RESUMEN
The pedigree file of the Boer and Nubian goat breeds in Mexico was constructed using the national database provided by the Asociación Mexicana de Criadores de Ganado Caprino de Registro. Field technicians routinely updated the goat national database by recording information from flocks participating in the performance-recording system. Information on animal identification number, parents, birth date, sex, breed, and farm of origin were used to undertake pedigree analyses using the ENDOG program (version 4.8). This paper presents a pedigree data file, tables and figures of characteristics of pedigree data, pedigree analyses, pedigree integrity, effective population size and genetic conservation index. The data can be used to estimate other population parameters, to monitor the genetic diversity of the Boer and Nubian goat breeds in Mexico, and also to design balanced breeding programs, maintaining genetic variation at reasonable levels and maximizing genetic progress in these populations.
RESUMEN
The prion protein (PrPC) binds copper and affects copper metabolism, albeit among a poorly understood functional landscape. Much of the data on physiological roles of PrPC were obtained in mice of mixed genetic background deficient of the PrPC-coding gene Prnp. This strategy is currently under scrutiny due to the flanking gene problem, in particular related with a polymorphism, typical of both the 129Sv and 129Ola mouse substrains, in the Sirpa gene located in the vicinity of Prnp. Here we report an investigation of biochemical properties of Cu(I)-ATPases as a function of genotype in two strains of PrPC-deficient mice. We found that both the brain and liver of Prnp-null mice of mixed B6;129Sv background had diminished activity, accompanied by increased catalytic phosphorylation of Cu(I)-ATPase, as compared with the respective wild-type animals. However, no such differences were found between Prnp-null and wild-type mice of a B10;129Ola background. Activity of Cu(I)-ATPase was strongly reduced in brain tissue from mice of 129Sv strain, when compared with wild-type either of B6;129Sv, and especially of mice of the B6 strain. No differences between wild-type and Prnp-null brain tissue were noted in the expression of either Atp7a or b genes, and RFLP analysis indicated that the Sirpa129 polymorphism was present in both the B6;129Sv and B10;129Ola Prnp-null mouse colonies used in this study. The results suggest a novel substrain-dependent effect of 129Sv, but not 129Ola, genotype upon the regulation of the Cu(I)-ATPase catalytic cycle in Prnp-null mice, rather than either a Prnp-dependent, or a 129 strain-dependent effect.
Asunto(s)
Encéfalo/metabolismo , ATPasas Transportadoras de Cobre/metabolismo , Proteínas Priónicas/metabolismo , Animales , Hipocampo/metabolismo , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Fosforilación , Proteínas Priónicas/genética , Especificidad de la EspecieRESUMEN
The stereospecific removal of iodine from thyroid hormones is an essential first step for T3 action and is catalyzed by three different deiodinases: D2 and D3 remove iodine only from the outer or inner ring, respectively, whereas D1 catalyzes both pathways. We used in silico predictions from vertebrate deiodinase sequences to identify two domains: the N-terminal variable region (VR) containing the transmembrane, hinge and linker domains, and the conserved or globular region (CR). Given the high sequence and structural identity of the CR among paralogs as well as of the VR among orthologs but not paralogs, we hypothesized that both the catalytic properties and the subcellular localization rely on the VR. We used shark D2 and D3 as templates to build the chimeric enzymes D2VR/D3CR and D3VR/D2CR. Biochemical characterization revealed that D3VR/D2CR has inner-ring deiodination activity and T3 as preferred substrate, whereas D2VR/D3CR showed no deiodinating activity. Also, D2VR/D3CR and D3VR/D2CR reside in the endoplasmic reticulum and plasmatic membrane, respectively, as do their D2 and D3 wild-type counterparts. We conclude that the VR determines the subcellular localization and is critical in defining the catalytic properties and activity of thyroid hormone deiodinases.
