RESUMEN
INTRODUCTION: In metropolitan France, nearly 20 new cases of leprosy are diagnosed each year. The incidence of tuberculosis in France is 8/100,000 inhabitants and there are very few accounts of association of these two mycobacteria. Herein we report a case of co-infection with borderline tuberculoid (BT) leprosy and disseminated tuberculosis diagnosed in metropolitan France. PATIENTS AND METHODS: A male subject presented with diffuse painless infiltrated erythematous plaques. The biopsy revealed perisudoral and perineural lymphohistiocytic epithelioid cell granuloma as well as acid-alcohol-fast bacilli on Ziehl staining. PCR was positive for Mycobacterium leprae, confirming the diagnosis of leprosy in the BT form. The staging examination revealed predominantly lymphocytic left pleural effusion, right-central necrotic adenopathy without histological granuloma, negative screening for BK, a positive QuantiFERON-TB™ test, and a positive intradermal tuberculin reaction. The clinical and radiological results militated in favour of disseminated tuberculosis. Combined therapy (rifampicin, isoniazid, ethambutol and pyrazinamide) together with clofazimine resulted in regression of both cutaneous and extra-cutaneous lesions. This rare co-infection combines leprosy, often present for several years, and tuberculosis (usually pulmonary) of subsequent onset. The pathophysiological hypothesis is that of cross-immunity (with anti-TB immunity protecting against subsequent leprosy and vice versa), supported by the inverse correlation of the two levels of prevalence and by the protection afforded by tuberculosis vaccination. In most cases, treatment for TB and leprosy improves both diseases. Patients presenting leprosy should be screened for latent tuberculosis in order to avoid reactivation, particularly in cases where corticosteroid treatment is being given.
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Lepra Dimorfa , Lepra Tuberculoide , Lepra , Tuberculosis , Humanos , Lepra Dimorfa/diagnóstico , Lepra Dimorfa/tratamiento farmacológico , Lepra Tuberculoide/diagnóstico , Lepra Tuberculoide/tratamiento farmacológico , Masculino , Mycobacterium leprae , PielRESUMEN
We analyzed women and newborn outcome after maternal exposure to BPs. BPs have no teratogenic effect on the 36 analyzed pregnancies compared to unexposed controls matched on women underlying diseases (either systemic disease, either "bone" disease) but some outcome differed: neonatal complications rate in systemic diseases and live birth rate in bone diseases). INTRODUCTION: The effect of bisphosphonates (BPs) during pregnancy remains unclear. We aimed to study pregnancy outcomes in women exposed to BPs during pregnancy. METHODS: Data for cases and controls were from the French Reference Centre of Teratogenic Agents. Cases were women who received BPs in the 6 weeks before or during a pregnancy and had systemic or bone diseases. We included two respectively matched control groups: women with systemic diseases not exposed to BPs and healthy women not exposed to BPs or any teratogenic agent. Four controls were assigned to each case. RESULTS: Thirty-six women were exposed to BPs including 5 just before pregnancy and 30 during the first trimester; 23 had systemic diseases (systemic lupus erythematosus, n = 5; rheumatoid arthritis, n = 5; other, n = 13) and 13 had bone diseases. Rate of observed congenital malformations did not differ in women with a systemic or a bone disease compared to their respective controls (respectively 2/23 [8.7%] vs 2/92 [2.2%], p = 0.178 and 0/13 [0%] vs 0/52 [0%], p = 1.00). Among women with systemic diseases, non-specific neonatal complications were more frequent for cases (4/16 [25.0%] vs 4/64 [6.3%], p = 0.027). Among women with bone disorders, the live birth rate was lower for cases than healthy controls (8/10 [80%] vs 50/50 [100%], p = 0.025). CONCLUSION: We found no major teratogenic effects of BPs, but rates of neonatal complications were increased for women with systemic diseases, as were spontaneous abortions for women with bone diseases likely linked to the severity of the underlying diseases and concomitant medications.
