• Title/Summary/Keyword: Molecular elimination

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Hydrolytic Reactivity and Holographic Quantitative Structure-Activity Relationship Analyses on the Melanogenesis Inhibitory Activities of Alkyl-3,4-dihydroxybenzoate and N-Alkyl-3,4-dihydroxybenzamide Derivatives (Alkyl-3,4-dihydroxybenzoate와 N-Alkyl-3,4-dihydroxybenzamide 유도체들의 가수분해 반응성과 멜라닌 생성 저해활성에 관한 홀로그램(H) QSAR 분석)

  • Sung Nack-Do;Jung Hoon-Sung;Kim Sang-Jin
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.4 s.48
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    • pp.491-497
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    • 2004
  • Holographic quantitative structure activity relationships (HQSAR) between the melanogenesis inhibitory activities of alkyl-3,4-dihydroxybenzoate (A) and N-Alkyl-3,4-dihydroxybenzamide (B) derivatives were analyzed and discussed. The statistical results of HQSAR model for the activities showed the best predictability of the activities based on the cross-validated $r^2_{cv}\;(q^2=0.674),$ non-cross-validated, conventional coefficient $(r^2_{ncv}=0.936).$ The melanogenesis inhibitory activities and hydrolytic reactivity of (A) were slightly higher than that of (B) (A>B) and the activities depends upon the $R_1-substituents\;(R_1>R_2).$ It has been found using frontier molecular orbital (FMO) theory that the hydrolysis reactions of (A) and (B) proceeded to an orbital-controlled reactions, while the nucleophillc addition-elimination reactions $(Ad_{N-E})$ between LUMO energy of (A) and (B) and HOMO energy of water molecule are occurred.

COMPARISON OF AFRIKANER- AND BRAHMAN- CROSS CATTLE IN PAPUA NEW GUINEA

  • Holmes, J.H.G.;McKinnon, M.J.;Seifert, G.W.;Schottler, J.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.5 no.3
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    • pp.419-426
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    • 1992
  • After the virtual eradication of cattle during World War II, Papua New Guinea herds were rebuilt with Shorthorn and Aberdeen Angus cattle from Australia. These, and Red Sindhi and Sahiwal, imported in 1952, were considered unsuitable breeds. In 1954, Department of Agriculture, Stock and Fisheries imported three Brahman bulls and three heifers from Texas and in 1960 began importations of Afrikaner from Queensland. In Central Province, Brahmans were crossed with Angus and at Erap (Morobe) the hottest place in Papua New Guinea, Shorthorns were crossed with Afrikaners. In 1965, Brahman and Brahman-cross were sent to Erap. Records of breeding and growth rates were collected for use in upgrading in cattle of the basis of performance, not pedigree. The data are not ideal for genetic analysis, since no control groups were maintained. Birth weights (BWT), weaning weights (WWT) and calving intervals (CI) were analysed for the period 1969-1978. After exclusion of unsatisfactory data, 2,514 calf records were used, including both breeds from 1969 to 1973, but only Brahman-cross subsequently. Breed mean BWT ranged only from 30.6 to 33.8 kg. As Brahman content increased, BWT decreased and WWT increased; within a genotype, there was a negative maternal effect of high Brahman content on BWT and a positive effect on WWT which ranged from 138 to 174 kg. Afrikaner calves had heavier BWT but lighter WWT. As expected, bulls were heaviest, heifers lightest and mature cows bore and reared heavier calves. Calving interval (405 days, equivalent to 90% calving) was unaffected by breed but 4-year old cows averaged 423 days. Breed differences in BWT and WWT are consistent with the body of literature on performance of Brahmans and Afrikaners. Since cattle tick are not present and internal parasites are insignificant at Erap, the superiority of Brahmans indicates that they were better at utilizing the mediocre quality grazing of the Markham Valley or were more heat tolerant. Performance selection over ten years resulted in the virtual elimination of Afrikaners, with the final genotype approximately 9/16 Brahman, 3/8 Shorthorn and 1/16 Afrikaner.

