RESUMEN
The high-specific-activity factor IX (FIX) variant Padua (R338L) is the most promising transgene for hemophilia B (HB) gene therapy. Although R338 is strongly conserved in mammalian evolution, amino acid substitutions at this position are underrepresented in HB databases. We therefore undertook a complete 20 amino acid scan and determined the specific activity of human (h) and canine (c) FIX variants with every amino acid substituted at position 338. Notably, we observe that hFIX-R338L is the most active variant and cFIX-R338L is sevenfold higher than wild-type (WT) cFIX. This is consistent with the previous identification of hFIX-R338L as a cause of a rare X-linked thrombophilia risk factor. Moreover, WT hFIX and cFIX are some of the least active variants. We confirmed the increased specific activity relative to FIX-WT in vivo of a new variant, cFIX-R338I, after gene therapy in an HB dog. Last, we screened 232 pediatric subjects with thromboembolic disease without identifying F9 R338 variants. Together these observations suggest a surprising evolutionary pressure to limit FIX activity with WT FIX rather than maximize FIX activity.
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Factor IX , Hemofilia B , Animales , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Niño , Perros , Factor IX/genética , Terapia Genética , Hemofilia B/genética , Hemofilia B/terapia , HumanosRESUMEN
Changes in serum cytokines after autologous hematopoietic stem cell transplantation (AHSCT) in multiple sclerosis (MS) patients were documented. Thirty-six consecutive MS patients who had their Expanded Disability Status Scale (EDSS) scored before AHSCT were prospectively enrolled. Cyclophosphamide (Cy) was infused at 200 mg/kg in two administrations given 10 days apart: the first dose for mobilization, the second as the conditioning regimen. Patients were mobilized with 10 µg/kg/day subcutaneous G-CSF. Serum was collected 14 days before and 14 after AHSCT. IL-6, IL-9, IL-10, IL 17-A, IL-21, IL-22, IL-23, TNF-A, CCL2, CCL3, and CCL4 were measured by magnetic bead-based immunoassay. t Test and Wilcoxon test were used to compare cytokine levels before and after AHSCT. There were 28 women and 8 men with a median age of 46 (15-62) years, median duration of MS was 9.5 (1-32) years, and EDSS score was 5.7 (1.5-8.0). Patients had a decrement of pro-inflammatory IL-21 and IL-22 (p = .003 and p = .028) and an increment of anti-inflammatory CCL2 and CCL4 (p < .001 and p = .039) after AHSCT. Decrease of IL-21 and IL-22 coupled with an increment of CCL2 and CCL4 could reflect the immunomodulatory effect of auto-HSCT and be an early indicator of its efficacy.
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Trasplante de Células Madre Hematopoyéticas , Esclerosis Múltiple , Quimiocina CCL2 , Citocinas , Femenino , Humanos , Interleucinas , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Prueba de Estudio Conceptual , Acondicionamiento Pretrasplante , Trasplante Autólogo , Resultado del Tratamiento , Interleucina-22RESUMEN
OBJECTIVE: Populations of Mexican American ancestry are at an increased risk for nonalcoholic fatty liver disease. The objective of this study was to determine whether loci in known and novel genes were associated with variation in aspartate aminotransferase (AST) (n = 3,644), alanine aminotransferase (ALT) (n = 3,595), and gamma-glutamyl transferase (GGT) (n = 1,577) levels by conducting the first genome-wide association study (GWAS) of liver enzymes, which commonly measure liver function, in individuals of Mexican American ancestry. METHODS: Levels of AST, ALT, and GGT were determined by enzymatic colorimetric assays. A multi-cohort GWAS of individuals of Mexican American ancestry was performed. Single-nucleotide polymorphisms (SNP) were tested for association with liver outcomes by multivariable linear regression using an additive genetic model. Association analyses were conducted separately in each cohort, followed by a nonparametric meta-analysis. RESULTS: In the PNPLA3 gene, rs4823173 (P = 3.44 × 10-10 ), rs2896019 (P = 7.29 × 10-9 ), and rs2281135 (P = 8.73 × 10-9 ) were significantly associated with AST levels. Although not genome-wide significant, these same SNPs were the top hits for ALT (P = 7.12 × 10-8 , P = 1.98 × 10-7 , and P = 1.81 × 10-7 , respectively). The strong correlation (r2 = 1.0) for these SNPs indicated a single hit in the PNPLA3 gene. No genome-wide significant associations were found for GGT. CONCLUSIONS: PNPLA3, a locus previously identified with ALT, AST, and nonalcoholic fatty liver disease in European and Japanese GWAS, is also associated with liver enzymes in populations of Mexican American ancestry.
