Search PubMed⌕ Search

Biomedical subjects

I Lambert

Publications and source records attributed to I Lambert.

At least 37 records · Page 2Linked to original sources
PubMed1985

1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) and related compounds as inducers of hepatic monooxygenases. Structure-activity effects.

1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) resembles phenobarbital (PB) in its mode of induction of the hepatic drug-metabolizing enzymes in mice. The structural features of this molecule include: a linear tricyclic aromatic ether ring system, an internal 1,4-disubstituted benzene ring and two 3,5-dichloropyridyloxy substituents. Ten analogs of TCPOBOP have been synthesized and their activities as microsomal enzyme inducers evaluated. Dose-response induction of mice hepatic microsomal cytochrome P-450, aldrin epoxidase and dimethylaminoantipyrine N-demethylase gave ED50 values for TCPOBOP and five homologs. The results illustrate that changes in the structure of the pyridyloxy ring markedly affect enzyme induction activity. The order of activity for the substituents was 3,5-dibromopyridyloxy approximately 3,5-dichloropyridyloxy greater than 5-bromopyridyloxy approximately 5-chloropyridyloxy greater than 3-chloropyridyloxy greater than pyridyloxy. In addition, the effects of altered substitution pattern of the benzene ring and structural alterations of the internal ring moiety were evaluated by measuring hepatic microsomal coumarin hydroxylase activity. The results confirm the microsomal monooxygenase enzyme induction activity of TCPOBOP, and the observed structure-dependent potencies of several related homologs support a receptor-mediated mechanism of action for the process.

Animals↗
PubMed1984

PCBs and PBBs: biologic and toxic effects on C57BL/6J and DBA/2J inbred mice.

Treatment of genetically inbred "responsive" C57BL/6J and "non-responsive" DBA/2J mice with Aroclor 1254 or fireMaster BP-6 resulted in the induction of hepatic microsomal benzo[a]pyrene hydroxylase only in the former mouse strain and aminopyrine N-demethylase in both strains of mice. In contrast, 3,3',4,4',5-pentachlorobiphenyl and 3,3',4,4'-tetrabromobiphenyl, induced benzo[a]pyrene hydroxylase in both C57BL/6J and DBA/2J but did not enhance aminopyrine N-demethylase in either strain of mouse. Both these coplanar halogenated biphenyls also caused thymic atrophy in the responsive and non-responsive mice and their effects resembled those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Treatment of the inbred mice with several mono-ortho substituted analogs of the coplanar halogenated biphenyls, including 2,3,3',4,4'-pentachloro-, 2,3',4,4',5-pentabromo-, 2,3,3',4,4',5-hexachloro- and 3',4'-dibromo-2,3,4,5-tetrachlorobiphenyl, gave hepatic enzyme-induction results similar to those observed for the commercial halogenated biphenyls. At dose levels of 1500 mumol/kg, most of these compounds caused thymic atrophy in C57BL/6J mice but not in DBA/2J mice. The structure-activity correlations in the mice complement similar studies with the halogenated biphenyls in rats and support the proposed receptor-mediated mechanism for the toxic halogenated aromatics.

Aminopyrine N-Demethylase↗
PubMed1983

Polychlorinated biphenyls as phenobarbitone-type inducers of microsomal enzymes. Structure-activity relationships for a series of 2,4-dichloro-substituted congeners.

