RESUMO
Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the -675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the -675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The -675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81-3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62-4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31-2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84-3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the -675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.
Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Adolescente , Adulto , Alelos , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Doença Crônica/tratamento farmacológico , Doença Crônica/epidemiologia , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Dislipidemias/epidemiologia , Dislipidemias/genética , Feminino , Frequência do Gene , Hematócrito , Hemoglobinas/análise , Heterozigoto , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/genética , Polimorfismo de Fragmento de Restrição , Prednisona/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: It was not until the advent of endoscopic retrograde cholangiopancreatography (ERCP) that Oddi's sphincter manometry was performed directly. Use of opioids for the intravenous (IV) sedation of these patients is controversial. OBJECTIVE: To evaluate with manometry the effect of fentanyl at different doses as well as the effect of butylhyoscine on the rabbit's Oddi's sphincter. METHODS: This is an experimental, randomized, double-blind study conducted in New Zealand rabbits distributed in 4 groups (control, fentanyl at doses of 1, 5 and 10 µg/kg of weight) that, after laparotomy and duodenotomy, underwent direct Oddi's sphincter manometry. The analyzed variables included sphincter pressure, wave frequency, amplitude and duration. RESULTS: The baseline measurements of the study variables did not show any differences among the groups. The administration of fentanyl at 1 µg/kg reduced Oddi's sphincter pressure compared with the baseline value (p = 0.003), while the doses of 5 and 10 µg/kg significantly increased it (p <0.0001). Butylhyoscine decreased the sphincter pressure, frequency, amplitude and duration of the waves in all the groups and antagonized the increase in pressure produced by fentanyl. CONCLUSIONS: Fentanyl at 1 µg/kg of body weight relaxes the rabbit's Oddi's sphincter and butylhyoscine can antagonize the increased pressure of the sphincter caused by fentanyl at 5 and 10 µg/kg of weight. These finding suggest a potential beneficial for the ERCP in clinical controlled trials in humans.
Assuntos
Analgésicos Opioides/farmacologia , Sedação Consciente/métodos , Fentanila/farmacologia , Manometria/métodos , Antagonistas Muscarínicos/farmacologia , Escopolamina/farmacologia , Esfíncter da Ampola Hepatopancreática/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Fentanila/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Relaxamento Muscular/efeitos dos fármacos , Coelhos , Escopolamina/administração & dosagemRESUMO
We studied whether mitochondrial functions and Ca2+ metabolism were altered in Wistar Kyoto normotensive (WKY) and spontaneous hypertensive rats (SHR). Ca2+ uptake was decreased in SHR compared to WKY rats. Accumulation of Ca2+ was more efficient in WKY than in SHR rats. mDeltaPsi was lower in SHR compared to WKY rats. Basal complex IV activity was higher in SHR than WKY rats, whereas basal L-citrulline production, an indicator of nitric oxide synthesis, was decreased in SHR and dependent on Ca2+ concentration (p<0.05). Impact of Ca2+ was counteracted by EGTA. These data show an age-dependent decreased mitochondrial functions in brain mitochondria during hypertension.
Assuntos
Envelhecimento/metabolismo , Cálcio/metabolismo , Cálcio/farmacologia , Hipertensão/metabolismo , Mitocôndrias/metabolismo , Animais , Encéfalo/ultraestrutura , Citrulina/análise , Citrulina/biossíntese , Ácido Egtázico/farmacologia , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/genética , Óxido Nítrico Sintase/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Especificidade da Espécie , Espectrometria de Fluorescência , Fatores de TempoRESUMO
Objetivos: determinar la mobimortalidad de los pacientes ≤ 5 años de edad, ingresados en la unidad de cuidados intensivos pediátricos (UCIP), en relación al estado nutricional de los mismos. Estudio de cohorte, prospectivo. Pacientes con edad ≤ 5 años que ingresaron a la UCIP de enero a noviembre de 2003. Fueron excluidos los recién nacidos, pacientes con antecedentes de prematurez, enfermedad crónica, malformaciones congénitas y con edema al ingreso. El estado nutricional se evaluó a través del sistema Epi nut. Se utilizó el score z P/E para los niños 0,05.Las IN fueron similar en los MNG 30% vs EU 19% RR=1,6(IC 95% 0,6 û 4) p> 0,05.Los desnutridos severos tuvieron significativamente mas IN nososcomiales (56%) comparando con los EU por un lado y resto de la cohorte estudiada. El promedio de días de internación fue de 6,7±4 en los EU y de 8,7±5 en lso MNG p>0,05.Sin embargo fue significativamente mayor en los DS (11,8±6) comparado con el EU y el resto de la cohorte .La mortalidad fue similar en los EU y los MNG 12% vs 32% respectivamente p>0,05.Sin embargo los DN tuvieron una mortalidad de 78% vs 12% de los EU RR=7 (IC95% 2-20) p< 0,001 y 78% vs 17% resto de la cohorte RR=4,5 (IC95% 2,4.8,8) p< 0,001. Los DS tuvieron más frecuentemente IN, mas de días de internación y mayor mortalidad comparados con los EU y con el resto de la cohorte (EU y otros grupos de mal nutridos).
