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C Lambert

Publications and source records attributed to C Lambert.

At least 55 records · Page 3Linked to original sources
PubMed1989

Anthralin-derived transients--I. The triplet state and the products of its reaction with oxygen in benzene.

Direct laser excitation in benzene of 1,8-dihydroxy-9-anthrone (anthralin) does not lead to transient species with lifetimes in the nanosecond time regime or longer. The triplet state has been produced in benzene by pulse radiolysis and characterised in terms of its absorption spectrum (lambda max 560 nm), natural lifetime (11 microseconds), self-quenching properties (kmicrosecond = 2.6 x 10(7) l mol-1 s-1) and triplet energy (234 kJ mol-1). There is no tendency in the non-polar medium for production of either the triplet or ground state in a tautomeric form. The observed triplet state reacts with oxygen with a typical rate constant, 2.2 x 10(9) l mol-1 s-1. The products of this reaction are singlet oxygen (approximately 64%) and the anthralin radical (approximately 14%).

Anthralin↗
PubMed1989

Opposite effects of lidocaine and diltiazem on electrophysiologic alterations in acutely ischemic porcine myocardium.

To investigate the actions of lidocaine and diltiazem on the ischemic alterations associated with the onset of acute ischemic arrhythmias, the left anterior descending coronary artery was occluded for 6-min periods separated by 30 min of reperfusion, under control conditions and after injection of lidocaine (2.4-3.8 micrograms/mL of plasma) or diltiazem (390-510 ng/mL) in open-chest anesthetized pigs. Sixty-one unipolar electrograms were continuously recorded in the ischemic zone. Isochronal maps and isopotential maps were determined by computer analysis. The magnitude of beat-to-beat alternation of unipolar waveforms was described by the difference between the time integrals subtended by electrograms of consecutive beats. Activation times were prolonged by ischemia and the ST segment became elevated. Delay and ST elevation developed at a faster rate in the presence of lidocaine than under control conditions, but were reduced by diltiazem. ST-T alternation was not significantly different between control and lidocaine occlusions, but the incidence of negative T waves and that of ventricular tachycardia degenerating to fibrillation were higher in lidocaine occlusions than in control occlusions. In contrast, unipolar waveform alternation and negative T waves were virtually abolished by diltiazem, even at fast pacing rates (180-210 beats/min) at which diltiazem did not reduce ST elevation. Ventricular arrhythmias also were abolished by diltiazem. Thus, lidocaine and diltiazem produce opposite effects on the ischemic alterations most closely associated with the initiating mechanism of tachycardia. This could be related to differences between these drugs with regard to their actions on transmembrane currents during repolarization.

Animals↗
PubMed1989

Serum cytokine changes in systemic vasculitis.

Cytokines are known to alter a number of vascular tissue cell functions. The aim of this retrospective study was to determine serum cytokine levels in patients with vasculitis and to analyse the possible relation to the severity of the disease. Tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1)beta, IL-2, interferon (IFN)- and IFN-gamma were assayed in 33 patients with polyarteritis nodosa (PAN) or Churg and Strauss angiitis (CSA), and three with Wegener granulomatosis (WG). Serum cytokine changes were observed in most patients with active disease, i.e. before treatment was started. In the majority of patients with PAN or CSA, there was a marked increase in serum IFN-alpha and IL-2 levels, while TNF-alpha and IL-beta levels were moderately elevated. Serum IFN-gamma remained undetectable in all but one of these patients. In patients with WG, serum IFN-alpha and IL-2 levels were also elevated, whereas IL-1 beta, IFN-gamma and TNF alpha levels remained within normal limits. In paired samples of patients with PAN, IFN-alpha and IL-2 levels were significantly higher before than after treatment. These preliminary data suggest that a particular pattern of cytokine changes is associated with vasculitis and that cytokines might be involved in the pathogenesis of PAN/CSA and WG. Prospective studies are warranted to determine whether cytokines could be considered for the monitoring of disease activity and therapy.

Biological Factors↗
PubMed1988

Inhibition of human leukocyte 5-lipoxygenase by 15-HPETE and related eicosanoids.

The inhibition of human leukocyte 5-lipoxygenase by 15-hydroperoxyeicosatetraenoic acid and its chemical or enzymatic rearrangement products was investigated. 15-Hydroperoxyeicosatetraenoic acid was the most potent inhibitor tested. The inhibition was found to be time dependent and is not due to chemical or enzymatic decomposition products nor metabolism of 15-hydroperoxyeicosatetraenoic acid to 5,15-dihydroperoxyeicosatetraenoic acid.