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Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Osteoporosis/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Adulto , Conservadores de la Densidad Ósea/uso terapéutico , Estudios de Casos y Controles , Anomalías Congénitas/etiología , Bases de Datos Factuales , Difosfonatos/uso terapéutico , Femenino , Humanos , Recién Nacido , Intercambio Materno-Fetal , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamenteRESUMEN
Acute cholangitis is an infection of the bile and biliary tract which in most cases is the consequence of biliary tract obstruction. The two main causes are choledocholithiasis and neoplasia. Clinical diagnosis relies on Charcot's triad (pain, fever, jaundice) but the insufficient sensitivity of the latter led to the introduction in 2007 of a new score validated by the Tokyo Guidelines, which includes biological and radiological data. In case of clinical suspicion, abdominal ultrasound quickly explores the biliary tract, but its diagnostic capacities are poor, especially in case of non-gallstone obstruction, as opposed to magnetic resonance cholangiopancreatography and endoscopic ultrasound, of which the diagnostic capacities are excellent. CT scan is more widely available, with intermediate diagnostic capacities. Bacteriological sampling through blood cultures (positive in 40% of cases) and bile cultures is essential. A wide variety of bacteria are involved, but the main pathogens having been found are Escherichia coli and Klebsiella spp., justifying first-line antimicrobial therapy by a third-generation cephalosporin. Systematic coverage of Enterococcus spp. and anaerobic infections remains debated, and is usually recommended, in case of severity criteria for Enterococcus severity levels, or anaerobic bilio-digestive anastomosis for anaerobes. Presence of a biliary stent is the only identified risk-factor associated with infections by multidrug-resistant pathogens. Along with antimicrobial therapy, endoscopic or radiological biliary drainage is a crucial management component. Despite improved management, mortality in cases of acute cholangitis remains approximately 5%.
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Colangitis/diagnóstico , Colangitis/terapia , Dolor Abdominal/etiología , Enfermedad Aguda , Algoritmos , Antibacterianos/uso terapéutico , Sistema Biliar/diagnóstico por imagen , Colangiopancreatografia Retrógrada Endoscópica , Colangitis/etiología , Colestasis/terapia , Drenaje , Fiebre/etiología , Humanos , Ictericia/etiología , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
The active transport of oxidized glutathione and glutathione S-conjugates has been demonstrated for the first time in erythrocytes and this cell remained the main subject of research on the "glutathione S-conjugate pump" for years. Further studies identifled the "glutathione S-conjugate pump" as multidrug resistance-associated protein (MRP). Even though cells overexpressing MRP and isolated MRP provide useful information on MRP structure and function, the erythrocyte remains an interesting model cell for studies of MRP1 in its natural environment, including the substrate specificity and ATPase activity of the protein.
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Transportadoras de Casetes de Unión a ATP/sangre , Eritrocitos/metabolismo , Aniones/sangre , Proteínas Portadoras/sangre , Resistencia a Múltiples Medicamentos , Glutatión/análogos & derivados , Glutatión/sangre , Disulfuro de Glutatión/sangre , Humanos , Técnicas In Vitro , Transporte Iónico , Cinética , Proteínas de Transporte de Membrana , Modelos Biológicos , Proteínas Asociadas a Resistencia a Múltiples MedicamentosRESUMEN
Upper Silesian Industrial Zone (Katowice Voivodship, Poland), the country most industrialized and densely populated region is well recognized for the magnitude of environmental problems. Due to local lead mining and processing environmental exposure to lead is considered one of the most important hazards to the health of children. In the past, clinically confirmed cases of lead intoxication in children have been found and recent blood lead monitoring in major point source impact areas have documented increased blood lead concentration in children. However, much less is known about blood lead concentrations in general population of children who are exposed to increased levels of lead in ambient and soil. The study was undertaken in order to estimate the mean blood lead concentration (PbB) and its range in children aged seven years residing in urban non-point source impact area of Katowice Voivodship, and to examine potential determinants of increased blood lead concentration in these children. In a systematic sample of 431 children aged 7 years (208 girls and 223 boys), living in two large cities in the centre of Upper Silesian Industrial Zone the geometric mean and standard deviation of PbB was 7.94 +/- 1.48 micrograms/dl (range 4.0-38.0 micrograms/dl) and did not depend on sex or the city of residence. PbB equal to or larger than 15 micrograms/dl was found in 8.1% of children and PbB equal to or larger than 10 micrograms/dl in 27.4% of children. Blood lead concentration was associated with a number of factors that could be classified as family factors, housing and environmental factors. The identified risk factors add credibility to suggested directions of preventive measures that should extend beyond already implemented lead emission control in the industry and involve increased use of unleaded gasoline, upgrading of housing conditions and promotion of proper hygienic standards on a household level. The findings of the study indicate that children living in urban area of Upper Silesian Industrial Zone are at risk of overexposure to lead in environment, and justify the implementation of population-based screening program targeting children in younger age groups in the region.