A Critical Evaluation of DNA Adducts as Biological Markers for Human Exposure to Polycyclic Aromatic Compounds

  • Godschalk, Roger W.L.;Van Schooten, Frederik-Jan;Bartsch, Helmut
    • BMB Reports
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    • v.36 no.1
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    • pp.1-11
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    • 2003
  • The causative role of polycyclic aromatic hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention of chemoprevention studies. The successful applicability of DNA adducts as early endpoints depends on several criteria:i.adduct levels in easily accessible surrogate tissues should reflect adduct levels in target-tissues, ii. toxicokinetics and the temporal relevance should be properly defined.iii. sources of inter- and intra-individual variability must be known and controllable, and finally iv. adduct analyses must have advantages as compared to other markers of PAH-exposure. In general, higher DNA adduct levels or a higher proportion of subjects with detectable DNA adduct levels were found in exposed individuals as compared with non-exposed subjects, but saturation may occur at high exposures. Furthermore, DNA adduct levels varied according to changes in exposure, for example smoking cessation resulted in lower DNA adduct levels and adduct levels paralleled seasonal variations of air-pollution. Intra-individual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Inter-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH-metabolism and deserves further investigation. DNA adduct measurement may have three advantages over traditional exposure assessment: i. they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over a longer period of time. Therefore, DNA adduct assessment may reduce the monitoring effort. ii. Biological monitoring of DNA adducts accounts for all exposure routes. iii. DNA adducts may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. In conclusion, there is now a sufficiently large scientific basis to justify the application of DNA adduct measurement as biomarkers in exposure assessment and intervention studies. Their use in risk-assessment, however, requires further investigation.

Dialysis Related Treatment to Increase Elimination of Toxic Agent (독성 물질 제거에 있어서 투석과 연관된 치료)

  • Kim, Heung-Soo;Shin, Gyu-Tae
    • Journal of The Korean Society of Clinical Toxicology
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    • v.1 no.1
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    • pp.6-11
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    • 2003
  • Various forms of dialytic techniques are available for detoxification. Hemodialysis, hemoperfusion and hemofiltration (hemodialfiltration) are the main treatment modalities. Because these modalities are rather invasive and expensive, it must be decided in balance of the risk and benefit to the patient. The prime consideration in the decision is based on the clinical features of poisoning; hemodialysis or hemoperfusion should be considered in general if the patient's condition progressively deteriorates despite intensive supportive therapy. The hemodialysis technique relies on passage of the toxic agent through a semipermeable membrane so that it can equilibrate with the dialysate and subsequently removed. It needs a blood pump to pass blood next to a dialysis membrane, which allows agents permeable to the membrane to pass through and reach equilibrium. Solute (or drug) removal by dialysis has numerous determinants such as solute size, its lipid solubility, the degree to which it is protein bound, its volume of distribution etc. The technique of hemoperfusion is similar to hemodialysis except there is no dialysis membrane or dialysate involved in the procedure. The patient's blood is pumped through a perfusion cartridge, where it is in direct contact with adsorptive material (usually activated charcoal) that has a coating material such as cellulose. This method can be used successfully with lipid-soluble compounds and with higher-molecular-weight compounds than for hemodialysis. Protein binding does not significantly interfere with removal by hemoperfusion. In conclusion, hemodialysis, hemoperfusion and hemofiltration can be used effectively as adjuncts to the management of severely intoxicated patients.

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Studies on Cysteine desulfhydrase Produced by Bacteria(Part II) Enzymatic Preparation of L-Cysteine Derivatives by Cysteinedesulfhydrase from Aerobacter aerogenes. (Bacteria가 생산하는 Cysteinedesulfhydrase에 관한 연구(제이보) L-Cysteine 유도체의 효소적 합성에 관하여)

  • 최용진;양한철
    • Microbiology and Biotechnology Letters
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    • v.2 no.1
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    • pp.45-50
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    • 1974
  • 1 With cysteinedesulfhydrase (E. C.4.4.1.1.) from Aerobactor aerogenes, an enzyme which catalyzes the stoichiometric conversion of L-cysteine to pyruvate, ammonia and sulfide, reversibility of the degradation of L-cysteine was investigated. It was found that the enzyme also catalized the reverse reaction of $\alpha$, $\beta$-elimination to synthesize L-cysteine derivatives from pyruvate, ammonia and sulfides when large amounts of substrates were added to the reaction mixtures. 2. The synthetic reaction by cysteinedesulfhydrase proceeded linearly with incubation time and enzyme concentrations. The optimal pH for the synthetic reaction was 10.0. 3. The results of the isolation and identification of the products showed that the L-cysteine derivatives synthesized by this enzymatic method were identical with S-methyl-L-cysteine and S-ethyl-L-cysteine respectively.

