Ludivina Robles-Osorio

Publications of Ludivina Robles-Osorio

• Iodine nutrition status in pregnant women in Mexico.

  Authors: Pablo García-Solís, Juan Carlos Solís-S, Ana Cristina García-Gaytán, Vanessa Amaranta Reyes-Mendoza, Ludivina Robles-Osorio, Hebert Luis Hernández-Montiel, Guillermo Enrique Leo-Amador

  Thyroid : official journal of the American Thyroid Association. 12/2011; 21(12):1367-71.

  Iodine nutrition during pregnancy has become an important public health concern because of the deleterious impact of iodine deficiency on brain development during fetal and early postnatal life.Iodine nutrition during pregnancy has become an important public health concern because of the deleterious impact of iodine deficiency on brain development during fetal and early postnatal life. Iodine nutrition status can be assessed in a population by the median urinary iodine concentration (UIC). World Health Organization, the United Nations Children's Fund, and the International Council for Iodine Deficiency Disorders have established that a median of UIC between 150 and 249 μg/L in pregnant women indicates an adequate iodine intake. The aim of this study was to assess iodine nutrition status in Mexican pregnant women. Two hundred ninety-four pregnant women receiving prenatal care in the Public Medical Units of the State Ministry of Health for each pregnancy trimester (first, n=60; second, n=103; and third, n=131) in Queretaro, Mexico, were enrolled to assess UIC by the Sandell-Kholtoff method. The median of UIC was 273, 285, and 231 μg/L in the first, second, and third trimesters of gestation, respectively. Globally, the median (range) of UIC was 260 (5-1320) μg/L, and the percentage of samples with UIC below 150 μg/L was 28%. There was no significant difference between the UIC of women using iodine-containing multivitamins compared with those who reported the consumption of noniodized multivitamins (p>0.05). In addition, we found no difference between the UIC of women using iodized table salt compared with those who employed noniodized table salt, with those who did not know whether their table salt was iodized (p>0.05). Based on the median UIC, iodine intake in Queretaro, Mexico, is slightly above requirements during the first two trimesters, and adequate in the third trimester. The wide Mexican universal iodized salt program seems to supply adequate dietary iodine to pregnant women without health insurance in this region. However, regular monitoring of iodine status is recommended during pregnancy throughout Mexico.

• Inhibition of intrathyroidal dehalogenation by iodide.

  Authors: Juan C Solis-S, Patricia Villalobos, Aurea Orozco, Guadalupe Delgado, Andres Quintanar-Stephano, Pablo Garcia-Solis, Hebert L Hernandez-Montiel, Ludivina Robles-Osorio, Carlos Valverde-R

  The Journal of endocrinology. 10/2010; 208(1):89-96.

  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 recyclingIodide 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.

• Analysis of fasting plasma glucose values for optimal detection of abnormal responses on the oral glucose tolerance test in at-risk study subjects.

  Authors: Ludivina Robles-Osorio, Carlos A Aguilar-Salinas, Roopa Mehta, Francisco J Gómez-Pérez, Juan A Rull

  Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 10/2007; 13(6):583-9.

  OBJECTIVE: To identify the fasting plasma glucose (FPG) value with the best performance for detecting an abnormal response on the oral glucose tolerance test (OGTT) in patients at risk for havingOBJECTIVE: To identify the fasting plasma glucose (FPG) value with the best performance for detecting an abnormal response on the oral glucose tolerance test (OGTT) in patients at risk for having type 2 diabetes. METHODS: All patients who underwent a 2-hour OGTT during an 18-month period were included in this study. Pretest and posttest odds, likelihood ratios, and receiver operating characteristic curves were used to identify the FPG value most strongly associated with an abnormal result on the OGTT (either diabetes or impaired glucose tolerance [IGT]). RESULTS: Of the 1,371 patients who underwent an OGTT during the designated study period, 1,239 fulfilled the inclusion criteria. The prevalence of IGT was 25.34% (314 patients). Diabetes was diagnosed in 141 patients (11.38%). IGT was more commonly found in the FPG strata below 115 mg/dL; above this value, diabetes was more frequently diagnosed. In general, the percentage of cases of IGT increased progressively throughout the "normal" FPG range. The prevalence varied from 11.4% (in patients with FPG values <80 mg/dL) to 32% (in those with FPG levels from 95 to 99.9 mg/dL). FPG values between 95 and 99.9 mg/dL had a likelihood ratio of 2.1 for detecting an abnormal OGTT response, of 1.8 for detecting diabetes, and of 1.66 for detecting IGT. The odds ratio for detecting either IGT or diabetes was increased 2-fold by performing an OGTT. The FPG threshold with the best ability for detecting an abnormal response on the OGTT was 95 mg/dL (sensitivity of 0.72 and specificity of 0.65). CONCLUSION: In patients at risk for type 2 diabetes, the FPG cut point (95 mg/dL) most useful for detecting an abnormal OGTT response is included in the normal range of the FPG.

