Objcetive To evaluate the clinical significance of bone biochemical metabolic markers in osteoporosis( OP),and investigate the clinical application value of the determination.Methods BMD at various skeletal sites was measured by XR-36 dual energy X-ray absorptiometry for 65 patients.Enzyme linked immunosorbent assay (ELISA) were used to determine bone biochemical metabolic markers in sera of 65 patients with osteoporosis and 62healthy controls.Results The levels of serum TRACP5b and 25-OH-VD3/25-OH-VD2 in OP group were higher than that in control group( P ＜0.05),meanwhile the level of BGP,BAP and Ca were varying degrees higher than that in control group,but the level of P was lower than that in control group.Conclusion TRACP5b,BGP,BAP,VD3/2 and other bone metabolic markers can be used as indicators of early detection of osteoporosis,in order to provide valuable data for early treatment of osteoporosis.

AIM:To investigate whether Smad pathway participates the process of extracellular signal regulated kinase (ERK) induced the proliferation of vascular smooth muscle cells (VSMCs). METHODS: Human umbilical artery smooth muscle cells (hUASMCs) were divided into four groups: control group, PDGF (platelet derived growth factor) group, ERK blocking agent group and PDGF+ERK blocking agent group. MTT assay was used to detect the proliferation of hUASMCs (A value). Immunohistochemical technique was used to detect the expression of PCNA, phosphorylated ERK (p-ERK) and phosphorylated Smad2/3 (p-Smad2/3) protein in hUASMCs. The expression of Smad2/3 mRNA in hUASMCs was detected by RT-PCR. RESULTS: The proliferation of hUASMCs and the expression of PCNA, p-ERK and p-Smad2/3 proteins in hUASMCs in PDGF group were increased obviously than those in other groups (P

OBJECTIVETacrolimus (FK506) is an immunosuppressive drug, which is widely used to prevent rejection of transplanted organs. However, chronic administration of FK506 leads to hypertension in solid organ transplantation patients, and its molecular mechanisms are much more complicated. In this review, we will discuss the above-mentioned molecular mechanisms of FK506-induced hypertension in solid organ transplantation subjects.

DATA SOURCESThe data analyzed in this review were mainly from relevant articles without restriction on the publication date reported in PubMed. The terms "FK506" or "tacrolimus" and "hypertension" were used for the literature search.

STUDY SELECTIONOriginal articles with no limitation of research design and critical reviews containing data relevant to FK506-induced hypertension and its molecular mechanisms were retrieved, reviewed and analyzed.

RESULTSThere are several molecular mechanisms attributed to FK506-induced hypertension in solid organ transplantation subjects. First, FK506 binds FK506 binding protein 12 and its related isoform 12.6 (FKBP12/12.6) and removes them from intracellular ryanodine receptors that induce a calcium ion leakage from the endoplasmic/sarcoplasmic reticulum. The conventional protein kinase C beta II (cPKCβII)-mediated phosphorylation of endothelial nitric oxide (NO) synthase at Thr495, which reduces the production of NO, was activated by calcium ion leakage. Second, transforming growth factor receptor/SMAD2/3 signaling activation plays an important role in Treg/Th17 cell imbalance in T cells which toget converge to cause inflammation, endothelial dysfunction, and hypertension following tacrolimus treatment. Third, the activation of with-no-K(Lys) kinases/STE20/SPS1-related proline/alanine-rich kinase/thiazide-sensitive sodium chloride co-transporter (WNKs/SPAK/NCC) pathway has a central role in tacrolimus-induced hypertension. Finally, the enhanced activity of renal renin-angiotensin-aldosterone system seems to play a crucial role in the pathophysiology of FK506-induced hypertension.

CONCLUSIONFK506 plays a predominant role in the pathophysiology of hypertension in solid organ transplantation subjects.

Humans ; Hypertension ; chemically induced ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Organ Transplantation ; adverse effects ; Tacrolimus ; adverse effects ; therapeutic use