Identification of a parathyroid hormone in the fish Fugu rubripes.

A PTH gene has been isolated from the fish Fugu rubripes. The encoded protein of 80 amino acid has the lowest homology with any of the PTH family members. Fugu PTH(1-34) had 5-fold lower potency than human PTH(1-34) in a mammalian cell system. INTRODUCTION: Parathyroid hormone (PTH) is the major hypercalcemic hormone in higher vertebrates. Fish lack parathyroid glands, but there have numerous attempts to identify and isolate PTH from fish. MATERIALS AND METHODS: Polymerase chain reaction (PCR) was performed with primers based on preliminary data from the Joint Genome Institute database. PCR amplification was performed on genomic DNA isolated from Fugu rubripes. PCR products were purified and DNA was sequenced. All sequence was confirmed from more than one independently amplified PCR product. Multiple sequence alignments were carried out, and the percentage of identities and similarities were calculated. An unrooted phylogenetic tree, using all the known PTH and PTH-related protein (PTHrP) amino acid sequences, was determined. Synthetic peptides were tested in a biological assay that measured cyclic adenosine 3',5'-monophosphate formation in UMR106.1 cells. Rabbit polyclonal antisera specific for N-terminal human PTHrP and one rabbit polyclonal antiserum specific for N terminus hPTH were used to test the cross-reactivity with fPTH(1-34) in immunoblots.     

Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage

Journal of Thrombosis and Thrombolysis - Limited data exists regarding the clinical outcomes of andexanet alfa and four factor prothrombin complex concentrate (4F-PCC) for reversal of apixaban or...     

Effects of Amylin Deficiency on Trabecular Bone in Young Mice Are Sex-Dependent

Amylin deficiency in mice results in late-onset osteopenia. Sex differences have been identified in insulin secretion in Amylin-overexpressing transgenic mice, suggesting a possible interaction of sex steroids, growth factors, or cytokines and amylin. The aim of the current study was to compare the effects of amylin deficiency on bone in young and adult male and female mice. The metaphyses of the distal femora from male and female Amylin-deficient mice at 4, 6, and 26 weeks of age were assessed by bone histomorphometry. Femoral length was increased in Amylin-deficient male mice compared to wild-type (WT) mice at 26 weeks of age (P < 0.005) but not in females. This was associated with an increase in growth plate height in Amylin-deficient males at 4 (P < 0.01) and 6 (P < 0.05) weeks of age. Furthermore, young Amylin-deficient males had decreased trabecular number at 4 weeks of age (P < 0.05) and increased trabecular thickness at 4 and 6 weeks of age (P < 0.05) compared to WT mice, with no net change in trabecular bone volume. These effects of amylin deficiency were not observed in female mice. In conclusion, this study demonstrates that amylin deficiency exerts effects on bone during growth that are sex-dependent and suggest a possible interaction between amylin and testosterone, growth factors, or cytokines to regulate bone cell metabolism.     

Popular knowledge related to back pain in northeastern Brazilian women

Analyzing and understanding people's conceptions and actions regarding back pain is relevant since they can be part of the disease's explanation and cure. The nature of this study is qualitative with an anthropological focus. It was carried out from January to February, 2005 with nine women between 45 and 58 years of age with chronic back pains who participated in a health support group for menopausal women in a teaching institution in Fortaleza, Ceará. Nine (9) in-depth ethnographic interviews were conducted with key informants exploring their problems, worries, coping strategies, their notion of quality of life and barriers to achieving this, especially as related to back pain. It was observed that back pain encompasses problems and solutions ranging from psychological, socioeconomic and political to educational aspects. Despite informants' low educational levels, they present a holistic view of health and a rich coping and cure-seeking experience. Because daily life activities can be considered as cultural risk, they need to be considered. It is, thus, necessary to consider the socio-cultural, economic, political and environmental context, in order to develop educational actions to promote health.     