• Genetic heterogeneity of autosomal dominant hypercholesterolemia in Mexico.

  Authors: Ludivina Robles-Osorio, Alejandra Huerta-Zepeda, Ma Luisa Ordóñez, Samuel Canizales-Quinteros, Andrea Díaz-Villaseñor, Ruth Gutiérrez-Aguilar, Laura Riba, Adriana Huertas-Vázquez, Maribel Rodríguez-Torres, Rita A Gómez-Díaz [......] Laura Ongay-Larios, Guadalupe Codiz-Huerta, Minerva Mora-Cabrera, Roopa Mehta, Francisco J Gómez-Pérez, Juan A Rull, Jean-Pierre Rabès, Ma Teresa Tusié-Luna, Socorro Durán-Vargas, Carlos A Aguilar-Salinas

  Archives of medical research. 02/2006; 37(1):102-8.

  BACKGROUND: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are relatively common lipid disorders caused by mutations of the low-density lipoprotein receptorBACKGROUND: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are relatively common lipid disorders caused by mutations of the low-density lipoprotein receptor (LDLR) and apolipoprotein B (apoB) genes, respectively. A third locus on chromosome 1p34.1-p32 was recently linked to FH and the responsible gene has been identified [protein convertase subtilisin/kexin type 9 (PCSK9)]. METHODS: We assessed the contribution of the LDLR, apoB, and PCSK9 genes as cause of FH in Mexico. Forty six unrelated probands, as well as 68 affected and 60 healthy relatives, were included. RESULTS: All index cases were diagnosed as having heterozygous autosomal dominant FH. Seventeen of the 46 index cases had LDLR gene mutations, four of which were novel (Fs92ter108, C268R, Q718X, and Fs736ter743); and only one patient had an apoB mutation (R3500Q). We sequenced the PCSK9 gene in the remainder of the 28 probands with no identified LDLR or APOB gene defects; however, no PCSK9 mutations were found, including one large kindred with positive linkage to the 1p34.1-32 locus (multipoint LOD score of 3.3) and two small pedigrees. Linkage was excluded from these three loci in at least four kindreds suggesting that other yet uncharacterized genes are involved. CONCLUSIONS: Our results underline substantial genetic heterogeneity for FH in the Mexican population.

• A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia.

  Authors: Samuel Canizales-Quinteros, Carlos A Aguilar-Salinas, Adriana Huertas-Vázquez, María L Ordóñez-Sánchez, Maribel Rodríguez-Torres, José L Venturas-Gallegos, Laura Riba, Salvador Ramírez-Jimenez, Rocío Salas-Montiel, Giovani Medina-Palacios, Ludivina Robles-Osorio, Angel Miliar-García, Luis Rosales-León, Blanca H Ruiz-Ordaz, Alejandro Zentella-Dehesa, Adrian Ferré-D'Amare, Francisco J Gómez-Pérez, Ma Teresa Tusié-Luna

  Human genetics. 01/2005; 116(1-2):114-20.

  Autosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this conditionAutosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this condition (1p35, 15q25-q26 and 13q). Recently, the responsible gene at the 1p35 locus, encoding an LDL receptor adaptor protein (ARH) has been identified. We studied a Mexican ARH family with two affected siblings. Sequence analysis of the ARH gene (1p35 locus) revealed that the affected siblings are homozygous for a novel mutation (IVS4+2T>G) affecting the donor splice site in intron 4, whereas both the parents and an unaffected sister are heterozygous for this mutation. The IVS4+2T>G mutation results in a major alternative transcript derived from a cryptic splice site, which carries an in-frame deletion of 78 nucleotides in the mature mRNA. The translation of this mRNA yields a mutant protein product (ARH-26) lacking 26 amino acids, resulting in the loss of beta-strands beta6 and beta7 from the PTB domain. This is the first case where a naturally occurring mutant with an altered PTB domain has been identified.

• Familial hypercholesterolemia due to ligand-defective apolipoprotein B100: first case report in a Mexican family.

  Authors: Ludivina Robles-Osorio, Ma Luisa Ordoñez, Carlos A Aguilar-Salinas, Moisés Aurón-Gómez, Ma Teresa Tusié-Luna, Francisco J Gómez-Pérez, Juan A Rull-Rodrigo

  Archives of medical research. 34(1):70-5.

  BACKGROUND: Familial defective apolipoprotein B100 (FDB) is one of the known causes of familial hypercholesterolemia (FH). Its frequency among subjects with FH varies among ethnic groups; informationBACKGROUND: Familial defective apolipoprotein B100 (FDB) is one of the known causes of familial hypercholesterolemia (FH). Its frequency among subjects with FH varies among ethnic groups; information on FH is insufficient for populations from Latin America. We proposed to describe prevalence of FDB in a cohort of Mexican FH probands (n = 30). METHODS: We searched for the known FDB mutations using polymerase chain reaction assays. In this set of patients, mean lipid values were representative of FH (cholesterol 351 mg/dL, LDL cholesterol 274 mg/dL, HDL cholesterol 51 mg/dL, and triglycerides 132 mg/dL). RESULTS: One subject with Arg3500Gln mutation was found: a 44-year-old male with a history of coronary heart disease (CHD) among paternal relatives. His lipid profile was cholesterol 370 mg/dL, LDL-cholesterol 300 mg/dL, HDL-cholesterol 32 mg/dL, and triglycerides 189 mg/dL. Tendinous xanthomata were detected. Three of four siblings, one of three sons, and one of nine nieces and nephews carried the mutation. The mutation was confirmed by automated sequencing. Tendinous xanthomata were absent in affected subjects younger than age 20 years; additionally, the subjects had borderline cholesterol levels. CONCLUSIONS: Our data suggest that FDB explains the small number of FH cases in Mexico. Inclusion of molecular biology assays to the clinical laboratory makes it possible to diagnose affected individuals with borderline cholesterol levels or without tendinous xanthomata.

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• [Bioactivity of thyroid hormones. Clinical significance of membrane transporters, deiodinases and nuclear receptors].

  Authors: Juan Carlos Solís, Aurea Orozco, Carlota García, Ludivina Robles-Osorio, Carlos Valverde

  Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición. 63(3):287-308.

  The study of the different factors regulating the bioactivity of thyroid hormones is of utmost relevance for an adequate understanding of the glandular pathophysiology. These factors must beThe study of the different factors regulating the bioactivity of thyroid hormones is of utmost relevance for an adequate understanding of the glandular pathophysiology. These factors must be considered by the clinician in order to achieve a successful diagnosis and treatment of glandular diseases. Among the factors regulating bioactivity of thyroid hormones are the following: A) Plasmatic membrane hormone transporters, which tissue-specific expression is responsible for the cellular uptake of hormones, B) A set of deiodinating enzymes which activate or inactivate intracellular thyroid hormone, and C) Nuclear receptors which are responsible for the different cellular responses at the transcriptional level. This review compiles analysis and discusses the most recent findings regarding the regulation of thyroid hormone bioactivity, as well as the clinical relevance of different polymorphisms and mutations currently described for membrane transporters and deiodinases. In addition, the main issues and present and future study areas are identified.