RESUMO
TR-701 is the orally active prodrug of TR-700, a novel oxazolidinone that demonstrates four- to eightfold-greater activity than linezolid (LZD) against Staphylococcus and Enterococcus spp. In this study evaluating the in vitro sensitivity of LZD-resistant isolates, TR-700 demonstrated 8- to 16-fold-greater potency than LZD against all strains tested, including methicillin-resistant Staphylococcus aureus (MRSA), strains of MRSA carrying the mobile cfr methyltransferase gene, and vancomycin-resistant enterococci. The MIC(90) for TR-700 against LZD-resistant S. aureus was 2 microg/ml, demonstrating the utility of TR-700 against LZD-resistant strains. A model of TR-700 binding to 23S rRNA suggests that the increased potency of TR-700 is due to additional target site interactions and that TR-700 binding is less reliant on target residues associated with resistance to LZD.
Assuntos
Acetamidas/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Enterococcus/efeitos dos fármacos , Oxazolidinonas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/metabolismo , Sítios de Ligação , Humanos , Linezolida , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana/normas , Modelos Moleculares , Oxazolidinonas/química , Oxazolidinonas/metabolismo , Pró-Fármacos/química , Pró-Fármacos/farmacologiaRESUMO
Plasma prorenin levels are elevated in normal pregnant women. Current evidence suggests renin production by tissues of the uteroplacental unit contribute to this elevation. The purpose of this investigation was to define the source of renin biosynthesis within the human uteroplacental unit and to characterize the renin produced. RNA extraction and Northern blot analysis consistently demonstrated renin mRNA expression in uterine lining both in the pregnant (decidua) and nonpregnant states (endometrium) and in fetal chorion laeve, which is inseparable from the decidua. In contrast, renin mRNA expression was not detected in basal plate and intertwin chorion (which is separate from decidua), amnion, myometrium, or placental villi. The total renin content in decidual homogenates was two- to threefold greater than in endometrial homogenates, and cultured human decidual cells produced significantly more total renin than cultured human endometrial cells, suggesting that pregnancy enhanced renin production by the cells lining the uterus. Immunoblot analysis and [3H]leucine incorporation identified 47,000-mol wt prorenin as the major form of renin produced by cultured human decidual cells. These studies indicate that maternal decidua is the major source of prorenin in the uteroplacental unit.
Assuntos
Decídua/enzimologia , Renina/isolamento & purificação , Adulto , Northern Blotting , Células Cultivadas , Córion/enzimologia , Meios de Cultura/análise , Decídua/citologia , Endométrio/enzimologia , Feminino , Regulação da Expressão Gênica , Humanos , Immunoblotting , Gravidez , Renina/biossíntese , Renina/genéticaRESUMO
Deletion mutations ending in the 5'-flanking sequences of the Saccharomyces cerevisiae SUP4-o gene have been analyzed for their effects on gene expression. This ochre-suppressing tRNATyr gene was cloned into a S. cerevisiae centromeric plasmid, and its level of in vivo expression was monitored by observing the suppressor phenotype of the gene after transformation into S. cerevisiae. A deletion mutant that retains only four base pairs of the 5'-flanking sequence is profoundly deficient in expression; deletion mutants extending to positions -18, -17, -16, or -15 are moderately deficient; deletion mutants extending to positions -36 or -27 are slightly defective; and mutants retaining more than 60 base pairs of the original 5'-flanking DNA are expressed normally. In some cases, the cloning procedure led to the introduction of multiple BamHI linkers at the SUP4-o-vector fusion site, and in one instance, the resulting structure dramatically affects gene function: the presence of three linkers abutting a -18 deletion completely inhibits the in vivo expression of SUP4-o. In contrast, three linkers that abut a -77 deletion have no effect on in vivo expression. The template properties of these plasmids in a homologous in vitro transcription system parallel the levels of in vivo expression, suggesting that the mutations predominantly affect transcription. The data demonstrate that there are significant functional constraints on the 5'-flanking sequences of this RNA polymerase III-transcribed gene. The dramatic effects of the multiple linker insertion at position -18 suggest that there may be extensive melting of the DNA in this region during normal transcription initiation.
