Higher Alkaline Phosphatase Levels Research Articles

Clinical profile of primary biliary cirrhosis with features of autoimmune hepatitis: Importance of corticosteroid therapy

The aim of this study was to elucidate the clinical and histological features, response to corticosteroid therapy and long-term outcome of primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH). Among 280 PBC patients under ursodeoxycholic acid administration, we identified 28 patients with AIH features fulfilling the following criteria: sustained high levels of serum aminotransferases and high immunoglobulin G levels with positivity for antinuclear antibodies or anti-smooth muscle antibodies (ASMA) and/or histological features of moderate to severe interface hepatitis or moderate to severe lobular hepatitis. We analyzed PBC patients with AIH features, focusing mainly on therapeutic responses to corticosteroids. Patients with PBC with AIH features included 26 women (93%). Their median age was 55 years, and the median follow-up period was 7.5 years. Eight of these 28 patients were not actually treated with corticosteroids due to medical conditions. Among the 20 patients receiving corticosteroid therapy, 15 were responders and five were non-responders. A high alkaline phosphatase (ALP) level, negativity for ASMA and positivity for gp210 were identified as risk factors for lack of a response to corticosteroid therapy. Among 28 PBC patients with AIH features, the responders to corticosteroids had an excellent prognosis, while those who could not be treated with corticosteroids and non-responders to corticosteroids had a poor outcome. Patients with PBC with AIH features benefit from corticosteroid therapy. Features of PBC such as high ALP level, negativity for ASMA and positivity for gp210 appear to predict a poor response to corticosteroids.

Progression of Osteogenic Cell Cultures Grown on Microtopographic Titanium Coated With Calcium Phosphate and Functionalized With a Type I Collagen‐Derived Peptide

The functionalization of metallic surfaces aims at promoting the cellular response at the biomaterial-tissue interface. This study investigates the effects of the functionalization of titanium (Ti) microtopography with a calcium phosphate (CaP) coating with and without peptide 15 (P-15), a synthetic peptide analog of the cell-binding domain of collagen I, on the in vitro progression of osteogenic cells. Sandblasting and acid etching (SBAE; control) Ti microtopography was coated with CaP, enabling the loading of two concentrations of P-15: 20 or 200 μg/mL. A machined Ti was also examined. Rat calvarial osteogenic cells were cultured on Ti disks with the surfaces mentioned above for periods up to 21 days (n = 180 per group). CaP coating exhibited a submicron-scale needle-shaped structure. Although all surfaces were hydrophobic at time zero, functionalization increased hydrophilicity at equilibrium. Microtopographies exhibited a lower proportion of well-spread cells at 4 hours of culture and cells with long cytoplasmic extensions at day 3; modified SBAE supported higher cell viability and larger extracellular osteopontin (OPN) accumulation. For SBAE and modified SBAE, real-time polymerase chain reaction showed the following results: 1) lower levels for runt-related transcription factor 2 at 7 days and for bone sialoprotein at days 7 and 10 as well as higher OPN levels at days 7 and 10 compared to machined Ti; and 2) higher alkaline phosphatase levels at day 10 compared to day 7. At 14 and 21 days, modified SBAE supported higher proportions of red-dye-stained areas (calcium content). Addition of a CaP coating to SBAE Ti by itself may affect key events of in vitro osteogenesis, ultimately resulting in enhanced matrix mineralization; additional P-15 functionalization has only limited synergistic effects.

Paget's disease of maxilla: A case report

Paget disease of bone (PDB) is a metabolic bone disease characterized by increased and disorganized bone turnover. Its etiology is not clear, but includes endocrine, genetics and inflammatory factors. Some patients are asymptomatic, whereas others develop complications such as pain, osteoarthritis, fracture, deformity, deafness, and nerve compression syndromes. Diagnosis of PDB is usually made incidentally by radiographic examinations obtained for other reasons or during evaluation of high serum alkaline phosphatase levels. In this study, we present a case of a 57-year-old female patient with complaint of swelling in the maxilla. Panoramic radiography accompanied by laboratory studies confirmed the diagnosis which was very important for choosing the proper treatment.

Genetic Analysis of Recently Identified Osteoporosis Susceptibility Genes in Southern Chinese

Fifty-six genomic loci recently were identified as associated with bone mineral density (BMD) in a large meta-analysis study of mainly European-descent subjects. Circulating factors related to calcium and phosphate metabolism, eg, serum levels of calcium, phosphate, vitamin D metabolites, PTH, and alkaline phosphatase (ALP), may affect bone turnover and metabolism. We aimed to investigate the effects of these reported variants, as well as their interactions with 5 studied circulating factors, on BMD in a southern Chinese prospective cohort (n = 2670). The identified interactions were further replicated in an independent cohort of 800 Chinese females. Approximately half (n = 27) of the reported variants were successfully replicated in our sample of southern Chinese individuals. We further demonstrated a significant interaction between MARK3 and serum ALP levels (Pmeta = 9.89 ×10(-6)); the effect of MARK3 rs11623869 on BMD was stronger in the presence of high serum levels of ALP. In addition, several interactions between other genes and circulating factors were suggested. Our study has provided an independent replication of associations between several reported loci and BMD in a large sample of southern Chinese individuals. These replicated loci may represent osteoporosis susceptibility genes in both Chinese and European-descent populations. Furthermore, we have shown that serum ALP levels modified the association of MARK3 with BMD. Understanding the mechanisms of the interactions between BMD-related loci and circulating factors may help to determine the pathogenesis of susceptibility to osteoporosis and could have implications for clinical care.

