RESUMO
The characteristics of the uptake of L-homocysteine by cultures of human umbilical vein endothelial cells have been examined. Uptake occurred by Na(+)-dependent and Na(+)-independent systems, but was essentially independent of the pH of the uptake medium. The Na(+)-independent system corresponded to system L, being totally inhibited by the presence of beta-2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH) a system L analogue. It was concluded on the basis of starvation experiments coupled with failure to detect any inhibition in the presence of 2-methylaminoisobutyric acid (MeAIB), a system A analogue, that the Na(+)-dependent uptake was wholly accounted for by system ASC. The kinetic properties of systems L and ASC were determined by omitting Na+ from the uptake medium and incorporating BCH in the medium, respectively. It has been concluded on the basis of the inhibitory effects of a number of amino acids that uptake of homocysteine occurs by those systems which transport cysteine.
Assuntos
Endotélio Vascular/metabolismo , Homocisteína/metabolismo , Aminoácidos/farmacologia , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Cisteína/metabolismo , Humanos , Técnicas In Vitro , Cinética , Sódio/fisiologiaRESUMO
The present report is an analysis of the course of peripheral vascular disease (PVD) in 619 patients with non-insulin-dependent diabetes (NIDDM) recruited within 1 yr of diagnosis and followed quarterly for up to 14 yr (X = 10.5 yr). At 13 yr duration, the actuarially determined cumulative risks for intermittent claudication (IC), nonpalpable dorsalis pedis pulse (NPUL), and arterial calcification (CALC) were, respectively, 37.9%, 34.5%, and 60.9% for men and 24.3%, 37.6%, and 32.2% for women. Major amputations (AMP) occurred in only 1.3% of the patients, equivalent to approximately one case per 1000 patients per year. The corresponding incidences of IC, NPUL, and CALC were, respectively, 29, 27, and 47 per 1000 men and 19, 27, and 25 per 1000 women per year. CALC and NPUL were strongly related to mortality. Baseline risk factors with probability levels that suggest a relationship to PVD were, in women, age versus CALC (P less than 0.01), age versus NPUL (P less than 0.05), weight versus NPUL (P less than 0.05), systolic BP versus CALC (P less than 0.01), summed glucose tolerance test versus CALC (P less than 0.01), and triglyceride level versus CALC (P less than 0.05). In men, the only significant risk factors were diminished vibration perception, which was related to NPUL (P less than 0.05), and the serum triglyceride level, which was related to IC (P less than 0.05). In patients who are carefully followed prospectively, IC is far more common, but AMP is far less common than has been generally appreciated. Further studies are needed to clarify the roles of the diverse risk factors that are possibly related.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Amputação Cirúrgica , Artérias , Calcinose/etiologia , Feminino , Humanos , Claudicação Intermitente/etiologia , Masculino , Pessoa de Meia-Idade , Risco , Fatores de TempoRESUMO
OBJECTIVE: Little is known about medial arterial calcification (MAC) other than its association with age, sex, diabetes, and diabetes complications. Familial aggregation of this disorder was studied to determine the importance of potential genetic factors and to assess whether such familial aggregation was independent of that of diabetes. RESEARCH DESIGN AND METHODS: Members of 1,256 Pima Indian nuclear families with 3,339 offspring were examined radiologically for MAC of the feet. Multiple logistic regression analyses were used to compare the presence of the disorder in a parent with the presence of MAC in an offspring and to determine whether familial aggregation of MAC was independent of parental diabetes. RESULTS: Controlled for age, sex, diabetes, serum cholesterol, and blood pressure, offspring of one parent with MAC had 3.3 (95% CI 1.5-7.6) times the odds of MAC as did offspring of parents without MAC, and offspring with both parents affected had an even higher risk (odds ratio, 8.1; 95% CI 3.4-18.8). Controlled for offspring age and sex and for parental age and diabetes, parental MAC was associated with the disorder in offspring (P < 0.001), but the effect of parental diabetes on MAC in the offspring was not significant when controlled for parental MAC (P = 0.36). Furthermore, offspring of nondiabetic parents with MAC, controlled for age, sex, diabetes, and diabetes duration, had 1.7 (95% CI 0.9-3.1) times the odds of MAC than did offspring of diabetic parents with MAC. CONCLUSIONS: Independent of parental age and diabetes and offspring age, sex, diabetes, and diabetes complications, parental MAC confers an increased risk of MAC in offspring. These findings suggest that the factors responsible for the familial clustering of MAC may be different from those for diabetes.