Assuntos
RNA Polimerases Dirigidas por DNA/genética , Regulação da Expressão Gênica , RNA Polimerase III/genética , RNA de Transferência/genética , Saccharomyces cerevisiae/genética , Deleção Cromossômica , DNA Fúngico/genética , Ligação Genética , Mutação , Óperon , Transcrição Gênica , TirosinaRESUMO
k9 killer toxin from Hansenula mrakii was used to select a number of resistant mutants from Saccharomyces cerevisiae. Preliminary biochemical and genetic studies showed that some of them acquired structural defects in the cell wall. One of these mutants, the knr4-1 mutant, displays a number of cell wall defects, including osmotic sensitivity; sensitivity to cercosporamide, a known antifungal agent; and resistance to Zymolyase, a (1,3)-beta-glucanase. We report here the isolation and analysis of the KNR4 gene. DNA sequence analysis revealed an uninterrupted open reading frame which contains five potential start codons. The longest coding template encodes a protein of 505 amino acids with a calculated molecular mass of 57,044 Da. A data base search revealed 100% identity with a nuclear protein, SMI1p. Disruption of the KNR4 locus does not result in cell death; however, it leads to reduced levels of both (1,3)-beta-glucan synthase activity and (1,3)-beta-glucan content in the cell wall. The gene was mapped to the right arm of chromosome VII.
Assuntos
Resistência Microbiana a Medicamentos/genética , Proteínas Fúngicas/biossíntese , Genes Fúngicos , Glucanos/biossíntese , Glucosiltransferases/biossíntese , Proteínas de Membrana , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Schizosaccharomyces pombe , beta-Glucanas , Sequência de Aminoácidos , Sequência de Bases , Benzofuranos/toxicidade , Western Blotting , Cromossomos Fúngicos , Clonagem Molecular/métodos , DNA Fúngico/isolamento & purificação , DNA Fúngico/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/isolamento & purificação , Glucosiltransferases/metabolismo , Hidrolases/toxicidade , Fatores Matadores de Levedura , Cinética , Dados de Sequência Molecular , Peso Molecular , Fases de Leitura Aberta , Pichia/metabolismo , Biossíntese de Proteínas , Proteínas/toxicidade , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Mapeamento por Restrição , Saccharomyces cerevisiae/efeitos dos fármacos , Homologia de Sequência de Aminoácidos , Fatores de TranscriçãoRESUMO
Despite recent advances in microfluidic-based integrated diagnostic systems, the sample introduction interface, especially with regards to large volume samples, has often been neglected. We present a sample introduction interface that allows direct on-chip processing of crude stool samples for the detection of Helicobacter pylori (H. pylori). The principle of IFAST (immiscible filtration assisted by surface tension) was adapted to include a large volume sample chamber with a septum-based interface for stool sample introduction. Solid chaotropic salt and dry superparamagnetic particles (PMPs) could be stored on-chip and reconstituted upon sample addition, simplifying the process of release of DNA from H. pylori cells and its binding to the PMPs. Finally, the PMPs were pulled via a magnet through a washing chamber containing an immiscible oil solution and into an elution chamber where the DNA was released into aqueous media for subsequent analysis. The entire process required only 7 min while enabling a 40-fold reduction in working volume from crude biological samples. The combination of a real-world interface and rapid DNA extraction offers the potential for the methodology to be used in point-of-care (POC) devices.
Assuntos
DNA Bacteriano/análise , Fezes/microbiologia , Helicobacter pylori/genética , Dispositivos Lab-On-A-Chip , Helicobacter pylori/isolamento & purificação , HumanosRESUMO
In order to determine the influence of proximal 5'-flanking DNA of the human renin gene (REN) in cells that express human renin, transient expression analyses were carried out in chorio-decidual cells. Constructs containing different lengths of REN promoter DNA, extending as far as 2595 bp upstream of the transcription start site, were unable to drive transcription of a chloramphenicol acetyl transferase reporter gene in chorio-decidual cells, nor in noncognate 293 or JEG-3 cells. The tk promoter was similarly inactive in constructs containing -2595 to -453 fragments of REN 5'-flanking DNA. In each cell type, the -2595 to -1300 DNA exerted a negative influence. Additional promoter- and cell type-dependent negative influences were noted for other regions of REN 5'-flanking DNA and the -453 to -145 DNA increased tk promoter activity 2.5-fold in chorio-decidual cells. By introducing the SV40 enhancer into constructs, a weak stimulation of the REN promoter was observed in chorio-decidual cells, but not in noncognate, JEG-3 cells, although the -2595 to -1300 DNA retained its negative influence in the cognate cell type. These results show that the proximal 2.6 kb of REN 5'-flanking DNA is unable to drive reporter gene activity in renin-synthesizing, chorio-decidual cells under basal conditions and suggest that trans-acting factors unique to at least this cell type, together with enhancer(s) located outside of the proximal 2.6 kb of REN promoter DNA tested, could be required for human renin promoter activity.
