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PubMed2005

Spinal N-methyl-D-aspartate receptors may mediate the analgesic effects of emulsified halogenated anesthetics.

The present study was designed to investigate the relationship between spinal cord N-methyl-D-aspartate (NMDA) receptors and the analgesic effects of emulsified halogenated anesthetics. After having established the mouse model of analgesia by intraperitoneally or subcutaneously injecting appropriate doses of emulsified enflurane, isoflurane or sevoflurane, we intrathecally injected different doses of NMDA and then observed the effects on the pain threshold using the hot-plate test and the acetic acid-induced writhing test. The results showed that intrathecal injection of NMDA (2.5, 5 and 10 ng) did not affect the pain threshold on the hot-plate test or the writhing times in conscious mice (p > 0.05); in contrast, NMDA (2.5, 5 and 10 ng intrathecally) can significantly and dose dependently decrease the pain threshold on the hot-plate test (p < 0.05 or p < 0.01) and increase the writhing times (p < 0.05 or p < 0.01) in the mice treated with emulsified anesthetics. These results suggest that spinal NMDA receptors may be important targets for the analgesic effects of emulsified enflurane, isoflurane and sevoflurane.

Analgesics↗
PubMed1995

Halogenated anesthetics form liver adducts and antigens that cross-react with halothane-induced antibodies.

Two halogenated anesthetics, enflurane and isoflurane, have been associated with an allergic-type hepatic injury both alone and following previous exposure to halothane. Halothane hepatitis appears to involve an aberrant immune response. An antibody response to a protein-bound biotransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cross-reactivity between enflurane and isoflurane with the hypersensitivity induced by halothane. The subcellular and lobular production of hepatic neoantigens recognized by halothane-induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoantigens was investigated in two animal models. Enflurane administration resulted in neoantigens detected in both the microsomal and cytosolic fraction of liver homogenates and in the centrilobular region of the liver. In the same liver, biochemical analysis detected fluorinated liver adducts that were up to 20-fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and/or isoflurane could produce a hypersensitivity condition similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to these antigens.

Anesthetics, Inhalation↗
PubMed1998

A new immunocytochemical technique for ultrastructural analysis of DNA replication in proliferating cells after application of two halogenated deoxyuridines.

We describe a colloidal gold immunolabeling technique for electron microscopy which allows one to differentially visualize portions of DNA replicated during different periods of S-phase. This was performed by incorporating two halogenated deoxyuridines (IdUrd and CldUrd) into Chinese hamster cells and, after cell processing, by detecting them with selected antibodies. This technique, using in particular appropriate blocking solutions and also Tris buffer with a high salt concentration and 1% Tween-20, prevents nonspecific background and crossreaction of both antibodies. Controls such as digestion with DNase and specific staining of DNA with osmium ammine show that labeling corresponds well to replicated DNA. Different patterns of labeling distribution, reflecting different periods of DNA replication during S-phase, were characterized. Cells in early S-phase display a diffuse pattern of labeling with many spots, whereas cells in late S-phase show labeling confined to larger domains, often at the periphery of the nucleus or associated with the nucleolus. The good correlation between our observations and previous double labeling results in immunofluorescence also proved the technique to be reliable.

Animals↗
PubMed1981

Comparison between two non-halogenated glucocorticoid ointments in psoriasis.

Observations made in a controlled double-blind investigation of two non-halogenated topical steroids, hydrocortisone-17-butyrate (HCB) and budesonide in thirty-six patients with psoriasis revealed a clear difference in therapeutic effect between the two ointments, indicating that they belong to different groups of topical steroids according to a classification accepted in the Nordic countries. Budesonide had a good therapeutic effect in all the patients studied, while, as a rule, HCB was clearly less effective.

Administration, Topical↗
PubMed2002

Synthesis and insecticidal activity of novel 4beta-halogenated benzoylamino podophyllotoxins against Pieris rapae Linnaeus.

Twelve new 4beta-halogenated benzoylamino compounds (7.1-7.12) of podophyllotoxin have been synthesized, and their structures were confirmed by IR, 1H-NMR, MS spectra as well as CHN elemental analysis. These compounds showed delayed insecticidal activity against 5th instar larvae of Pieris rapae Linnaeus in vivo, when tested by a leaf-dipping method at a concentration of 250ppm. By preliminary qualitative structure-activity relationship analysis, we found the following results: 1) Compounds 7.2, 7.5-7.9 were more potent than the nature parent product in the mortality after 15 d against P. rapae in vivo. Especially compounds 7.5 and 7.6 bearing meta- and para-chlorobenzene substituents respectively, were the most potent of these compounds; 2) Substitution on the benzene ring moiety of 4beta-benzoylamino podophyllotoxin (PPT) with Cl, Br, I at the para or at the meta position yielded compounds which were as potent or more potent than those containing the corresponding substituting group at the ortho position. 3) Substitution on the benzene ring moiety of 4beta-benzoylamino podophyllotoxin with I either at the ortho, meta or para position yielded less potent compounds (7.10-7.12) when compared with PPT.

