69 research outputs found

    Central control of bone remodeling by neuromidin U.

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    Bone remodeling, the function affected in osteoporosis, the most common of bone diseases, comprises two phases: bone formation by matrix-producing osteoblasts 1 and bone resorption by osteoclasts 2 . The demonstration that the anorexigenic hormone leptin 3-5 inhibits bone formation through a hypothalamic relay Bone mass is maintained at a constant level between puberty and menopause by a succession of bone-resorption and bone-formation phases NMU is a small peptide produced by nerve cells in the submucosal and myenteric plexuses in the small intestine, and also by structures in the brain, including the dorsomedial nucleus of the hypothalamus 9 . It is generally assumed that NMU acts as a neuropeptide to regulate various aspects of physiology, including appetite, stress response and SNS activation 9 . Indeed, NMU-deficient (Nmu -/-) mice develop obesity due to increased food intake and reduced locomotor activity that is believed, at least in part, to be leptin independent 8 . In addition, expression of NMU is diminished in leptin-deficient (Lep ob ) mice 18 , but can be induced in these mice by leptin treatment When assessed at 3 and 6 months of age, both male and female Nmu -/-mice showed a high bone mass phenotype as compared to the wild type (WT), with male mice more severely affected than female mic

    Phamacogenomics of Clozapine-Induced Agranulocytosis

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    Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

    Association between FGF23, α-Klotho, and Cardiac Abnormalities among Patients with Various Chronic Kidney Disease Stages.

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    Several experimental studies have demonstrated that fibroblast growth factor 23 (FGF23) may induce myocardial hypertrophy via pathways independent of α-Klotho, its co-factor in the induction of phosphaturia. On the other hand, few studies have clearly demonstrated the relationship between FGF23 level and left ventricular hypertrophy among subjects without chronic kidney disease (CKD; i.e., CKD stage G1 or G2).To investigate the data from 903 patients admitted to the cardiology department with various degrees of renal function, including 234 patients with CKD stage G1/G2.Serum levels of full-length FGF23 and α-Klotho were determined by enzyme immunoassay. After adjustment for sex, age, and estimated glomerular filtration rate (eGFR), the highest FGF23 tertile was significantly associated with left ventricular hypertrophy among patients with CKD stage G1/G2 and those with CKD stage G3a/G3b/G4 as compared with the lowest FGF23 tertile, and the association retained significance after further adjustment for serum levels of corrected calcium, inorganic phosphate, and C-reactive protein, as well as diuretic use, history of hypertension, and systolic blood pressure. FGF23 was also associated with low left ventricular ejection fraction among patients with CKD stage G1/G2 and those with CKD stage G3a/G3b/G4 after adjusting for age, sex, eGFR, corrected calcium, and inorganic phosphate. On the other hand, compared with the highest α-Klotho tertile, the lowest α-Klotho tertile was associated with left ventricular hypertrophy and systolic dysfunction only among patients with CKD stage G3b and stage G3a, respectively.An association between FGF23 and cardiac hypertrophy and systolic dysfunction was observed among patients without CKD as well as those with CKD after multivariate adjustment. However, the association between α-Klotho and cardiac hypertrophy and systolic dysfunction was significant only among patients with CKD G3b and G3a, respectively
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