RESUMEN
BACKGROUND: Epidemiological studies indicate environmental pollutants to be involved in the increase in the prevalence of allergic diseases. In human exposure studies, volatile organic compounds (VOCs) have been shown to cause exacerbations of allergic asthma whereas, no data concerning atopic eczema (AE) are available. OBJECTIVE: We investigated the effect of airborne VOCs on the skin of patients with AE and controls in the presence or absence of house dust mite allergen, Der p 1. METHODS: In a double-blind crossover study, 12 adults with AE and 12 matched healthy volunteers were exposed on their forearms to Der p 1 and subsequently to a mixture of 22 VOCs (M22, 5 mg/m(3)) in a total body exposure chamber for 4 h. Transepidermal water loss (TEWL) and skin blood flow were measured in all subjects before, during and after exposure. Additionally, an atopy patch test (APT) with Der p 1 was applied to the skin after exposure. RESULTS: A significant increase in transepidermal water loss was observed 48 h after exposure to VOCs as compared with exposure with filtered air in all individuals (mean difference: +34%; 95% Confidence Interval: 7-69%). Prior Der p 1 exposure resulted in a significant rise of dermal blood flow after 48 h in patients with AE but not in controls. Six out of seven patients showed enhanced atopy patch test (APT) reactions to HDM allergen after previous exposure to VOCs. CONCLUSION: Our results show that exposure to VOCs - at concentrations commonly found in indoor environments - can damage the epidermal barrier and enhance the adverse effect of Der p 1 on sensitized subjects with AE. These findings may contribute to a better understanding of the mechanisms underlying the increase in prevalence and exacerbation of AE.
Asunto(s)
Antígenos Dermatofagoides/farmacología , Dermatitis Atópica/fisiopatología , Contaminantes Ambientales/farmacología , Piel/irrigación sanguínea , Pérdida Insensible de Agua/efectos de los fármacos , Adulto , Contaminación del Aire Interior , Alérgenos/farmacología , Proteínas de Artrópodos , Cisteína Endopeptidasas , Dermatitis Atópica/inmunología , Exposición a Riesgos Ambientales/efectos adversos , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas del Parche/métodos , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/inmunología , Piel/inmunología , Volatilización , Pérdida Insensible de Agua/inmunologíaRESUMEN
This investigation was directed toward the tissue reaction and wound healing response of an ePTFE prosthesis implanted in a human subject as an arteriovenous fistulae for over 7 years. Due to the frequent puncture of the prosthesis for hemodialysis access, the pattern of healing is markedly different from that normally observed in ePTFE grafts in humans. The ePTFE graft material of the AV fistula was completely incorporated in fibrous tissue with prominent pseudointima formation (inner capsule), fibrous tissue within the graft and a well-adhered periadventitial layer (outer capsule). In the portion of the graft most frequently punctured, the wall of the graft was composed mainly of fibrous tissue containing dissociated fragments of ePTFE. Biochemical analysis of the fibrous tissue across the wall of the graft revealed that it contained types I, III, and V collagen, with type I greater than III greater than V. The type V collagen was present in largest percentage at the luminal surface and in decreasing percentage in the ePTFE material and outer capsule. This analysis suggests that collagen type deposition in this prosthesis occurs in a manner similar to a normal healing wound, except for the unusual pattern of type V collagen deposition, which may be an adaptive variation of the healing response.
Asunto(s)
Derivación Arteriovenosa Quirúrgica , Prótesis Vascular , Politetrafluoroetileno , Cicatrización de Heridas , Adulto , Colágeno/análisis , Glomerulonefritis/complicaciones , Glomerulonefritis/microbiología , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Masculino , Diálisis Renal , Infecciones Estreptocócicas/complicacionesRESUMEN
Radioisotopic, pH 6.8 assays were designed to measure hepatic cortisol sulfation in chickens, gerbils, and hamsters of both sexes. Enzyme levels with 40 microM cortisol were similar in males of all three species and due mostly to low Km enzymes with 10-30 microM cortisol Km's. Maximum enzyme activity in male chickens required 40 microM cortisol. In the other species, the much higher maximum enzyme activity observed required 500 microM cortisol owing to sulfotransferases with Km's for the hormone near 300 microM. Coenzyme 3'-phosphoadenosine-5'-phosphosulfate requirements also varied between species. Sex differences of the enzyme levels were found only in hamsters. There, males possessed only 24-33% of the enzyme levels found in females. Cortisol 21-sulfate was the reaction product in all of the species. Sexual dimorphism in hamsters appeared to be due to repressive effects of androgens. pH optima of enzyme activities in the three species ranged from pH 6 to 7. Routine use of pH 6.8 assays allowed representative interspecies comparisons. DEAE-Sephadex fractionation of cytosol showed that chicken liver contained mostly two enzymes with different pH optima that catalyzed cortisol sulfation. These differed from the enzymes that catalyzed dehydroepiandrosterone and estradiol sulfation. In the gerbil four enzymes with similar pH optima catalyzed cortisol sulfation. The second of these to elute from DEAE-Sephadex columns was the low Km form. In hamsters most glucocorticoid sulfotransferase activity appeared to be due to one enzyme. The molecular weights of the low Km gerbil enzyme and the main hamster enzyme were 98 300 +/- 6100 and 105 000 +/- 8100. Hamsters and gerbils responded to injection of cortisol by hepatic tyrosine aminotransferase induction.