Asunto(s)
Proteínas de Peces/química , Yoduro Peroxidasa/química , Tiburones , Secuencia de Aminoácidos , Animales , Dominio Catalítico , Células Cultivadas , Clonación Molecular , Proteínas de Peces/metabolismo , Yoduro Peroxidasa/metabolismo , Cinética , Datos de Secuencia Molecular , Transporte de Proteínas , Tiroxina/química , Triyodotironina/química , Xenopus laevisRESUMEN
Recent studies in our laboratory have shown that in some teleosts, 3,5-di-iodothyronine (T2 or 3,5-T2) is as bioactive as 3,5,3'-tri-iodothyronine (T3) and that its effects are in part mediated by a TRß1 (THRB) isoform that contains a 9-amino acid insert in its ligand-binding domain (long TRß1 (L-TRß1)), whereas T3 binds preferentially to a short TRß1 (S-TRß1) isoform that lacks this insert. To further understand the functional relevance of T2 bioactivity and its mechanism of action, we used in vivo and ex vivo (organotypic liver cultures) approaches and analyzed whether T3 and T2 differentially regulate the S-TRß1 and L-TRß1s during a physiological demand such as growth. In vivo, T3 and T2 treatment induced body weight gain in tilapia. The expression of L-TRß1 and S-TRß1 was specifically regulated by T2 and T3 respectively both in vivo and ex vivo. The TR antagonist 1-850 effectively blocked thyroid hormone-dependent gene expression; however, T3 or T2 reversed 1-850 effects only on S-TRß1 or L-TRß1 expression, respectively. Together, our results support the notion that both T3 and T2 participate in the growth process; however, their effects are mediated by different, specific TRß1 isoforms.
Asunto(s)
Diyodotironinas/farmacología , Receptores beta de Hormona Tiroidea/metabolismo , Tilapia/crecimiento & desarrollo , Tilapia/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Diyodotironinas/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Yoduro Peroxidasa/genética , Yoduro Peroxidasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Isoformas de Proteínas , Receptores beta de Hormona Tiroidea/agonistas , Receptores beta de Hormona Tiroidea/antagonistas & inhibidores , Tilapia/genética , Triyodotironina/metabolismo , Yodotironina Deyodinasa Tipo IIRESUMEN
Ca2+ pumps are important players in smooth muscle contraction. Nevertheless, little information is available about these pumps in the vas deferens. We have determined which subtype of sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca2+-ATPase from a membrane fraction containing the highest SERCA levels in the RVD homogenate has the same molecular mass (â¼115â kDa) as that of SERCA2 from the rat cerebellum. It has a very high affinity for Ca2+ (Ca0.5 = 780â nM) and a low sensitivity to vanadate (IC50 = 41â µM). These facts indicate that SERCA2 is present in the RVD. Immunoblotting for CaM and Ca2+/calmodulin-dependent protein kinase II (CaMKII) showed the expression of these two regulatory proteins. Ca2+ and CaM increased serine-phosphorylated residues of the 115-kDa protein, indicating the involvement of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is accompanied by an 8-fold increase of thapsigargin-sensitive Ca2+ accumulation in the lumen of vesicles derived from these membranes. These data establish that SERCA2 in the RVD is modulated by Ca2+ and CaM, possibly via CaMKII, in a process that results in stimulation of Ca2+ pumping activity.
Asunto(s)
Proteínas de Unión al Calcio/metabolismo , ATPasas Transportadoras de Calcio/metabolismo , Calmodulina/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Conducto Deferente/metabolismo , Animales , Masculino , Contracción Muscular , Fosforilación , Ratas , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismoRESUMEN
Ca2+ pumps are important players in smooth muscle contraction. Nevertheless, little information is available about these pumps in the vas deferens. We have determined which subtype of sarco(endo)plasmic reticulum Ca2+-ATPase isoform (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca2+-ATPase from a membrane fraction containing the highest SERCA levels in the RVD homogenate has the same molecular mass (∼115 kDa) as that of SERCA2 from the rat cerebellum. It has a very high affinity for Ca2+ (Ca0.5 = 780 nM) and a low sensitivity to vanadate (IC50 = 41 µM). These facts indicate that SERCA2 is present in the RVD. Immunoblotting for CaM and Ca2+/calmodulin-dependent protein kinase II (CaMKII) showed the expression of these two regulatory proteins. Ca2+ and CaM increased serine-phosphorylated residues of the 115-kDa protein, indicating the involvement of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is accompanied by an 8-fold increase of thapsigargin-sensitive Ca2+ accumulation in the lumen of vesicles derived from these membranes. These data establish that SERCA2 in the RVD is modulated by Ca2+ and CaM, possibly via CaMKII, in a process that results in stimulation of Ca2+ pumping activity.