Animals↗
PubMed1977

Influence of aliphatic alcohols on the hepatic response to halogenated olefins.

The role of alcohols in potentiating the toxicity of halogenated hydrocarbon solvents has been reviewed. The toxicity of carbon tetrachloride and chloroform can be markedly potentiated by prior treatment with ethanol or phenobarbital. Trichloroethylene toxicity may also be potentiated by ethanol ingestion. Prior ethanol ingestion acts by altering biochemical parameters that result in an increased response to subsequent solvent exposure. Simultaneous exposure to both ethanol and trichloroethylene allows for competitive substrate inhibition of metabolism since these compounds share several common enzymatic pathways. Thus the toxic response to multiple exposures varies depending upon the time sequence and the comparative levels of the individual components. Phenobarbital apparently potentiates solvent toxocity by induction of the microsomal mixed function oxidase system. Ethanol, either on a chronic or single dose basis, also has the ability to stimulate this enzyme system. Although alteration of the microsomal mixed function oxidase system by chronic ethanol ingestion may play an important role in potentiation of solvent toxicity, the potentiation seen following a single dose of ethanol cannot be fully accounted for by the known effects of ethanol on the mixed function oxidase system. In addition to ethanol a large number of other alcohols will markedly potentiate the hepatotoxic response to solvents such as carbon tetrachloride and chloroform. The mechanisms involved in such potentiation are not known at the present time.

Alcohols↗
PubMed1985

Effects of structure on binding to the 2,3,7,8-TCDD receptor protein and AHH induction--halogenated biphenyls.

The quantitative structure-activity relationships (QSARs) for polychlorinated biphenyl (PCB) congeners have been determined by comparing the EC50 values for three in vitro test systems, namely, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction in rat hepatoma H-4-II-E cells and competitive binding avidities to the rat cytosolic receptor protein (using 2,3,7,8-tetrachlorodibenzo-p-dioxin as a radioligand). For several PCB congeners that are in vivo inducers of rat hepatic microsomal AHH, there was a linear correlation between the -log EC50 values for receptor and the -log EC50 values for AHH (or EROD) induction; moreover, a comparable linear relationship was observed between the -log EC50 values for AHH and EROD induction. Previous in vivo studies have shown that the most active PCB congeners 3,3',4,4'-tetra-, 3,4,4',5-tetra-, 3,3',4,4',5-penta-, and 3,3',4,4',5,5'-hexachlorobiphenyl, cause many of the biologic and toxic effects reported for the highly toxic halogenated aryl hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Moreover, the monoortho-substituted homologs of the four coplanar PCBs also elicit comparable in vivo biologic and toxic responses. It was evident from the QSARs for PCBs that there was an excellent correspondence between the in vivo and in vitro potencies of the individual PCB congeners. The effects of substituents on both receptor binding and AHH/EROD induction was determined for a series of 4'-substituted (X)-2,3,4,5-tetrachlorobiphenyls (where X = H, Cl, Br, I, OH, OCH3, NO2, COCH3, F, CF3, CH3, C2H5, i-C3H7, n-C4H9 and t-C4H9). Not unexpectedly, there was a linear relationship between the -log EC50 values for AHH and EROD induction, and these results confirm that both enzymatic oxidations are catalyzed by the same cytochrome P-450 isozyme(s). The effects of substituent structure on receptor binding for 12 substituents was subjected to multiple regression analysis which correlates the relative binding affinities of the compounds with the physical chemical characteristics of the substituents. The analysis gave the following equation: log (1/EC50) = 1.53 sigma + 1.47 pi + 1.09 HB + 4.08 for n = 12, s = 0.18, r = 0.978; where n is the number of substituents, s is the standard deviation, r is the correlation coefficient, and sigma = electronegativity, pi = hydrophobicity (log P) and HB = hydrogen bonding capacity for the substituent groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

The treatment of perennial rhinitis with a new, non-halogenated, topical, aerosol packed, steroid, Budesonide.

