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Biomedical subjects

G F Huang

Publications and source records attributed to G F Huang.

At least 37 records · Page 2Linked to original sources

Morphine depresses the transmission of noxious messages in the spino(trigemino)-ponto-amygdaloid pathway.

We had recently demonstrated that a subregion of the parabrachial area relays nociceptive information in the spino(trigemino)-ponto-amygdaloid pathway. The aim of the present study was to investigate, in halothane-anesthetized rats, the effect of i.v. administration of morphine on nociceptive specific neurons located in the parabrachial area with some cells being antidromically driven from the amygdala. Morphine induced a marked depression of responses elicited by noxious thermal stimuli (waterbath, 50 degrees C) dose relatedly (1, 3, 9 mg/kg) and naloxone reversibly, with an ED50 = 1.8 mg/kg. This effect of morphine probably not only reflects the direct action of this drug at the spinal level, but could also involve a direct action at the parabrachial level. These results could account at least in part for the effect of morphine on the emotional-affective aspects of pain.

Amygdala↗

Nucleus centralis of the amygdala and the globus pallidus ventralis: electrophysiological evidence for an involvement in pain processes.

1. Neurons (n = 177) were recorded with extracellular micropipettes in and around the nucleus centralis of the amygdala (Ce), in anesthetized rats. The spontaneous activity of these neurons was variable (0.25 less than 3 less than 35 Hz, n = 175; 10th percentile less than median less than 90th percentile). A majority (80%) of these neurons were excited or inhibited exclusively or preferentially by noxious stimuli. These units were separated into two groups: 1) a group of neurons excited by noxious stimuli (46% of the whole population) and 2) a group of neurons inhibited by noxious stimuli (34% of the whole population). 2. The receptive fields of both groups of neurons were very large: in about one-half the cases the neurons responded similarly from all parts of the body, and in the other cases the responses were greater when the stimuli were applied to a restricted part of the body. 3. Seventy-seven percent of the excited neurons had responses of relatively high magnitudes. In this group, most cells (75%) were exclusively driven by noxious stimuli; the others (25%) were preferentially activated by noxious stimuli. These neurons responded to mechanical (pinch or squeeze) and/or thermal (water bath or water jet greater than 44 degrees C) noxious stimuli with a marked and sustained activation. 4. Sixty percent of the inhibited neurons had a marked decrease of activity in response to noxious stimuli. In this group, most of them (81%) were exclusively inhibited by noxious stimuli, whereas the remainder (19%) were preferentially inhibited by noxious stimuli. These neurons responded to mechanical (pinch or squeeze) and/or thermal (water bath or waterjet greater than 44 degrees C) noxious stimuli with a suppression or a marked and sustained decrease in activity. 5. All of the nociceptive neurons responded to intense transcutaneous electrical stimulation with one or several components of activation or inhibition. According to their latencies, three types of components were distinguished: early, intermediate, and late components. We estimate that the early and the intermediate components would be triggered by the activity of peripheral fibers in the 6- to 20-m/s range and therefore could be in the A delta fibers range, whereas the late component would be triggered by fibers in the 0.5- to 1-m/s range and therefore could be in the C fibers range. 6. The neurons excited or inhibited by noxious stimuli were not homogeneously distributed in and around the Ce.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Effect of noxious somesthetic stimulation on the activity of neurons of the nucleus centralis of the amygdala.

Neurons (n = 107) were recorded, in anaesthetized rats, with extracellular micropipettes, in the nucleus centralis of the amygdala (Ce). The activity of a large majority (77%) was exclusively or preferentially affected by noxious stimuli applied in any area of the body. The rest of the neurons was not activated by any stimuli (21%) or responded only to innocuous stimuli (2%). The nociceptive neurons were classified into two groups: the neurons in the first group (34% of the whole population) were activated by mechanical and thermal noxious stimuli; the neurons in the second group (43% of the whole population) were inhibited by noxious stimuli. Neurons in two groups precisely encoded thermal stimuli in the noxious range. Transcutaneous electrical stimulation suggested that the Ce nociceptive neurons were under the influence of A delta and C fibers. These results demonstrate important nociceptive input to the Ce which according to previous studies probably relays in the pontine parabrachial nucleus. In addition, they are in good agreement with the involvement of the amygdala in emotional, autonomic and/or behavioral reactions to noxious events.