Asunto(s)
Animales , Masculino , Ratas , Proteínas de Unión al Calcio/metabolismo , ATPasas Transportadoras de Calcio/metabolismo , Calmodulina/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Conducto Deferente/metabolismo , Contracción Muscular , Fosforilación , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismoRESUMEN
Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the rate-limiting step for TH synthesis; therefore, thyroidal iodide uptake and recycling during TH synthesis are of major importance in maintaining an adequate supply. In the rat, the thyroid gland co-expresses a distinctive pair of intrathyroidal deiodinating enzymes: the thyroid iodotyrosine dehalogenase (tDh) and the iodothyronine deiodinase type 1 (ID1). In the present work, we studied the activity of these two dehalogenases in conditions of hypo- and hyperthyroidism as well as during acute and chronic iodide administration in both intact and hypophysectomized (HPX) rats. In order to confirm our observations, we also measured the mRNA levels for both dehalogenases and for the sodium/iodide symporter, the protein responsible for thyroidal iodide uptake. Our results show that triiodothyronine differentially regulates tDh and ID1 enzymatic activities, and that both acute and chronic iodide administration significantly decreases rat tDh and ID1 activities and mRNA levels. Conversely, both enzymatic activities increase when intrathyroidal iodide is pharmacologically depleted in TSH-replaced HPX rats. These results show a regulatory effect by iodide on the intrathyroidal dehalogenating enzymes and suggest that they contribute to the iodide-induced autoregulatory processes involved in the Wolff-Chaikoff effect.
Asunto(s)
Hidrolasas/metabolismo , Yoduro Peroxidasa/metabolismo , Yoduros/farmacología , Glándula Tiroides/metabolismo , Análisis de Varianza , Animales , Hidrolasas/genética , Hipofisectomía , Yoduro Peroxidasa/genética , Yoduros/metabolismo , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Simportadores/genética , Simportadores/metabolismo , Glándula Tiroides/efectos de los fármacos , Tirotropina/metabolismo , Tirotropina/farmacología , Tiroxina/metabolismo , Tiroxina/farmacología , Triyodotironina/metabolismo , Triyodotironina/farmacologíaRESUMEN
The three distinct but related isotypes of the iodothyronine deiodinase family: D1, D2, and D3, have been amply studied in vertebrate homeotherms and to a lesser extent in ectotherms, particularly in reptiles. Here, we report the molecular and kinetic characteristics of both the native and the recombinant hepatic D3 from the pine snake Pituophis deppei (PdD3). The complete PdD3 cDNA (1680 bp) encodes a protein of 287 amino acids (aa), which is the longest type 3 deiodinase so far cloned. PdD3 shares 78% identity with chicken and 71% with its other orthologs. Interestingly, the hinge domain in D3s, including PdD3, is rich in proline. This structural feature is shared with D1s, the other inner-ring deiodinases, and deserves further study. The kinetic characteristics of both native and recombinant PdD3 were similar to those reported for D3 in other vertebrates. True K(m) values for T(3) IRD were 9 and 11 nM for native and recombinant PdD3, respectively. Both exhibited a requirement for a high concentration of cofactor (40 mM DTT), insensitivity to inhibition by PTU (>2 mM), and bisubstrate, sequential-type reaction kinetics. In summary, the present data demonstrate that the liver of the adult pine snake P. deppei expresses D3. Furthermore, this is the first report of the cloning and expression of a reptilian D3 cDNA. The finding of hepatic D3 expression in the adult pine snake P. deppei is consistent with results in adult piscine species in which the dietary T(3) content seems to regulate liver deiodinase expression. Thus, our present results support the proposal that hepatic D3 in adult vertebrates plays a sentinel role in avoiding an inappropriate overload of exogenous T(3) secondary to feeding in those species that devour the whole prey.
