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PubMed1994

Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis. Application to cases from industrial rubber products.

3 cases of allergic contact dermatitis from industrial rubber products were investigated using a combination of patch testing in patients and chemical analysis of causative rubber products by gas chromatography (GC), GC-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Our studies revealed N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), a typical rubber allergen, as a causative chemical in a case from a brand of heavy-duty rubber gloves and a case from a black rubber ring for car manufacture, and zinc ethylphenyldithiocarbamate (ZEPC), a dithiocarbamate (DTC)-type accelerator, as a causative chemical in a case from a brand of rubber work gloves: both IPPD and ZEPC, which showed positive patch test reactions, were confirmed in the extracts of the causative rubber products by GC, GC-MS and/or HPLC.

Adult↗
PubMed1989

QSAR study on species differences in microsomal N-oxygenation of N,N-dimethylalkylamines.

The metabolic N-oxygenation of nine long chain N,N-dimethylalkylamines and tri-n-butylamine has been studied using hepatic microsomal homogenates from mice, dogs and guinea-pigs. The relative oxidizability of amines (ROA) was correlated with structure, lipophilicity and nucleophilicity parameters of substrates and corresponding amine oxides formed in this biological reaction. The highest conversion of amines to N-oxides was found with male guinea-pig, followed by dog (male, female) and the lowest amount of amine oxides has been produced with male mice microsomal homogenates. The analyses were carried out by GLC and the results quantified using QSAR methodology. ROA is parabolically dependent upon structure and physicochemical properties of the substrates and products which was proved by the high statistical significance of the regression equations. The biological N-oxygenation of these amines is controlled by lipophilicity, stereochemistry and electronic effects.

Animals↗
PubMed1990

Cut-off effect in antimicrobial activity and in membrane perturbation efficiency of the homologous series of N,N-dimethylalkylamine oxides.

The antimicrobial activity of the homologous series of N,N-dimethylalkylamine oxides (DMAO) was found to be quasi parabolically dependent on alkyl chain length with a maximum at n approximately 15 and n approximately 12 for Staphylococcus aureus and Escherichia coli, respectively. The physiochemical properties of DMAOs as characterized by critical micelle concentrations, retention times of 1-alkenes generated from DMAOs by gas-liquid chromatography, Rm values in reversed phase chromatography, and bacterial lipid/aqueous phase partition coefficients were found to correlate with the alkyl chain length. The effect of DMAOs on the structure of the model membrane prepared from isolated lipids from Escherichia coli as detected by a spin probe method was maximal for the alkyl chain length n approximately 10-12 coinciding with the maximum in the antimicrobial activity observed with Escherichia coli. It is suggested that the cut-off in the DMAO antimicrobial activity is caused by the cut-off in the DMAO perturbing effect on the membrane structure.

Anti-Bacterial Agents↗
PubMed1974

Ionic mechanisms and receptor properties underlying the responses of molluscan neurones to 5-hydroxytryptamine.

1. Molluscan neurones have been found to show six different types of response (three excitatory and three inhibitory) to the iontophoretic application of 5-hydroxytryptamine (5-HT). The pharmacological properties of the receptors and the ionic mechanisms associated with these responses have been analysed.2. Four of the responses to 5-HT (named A, A', B and C) are consequent upon an increase in membrane conductance whereas the other two (named alpha and beta) are caused by a decrease in membrane conductance.3. The A-response to 5-HT consists of a ;fast' depolarization due to an increase mainly in Na(+)-conductance; the A'-response is a ;slow' depolarization also associated with a Na(+)-conductance increase. Receptors mediating the A- and A'-depolarizations have different pharmacological properties and may exist side by side on the same neurone.4. Both the B- and C-responses are inhibitory. The B-response is a ;slow' hyperpolarization due to an increase in K(+)-conductance, the C-response is a fast hyperpolarization associated with an increase in Cl(-)-conductance.5. The alpha-response to 5-HT is a depolarization which becomes reduced in amplitude with cell hyperpolarization and reverses at -75 mV; it is caused by a decrease in K(+)-conductance. The beta-response is an hyperpolarization which increases in amplitude with cell hyperpolarization and reverses at -20/-30 mV. It results from a decrease in conductance to both Na(+) and K(+) ions.6. The receptors involved in the 5-HT responses associated with a conductance increase may be recognized by the action of specific antagonists: 7-methyltryptamine blocks only the A-receptors, 5-methoxygramine only the B-receptors and neostigmine only the C-receptors. Curare blocks the A- and C-receptors and bufotenine, the A-, A'- and B-receptors. No specific antagonists have yet been found for the 5-HT responses caused by a conductance decrease.7. The significance of the multiplicity of receptors is discussed. Their functional significance at synapses is analysed in the following paper.