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Alanina Transaminasa/genética , Aspartato Aminotransferasas/genética , Lipasa/genética , Proteínas de la Membrana/genética , Americanos Mexicanos/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Adulto , Femenino , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Modelos Lineales , Hígado/enzimología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/etnología , Polimorfismo de Nucleótido Simple , gamma-Glutamiltransferasa/genéticaRESUMEN
Background: Previously we reported the use of a monoclonal antibody-based (HP10) antigen (Ag) detection lateral flow assay (LFA) for the diagnosis of extraparenchymal neurocysticercosis (EP-NCC). The assay performed well when used with cerebrospinal fluid (CSF) samples but not with their paired serum samples, due to false-positive reactions in some known negative control cases. Methods: Our novel modification involves pretreatment of serum samples using a combination of sodium deoxycholate and dithiothreitol. Results: The modification overcomes the problem of false positives when using negative serum samples from clinically characterized cases of EP-NCC and bovine cysticercosis. In general, there was good agreement between HP10 Ag enzyme-linked immunosorbent assay (ELISA) and the HP10 Ag-LFA, but the HP10 Ag-ELISA was marginally more sensitive than the modified HP10 Ag-LFA. Conclusions: The modified HP10 Ag-LFA provides a field test for the rapid identification of endemic human and bovine cysticercosis.
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Bioensayo/métodos , Sangre/parasitología , Cisticercosis/sangre , Cisticercosis/diagnóstico , Cysticercus/aislamiento & purificación , Animales , Bovinos , Ácido Desoxicólico , Ditiotreitol , Ecuador/epidemiología , Reacciones Falso Positivas , Femenino , Humanos , MasculinoRESUMEN
Prevalence of diabetes and obesity in Mexican Pima Indians is low, while prevalence in US Pima Indians is high. Although lifestyle likely accounts for much of the difference, the role of genetic factors is not well explored. To examine this, we genotyped 359 single nucleotide polymorphisms, including established type 2 diabetes and obesity variants from genome-wide association studies (GWAS) and 96 random markers, in 342 Mexican Pimas. A multimarker risk score of obesity variants was associated with body mass index (BMI; ß = 0.81 kg/m2 per SD, P = 0.0066). The mean value of the score was lower in Mexican Pimas than in US Pimas (P = 4.3 × 10-11 ), and differences in allele frequencies at established loci could account for approximately 7% of the population difference in BMI; however, the difference in risk scores was consistent with evolutionary neutrality given genetic distance. To identify loci potentially under recent natural selection, allele frequencies at 283 variants were compared between US and Mexican Pimas, accounting for genetic distance. The largest differences were seen at HLA markers (e.g., rs9271720, difference = 0.75, P = 8.7 × 10-9 ); genetic distances at HLA were greater than at random markers (P = 1.6 × 10-46 ). Analyses of GWAS data in 937 US Pimas also showed sharing of alleles identical by descent at HLA that exceeds its genomic expectation (P = 7.0 × 10-10 ). These results suggest that, in addition to the widely recognized balancing selection at HLA, recent directional selection may also occur, resulting in marked allelic differentiation between closely related populations.