Asunto(s)
Yoduro Peroxidasa/metabolismo , Serpientes/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Yoduro Peroxidasa/química , Yoduro Peroxidasa/genética , Datos de Secuencia Molecular , Radioinmunoensayo , Proteínas de Reptiles/genética , Proteínas de Reptiles/metabolismoRESUMEN
The emergence of opportunities for support from the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) for HIV-related projects has so far generated funding of over US$75 million for three proposals in Peru. The size of this investment creates the need for close monitoring to ensure a reasonable impact. This paper describes the effects of collaboration with the GFATM on key actors involved in HIV-related activities and on decision-making processes; on health sector divisions; on policies and sources of financing; on equity of access; and on stigma and discrimination of vulnerable and affected populations. Data analysed included primary data collected through interviews with key informants, in-depth interviews and group discussions with vulnerable and affected populations, as well as several public documents. Multisectorality, encouraged by the GFATM, is incipient; centralist proposals with limited consultation, a lack of consensus and short preparation times prevail. No accountability mechanisms operate at the Country Coordinating Mechanism (CCM) level regarding CCM members or society as a whole. GFATM-funded activities have required significant input from the public sector, sometimes beyond the capacity of its human resources. A significant increase in HIV funding, in absolute amounts and in fractions of the total budget, has been observed from several sources including the National Treasury, and it is unclear whether this has implied reductions in the budget for other priorities. Patterns of social exclusion of people living with HIV/AIDS are diverse: children and women are more valued; while transgender persons and sex workers are often excluded.
Asunto(s)
Infecciones por VIH/prevención & control , Accesibilidad a los Servicios de Salud/economía , Agencias Internacionales/economía , Malaria/prevención & control , Tuberculosis/prevención & control , Poblaciones Vulnerables , Femenino , Apoyo Financiero , Salud Global/economía , Infecciones por VIH/economía , Infecciones por VIH/epidemiología , Gastos en Salud , Implementación de Plan de Salud , Accesibilidad a los Servicios de Salud/normas , Disparidades en Atención de Salud , Homosexualidad , Humanos , Malaria/economía , Malaria/epidemiología , Masculino , Perú/epidemiología , Prevalencia , Evaluación de Programas y Proyectos de Salud , Trabajadores Sexuales , Estigma Social , Personas Transgénero , Tuberculosis/economía , Tuberculosis/epidemiologíaRESUMEN
Until recently, 3,5-diiodothyronine (3,5-T(2)) has been considered an inactive by-product of triiodothyronine (T(3)) deiodination. However, studies from several laboratories have shown that 3,5-T(2) has specific, nongenomic effects on mitochondrial oxidative capacity and respiration rate that are distinct from those due to T(3). Nevertheless, little is known about the putative genomic effects of 3,5-T(2). We have previously shown that hyperthyroidism induced by supraphysiological doses of 3,5-T(2) inhibits hepatic iodothyronine deiodinase type 2 (D2) activity and lowers mRNA levels in the killifish in the same manner as T(3) and T(4), suggesting a pretranslational effect of 3,5-T(2) (Garcia-G C, Jeziorski MC, Valverde-R C, Orozco A. Gen Comp Endocrinol 135: 201-209, 2004). The question remains as to whether 3,5-T(2) would have effects under conditions similar to those that are physiological for T(3). To this end, intact killifish were rendered hypothyroid by administering methimazole. Groups of hypothyroid animals simultaneously received 30 nM of either T(3), reverse T(3), or 3,5-T(2). Under these conditions, we expected that, if it were bioactive, 3,5-T(2) would mimic T(3) and thus reverse the compensatory upregulation of D2 and tyroid receptor beta1 and downregulation of growth hormone that characterize hypothyroidism. Our results demonstrate that 3,5-T(2) is indeed bioactive, reversing both hepatic D2 and growth hormone responses during a hypothyroidal state. Furthermore, we observed that 3,5-T(2) and T(3) recruit two distinct populations of transcription factors to typical palindromic and DR4 thyroid hormone response elements. Taken together, these results add further evidence to support the notion that 3,5-T(2) is a bioactive iodothyronine.