Acoustic Stimulation↗

[Treatment of severe electrical burn of the skull].

From Jan. 1970 to Feb. 1989, 10 cases of severe electrical burns of the skull were treated. There were necroses of the full skull bone layer and skin in 4 cases and necroses of the skull skin and external skull bone layer in 6 cases. Cure in 8 cases and death in 2 cases. The authors consider that in the early-stage protecting and reserving the skull intact is important. Repairing wound with full-circulatory skin flap or myocutaneous flap is a reasonable selection. In the later-stage, the wound may be repaired with skin graft on the granulating wound after removing the necrotic bone.

Adolescent↗

Antiviral, antimetabolic, and cytotoxic activities of 5-substituted 2'-deoxycytidines.

Various 5-substituted 2'-deoxycytidines, including 5-bromo-dCyd, 5-iodo-dCyd, 5-nitro-dCyd, 5-ethynyl-dCyd, 5-propyl-dCyd, (E)-5-(2-bromovinyl)-dCyd, and (E)-5-(2-iodovinyl)-dCyd, were evaluated for their antiviral and antimetabolic properties in primary rabbit kidney (PRK) cell cultures and for their inhibitory effects on murine L1210 cell proliferation. All dCyd analogues proved to be selective inhibitors of herpes simplex virus (HSV) replication: 5-bromo-dCyd, 5-iodo-dCyd, 5-nitro-dCyd, and 5-ethynyl-dCyd were more selective in their anti-HSV activity than were the corresponding 5-substituted 2'-deoxyuridines, whereas 5-propyl-dCyd, (E)-5-(2-bromovinyl)-dCyd, and (E)-5-(2-iodovinyl)-dCyd were as selective as their dUrd counterparts. The dCyd analogues were also less cytotoxic (for both PRK and L1210 cells), as could be monitored by inhibition of either cell proliferation or host-cell DNA synthesis (incorporation of radiolabeled precursors). Of all 5-substituted 2'-deoxycytidines tested, the (E)-5-(2-halogenovinyl) derivatives emerged as the most potent and most selective inhibitors of HSV (Type 1) replication.

Animals↗

Chemistry and mutagenicity of alpha-hydroxy nitrosamines.

N-Nitroso-N-(hydroxymethyl)alkylamines, which are key intermediates in the metabolic activation of nitrosamines having a methyl group, were synthesized and their chemical and mutagenic properties were examined. Six N-nitroso-N-(hydroxymethyl)alkylamines (alkyl = methyl, ethyl, n-propyl, n-butyl, sec-butyl, tert-butyl) were prepared by the deoxygenation of N-nitroso-N-(hydroperoxymethyl)alkylamines. Their stability in aqueous solution was highly dependent on pH, being stable in acidic media, but unstable in neutral or alkaline media. The structure also exerted a profound effect on the stability. Thus a branched alkyl group accelerated the decomposition, although compounds with a normal alkyl group showed a similar response to the change of pH. The alkylating activity of the compounds toward deoxyguanosine and thymidine was demonstrated, and was dependent on the reaction solvent used. The overall alkylating activity was found to be highest with the compound ultimately yielding a methylating agent, while a more selective alkylation towards the oxygen, compared to the nitrogen, was observed with the ethylating, propylating and butylating species. Reactions with cysteine and histidine were also observed. A potent mutagenic effect of the N-nitroso-N-(hydroxymethyl)alkylamines was demonstrated in Salmonella typhimurium TA1535 and Escherichia coli WP2 and WP2 hcr-, in the absence of the S9 mix. A good correlation of the activities of the N-nitroso-N-dialkylamines and the N-nitroso-N-(hydroxymethyl)alkylamines with the same alkyl group was demonstrated.

Alkylation↗

Synthesis and antiviral activity of 5-[(cyanomethylene)oxy]-2'-deoxyuridine.