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Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/genética , Antígenos HLA/genética , Indígenas Norteamericanos/genética , Obesidad/etnología , Obesidad/genética , Alelos , Índice de Masa Corporal , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , México , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Epidemiological studies have found coffee consumption is associated with a lower risk for type 2 diabetes mellitus, but the underlying mechanisms remain unclear. Thus, the aim of this randomised, cross-over single-blind study was to investigate the effects of regular coffee, regular coffee with sugar and decaffeinated coffee consumption on glucose metabolism and incretin hormones. Seventeen healthy men participated in five trials each, during which they consumed coffee (decaffeinated, regular (containing caffeine) or regular with sugar) or water (with or without sugar). After 1 h of each intervention, they received an oral glucose tolerance test with one intravenous dose of [1-13C]glucose. The Oral Dose Intravenous Label Experiment was applied and glucose and insulin levels were interpreted using a stable isotope two-compartment minimal model. A mixed-model procedure (PROC MIXED), with subject as random effect and time as repeated measure, was used to compare the effects of the beverages on glucose metabolism and incretin parameters (glucose-dependent insulinotropic peptide (GIP)) and glucagon-like peptide-1 (GLP-1)). Insulin sensitivity was higher with decaffeinated coffee than with water (P<0·05). Regular coffee with sugar did not significantly affect glucose, insulin, C-peptide and incretin hormones, compared with water with sugar. Glucose, insulin, C-peptide, GLP-1 and GIP levels were not statistically different after regular and decaffeinated coffee compared with water. Our findings demonstrated that the consumption of decaffeinated coffee improves insulin sensitivity without changing incretin hormones levels. There was no short-term adverse effect on glucose homoeostasis, after an oral glucose challenge, attributable to the consumption of regular coffee with sugar.
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Cafeína/administración & dosificación , Café/química , Resistencia a la Insulina , Adulto , Glucemia , Cafeína/química , Estudios Cruzados , Diabetes Mellitus Tipo 2/prevención & control , Prueba de Tolerancia a la Glucosa , Humanos , Insulina , Masculino , Método Simple Ciego , Adulto JovenRESUMEN
CONTEXT AND OBJECTIVE: We examined whether a prevalent caveolin-1 gene (CAV1) variant, previously related to insulin resistance, is associated with metabolic syndrome (MetS). PATIENTS AND METHODS: We included subjects genotyped for the CAV1 variant rs926198 from two cohorts: 735 Caucasians from the HyperPATH multicenter study, and 810 Hispanic participants from the HTN-IR cohort. RESULTS: Minor allele carriers from HyperPATH cohort (57% of subjects) had higher Framingham risk scores, higher odds of diabetes (10.7% vs 5.7%, p=0.016), insulin resistance (44.3% vs 35.1%, p=0.022), low HDL (49.3% vs 39.6%, p=0.018) and MetS (33% vs 20.5%, p<0.001) but similar BMI. Consistently, minor allele carriers exhibited higher odds of MetS, even when adjusted for confounders and relatedness (OR 2.83 (1.73-4.63), p<0.001). The association with MetS was replicated in the Hispanic cohort HTN-IR (OR 1.61, [1.06-2.44], p=0.025). Exploratory analyses suggest that MetS risk is modified by a CAV1 variant-BMI status interaction, whereby the minor allele carrier status strongly predicted MetS (OR 3.86 [2.05-7.27], p<0.001) and diabetes (OR 2.27 [1.07-4.78], p=0.03) in non-obese, but not in obese subjects. In addition, we observed a familial aggregation for MetS diagnosis in minor allele carriers. CONCLUSION: The prevalent CAV1 gene variant rs926198 is associated with MetS in separate Caucasian and Hispanic cohorts. These findings appear to be driven by an interaction between the genetic marker and obesity status, suggesting that the CAV1 variant may improve risk profiling in non-obese subjects. Additional studies are needed to confirm the clinical implications of our results.
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Caveolina 1/genética , Hispánicos o Latinos/genética , Síndrome Metabólico/genética , Población Blanca/genética , Adulto , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D.
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Glucemia/genética , Diabetes Mellitus Tipo 2/metabolismo , Variación Genética , Homeostasis/fisiología , Glucemia/metabolismo , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/etnología , Regulación de la Expresión Génica/fisiología , Genoma , Estudio de Asociación del Genoma Completo , Genotipo , Hispánicos o Latinos , Homeostasis/genética , HumanosRESUMEN
OBJECTIVES: To study the effect of the initiation time of posaconazole treatment from 1 to 3 days after systemic infection by Trichosporon asahii in mice. METHODS: BALB/c mice, 4-5 weeks old, were intravenously infected with 1 × 10(7) cfu/mouse of T. asahii. The onset of treatment varied from 1 to 3 days after infection. Orally administered posaconazole at 0.5, 1, 2, 5 or 10 mg/kg body weight/day was compared with orally administered fluconazole (at 10 mg/kg/day) and intraperitoneally administered amphotericin B (at 1 mg/kg) on alternating days. Livers, kidneys and spleens of mice that died or survived to day 25 were removed to determine fungal tissue burdens. RESULTS: When therapy began 1 day after challenge, posaconazole at ≥ 1 mg/kg significantly prolonged survival of mice compared with that of the control group and considerably reduced the fungal tissue burden over the control group. On the other hand, when treatment was started 3 days after infection, regimens of 5 and 10 mg/kg posaconazole significantly prolonged mice survival over that of the control group and appreciably diminished the fungal load compared with untreated mice. In this model, as the severity of trichosporonosis increased, higher doses of posaconazole were required to achieve equivalent activity levels. Fluconazole and amphotericin B were ineffective in preventing mice death and in significantly reducing fungal tissue burden. Posaconazole displayed potent in vivo activity against the strain tested. CONCLUSIONS: Posaconazole may be a suitable option in the treatment of disseminated T. asahii infection.
