Synthesis and Characterization of Specific Reverse Transcriptase Inhibitors for Mammalian LINE-1 Retrotransposons.

Retrotransposons are a type of transposable element (TE) that have amplified to astonishing numbers in mammalian genomes, comprising more than a third of the human and mouse genomes. Long interspersed element class 1 (LINE-1 or L1) retrotransposons are abundant and currently active retroelements in the human and mouse genomes. Similarly, long terminal repeat (LTR)-containing retrotransposons are abundant in both genomes, although only active in mice. LTR- and LINE-1-retroelements use different mechanisms for retrotransposition, although both involve the reverse transcription of an intermediate retroelement-derived RNA. Retrotransposon activity continues to effect the germline and somatic genomes, generating interindividual variability over evolution and potentially influencing cancer and brain physiology, respectively. However, relatively little is known about the functional consequences of retrotransposition. In this study, we have synthesized and characterized reverse transcriptase inhibitors specific for mammalian LINE-1 retrotransposons, which might help deciphering the functional impact of retrotransposition in vivo.

Bone speed of sound throughout lifetime assessed with quantitative ultrasound in a Mexican population.

The purpose of this study was to assess the bone speed of sound (SoS) through lifetime of a large Mexican population sample by determining the SoS from the radius and tibia using quantitative ultrasound (QUS). This is a cross-sectional evaluation of participants in the Mexican Health Workers Cohort Study. QUS measurements were performed using Sunlight Omnisense 8000P; Z- and T-scores were calculated for both sexes at the distal third of the radius and midshaft tibia, both on the nondominant side. A locally weighted regression smoothing scatterplot model was used to identify different phases of bone accretion and loss. A total of 9128 participants aged 1-75 yr were measured with QUS. Bone SoS accretion began 5 yr earlier in girls than boys (p<0.05). Maximal SoS or peak bone SoS was noted at 28 yr in the radius and at 22 yr in the tibia. Postmenopausal women (45-50 yr) showed significant SOS decrease at both sites (p<0.05) compared with men. Using the locally weighted regression smoothing scatterplot model, we found 5 different phases that constitute the biological development of bone over the life course, from ages 1-6, 7-12, 12-25, 25-50, and 50-75 yr (p<0.05). Our study shows the age- and sex-dependent changes and different phases of bone development expressed by SoS measurements of the radius and tibia. The values reported in this study can be used as a reference for urban Mexican population.

Enhancing effect of glucose microspheres in the viability of human mesenchymal stem cell suspensions for clinical administration.

PURPOSE: A critical limiting factor of cell therapy is the short life of the stem cells. In this study, glucose containing alginate microspheres were developed and characterized to provide a sustained release system prolonging the viability of human mesenchymal stem cells (hMSCs) in a suspension for clinical application. METHODS: The glucose microspheres were satisfactorily elaborated with alginate by emulsification/internal gelation method. Particle size was evaluated by light diffraction and optical microscopy. Shape and surface texture by scanning electron microscopy (SEM). Zeta potential, infrared spectra and release studies were also conducted. Also, rheological properties and stability of hMSCs suspensions with microspheres were tested. The viability of hMSCs was determined by trypan blue dye exclusion staining. RESULTS: Microspheres of 86.62 µm, spherical shaped and -32.54 mV zeta potential with excellent stability, good encapsulation efficiency and providing an exponential release of glucose were obtained. hMSCs had better survival rate when they were packed with glucose microspheres. Microspheres maintained the aseptic conditions of the cell suspension without rheological, morphological or immunophenotypic disturbances on hMSCs. CONCLUSIONS: Developed microspheres were able to enhance the functionality of hMSC suspension. This strategy could be broadly applied to various therapeutic approaches in which prolonged viability of cells is necessary.

Epidemiology of osteoporosis in Mexico. Present and future directions.

This position paper has been written by a multidisciplinary group of experts appointed by the National Institutes of Health (NIH). Its aim is to present the state of the art of knowledge about osteoporosis in Mexico. A review of the scientific papers in Mexico and information about diagnostics tools and treatment is discussed along with some research recommendations for the future.

Synthesis of pentahydroxylated pyrrolizidines and indolizidines.

1,3-Dipolar cycloaddition reaction of nitrone 7 and chemo-enzymatically obtained alkenediols 12 and 13 has been used in the synthesis of pentahydroxylated pyrrolizidines (8 and 10) and indolizidines (9 and 11). The pyrrolizidinic and indolizidinic skeletons were built after internal n-alkylation of the suitably functionalized pyrroloisoxazolidine intermediates obtained by the necessary protecting group manipulations. This method expands the scope of cycloaddition reactions in the synthesis of new and highly polyhydroxylated sugar-like alkaloids.

Direct costs of osteoporosis and hip fracture: an analysis for the Mexican Social Insurance Health Care System.

OBJECTIVE: To compare costs of diagnosis and annual treatment of osteoporosis and hip fracture between the Instituto Nacional de Rehabilitación (INR) and the protocol used by the Seguro Popular de Salud (SPSS). METHODS: Direct costs gathered in a prospective study with real cases at the INR are presented, and then this data is re-analyzed with the methodology and protocol for the SPSS to estimate the costs of those cases if treated with the SPSS protocol. RESULTS: Important differences were found in the cost of hip fracture: the SPSS estimates ($37,363.73 MXN) almost double the INR cost ($20,286.86 MXN ). This discrepancy was caused by the different types of surgeries the INR and SPSS protocols call for (the SPSS assumes that all hip fractures will necessitate a hip replacement) and the cost of subsequent hospitalization. A prospective study at the SPSS is needed to validate these results. CONCLUSIONS: Important differences were found between treatment of the same osteoporosis related problems at the INR and SPSS. We recommend revising the SPSS protocol to include less costly surgical treatments.

