CtpB is a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis.

BACKGROUND: The intracellular concentration of heavy-metal cations, such as copper, nickel, and zinc is pivotal for the mycobacterial response to the hostile environment inside macrophages. To date, copper transport mediated by P-type ATPases across the mycobacterial plasma membrane has not been sufficiently explored. RESULTS: In this work, the ATPase activity of the putative Mycobacterium tuberculosis P1B-type ATPase CtpB was associated with copper (I) transport from mycobacterial cells. Although CtpB heterologously expressed in M. smegmatis induced tolerance to toxic concentrations of Cu2+ and a metal preference for Cu+, the disruption of ctpB in M. tuberculosis cells did not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper. In addition, the Cu+ ATPase activity of CtpB embedded in the plasma membrane showed features of high affinity/slow turnover ATPases, with enzymatic parameters KM 0.19 ± 0.04 µM and Vmax 2.29 ± 0.10 nmol/mg min. In contrast, the ctpB gene transcription was activated in cells under culture conditions that mimicked the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper. CONCLUSIONS: The overall results suggest that M. tuberculosis CtpB is associated with Cu+ transport from mycobacterial cells possibly playing a role different from copper detoxification.

CtpB is a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis

BACKGROUND: The intracellular concentration of heavy-metal cations, such as copper, nickel, and zinc is pivotal for the mycobacterial response to the hostile environment inside macrophages. To date, copper transport mediated by P-type ATPases across the mycobacterial plasma membrane has not been sufficiently explored. RESULTS: In this work, the ATPase activity of the putative Mycobacterium tuberculosis P1B-type ATPase CtpB was associated with copper (I) transport from mycobacterial cells. Although CtpB heterologously expressed in M. smegmatis induced tolerance to toxic concentrations of Cu2+ and a metal preference for Cu+, the disruption of ctpB in M. tuberculosis cells did not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper. In addition, the Cu+ ATPase activity of CtpB embedded in the plasma mem-brane showed features of high affinity/slow turnover ATPases, with enzymatic parametersKM 0.19 ± 0.04 µM and Vmax 2.29 ± 0.10 nmol/mg min. In contrast, the ctpB gene transcription was activated in cells under culture conditions that mimicked the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper. CONCLUSIONS: The overall results suggest that M. tuberculosis CtpB is associated with Cu+ transport from mycobacterial cells possibly playing a role different from copper detoxification.

From mother to baby: antenatal exposure to monoclonal antibody biologics.

INTRODUCTION: More women with autoimmune and inflammatory conditions are being treated with monoclonal antibody biologics (mAbs) during their pregnancy, to maintain clinical remission. The use of anti-tumor necrosis factor alpha agents in pregnancy appears to be safe but less is known regarding other mAbs, such as anti-integrins and anti-cytokine agents. There are currently no comprehensive guidelines on how to manage the exposed infants. Areas covered: We review recent literature to assess the impact of mAbs on birth and early infant outcomes, including what is currently known about maternal and infant drug levels at birth and drug clearance in the infant. We describe the potential risks of infections and reported hematological and immunological effects of antenatal mAbs exposure on the infant and provide guidance on the management of the exposed infant. Expert opinion: Exposed infants should be monitored closely. Certain mAb exposures require specific testing and management. Safety monitoring should be done in a multidisciplinary approach and should include pediatric care providers. The current clinical experience with anti-tumor necrosis factor agents in pregnancy cannot be extrapolated to other mAbs. Long-term observational studies and a multicenter international registry are needed to better appreciate the impact of exposure, especially to newer mAbs.

Our patients do not need endocarditis prophylaxis for genitourinary tract procedures: insights from the 2007 American Heart Association guidelines.

The 2007 American Heart Association guidelines for the prevention of infective endocarditis have dramatically reduced both the types of eligible procedures and the types of eligible cardiac lesions that require prophylaxis. Antibiotic prophylaxis to prevent infective endocarditis is not indicated for any patient undergoing obstetric and/or gynaecological procedures, not even for patients with underlying cardiac lesions with the highest risk of developing complications from endocarditis. This sharp departure from previously published guidelines relies on the recognition that endocarditis is more likely to develop from "randomly occurring" bacteremia (e.g., from brushing teeth) than from invasive procedures and that antibiotic prophylaxis has not been proven to be effective. A short discussion on enterococcal infections associated to obstetric and gynaecological procedures and therapeutic implications is presented.

Registro de la enfermedad cerebrovascular: frecuencia, tipos de ictus y factores de riesgos asociados / Registration of the cerebrovascular illness: frequency, ictus types and associate factors of risk

Introdución. La enfermedad cerebrovascular es una entidad devastadora, con una alta tasa de recidiva y mortalidad (segunda causa de muerte en el mundo). Una tercera parte de los pacientes afectados fallecen en los seis meses siguientes al ictus y otro 30 por ciento sufre incapacidad permanente. Se requiere un amplio conocimiento de su características para afrontarla adecuadamente. Objetivo. Analizar los aspectos epidemiológicos, la presentación clínica y los hallazgos imagenológicos de una cohorte de pacientes con enfermedad cerebrovascular atendida en el hospital universitario de Cali. Material y métodos. Se estudiaron en forma prospectiva 450 pacientes atendidos en el servicio de neurología del Hospital universitario del Valle (Cali), entre febrero 1 de 2003 y enero 31 de 2004. Se utilizó un protocolo sistemático de evaluación diagnóstica que permitió definir el tipo de ictus y el diagnóstico etiológico en cada caso. Resultados. La enfermedad cerebrovascular predomino en el género femenino 56 por ciento, y en individuos de raza mestiza 67 por ciento. 68 por ciento de los sujetos tuvieron edades superiores a los 60 años. La enfermedad fue isquémica en el 65,5 por ciento y hemorrágica, incluyendo la hemorragia subaracnoidea, en 34,5 por ciento. Se realizó TAC cerebral al 82 por ciento de los pacientes en las primeras 12 horas de síntomas. En 217 sujetos, 48 por ciento el ictus fue de tipo aterotrombótico. La hipertensión arterial fue el factor de riesgo más frecuente en todas las formas de ictus. Conclusiones. Salvo en su presentación por género y raza, esta cohorte reproduce las características epidemiológicas halladas en otros estudios de base hospitalaria. La hipertensión arterial fue el factor de riesgo más frecuente. Se requiere un amplio conocimiento de la enfermedad cerebrovascular para su mejor tratamiento