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Antifúngicos/uso terapéutico , Triazoles/uso terapéutico , Trichosporon/efectos de los fármacos , Tricosporonosis/tratamiento farmacológico , Administración Oral , Anfotericina B/uso terapéutico , Animales , Recuento de Colonia Microbiana , Fluconazol/uso terapéutico , Inyecciones Intraperitoneales , Riñón/microbiología , Hígado/microbiología , Masculino , Ratones , Ratones Endogámicos BALB C , Bazo/microbiología , Resultado del TratamientoRESUMEN
OBJECTIVE: The GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI). METHODS: GUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican-American individuals in 1,346 pedigrees. Insulin sensitivity (SI ), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components. RESULTS: Across studies, age, and gender-adjusted heritability of insulin sensitivity (SI , M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to -0.59 for AIRg and MCRI (all P < 0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P < 0.0001); and -0.16 to -0.36 for AIRg and MCRI (P < 0.0001-0.06). CONCLUSIONS: These data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.
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Diabetes Mellitus Tipo 2/genética , Resistencia a la Insulina/genética , Insulina/metabolismo , Tasa de Depuración Metabólica/genética , Americanos Mexicanos/genética , Adulto , Anciano , Estudios de Cohortes , Colorado , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Estudio de Asociación del Genoma Completo , Técnica de Clampeo de la Glucosa , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Estudios Retrospectivos , TexasRESUMEN
To study diagnostic epitopes within the Taenia solium 8 kDa antigen family, six overlapping synthetic peptides from an 8 kDa family member (Ts8B2) were synthesized and evaluated by ELISA and MABA with sera from patients with neurocysticercosis (NCC), from infected pigs and from rabbits immunized with recombinant Ts8B2 protein. The pre-immune rabbit sera and the Ts8B2 recombinant protein served as negative and positive controls, respectively. A similar analysis was done with the already described antigenic peptides from another member of the 8 kDa family, highly similar to Ts8B2, the CyDA antigen. Surprisingly, neither the Ts8B2 peptides nor the CyDA peptides were recognized by infected human and porcine sera. However, the entire Ts8B2 recombinant, as well as amino and carboxy-terminal halves were recognized by the positive serum samples. The observed lack of recognition of linear Ts8B2 peptides suggests that the principal serological response to the Ts8B2 family is focused on conformational epitopes in contrast to the previously observed antigenicity of the CyDA peptides. This differential antigenicity of 8 kDa family peptides could be related with parasite antigenic variability. The fact that rabbits experimentally immunized with Ts8B2 did make anti-peptide antibodies to peptides Ts8B2-6 and CyDA-6, located in the carboxy-terminal region demonstrated that the Ts8B2 peptides are not intrinsically non-immunogenic.