Assuntos
Desnutrição , Desnutrição/mortalidade , Estado Nutricional , Unidades de Terapia Intensiva PediátricaRESUMO
A 1999 ordinance by the Government of Mexico City bans 1993 model-year vehicles from on-road operation if their catalytic converters are not replaced with new ones. To validate the benefits of this action, we examined three issues related to exhaust emissions of vehicles equipped with catalytic converters. After selecting representative fleets of in-use vehicles, a comparison between emissions and catalyst efficiency in cars with two categories of exhaust emission limits was carried out. For that purpose, two fleets were selected, each made up of 10 vehicles run under similar conditions. A third, larger fleet with emissions control systems was used to evaluate and simulate real-world conditions of vehicles in a controlled laboratory. Finally, the aging effect on the catalytic converter was studied on vehicles run for 100,000 km, replacing their old emission control devices for new ones. The 1991-1992 model-year vehicles showed a high percentage of compliance with the corresponding emissions standard (90%) in comparison with 1993 model-year and later vehicles (Tier 0). However, NOx emissions were higher for the newer vehicles. Fifty percent of the 1991-1992 model-year vehicles evaluated under the official inspection/maintenance (I/M) procedure did not meet the regulated emissions standard when the results were compared with those of the U.S. Federal Test Procedure FTP-75. Our results suggest that the replacement of old catalytic converters with new ones will have little effect on decreasing polluting emissions because these vehicles were in very bad mechanical condition. Results of catalytic activity as a function of mileage indicated inefficient catalyst performance for the fleets tested. All pollutant conversions were below 90% efficiency, and they deteriorated by an average of 30% after the vehicles were run for 100,000 km.
Assuntos
Poluição do Ar/prevenção & controle , Veículos Automotores , Emissões de Veículos , Poluentes Atmosféricos/análise , Catálise , Desenho de Equipamento , Humanos , México , População UrbanaRESUMO
In this work, the primary objective was to assess the impact of oxygenated fuel on the exhaust emissions from an important fraction of vehicles in the Metropolitan Area of Mexico City (MAMC). The results aim to provide information on the actual effect of MTBE on a fleet that represents more than 60% of the in-use vehicles in the MAMC. Ten vehicles were tested with a low-octane base gasoline, and 10 more with a regular-grade unleaded base gasoline. Three MTBE concentrations, 5, 10, and 15 vol %, were tested following the U.S. Federal Test Procedure (FTP). CO, total HC, and NOx from the exhaust gases were quantitatively evaluated and also characterized for FTP speciated organic emissions. From this data, the O3-forming potential of the fuels was calculated. Results show that for the fleet using low-octane gasoline, the addition of 10% MTBE substantially reduced CO emissions, but total HC concentration in the exhaust showed a modest decrease. For the regular gasoline, the 10% MTBE blend seemed to be the best choice, but there was not a significant decrease in emissions. The specific reactivity of each fuel, expressed in grams of O3 per gram of nonmethane organic gases, increased with MTBE concentration in both cases. This result is important to consider, especially for a region like Mexico City, which has high atmospheric O3 concentrations.
Assuntos
Poluentes Atmosféricos/análise , Éteres Metílicos/análise , Veículos Automotores , Ozônio/análise , Emissões de Veículos/análise , Poluentes Atmosféricos/química , Gasolina , Humanos , Éteres Metílicos/química , México , Saúde Pública , População UrbanaRESUMO
The environmental agency in the metropolitan area of Mexico City has launched a program to introduce more energy-efficient modes of transport, one of which is the use of alternative and less polluting fuels. With the perspective in mind, a liquefied petroleum gas (LPG) fleet of vehicles is exempt of the mandatory "one day without a car" program if the emission of pollutants is below the standard authorized for that specific purpose. Today, about 28,000 light-duty vehicles and heavy-duty trucks circulate in the area, most of them as aftermarket converted vehicles. In this work, we evaluated regulated exhaust emission and other parameters on 134 representative vehicles of that fleet. From the data obtained, an estimate of emission factors and their contribution to the global emission in the metropolitan area is provided. It is concluded that more than 95% of the in-use vehicles using LPG presented regulated emissions which exceeded in one or more the environmental regulations values required for certification. The poor maintenance of the vehicles and the type of conversion kit installed could be the culprits of the results obtained.