Adrenergic beta-Antagonists↗
PubMed1974

On the transmitter function of 5-hydroxytryptamine at excitatory and inhibitory monosynaptic junctions.

1. Two symmetrical giant neurones located in the cerebral ganglion of Aplysia californica contain 4-6 p-mole 5-hydroxytryptamine (5-HT) and are able to synthesize it (Weinreich, McCaman, McCaman & Vaughn, 1973; Eisenstadt, Goldman, Kandel, Koike, Koester & Schwartz, 1973). Stimulation of each of these neurones evokes excitatory and inhibitory potentials in various cells of the ipsilateral buccal ganglion. In nine buccal neurones it evokes excitatory potentials, in other three, ;classical' inhibitory potentials and in one neurone an ;atypical' inhibitory potential.2. The connexion between the giant cerebral neurone and the cells receiving either an excitatory or a ;classical' inhibitory input from it are monosynaptic. TEA injection into the cerebral giant neurone, which prolongs the presynaptic spike, causes a gradual increase of both the excitatory and the inhibitory potentials. On the other hand, high Ca(2+) media, which block polysynaptic pathways, do not suppress these synaptic potentials.3. The iontophoretic application of 5-HT to the buccal neurones receiving excitatory input from the giant cerebral neurones evokes depolarizations showing the pharmacological properties of both A- and A'-responses to 5-HT (see preceding paper). Antagonists which block only the A-receptors (curare, 7-methyltryptamine, LSD 25) block partially the synaptic depolarizing potentials. Bufotenine, which blocks both the A- and A'-receptors, completely blocks the excitatory potentials. Thus, the post-synaptic membrane of these buccal neurones appears to be endowed with both A- and A'-receptors to 5-HT.4. The ;classical' inhibitory potentials elicited in three buccal neurones are hyperpolarizations which reverse at - 80 mV and are due to an increase in K(+)-conductance. The iontophoretic application of 5-HT to these post-synaptic neurones evokes hyperpolarizing B-responses which are also generated by an increase in K(+)-conductance. Antagonists which block the B-responses (bufotenine, methoxygramine) also block the inhibitory potentials.5. The ;atypical' inhibitory potential evoked in one buccal neurone consists in an hyperpolarization which increases in amplitude with cell hyperpolarization. Iontophoretic application of 5-HT to this buccal cell evokes an hyperpolarizing beta-response which also increases in amplitude with cell polarization and results from a decrease in both Na(+)- and K(+)- conductances. The monosynaptic character of the ;atypical' inhibitory potential is not yet fully proven.6. It can be concluded that the excitatory and inhibitory synaptic effects evoked in the buccal neurones by the stimulation of the 5-HT-containing-giant cerebral neurones are very likely mediated by 5-HT.

Action Potentials↗
PubMed1996

Time-dependent current decline in cyclic GMP-gated bovine channels caused by point mutations in the pore region expressed in Xenopus oocytes.