Asunto(s)
Diyodotironinas/farmacología , Fundulidae/fisiología , Hormona del Crecimiento/sangre , Yoduro Peroxidasa/metabolismo , Glándula Tiroides/fisiología , Receptores beta de Hormona Tiroidea/metabolismo , Animales , Diyodotironinas/sangre , Regulación Enzimológica de la Expresión Génica/fisiología , Hipertiroidismo/metabolismo , Hipertiroidismo/fisiopatología , Hipotiroidismo/metabolismo , Hipotiroidismo/fisiopatología , Yoduro Peroxidasa/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , ARN Mensajero/metabolismo , Elementos de Respuesta/fisiología , Glándula Tiroides/efectos de los fármacos , Regulación hacia Arriba/fisiología , Yodotironina Deyodinasa Tipo IIRESUMEN
The initial characterization of a thyroid iodotyrosine dehalogenase (tDh), which deiodinates mono-iodotyrosine and di-iodotyrosine, was made almost 50 years ago, but little is known about its catalytic and kinetic properties. A distinct group of dehalogenases, the so-called iodothyronine deiodinases (IDs), that specifically remove iodine atoms from iodothyronines were subsequently discovered and have been extensively characterized. Iodothyronine deiodinase type 1 (ID1) is highly expressed in the rat thyroid gland, but the co-expression in this tissue of the two different dehalogenating enzymes has not yet been clearly defined. This work compares and contrasts the kinetic properties of tDh and ID1 in the rat thyroid gland. Differential affinities for substrates, cofactors and inhibitors distinguish the two activities, and a reaction mechanism for tDh is proposed. The results reported here support the view that the rat thyroid gland has a distinctive set of dehalogenases specialized in iodine metabolism.
Asunto(s)
Hidrolasas/metabolismo , Yoduro Peroxidasa/metabolismo , Glándula Tiroides/enzimología , Animales , Activación Enzimática , Femenino , Hidrolasas/análisis , Yoduro Peroxidasa/análisis , Radioisótopos de Yodo/metabolismo , Masculino , NADP/metabolismo , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
Substrate availability has been thought to be a major regulator of the outer-ring deiodinating pathway (ORD) in fish. However, current information strongly suggests that while fish iodothyronine deiodinase type 2 (D2) responds to iodothyronines in the same manner as its mammalian counterpart, fish deiodinase type 1 (D1) exhibits a distinct response. Furthermore, 3,5-T2, generally considered to be an inactive product of iodothyronine metabolism, has recently been described as bioactive, but its effects upon D1 and D2 are not yet known. We examined the effect that short-term immersion in T4, T3, and 3,5-T2 (0.1 microM; 12 or 24 h) exerts on both D1 and D2 activities and on the levels of expression of D1 and D2 mRNAs in killifish liver. In agreement with previous reports in teleosts, no iodothyronine exerted a significant effect on D1 enzymatic activity. However, all three iodothyronines significantly decreased D2 activity. Furthermore, at 24 h post-immersion T4, T3, and 3,5-T2 inhibited both D1 and D2 transcription. Together, the present results confirm the differential effect of iodothyronines upon the hepatic ORD pathway in fish and show that this effect can occur at a transcriptional level. Furthermore, we provide the first evidence that 3,5-T2 can affect both activity and transcription of hepatic deiodinases in teleosts.