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Antígenos Helmínticos/inmunología , Cisticercosis/diagnóstico , Epítopos/inmunología , Taenia solium/inmunología , Secuencia de Aminoácidos , Animales , Variación Antigénica , Antígenos Helmínticos/química , Antígenos Helmínticos/genética , Clonación Molecular , Cisticercosis/inmunología , Cisticercosis/parasitología , Cysticercus/genética , Cysticercus/inmunología , Cysticercus/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Epítopos/química , Epítopos/genética , Regulación de la Expresión Génica , Humanos , Immunoblotting , Conejos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Sensibilidad y Especificidad , Alineación de Secuencia , Porcinos , Taenia solium/genética , Taenia solium/aislamiento & purificaciónRESUMEN
The aim of the study was to evaluate the contribution of lactation to insulin sensitivity in women 12 to 18 month postpartum using an oral glucose tolerance test (OGTT). Mean lactation index (LI), a scoring system that considers the establishment and maintenance of the lactation was used. Lactation index was calculated according to the number of months of breast-feeding per child with a maximum of 72 points. The mean LI was calculated by dividing the total number of points by the number of children. A cutoff point of 72 was considered for the LI. We investigated the inverse of the homeostasis model assessment (HOMA(Sens)) and the Cederholm index. Healthy women went through standardized interview and anthropometry. After a 10- to 12-h overnight fast, a 2-h OGTT was performed. Multiple regression analysis was performed with HOMA(Sens) and Cederholm index, which were adjusted for parity, percentage body fat, LI and presence/absence of breast-feeding. Both HOMA(Sens) and Cederholm index were negatively associated with percentage body fat (P<.01), and Cederholm index was positively associated with LI (P=.01). Mean 120-min insulin levels were significantly lower in women with LI=72 when compared with LI<72 women. Insulin sensitivity measured by the Cederholm index is positively associated with prolonged and sustained lactation, while percentage body fat presented a negative association. In this way, sustained lactation-associated metabolic changes are considered protective to women's health.
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Lactancia Materna , Resistencia a la Insulina , Lactancia/metabolismo , Tejido Adiposo/metabolismo , Adulto , Antropometría , Glucemia/análisis , Índice de Masa Corporal , Ayuno , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Homeostasis , Humanos , Insulina/sangre , Periodo Posparto , Análisis de Regresión , Factores SocioeconómicosRESUMEN
OBJECTIVE: To describe the off-label use of recombinant factor VIIa (rFVIIa) in tertiary care pediatric hospitals across the United States and to assess thrombotic events. STUDY DESIGN: A retrospective multi-center cohort study using the Pediatric Health Information System administrative database. Children 18 years of age or younger who received rFVIIa between 2000 and 2007 were included. A label admission was defined as an admission with an International Classification of Diseases diagnostic code for hemophilia or factor VII deficiency; admissions without these codes were classified as off-label. RESULTS: There were 4942 rFVIIa admissions, representing 3764 individual subjects; 74% (3655) of the admissions were off-label. There was a 10-fold increase in the annual rate of off-label admissions from 2000 to 2007 (from 2 to 20.8 per 10 000 hospital admissions, P < .001). The mortality rate in the off-label group was 34% (1258/3655). Thrombotic events occurred in 10.9% (399/3655) of the off-label admissions. CONCLUSIONS: The off-label use of rFVIIa in hospitalized children is increasing rapidly despite the absence of adequate clinical trials demonstrating safety and efficacy. Thrombotic events are common and mortality is high among patients receiving off-label rFVIIa. Further studies are warranted to determine whether these adverse events are attributable to rFVIIa.
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Factor VIIa/efectos adversos , Hemofilia A/tratamiento farmacológico , Uso Fuera de lo Indicado , Trombosis/epidemiología , Adolescente , Niño , Preescolar , Factor VIIa/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Trombosis/inducido químicamente , Estados Unidos/epidemiologíaRESUMEN
El reflejo óculo-cardíaco es un fenómeno muy conocido en la cirugía oftalmológica y desde su descubrimiento los oftalmólogos y anestesiólogos lo consideran como un problema intraoperatorio significativo, describen disritmias que causaron morbosidad y muerte. Objetivo: realizar una revisión sobre las consideraciones anestésicas ante la presencia del reflejo óculo-cardíaco. Método: se realizó una revisión bibliográfica sobre el tema, en el cual se aborda la Anatomía, la Fisiología, las particularidades anestésicas y el tratamiento del mismo una vez presente. Conclusiones: El conocimiento exhaustivo de la ocurrencia del reflejo óculo-cardíaco causará beneficio a los pacientes sometidos a la cirugía oftalmológica (AU)
Oculocardiac reflex is a very well-known phenomenon in the ophthalmologic surgery and since its discovery oculists and anesthesiologists consider it as a significant intraoperative problem, they describe dysrhythmia that caused morbidity and death. Objective: to carry out a revision on anesthetic considerations in the face of oculocardiac reflex. Method: a bibliographical revision on the topic, in which is approached anatomy, physiology, anesthetic particularities and treatment once it is presented. Conclusions: The exhaustive knowledge of the occurrence of oculocardiac reflex caused benefit to patients underwent to the ophthalmologic surgery (AU)
Asunto(s)
Humanos , Reflejo Oculocardíaco/fisiología , Procedimientos Quirúrgicos Oftalmológicos/efectos adversos , Anestesia/efectos adversos , Complicaciones Intraoperatorias/prevención & controlRESUMEN
Fundamento: el reflejo óculo-cardíaco es un fenómeno muy conocido en la cirugía oftalmológica y desde su descubrimiento los oftalmólogos y anestesiólogos lo consideran como un problema intraoperatorio significativo, describen disritmias que causaron morbosidad y muerte. Objetivo: realizar una revisión sobre las consideraciones anestésicas ante la presencia del reflejo óculo-cardíaco. Método: se realizó una revisión bibliográfica sobre el tema, en el cual se aborda la Anatomía, la Fisiología, las particularidades anestésicas y el tratamiento del mismo una vez presente. Conclusiones: El conocimiento exhaustivo de la ocurrencia del reflejo óculo-cardíaco causará beneficio a los pacientes sometidos a la cirugía oftalmológica.