Several polychlorinated biphenyl (PCB) isomers and congeners resemble phenobarbitone (PB) in their mode of induction of the hepatic drug-metabolizing enzymes; however, unlike PCBs which induce aryl hydrocarbon hydroxylase, no apparent structure-activity correlations have been reported. This study examines the effects of structure on the activity of a series of 2,4-dichloro-substituted biphenyls as inducers of several microsomal enzyme activities including dimethylaminoantipyrine N-demethylase, benzo[a]pyrene hydroxylase, aldrin epoxidase, and ethoxyresorufin O-deethylase. The results clearly illustrate a marked effect of structure on activity: all of the 2,4-dichloro-substituted PCBs resembled PB in their mode of induction. However, the potency of the induction response was dependent on the substitution pattern of the second phenyl ring (i.e. 2,3,4,5-tetrachloro greater than or equal to 2,3,4,5,6-pentachloro greater than 2,3,4,6-tetrachloro greater than 2,3,5,6-tetrachloro greater than 2,4,6-trichloro); the structure of the lower chlorinated ring also determined induction potency since the 2,4-dichloro-substituted PCBs were generally more active than their 4-chloro-substituted analogs, whereas the 2-substituted PCB homologs were inactive. The structural factors which typify the most active PB-type inducer, 2,2',3,4,4',5-hexachlorobiphenyl, include the presence of two para-, at least two meta- and two ortho-chloro substituents. In addition to the structure-activity correlations noted for PCBs, the 2,2',3,4,4',5-hexachlorobiphenyl congener also elicited a dose-response induction of two PB-inducible enzymes, aldrin epoxidase and dimethylaminoantipyrine N-demethylase.

Animals↗
PubMed1983

The comparative biologic and toxic potencies of polychlorinated biphenyls and polybrominated biphenyls.

Aroclor 1254 and fireMaster BP-6, two commercial polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) preparations, exhibit comparable biologic and toxic effects. In the present study the commercial PBB was more active than Aroclor 1254 in causing thymic atrophy in male Wistar rats. However, a direct comparison of the relative effects of bromine vs chlorine substituents is not possible with the commercial PBB and PCB mixtures due to their complex congeneric composition. This study reports the synthesis and biologic and toxic effects of a series of laterally substituted 3,3',4,4'-tetrahalobiphenyls which contain the following variable molecular Cl/Br ratios; Br4, Br3Cl, Br2Cl2 (two isomers), BrCl3, and Cl4. 3,3',4,4'-Tetrabromobiphenyl and 3,4,4'-tribromo-3'-chlorobiphenyl (150 mumol/kg)-pretreated animals significantly inhibited the growth rate of and caused thymic atrophy in immature male Wistar rats whereas those isostereomers with reduced Br (and increased Cl) content were either less active or inactive. Pretreatment of male Wistar rats with 10 mumol/kg of the 3,3',4,4'-tetrahalobiphenyls and determination of their effects as inducers of the hepatic microsomal drug-metabolizing enzymes also illustrated the effects of the relative Cl/Br ratios on induction potencies. Both 3,3',4,4'-tetrabromo- and 3,4,4'-tribromo-3'-chlorobiphenyl maximally induced the cytochrome P-448-dependent monooxygenases, benzo[a]pyrene and 4-chlorobiphenyl hydroxylase; the order of potency of the other isostereomers was 4,4'-dibromo-3,3'-dichloro- congruent to 3,4-dibromo-3',4'-dichlorobiphenyl greater than 4-bromo-3,3',4'-trichloro- greater than 3,3',4,4'-tetrachlorobiphenyl. With few exceptions this order of potency was observed for the induction of benzo[a]pyrene hydroxylase and ethoxyresorufin O-deethylase in rat hepatoma cells in culture and for their relative binding affinities to the rat cytosolic receptor protein. The data clearly demonstrate that the biologic activities of this group of isosteric halogenated biphenyls are enhanced with increasing bromine substitution and also support the hypothesis that the activities of this class of chemicals are mediated through the receptor.

Animals↗
PubMed1983

Effects of hypo and hyperosmotic media on rabbit renal cortical slices.

Rabbit kidney cortex slices behave as osmometers when withstanding either hyperosmotic shocks or hypo-osmotic shocks of amplitude up to P1/P2 = 1.25. For hypo-osmotic shocks of amplitude larger or equal to P1/P2 = 1.5 a volume regulation process occurs. Na+ is the main osmotic effector implicated in volume control.

Animals↗
PubMed1983

Effect of osmotic shocks on rabbit kidney cortex slices.