Asunto(s)
Hígado/metabolismo , Esteroides/metabolismo , Sulfotransferasas , Sulfurtransferasas/metabolismo , Animales , Pollos , Cricetinae , Estradiol/farmacología , Femenino , Gerbillinae , Glucocorticoides/metabolismo , Masculino , Peso Molecular , Testosterona/farmacología , Tirosina Transaminasa/biosíntesisRESUMEN
The effects of ten drugs on hepatic glucocorticoid sulfotransferase activity (HGSTA) were examined in male rats. The enzyme activity per 100 g body weight was elevated 152, 94.9, 140, 140, 73.1, 63.9, 76.9, and 140% after administration of daily i.p. doses of 111 mg spironolactone/kg (6-10 days), 66.7 mg WIN-24540/kg (6-10 days), 150 mg metyrapone/kg (19-31 days), 33.3 mg pentachlorophenol/kg (9-16 days), 16.5 mg aspirin/kg (10-16 days), 90.5 mg alloxan/kg (23.27 days), 104 mg aminoglutethimide/kg (12-20 days), and 16.8 mg propranolol/kg (21-27 days). Shorter experimental periods or lower drug doses caused smaller effects on HGSTA. Most notably, spironolactone (111 mg/kg) and WIN-24540 (66.7 mg/kg) caused 50-75% elevation of HGSTA in 2 days. Effects of WIN-24540, aspirin and pentachlorophenol were due mostly to elevation of hepatic levels of sulfotransferase III (STIII), the glucocorticoid-preferring sulfotransferase of rat liver. Effects of the other test drugs were due to elevation of hepatic levels of sulfotransferases I and II (STI and STII), which much prefer dehydroepiandrosterone as substrate, but also catalyze glucocorticoid sulfation. Enzyme inhibition studies showed that the test drugs interacted with the HGSTA in vitro in a fashion that appeared to be related to the in vivo effects already described. None of the drugs interacted exclusively with STI, STII or STIII in vitro. However, some differences of the strengths of individual drug-sulfotransferase interactions were observed. The drug effects are discussed in relation to drug and glucocorticoid actions.
Asunto(s)
Hígado/enzimología , Sulfotransferasas , Sulfurtransferasas/análisis , Animales , Citosol/enzimología , Femenino , Técnicas In Vitro , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas F344 , Sulfurtransferasas/antagonistas & inhibidoresRESUMEN
The metabolism and intracellular compartmentalization of adenine nucleotides in a preparation of adult rat heart myocytes showing good morphology, viability, and tolerance to calcium ion has been examined by high performance liquid chromatography. These myocytes contain an average of 23 nmol adenine nucleotide per milligram protein which is about 60% of the adenine nucleotide content of intact rat heart tissue. The loss of adenine nucleotide occurs during the incubation and washing steps that increase the yield of viable cells, rather than during the collagenase perfusion. An analysis of cellular compartments shows that the adenine nucleotide of the cell consists of 17 nmol adenine nucleotide in the cytosol, 5 nmol in the mitochondria, and 1.3 nmol adenosine diphosphate bound to myofibrils per milligram cell protein. Myocytes lose both adenosine triphosphate and adenine nucleotide when incubated anaerobically in the absence of glucose, and the lost adenine nucleotide can be accounted for as increased inosine, adenosine, and inosine monophosphate. Myocytes that contain less than 0.1 nmol of cytosol adenosine triphosphate per milligram cell protein maintain an intact sarcolemma, but are unable to carry out anaerobic glycolysis. Reoxygenation of anaerobic cells results in restoration of energy charge and a net resynthesis of about 2 nmol adenine nucleotide per milligram protein. Adenosine and inosine monophosphate decrease on reaeration of anaerobic cells, whereas inosine levels increase. When iodoacetate is added to block glycolysis, the decline in adenine nucleotide and production of inosine monophosphate are accelerated and there is no resynthesis of adenine nucleotide when anaerobic cells are reoxygenated . Large accumulations of inosine monophosphate are also seen in myocytes treated with an uncoupler of oxidative phosphorylation.