What is the differential diagnosis for extremely elevated (5× normal) alkaline phosphatase?

Evidence-Based Answer In patients with very high alkaline phosphatase levels (>1,000 IU/L), the differential diagnosis includes sepsis, malignant obstruction within the hepatic system, liver metastasis, infiltrative liver disease, and AIDS (SOR: C, case series).

Prognostic Importance of Serum Alkaline Phosphatase in CKD Stages 3-4 in a Clinical Population

Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients. Retrospective cohort study. 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2)) were identified using the Cleveland Clinic CKD Registry. CKD was defined as 2 estimated glomerular filtration rate values <60 mL/min/1.73 m(2) drawn more than 90 days apart using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. ALP levels measured using the calorimetric assay were examined as quartiles (quartile [Q]1, <66 U/L; Q2, 66-81 U/L; Q3, 82-101 U/L; and Q4, ≥102 U/L) and as a continuous measure. All-cause mortality and end-stage renal disease (ESRD) were ascertained using the Social Security Death Index and US Renal Data System. After a median follow-up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in risk of mortality with higher ALP quartiles (Q2, Q3, and Q4) compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications, and liver function test results. The highest ALP quartile was associated with an HR for ESRD of 1.38 (95% CI, 1.09-1.76). Each 1-SD (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09-1.22) and 16% (95% CI, 1.14-1.18) increased risk of ESRD and mortality, respectively. Single-center observational study; lack of complete data, including parathyroid hormone level, for all study participants, and attrition bias. Higher serum ALP levels in patients with CKD stages 3-4 were associated independently with all-cause mortality and ESRD.

Prognostic factors for teenage and adult patients with high-grade osteosarcoma: an analysis of 240 patients

The aim of this retrospective, multicenter study was to evaluate clinicopathological characteristics, prognostic factors and treatment outcomes of teenage and adult patients with high-grade osteosarcoma. A total of 240 osteosarcoma patients who were diagnosed and treated from March 1995 to September 2011 were analyzed. Median age was 20 years (range 13-74 years), and 153 patients (63.8%) were male. Primary tumor localization was extremity in 204 patients (85.4 %), trunk in 21 patients (8.8%) and head and neck region in 14 patients (5.9%). According to American Joint Committee on Cancer staging system, 186 patients (77.5%) were stage II, 3 (1.3%) were stage III and 48 (20.0%) were stage IV. Median overall survival (OS) was 55 months (95 % CI 36.8-73.1 months). OS after 2, 5 and 10 years were 67, 49 and 42%, respectively. Univariable analysis for OS showed that male gender (p = 0.032), high baseline lactate dehydrogenase (LDH) level (p < 0.001), high baseline serum alkaline phosphatase level (p = 0.002), telangiectatic subtype (p = 0.023), presence of metastasis at diagnosis (p < 0.001), presence of tumor positive margins after primary surgery (p = 0.015), poor pathological response to preoperative chemotherapy (p = 0.006) and presence of recurrent disease during follow-up period (p < 0.001) were significantly associated with poor survival. Patients who received postoperative methotrexate plus doxorubicin plus cisplatin (M + A + P) combination regimen (p = 0.019), underwent surgery for recurrent disease (p < 0.001) and received chemotherapy for recurrent disease (p < 0.001) had longer OS. In multivariable analysis for OS, only high LDH level (p = 0.002) and the presence of metastasis at diagnosis (p = 0.011) were associated with poor OS, whereas the patients who received chemotherapy for recurrent disease had a longer OS (p = 0.009).

AB1016 Zoledronic acid: Five years experience results in patients with bone mineral pathology

BackgroundIt has been demonstrated that Zoledronic acid reduces the risk of fractures, both vertebral and non-vertebral, in postmenopausal osteoporosis. Results of the 6-year extension study HORIZON-PFT have recently been published1....