Arachidonate Lipoxygenases↗
PubMed1988

A yeast DNA repair gene partially complements defective excision repair in mammalian cells.

The RAD10 gene of Saccharomyces cerevisiae is required for nucleotide excision repair of DNA. Expression of RAD10 mRNA and Rad10 protein was demonstrated in Chinese hamster ovary (CHO) cells containing amplified copies of the gene, and RAD10 mRNA was also detected in stable transfectants without gene amplification. Following transfection with the RAD10 gene, three independently isolated excision repair-defective CHO cell lines from the same genetic complementation group (complementation group 2) showed partial complementation of sensitivity to killing by UV radiation and to the DNA cross-linking agent mitomycin C. These results were not observed when RAD10 was introduced into excision repair-defective CHO cell lines from other genetic complementation groups, nor when the yeast RAD3 gene was expressed in cells from genetic complementation group 2. Enhanced UV resistance in cells carrying the RAD10 gene was accompanied by partial reactivation of the plasmid-borne chloramphenicol acetyltransferase (cat) gene following its inactivation by UV radiation. The phenotype of CHO cells from genetic complementation group 2 is also specifically complemented by the human ERCC1 gene, and the ERCC1 and RAD10 genes have similar amino acid sequences. The present experiments therefore indicate that the structural homology between the yeast Rad10 and human Ercc1 polypeptides is reflected at a functional level, and suggest that nucleotide excision repair proteins are conserved in eukaryotes.

Animals↗
PubMed1988

Arachidonic acid metabolism in Ascidia ceratodes eggs: role of lipid peroxidation.

1. Addition of arachidonic acid (AA) to Ascidia ceratodes oocyte homogenates results in its rapid oxidation to several polar products. 2. AA oxidation in homogenates has both calcium independent and calcium stimulated components. 3. Calcium or AA addition to an oocyte homogenate stimulates O2-consumption. 4. Stimulation of homogenate O2-consumption by AA and calcium is additive. 5. Intact eggs oxidize AA to products similar to those detected in vitro. 6. Quantitatively total AA oxidation was similar for unfertilized and fertilizing eggs and dividing embryos, while qualitative differences were detected for the three stages. 7. These results demonstrate the presence of lipoxygenase-like, peroxidizing activity, in Ascidia eggs that is capable of producing products potentially important to the control of early metabolic events during development.

Animals↗
PubMed1988

A comparative study of the formation of chemically reactive drug metabolites by human liver microsomes.

1. The metabolism of amodiaquine (A), ethinyloestradiol (E), mianserin (M), phenytoin (Ph), sulphanilamide (S) and paracetamol (Pa) to both stable and chemically reactive, i.e. irreversibly protein bound, metabolites was investigated using microsomes prepared from histologically normal human liver obtained from eight kidney donors. 2. All drugs, except amodiaquine, were metabolized by NADPH-dependent microsomal enzymes to chemically reactive metabolites. The degree of NADPH-dependent binding varied between drugs (E, 11.5 +/- 5.8% incubated drug; M, 3.0 +/- 1.9%; Ph, 0.10 +/- 0.09%; S, 0.57 +/- 0.38%; Pa, 1.2 +/- 1.2%; mean of eight livers +/- s.d.). 3. Inclusion of glutathione (1 mM) or ascorbic acid (1 mM) in the incubation reduced the NADPH-dependent binding for all substrates, indicating the involvement of electrophilic oxidation products. 4. Binding of M and Pa correlated with each other (Spearman's r = 0.86) and with total cytochrome P-450 content (r = 0.76 and 0.78 respectively). E binding also correlated with the binding of M (r = 0.79) and Pa (r = 0.81) but not with cytochrome P-450. Binding of Ph and S did not correlate with any of the other measured metabolic parameters.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1988

An in vitro study of the microsomal metabolism and cellular toxicity of phenytoin, sorbinil and mianserin.