Asunto(s)
Nucleótidos de Adenina/metabolismo , Miocardio/metabolismo , Adenosina Trifosfato/metabolismo , Aerobiosis , Anaerobiosis , Animales , Cromatografía Líquida de Alta Presión , Técnicas Histológicas , Masculino , Miocardio/análisis , Miocardio/citología , Miocardio/ultraestructura , Nucleótidos/análisis , Ratas , Distribución TisularRESUMEN
Routine ultrasonographic screening and examination of patients with and without specific symptoms of carotid artery disease now provides greater understanding of the natural history of the disease. In one year, 194 ulcers were detected, classified, and followed. No initially asymptomatic ulcer shallower than 2 mm later became asymptomatic, and it is than 2 mm later because asymptomatic, and it is concluded that a trial of antiplatelet therapy in these patients would be inconclusive. More than a third of the initially asymptomatic ulcers from 2 to less than 4 mm in depth gave rise to lateralizing symptoms that required surgery. The effects of antiplatelet therapy in this vulnerable population could be readily followed by ultrasonographic monitoring. All patients with ulcers 4 mm or more in depth were initially symptomatic and so required surgery.
Asunto(s)
Enfermedades de las Arterias Carótidas/diagnóstico , Ultrasonografía , Enfermedades de las Arterias Carótidas/cirugía , Endarterectomía , Humanos , Úlcera/diagnósticoRESUMEN
The use of expanded PTFE grafts as a vascular substitute has been well established. PTFE is an acceptable alternative for patients in whom the saphenous vein is unusable. Nonreinforced PTFE grafts do a better job of resisting infection, permitting cellular ingrowth, and allowing the development of a true neointima. During a 6 year period ending in April 1981, 129 grafts were placed in various positions. Most of these were placed primarily in the femoropopliteal position. One death occurred as a direct result of the surgery. Only two infections were encountered, both were delayed and patient-induced. There were no true aneurysms in the PTFE grafts of our patients. The use of smooth noncrushing clamps applied gently with just enough pressure to stop blood flow will lessen the likelihood of aneurysmal formation. Careful surgical technique can minimize problems. False aneurysm in vascular reconstruction can largely be prevented by the proper establishment of hemostasis at the suture line. Selection of an appropriate needle and suture along with the use of proper technique in their placement will help provide the best possible results. One should follow the curve of the needle at the time of suturing to help prevent elongation of the suture holes, which may contribute to difficulties in establishing hemostasis at the suture line. Thrombosis is the most common problem associated with the use of this graft; correction requires careful balloon catheter techniques. Salvage of the graft can be obtained by endarterectomy, patch grafting, or jump grafts so that the entire prosthesis does not have to be replaced.
Asunto(s)
Prótesis Vascular/efectos adversos , Politetrafluoroetileno , Complicaciones Posoperatorias/cirugía , Aneurisma/etiología , Aneurisma/cirugía , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/cirugía , Arteria Femoral/cirugía , Humanos , Arteria Poplítea/cirugía , Complicaciones Posoperatorias/prevención & control , Trombosis/etiología , Trombosis/cirugíaRESUMEN
Adult rat heart myocytes prepared by collagenase perfusion show a progressive loss of adenylate energy charge and total adenine nucleotide as a function of time of anaerobic incubation in the absence of glucose. Re-aeration of the rod-shaped anaerobic cells produces a population of viable rounded cells in hypercontracture. The round cells show extensive morphological dislocations but remain metabolically competent in that they 1) restore adenosine 5'-triphosphate levels to the extent permitted by the depleted adenine nucleotide pool: 2) reestablish a low Na+-K+ ratio; and 3) restore creatine phosphate to 73% of control. The hypercontracture on re-aeration of anaerobic myocytes closely resembles an analogous contracture of heart cells in situ produced when hypoxic perfused hearts are reoxygenated, the so-called "oxygen paradox." Both processes are eliminated by inclusion of glucose during the anaerobic phase and by inhibitors of respiration and uncouplers of oxidative phosphorylation added before reoxygenation. Mitochondria in the hypercontracted myocytes retain high acceptor control ratios. Contracture on re-aeration occurs to nearly the same extent in the presence of either mM Ca2+ or 0.1 mM EGTA. Contracture appears related to dislocations in intracellular Ca metabolism that result from the declining energy charge and depleted nucleotide pool produced during anoxic incubation.