Assuntos
Arteriopatias Oclusivas/genética , Calcinose/genética , Angiopatias Diabéticas/genética , Indígenas Norte-Americanos , Núcleo Familiar , Adulto , Fatores Etários , Idoso , Arizona/epidemiologia , Arteriopatias Oclusivas/epidemiologia , Arteriopatias Oclusivas/fisiopatologia , Pressão Sanguínea , Calcinose/epidemiologia , Calcinose/fisiopatologia , Colesterol/sangue , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Medição de Risco , Fatores de Risco , Caracteres SexuaisRESUMO
Homocysteine induced toxicity has been examined in cultures of human umbilical vein endothelial cells. The toxic effects of the amino acid alone and the amino acid plus Cu2+ could be prevented by catalase and decreased by desferal, when either was present in the culture medium. When desferal was allowed to accumulate intracellularly, no significant protection from homocysteine induced toxicity was observed. Even though lipid peroxidation accompanied the toxicity induced by homocysteine and homocysteine plus Cu2+, inhibition of lipid peroxidation in either case had no effect on cell viability. The significance of these results is discussed.
Assuntos
Endotélio Vascular/metabolismo , Homocisteína/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Catalase/farmacologia , Sobrevivência Celular , Células Cultivadas , Desferroxamina/farmacologia , Humanos , Peróxido de Hidrogênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico , Veias UmbilicaisRESUMO
In response to homocysteine induced toxicity in human umbilical vein endothelial cells, minimal changes in the concentration of cellular protein thiols but substantial changes in the concentration of intracellular soluble thiols were observed. The latter correlated closely with changes in cellular glutathione levels. No correlation existed between cellular glutathione levels and cell viability, whereas a close correlation between NAD+ levels and cell viability was demonstrated. Large decreases in cellular NAD+ occurred in response to homocysteine induced toxicity which were accompanied by the production of single stranded DNA. 3-Aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase preserved cell viability and cellular NAD+ levels. Evidence that DNA synthesis was also compromised was revealed by the decreased capacity of homocysteine treated cells to incorporate deoxyuridine. Radical scavengers were also effective in preventing homocysteine induced toxicity. It is likely that the major threat to cells derives from radicals generated intracellularly. Eicosanoid metabolism and the xanthine oxidase system have been identified as two potential sources of radicals.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Homocisteína/farmacologia , Benzamidas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA/biossíntese , DNA/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Eicosanoides/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Glutationa/metabolismo , Humanos , NAD/efeitos dos fármacos , NAD/metabolismo , Estresse Oxidativo , Inibidores de Poli(ADP-Ribose) Polimerases , Compostos de Sulfidrila/metabolismo , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacos , Veias Umbilicais/metabolismo , Xantina Oxidase/metabolismoRESUMO
After undergoing bilateral breast reconstruction with latissimus dorsi flaps, a 34-year-old woman developed right-sided thoracic outlet syndrome. At operation, the latissimus dorsi flap was found to have formed a constrictive muscle sling that compressed the thoracic outlet. To the author's knowledge, thoracic outlet syndrome has not previously occurred under these circumstances.
Assuntos
Mama/cirurgia , Retalhos Cirúrgicos/efeitos adversos , Síndrome do Desfiladeiro Torácico/etiologia , Adulto , Feminino , HumanosRESUMO
The uptake of L-cystine into cultured human umbilical vein endothelial cells has been shown to occur by a Na+-independent system which is inhibited by L-glutamate and L-homocysteine, but not by other amino acids. It is likely that the system transporting L-cystine is shared by L-glutamate. Thiol groups associated with membrane bound components appear to be essential for L-cystine uptake but it is not yet evident whether these constitute an integral part of the transporter per se.
Assuntos
Cistina/metabolismo , Endotélio/metabolismo , Transporte Biológico , Células Cultivadas , Humanos , Veias Umbilicais/metabolismoRESUMO
Rats were given different doses (0.25-25 mg) of two forms of PVC past polymers and polystyrene by intratracheal instillation and monitored for cellular and biochemical changes in the lung lavage fluid and remaining lung tissue after 1 and 4 weeks of exposure. Changes were observed in free cell morphology, the level of pulmonary surfactant, and hydrolytic enzyme activities with all three compounds at high concentrations. Some differences in the extent of changes produced per given mass identified were noted with different formulations and the relationship between particle numbers, surface areas, and detergent coatings of samples is discussed. It is argued that PVC paste polymers and polystyrene cannot be considered totally biologically inert but that, in comparison with active cytoxic and inflammatory minerals such as chrysotile asbestos, the extent of their initial reaction in the lung is relatively weak.