1. The cytotoxicity of metabolites generated from phenytoin, sorbinil and mianserin by human and mouse liver microsomes was assessed by co-incubation with human mononuclear leucocytes as target cells. Cytotoxicity was determined by trypan blue dye exclusion. 2. Phenytoin and sorbinil were metabolised by NADPH-dependent murine microsomal enzymes to cytotoxic metabolites. Cytotoxicity produced by both drugs was significantly enhanced by the epoxide hydrolase inhibitor trichloropropane oxide (TCPO). No significant cytotoxicity was observed in the presence of human liver microsomes. 3. Mianserin was metabolised by both human and mouse liver microsomes to a cytotoxin. Cytotoxicity was greater in the presence of human liver microsomes (13.7 +/- 2.2%; mean +/- s.d. for four livers, compared with 6.0 +/- 2.4%, mean +/- s.d., n = 4, with mouse liver microsomes), and was unaffected by pretreatment with TCPO. 4. Stable metabolites were quantified by radiometric high performance liquid chromatography. Phenytoin and sorbinil were metabolised to 5-(p-hydroxyphenyl)-5-phenyl-hydantoin (0.3-0.5% of incubated radioactivity) and 2-hydroxysorbinil (0.4-2.7% of incubated radioactivity), respectively, by both human and mouse liver microsomes. 5. Mianserin was metabolised to 8-hydroxymianserin and desmethylmianserin by both human and mouse liver microsomes. Desmethylmianserin was the major product in incubations with human liver microsomes (32.3 +/- 12%, mean +/- s.d. for four livers), whereas 8-hydroxymianserin was the predominant metabolite generated by mouse liver microsomes (25.9 +/- 1.5%, mean +/- s.d., n = 4). 6. Generation of electrophilic metabolites was assessed by determination of the amount of radiolabelled material which became irreversibly bound to protein. Only mouse liver microsomes activated phenytoin to a chemically reactive metabolite, whereas both mouse and human liver microsomes generated reactive metabolites from sorbinil and mianserin. 7. These studies show that drug cytotoxicity can be mediated by low concentrations (circa microM) of metabolites generated by NADPH-dependent hepatic microsomal enzymes; however demonstration of cytotoxicity in vitro has not been established as a means of predicting in vivo toxicity.

Adult↗
PubMed1988

Pharmacokinetics of bupivacaine after short and prolonged infusions in conscious dogs.

A conscious dog model was used to study pharmacokinetics of bupivacaine after a short infusion (SI) (15 min) and a prolonged infusion (PI) (24 hours). Bupivacaine was infused in six mongrel dogs at least 10 days after implantation of femoral arterial and venous catheters. Each dog received both the SI and the PI in a random crossover design at a one week interval. Bupivacaine concentration was measured in serum sampled during the SI, during the last hour of the PI, and at frequent intervals during eight hours after cessation of infusion. Indocyanine green (ICG) clearance also was measured during the last hour of the PI and 90 min after cessation of both the SI and the PI. The terminal half-life (T1/2Z) of bupivacaine increased after the PI compared with the SI, 167 +/- 86 vs 53 +/- 13 min, respectively (mean +/- SD; P less than 0.05), and total body clearance (Cl) decreased, 3.4 +/- 1.2 vs 9.5 +/- 4.5 ml.min-1.kg-1, (P less than 0.05), although the volumes of distribution (VZ and VSS) did not change. A decrease in hepatic blood flow did not cause the decrease in Cl because ICG clearance did not change during the three sets of measurements. Thus, the observed increase in T1/2Z and decrease in Cl after the PI as compared with the SI are due to a decrease in hepatic intrinsic clearance of bupivacaine. Differences in the kinetic profile of the two enantiomers of bupivacaine cannot be excluded as a cause. We conclude that the extrapolation of kinetic data of bupivacaine obtained after a short infusion (or a bolus injection) to prolonged dosage must be done with care.

Anesthetics, Local↗
PubMed1987

Efficacy and safety of intravenous and oral diltiazem for Wolff-Parkinson-White syndrome.

The electrophysiologic effects and safety of diltiazem administered either intravenously or orally were studied in 14 patients with Wolff-Parkinson-White syndrome during orthodromic reentrant tachycardia and atrial fibrillation (AF). Anterograde and retrograde effective refractory periods of the accessory pathway did not change significantly from baseline during either i.v. or oral administration. Administration by either route prevented induction of sustained reentrant tachycardia in 8 patients. In 6 patients, the reentrant tachycardia was either nonsustained (2 patients) or sustained at much slower rates than the baseline rates (mean +/- standard deviation, baseline, 290 +/- 41 ms; i.v., 355 +/- 40 ms [p less than 0.001]; and oral, 377 +/- 33 ms [p less than 0.001]). In these patients anterograde atrioventricular conduction was prolonged significantly from the mean baseline value of 163 +/- 36 ms to 212 +/- 35 ms with i.v. administration (p less than 0.005) and 225 +/- 33 ms with oral administration (p less than 0.005). Retrograde conduction via the accessory pathway did not change significantly after administration of diltiazem. The shortest preexcited RR intervals during AF were significantly reduced during i.v. but not during oral administration: control, 327 +/- 47 ms; i.v., 270 +/- 28 ms (p less than 0.001); and oral, 323 +/- 44 ms (difference not significant). In 5 patients AF was sustained for a mean of 20 minutes after i.v. and for 12 minutes after oral administration (p less than 0.20), compared with a baseline mean value of 0.83 minute.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Effect of high-dose ibuprofen on 24-hour blood pressure in healthy women.