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Protección a la Infancia , Contaminantes Ambientales/sangre , Plomo/sangre , Salud Urbana , Contaminación del Aire/efectos adversos , Distribución de Chi-Cuadrado , Niño , Demografía , Femenino , Humanos , Intoxicación por Plomo/epidemiología , Modelos Logísticos , Masculino , Polonia/epidemiología , Valores de Referencia , Características de la Residencia , Factores de RiesgoRESUMEN
In 1996 a Committee for antibiotic resistance surveillance in Croatia was founded by the Croatian Academy of Medical Sciences. In this study antibiotic surveillance results for the period June 1-December 31, 1997 from 12 microbiology laboratories throughout Croatia are presented. Sensitivity to antibiotics was determined by disk diffusion method for the following bacteria: Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus spp., Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa. In general, high proportion of resistant isolates was recorded throughout Croatia, although some regional variations were noticed. Mean resistance of pneumococci to penicillin was 38%, in S. aureus resistance to methicillin was 47%, and 3rd generation cephalosporin-resistance in E. coli was 6% and in Klebsiella spp. 21%. In P. aeruginosa resistance to gentamicin averaged 50%, to imipenem 13% and to ceftazidim 8%. Future aims of the Committee are to continue routine antibiotic resistance surveillance during certain periods every year, and to estimate clinical significance of resistant bacteria, detect mechanisms of resistance and improve the quality of laboratory work through education and quality control projects.
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Farmacorresistencia Microbiana , CroaciaAsunto(s)
Artritis/diagnóstico , Disnea/diagnóstico , Eritema/diagnóstico , Pancreatitis Alcohólica/diagnóstico , Paniculitis/diagnóstico , Anciano , Tobillo , Artritis/complicaciones , Diagnóstico Diferencial , Disnea/complicaciones , Eritema/complicaciones , Humanos , Masculino , Pancreatitis Alcohólica/complicaciones , Paniculitis/complicaciones , SíndromeRESUMEN
Heart muscle ischemia-reperfusion provokes a pronounced cardiomyocyte oxidative stress. In the present study, we examined a possible protective effect of the cardioprotective drug, 2,3-butanedione monoxime (BDM), on the cultured neonatal cardiac myocytes exposed to oxidative stress induced by hypochlorous acid (HOCl), that may be formed by activated polymorphonuclear neutrophils in myocardium ischemic-reperfusion areas, and a useful model oxidant, tert-butyl hydroperoxide (tBHP). Using isolated rat cardiomyocytes substantial cytotoxicity of HOCl and tBHP was demonstrated: The concentrations of HOCl and tBHP causing a 50% decrease of cardiomyocyte cell viability were estimated to be 55 +/- 5 microM and 36 +/- 6 microM, respectively. The cell viability measured immediately after the tBHP oxidative treatment was significantly higher than that measured after 22 h of cell post-incubation in a fresh culture medium. This showed delayed cell death after removing tBHP. Hypochlorous acid treatment of cardiomyocytes did not change cellular viability during the cellular post-incubation in a fresh medium. Even a long-term (22 h) incubation of oxidatively damaged cardiomyocytes with BDM (5 mM) added after the HOCl removal did not recover the viability of the HOCl-exposed cells. In the presence of BDM, the cytotoxicity of HOCl significantly increased probably due to a direct reaction of both compounds and toxic chlorinated derivative formation. 2,3-Butanedione monoxime (5 mM) did not reduce cytotoxicity of tBHP, either. Such well-known antioxidative agents as melatonin or glutathione considerably prevented oxidant-induced cell death in a concentration-dependent manner.