Assuntos
Córion/metabolismo , Decídua/metabolismo , Regiões Promotoras Genéticas , Renina/genética , Elementos Facilitadores Genéticos , Feminino , Regulação Enzimológica da Expressão Gênica , Genes , Humanos , RNA Mensageiro/genéticaRESUMO
The sites of insertion of the transposable kanamycin-neomycin resistance-determining element, Tn5, in the E. coli K-12 chromosome were assessed in a collection of over 300 auxotrophs. Although mutations in at least 45 different cistrons were obtained, the distribution of insertion sites was not completely random: proA or proB; cysG; and cysH, cysD or cysC mutants were found in excess.
Assuntos
Cromossomos Bacterianos , Elementos de DNA Transponíveis , Escherichia coli/genética , Mutação , Recombinação Genética , Mapeamento Cromossômico , Resistência Microbiana a Medicamentos , Canamicina/farmacologia , Neomicina/farmacologiaRESUMO
The properties of 22 isoleucine-valine auxotrophs induced in Escherichia coli K-12 by the transposable element, Tn5, were characterized on the basis of growth requirements, cross-feeding behavior, and enzyme activity. Mutants defective in ilvA, ilvC, ilvD and ilvE were found. Mutation in ilvE were not completely polar on ilvD and ilvA enzyme activities (that is, ilvE mutants possessed a low constitutive level of expression of the enzymes coded by ilvD and ilvA), while mutations in ilvD were completely polar on ilvA enzyme activity. The data suggest that there is an internal promoter between the sites of Tn5 insertion in ilvE and ilvD.
Assuntos
Elementos de DNA Transponíveis , Escherichia coli/genética , Isoleucina/genética , Mutação , Valina/genética , Escherichia coli/crescimento & desenvolvimento , Transaminases/genéticaRESUMO
Three genes code for isozymes of acetohydroxy acid synthase (AHAS) in Escherichia coli K-12. To test the previously published supposition that one of them, ilvG, is silent in ilvO+ strains, we isolated mutants which had deletions of various lengths in the ilvGEDA operon. Some of these mutants have severely reduced levels of AHAS activity. We conclude that ilvG is expressed in ilvO+ strains but is deleted in these mutants. In addition, we find that AHAS II, the ilvG gene product, is sensitive to feedback inhibition by valine. We hypothesize that ilvO- mutations are ilvG frameshift mutations which render AHAS II valine resistant and enhance transcription of distal genes.
Assuntos
Acetolactato Sintase/genética , Escherichia coli/genética , Genes , Isoenzimas/genética , Oxo-Ácido-Liases/genética , Aminoácidos de Cadeia Ramificada , Deleção Cromossômica , Elementos de DNA Transponíveis , Mutação , FenótipoRESUMO
The amino acid (aa) sequence of rat V-1, a developmentally regulated brain protein, was used to isolate clones encoding mouse V-1, a protein of 118 aa, from an embryoid body cDNA library. The aa sequences of rat and mouse V-1 are identical. V-1 shares several properties (including a 23 of 24 aa match of a tryptic peptide) with myotrophin, a protein that induces cardiac myocyte hypertrophy. Attempts to show that V-1 produced in Escherichia coli could induce the cardiac myocyte hypertrophy ascribed to myotrophin were unsuccessful.
Assuntos
Cardiomegalia/induzido quimicamente , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas do Tecido Nervoso/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/genética , Escherichia coli/genética , Biblioteca Gênica , Substâncias de Crescimento/farmacologia , Camundongos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/farmacologia , Proteínas Recombinantes de Fusão/biossíntese , Homologia de Sequência de AminoácidosRESUMO
The dipeptide mimic Val psi[CH(CONH2)NH]His (4) was incorporated into angiotensin II (AII) analogues to provide an octapeptide saralasin derivative (29) as well as tetrapeptide analogue 19. Three C-terminal tetrapeptides (21, 25, and 28) were also prepared. All compounds were tested for their ability to displace 3H-AII from rabbit adrenal gland homogenate and as antagonists of AII and AI on guinea pig ileum. The octapeptide analogue 29 was 700 times less active than the parent peptide 30. All the C-terminal fragments 19, 21, 25, and 28 have no measurable AII antagonist activity. Of the four tetrapeptide fragments, only 21 showed any appreciable binding activity.
