Efecto del factor de crecimiento de fibroblastos 21 / Fibroblast growht factor 21 effects over phosphatase SHP-2 expression in Malme-3 cells

Almost 50 percent of Noonan syndrome patients, characterized by short stature, present activating mutations of the citoplasmatic phosphatase SHP-2, which induce hyperactivation of the Ras/MAPK pathway. On the other hand, the fibroblast growth factor 21 (FGF-21), recently suggested as a FGF with “endocrine” function, would affect longitudinal growth inhibiting growth hormone signaling at chondrocytes level. Union and activation of FGF-21 to its receptor is regulated by the co-factor beta Klotho (KLB). Aims: To determine if FGF-21 and/or FGF-21+KLB are able to modify the genetic expression of SHP-2 ina human skin fibroblast cell line (Malme-3). Methods: cells were incubated with or without FGF-21, FGF-21 + KLB. At 12 and 24 hours after induction total RNA was extracted andSHP-2 mRNA levels were determine by quantitative PCR. Expression of GADPH gene was employed for normalization. Results: Incubation with FGF-21 produce a 36 percent (p = < 0,05)increment in SHP-2 expression, which was not modified with KLB co-incubation. Discussion: it is shown by the first time that FGF-21 is able to produce an increase in SHP-2 gene expression in human fibroblast, which was independent of KLB presence...

Analysis of genetic diversity in Bolivian llama populations using microsatellites.

South American camelids (SACs) have a major role in the maintenance and potential future of rural Andean human populations. More than 60% of the 3.7 million llamas living worldwide are found in Bolivia. Due to the lack of studies focusing on genetic diversity in Bolivian llamas, this analysis investigates both the genetic diversity and structure of 12 regional groups of llamas that span the greater part of the range of distribution for this species in Bolivia. The analysis of 42 microsatellite markers in the considered regional groups showed that, in general, there were high levels of polymorphism (a total of 506 detected alleles; average PIC across per marker: 0.66), which are comparable with those reported for other populations of domestic SACs. The estimated diversity parameters indicated that there was high intrapopulational genetic variation (average number of alleles and average expected heterozygosity per marker: 12.04 and 0.68, respectively) and weak genetic differentiation among populations (FST range: 0.003-0.052). In agreement with these estimates, Bolivian llamas showed a weak genetic structure and an intense gene flow between all the studied regional groups, which is due to the exchange of reproductive males between the different flocks. Interestingly, the groups for which the largest pairwise FST estimates were observed, Sud Lípez and Nor Lípez, showed a certain level of genetic differentiation that is probably due to the pattern of geographic isolation and limited communication infrastructures of these southern localities. Overall, the population parameters reported here may serve as a reference when establishing conservation policies that address Bolivian llama populations.

Analysis of mitochondrial DNA in Bolivian llama, alpaca and vicuna populations: a contribution to the phylogeny of the South American camelids.

The objectives of this work were to assess the mtDNA diversity of Bolivian South American camelid (SAC) populations and to shed light on the evolutionary relationships between the Bolivian camelids and other populations of SACs. We have analysed two different mtDNA regions: the complete coding region of the MT-CYB gene and 513 bp of the D-loop region. The populations sampled included Bolivian llamas, alpacas and vicunas, and Chilean guanacos. High levels of genetic diversity were observed in the studied populations. In general, MT-CYB was more variable than D-loop. On a species level, the vicunas showed the lowest genetic variability, followed by the guanacos, alpacas and llamas. Phylogenetic analyses performed by including additional available mtDNA sequences from the studied species confirmed the existence of the two monophyletic clades previously described by other authors for guanacos (G) and vicunas (V). Significant levels of mtDNA hybridization were found in the domestic species. Our sequence analyses revealed significant sequence divergence within clade G, and some of the Bolivian llamas grouped with the majority of the southern guanacos. This finding supports the existence of more than the one llama domestication centre in South America previously suggested on the basis of archaeozoological evidence. Additionally, analysis of D-loop sequences revealed two new matrilineal lineages that are distinct from the previously reported G and V clades. The results presented here represent the first report on the population structure and genetic variability of Bolivian camelids and may help to elucidate the complex and dynamic domestication process of SAC populations.

Porcine colonization of the Americas: a 60k SNP story.