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Diacetil/análogos & derivados , Inhibidores Enzimáticos/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Animales Recién Nacidos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Diacetil/farmacología , Ácido Hipocloroso/toxicidad , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/citología , Soluciones Preservantes de Órganos/farmacología , Oxidantes/toxicidad , Ratas , terc-Butilhidroperóxido/toxicidadRESUMEN
Uncouplers of mitochondrial oxidative phosphorylation, dinitrophenol (DNP) and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), were found to stimulate Mg(2+)-ATPase activity of human erythrocyte membranes in a manner competitive with respect to 2,4-dinitrophenyl-S-glutathione (DNP-SG) which suggested that these compounds may also be substrates of the glutathione-S-conjugate pump. We confirm that the stimulation of erythrocyte membrane ATPase activity by DNP and by another uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), is competitive with respect to DNP-SG. However, we found no evidence for active transport of DNP and CCCP out of erythrocytes and demonstrate that they inhibit the low-affinity component of DNP-SG transport noncompetitively while stimulating the high-affinity DNP-SG transport (mediated by multidrug resistance-associated protein, MRP1). Implications of these findings may indicate the electrogenic nature of MRP1-mediated transport of glutathione-S conjugates and stimulation of aminophospholipid translocase (flippase) rather than the glutathione-S-conjugate pump by the uncouplers.
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Adenosina Trifosfatasas/metabolismo , Eritrocitos/metabolismo , Glutatión/análogos & derivados , Mitocondrias/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Eritrocitos/ultraestructura , Glutatión/metabolismo , Humanos , Fosforilación OxidativaRESUMEN
Erythrocyte membrane Mg(2+)-ATPase activity was stimulated by echinocytogenic agents (2,4-dinitrophenol and salicylate), a stomatocytogenic agent Triton X-100 and other membrane-disturbing agents including hydrophobic organic anions, alcohols and detergents. Various possible mechanisms of the stimulation are possible but apparently most probable one consists in induction of membrane phospholipid scrambling by the compounds studied (as demonstrated for DNP) and of aminophospholipid translocase (flippase) activity.
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ATPasa de Ca(2+) y Mg(2+)/metabolismo , Dinitrofenoles/farmacología , Membrana Eritrocítica/enzimología , 2,4-Dinitrofenol , Membrana Celular/efectos de los fármacos , Membrana Eritrocítica/efectos de los fármacos , Humanos , Cinética , Octoxinol/farmacologíaRESUMEN
Curcumin is a well-known natural compound with antiinflammatory properties. Its antiproliferative effect and ability to modulate apoptotic response are considered essential in cancer therapy. The physicochemical properties of curcumin suggest membranous localization, which prompted an investigation of the mechanisms of membrane disturbances evoked by curcumin. We chose the erythrocyte as a convenient model for studying membrane effects of curcumin and showed its nonspecific, apoptosis-independent way of action. Curcumin was found to expand the cell membrane, inducing echinocytosis. Changes in cell shape were accompanied by transient exposure of phosphatidylserine. Membrane asymmetry was recovered by the action of aminophospholipid translocase, which remained active in the presence of curcumin. Lipids rearrangements and drug partitioning caused changes of lipid fluidity. Such nonspecific effects of curcumin on cellular membranes would produce artifacts of apoptosis measurement, since several methods are based on membrane changes.
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Apoptosis , Curcumina/farmacología , Membrana Eritrocítica/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Proteínas de Transferencia de Fosfolípidos , Adulto , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/farmacología , Coagulación Sanguínea/efectos de los fármacos , Proteínas Portadoras/metabolismo , Tamaño de la Célula/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Membrana Eritrocítica/metabolismo , Eritrocitos/citología , Eritrocitos/metabolismo , Citometría de Flujo , Humanos , Metabolismo de los Lípidos , Fluidez de la Membrana/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Fragilidad Osmótica/efectos de los fármacos , Fosfatidilserinas/farmacología , Temperatura , Factores de TiempoRESUMEN
Isolated hepatocytes appear to be a suitable in vitro model for the testing of the efficacy of chelating agents. In this study hepatocytes were isolated from rats exposed to CdCl2 (50 mg Cd2+/l) in drinking water for 3 months. The cells were incubated in a Krebs-Henseleit buffer for 2 hrs and the cytotoxicity was assessed using 5 types of parameters. N-benzyl-D-glucaminedithiocarbamate (BGDTC) and meso-2,3-dimercaptosuccinic acid (DMSA) were tested. Individual chelators in various concentrations were added to the incubation medium at the beginning of the experiment (t = 0). The concentration of Cd in the extracellular fluid was measured every 30 mins using flame AAS. Exposed hepatocytes did not show the signs of damage. Both chelators did not exhibit any cytotoxic effect. BGDTC was found to be efficient in the mobilization of Cd, while DMSA was ineffective.