The nonsteroidal antiinflammatory drug (NSAID) indomethacin has been shown to increase blood pressure in normotensive individuals. The effect of other NSAID on blood pressure has not been as well studied. We evaluated the effects of ibuprofen, an NSAID currently available without a prescription, on 24-hour ambulatory blood pressure in ten young, healthy, normotensive women. Using a randomized, crossover, double-blind design, subjects received ibuprofen 800 mg and a placebo identical in appearance to ibuprofen three times a day for eight days with a washout period between regimens. Subjects were instructed to follow a no-added salt diet during the study. Twenty-four-hour blood pressure monitoring and 24-hour urine collection for prostaglandin E2, creatinine, and sodium were performed on days 1 and 8 of each study week. Tablet counts and a 40 percent reduction in urinary prostaglandin E2 documented compliance with ibuprofen. Ibuprofen had no significant effect on systolic or diastolic blood pressure at any hour during the 24-hour period. Mean blood pressure for the 24-hour period was 112/73 and 111/73 mm Hg on day 1 and 111/73 and 112/73 mm Hg on day 8 for placebo and ibuprofen, respectively. We conclude that ibuprofen at doses as high as 2400 mg/d for up to seven days has no effect on blood pressure in normotensive women. Further studies are needed in hypertensive subjects.

Adult↗
PubMed1987

Lack of relation between the ventricular refractory period prolongation by amiodarone and the thyroid state in rats.

We investigated the possibility that the prolongation of the ventricular effective refractory period (VERP) by amiodarone might be mediated, at least in part, by inhibition of thyroid influence on the heart. VERP values were measured in vitro in isolated septal preparations obtained from control, thyroidectomized and thyroxine (tetraiodothyronine; T4)- or triiodothyronine (T3)-treated rats. Differences in thyroid influence on the heart between these groups were assessed by changes in the myosin isozyme (V1, V2, V3) pattern. VERP measurements were also done in similar groups treated with amiodarone for 7 days (50 mg/kg/day i.p.). VERP tended to be increased by thyroidectomy and was significantly reduced by T4 or T3 treatment when compared with the control group. Amiodarone treatment significantly prolonged VERP in control (33.4 +/- 1.9 to 45.0 +/- 4.5 msec), thyroidectomized (39.9 +/- 1.7 to 48.3 +/- 2.8 msec), T4-treated (26.2 +/- 1.0 to 37.4 +/- 1.3 msec) and T3-treated rats (25.6 +/- 1.1 to 34.3 +/- 1.3 msec). However, the magnitudes of the VERP prolongation by amiodarone were not significantly different among the four groups. The action of amiodarone on action potential duration was similar to its action on VERP. The myocardial concentrations of amiodarone and desethylamiodarone were not significantly different among the four groups. Amiodarone treatment produced a significant reduction of serum T3 levels in the control and in the T4-treated groups and an increase in reverse T3 levels. Thus, the class III action of amiodarone was not affected, in the present model, by experimental modification of thyroid influence on the heart.

Action Potentials↗
PubMed1987

Relation of transient silent ischemic episodes to daily activities.

In patients with coronary disease, asymptomatic ST segment depression during daily life is a reliable indicator of silent myocardial ischemia and is the most frequent form of ischemia in both symptomatic and asymptomatic patients. Silent ischemic episodes usually occur during activities not ordinarily thought to be ischemia provoking, and not necessarily with the same frequency, duration, or magnitude as painful episodes and may be the only type of ischemia detected in some patients. Some features suggest an important reduction in myocardial oxygen supply, in addition to an increase in demand, as a mechanism for silent ischemic episodes occurring during daily life.

Activities of Daily Living↗
PubMed1986

Effect of the induction of amiodarone biotransformation on ventricular refractory periods in rats.