Direct costs of osteoporosis and hip fracture: an analysis for the Mexican Social Insurance Health Care System / Costos directos de la osteoporosis y fracturas de cadera: un análisis para el sistema de salud mexicano

OBJECTIVE: To compare costs of diagnosis and annual treatment of osteoporosis and hip fracture between the Instituto Nacional de Rehabilitación (INR) and the protocol used by the Seguro Popular de Salud (SPSS). METHODS: Direct costs gathered in a prospective study with real cases at the INR are presented, and then this data is re-analyzed with the methodology and protocol for the SPSS to estimate the costs of those cases if treated with the SPSS protocol. RESULTS: Important differences were found in the cost of hip fracture: the SPSS estimates ($37 363.73 MXN) almost double the INR cost ($20 286.86 MXN ). This discrepancy was caused by the different types of surgeries the INR and SPSS protocols call for (the SPSS assumes that all hip fractures will necessitate a hip replacement) and the cost of subsequent hospitalization. A prospective study at the SPSS is needed to validate these results. CONCLUSIONS: Important differences were found between treatment of the same osteoporosis related problems at the INR and SPSS. We recommend revising the SPSS protocol to include less costly surgical treatments.

OBJETIVO: Realizar una comparación de costos de diagnóstico y tratamiento anual de la osteoporosis y la fractura de cadera entre el Instituto Nacional de Rehabilitación (INR) y el protocolo utilizado por el Seguro Popular de Salud (SPSS). MATERIAL Y MÉTODOS: Los costos directos obtenidos en un estudio prospectivo con casos reales en el INR fueron utilizados para realizar un escenario considerando la metodología y protocolo del SPSS para estimar los costos de este último. RESULTADOS: Existen diferencias importantes en el costo de la fractura de cadera utilizando el escenario de SPSS; los costos estimados en SPSS fueron casi del doble respecto al INR ($37 363.73 vs. $20 286.86 pesos). Las diferencias están dadas por el tipo y costo de la cirugía (el SPSS asume que todas las fracturas de cadera tengan un remplazo total de cadera) y el costo de la hospitalización. Se requiere un estudio prospectivo para validar estos resultados en el SPSS. CONCLUSIONES: Se encontraron diferencias importantes entre el tratamiento de problemas relacionados con osteoporosis en el INR y el SPSS. Se recomienda revisar el protocolo del SPSS para incluir tratamientos quirúrgicos menos costosos.

Diastereoselective synthesis of quaternary alpha-amino acids from diketopiperazine templates.

Sequential enolate alkylations of (S)-N(1)-methyl-5-methoxy-6-isopropyl-3,6-dihydropyrazin-2-one and (S)-N(1)-p-methoxybenzyl-5-methoxy-6-isopropyl-3,6-dihydropyrazin-2-one proceed with excellent levels of diastereoselectivity (>90% de) affording quaternary alpha-amino acids in high enantiomeric excess (>98% ee) after deprotection and hydrolysis.

Asymmetric conjugate reductions with samarium diiodide: asymmetric synthesis of (2S,3R)- and (2S,3S)-[2-2H,3-2H]-leucine-(S)-phenylalanine dipeptides and (2S,3R)-[2-(2)H,3-2H]-phenylalanine methyl ester.

The highly diastereoselective samarium diiodide and D(2)O-promoted conjugate reduction of homochiral (E)- and (Z)-benzylidene and isobutylidene diketopiperazines (E)-5,7 and (Z)-6,8 has been demonstrated. This methodology allows the asymmetric synthesis of methyl (2S,3R)-dideuteriophenylalanine 27 in > or = 95% de and >98% ee, and (2S,3R)- or (2S,3S)-dideuterioleucine-(S)-phenylalanine dipeptides 37 and 38 in moderate de, 66% and 74% respectively. A mechanism is proposed to account for this process.

Diastereoselective conjugate reduction with samarium diiodide: asymmetric synthesis of methyl (2S,3R)-N-acetyl-2-amino-2,3-dideuterio-3-phenylpropionate.

A highly diastereoselective conjugate reduction using SmI2 and D2O has been demonstrated on a homochiral benzylidene diketopiperazine template, giving methyl (2S,3R)-N-acetyl-2-amino-2,3-dideuterio-3-phenylpropionate in 93% de and 90% ee after deprotection, hydrolysis and N-acetylation.

Tumor pardo de hiperparatiroidismo secundario: informe de un caso asociado a sindrome de absorción intestinal deficiente en una paciente con esclerosis sistemica progresiva / Brown tumor of secondary hyperparathyroidism: a case associated with severe intestinal malabsortion in a patient with progressive systemic sclerosis

Se describe el caso de una mujer de 44 años con esclerosis sistémica progresiva que cursó con síndrome de absorción intestinal deficiente de larga evolución, hipocalcemia grave y una lesión lítica humeral. La imagen histológica fue de un tumor pardo, con células gigantes multinucleadas de tipo osteoclástico, áreas de degeneración quística y hueso fibroso. La determinación de hormona paratiroidea resultó elevada, así como la fosfatasa alcalina. La asociación de tumor pardo con hiperparatiroidismo secundario es rara, y sido descrita casi exclusivamente en pacientes con hiperparatiroidismo secundario a enfermedad renal crónica. En este caso, un síndrome de absorción intestinal deficiente grave en una paciente con esclerosis sistémica causó hipocalcemia importante e hiperparatiroidismo secundario con enfermedad ósea prominente