Asunto(s)
Diyodotironinas/farmacología , Fundulidae/metabolismo , Yoduro Peroxidasa/metabolismo , Hígado/enzimología , Glándula Tiroides/metabolismo , Animales , Activación Enzimática/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Yoduro Peroxidasa/genética , Masculino , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , Tiroxina/farmacología , Triyodotironina/farmacología , Yodotironina Deyodinasa Tipo IIRESUMEN
Objetivo: Estimar la prevalencia de sifilis y vih e identificar los comportamientos de riesgos asociados en personas privadas de libertad (PPL). Materiales y métodos: Estudio transversal realizado durante el año 1999 en 22 establecimientos penitenciarios peruanos. Se realizó RPR para la detección de sífilis (datos ligados) y ELISA para tamizaje de vih (datos no ligados), confirmándose con IFI o Western Blot. Se realizó una encuesta estructurada y se analizaron los datos mediante los programas SPSS 9,0 y AMOS 4. Resutados: Particparon 6 963 PPL. La prevalencia de vih fue 1,1 por ciento y de sífilis 4,1 por ciento. Los comportamiento de riesgo asociados a vih más significativos fueron: consumo de drogas (OR:2,7), infecciones de transmisión sexual (OR:2,3), relaciones sexuales entre hombres (OR:2,2), uso de cocaína (OR: 2,1), úlcera genital (OR: 2,1), haber sido encarcelado previamente (OR: 2) y tener tatuajes (OR: 1,99). Mientras los asociados a sífilis fueron: tener relaciones sexuaqles entre hombres (OR: 2,8), infecciones de transmisión sexual (OR:2,4), úlcera genital (OR 1,8), haber tenido relaciones sexuales con trabajadora sexual (OR:1,5) y tener más de dos parejas sexuales (OR: 1,5). Utilizando un modelo de ecuaciones estructurales se asoció VIH con el reporte de tener tatuaje, más de dos parejas sexuales, mós de un encarcelamiento previo y úlcera genital. Conclusiones: Se encontraron importantes valores de prevalencia de VIH y sífilis en este grupo de personas, siendo necesario continuar realizando estudios similares que nos permitan conocer las tendencias (vigilancia de segunda generación) y conocer el impacto de posibles intervenciones
Asunto(s)
Factores de Riesgo , VIH , Sífilis/epidemiología , PerúRESUMEN
The presence of a type 1 deiodinase (D1) in the liver of teleosts has been a controversial issue. Recently we characterized the deiodinase activity in rainbow trout and killifish liver and found that the liver of both species co-expresses the two enzymes (D1 and D2) that catalyze the outer ring-deiodinating pathway. We here report the cloning and characterization of an mRNA from the liver of the killifish Fundulus heteroclitus that encodes a D1 (FhD1). The cDNA amplified by RT-PCR from F. heteroclitus liver is 1314 nt long and encodes a protein of 248 aa. It contains a TGA codon in its open reading frame and a selenocysteine insertion sequence in its 3(') untranslated region, consistent with the structure of a selenoenzyme mRNA. The deduced peptide sequence is 73% identical to that encoded by the tilapia D1 cDNA cloned from kidney and 46% identical to the D1s reported in other vertebrates. Northern blot analysis shows that FhD1 mRNA is expressed in F. heteroclitus liver, consistent with prior biochemical evidence for hepatic D1 activity. Furthermore, heterologous expression of the FhD1 cDNA resulted in a protein with properties similar to the D1-like activity in F. heteroclitus liver. The cloned enzyme, like the native species, is relatively insensitive to inhibition by PTU, but mutation of Ser-159 in FhD1 to the Pro residue found in D2 and D3 isoforms increased the sensitivity to PTU. Our results show that, under basal conditions, killifish liver indeed expresses a D1 enzyme that is homologous to mammalian D1s, establishing this as a useful model in which to study the regulation of D1 and D2 concurrently.