Background: oculocardiac reflex is a very well-known phenomenon in the ophthalmologic surgery and since its discovery oculists and anesthesiologists consider it as a significant intraoperative problem, they describe dysrhythmia that caused morbidity and death. Objective: to carry out a revision on anesthetic considerations in the face of oculocardiac reflex. Method: a bibliographical revision on the topic, in which is approached anatomy, physiology, anesthetic particularities and treatment once it is presented. Conclusions: The exhaustive knowledge of the occurrence of oculocardiac reflex caused benefit to patients underwent to the ophthalmologic surgery.
RESUMEN
The WHO has developed new growth curves based on breast-fed infants. Recommendations for energy intake have been adopted based on measurements of total energy expenditure. Data on human milk (HM) intake are needed to estimate the energy intake from this food source. However, objective HM data from around the world have not been available, because these measurements are difficult to obtain. Stable isotope methods have been developed to provide objective measurements over a 14-d period. A pooled analysis of 1115 data points of HM intake, obtained using the dose to the mother deuterium oxide turnover method, was undertaken in infants aged 0-24 mo from 12 countries across 5 continents. A hierarchical model was needed to estimate mean HM intake and its variance within and between countries given the complexity of the data. The overall mean HM intake was 0.78 (95% CI = 0.72, 0.84) kg/d, and the age-specific estimates indicated that intake increased over the first 3-4 mo and remained above 0.80 kg/d until 6-7 mo. The variability of intake increased in late infancy. Boys consumed 0.05 kg/d more than girls (P < 0.01). HM intake was strongly, inversely associated with non-HM water intake [r = -0.448 (95% CI -0.511 to -0.385); P < 0.0001]. These objective isotope values of HM intake improve our understanding of the magnitude and variability of HM intake within and across populations and help to estimate nutrient intakes in breast-fed infants.
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Alimentos Infantiles , Leche Humana , Femenino , Humanos , Lactante , Isótopos , MasculinoRESUMEN
It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.
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Transportadoras de Casetes de Unión a ATP/genética , HDL-Colesterol/sangre , Indígenas Norteamericanos/genética , Selección Genética , Transportador 1 de Casete de Unión a ATP , Transportadoras de Casetes de Unión a ATP/fisiología , Adulto , Alelos , HDL-Colesterol/genética , Femenino , Frecuencia de los Genes , Genética de Población , Estudio de Asociación del Genoma Completo , Geografía , Haplotipos , Humanos , Desequilibrio de Ligamiento , MasculinoRESUMEN
There is a paucity of quantitative data on the status of porcine cysticercosis in Venezuela, information which is essential for understanding the level of disease transmission. This study was, therefore, conducted in a typical small rural community in Yaracuy State, Venezuela, where previous cases of human Taenia solium taeniasis/cysticercosis had been reported and where the free-ranging pig management practices and the lack of rudimentary sanitary facilities indicated an obvious risk for transmission of the disease. Serum samples from 52 village pigs were screened by enzyme-linked immunosorbent assays for anti-cysticercal antibodies (Ab-ELISA), using T. solium cyst fluid as the antigen and the HP10, monoclonal antibody-based, antigen trapping ELISA for parasite antigen (HP10 Ag-ELISA). Significantly, a high proportion of the animals (65.4% for the Ab-ELISA and 42.3% for the HP10 Ag-ELISA) were sero-positive. Five of the pigs, which were selected on that basis of positive tongue palpation, were killed for autopsy, and large numbers of viable cysticerci were found in the carcases. This unequivocal documentation of porcine cysticercosis in Venezuelan pigs presents clear evidence that T. solium is actively transmitted in Venezuela. Further detailed studies and implementation of appropriate control measures are therefore indicated.