The pig, Sus scrofa, is a foreign species to the American continent. Although pigs originally introduced in the Americas should be related to those from the Iberian Peninsula and Canary islands, the phylogeny of current creole pigs that now populate the continent is likely to be very complex. Because of the extreme climates that America harbors, these populations also provide a unique example of a fast evolutionary phenomenon of adaptation. Here, we provide a genome wide study of these issues by genotyping, with a 60k SNP chip, 206 village pigs sampled across 14 countries and 183 pigs from outgroup breeds that are potential founders of the American populations, including wild boar, Iberian, international and Chinese breeds. Results show that American village pigs are primarily of European ancestry, although the observed genetic landscape is that of a complex conglomerate. There was no correlation between genetic and geographical distances, neither continent wide nor when analyzing specific areas. Most populations showed a clear admixed structure where the Iberian pig was not necessarily the main component, illustrating how international breeds, but also Chinese pigs, have contributed to extant genetic composition of American village pigs. We also observe that many genes related to the cardiovascular system show an increased differentiation between altiplano and genetically related pigs living near sea level.

Síndrome metabólico en niñas púberes con hiperplasia suprarrenal congénita clásica / Metabolic syndrome among puberal girls with classic congenital adrenal hyperplasia

Background: Adult women with adrenal congenital hyperplasia (AH) have a higher risk for insulin resistance, dyslipidemia, hypertension, high body mass index (BMI) and increased body fat. All these factors are associated with cardiovascular risk and metabolic syndrome (MS). Aim: To evaluate the presence of MS in pubertal classic AH girls (CAH) and a control group (C). Material and Methods: We studied 15 pubertal AH patients (12.0 +/- 1.9 years) and 26 controls (11.7+/- 0.3 years) matched by age and tanner stage. Weight, height, BMI, waist/hip ratio, blood pressure and serum lipids were measured. An oral glucose tolerance test (OGTT) and insulin curve was performed in CAH girls whereas in controls basal insulin and glucose were determined. The homeostasis model assessment for insulin resistance (HOMAIR) was calculated. Cook, Ferranti and international diabetes federation (IDF) criteria were used to determine the presence of MS. Results: CAH and C girls had similar BMI (22.0 +/- 5.1 and 20.1 +/- 3.6 kg/m2 respectively; p = 0,11). CAH girls had higher basal blood glucose (80.8 +/- 7.7 and 60.6 +/- 10.6 mg/dl respectively, p < 0.01) and controls had higher triglyceride levels (147.0 +/- 69.3 and 79.7 +/-16.3 mg/dl respectively, p < 0.01) and lower HDL cholesterol levels (45.8 +/- 12.8 and 56.9 +/- 17.5 mg/dl respectively, p = 0.02). According to cook criteria 4 percent of CAH girls and 23 percent of controls has MS. These figures were 14 and 32 percent respectively according to Ferranti criteria and 0 and 5 percent respectively according to IDF criteria. Conclusions: CAH puberal patients do not have a higher prevalence of metabolic syndrome, compared with controls with similar Tanner stage and BMI.

Relación entre el polimorfismo -34 Bp de la región promotora del gen CYP17 con el perfil hormonal y metabólico en mujeres con diabetes mellitus tipo 1 / Relationship of -34 Bp polymorphism in the promoter of Cyp17 gene with hormonal and metabolic profile in women with type 1 diabetes mellitus

The P450c17a enzyme has a central role in ovarian hyperandrogenism, which is a characteristic of polycystic ovary syndrome (PCOS). Several studies have suggested a possible role for the CYP17 gene, which codes for the enzyme P450c17a and the -34bp T-C polymorphism in the development of hyperandrogenism. The presence of the cytosine, know as A2 allele, has been associated with hyperandrogenism in patients with PCOS. Objective: To evaluate the frequency and association of the -34bp polymorphism in the CYP17 gene and determine its association with hormonal and metabolic characteristics in women with DM1. Patients and Methods: The CYP17 polymorphism was studied in 72 DM1 and 71 control women by PCR and RFLP analysis. The CYP17 genetic dosage was compared with the antropometrical characteristics and the serum concentrations of testosterone, androstenedione, DHEAS and 17OH progesterone in women with DM1. Results: Genotype A2/A2 was present in 20.8 percent and 7.1 percent of DM1 and controls, respectively (p = 0,034). Allele A2 was present in 40.3 percent and 27.5 percent of DM1 and healthy women, respectively (p = 0,031). No association between CYP17 genotypes and hormonal or metabolic characteristics was observed. Conclusion: This study shows that the frequency of the A2/A2 genotype was higher in women with DM1 than in the control group. However, no association between the presence of the polymorphism and circulating steroid levels or BMI was observed.

[IGF-I sensitivity in small for gestational age children]. / Sensibilidad a IGF-I en niños pequeños para la edad gestacional.