Assuntos
Poluição do Ar/prevenção & controle , Combustíveis Fósseis , Emissões de Veículos/análise , MéxicoRESUMO
The relationship between aflatoxins and liver cancer is well established. In addition the inhalation exposure to carcinogen aflatoxin B1 (AFB 1) is considerable. Genotoxic chemical is known to react with DNA either directly or after metabolic activation to form adducts, a step thought to be relevant with respect to chemical carcinogenesis. The presence and the amount of specific DNA adducts provide a good indication of chemical exposure and genetic damage resulting the exposure to carcinogens and account for same of factors affecting individual susceptibility to cancer. Analysis of DNA adducts requires that the sensitivity of the methods to be sufficient high to allow detection of about 1 adduct/109 normal nucleotides. Most suitable method is based in physiochemical technique such as HPLC. Because circumstantial epidemiological evidence suggests that AFB1 inhalation may cause primary lung cancer. We investigate AFB1 by HPLC in three different tobacco sources, and in 39 patients with compatible lung cancer or chronic bronchitis. The patients were divided by clinical manifestations in lung cancer (n: 25) and chronic bronchitis (n: 14). Twenty-three of 25 patients presented epidermoid lung cancer within smoking habit, and 2 of 25 presented adenocarcinoma without smoking habit. In chronic bronchitis group 12 of 14 cases presented smoking habit. The control PBS liquid was negative to AFB1; the different tobacco sources, a) Virginia of Jujuy, b) Brasilero and c) black of Salta presented AFB1 positive determinations respectively. The bronchial tissues obtained by lung biopsies presented positive AFB1 in lung epidermoid cancer at 0.68 +/- 0.82 mg/L. The adenocarcinoma presented AFB1 negative determinations. In chronic bronchitis patients with smoking habit (n: 12) presented AFB1 positive with a level less than the epidermoid lung cancer group, 0.21 +/- 0.109 mg/L, p < .025.
Assuntos
Adenocarcinoma/química , Aflatoxina B1/análise , Bronquite/induzido quimicamente , Carcinoma de Células Escamosas/química , Neoplasias Pulmonares/química , Nicotiana/química , Plantas Tóxicas , Adenocarcinoma/induzido quimicamente , Adulto , Aflatoxina B1/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma de Células Escamosas/induzido quimicamente , Distribuição de Qui-Quadrado , Doença Crônica , Feminino , Humanos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Pessoa de Meia-IdadeRESUMO
The relationship between aflatoxins and liver cancer is well established. In addition the inhalation exposure to carcinogen aflatoxin B1 (AFB 1) is considerable. Genotoxic chemical is known to react with DNA either directly or after metabolic activation to form adducts, a step thought to be relevant with respect to chemical carcinogenesis. The presence and the amount of specific DNA adducts provide a good indication of chemical exposure and genetic damage resulting the exposure to carcinogens and account for same of factors affecting individual susceptibility to cancer. Analysis of DNA adducts requires that the sensitivity of the methods to be sufficient high to allow detection of about 1 adduct/109 normal nucleotides. Most suitable method is based in physiochemical technique such as HPLC. Because circumstantial epidemiological evidence suggests that AFB1 inhalation may cause primary lung cancer. We investigate AFB1 by HPLC in three different tobacco sources, and in 39 patients with compatible lung cancer or chronic bronchitis. The patients were divided by clinical manifestations in lung cancer (n: 25) and chronic bronchitis (n: 14). Twenty-three of 25 patients presented epidermoid lung cancer within smoking habit, and 2 of 25 presented adenocarcinoma without smoking habit. In chronic bronchitis group 12 of 14 cases presented smoking habit. The control PBS liquid was negative to AFB1; the different tobacco sources, a) Virginia of Jujuy, b) Brasilero and c) black of Salta presented AFB1 positive determinations respectively. The bronchial tissues obtained by lung biopsies presented positive AFB1 in lung epidermoid cancer at 0.68 +/- 0.82 mg/L. The adenocarcinoma presented AFB1 negative determinations. In chronic bronchitis patients with smoking habit (n: 12) presented AFB1 positive with a level less than the epidermoid lung cancer group, 0.21 +/- 0.109 mg/L, p < .025.