Assuntos
Látex/farmacologia , Pulmão/efeitos dos fármacos , Cloreto de Polivinila/farmacologia , Polivinil/farmacologia , Surfactantes Pulmonares/metabolismo , Animais , Ácido Aspártico Endopeptidases , Benzenossulfonatos/farmacologia , Detergentes/farmacologia , Desinfetantes/farmacologia , Endopeptidases/metabolismo , Hemólise/efeitos dos fármacos , Pulmão/citologia , Pulmão/metabolismo , Masculino , Tamanho da Partícula , Ratos , Ribonucleases/metabolismo , Dodecilsulfato de Sódio/farmacologiaRESUMO
The formation of sulphoconjugates is a ubiquitous phenomenon and the addition of the sulphate moiety to a variety of endogenous and exogenous molecules dramatically alters their physico-chemical properties and also their biological functions. Large numbers of different types of sulphoconjugate exist and their formation is catalysed by the versatile sulphotransferases. An equally versatile family of enzymes, the sulphohydrolases exist that are capable of accomplishing the reverse reaction. This paper comprises an appraisal of sulphoconjugation and sulphohydrolysis in the metabolism of xenobiotics and addresses the wider issues of sulphur availability and the interplay between mammalian and microbial enzyme systems in the sulphate cycle.
Assuntos
Enxofre/metabolismo , Animais , Humanos , Hidrolases/metabolismo , Hidrólise , Fígado/metabolismo , Sulfatases/metabolismo , Sulfotransferases/metabolismoRESUMO
Rats inhaled a paste polymer polyvinyl chloride dust at an aerosol concentration of 10 mg/m3 for 6 hr/day, 5 days/wk for a 15-wk period. A small number of randomly scattered lung lesions were detected at 15 wk; these lesions were also present 15 wk after exposure to polyvinyl chloride had ceased. Few if any biochemical changes were detected at the alveolar surface in lung tissues or other organs of polyvinyl chloride-exposed rats. It is therefore concluded that at "nuisance" dust level this form of polyvinyl chloride polymer exhibits a weak biological reactivity.
Assuntos
Cloreto de Polivinila/toxicidade , Polivinil/toxicidade , Aerossóis , Animais , Poeira , Feminino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Metabolismo/efeitos dos fármacos , RatosAssuntos
Nucleotídeos de Adenina , Fígado/enzimologia , Sulfatases , Ácidos Sulfúricos , Animais , Anelídeos/enzimologia , Anuros , Galinhas , Cobalto , Cyprinidae , Ativação Enzimática , Concentração de Íons de Hidrogênio , Insetos , Fígado/citologia , Lagartos , Lisossomos/enzimologia , Moluscos/enzimologia , Nucleotidases , Ratos , Sulfatases/isolamento & purificação , Isótopos de Enxofre , Turbelários/enzimologiaAssuntos
Fígado/enzimologia , Sulfatases/isolamento & purificação , Fosfatase Ácida/análise , Monofosfato de Adenosina , Aminoácidos/análise , Sulfato de Amônio , Animais , Bovinos , Cromatografia DEAE-Celulose , Cromatografia em Gel , Eletroforese Descontínua , Eletroforese em Gel de Poliacrilamida , Glucose-6-Fosfatase/análise , Fígado/citologia , Lisossomos/enzimologia , Peso Molecular , Nucleotidases/análise , Ácidos Fosfóricos , Dodecilsulfato de Sódio , Frações Subcelulares/enzimologia , Sulfatases/análise , Isótopos de Enxofre , Ácidos Sulfúricos , Sulfurtransferases/análiseAssuntos
Sulfetos/metabolismo , Administração Oral , Animais , Autorradiografia , Cromatografia em Papel , Cromatografia em Camada Fina , Eletroforese , Eletroforese em Papel , Fezes/análise , Técnicas In Vitro , Injeções Intraperitoneais , Fígado/metabolismo , Oxirredução , Ratos , Ratos Endogâmicos , Sódio/metabolismo , Sulfetos/administração & dosagem , Sulfetos/sangue , Sulfetos/urina , Isótopos de Enxofre , Fatores de TempoRESUMO
Until recently little was known about the biological roles played by sulphatase enzymes, owing in part to the selection of assay substrates that were convenient but only removely related to the natural substrates. Once this was recognized the elucidation of function proceeded more rapidly. Microbial sulphatases appear to have roles to play in the nutrition of individual microorganisms whilst collectively they enable sulphur, returned to soils and waters in the form of sulphate esters, to be made available for recycling. In contrast, with one or two important exceptions, mammalian sulphatases are concerned, in association with other enzymes, with the turnover of macromolecules. Still defying understanding are the roles of sulphatases acting on adenosine 5'-phosphosulphate (APT) and 3'-phosphoadenosine 5'-phosphosulphate (PAPA). APS sulphatases have now been purified from ox-liver lysosomes and cytosol and from a strain of Comamonas terrigena. The lysosomal enzyme shows wide specificity and can hydrolyse ATP, ADP, FED and pyrophosphate. The cytosol enzyme is apparently specific and may be active only when cellular concentrations of ATP are low. The bacterial enzyme is also specific and has properties and a cellular localization that suggest the possibility of its involvement in sulphate transport.