Rabbit kidney cortex slices behave an osmometers when withstanding hyperosmotic or hyposmotic shocks of amplitude up to pi 1/pi 2 = 1.25. For hyposmotic shocks of amplitude larger than or equal to pi 1/pi 2 = 1.50, the maximum swelling achieved is less than what can be expected on the basis of the van't Hoff relation, thereby indicating that a volume regulation process is taking place. Volume regulation in kidney slices can be dissociated into two distinct phases. The first one, of swelling limitation, is very rapid and keeps maximum cell volume at values lower than expected when the tissue is considered as an osmometer. This phase is followed by a slow volume readjustment process during which volume progressively decreases towards control values. The major intracellular osmotic effector loss during both swelling limitation and volume readjustment is Na+. The overall volume regulation process is insensitive to furosemide, vanadate, and bumetanide. Swelling limitation is blocked by addition of ouabain. Contrary to what has been believed previously, there is, however, no need to implicate control of the activity of a ouabain-sensitive, Na+/K+ pump in the Na-dependent volume regulation mechanism.

Amino Acids↗
PubMed1979

[Immunochemical properties and therapeutic usefulness of the preparation Igalina produced by Biomed].

In order to obtain higher concentration of IgA-antibodies in commercial gammaglobulin preparations, used for treatment of hipo - and dysimmunoglobulinemia states, there are produced two preparations: "Gamma-A- Konzentrat " of Behringwerke and " Igalina " of Biomed . The first one was examined and described by us previously (4, 12). Now we present our studies on Igalina . The examinations were performed using electrophoresis on cellulose acetate, double diffusion in agar gell using 15 specific antisera to plasma proteins and immunoelectrophoresis with anti-IgG, IgA and IgM. There were detected traces of albumin, transferin , alfa2 macroglobulin, haptoglobin fibrinogen and presence of IgA, IgG and IgM. We also observed the split of IgG line in immunoelectrophoresis at the cathode and to Fc and Fab fragments. The concentrations of IgA, IgG and IgM were evaluated using Mancini method (IgA--920 IU/ml, IgG--1640 IU/ml IgM 2500 IU/ml). Concentrations of chosen antibodies in Igalina were: ASO--1000 U/ml, anti- Staphylolisins 8 U/ml, agglutinins antistaphilococal 1 : 320, diphtheria antitoxins 42 U/ml, agglutinins antithyphi 1 : 20----1 : 640. They were 4 to 100 times higher than in plasma serum. Isohaemagglutinins were not detected. Igalina was used for preventive treatment of children contacted with viral infections or therapeutically for children who demonstrated first symptoms of viral infections of respiratory tracts. Preparation was given 48 times to 40 children. This group included 19 newborns and 10 children with I and IV type of dysimmunoglobulinemia or hipoimmunoglobulinemia . Doses ranged from 0,5 ml up to 1,0 ml/kg body weight. Estimations of IgA, IgG and IgM concentrations in serum and saliva of children (using Mancini method) were carried out before injection of Igalina and on the third and seventh day after injection. Results of studies were statistically evaluated, and besides the lack of significant differences we found some rise of IgA and IgG concentrations. We would like to underline also that in 6 children with hipo or dysimmunoglobulinemia the levels of IgA and IgG reached normal value on the third day after injection of Igalina . Investigations of secretory piece in saliva in the same period were carried out too. In three patients we could find the presence of secretory piece just after injection of Igalina . We did not found antibodies to IgA in patients' sera after treatment. The clinical results of treatment as well as toleration of the drug were good and very good.

Adjuvants, Immunologic↗
PubMed1975

[Investigation on protein and protein fractions concentration in the serum of healthy children over one year old (author's transl)].

Protein concentration and the relative percentage of protein fractions in serum have been studied in 2 to 15 years old 226 healthy children. The mean values and standard deviation were calculated for every year of child life. The correlation analysis of all parameters investigated with the age of the children was also presented, as well as the relationships between the various parameters.

Adolescent↗