RESUMO
In the present paper, we report that an inositolphosphoglycan (IPG), derived from a Trypanosoma cruzi glycoinositolphosphoceramide (LPPG), is able to inhibit ACTH-mediated accumulation of a glucocorticoid, cortisol, in calf adrenocortical cells. This IPG is also able to inhibit the stimulation by ACTH of the production of the main glucocorticoid, corticosterone and the main mineralocorticoid, aldosterone, in rat adrenocortical cells. Nitrous acid deamination confirmed that IPG is responsible for this inhibition. In order to study the involvement of glycosylphosphatidylinositol (GPI) in ACTH response in rat adrenal cortex, the activation of a phospholipase that hydrolyzes GPI (GPI-PLC) was evaluated. It was found that the release of alkaline phosphatase, a GPI-anchored enzyme, to the extracellular medium is increased in rat adrenocortical cells by ACTH treatment. In addition, ACTH stimulates the release of ceramide from the glycoinositolphosphoceramide purified from T. cruzi. These data suggest that ACTH activates a GPI-PLC in rat adrenal cortex, which is in agreement with our previous data in calf adrenocortical cells; thus, the hydrolysis of GPI provoked by ACTH takes place in different mammals and the IPG released could inhibit ACTH-mediated synthesis of aldosterone, corticosterone and cortisol.
Assuntos
Córtex Suprarrenal/efeitos dos fármacos , Hormônio Adrenocorticotrópico/farmacologia , Glucocorticoides/biossíntese , Mineralocorticoides/biossíntese , Oligossacarídeos/farmacologia , Fosfolipases Tipo C/metabolismo , Córtex Suprarrenal/metabolismo , Aldosterona/biossíntese , Animais , Bovinos , Corticosterona/biossíntese , Ativação Enzimática/efeitos dos fármacos , Glicolipídeos/química , Glicolipídeos/metabolismo , Glicosilfosfatidilinositol Diacilglicerol-Liase , Hidrocortisona/biossíntese , Fosfatos de Inositol/química , Fosfatos de Inositol/metabolismo , Masculino , Fosfatidilinositol Diacilglicerol-Liase , Polissacarídeos , Ratos , Ratos Sprague-Dawley , Trypanosoma cruzi/químicaRESUMO
In this paper, we studied the effect of heme availability on corticosterone and aldosterone synthesis in rat adrenal. We found that hemin stimulated corticosterone and aldosterone production in adrenal homogenates in a dose-dependent fashion. Hemin administration to rats also provoked an increase in both corticosterone and aldosterone content in adrenal. 3,5-Diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC), an inhibitor of liver ferrochelatase activity, was able to inhibit this enzyme in rat adrenal. This resulted in an impairment of heme concentration and consequently adrenal ALA-synthase and porphyrin content were increased. Thus, it was proven that DDC inhibits heme biosynthesis in adrenal as it does in liver. In vivo experiments with rats showed that DDC was able to partially blocked ACTH-mediated corticosterone and aldosterone production while hemin administration was able to partially restore it. These data indicate that heme availability affects steroid biosynthesis in rat adrenal.
Assuntos
Glândulas Suprarrenais/metabolismo , Aldosterona/biossíntese , Corticosterona/biossíntese , Heme/metabolismo , 5-Aminolevulinato Sintetase/metabolismo , Glândulas Suprarrenais/efeitos dos fármacos , Hormônio Adrenocorticotrópico/farmacologia , Animais , Desoxicorticosterona/metabolismo , Dicarbetoxi-Di-Hidrocolidina/farmacologia , Ferroquelatase/efeitos dos fármacos , Ferroquelatase/metabolismo , Hemina/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Porfirinas/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The aim of this work was to compare the benefits and problems of low molecular weight heparin use in chronic hemodialysis, compared to conventional heparin. We studied 35 patients that received low molecular weight heparine (Enoxaparine, molecular weight 4000) during 115 consecutive hemodialysis procedures and conventional heparin during the subsequent 35 procedures. We assessed the heparin dose, partial thromboplastin time before dialysis and at 3 and 120 min during the procedure, arterio-venous fistula compression time, clot formation in the circuit and residual volume of filters. Median total dose of conventional heparin was 6289 U (range 3000-10000) compared to 5555 U (range 2000-8000) of low molecular weight heparin. When the dose was calculated per kg of body weight, it was lower for low molecular weight heparin than for conventional heparin (87.8 U (range 33-100) vs 100 U (range 50-176). Partial thromboplastin time achieved was lower with low molecular weight heparin, compared with conventional heparin, at 3 (64.26 vs 125.2 sec) and 120 min (39.1 vs 84.45 sec). Clot formation, arteriovenous fistula compression time and residual volume of filters were similar for both types of heparin. It is concluded that a single dose of low molecular weight heparin simplifies anticoagulation during hemodialysis, modifies less the partial thromboplastin time and does not alter filter re-utilization