Redd1 is a novel marker of testis development but is not required for normal male reproduction

In an effort to identify novel candidate genes involved in testis determination, we previously used suppression subtraction hybridisation PCR on male and female whole embryonic (12.0-12.5 days post coitum) mouse gonads. One gene to emerge from our screen was Redd1. In the current study, we demonstrate by whole-mount in situ hybridisation that Redd1 is differentially expressed in the developing mouse gonad at the time of sex determination, with higher expression in testis than ovary. Furthermore, Redd1 expression was first detected as Sry expression peaks, immediately prior to morphological sex determination, suggesting a potential role for Redd1 during testis development. To determine the functional importance of this gene during testis development, we generated Redd1-deficient mice. Morphologically, Redd1-deficient mice were indistinguishable from control littermates and showed normal fertility. Our results show that Redd1 alone is not required for testis development or fertility in mice. The lack of a male reproductive phenotype in Redd1 mice may be due to functional compensation by the related gene Redd2.     

Osteoblast deletion of exon 3 of the androgen receptor gene results in trabecular bone loss in adult male mice.

The mechanism of androgen action on bone was studied in male mice with the AR deleted in mature osteoblasts. These mice had decreased trabecular bone volume associated with a decrease in trabecular number, suggesting that androgens may act directly on osteoblasts to maintain trabecular bone. INTRODUCTION: Androgens modulate bone cell activity and are important for the maintenance of bone mass. However, the mechanisms by which they exert these actions on bone remain poorly defined. The aim of this study was to investigate the role of androgens acting through the classical androgen receptor (AR) signaling pathways (i.e., DNA-binding dependent pathways) in osteoblasts using male mice in which exon 3 of the AR gene was deleted specifically in mature osteoblasts. MATERIALS AND METHODS: Mice with a floxed exon 3 of the AR gene were bred with Col 2.3-cre transgenic mice, in which Cre recombinase is expressed in mineralizing osteoblasts. The skeletal phenotype of mutant mice was assessed by histomorphometry and quantitative microCT at 6, 12, and 32 weeks of age (n=8 per group). Wildtype, hemizygous exon 3 floxed and hemizygous Col 2.3-cre male littermates were used as controls. Data were analyzed by one-way ANOVA and Tukey's posthoc test. RESULTS: microCT analysis of the fifth lumbar vertebral body showed that these mice had reduced trabecular bone volume (p<0.05) at 32 weeks of age compared with controls. This was associated with a decrease in trabecular number (p<0.01) at 12 and 32 weeks of age, suggesting increased bone resorption. These effects were accompanied by a reduction in connectivity density (p<0.01) and an increase in trabecular separation (p<0.01). A similar pattern of trabecular bone loss was observed in the distal femoral metaphysis at 32 weeks of age. CONCLUSIONS: These findings show that inactivation of the DNA binding-dependent functions of the AR, specifically in mature osteoblasts in male mice, results in increased bone resorption and decreased structural integrity of the bone, leading to a reduction in trabecular bone volume at 32 weeks of age. These data provide evidence of a role for androgens in the maintenance of trabecular bone volume directly through DNA binding-dependent actions of the AR in mature osteoblasts.     

Philosophy of Healthcare Ethics Practice Statements: Quality Attestation and Beyond

One element of the American Society for Bioethics and Humanities’ recently-piloted quality attestation portfolio for clinical ethics consultants is a “philosophy of clinical ethics consultation statement” describing the candidate’s approach to clinical ethics consultation. To date, these statements have been under-explored in the literature, in contrast to philosophy statements in other fields such as academic teaching. In this article, I argue there is merit in expanding the content of these statements beyond clinical ethics consultation alone to describe the author’s approach to other important “domains” of healthcare ethics practice (e.g., organizational policy development/review and ethics teaching). I also claim such statements have at least three additional uses outside quality attestation: (1) as a reflective practice learning tool to increase role clarity among practicing healthcare ethicists and bioethics fellows; (2) assisting practicing healthcare ethicists in clarifying role expectations with those they work with; and (3) helping inform developing professional practice standards.