Assuntos
1-Sarcosina-8-Isoleucina Angiotensina II/análogos & derivados , Angiotensina II/análogos & derivados , Dipeptídeos , Oligopeptídeos/síntese química , Glândulas Suprarrenais/metabolismo , Sequência de Aminoácidos , Angiotensina I/antagonistas & inibidores , Angiotensina II/antagonistas & inibidores , Angiotensina II/metabolismo , Antagonistas de Receptores de Angiotensina , Animais , Fenômenos Químicos , Físico-Química , Cobaias , Íleo/fisiologia , Dados de Sequência Molecular , Contração Muscular/efeitos dos fármacos , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/farmacologia , Coelhos , Receptores de Angiotensina/metabolismo , Saralasina/análogos & derivados , Saralasina/química , Saralasina/farmacologiaRESUMO
A number of unsymmetrically substituted 1,4-bis[(aminoalkyl)amino]anthracene-9,10-diones have been synthesized and evaluated for their antitumor activity against L1210 in vitro and in vivo. The high activity of several compounds observed in vitro was not paralleled by comparable activity in vivo. The activities of the substituted 1,4-bis[(aminoalkyl)amino]anthracene-9,10-diones as inhibitors of cell growth were generally much higher than those of the related 1-[(aminoalkyl)amino]-4-methoxyanthracene-9,10-diones, and this correlated with the relative abilities of compounds of the two types to interact with calf thymus DNA.
Assuntos
Antracenos/síntese química , Antineoplásicos/uso terapêutico , Animais , Antineoplásicos/síntese química , Bovinos , Divisão Celular/efeitos dos fármacos , DNA/metabolismo , Leucemia L1210/tratamento farmacológico , CamundongosRESUMO
The cardiotonic agent 4-ethyl-1,3-dihydro-5-4-(2-methyl-1H-imidazol-1-yl)benzoyl]-2H- imidazol-2-one (1) was found to have low bioavailability when administered orally to rats and dogs. A series of N-acyl derivatives, an underutilized prodrug of acidic NH compounds, has been synthesized and tested for their ability to improve the oral bioavailability of 1. Reaction of the monosodium salt of 1 with various anhydrides afforded the N-1 monoacylimidazolones with surprisingly high regioselectivity. In addition to the prodrugs, acylation of 1 with propionic or phenylacetic anhydride led to the novel 3H-pyrrolo[1,2-c]imidazole-3,5(2H)-diones 6. The prodrugs showed a significant increase in the partition coefficients with a minor decrease in the aqueous solubility. The benzoyl derivative 4b exhibited the highest stability in both pH 1.5 and 7.4 buffer solutions. Further evaluation of 4b showed rapid conversion to 1 in canine plasma (t1/2 = 38 min), and human plasma (t1/2 = 10 min). Oral studies indicated that the bioavailability of 4b was increased to greater than 75% (compared to less than 20% for 1), and hemodynamic studies demonstrated that the selective inotropic profile of 1 was retained.