Amiodarone is a potent class III antiarrhythmic agent that has a slow onset of action in patients (ca. 20 days). To determine if myocardial accumulation of desethylamiodarone (DEA), its main metabolite, influences its antiarrhythmic activity, three groups of six Wistar rats were given amiodarone, 50 mg/kg/day i.p. (A groups), and three groups received the same dose of amiodarone in combination with 80 mg/kg/day of phenobarbital to induce hepatic biotransformation (AP groups). After 3, 7 or 21 days, the rats were sacrificed and the ventricular effective refractory period (VERP) was determined by the extrastimulus technique in endocardial preparations superfused in the tissue bath. Control measurements of VERP were done in untreated rats. Myocardial concentrations of DEA measured by high-performance liquid chromatography were significantly higher in the AP groups than in the A groups (7.5 +/- 0.83 vs. 2.27 +/- 0.11 micrograms/g at 3 days, 6.09 +/- 0.70 vs. 2.82 +/- 0.30 micrograms/g at 7 days and 11.93 +/- 1.22 vs. 4.79 +/- 1.84 micrograms/g at 21 days: mean +/- S.E.). Control VERP value was 33.4 +/- 1.2 msec and was increased by 9, 35 and 42% after 3, 7 and 21 days in the A groups, and by 9, 38 and 39% in the AP groups. After 7 days of DEA administration yielding myocardial concentrations similar to those obtained after amiodarone treatment, there was a slight but nonsignificant prolongation of the VERP (12%). Thus, the prolongation of VERP after amiodarone administration did not appear to depend on myocardial DEA accumulation, suggesting that the slow onset of amiodarone class III action may not be related to DEA disposition.

Action Potentials↗
PubMed1986

[Localization of transcription regulatory sequences. Application to the genes of the prolactin family].

We are studying nucleotide sequences responsible for the regulation of eukaryotic gene expression. Our test system comprises the human genes coding for prolactin (hPRL), growth hormone (hGH-N) and placental lactogen (hCS-B). We have cloned these genes and are searching within their sequences for in vitro binding sites of the human glucocorticoid receptor on the hGH-N and hCS-B genes; the in vivo activity of such DNA sequences by assaying hybrid gene expression in transfected cells; in vivo "enhancer" activity of different hPRL gene fragments linked to a marker gene and transfected in cultured cells.

Base Sequence↗
PubMed1985

Antagonistic effects of thyrotropin and epidermal growth factor on thyroglobulin mRNA level in cultured thyroid cells.

Both thyrotropin (TSH) and epidermal growth factor (EGF) are potent mitogenic agents when added to dog thyroid cells in primary culture [Roger, P. P. and Dumont, J. E. (1984) Mol. Cell. Endocrinol. 36, 79-93]. The concomitant effect of these agents on the differentiation state of the cells was appreciated using cell morphology, iodide trapping, thyroglobulin synthesis and cytoplasmic thyroglobulin mRNA content as markers. Together with previous results [Mol. Cell. Endocrinol. 36, 79-93 (1984)] it is shown that cells cultured in the continuous presence of TSH maintain all the parameters at a near normal level. In the absence of TSH, thyroglobulin mRNA decreased to very low, though still detectable levels. Addition of TSH restored subnormal mRNA levels. Culture of cells in the presence of EGF for 4-6 days affected profoundly their morphology, abolished iodide trapping and decreased thyroglobulin synthesis and cytoplasmic mRNA content to undetectable levels. Addition of TSH to cells previously exposed to EGF reversed the growth factor effect on all four indexes. The redifferentiating effect of TSH was well observed within 3-4 days and was mimicked by the adenylate cyclase activators, forskolin and cholera toxin. When administered simultaneously, TSH and EGF achieved an intermediate situation, EGF antagonizing partially the effect of TSH on the expression of thyroglobulin gene. Another growth factor, fibroblast growth factor, while promoting thyroid cell proliferation also, did not interfere at all with TSH effects on cytoplasmic thyroglobulin mRNA content. Our results make the dog thyroid cell in primary culture an appropriate model to study the mechanisms involved in gene regulation by cyclic AMP and growth factors.

Animals↗
PubMed1985

The Keyes technique and self-inflicted injuries. Three case reports.

Three cases of self-inflicted gingival injuries resulting from the improper use of the Keyes technique are presented. The profession must assume responsibility for studies to determine the safety of the methods of application of the hydrogen peroxide, salt and baking soda mixtures and disseminate this information for the public interest.

Bicarbonates↗