The investigation of a recently synthesized non-halogenated steroid with a high local anti-inflammatory effect and low systemic glucocorticoid effect, on 36 patients with perennial rhinitis was carried out using a double-blind, cross-over technique, where the patients were treated with an aerosol spray containing a concentration corresponding to 200 micrograms/day and 400 micrograms/day of the active compound Budesonide, as well as placebo. There was a significantly better effect from the active compound than from placebo. A dosage-dependent effect was demonstrated for the symptoms nasal blockage and nasal discharge, while this was not so for sneezing bouts. No effect was observed on the function of the suprarenal glands. Local side effects were few and of no importance.

Administration, Topical↗
PubMed1979

Avian metabolism of halogenated biphenyls.

1. The metabolism of several halogenated biphenyls has been studied using poultry as a model system. The substrates 4-chlorobiphenyl and 4-bromobiphenyl each yielded two metabolites (4'-chloro-4-biphenylol, 4'-chloro-3,4-biphenyldiol; 4'-bromo-4-biphenylol, 4'-bromo-3,4-biphenyldiol), while 4,4'-dichlorobiphenyl yielded only one metabolite (4,4-dichloro-3-biphenylol). 2. Metabolites were not found in eggs collected for 7 days following the administration of the substrate.

Animals↗
PubMed2005

In vitro and in vivo efficacy of new blue light emitting diode phototherapy compared to conventional halogen quartz phototherapy for neonatal jaundice.

High intensity light emitting diodes (LEDs) are being studied as possible light sources for the phototherapy of neonatal jaundice, as they can emit high intensity light of narrow wavelength band in the blue region of the visible light spectrum corresponding to the spectrum of maximal bilirubin absorption. We developed a prototype blue gallium nitride LED phototherapy unit with high intensity, and compared its efficacy to commercially used halogen quartz phototherapy device by measuring both in vitro and in vivo bilirubin photodegradation. The prototype device with two focused arrays, each with 500 blue LEDs, generated greater irradiance than the conventional device tested. The LED device showed a significantly higher efficacy of bilirubin photodegradation than the conventional phototherapy in both in vitro experiment using microhematocrit tubes (44+/-7% vs. 35+/-2%) and in vivo experiment using Gunn rats (30+/-9% vs. 16+/-8%). We conclude that high intensity blue LED device was much more effective than conventional phototherapy of both in vitro and in vivo bilirubin photodegradation. Further studies will be necessary to prove its clinical efficacy.

Animals↗
PubMed2000

New halogenated agents: should I change my practice?

Sevoflurane and Desflurane are relatively new halogenated agents which make induction and control of depth of anaesthesia easier, recovery rapid and of good quality and they have less side-effects and toxicity. In children sevoflurane could replace halothane because it provides smooth and rapid induction with less cardiovascular depression and arrhythmias. Desflurane is not used because of its pungent odour. In adults sevoflurane could be preferred to desflurane because it allows rapid induction and laryngeal mask insertion or tracheal intubation without myorelaxants, a similar time of recovery, no clinical evidence for renal and hepatic toxicity, no more costs for anaesthesia for a lower MAC.

Anesthesia, Inhalation↗
PubMed2002

Effect-directed fractionation and identification of cytochrome p4501A-inducing halogenated aromatic hydrocarbons in a contaminated sediment.

On the basis of a new fractionation method combined with in vitro ethoxyresorufin-O-deethylase (EROD) induction in a rainbow trout liver cell line (RTL-W1) and chemical analysis, halogenated aromatic hydrocarbons with dioxin-like activity were identified in a sediment extract from Bitterfeld, Germany. The fractionation method allowed a separation of different nonplanar and coplanar polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) with different degrees of chlorination. The dioxin-like activity at the investigated site could be quantitatively assigned to PCDD/Fs. Both PCBs and PCNs could be excluded as the cause of the measured effects on the basis of the fractionation procedure and bioanalytical results. Thus, the method allowed the chemical analysis to focus on PCDD/Fs, with significant reduction of the analytical expense. The EROD-induction potency of sediment-extract fractions was quantified, and toxicants were confirmed by the application of induction equivalent quantities on the basis of fixed-effect-level concentrations that exhibit 15% of the maximum induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin. This approach was designed to minimize methodological limitations due to superimposing inhibitory effects.

Animals↗
PubMed1977

In vitro inhibition of rho-aminohippurate transport by halogenated anesthetics.