BACKGROUND: The lack of catch up growth (CUG) in small for gestational age (SGA) children may be related to a reduced sensitivity to insulin growth factor 1 (IGF-I). AIM: To assess the sensitivity to IGF-I in small for gestational age children, measuring basal and post IGF-I nocturnal profile of growth hormone (GH). PATIENTS AND METHODS: We studied 34 prepubertal SGA children aged 4 to 11 years. Twenty three had CUG and 11 did not have CUG. As an IGF-I sensitivity test, nocturnal GH levels were measured every 20 minutes from 23:00 h to 07:00 h, both under baseline conditions and after the administration of a subcutaneous bolus of 1 mg/kg/body weight of the IGF-I + IGFBP-3 complex (Somatokine). RESULTS: At the time of the study, the Z scores for height among children with and without CUG were -1.55 +/- 0.22 and -3.24 +/- 0.28, respectively (p <0.0001). There were no statistical differences between CUG + vs CUG- patients in mean basal GH (6.6 +/- 0.5 and 5.6 +/- 0.6 ng/ml, respectively). After Somatokine administration, mean GH, and the mean GH area under the curve (AUC) decreased significantly in both groups. However, mean overnight GH AUC decreased in all SGA children with CUG, after Somatokine administration, whereas 3 out of 11 SGA children without CUG had an increase in their mean GH AUC in response to Somatokine. CONCLUSIONS: These findings suggest that pituitary sensitivity to IGF-I may be decreased in some SGA children without CUG.

Sensibilidad a IGF-I en niños pequeños para la edad gestacional / IGF-I sensitivity in small for gestational age children

Background: The lack of catch up growth (CUG) in small for gestational age (SGA) children may be related to a reduced sensitivity to insulin growth factor 1 (IGF-I). Aim: To assess the sensitivity to IGF-I in small for gestational age children, measuring basal and post IGF-I nocturnal profile of growth hormone (GH). Patients and methods: We studied 34 prepubertal SGA children aged 4 to 11 years. Twenty three had CUG and 11 did not have CUG. As an IGF-I sensitivity test, nocturnal GH levels were measured every 20 minutes from 23:00 h to 07:00 h, both under baseline conditions and after the administration of a subcutaneous bolus of 1 mg/kg/body weight of the IGF-I + IGFBP-3 complex (Somatokine®). Results: At the time of the study, the Z scores for height among children with and without CUG were -1.55 ± 0.22 and -3.24 ± 0.28, respectively (p <0.0001). There were no statistical differences between CUG + vs CUG- patients in mean basal GH (6.6 ± 0.5 and 5.6 ± 0.6 ng/ml, respectively). After Somatokine® administration, mean GH, and the mean GH area under the curve (AUC) decreased significantly in both groups. However, mean overnight GH AUC decreased in all SGA children with CUG, after Somatokine® administration, whereas 3 out of 11 SGA children without CUG had an increase in their mean GH AUC in response to Somatokine®. Conclusions: These findings suggest that pituitary sensitivity to IGF-I may be decreased in some SGA children without CUG.

Test de estimulación intraarterial selectiva con calcio en el diagnóstico de localización de insulinomas: Casos clínicos / Selective intra arterial calcium stimulation for the localization of insulinomas: Report of two cases

Insulinoma is the most common neuroendocrine tumor. Its clinical manifestations are frequently confounded with neuropsychiatric symptoms, and definitive diagnosis can be delayed for a long time. These tumors are usually small, of less than 2 cm. Thus, their preoperative localization is difficult. We report two patients with a clinical diagnosis of insulinoma, in whom the preoperative imaging study was negative. Both fulfilled diagnostic criteria, with high serum insulin levels in the presence of a blood glucose of less than 45 mg/dl. The imaging study, including abdominal computed tomography and pancreatic endoscopic ultrasonography did not disclose the location of the tumor. A pancreatic angiography with selective stimulation with intra arterial calcium and venous sampling for insulin measurements, was performed in both patients. This test allowed the exact localization of the tumors and their successful excision. A review of other localization diagnostic tests is done (Rev Méd Chile 2004; 132: 71-5).