Asunto(s)
Fundulidae/metabolismo , Yoduro Peroxidasa/genética , Hígado/enzimología , ARN Mensajero/análisis , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Elementos Transponibles de ADN/genética , ADN Complementario/química , Femenino , Fundulidae/genética , Expresión Génica , Yoduro Peroxidasa/química , Masculino , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Oocitos/enzimología , Propiltiouracilo/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Transfección , Xenopus laevisRESUMEN
We here analyzed the effect of a mild hyperosmotic challenge on the activities of deiodinases type I (D1) and II (D2) in the trout liver, and D1 in kidney and gill, two organs involved in osmoregulation. FW-adapted immature rainbow trout were transferred to 5 per thousand SW and killed 0.5, 1, 2, 4, 8 12, 24 and 48 h post-transfer (PT). Fish maintained in FW served as controls. Hepatic, renal and branchial D1 and hepatic D2 activities were assessed as well as circulating levels of T(3), T(4) and cortisol. Hyperosmotic challenge elicited significant and sustained decreases in kidney D1 and liver D2 activities at 8 h PT, which returned to control values at 48 h PT. In contrast, liver and gill D1 activities exhibited no significant change throughout the study. Also, significant increases in circulating T(4) at 2-4 and 48 h PT were observed. Circulating T(3) remained unmodified until 24-48 h PT, when it rose sharply. Simultaneously, cortisol showed a trend towards increase during the initial 4 h PT, which attained significance at 48 h PT. The present findings demonstrate that a mild hypertonic challenge is sufficient to elicit responses in the trout thyroidal axis. Hormonal changes in the circulatory compartment are in accordance with those previously described for migratory salmonids. A novel aspect of our findings is the organ-specific differential response exhibited by ORD-enzymes when trout are exposed to a mildly different osmotic environment. Our findings further establish the uniqueness of fish thyroid physiology, and can be of value in further understanding the evolutionary aspects of this ORD family of deiodinases.
Asunto(s)
Agua Dulce/química , Branquias/enzimología , Yoduro Peroxidasa/metabolismo , Riñón/enzimología , Hígado/enzimología , Oncorhynchus mykiss/metabolismo , Animales , Branquias/efectos de los fármacos , Hidrocortisona/metabolismo , Concentración de Iones de Hidrógeno , Riñón/efectos de los fármacos , Cinética , Hígado/efectos de los fármacos , Concentración Osmolar , Radioinmunoensayo , Cloruro de Sodio/farmacología , Temperatura , Tiroxina/metabolismo , Triyodotironina/metabolismoRESUMEN
OBJECTIVE: The administration of recombinant human erythropoietin (rHuEPO), started after the first 2 weeks of life, reduces the transfusion requirement in premature infants. However, its use throughout the first 2 weeks of life, when anemia results predominantly from phlebotomy losses, remains controversial. We investigated whether early use of rHuEPO would reduce the total transfusion requirement and/or the number of transfusions throughout the first 2 weeks of life. METHODS: We randomized 114 infants with birth weight (BW) <1250 g to receive rHuEPO (1250 units/kg/week; IV; early group: n = 57) or placebo (late group: n = 57) from day 2 to day 14 of life; subsequently, all the patients received rHuEPO (750 units/kg/week, subcutaneously) for 6 additional weeks. All infants were given oral iron (6 mg/kg/day) and folic acid (2 mg/day). RESULTS: The early group showed higher hematocrit and reticulocyte counts than the late group in the first 3 weeks of life, but there was no difference in the total number of transfusions (early: 1.8 +/- 2.3 vs late: 1.8 +/- 2.5 transfusion/patient) or the transfusion requirement throughout the first 2 weeks of life (early:.8 +/- 1.1 vs late:.9 +/- 1.3) could be demonstrated. In infants with BW <800 g and total phlebotomy losses >30 mL/kg (n = 29), a lower number of transfusions was received by infants in the early group, compared with late group, from the second week to the end of the treatment (early: 3.4 +/- 1.1 vs late: 5.4 +/- 3.7 transfusion/patient). No clinical adverse effects were observed. Thrombocytosis was detected during the treatment with rHuEPO in 31% of the infants. CONCLUSIONS: In the whole population, the early administration of rHuEPO induced a rise of reticulocyte counts, but not enough to reduce the transfusion requirement. The most severely ill infants (BW <800 g and phlebotomy losses >30 mL/kg) seemed to benefit from early use of rHuEPO, and this deserves additional study.