Asunto(s)
Cisticercosis/veterinaria , Enfermedades de los Porcinos/transmisión , Crianza de Animales Domésticos , Animales , Cisticercosis/epidemiología , Cisticercosis/transmisión , Ensayo de Inmunoadsorción Enzimática/veterinaria , Estudios Seroepidemiológicos , Porcinos , Enfermedades de los Porcinos/epidemiología , Enfermedades de los Porcinos/parasitología , Venezuela/epidemiologíaRESUMEN
TCR signaling leads to the activation of kinases such as inducible tyrosine kinase (Itk), a key regulatory protein in T-lymphocyte activation and function. The homolog of Itk in B cells is Bruton's tyrosine kinase, previously shown to bind and phosphorylate the transcription factor TFII-I. TFII-I plays major roles in transcription and signaling. Our purpose herein was twofold: first, to identify some of the molecular determinants involved in TFII-I activation downstream of receptor crosslinking in T cells and second, to uncover the existence of Itk-TFII-I signaling in T lymphocytes. We report for the first time that TFII-I is tyrosine phosphorylated upon TCR, TCR/CD43, and TCR/CD28 co-receptor engagement in human and/or murine T cells. We show that Itk physically interacts with TFII-I and potentiates TFII-I-driven c-fos transcription. We demonstrate that TFII-I is phosphorylated upon co-expression of WT, but not kinase-dead, or kinase-dead/R29C mutant Itk, suggesting these residues are important for TFII-I phosphorylation, presumably via an Itk-dependent mechanism. Structural analysis of TFII-I-Itk interactions revealed that the first 90 residues of TFII-I are dispensable for Itk binding. Mutations within Itk's kinase, pleckstrin-homology, and proline-rich regions did not abolish TFII-I-Itk binding. Our results provide an initial step in understanding the biological role of Itk-TFII-I signaling in T-cell function.
Asunto(s)
Linfocitos B/inmunología , Proteínas Tirosina Quinasas/metabolismo , Linfocitos T/inmunología , Factores de Transcripción TFII/metabolismo , Animales , Linfocitos B/metabolismo , Antígenos CD28/inmunología , Antígenos CD28/metabolismo , Complejo CD3/inmunología , Complejo CD3/metabolismo , Genes fos/genética , Genes fos/inmunología , Humanos , Células Jurkat , Leucosialina/inmunología , Leucosialina/metabolismo , Ratones , Fosforilación/inmunología , Regiones Promotoras Genéticas/genética , Regiones Promotoras Genéticas/inmunología , Linfocitos T/metabolismoRESUMEN
OBJECTIVE: To review the incidence of postoperative bleeding in children with type 1 von Willebrand disease (VWD) who were treated with a single institution protocol. STUDY DESIGN: We performed a retrospective study to determine the postoperative hemorrhage rate in pediatric patients with type 1 VWD who were treated via the Children's Hospital of Philadelphia institutional protocol. This protocol utilizes intravenous desmopressin (DDAVP), oral aminocaproic acid, and overnight observation. RESULTS: Between the years of 2000 to 2006, 41 children with type 1 VWD underwent an adenotonsillar procedure and were treated with this protocol. Seven patients (17%) experienced delayed (>24 hours after surgery) postoperative hemorrhage requiring intervention. Five of the 7 patients required cautery to control the bleeding, and the remaining 2 patients responded to DDAVP and aminocaproic acid alone. Older age and lower VW antigen levels were associated with postoperative hemorrhage (P = .05). CONCLUSIONS: Despite therapeutic intervention to decrease the risk of postoperative hemorrhage, the incidence of hemorrhage was higher in pretreated patients with type 1 VWD than in children without bleeding disorders. Further prospective studies are necessary to determine the optimal treatment to reduce bleeding complications in these patients.