Assuntos
Cardiotônicos/síntese química , Imidazóis/química , Pró-Fármacos/síntese química , Animais , Disponibilidade Biológica , Cardiotônicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Cães , Estabilidade de Medicamentos , Meia-Vida , Humanos , Concentração de Íons de Hidrogênio , Imidazóis/farmacocinética , Imidazóis/farmacologia , Estrutura Molecular , Pró-Fármacos/farmacocinética , Relação Estrutura-AtividadeRESUMO
Factor Xa (FXa) is a trypsin-like serine protease that plays a key role in blood coagulation linking the intrinsic and extrinsic pathways to the final common pathway of the coagulation cascade. During our initial studies, we observed facile photochemical conversion of the known FXa/tPA inhibitor, BABCH ¿(E,E)-2, 7-bis(4-amidinobenzylidene)cycloheptan-1-one, 1a, to the corresponding (Z,Z) olefin isomer, 1c (FXa K(i) = 0.66 nM), which was over 25,000 times more potent than the corresponding (E,E) isomer (1a, FXa K(i) = 17 000 nM). In order to determine the scope of this observation, we expanded on our initial investigation through the preparation of the olefin isomers in a homologous series of cycloalkanone rings, 4-substituted cyclohexanone analogues, and modified amidine derivatives. In most cases the order of potency of the olefin isomers was (Z,Z) > (E,Z) > (E,E) with the cycloheptanone analogue (1c) showing the most potent factor Xa inhibitory activity. In addition, we found that selectivity versus thrombin (FIIa) can be dramatically improved by the addition of a carboxylic acid group to the cycloalkanone ring as seen with 8c (FXa K(i) = 6.9 nM, FIIa K(i) > 50,000 nM). Compounds with one or both of the amidine groups substituted with N-alkyl substituents or replaced with amide groups led to a significant loss of activity. In this report we have demonstrated the importance of the two amidine groups, the cycloheptanone ring, and the (Z,Z) olefin configuration for maximum inhibition of FXa within the BABCH template. The results from this study provided the foundation for the discovery of potent, selective, and orally active FXa inhibitors.
Assuntos
Compostos de Benzilideno/síntese química , Compostos de Benzilideno/farmacologia , Inibidores do Fator Xa , Inibidores de Serina Proteinase/síntese química , Inibidores de Serina Proteinase/farmacologia , Compostos de Benzilideno/química , Humanos , Espectroscopia de Ressonância Magnética , Inibidores de Serina Proteinase/química , Relação Estrutura-AtividadeRESUMO
Histone-like proteins of the HU family are small, sequence-independent DNA binding proteins that facilitate a variety of DNA transactions. Here we report isolation from cell-free extracts of Staphylococcus aureus of HSa, a new member of the HU family. The NH2-terminal amino acid sequence of HSa led to identification of the corresponding gene (hsa) using the genome sequence of S. aureus. HSa is 90 amino acids long (Mr = 9 620) and shares 64 to 80% identity with homologs found in the genus Bacillus.
Assuntos
Proteínas de Ligação a DNA/isolamento & purificação , Proteínas de Ligação a DNA/metabolismo , Proteínas de Escherichia coli , Staphylococcus aureus/metabolismo , Sequência de Aminoácidos , Eletroforese em Gel de Poliacrilamida , Dados de Sequência Molecular , Peso MolecularRESUMO
BACKGROUND: Because of donor oocyte programs, women who previously were considered too old to successfully achieve conception and delivery can now bear children. To our knowledge, there have been no previous reports of pregnancy outcome in women over age 50 who conceived using donor oocytes. This study presents the pregnancy and delivery data on two women who delivered at age 52. CASES: Case 1 was a 51-year-old woman, gravida 3, para 3, whose three children had been conceived with her first husband more than 20 years previously. She had remarried 18 years before presentation and had been actively trying to conceive for the last 7 years. She was diagnosed as being in menopause based on elevated gonadotropins, amenorrhea, and failure to have progesterone-withdrawal menses. She conceived on her first embryo transfer cycle with embryos derived from donor oocytes and fertilized by her husband's sperm (oocytes were donated by a woman who was undergoing retrieval for in vitro fertilization). During pregnancy she remained healthy, but had uterine prolapse at 20 weeks. She delivered a normal healthy male at 40.5 weeks; cesarean was performed because of a presumptive diagnosis of fetal distress after 3 hours of labor, when monitoring revealed fetal heart decelerations. Case 2 was also a 51-year-old woman, gravida 6, para 4, who wished to conceive with her second husband's sperm through the donor oocyte program. She had amenorrhea of 2 years' duration and elevated gonadotropins. Conception occurred after fertilization of a donor oocyte by her husband's sperm. She had an uneventful pregnancy, but labor was induced at 38 weeks' gestation given the supposed high-risk status of this age group. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. CONCLUSION: Theoretically, the risks of pregnancy complications in older patients are magnified given the aging maternal cardiovascular system, which may predispose these women to placental insufficiency. These first two cases of donor oocyte pregnancies in women over age 50 found no maternal or fetal age-related complications. We hope these reports will encourage all researchers to share their findings so that prospective patients can make better, more informed decisions as to whether they want to participate in donor oocyte programs.