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Intoxicación por Cadmio/sangre , Cadmio/farmacocinética , Terapia por Quelación , Hígado/efectos de los fármacos , Sorbitol/análogos & derivados , Succímero/farmacología , Tiocarbamatos/farmacología , Animales , Células Cultivadas , Hígado/metabolismo , Ratas , Ratas Endogámicas , Sorbitol/farmacologíaRESUMEN
Molecular masses of functional units of two components of 2, 4-dinitrophenyl-S-glutathione (DNP-SG) transport across the erythrocyte membrane determined by radiation inactivation were 437 +/- 69 kDa for the high-affinity component and 466 +/- 67 kDa for the low-affinity component. These results confirm that the multidrug resistance-associated protein (MRP) 1 is responsible for the high-affinity DNP-SG transport across the erythrocyte membrane and suggest that MRP1 exists in the membrane as a dimer. The molecular size of the low-affinity transporter is similar if not identical to that of MRP1. Moreover, while the molecular mass of the DNP-SG-ATPase activity of the erythrocyte membrane corresponds also to that of MRP (375 +/- 36 kDa), the molecular mass of the functional unit of dinitrophenol-stimulated ATPase is significantly lower (232 +/- 26 kDa), which suggests that thisactivity is linked to a different protein, perhapsaminophospholipid translocase.
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Transportadoras de Casetes de Unión a ATP/química , Membrana Eritrocítica/química , 2,4-Dinitrofenol/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfatasas/metabolismo , Adulto , Transporte Biológico/efectos de la radiación , Dimerización , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/efectos de la radiación , Glutatión/análogos & derivados , Glutatión/metabolismo , Humanos , Técnicas In Vitro , Proteínas Asociadas a Resistencia a Múltiples MedicamentosRESUMEN
A hypothesis of the flippase nature of the glutathione S-conjugate transport is presented. Experimental premises for this hypothesis include interaction of glutathione S-conjugates with the membrane, as demonstrated by their effects on membrane fluidity, quenching of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene fluorescence and induction of echinocytosis by 2,4-dinitrophenyl-S-glutathione (DNP-SG). This hypothesis can rationalize, i. a., observations of the enhancement of DNP-SG transport by butanol and stimulation of erythrocyte membrane Mg(2+)-ATPase activity by albumin-coupled DNP-SG.
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Proteínas Portadoras/sangre , Proteínas de la Membrana/sangre , Proteínas de Transferencia de Fosfolípidos , 1-Butanol/farmacología , Transporte Biológico/efectos de los fármacos , ATPasa de Ca(2+) y Mg(2+)/sangre , Tamaño de la Célula/efectos de los fármacos , Dinitrofenoles/sangre , Dinitrofenoles/farmacología , Membrana Eritrocítica/enzimología , Glutatión/análogos & derivados , Glutatión/sangre , Glutatión/farmacología , Humanos , Proteínas de Transporte de Membrana , Albúmina Sérica Bovina/farmacologíaRESUMEN
Pig erythrocyte membrane Mg2+-ATPase activity was stimulated by various glutathione S-conjugates. For alkyl S-conjugates, the Km for the stimulation was lower, the more hydrophobic was the conjugate. 2,4-Dinitrophenyl-S-(N-acetyl)cysteine also stimulated the Mg2+-ATPase activity, suggesting a low specificity of the ¿glutathione S-conjugate pump¿. The Km values for the stimulation by 2,4-dinitrophenyl conjugates were lower than predictable on the basis of hydrophobicity which indicates a high affinity of the transporter for these conjugates.