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Skeletal Ryanodine Receptor 1-Heterozygous PSE (Pale, Soft and Exudative) Meat Contains a Higher Concentration of Myoglobin than Genetically Normal PSE Meat in Pigs

  • Obi, T.;Matsumoto, M.;Miyazaki, K.;Kitsutaka, K.;Tamaki, M.;Takase, K.;Miyamoto, A.;Oka, T.;Kawamoto, Y.;Nakada, T.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.9
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    • pp.1244-1249
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    • 2010
  • Comparisons of properties between skeletal ryanodine receptor 1 (sRyR1)-heterozygous-mutated and normal types of meat were carried out in pigs using PSE (pale, soft and exudative) meat found during the butchering process. All samples considered to be PSE meat showed irregular running and disorder of the muscle fibers and a wider inter-fiber space upon light microscopic observation. Electron microscopy revealed disintegration, twisting, and disorder of the myofibril arrangement and elimination of the Z line in PSE meat, compared with normal meat. Meat property tests demonstrated greater decreases in water holding capacity, moisture and sarcoplasmic protein, and higher $L^*$ values for the meat color index in PSE meat than in normal meat, but there were no differences in these factors between genetically normal and sRyR1-heterozygous PSE meat. On the other hand, higher $a^*$ and $b^*$ values were observed in sRyR1-heterozygous than in normal PSE meat, and similar alterations to the a* value were observed in terms of the amount of myoglobin and density of the 17-kDa protein band, corresponding to the molecular mass of myoglobin, on SDS-PAGE gels. These results suggest that sRyR1-heterozygous PSE pork contains much more myoglobin than genetically normal PSE meat.

Environmental Genomics Related to Environmental Health Biomarker

  • Kim, Hyun-Mi;Kim, Dae-Seon;Chung, Young-Hee
    • Molecular & Cellular Toxicology
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    • v.2 no.2
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    • pp.75-80
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    • 2006
  • Biomarkers identify various stages and interactions on the pathway from exposure to disease. The three categories of biomarkers are those measuring susceptibility, exposure and effect. Susceptibility biomarkers are identifiable genetic variations affecting absorption, metabolism or response to environmental agents. Biomarkers of exposure indicate the amount of a foreign compound that is absorbed into the body. Biological measurements performed on human tissues are vastly expanding the capabilities of classical epidemiology, which has relied primarily on estimates of human exposure derived form chemical levels in the air, water, and other exposure routes. Biomarkers of exposure indicate the amount of a foreign compound that is absorbed into the body. Biological measurements performed on human tissues are vastly expanding the capabilities of classical epidemiology, which has relied primarily on estimates of human exposure derived form chemical levels in the air, water, and other exposure routes. The biomarker response is typical of chemical pollution by specific classes of compound, such as (i) heavy metals (mercury, cadmium, lead, zinc), responsible for the induction of metallothionein synthesis, and (ii) organochlorinated pollutants (PCBs, dioxins, DDT congeners) and polycyclic aromatic hydrocarbons (PAHs), which induce the mixed function oxygenase (MFO) involved in their bio transformations and elimination. Currently genomic researches are developed in human cDNA clone subarrays oriented toward the expression of genes involved in responses to xenobiotic metabolizing enzymes, cell cycle components, oncogenes, tumor suppressor genes, DNA repair genes, estrogen-responsive genes, oxidative stress genes, and genes known to be involved in apoptotic cell death. Several research laboratories in Korea for kicking off these Environmental Genomics were summarized.

