Alendronate increases BMD at appendicular and axial skeletons in patients with established osteoporosis

<p>Abstract</p> <p>Background</p> <p>To identify high-risk patients and provide pharmacological treatment is one of the effective approaches in prevention of osteoporotic fractures. This study investigated the effect of 12-month Alendronate treatment on bone mineral density (BMD) and bone turnover biochemical markers in postmenopausal women with one or more non-traumatic fractures, i.e. patients with established osteoporosis.</p> <p>Methods</p> <p>A total of 118 Hong Kong postmenopausal Chinese women aged 50 to 75 with low-energy fracture at distal radius (Colles' fracture) were recruited for BMD measurement at lumbar spine and non-dominant hip using Dual-Energy X-ray Absorptiometry (DXA). 47 women with BMD T-score below -2 SD at either side were identified as patients with established osteoporosis and then randomized into Alendronate group (n = 22) and placebo control group (n = 25) for BMD measurement at spine and hip using DXA and distal radius of the non-fracture side by peripheral quantitative computed tomography (pQCT), and bone turnover markers, including bone forming alkaline phosphatase (BALP) and bone resorbing urinary Deoxypyridinoline (DPD). All measurements were repeated at 6 and 12 months.</p> <p>Results</p> <p>Alendronate treatment significantly increased BMD, more in weight-bearing skeletons (5.1% at spine and 2.5% at hip) than in non-weight bearing skeleton (0.9% at distal radius) after 12 months treatment. Spine T-score was significant improved in Alendronate group (p < 0.01) (from -2.2 to -1.9) but not in control placebo group. The Alendronate treatment effect was explained by significant suppression of bone turnover.</p> <p>Conclusion</p> <p>12 months Alendronate treatment was effective to increase BMD at both axial and appendicular skeletons in postmenopausal women with established osteoporosis.</p

Magnetic Resonance Water Proton Relaxation in Protein Solutions and Tissue: T1ρ Dispersion Characterization

BACKGROUND: Image contrast in clinical MRI is often determined by differences in tissue water proton relaxation behavior. However, many aspects of water proton relaxation in complex biological media, such as protein solutions and tissue are not well understood, perhaps due to the limited empirical data. PRINCIPAL FINDINGS: Water proton T(1), T(2), and T(1rho) of protein solutions and tissue were measured systematically under multiple conditions. Crosslinking or aggregation of protein decreased T(2) and T(1rho), but did not change high-field T(1). T(1rho) dispersion profiles were similar for crosslinked protein solutions, myocardial tissue, and cartilage, and exhibited power law behavior with T(1rho)(0) values that closely approximated T(2). The T(1rho) dispersion of mobile protein solutions was flat above 5 kHz, but showed a steep curve below 5 kHz that was sensitive to changes in pH. The T(1rho) dispersion of crosslinked BSA and cartilage in DMSO solvent closely resembled that of water solvent above 5 kHz but showed decreased dispersion below 5 kHz. CONCLUSIONS: Proton exchange is a minor pathway for tissue T(1) and T(1rho) relaxation above 5 kHz. Potential models for relaxation are discussed, however the same molecular mechanism appears to be responsible across 5 decades of frequencies from T(1rho) to T(1)

Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats

BACKGROUND: Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic rather than genetic processes. However, epigenetic changes at a single gene promoter are unlikely to account for the range of outcomes and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. METHODOLOGY/PRINCIPAL FINDINGS: We examine here using high-density oligonucleotide array the state of DNA methylation, histone acetylation and gene expression in a 7 million base pair region of chromosome 18 containing the NR3C1 gene in the hippocampus of adult rats. Natural variations in maternal care are associated with coordinate epigenetic changes spanning over a hundred kilobase pairs. The adult offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends associated with higher transcriptional activity across many genes within the locus examined. Other genes in this region remain unchanged, indicating a clustered yet specific and patterned response. Interestingly, the chromosomal region containing the protocadherin-α, -β, and -γ (Pcdh) gene families implicated in synaptogenesis show the highest differential response to maternal care. CONCLUSIONS/SIGNIFICANCE: The results suggest for the first time that the epigenetic response to maternal care is coordinated in clusters across broad genomic areas. The data indicate that the epigenetic response to maternal care involves not only single candidate gene promoters but includes transcriptional and intragenic sequences, as well as those residing distantly from transcription start sites. These epigenetic and transcriptional profiles constitute the first tiling microarray data set exploring the relationship between epigenetic modifications and RNA expression in both protein coding and non-coding regions across a chromosomal locus in the mammalian brain

Clear cell carcinoid tumor of the distal common bile duct

BACKGROUND: Carcinoid tumors rarely arise in the extrahepatic bile duct and can be difficult to distinguish from carcinoma. There are no reports of clear cell carcinoid (CCC) tumors in the distal bile duct (DBD) to the best of our knowledge. Herein, we report a CCC tumor in the DBD and review the literature concerning extrahepatic bile duct carcinoid tumors. CASE PRESENTATION: A 73-old man presented with fever and occult obstructive jaundice. Ultrasonography, computed tomography (CT) and magnetic resonance cholangiopancreaticography (MRCP) demonstrated a nodular tumor projection in the DBD without regional lymph node swelling. Under suspicion of carcinoma, we resected the head of the pancreas along with 2(nd )portion duodenectomy and a lymph node dissection. The surgical specimen showed a golden yellow polypoid tumor in the DBD (0.8 × 0.6 × 0.5 cm in size). The lesion was composed of clear polygonal cells arranged in nests and a trabecular pattern. The tumor invaded through the wall into the fibromuscular layer. Immunohistochemical stains showed that neoplastic cells were positive for neuron-specific enolase (NSE), chromogranin A, synaptophysin, and pancreatic polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and somatostatin. The postoperative course was uneventful and he is living well without relapse 12 months after surgery. CONCLUSION: Given the preoperative difficulty in differentiating carcinoid from carcinoma, the pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors located within the intra-pancreatic bile duct

Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference