RESUMO
The compound 1-octen-3-ol is a strong attractant for some mosquito species. Based on chemical structure, this may be due to a terminal site of unsaturation or high electron density, a structural capability for hydrogen bonding, e.g., -OH, -NH2, NHR, NR2, etc., a saturated hydrocarbon chain of a certain minimum length, and a certain relative distance between the region of high electron density and the alcohol (or other hydrogen-bonding) functional group. Based on this hypothesis, 4 novel alkynol (triple-bonded) analogs were synthesized and evaluated alone or in combination with acetone and dimethyl disulfide, and with and without carbon dioxide in Mosquito Magnet-X suction traps. Attraction of laboratory-reared adult Aedes albopictus and Culex quinquefasciatus to these analogs and combinations was compared to 1-octen-3-ol as a standard in semi-field trials. For both species none of the alkynols, with and without carbon dioxide or acetone and dimethyl disulfide, were significantly different from 1-octen-3-ol. The compounds 2-octyn-4-ol and 2-nonyn-4-ol alone and with carbon dioxide suppressed Cx. quinquefasciatus collections. An additional 6 alkenol (double-bonded) analogs were tested in mixtures with 3-n-propylphenol and 4-methylphenol in a ratio of 4:1:8, respectively. Using the same trapping methods, Cx. quinquefasciatus catches containing 3-decen-1-ol were increased nearly 3-fold when combined with carbon dioxide. Aedes albopictus collections in traps with the 3-decen-1-ol/phenol mixture and carbon dioxide were significantly greater than similar traps with 1-octen-3-ol. Traps baited with the phenol blends that incorporated (Z)-3-nonen-1-ol, (Z)-8-nonen-3-ol, or 1-octen-3-ol were considerably suppressed in the presence of carbon dioxide.
Assuntos
Aedes/efeitos dos fármacos , Álcoois/farmacologia , Comportamento Animal/efeitos dos fármacos , Culex/efeitos dos fármacos , Feromônios/farmacologia , Álcoois/química , Animais , Bioensaio , Feminino , Estrutura Molecular , Feromônios/químicaRESUMO
The compound 1-octen-3-ol is a known attractant of some mosquito species, which has led to the hypothesis that olfactory stimulation by this alkenol may be associated with the following structural elements: a terminal site of unsaturation or high electron density; a structural capability for hydrogen bonding, e.g., -OH, -NH2, NHR, NR2, etc.; a saturated hydrocarbon chain of a certain minimum length; and a certain relative distance between the region of high electron density and the alcohol (or other hydrogen-bonding) functional group. Using this logic, we synthesized 20 alkenol analogs based on the octenol double-bonded carbon skeleton. The attraction of female Aedes albopictus and Culex quinquefasciatus to these analogs was compared with 1-octen-3-ol as a standard in semi-field trials. For both species, collections from Mosquito Magnet-X (MMX) suction traps baited with the alkenol analogs in the absence of carbon dioxide were not significantly different from octenol-only baited traps, with the exception of (Z)-3-hepten-1-ol which collected significantly more Ae. albopictus. In the presence of CO2, most of the collections from traps baited with an alkenol were considerably increased for both species but not different from octenol plus CO2, with the exception of Ae. albopictus where (Z)-3-decen-1-ol, (Z)-4-hexen-1-ol, 7-octen-2-ol, and 8-nonen-3-ol significantly depressed trap catches. Although no clearly identifiable structure-activity relationship could be determined from our collected data, we did find that MMX traps baited with carbon dioxide and 4-penten-2-ol or (E)-2-decen-4-ol significantly enhanced Cx. quinquefasciatus collections up to nearly 3-fold compared with octenol plus carbon dioxide.
Assuntos
Aedes , Comportamento Animal/efeitos dos fármacos , Culex , Octanóis/farmacologia , Feromônios/farmacologia , Animais , Feminino , Controle de Mosquitos , Octanóis/química , Feromônios/síntese químicaRESUMO
High nonphysiological doses of l-dopa are administered to Parkinson's disease (PD) patients, to replenish the depleted dopamine (DA). A large portion of the administered L-dopa and the newly formed DA undergoes methylation by reacting with S-adenosyl-L-methionine (SAM). In the process SAM, as well as L-dopa and DA, is utilized and great demands are placed on the transmethylation system. In this study we investigated whether L-dopa increases the transmethylation process by inducing methionine adenosyl transferase (MAT), the enzyme that produces SAM, and catechol-O-methyl transferase (COMT), the enzyme that transfers the methyl group from SAM to L-dopa and DA. Swiss Webster mice were injected with L-dopa, four times/day, for 1 to 16 days. Brain DA, 3-O-methyldopa (3-OMD), SAM, S-adenosylhomocysteine (SAH), MAT, and COMT were measured following a 24-h withdrawal period. An increase of 264% of brain DA occurred at days 2 and 3 after which it tapered to about 164% of control. The brain level of 3-OMD increased to 870% of the control. SAM was increased by 44% after the sixth day and SAH level was about double after the second day. After day 3, MAT activity was increased by about 35%. Western blot analysis showed that MAT is more clearly characterized in 10% mercaptoethanol reducing buffer in which 31.5-, 38- (beta), and 48-kDa (alpha1/alpha2) subunits were distinctly revealed. The induction of the 38-kDa and, more prominently, the 48-kDa subunits of MAT and the potential transactivator proteins of MAT, c-Jun/AP-1, was evident by day 6. The 31.5-kDa subunit was downregulated. COMT was detected as 24.7-, 30-, and 47.5-kDa bands in the brain, consistent with the membrane-bound COMT I (MB-COMT) and the dimeric COMT II. The 24.7- and the 30-kDa MB-COMT bands were induced in the brain by day 6 and peaked on day 9. The highlight of the study is the fact that L-dopa induces the enzymes MAT and COMT. In addition, the downturn in brain DA after the sixth day coincides with the increase in SAM and the 48-kDa MAT protein. Thus, during PD treatment with L-dopa the induction of MAT and COMT is likely to occur and in turn increase the methylation and reduction of L-dopa and DA that may help cause the tolerance or the wearing-off effect developed to L-dopa.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Catecol O-Metiltransferase/metabolismo , Levodopa/farmacologia , Metionina Adenosiltransferase/metabolismo , Tirosina/análogos & derivados , Animais , Western Blotting , Dopamina/metabolismo , Indução Enzimática/efeitos dos fármacos , Rim/enzimologia , Fígado/enzimologia , Masculino , Camundongos , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Fatores de Tempo , Tirosina/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Cadmium (Cd2+) is an environmental pollutant. In humans and animals it has no known biological benefit, but rather has genotoxic and carcinogenic effects. Comparative studies of cadmium-induced DNA single strand breaks in kidney and liver cells of female and male Harlan Sprague-Dawley rats were conducted, and the role of selenium in mitigating cadmium toxicity in male and female rats was also evaluated. Analysis of the results showed differences in organ and sex susceptibility to cadmium-induced DNA damage. There were more single strand breaks in DNA from liver and kidney cells of male rats than in those of the females. Concurrent administration of selenium with cadmium significantly (P<0.001) reduced DNA damage in male rats more than in female rats. However, administration of selenium alone induced DNA strand breaks in female rats at a rate which was significantly greater (P<0.001) than in male rats. These findings demonstrate differences in sex susceptibility to cadmium, and some variance in the ameliorative effects of selenium in male and female rats.
Assuntos
Cádmio/toxicidade , Dano ao DNA , DNA de Cadeia Simples/efeitos dos fármacos , Selênio/farmacologia , Animais , DNA de Cadeia Simples/genética , Feminino , Rim/crescimento & desenvolvimento , Fígado/crescimento & desenvolvimento , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fatores SexuaisRESUMO
Cadmium, unlike zinc, selenium and copper, has no known biological importance, and therefore, it is classified as a carcinogen in humans, as well as in animals. The effect(s) of levels of dermally-administered cadmium on cadmium genotoxicity and cytotoxicity was investigated in Harlan Sprague-Dawley rats for 14, 21, 28, 35 and 42 days at concentrations of 14 and 28 mg/kg/day. Exposure of rats to cadmium via dermal application caused lesions on the skin (hyperkeratosis, acanthosis and scabbing, alopecia and erythema) and tumors in the scrotum. Anatomical changes, such as distention of the stomach, atrophy of kidney and liver and loss of body weight were also observed in these rats. The toxic effects of cadmium on cell ultrastructure were nuclear membrane damage, chromatin condensation, regression of mitochondrial cristae and ultimately cell death. Analyses of the brain, kidney and liver cells of rats exposed to cadmium, clearly showed DNA damage. Of the three organs examined, DNA from kidney cells sustained the most damage followed by DNA in liver cells. There is a positive correlation between Cd dose(s) and duration of exposure and the extent of DNA damage.
Assuntos
Cloreto de Cádmio/toxicidade , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/ultraestrutura , Ensaio Cometa , Dano ao DNA , Rim/efeitos dos fármacos , Rim/patologia , Rim/ultraestrutura , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/ultraestrutura , Masculino , Microscopia Eletrônica , Testes de Mutagenicidade , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Pele/patologia , Pele/ultraestruturaRESUMO
The effect of intracellular glutathione on sensitivity to mercuric cations and arsenite anions was studied in Escherichia coli mutants that lack glutathione (gshA) with or without an additional mutation affecting the osmotregulant trehalose. The absence of glutathione increased cellular sensitivity to both Hg2+ and AsO2-. The double mutant was more sensitive to Hg2+ than the single mutant strain. The addition of plasmid resistance determinants of Hg2+ and AsO2- showed additivity between chromosomal genes and plasmid genes. Mercury resistance was increased in the plasmid-containing cells but not up to the level of wild-type cells. Plasmid arsenite resistance was not expressed in the gshA mutant of E. coli.
Assuntos
Arsenitos/farmacologia , Hidrocarboneto de Aril Hidroxilases , Sistema Enzimático do Citocromo P-450/biossíntese , Escherichia coli/efeitos dos fármacos , Glutationa/metabolismo , Cloreto de Mercúrio/farmacologia , Oxirredutases N-Desmetilantes/biossíntese , Cátions Bivalentes/farmacologia , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/genética , Relação Dose-Resposta a Droga , Resistência Microbiana a Medicamentos , Escherichia coli/genética , Genes Bacterianos , Mutação , Oxirredutases N-Desmetilantes/genética , Trealose/metabolismoRESUMO
Cadmium chloride-induced DNA damage was investigated in individual brain, kidney and liver cells isolated from rats gavaged 14 mg/kg/day cadmium chloride. Animals were sacrificed on days 2, 4, 8, 16, and 33, and DNA damage was determined using the recently developed alkaline microgel electrophoresis technique. Data for DNA migration from 50 randomly selected cells clearly show significant increases in DNA damage in cells from three different organs of cadmium chloride gavaged animals compared to saline treated control animals (33 day control, brain 64.7 +/- 5.3, kidney 75.5 +/- 9.4, liver 67.9 +/- 5.7 microm; 33 days experimental, brain 284.3 +/- 16.9, kidney 397.9 +/- 11.3, liver 315 +/- 22.5 microm; these values represent length of exposure in days and length of DNA migration in micron). There was an increase in DNA damage for all three cell types, with increasing duration of treatment. Cadmium (CdCl2) induced levels of DNA single strand breaks were more pronounced in kidney cells than in cells from the other two organs. Body and organ weights decreased of treated animals were decreased as compared to control. Results of this study indicate a potential of cadmium to be a genotoxic compound.
