light phase, as there are important differences in the temporal sequences for each of them. We conclude that the stimulation of GABA(A) receptors, of which the activity is decreased during alcohol withdrawal, significantly improves the disturbances in the sleep-wake states in the alcohol-dependent rats, in a time-related manner, and there are significant pharmacodynamic differences between muscimol and homotaurine.

Alcoholic Intoxication↗
PubMed1998

Continuous epidural infusion of ropivacaine for postoperative analgesia after major abdominal surgery: comparative study with i.v. PCA morphine.

We have compared the quality of three regimens of postoperative analgesia (continuous epidural administration of ropivacaine (Ropi. group), epidural ropivacaine and patient-controlled analgesia (PCA) with i.v. morphine (Ropi. + PCA group) and PCA morphine alone (PCA group)) during the first postoperative 24 h in a multicentre, randomized, prospective study. Postoperative analgesia was studied in 130 patients after major abdominal surgery performed under general anaesthesia. The ropivacaine groups received 20 ml of epidural bolus ropivacaine 2 mg ml-1 via the epidural route at the end of surgery, followed by continuous infusion of 10 ml h-1 for 24 h. The Ropi. + PCA group also had access to i.v. PCA morphine 1 mg, with a 5-min lockout. The PCA group received morphine as the sole postoperative pain treatment. The two ropivacaine groups had lower pain scores (P < 0.01) than the PCA group. Morphine consumption was higher in the PCA group (P < 0.05) than in the two ropivacaine groups. The quality of pain relief was rated as good or excellent in 79-85% of patients in the three groups. The percentage of patients without motor block increased between 4 and 24 h from 61% to 89% in the Ropi. group, and from 51% to 71% in the Ropi. + PCA group.

Abdomen↗
PubMed1997

New benzocycloalkylpiperazines, potent and selective 5-HT1A receptor ligands.

A series of 1-(benzocycloalkyl)-4-(benzamidolkyl)piperazine derivatives was prepared in order to obtain compounds with a high affinity and selectivity for 5-HT1A receptors. The modifications of aromatic substituents, the length of the alkyl chain, and the size of the ring were explored. Most of N-(1,2,3,4-tetrahydronaphthyl)-N'-(benzamidoethyl)piperazines (32-37) were bound to 5-HT1A receptors in a nanomolar range and presented a high degree of selectivity. After resolution, levorotatory enantiomers showed affinity and selectivity higher than those of dextrorotory ones for 5-HT1A sites. The agonist type activity of selected derivatives was also confirmed in vitro on the inhibition of the activation of adenylate cyclase induced by forskolin and, in vivo, on the induction of the lower lip retraction in rats.

Adenylyl Cyclases↗
PubMed1993

Effect of an antihypertensive hydrazine derivative on Ca2+ current of single frog cardiac cells.

The effects of MP 518, an acylated 2-chlorobenzylidene hydrazidone derivative with antihypertensive properties were investigated on the Ca current, ICa, recorded under whole-cell patch-clamp in single frog ventricular cells. MP 518 (1-100 microM) had no effect on ICa under control conditions. However, at 10 microM it significantly increased the beta-adrenergic stimulated ICa, an effect similar to that of isobutylmethyl-xanthine (IBMX), a non-specific phosphodiesterase inhibitor. The effects of MP 518 and IBMX were not, however, additive. This positive effect was also observed with both compounds, MP 518 and IMBX, when a submaximal dose of cyclic AMP was intracellularly perfused. In the presence of IBMX or at a high concentration (100 microM), MP 518 had a negative effect on beta-adrenergic stimulated ICa. It was thus considered that the main effect of MP 518 is an antiphosphodiesterase activity, since the increase in ICa induced by low concentrations of MP 518 could be related to inhibition of cAMP degradation; however, at higher concentrations, MP 518 antagonizes beta-adrenergic stimulation, possibly at several levels. Such an antiphosphodiesterase activity can account for the vasorelaxant effects as well as the tachycardic effects of MP 518.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Evaluation of the Clinitek 200 urinary test-strip reader in the analysis of dog and rat urines in pre-clinical toxicology studies.

The performance of a clinical urinary test-strip reader Clinitek 200 was evaluated for dog and rat urines, in the context of pre-clinical toxicology studies. No major discrepancies were found between data generated by visual estimation or automatic measurement. Analysis of spiked samples showed good agreement between actual concentrations and Clinitek 200 responses for ketone bodies and glucose although a lack of sensitivity was found for the latter. Results for proteins showed over- or underestimation in dog and rat urines respectively at low concentrations, and overestimation at high concentrations in both species. Reproducibility of responses was excellent for ketone bodies, glucose and proteins but was weaker for haemoglobin and bilirubin. High bilirubin concentrations were found to interfere with the haemoglobin reaction. The pH measurements were found to be accurate only around pH 7. Specific gravity measurements were unreliable. Overall, the Clinitek 200 as a screening tool proved sufficiently reliable in the measurement of all parameters tested, with the exception of specific gravity.

Animals↗
PubMed1993

[Characteristics of the audiogenic convulsive crisis in mice made sensitive by magnesium deficiency].

Mice of the OF1, C57BL/6, AKR, C3H/He, DBA/2, BALB/C, B6D2F1 and CBA strains are susceptible to audiogenic seizures after 40 or 20 days of acute magnesium deficiency. The duration of the various phases of the audiogenic seizure response (at 100 dBA) (wild running latency period, convulsions latency period and the clonic and tonic convulsions) among these mice was measured. Using the Kruskall-Wallis test, no difference was recorded using these measurements and those obtained for genetically audio-susceptible animals. This shows that acute magnesium deficiency-induced audiogenic seizures develop in exactly the same way as in genetically audio-susceptible animals (21-days-old DBA/2 mice). Lower intensity (60 and 80 dBA) produced only audiogenic seizures in magnesium deficient mice. Repeated auditory stimulation caused an increase in the number of lethal seizures. Sound-induced seizures in magnesium deficient mice provide a sensitive screening test for anti convulsive drug, and for drugs use in magnesium depletion.

Acoustic Stimulation↗
PubMed1992

Effects of alcohol dependence on shock-induced fighting: action of muscimol and homotaurine.

We have applied the electroshock-induced fighting behavior to the study of experimental alcohol dependence. Adult Wistar rats were intoxicated chronically with ethanol (10 g/kg/24 h) for 13 days. Electroshock-induced fighting behavior was studied during chronic intoxication and withdrawal in comparison with normal rats receiving a water-carbohydrate solution isocaloric to ethanol. Rats were divided into groups receiving respectively muscimol (0.25 mg/kg), a GABAA agonist; homotaurine (140 mg/kg) a GABA mimetic; and physiological saline (10 ml/kg), intraperitoneally. During chronic intoxication, rats showed an increase in defensive-fighting behavior. Withdrawal accentuated the aggressive behavior and muscimol and homotaurine inhibited it. These results confirm the relevance of the electroshock-induced defensive fighting behavior test in chronic intoxication with alcohol, but to show the involvement of GABAergic transmission in the behavioral effects of alcohol withdrawal, additional experiments with other GABA mimetics and with GABA antagonists should be considered.

Aggression↗
PubMed1992

Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats.

Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H-GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour.

Acamprosate↗
PubMed1990

Circadian variations in vigilance states in the alcohol-dependent rat.

Waking and sleep states were studied in the alcohol-dependent rat after administration of ethanol (416 mg/kg/hr) by indwelling intragastric catheter (IGC) for 13 days. Electropolygraphic recordings performed for a total of 24 hr from the start of withdrawal were compared with those of control rats receiving water by IGC and showed 1) that rapid eye movement sleep was the most sensitive of the four vigilance states studied. A decrease was noted both for the total duration of recording and for the light period; 2) that nonactive wakefulness was the only vigilance state to show an inversion of percentages between the light and dark period; 3) that the light period was the best time for studying changes in vigilance states. Changes included increased percentages of active and nonactive wakefulness and decreased percentages of slow-wave and rapid eye movement sleep. This was due to a change in the number of episodes rather to a change in their mean duration. No significant change occurred during the dark period.

Alcohol Withdrawal Delirium↗
PubMed1990

Acamprosate appears to decrease alcohol intake in weaned alcoholics.

Five hundred and sixty-nine alcoholics were included in a double-blind placebo-controlled randomized multicenter study of the effects of Acamprosate (calcium acetylhomotaurinate (CA), 1.3 g/day) on indicators of alcoholic relapse after withdrawal. One hundred and eighty-one patients in the CA group versus 175 in the placebo group completed the three-month study. The major efficacy criterion was plasma gamma-glutamyl transpeptidase (GGT), as an indicator of recent alcohol ingestion. This analysis was completed by criteria concordance analysis on a number of indicators of alcohol intake. Patients in both groups were similar initially. After 3 months of treatment, the patients in the CA group had significantly lower GGT (1.4 +/- 1.56 versus 2.0 +/- 3.19 times normal, P = 0.016). All significant differences (P less than 0.05) or trends (0.10 greater than P greater than 0.05) were in favor of a superior effect of CA over placebo. The major side-effect of CA was diarrhea (present in 13% of CA patients versus 7% of placebo, P = 0.04). CA proved superior to placebo on the evolution of markers of alcohol ingestion at three months, in this large-scale multicenter study. It could be a new modality in the drug therapy of alcoholism, not involving an antabuse effect, an antidepressant action, or conditioning.

Acamprosate↗
PubMed1985

Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics.

After they had been weaned off alcohol in hospital 85 severe alcoholics (above 200 g alcohol/day) were included in a double-blind study of calcium bis acetyl homotaurine (Ca AOTA, 25 mg/kg/day), a new gamma-aminobutyric acid agonist, versus placebo. Patients were treated as outpatients during the 3-month study. The only other treatment that patients received was meprobamate, 800 to 1200 mg/day, in the first month. The criterion for success was abstinence at 3 months (with normal gamma-glutamyl transpeptidase being one of the criteria). Of the 70 patients who completed the study, 33 received Ca AOTA and 37 placebo. 20 patients on Ca AOTA did not relapse, compared with 12 on placebo (p less than 0.02 by X2 test). Side-effects were noted by 7 patients on Ca AOTA and 2 on placebo. The results suggest that Ca AOTA may be useful in helping severe alcoholics who have been weaned off alcohol not to relapse.

Acamprosate↗