The effects of four commonly used halogenated anesthetic agents (methoxyflurane, halothane, enflurane and fluroxene) on rho-aminohippurate (PAH) uptake by rabbit renal cortical slices were examined. All agents depressed PAH uptake in a linear dose-dependent manner after 60 minutes of incubation and the effect was reversible. When the data were normalized for anesthetic potency, all agents exhibited a parallel dose-response curve. Since these agents do not share a common metabolite, it is concluded that the depression of PAH transport is mediated primarily by a direct effect of the agents acting through a common pathway. Exposure of kidney slices to perithreshold concentrations of halothane and enflurane for 180 minutes did not result in a cumulative inhibitory effect on PAH transport. A slight time-dependent effect was seen with methoxyflurane. It is suggested that with prolonged exposure metabolic conversion of methoxyflurane may occur leading to further inhibition of PAH uptake.

Aminohippuric Acids↗
PubMed1992

Halogenated isoniazid derivatives as possible antitubercular and antineoplastic agents. Note 1.

Halogenated arylhydrazones, 2-aryl-4-thiazolidinones and their 1,1-dioxides containing isoniazid (INI) moieties were prepared and explored for antimicrobial (against bacteria, Candida and mycobacteria) and antitumor activities. None of the tested compounds showed any marked antimicrobial effect. Furthermore, among the compounds submitted to NCI in vitro primary antitumor screening, those bearing 3-fluoro or -chlorophenyl substituents were found to possess selective inhibitory effects on the growth of non small cell lung cancer, whereas those with para-phenyl substituents displayed selective effects, sometimes statistically significant, against leukemias.

Antineoplastic Agents↗
PubMed2004

Squaraine dyes for photodynamic therapy: mechanism of cytotoxicity and DNA damage induced by halogenated squaraine dyes plus light (>600 nm).

Halogenated squaraine dyes 1 and 2 possess favorable photophysical and in vitro photobiological properties that make these new class of molecules interesting for photodynamic therapeutic applications. For a better understanding of the mechanism of their photobiological activity, we have analyzed the DNA damage and the cytotoxicity induced by these photosensitizers in mammalian cells and cell-free systems in the presence and absence of various additives and scavengers. Both photoactivated squaraines were found to be similar efficient in inducing single-strand breaks (SSB) in cell-free DNA when compared with the cellular DNA. Superoxide dismutase and catalase did not show any influence. However, the presence of tert-butanol and glutathione inhibited the formation of the DNA SSB, indicating an indirect (possibly squaraine radical mediated) mechanism under cell-free conditions. Replacing H2O in the buffer by D2O resulted in a five- to six-fold increase in the number of the SSB in cell-free DNA and a significant enhancement of the photocytotoxicity in mouse lymphoma cells. The results demonstrate that singlet oxygen is the major reactive species under cell-free and cellular conditions and confirm that squaraine-based sensitizers 1 and 2 can have potential applications in photodynamic therapy.

Animals↗
PubMed2004

Temperature rise in the pulp chamber induced by a conventional halogen light-curing source and a plasma arc lamp.

PURPOSE: To assess and compare the pulp chamber temperature increase during resin-based composite polymerization with two different light-curing units. METHODS: A Class I cavity was prepared in an extracted lower molar under standardized conditions using a specially designed industrial robot system. The dentin layer between the pulp chamber and the floor of the cavity was 1 mm thick. Pulp chamber temperature rises (starting temperature: 20.0 +/- 0.1 degrees C) were recorded for four different series of investigations using both the halogen curing lamp Elipar Visio (light-curing: 40 s) and the plasma arc lamp Apollo 95E (light-curing: 3 seconds): Group A: Operation of the light-curing units directly over the untreated, empty cavity; Group B: Resin-based composite polymerization without previously applied cement base or bonding agent; Group C: Resin-based composite polymerization with a previously applied cement base; Group D: Resin-based composite polymerization with a previously applied bonding agent. In each of the four groups 10 measurements were carried out for every light-curing unit. Data were statistically analyzed using ANOVA, post-hoc Scheffé test and t-test. RESULTS: The lowest temperature increase (0.3 degrees C) was recorded during composite polymerization with a previously applied cement base using the Apollo 95E unit (Group C, P < 0.05). The highest temperature increase was induced when using the Elipar Visio unit directly over the untreated cavity (Group A, P < 0.05). In Groups A, C and D higher pulp chamber temperature measurements were obtained when using the Elipar Visio unit as compared to the Apollo 95E plasma arc lamp (P < 0.01). In Group B, no significant differences were recorded during the composite polymerization when using the two different light-curing units (P > 0.05).

Analysis of Variance↗