Assuntos
Encéfalo/efeitos dos fármacos , Cloreto de Cádmio/toxicidade , Dano ao DNA , DNA/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Teratogênicos/toxicidade , Animais , Encéfalo/citologia , Dano ao DNA/efeitos dos fármacos , DNA de Cadeia Simples/efeitos dos fármacos , Humanos , Rim/citologia , Fígado/citologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Our studies on the association of penicillinase plasmid (pI524) DNA with its host bacterial (Staphylococcus aureus) membrane revealed that the membrane-associated forms of this plasmid could be isolated from exponentially grown cells lysed on neutral sucrose gradient. Analysis of putative plasmid-membrane complexes isolated from the clear lysates on sucrose gradients indicated that approximately 23% of plasmid (pI524) DNA was stably associated with the bacterial cell membrane fractions. This suggested that one of the three or four copies of this plasmid per cell was complexed to the cellular membrane. Examination of the effect of various enzymes, e.g., ribonuclease and protease, as well as antibiotics (rifampicin and chloramphenicol), on complexing have shown the possible involvement of protein(s) rather than RNA in mediating the complexing of this plasmid to the cell membrane. The specificity of plasmid pI524 to its host cell membrane was observed in an experiment where R6k was included in binding assay.
Assuntos
DNA Bacteriano/isolamento & purificação , Penicilinase/genética , Plasmídeos , Staphylococcus aureus/enzimologia , Sítios de Ligação , Ligação Competitiva , Fracionamento Celular/métodos , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Centrifugação com Gradiente de Concentração , DNA Bacteriano/metabolismo , Penicilinase/biossíntese , Staphylococcus aureus/genéticaRESUMO
Examination of the ilvF locus at 54 min on the Escherichia coli K-12 chromosome revealed that it is a cryptic gene for expression of a valine-resistant acetohydroxy acid synthase (acetolactate synthase; EC 4.1.3.18) distinct from previously reported isozymes. A spontaneous mutation, ilvF663, yielded IlvF+ enzyme activity that was multivalently repressed by all three branched-chain amino acids, was completely insensitive to feedback inhibition, was highly stable at elevated temperatures, and expressed optimal activity at 50 degrees C. The IlvF+ enzyme activity was expressed in strains in which isozyme II was inactive because of the ilvG frameshift in the wild-type strain K-12 and isozymes I and III were inactivated by point mutations or deletions. Tn5 insertional mutagenesis yielded two IlvF- mutants, with the insertion in ilvF663 in each case. These observations suggest that the ilvF663 locus may be a coding region for a unique acetohydroxy acid synthase activity.
Assuntos
Acetolactato Sintase/análise , Escherichia coli/enzimologia , Genes Bacterianos , Isoleucina/biossíntese , Oxo-Ácido-Liases/análise , Valina/biossíntese , Acetolactato Sintase/genética , Mapeamento Cromossômico , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Temperatura Alta , Concentração de Íons de Hidrogênio , Isoleucina/genética , Peso Molecular , Mutação , Valina/genéticaRESUMO
Quantitatively expressed ideas are linkages of two or more characteristics presented by the author in tables or graphs. Such ideas also may be expressed as sentences in the text of the Results section. This study investigated the relative importance of quantitative ideas expressed in the two formats in the same article. A random sample of fifty articles from the lymphoma literature containing numerical relationship displays was selected and each article was carefully read in order to identify and extract the quantitative ideas expressed in the text. Only those ideas not presented in numerical displays were extracted. The final database consisted of records describing numerical relationships displayed in tables and/or graphs and records describing numerical relationships expressed only in the text of the Results section. In this way, the study could determine the added advantages of reading the Results sections, over and above the information provided by the displays of numerical relationships. The text ideas were more difficult to find and extract and were found to be less important when compared with ideas from numerical displays. This study further substantiated the method of extracting quantitatively expressed ideas from numerical displays for rapid technical processing of scientific documents.