Assuntos
Sulfatases/metabolismo , Monofosfato de Adenosina/metabolismo , Adenosina Fosfossulfato/metabolismo , Trifosfato de Adenosina/metabolismo , Alcaligenes/enzimologia , Animais , Bovinos , Escherichia coli/enzimologia , Fígado/enzimologia , Fosfoadenosina Fosfossulfato/metabolismo , Pseudomonas/enzimologiaRESUMO
The arylsulphatase C of rat kidney and spleen is localized predominantly in the microsomal fraction. The distribution pattern is paralleled by that of oestrogen sulphatase, as in rat liver. The general usefulness of arylsulphatase C as a microsomal marker enzyme is indicated.
Assuntos
Rim/enzimologia , Baço/enzimologia , Sulfatases/metabolismo , Animais , Arilsulfatases/metabolismo , Fracionamento Celular , Núcleo Celular/enzimologia , Citoplasma/enzimologia , Estrogênios , Lisossomos/enzimologia , Masculino , Microssomos/enzimologia , Mitocôndrias/enzimologia , RatosRESUMO
Cytosol preparations of rat liver and kidney were examined for their ability to transfer sulphate from adenosine 3'-phosphate 5'-sulphatophosphate to p-hydroxyphenylpyruvic acid. Little activity towards this substrate was observed, and the main product detected in the reaction mixtures was identified as p-hydroxybenzyl alcohol O-sulphate. This was not formed from p-hydroxybenzaldehyde, a spontaneous oxidation product of p-hydroxyphenylpyruvic acid, by sulphation followed by a rapid enzyme-catalysed reduction of the intermediate phydroxybenzaldehyde O-sulphate. This product was formed mainly by this sequence of reactions, but the reverse, reduction followed by sulphation, also appeared possible. p-Hydroxybenzyl alcohol itself was very readily sulphated by both preparations, and the liver also produced a sulpho-conjugate of homogentisic acid. These observations are important in calculating the turnover of L-tyrosine O-sulphate in the mammalian system, and establish that p-hydroxyphenylpyruvic acid O-sulphate is an end product of its metabolism, rather than an intermediate in its synthesis by reversed transamination.
Assuntos
Rim/metabolismo , Fígado/metabolismo , Ácidos Fenilpirúvicos/metabolismo , Ácidos Sulfúricos/metabolismo , Animais , Citosol/metabolismo , Cinética , Especificidade de Órgãos , RatosRESUMO
The use of topical salicylate-containing creams and ointments is widespread. A case is presented which implicates the use of one such cream (Aspercreme) as a potential cause of platelet coagulopathy after rhytidectomy.
Assuntos
Transtornos Plaquetários/induzido quimicamente , Face/cirurgia , Salicilatos/efeitos adversos , Administração Tópica , Idoso , Feminino , Humanos , Complicações Pós-Operatórias , Salicilatos/administração & dosagem , Cirurgia PlásticaRESUMO
Carefully selected head and neck tumor patients can safely undergo a wide variety of aesthetic surgical procedures. The malignancy must first be adequately treated and clinically controlled before elective surgery. Each tumor patient's general health and life expectancy must be honestly assessed prior to aesthetic surgery, because operating on an individual who cannot survive to enjoy the benefits is injudicious. Through the combined efforts of sophisticated oncology and plastic surgery, the patient survival rate can be improved as quality of life is enriched in appropriately selected and carefully managed individuals.
Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Cirurgia Plástica/métodos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Complicações Pós-OperatóriasRESUMO
1. Rat tissues have been shown to possess an aminotransferase that is active towards l-tyrosine O-sulphate and dependent on 2-oxoglutarate and pyridoxal phosphate. 2. Kidney, liver and pancreas have the greatest activity and the enzyme is localized mainly in the mitochondrial fraction in the liver and kidney cell. 3. The enzyme was shown to be distinct from l-tyrosine-2-oxoglutarate aminotransferase but its true identity was not established. 4. A procedure for the assay of the enzyme in crude tissue preparations was developed.
Assuntos
Sulfatos/metabolismo , Transaminases/metabolismo , Tirosina/metabolismo , Animais , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hidrocortisona/farmacologia , Técnicas In Vitro , Ácidos Cetoglutáricos , Rim/enzimologia , L-Lactato Desidrogenase/metabolismo , Fígado/enzimologia , Pâncreas/enzimologia , Fosfato de Piridoxal , Ratos , Frações Subcelulares/metabolismoRESUMO
Conditions based on previous assays with potassium p-acetylphenyl sulphate have been established for the specific assay of arylsulphatase C in rat tissues. The enzyme has optimum activity with 40mm substrate at pH8.0 in the presence of 0.1m-phosphate buffer. Under these conditions arylsulphatase C can be assayed without interference from the other arylsulphatase enzymes present and is useful as a marker for the endoplasmic reticulum in cell-fractionation studies.