Effects of 3 Years of Treatment with a Selective Estrogen Receptor Modulator for Postmenopausal Osteoporosis on Markers of Bone Turnover and Bone Mineral Density

Aim: The aim of the present study was to assess the changes in bone mineral density and bone turnover markers in long-term SERM. Methods: The study was performed on 25 female outpatients with primary osteoporosis treated at the Osteoporosis Department of Showa University School of Medicine. All patients had been on raloxifene (60mg/day) for ≥ 3 years. The mean patient age was 67.1 years and the women were, on average, 18.4 years postmenopausal. Levels of bone turnover markers (urinary naltrexone [NTX] and bone-specific alkaline phosphatase [BAP]) and bone mineral density (BMD; front lumbar vertebrae, three proximal femur sites, and two distal radius sites) were determined before and then annually after starting raloxifene for a period of 3 years. Results: Over the 3-year treatment period, significant decreases were seen in both urinary NTX and BAP levels. Although BMD of the lumbar vertebrae and distal radius was increased over the 3 years after initiation of raloxifene treatment, the difference failed to reach statistical significance. The BMD of the femoral neck decreased, whereas that of the femoral trochanter and femoral intertrochanter area increased. Conclusions: The selective estrogen receptor modulator raloxifene is suitable for the treatment of osteoporosis in postmenopausal patients because it reduces bone turnover while maintaining adequate bone density

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

As ações afirmativas em favor dos homossexuais : fundamentos jurídicos = Affirmative actions in favor of homosexuals : legal fundaments

A união homossexual é realidade da vida social embora tratada com preconceito e discriminação. Por um lado, negam-se a ela direitos básicos da cidadania e, por outro, implementam-se em seu favor as ações afirmativas, através de processos judiciais e extrajudiciais, com tendência de reconhecimentos de direitos, baseados na igualdade e na dignidade humana do homossexual. Se da união homossexual surgem efeitos pessoais e patrimoniais, observa-se a falta de legislação regulando este relacionamento, no Brasil. A lacuna é preenchida por analogia, costume e princípios gerais de direito. O Judiciário vem reconhecendo direitos aos parceiros homossexuais, tratando a sua união como uma nova espécie de família, no âmbito do Direito de Família, refletindo-se seus efeitos jurídicos no Direito Sucessório e demais ramos do Direito.Homosexual unions constitute a reality in social life, although they are still faced with prejudice and discrimination. Homosexual couples are denied the basic rights of citizenship. Aiming to rescue the equality and human dignity of homosexuals, affirmative actions have been implemented in favor of this group, through public policies and judicial actions. Personal and patrimonial consequences arouse from homosexual unions. However, there is no legislation regulating this modality in our legal system. To fill the gap, based on constitutional principles of rights, the Judiciary recognizes rights to homosexual partners, dealing with their union as a new type of family in the ambit of Family Law, reflecting its legal effects in the the Successory Right and in other sections of the law

An in vitro model of polycystic liver disease using genome-edited human inducible pluripotent stem cells

In the developing liver, bile duct structure is formed through differentiation of hepatic progenitor cells (HPC) into cholangiocytes. A subtype of polycystic liver diseases characterized by uncontrolled expansion of bile ductal cells is caused by genetic abnormalities such as in that of protein kinase C substrate 80 K-H (PRKCSH). In this study, we aimed to mimic the disease process in vitro by genome editing of the PRKCSH locus in human inducible pluripotent stem (iPS) cells. A proportion of cultured human iPS cell-derived CD13+CD133+ HPC differentiated into CD13− cells. During the subsequent gel embedding culture, CD13− cells formed bile ductal marker-positive cystic structures with the polarity of epithelial cells. A deletion of PRKCSH gene increased expression of cholangiocytic transcription factors in CD13− cells and the number of cholangiocytic cyst structure. These results suggest that PRKCSH deficiency promotes the differentiation of HPC-derived cholangiocytes, providing a good in vitro model to analyze the molecular mechanisms underlying polycystic diseases. Keywords: Human iPS cells, Polycystic liver disease, Genome editing, Cholangiocyt

Development of a Transgenic Mouse with R124H Human TGFBI Mutation Associated with Granular Corneal Dystrophy Type 2.

To investigate the phenotype and predisposing factors of a granular corneal dystrophy type 2 transgenic mouse model.Human TGFBI cDNA with R124H mutation was used to make a transgenic mouse expressing human protein (TGFBIR124H mouse). Reverse transcription PCR (RT-PCR) was performed to analyze TGFBIR124H expression. A total of 226 mice including 23 homozygotes, 106 heterozygotes and 97 wild-type mice were examined for phenotype. Affected mice were also examined by histology, immunohistochemistry and electron microcopy.RT-PCR confirmed the expression of TGFBIR124H in transgenic mice. Corneal opacity defined as granular and lattice deposits was observed in 45.0% of homozygotes, 19.4% of heterozygotes. The incidence of corneal opacity was significantly higher in homozygotes than in heterozygotes (p = 0.02). Histology of affected mice was similar to histology of human disease. Lesions were Congo red and Masson Trichrome positive, and were observed as a deposit of amorphous material by electron microscopy. Subepithelial stroma was also stained with thioflavin T and LC3, a marker of autophagy activation. The incidence of corneal opacity was higher in aged mice in each group. Homozygotes were not necessarily more severe than heterozygotes, which deffers from human cases.We established a granular corneal dystrophy type 2 mouse model caused by R124H mutation of human TGFBI. Although the phenotype of this mouse model is not equivalent to that in humans, further studies using this model may help elucidate the pathophysiology of this disease