RESUMO
Recent reports show a pro-oxidant activity of aminoguanidine. Aminoguanidine is able to generate hydrogen peroxide in the presence of Cu (II). These observations have been confirmed by the present studies in that aminoguanidine is, indeed, able to generate oxidants similar in reactivity to the hydroxyl radical and is also able to fragment BSA in a Cu (II)-dependent manner. Studies on glycated bovine serum albumin show that aminoguanidine can affect a number of parameters associated with the nonenzymatic glycation of protein. This includes an ability to decrease glucose attachment and levels of protein fluorescence termed glycophore, resulting from protein glycation. Aminoguanidine also increases the generation of dicarbonyl compounds by glycated protein. All of these effects on parameters of glycation appear to be Cu (II) dependent. Further studies show that one effect of protein glycation is to decrease its susceptibility to proteolysis. The reverse is true of protein oxidation, which has previously been shown to increase the susceptibility of proteins to proteolytic digestion. Evidence is presented suggesting that aminoguanidine is able to enhance the proteolytic digestion of glycated BSA, a protein shown to be protease resistant. Our observations are discussed within the context of current concepts of protein glycation in the development of diabetic complications and aminoguanidine's potential use as a prophylactic agent in diabetes mellitus.
Assuntos
Guanidinas/farmacologia , Oxidantes/farmacologia , Soroalbumina Bovina/metabolismo , Albumina Sérica/metabolismo , Quimotripsina/metabolismo , Diabetes Mellitus , Endopeptidases/metabolismo , Produtos Finais de Glicação Avançada , Peróxido de Hidrogênio/metabolismo , Pepsina A/metabolismo , Albumina Sérica/química , Soroalbumina Bovina/química , Tripsina/metabolismo , Albumina Sérica GlicadaRESUMO
A characteristic of the antioxidant, probucol, is its inability to inhibit apolipoprotein B fragmentation in low density lipoprotein (LDL), despite a pronounced ability to inhibit lipid oxidation on relatively lengthy exposure to Cu(II). Here we show that a short exposure of LDL to hydrogen peroxide and Cu(II) leads to 125I-labelled apolipoprotein B fragmentation, the production of malondialdehyde and hydroperoxides and leads to increased uptake by macrophages on subsequent culture. However, pre-loading LDL with probucol protects LDL from lipid oxidation but not protein fragmentation or macrophage uptake. The use of probucol to conduct studies on apolipoprotein B oxidation without extensive lipid oxidation may prove useful when studying LDL apolipoprotein damage on exposure to an aqueous free radical insult.
Assuntos
Apolipoproteínas B/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Apolipoproteínas B/efeitos dos fármacos , Transporte Biológico , Linhagem Celular , Cobre/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos , Oxirredução , Probucol/farmacologiaRESUMO
A project to determine if intraarticular corticosteroid therapy was deleterious to the racing Thoroughbred was carried out in the 1971, 1972, and 1973 racing seasons. Of 22 horses available for follow-up examination, 6 had radiographic evidence of deterioration; 1 of these was destroyed because of probable corticosteroid-induced arthropathy. The remaining 16 horses did not have any evidence of deterioration. One of the 16, a stakes winner, had been given 12 injections into the left front fetlock during the 3-year period. It was concluded that if proper and careful aftercare is adhered to, intraarticular injections of corticosteroids can be carried out with relative impunity.
Assuntos
Corticosteroides/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Artropatias/veterinária , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Animais , Artrite/induzido quimicamente , Artrite/veterinária , Doenças dos Cavalos/induzido quimicamente , Cavalos , Injeções Intra-Articulares , Artropatias/tratamento farmacológicoRESUMO
Atypical mycobacterial infections are becoming more common in dermatological practice due to increasing numbers of immunosuppressed patients. A case of cutaneous Mycobacterium chelonei infection with sporotrichoid spread in a renal transplant patient is described, and the current literature regarding clinical spectrum, histopathology and management of infection with this pathogen is reviewed.
Assuntos
Transplante de Rim , Infecções por Mycobacterium não Tuberculosas/etiologia , Dermatopatias Infecciosas/etiologia , Esporotricose/etiologia , Dermatomicoses/etiologia , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Pessoa de Meia-IdadeRESUMO
A metropolitan population of 238,000 in Perth, Western Australia, was screened for chronic ulceration of the leg. Patients with a chronic leg ulcer and a venous abnormality comprised 57 per cent of all patients with a chronic leg ulcer, giving a prevalence of 0.62 per 1000 population. There was an increasing prevalence with age; 90 per cent of patients were 60 years and older. This group comprised 16.7 per cent of the population, and had a prevalence of 3.3 per 1000. Although chronic venous ulcers were more common in women there was no difference in age related prevalence. In 36 per cent of patients with a venous abnormality, there was at least one other aetiological factor contributing to chronic ulceration of the leg; 96 per cent had either a history of deep venous thrombosis or a condition known to predispose to deep venous thrombosis.
Assuntos
Úlcera da Perna/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Causalidade , Doença Crônica , Feminino , Humanos , Úlcera da Perna/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prevalência , Tromboflebite/complicações , Varizes/cirurgia , Austrália Ocidental/epidemiologiaRESUMO
OBJECTIVE: To assess the effect of different dressings on venous ulcer healing. DESIGN: A randomised clinical trial. MATERIALS: Patients were randomised to treatment with one of three dressings: a zinc oxide impregnated bandage, a zinc oxide impregnated stockingette, or an alginate dressing. All patients were treated as outpatients and had compression bandaging with two minimal stretch bandages (Elastocrepe) and a stockingette (Tubigrip) to keep the bandages in place. METHODS: One hundred and thirteen patients (133 ulcerated limbs) with chronic ulceration of the leg due to venous disease alone, and attending Fremantle Hospital Leg Ulcer Clinic, Western Australia were entered into the study. Healing was measured as complete healing of the ulcerated limb or failure of the limb to heal within 9 months. RESULTS: There was no significant difference between the three groups in ulcer size, duration, and other parameters compared. Healing was affected significantly by ulcer size and which leg was ulcerated. There was significantly faster healing with the paste bandage. CONCLUSION: The use of a paste bandage significantly improved the healing of chronic venous ulcers when used in combination with compression bandaging, and compared to an alginate dressing and a zinc oxide impregnated stockingette.
Assuntos
Bandagens , Úlcera Varicosa/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Óxido de Zinco/administração & dosagemRESUMO
Chronic leg ulcers have many different causes and therefore need an accurate diagnosis in order to give the most effective treatment. A specialized clinic was set up in Fremantle Hospital in July 1988 with the aims of performing a thorough clinical and laboratory assessment to establish the cause of ulceration in every patient, and treating patients according to the cause of ulceration. Patients with arterial, neoplastic or dermatological conditions were treated as appropriate for their diagnosis and patients with other chronic ulcers were managed as outpatients where possible. Patients were seen between July 1988 and July 1989. Only 43% had purely venous ulcers, 32.6% had a venous component plus some other abnormality, and 5.2% were purely arterial. Using an outpatient treatment regimen, 67% of all ulcerated limbs and 73.7% of limbs with purely venous ulcers were healed within 6 months. Only 11 patients with venous ulceration (15 limbs) failed on this therapy and required admission during the observation period. The initial ulcer size was shown to influence the time to total healing of the limb. The healing rates achieved compare favourably with studies from other specialized centres and suggest that the majority of patients with chronic leg ulcers can be treated successfully using ambulatory outpatient dressing techniques.