Assuntos
Transferência Embrionária , Oócitos , Resultado da Gravidez , Feminino , Fertilização in vitro , Humanos , Trabalho de Parto Induzido , Idade Materna , Menopausa , Pessoa de Meia-Idade , Gravidez , Gravidez de Alto RiscoRESUMO
Three new proteins, FmhA, FmhB and FmhC, with significant identities to FemA and FemB were identified in the Staphylococcus aureus (ATCC 55748) genome database. They were mapped to the SmaI-C, SmaI-H and SmaI-A fragments of the S. aureus 8325 chromosome, respectively. Whereas insertional inactivation of fmhA and fmhC had no effects on growth, antibiotic susceptibility, lysostaphin resistance, or peptidoglycan composition of the strains, fmhB could not be inactivated, strongly suggesting that fmhB may be an essential gene. As deduced from the functions of FemA and FemB which are involved in the synthesis of the peptidoglycan pentaglycine interpeptide, FmhB may be a candidate for the postulated FemX thought to add the first glycine to the nascent interpeptide.
Assuntos
Proteínas de Bactérias/genética , Fases de Leitura Aberta/genética , Staphylococcus aureus/genética , Parede Celular/metabolismo , Mapeamento Cromossômico , Clonagem Molecular , Sondas de DNA , Genoma Bacteriano , Resistência a Meticilina/genética , Mutagênese , Proteoglicanas/metabolismo , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/metabolismo , TemperaturaRESUMO
The objective of this study was to determine if genes for cyclooxygenase (COX) and 5-lipoxygenase, key enzymes in the synthesis of eicosanoids, are expressed in human endometrium and to determine if the level of expression is affected by decidualization or preeclampsia, a form of pregnancy-induced hypertension. RT-PCR was used to detect mRNA in tissues obtained from various patients. Results demonstrated that COX and 5-lipoxygenase genes are expressed in endometrium and decidua. COX gene expression in endometrium is 2-3-fold greater than in decidua while 5-lipoxygenase gene expression is similar. Neither COX nor 5-lipoxygenase gene expression in decidua is altered by changes resulting from preeclampsia. Thus, genes for key enzymes in the synthesis of eicosanoids are expressed in human endometrium and decidua. Selective down-regulation is evident as decidualization results in a significant reduction in the gene expression of COX, while 5-lipoxygenase gene expression remains unchanged.
Assuntos
Decídua/enzimologia , Endométrio/enzimologia , Prostaglandina-Endoperóxido Sintases/genética , Araquidonato 5-Lipoxigenase/genética , Decídua/metabolismo , Regulação para Baixo , Endométrio/metabolismo , Feminino , Expressão Gênica , Humanos , Técnicas In Vitro , Reação em Cadeia da Polimerase , Pré-Eclâmpsia/enzimologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Prostaglandinas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Aminoglycosides have been cinically used since 1944. Although this class of antibacterial agents has some nephrotoxicity and ototoxtcity issues, they continue to be part of the hospital armamentarium because of then rapid bactericidal activity, especially in combination with ß-lactams. Bacterial resistance to aminoglycosides can be caused by modifying enzymes, changes in cell permeability, and changes in the cellular target. The clinical observation of high levels of aminoglycoside resistance most often results from the acquisition of genes that encode modifying enzymes and are often plasmid-borne. Aminoglycosides are inactivated by three classes of enzymes:
RESUMO
Forty-nine species (87 samples) of marine macroalgae from eastern Australia were analyzed by GC/MS for the key seafood flavor components 2- and 4-bromophenol, 2,4- and 2,6-dibromophenol, and 2,4, 6-tribromophenol. All five bromophenols were found in 62% of samples, four in 32% of samples, and three in the remaining 6% of samples. 2, 4,6-Tribromophenol was found in all samples and, with few exceptions, was present in the highest concentrations. The total bromophenol content determined on a wet-weight basis varied widely across species from 0.9 ng/g in the green alga Codium fragile to 2590 ng/g in the red alga Pterocladiella capillacea. Species with the highest concentrations of bromophenols were all collected from sites exposed at low tide. The study demonstrates the wide occurrence of bromophenols in marine algae and provides a possible source of such compounds in fish that feed predominantly on ocean plants. The possible effect that dietary marine algae has on the flavor of omnivorous ocean fish is discussed.