CYP2D6 P34S Polymorphism and Mirtazapine Responses in Koreans with Major Depression

  • Jeon, Si-On;Chang, Hun-Soo;Lee, Hwa-Young;Ham, Byung-Joo;Kang, Rhee-Hun;Jeong, Yoo-Jung;Lee, Min-Soo
    • Molecular & Cellular Toxicology
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    • v.5 no.4
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    • pp.346-353
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    • 2009
  • Drug metabolism is a critical determinant of the therapeutic and adverse effects of many psychotropic drugs. The metabolism depends on the pharmacokinetics of a drug, which includes its absorption, distribution, and elimination. Psychotropic drugs are metabolized mainly by cytochrome P450 (CYP) enzymes; about 20 of these enzymes exist and they are often responsible for the rate-limiting step of drug metabolism. CYP2D6 is the best-characterized P450 enzyme that exhibits polymorphism in humans. This study determined the relationship between the CYP2D6*10 (P34S) polymorphism and the response to mirtazapine in 153 Koreans with major depressive disorder (MDD). The genotype frequencies were compared using logistic regression analysis, and between-genotype differences in the decrease in the 21-item Hamilton Depression (HAMD21) score over the 12-week treatment period were analyzed using a linear regression analysis. The proportion of remitters was lower in patients with MDD possessing the S allele than in P allele carriers after 2 weeks of mirtazapine treatment. Similarly, the reductions in the HAMD21 and Clinical Global Impression (CGI) scores in S allele carriers were smaller than those in patients with the P allele after 2 weeks of mirtazapine treatment. In the analysis of depression symptoms, the sleep and delusion scores had smaller reductions in S allele carriers. Based on the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), the psychic adverse effects of mirtazapine were associated with CYP2D6 P34S, while weight gain was not. These results suggest that CYP2D6 P34S affects the outcome of mirtazapine treatment in patients with MDD, and that this polymorphism may be a good genetic marker for predicting the clinical outcome of mirtazapine treatment.

Glyceraldehyde-3-Phosphate, a Glycolytic Intermediate, Plays a Key Role in Controlling Cell Fate Via Inhibition of Caspase Activity

  • Jang, Mi;Kang, Hyo Jin;Lee, Sun Young;Chung, Sang J.;Kang, Sunghyun;Chi, Seung Wook;Cho, Sayeon;Lee, Sang Chul;Lee, Chong-Kil;Park, Byoung Chul;Bae, Kwang-Hee;Park, Sung Goo
    • Molecules and Cells
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    • v.28 no.6
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    • pp.559-563
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    • 2009
  • Glyceraldehyde-3-phosphate is a key intermediate in several central metabolic pathways of all organisms. Aldolase and glyceraldehyde-3-phosphate dehydrogenase are involved in the production or elimination of glyceraldehyde-3-phosphate during glycolysis or gluconeogenesis, and are differentially expressed under various physiological conditions, including cancer, hypoxia, and apoptosis. In this study, we examine the effects of glyceraldehyde-3-phosphate on cell survival and apoptosis. Overexpression of aldolase protected cells against apoptosis, and addition of glyceraldehyde-3-phosphate to cells delayed apoptosis. Additionally, delayed apoptotic phenomena were observed when glyceraldehyde-3-phosphate was added to a cell-free system, in which artificial apoptotic process was induced by adding dATP and cytochrome c. Surprisingly, glyceraldehyde-3-phosphate directly suppressed caspase-3 activity in a reversible noncompetitive mode, preventing caspase-dependent proteolysis. Based on these results, we suggest that glyceraldehyde-3-phosphate, a key molecule in several central metabolic pathways, functions as a molecule switch between cell survival and apoptosis.

Comparative Study of the Dehydrofluorination of the Structural Isomers of $C_2H_2F_4$ ($C_2H_2F_4$ 이성질체의 탈플루오르화 수소반응에 있어서의 비교연구)

  • Tschuikow-Roux E.;Maltman K. R.;Millward G. M.;Jung K. H.
    • Journal of the Korean Chemical Society
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    • v.23 no.3
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    • pp.132-135
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    • 1979
  • The thermal decomposition of a dilute mixture of 1,1,2,2,-$C_2H_2F_4$ in argon has been investigated in a single-pulse shock tube between 1146 and $1232^{\circ}K$ at total reflected shock pressures of about 3000 torr. Under these conditions the reaction proceeds exclusively by the molecular elimination of hydrogen fluoride. It has been found that the asymmetric isomer with the fully fluorinated ${\alpha}$-carbon requires the higher activation energy which may be attributed to the difference in atomic charge densities between isomers. The rate constant ratio is given by $log(k_1/k_2) = -0.069 {\pm} 0.021 +(1388{\pm}113) / 2.303RT$ in good agreement with previous independent studies.

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