Trasplante hepático en niños / Liver transplantation in children

Los trasplantes hepáticos constituyen el tratamiento más adecuado en gran número de pacientes con enfermedades crónicas y agudas terminales del hígado. La experiencia con este procedimiento es muy limitada en Chile. Se describen 11 niños que recibieron trasplantes hepáticos. La indicación más frecuente para hacerlo fue la atresia biliar. Se incluyeron receptores de alto riesgo como peso inferior a 10 kg, numerosas intervenciones quirúrgicas previas y hepatitis fulminante, pero no se registraron muertes intraoperatorias. En cuatro casos (36 por ciento) fue necesario hacer reducciones del hígado de los dadores para acomodarlos a receptores de bajo peso. Cinco receptores (45 por ciento) fueron tratados por rechazo agudo y no se han perdido injertos por causa inmunológica. Dos receptores fallecieron precozmente (uno por trombosis porta, otro por hipertensión intracraneana) y uno 15 meses después del trasplante por recidiva pulmonar y mediatínica de hepatoblastoma. La sobrevida actuarial es,hasta la fecha, 82 por ciento en un año. La serie demuestra que es posible realizar estos complejos procedimientos en el país, con similares resultados que en otros lugares del mundo

Experiencia de un centro en trasplante hepático en adultos y niños / Experience of a hepatic transplantation center in adults and children

Orthotopic liver transplantation (THO) is the treatment of choice for a variety of liver diseases. The national experience before 1993 has been scarce. In november 1993 we started our experience in THO at Clínica Las Condes, as part of a multiorgan transplant program (liver, kidney, pancreas). Until january 1995 we have performed 14 THO in 13 recipients (one retransplantation), of which 5 were in pediatric cases. The recipients range of age fluctuated between 1 and 61 years. In 2 pediatric cases a liver allograft reduction was performed. Six recipients (46 percent) required treatment for acute cellular rejection. One recipient had an hepatic artery thrombosis and had to be retransplanted. There was no operative mortality up to 30 days in cases of primary liver transplants. The retransplanted adult recipient and another pediatric recipient that died from a late recurrence of a hepatoblastoma, accounted for the mortality of this experience. After an average follow up to 10 months, the actual patient survival is 85 percent. Of the 11 surviving recipients, 9 are in excellent conditions with a very good quality of life. This experience shows that an active liver transplant program in our country can be succesfull in obtaining results comparable to those published by very experienced foreign transplant centers

[Evidence of a major gene in cleft lip/palate susceptibility by means of segregational analysis in the Chilean population]. / Evidencia de un gen mayor en la susceptibilidad a la fisura labiopalatina mediante analisis segregacional en la población Chilena.

The most generally accepted model for cleft lip/palate not associated to specific syndromes has been the one that postulates multifactorial inheritance with a threshold. Recent studies using complex analytical techniques have suggested the existence of a major gene with decreased penetrance in its etiology. Some authors have postulated that only a fraction of all cases of non-syndromic CL (P) would be explained by a single major gene. Other cases may be due to different genes, to environmental agents or to the interaction between them. The present study tests the monogenic inheritance model for CL (P) using segregation analysis in a sample of 211 extended pedigrees collected through CL (P) affected probands. The hypotheses of an autosomic recessive gene was analyzed in 151 sibships (size 2 or more) using "Apert's" method, "maximum likelihood method", "singles method" and "sib's, method" (single incomplete ascertainment). Results obtained do not support the hypotheses of autosomal recessive inheritance. Instead, the hypothesis of an autosomal dominant mode of inheritance with low penetrance is not rejected when analyzing the proportion of normal and affected progeny in certain types of matings in a subsample of 30 extended pedigrees with two or more affected individuals.

Bocio y tiroiditis linfocitaria crónica / Goiter and chronic lymphocitic thyroiditis

Se estudiaron 60 pacientes con bocio, de 3 a 16 años de edad, 58 eran mujeres, 38 (63%) de los cuales presentaba dos o más elementos sugerentes de tiroiditis linfocitaria crónica (TLC) (criterio de Fisher) destacando en ellos el compromiso de la función tiroidea 18/38 (47,4%) con hipotiroidismo y 7/38 (18,4%) con hipertiroidismo. Los demás pacientes con bocio difuso, que no cumplían los criterios de Fisher, fueron denominados "bocio no tiroiditis" (37%) y eran eutiroideos en proporción de 95%. En todos los pacientes con probable TLC se detectaron anticuerpos antimicrosomales en títulos relativamente altos. Sólo 32% tenían simultáneamente anticuerpos antimicrosomales y antitiroglobulinas positivos. Entre los 22 pacientes con "bocios no tiroiditis", 6 (28%) tenían anticuerpos antimicrosomales positivos, en títulos bajos (1 x 100 y 1 x 40, respectivamente). En un grupo control de 28 niños de edades similares a los propósitos, sin enfermedades endocrinas ni antecedentes familiares de afecciones tiroideas, sólo 3 (11%) presentaron anticuerpos positivos, en títulos bajos