To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated product 3-(cyanomethyl)-5-[(cyanomethylene)oxy]-2'-deoxyuridine (3) was the major product with a lesser amount of 3-(cyanomethyl)-5-hydroxy-2'-deoxyuridine (5) and only a trace amount of the desired product (2). In contrast, when 5-hydroxy-2'-deoxyuridine was alkylated in water in the presence of 1 equiv of KOH, compound 2 was the major product. In cultures of primary rabbit kidney (PRK) cells, compound 2 showed an anti-herpes virus activity that was comparable to that of 1 and ara-A. Compound 2 did not inhibit incorporation of [Me-3H]dThd or [1',2'-3H]dUrd into DNA of PRK cells; however, its anti-herpes virus activity was completely prevented upon the addition of either dThd or dUrd.

Animals↗

Mutagenicity of N-alkyl-N-(alpha-acetoxyalkyl) nitrosamines in V79 Chinese hamster cells in relation to alkylating activity.

Mutation to ouabain resistance and cytotoxicity were tested in V79 Chinese hamster cells after the cells had been treated for 2.5 hr with a series of N,N-dialkylnitrosamines (alkyl=methyl, ethyl, propyl, butyl or tert-butyl) monosubstituted at the alpha-carbon with an acetoxy group. The effects of the length of alkyl chain and the mode of substitution with the acetoxy group on the cytotoxicity and mutagenicity were examined. In the series of N-alkyl-N-(acetoxy-methyl) nitrosamines with an acetoxy group at the primary alpha-carbon, the methylating compound N-methyl-N-(acetoxymethyl) nitrosamine was the most cytotoxic and mutagenic, and the biological activities decreased in the order of ethyl, butyl and propyl homologs. N-tert-Butyl-N-(acetoxymethyl) nitrosamine was not mutagenic at the concentration tested. At equitoxic concentrations, N-ethyl-N-(acetoxymethyl) nitrosamine was found to be the most mutagenic. Of the two N-alkyl-N-(alpha-acetoxybutyl) nitrosamines having an acetoxy group at the secondary alpha-carbon, N-methyl-N-(alpha-acetoxybutyl) nitrosamine was more cytotoxic and mutagenic than N-butyl-N-(alpha acetoxybutyl) nitrosamine. A comparison of the corresponding N-alkyl-N-(acetoxymethyl) nitrosamines and N-alkyl-N-(alpha-acetoxybutyl) nitrosamines showed that the latter had stronger activities. A plot of the mutation frequency versus the ability of the alpha-acetoxy compounds to alkylate 4-(p-nitrobenzyl) pyridine was linear. This indicates that the chemical reactivity of the compounds plays an important role in inducing mutation in V79 Chinese hamster cells.

Alkylating Agents↗

Interferon induction by mismatched analogues of polyinosinic acid . polycytidylic acid [(Ix,U)n.(C)n].

Interruption of the (I)n strand of (I)n.(C)n by unpaired bases [(U)] yielded mismatched analogues, (Ix,U)n.(C)n which were still effective as inducers of interferon, provided the I:U ratio (x) was equal or greater than 10. In highly sensitive interferon-induction systems such as primary rabbit kidney cells and human skin fibroblasts superinduced with cycloheximide and actinomycin D, (I10,U)n.(C)n and (I50,U)n.(C)n proved nearly as active as (I)n.(C)n. By virtue of their increased susceptibility to degradation by nucleases, (Ix,U)n.(C)n complexes with 10 less than or equal to x less than or equal to 50 may be expected not to persist as long in biological fluids as (I)n.(C)n, hence to induce fewer side effects.

Animals↗

Carcinogenicity and mutagenicity of 4-nitropyridine 1-oxide derivatives.

Carcinogenicity and mutagenicity of 4-nitropyridine 1-oxide (4-NPO) and 7 kinds of its alkyl derivatives were tested on mice and on Salmonella typhimurium strains and Escherichia coli strains. 3-Methyl-4-NPO is the most potent carcinogen, followed by 3-ethyl-4-NPO and then 4-NPO. Mutagenicity was most potent in 3-methyl, 2,3-dimethyl, and 2,5-dimethyl derivatives, moderate in 4-NPO and 2-methyl and 2,6-dimethyl derivatives, and to a least extent in 3,5-dimethyl-4-NPO. Structure-mutagenicity relationship was discussed on the basis of molecular mechanism of the carcinogenesis of 4-nitroquinoline 1-oxide. Quantitative relationship between mutagenicity and carcinogenicity was not strictly found among the compounds examined.

Animals↗