Asunto(s)
Anemia Neonatal/prevención & control , Transfusión Sanguínea/estadística & datos numéricos , Eritropoyetina/administración & dosificación , Enfermedades del Prematuro/prevención & control , Anemia Neonatal/sangre , Humanos , Recién Nacido , Enfermedades del Prematuro/sangre , Hierro/uso terapéutico , Proteínas Recombinantes , Factores de TiempoRESUMEN
The kinetic characterization of the outer-ring deiodination pathway using rT(3) (rT(3)-ORD) in male, female, and pregnant female livers of an endemic lizard, Sceloporus grammicus, is reported. The ORD pathway does not have the characteristics of deiodinase type II; it is exclusively carried out by deiodinase type I (DI). DI enzymatic activity in lizard liver contains one of the highest activities reported in vertebrates. This activity is sexually dimorphic, with males presenting the highest activity during the reproductive season. The properties of this enzyme correspond to those described in mammals, such as specificity for rT(3), susceptibility to inhibition by 6-n-propyl-2-thiouracil and gold-thioglucose, cofactor requirement, and kinetic pattern. Unlike other vertebrates, the lizard DI exhibits conspicuous stability in the thermal range of 15 to 42 degrees C and in the pH range of 5.0 to 9.0. Male true kinetic constants exhibit a direct correlation with temperature. This is in agreement with short-term adaptation to microenvironmental changes and the feasible expression of enzymatic forms/variants which, together, endow this lizard species with a greater adaptation to natural daily ambient thermal fluctuations.
Asunto(s)
Yoduro Peroxidasa/metabolismo , Hígado/enzimología , Lagartos/metabolismo , Animales , Aurotioglucosa/farmacología , Ditiotreitol/farmacología , Inhibidores Enzimáticos/farmacología , Femenino , Concentración de Iones de Hidrógeno , Yoduro Peroxidasa/antagonistas & inhibidores , Cinética , Masculino , Embarazo , Propiltiouracilo/farmacología , Estaciones del Año , Caracteres Sexuales , Temperatura , Triyodotironina Inversa/metabolismoAsunto(s)
Humanos , Masculino , Adolescente , Pérdida de Hueso Alveolar/etiología , Aparatos Ortodóncicos/efectos adversos , Diastema , Procedimientos Innecesarios , Cierre del Espacio Ortodóncico/efectos adversos , Regeneración Tisular Dirigida , Maloclusión Clase I de Angle/diagnóstico , Maloclusión Clase I de Angle/terapia , Periodontitis/etiología , Periodontitis/terapia , Curetaje SubgingivalRESUMEN
PIP: The Cayetan Heredia University in Lima, Peru, developed a community-based intervention program on sexual and reproductive health of the youth. The Sexual Health in a Young City program covers all individuals aged 15-24 years living in two communities in Lima, Brena, and Pueblo Libre. The program departed from the argument that the youth could organize themselves and act for change in regard to their own sexual and reproductive lives. Rooted on the strategies of community education and empowerment, the intervention also seeks to mobilize community resources to improve the reproductive and sexual health of the youth. The 3 major components of the program are: 1) motivating and involving community actors; 2) strengthening and publicizing adolescent health services; and 3) designing and implementing a campaign for youth sexual health. However, the program encountered constraints and limitations. Despite these flaws, the program showed that the more important social actors in a community could be involved in coordinating efforts to promote reproductive and sexual health of the youth.^ieng