1. Amino acids with a charged or a polar residue in the putative pore region, between lysine 346 and glutamate 372 of the alpha-subunit of the cGMP-gated channel from bovine rods were mutated to a different amino acid. The mRNA encoding for the wild-type, i.e. the alpha-subunit, or mutant channels was injected in Xenopus laevis oocytes. 2. When glutamate 363 was mutated to asparagine, serine or alanine, the current activated by a steady cGMP concentration declined in mutant channels. No current decline was observed when glutamate 363 was mutated to aspartate, glutamine or glycine, when theronine 359, 360 and 364 were mutated to alanine or when other charged residues in the pore region were neutralized. 3. The amount of current decline and its time course were significantly voltage dependent. In mutant E363A the current decline developed within about 1.5 s at -100 mV, but in about 6 s at +100 mV. In the same mutant, the current declined to about 55% of its initial level at +100 mV and to about 10% at -100 mV. 4. The current decline in mutants E363A, E363S and E363N was only moderately dependent on the cGMP concentration (from 10 to 1000 microM) and was not caused by a reduced affinity of the mutant channels for cGMP. Analysis of current fluctuations at a single-channel level indicated that current decline was primarily caused by a decrease of the open probability. 5. The wild-type channel was not permeable to dimethylammonium. When glutamate 363 was replaced by a smaller residue such as serine, mutant channels became permeable to dimethylammonium. 6. The current decline observed in mutant channels is reminiscent of desensitization of ligand-gated channels and of inactivation of voltage-gated channels. These results suggest also that gating and permeation through the cGMP-gated channel from bovine rods are intrinsically coupled and that glutamate 363 is part of the molecular structure controlling both the gating and the narrowest region of the pore.

Amino Acid Sequence↗
PubMed1973

Monocular spatial distortions induced by marked accommodation.

Contraction of the ciliary muscle during marked accommodation causes the leading edge of the retina to advance as much as 0.5 centimeter. Near the posterior pole of the eye, the upward and downward extensional strains on the retina should be reasonably balanced. In the horizontal meridian an asymmetry is introduced because of the nasal location of the optic nerve head. Observers were asked to bisect the space between two parallel lines while fixating a movable line lying near the midpoint of the two lines. The test was conducted with the target far from and near the subject, in the horizontal and vertical meridians, and was repeated with accommodation paralyzed by a cycloplegic agent. Marked accommodation induced significant spatial distortions in the horizontal meridian. The effect is largely retinal.

Accommodation, Ocular↗
PubMed1977

Quantitation of dimethylnitrosamine in the whole mouse after biosynthesis in vivo from trace levels of precursors.

A simple and highly sensitive procedure is described for the recovery and quantitative identification of nanogram quantities of preformed N-nitroso compounds in the whole mouse. This procedure has also been applied to the quantitation of N-nitroso compounds after they have been biosynthesized from trace amounts of precursors. The whole animal is frozen in liquid nitrogen and homogenized to a frozen powder; the powder is then extracted and analyzed by a thermal energy analyzer interfaced to a gas-liquid and a high-pressure liquid chromatograph.

Animals↗
PubMed1973

Trial of the antiviral action of isoprinosine against rhinovirus infection of volunteers.

Isoprinosine (NPT-10381) was given orally to a group of 22 volunteers at a daily dose of 6 g for 7 days; a control group of 23 volunteers received placebo. Volunteers were inoculated intranasally with both rhinovirus type 9 and rhinovirus type 31, and the clinical picture, extent of virus shedding, and serological responses were assessed. There was no evidence that the compound had useful antiviral activity under the conditions of this trial.

Acetanilides↗
PubMed1973

Effect of isoprinosine against challenge with A(H3N2)-Hong Kong influenza virus in volunteers.

Volunteers were challenged with A(H(3)N(2))/Hong Kong/8/68 influenza virus while being given prophylaxis with either isoprinosine or placebo in a double-blind experiment. Isoprinosine, which had demonstrable antiviral activity in animal models, did not appear to protect humans from clinical influenza. The only beneficial effect of the drug observed was a slight, but significant, reduction in virus shedding.

Acetanilides↗
PubMed1974

Anti-herpesvirus action of isoprinosine.

