RESUMEN
INTRODUCTION: Listeriosis is an uncommon foodborne infection that may cause moderate maternal illness, but can be extremely serious for the fetus and the newborn. Several guidelines have been elaborated in order to help clinicians on the care of pregnant women with known or suspected exposure to Listeria monocytogenes. The aim of this review is to collect, assess and summarize them, in order to provide a comprehensive overlook and to highlight the grey areas in the guidance that could result in failure to detect some infected but asymptomatic women. Areas covered: A literature review was performed to provide an update on listeriosis infections, with a greater focus on diagnosis and management of pregnancy-related cases. Expert commentary: Since pregnancy-associated listeriosis causes potentially fatal consequences, it is important that healthcare providers recognize earlier symptoms, diagnosis methods and treatment of the infection. Listeriosis could be asymptomatic and/or a pregnant woman could not be aware of being exposed to Listeria, therefore a serological test is suggested to detect the presence of anti-listeriolysin O antibodies in blood. Finally, a final flowchart is proposed that could improve the early diagnosis of the infection in pregnant women.
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Listeria monocytogenes/aislamiento & purificación , Listeriosis/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Toxinas Bacterianas/inmunología , Femenino , Microbiología de Alimentos , Proteínas de Choque Térmico/inmunología , Proteínas Hemolisinas/inmunología , Humanos , Recién Nacido , Listeriosis/diagnóstico , Guías de Práctica Clínica como Asunto , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/microbiología , RiesgoRESUMEN
The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy.
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Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/patología , Comunicación Interdisciplinaria , Laminas/genética , Investigación Biomédica Traslacional , Enfermedades Genéticas Congénitas/diagnóstico , Humanos , Laminas/deficiencia , Laminas/fisiología , Lipodistrofia/genética , Lipodistrofia/patología , Distrofia Muscular de Emery-Dreifuss/diagnóstico , Distrofia Muscular de Emery-Dreifuss/genética , Distrofia Muscular de Emery-Dreifuss/patología , Membrana Nuclear/genética , Membrana Nuclear/patología , Progeria/genética , Progeria/patología , Enfermedades RarasRESUMEN
2-amino 3-carboxymuconate 6-semialdehyde decarboxylase (ACMSD, EC 4.1.1.45) plays a key role in tryptophan catabolism. By diverting 2-amino 3-carboxymuconate semialdehyde from quinolinate production, the enzyme regulates NAD biosynthesis from the amino acid, directly affecting quinolinate and picolinate formation. ACMSD is therefore an attractive therapeutic target for treating disorders associated with increased levels of tryptophan metabolites. Through an isoform-specific real-time PCR assay, the constitutive expression of two alternatively spliced ACMSD transcripts (ACMSD I and II) has been examined in human brain, liver and kidney. Both transcripts are present in kidney and liver, with highest expression occurring in kidney. In brain, no ACMSD II expression is detected, and ACMSD I is present at very low levels. Cloning of the two cDNAs in yeast expression vectors and production of the recombinant proteins, revealed that only ACMSD I is endowed with enzymatic activity. After purification to homogeneity, this enzyme was found to be a monomer, with a broad pH optimum ranging from 6.5 to 8.0, a K(m) of 6.5 microM, and a k(cat) of 1.0 s(-1). ACMSD I is inhibited by quinolinic acid, picolinic acid and kynurenic acid, and it is activated slightly by Fe(2+) and Co(2+). Site-directed mutagenesis experiments confirmed the catalytic role of residues, conserved in all ACMSDs so far characterized, which in the bacterial enzyme participate directly in the metallocofactor binding. Even so, the properties of the human enzyme differ significantly from those reported for the bacterial counterpart, suggesting that the metallocofactor is buried deep within the protein and not as accessible as it is in bacterial ACMSD.
Asunto(s)
Carboxiliasas/genética , Carboxiliasas/metabolismo , Perfilación de la Expresión Génica , Triptófano/metabolismo , Secuencia de Aminoácidos , Encéfalo/enzimología , Encéfalo/metabolismo , Carboxiliasas/química , Electroforesis en Gel de Poliacrilamida , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Riñón/enzimología , Riñón/metabolismo , Cinética , Hígado/enzimología , Hígado/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Molecular , Estructura Secundaria de Proteína , Ácido Quinolínico/química , Ácido Quinolínico/metabolismo , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Triptófano/químicaRESUMEN
NAD kinase is the only known enzyme catalyzing the formation of NADP, a coenzyme implicated in most reductive biosynthetic reactions and in many antioxidant defense systems. Despite its importance, nothing is known regarding its structure or mechanism of catalysis. Mycobacterium tuberculosis NAD kinase has been overexpressed in Escherichia coli and purified to homogeneity. The molecular and kinetic properties of the enzyme resulted in significant differences from those reported by others on a proteolytically degraded form of the protein. Indeed the full-length enzyme displays an allosteric behavior and shows a strict preference for inorganic polyphosphate as the phosphate donor. It is inhibited by the reaction product NADP and by both NADH and NADPH. The mycobacterial enzyme shares with all other known NAD kinases a highly conserved region (spanning residues 189-210), particularly rich in glycines, which differs from the primary sequences of all previously identified nucleotide-binding sites. Alanine-scanning mutagenesis performed on 11 conserved residues within this domain revealed its importance in catalysis. A total of 6 of 11 mutated proteins completely lost the enzymatic activity while retaining the same oligomeric state of the wild-type protein, as demonstrated by gel-filtration analysis. Substitutions of S199 and G208 with alanine rendered enzyme versions with reduced activity. Their kinetic characterization, performed on purified proteins, revealed kinetic parameters toward ATP and polyphosphate similar to those of the wild-type enzyme. On the contrary, when the kinetic analysis was performed by using NAD as the variable substrate, significant differences were observed with respect to both the allosteric behavior and the catalytic efficiency, suggesting that the mutated region is likely involved in NAD binding.