Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance.

Glucagon-like peptide-2 receptor agonists have therapeutic potential for the treatment of intestinal diseases. The native hGLP-2, a 33 amino acid gastrointestinal peptide, is not a suitable clinical candidate, due to its very short half-life in humans. In search of GLP-2 receptor agonists with better pharmacokinetic characteristics, a series of GLP-2 analogues containing Gly substitution at position 2, norleucine in position 10, and hydrophobic substitutions in positions 11 and/or 16 was designed and synthesized. In vitro receptor potency at the human GLP-2, selectivity vs the human GLP-1 and GCG receptors, and PK profile in rats were determined for the new analogues. A number of compounds more potent at the hGLP-2R than the native hormone, showing excellent receptor selectivity and very low systemic clearance (CL) were discovered. Analogues 69 ([Gly(2),Nle(10),D-Thi(11),Phe(16)]hGLP-2-(1-30)-NH2), 72 ([Gly(2),Nle(10),D-Phe(11),Leu(16)]hGLP-2-(1-33)-OH), 73 ([Gly(2),Nle(10),D-Phe(11),Leu(16)]hGLP-2-(1-33)-NH2), 81 ([Gly(2),Nle(10),D-Phe(11),Leu(16)]hGLP-2-(1-33)-NHEt), and 85 ([Gly(2),Nle(10),D-Phe(11),Leu(16)]hGLP-2-(1-33)-NH-((CH2)2O)4-(CH2)2-CONH2) displayed the desired profiles (EC50 (hGLP-2R) < 100 pM, CL in rat <0.3 mL/min/kg, selective vs hGLP-1R and hGCGR). Compound 73 (FE 203799) was selected as a candidate for clinical development.

Prevalence of nutritional deficiencies in Mexican adolescent women with early and late prenatal care.

The objective was to evaluate the prevalence of specific nutritional deficiencies in a group of pregnant adolescents according to the gestational age when they started to receive prenatal care. A group of 163 pregnant adolescents that attended the Instituto Nacional de Perinatología (Mexico City) for the first time to receive prenatal care was evaluated. An anthropometrical evaluation was performed and a blood sample taken to determine hemoglobin, ferritin, erythrocyte folate and plasma zinc to all cases. The mean age was 15 years (11 to 17 years). The mean gestational age when starting prenatal care was 27 +/- 7 gestation weeks and most of them tended to have low weight (97 +/- 12% expected weight for height and gestational age). Eight of every ten adolescents had anemia and iron deficiency. Late prenatal care (> or = 25 weeks) was associated with the risk of presenting anemia OR 5.11 (CI 95% 2.4-10.7) iron deficiency (OR 3.5; CI 95% 1.7 to 7.1) and zinc deficiency (OR 2.9; CI 95% 1.1 a 7.6). In relation to folate deficiency, the opposite effect was observed (OR 0.10; CI 95% 0.02 a 0.48). Lack of opportune prenatal care was associated with the presence of iron and zinc depletion. Probably iron deficiency contributes to an erythrocyte folate accumulation.

Embarazo gemelar: determinantes maternas del peso al nacer / Twin pregnancies: maternal determinants for the birth weight

Antecedentes: El embarazo múltiple incrementa el riesgo a presentar complicaciones materno-fetales, elevando las cifras de morbimortalidad para ambos. Hoy en día los cambios corporales de la madre, así como las recomendaciones nutricias se encuentran ampliamente documentados para embarazo único, sin embargo, dicha información en el caso de embarazo múltiple es escasa.Objetivo: Analizar los determinantes para el peso al nacer, en embarazos gemelares, con el objetivo de establecer criterios de ganancia de peso ideal. Metodología: Se recolectó información sobre estatura, peso, edad y gestaciones de mujeres con embarazo gemelar que acudieron a control prenatal de 1999 a 2000 en el Instituto Nacional de Perinatología, así como el peso al nacer, longitud y edad gestacional de sus productos. Resultados: La media para las características biológicas de las madres fue de 28 años, dos gestaciones previas, 155 cm de estatura y un porcentaje de peso para la talla y edad gestacional de 117.5 por ciento. Ambos gemelos pesaron al nacer menos de 2,500 g según el percentil 50. Aunque este valor significa un bajo peso al nacer, los valores de Apgar fueron de ocho o superiores. La mayoría de los embarazos se resolvieron en la semana 35. Los determinantes que mostraron sensibilidad para el bajo peso al nacer fueron: edad (< 17 años), estatura (< 150 cm), gestaciones (1) y por ciento P/T y Eg (< 115). Conclusiones: El bajo peso al nacer es un problema común de los embarazos gemelares. Las mujeres adolescentes, bajas de estatura, primigrávidas y con bajo por ciento P/T y Eg tienen el mayor riesgo a tener productos de bajo peso. Una ganancia de 115 por ciento ( por ciento P/T y Eg) se debe promover y vigilar.