Anti-herpesvirus effects of Isoprinosine were found to be condition-dependent in vitro and in vivo. A herpes type 1 strain, grown in primary rabbit kidney cells, was not susceptible to Isoprinosine when cytopathic effect was evaluated, but was modestly inhibited when plaque-forming methocel overlay was used in the same cell line. However, the growth of a herpes type 2 strain was inhibited by Isoprinosine in this system when cytopathic effect was evaluated. Both viruses produced an encephalitis in hamsters after application by corneal abrasion. The encephalitis produced by a 1.5 mean lethal dose of herpesvirus was strikingly suppressed by large doses of Isoprinosine given ad libitum in the drinking water; this protection was not seen, however, at 15 mean lethal doses. Anti-herpes effects of Isoprinosine were suppressed by additional treatment with cortisone, both in tissue culture and in vivo. Isoprinosine, in the absence of virus infection, produced significant effects on the metabolism, structure, and function of brain ribosomes. In vivo, RNA components were labeled more rapidly and gave up their radioactivity more slowly after treatment with Isoprinosine. This enhanced cytoplasmic radioactivity was associated with a loss of incorporated radioactivity located in the nucleus and an increase in radioactivity located in a ribonucleo-protein fraction >4S and <18S. Ribosomes from treated brains gave physical evidence of being more compact (less orthochromic). Isoprinosine treatment increased the incorporation of [(14)C]phenylalanine into nascent protein in a cell-free system examining protein synthesis in brain polyribosomes. The addition of the exogenous messenger ribonucleic acid, polyuridylic acid, produced a significant age-dependent inhibition in the incorporation of [(14)C] phenylalanine. This inhibition was significantly greater when ribosomes were isolated from animals pretreated with Isoprinosine. These and other observations suggest that the Isoprinosine stimulation of host ribonucleic acid metabolism may be coupled to the production of ribosomes that do not effectively translate exogenous messenger ribonucleic acid.

Acetanilides↗
PubMed1992

Electrical enhancement of biocide efficacy against Pseudomonas aeruginosa biofilms.

When applied within a low-strength electric field (+/- 12 V/cm) with a low current density (+/- 2.1 mA/cm2), several industrial biocides exhibited enhanced killing action against Pseudomonas aeruginosa biofilms grown on stainless steel studs. Biocide concentrations lower than those necessary to kill planktonic cells of P. aeruginosa (1, 5, and 10 ppm of the active ingredients of kathon, glutaraldehyde, and quaternary ammonium compound, respectively) were bactericidal within 24 h when applied within our electrified device.

Dimethylamines↗
PubMed1973

Volatile compounds produced in sterile fish muscle (Sebastes melanops) by Pseudomonas perolens.

Volatile compounds produced by Pseudomonas perolens ATCC 10757 in sterile fish muscle (Sebastes melanops) were identified by combined gas-liquid chromatography and mass spectrometry. Compounds positively identified included methyl mercaptan, dimethyl disulfide, dimethyl trisulfide, 3-methyl-1-butanol, butanone, and 2-methoxy-3-isopropylpyrazine. Compounds tentatively identified included 1-penten-3-ol and 2-methoxy-3-sec-butylpyrazine. The substituted pyrazine derivative 2-methoxy-3-isopropylpyrazine was primarily responsible for the musty, potato-like odor produced by P. perolens.

Alcohols↗
PubMed1974

In vitro production of N-nitrosodimethylamine and other amines by proteus species.

N-nitrosodimethylamine, a potent carcinogen, was produced by three strains each of Proteus mirabilis, P. morganii, and P. rettgeri, but not by three strains of P. vulgaris grown under the same conditions. Many of the alkaline-extractable volatile metabolites elaborated by these organisms are the same, but there are some qualitative and quantitative differences among species. Representative gas-liquid chromatographic profiles of the four species are presented, and the significance of the differences is discussed. Primary emphasis, however, is given to the importance of the production of N-nitrosodimethylamine by these microorganisms and the conditions under which it is produced.

Anhydrides↗