Frequency of Bone Metastases with Metabolic Super Scan in Cancer Breast Patients

Background: Metabolic skeletal changes particularly metabolic super scan (MSS) may provide unsuitable soil for survival and growth of tumor cells in cancer breast patients. We aimed to verify the presence of MSS in cancer breast patients in correlation with the available biomarker for bone metabolism and to explore its influence on the frequency of bone metastases compared to patients without MSS features. Methods: From July 2008 to December 2010, 450 histo-pathologically proved breast cancer patients referred to nuclear medicine department in national cancer institute (NCI), Cairo University, Egypt underwent whole body bone Scan. Bone metabolism was evaluated by laboratory biomarkers of serum alkaline phosphatase (ALP), serum calcium and parathormone (PTH) levels in addition to serum creatinine to assess renal function. Statistical correlations were done between bone scan, clinico-pathological data, radiological findings and serum biomarkers. Follow up within 16-24 months was done. Results: Based on the presence or absence of MSS features, breast cancer patients were classified into two groups: I) MSS group: - included 99 patients, with a mean age of 60.5 years ± 19.5. (II) NonMSS group: included 351 patients with a mean age of 57 years ± 22.0. Patients based data analysis showed that MSS was seen in 22% of the studied breast cancer patients with more prevalence in the post menopausal women and those treated with hormonal and bisphosphonate therapy. Moreover, a significantly lower frequency of bone metastases was noticed in MSS group (8%) compared to Non-MSS (18.2%) (P 0.05). Apart from significant higher level of alkaline phosphatase in MSS compared to Non-MSS group, no significant difference was noticed in the rest of the estimated metabolic biomarkers between both groups. Conclusion: MSS seems to be associated with low frequency of bone metastases in MSS compared to Non-MSS in cancer breast patients. MSS appears to be linked to menopausal status and treatment with hormonal and bisphosphonate therapy. Unfortunately MSS may have a negative impact on the accuracy of bone scan in detection of bone metastases

Determinants of Second-Order Bile Duct Visualization at CT Cholangiography in Potential Living Liver Donors

The purpose of this article is to investigate the determinants of second-order bile duct visualization at CT cholangiography in living potential liver donors. We retrospectively identified 143 potential living liver donors (83 men and 60 women; mean age, 37 years) evaluated with CT cholangiography, which included a slow infusion of iodipamide meglumine with CT acquisition 15 minutes after biliary contrast agent administration. Two readers independently scored the visualization of the second-order bile duct branches on a previously established 4-point scale (0 = not seen, 1 = faintly seen, 2 = well seen, and 3 = excellent visualization). Multivariate analysis was used to investigate the correlation between visualization scores and potential determinants of second-order bile duct opacification, specifically age, body mass index, creatinine level, total and direct bilirubin levels, alkaline phosphatase level, aspartate aminotransferase level, alanine aminotransferase level, patient maximum linear width, CT noise, and hepatosplenic attenuation difference at unenhanced CT. The mean (± SD) second-order bile duct visualization scores were 2.35 ± 0.66 and 2.55 ± 0.60 for readers 1 and 2, respectively. In the multivariate analysis, the only independent predictors of reduced second-order bile duct visualization were higher alkaline phosphatase level (p = 0.01) and higher CT noise (p = 0.02). Higher serum alkaline phosphatase level and higher CT noise in potential living liver donors indicate a higher risk of poor second-order bile duct visualization at CT cholangiography.

Clinical features of patients with primary biliary cirrhosis and anti-SP100 autoantibody positivity

To evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy. The clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test. There was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05). SP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

Abstract 1205: Circulating micro-RNAs can detect adaptive response to therapy and aggressive subset of prostate cancer.

Abstract Circulating markers that inform of the adaptive biology and the clinical virulence of prostate cancer do not exist. Small cell carcinoma of the prostate (SCPC) is an aggressive, androgen receptor (AR)-negative, morphological variant that arises often during the castration-resistant progression of typical adenocarcinoma. Its presence is associated with a poor response to hormonal therapies and predicts for a short survival. Micro-RNAs (miRNAs) regulate a range of processes, including establishment and maintenance of tissue differentiation, and are well-preserved in serum. Based on the observation that SCPC are characterized by a loss of prostate epithelial marker expression (such as AR and HOXB13) and an increase in the expression of proneural transcription factors (such as MYCN and ASCL1) we formulated the hypothesis that the SCPC display a miRNA profile distinct from that of typical AR-driven prostate carcinomas. We profiled the miR extracted from the serum samples of 13 men with biopsy-proven SCPC, and of 9 men with bone-predominant metastatic CRPC. Because SCPC is associated with large tumor burdens, we selected patients with bone-predominant CRPC that had abnormally high alkaline phosphatase levels and PSA &amp;gt; 20ng/mL. 322 miR were detected in at least one of the 22 samples. We identified two miR that were present in 10 and 11 of 13 (77% and 85%) patients with SCPC and 3 and 1 of 9 (33% and 11%) of men with unselected typical bone-predominant CRPC. Both of these miRs have been shown to control multiple genes regulating neuronal differentiation and to induce the conversion of human fibroblasts into neurons, a mechanism which may be shared by prostate adenocarcinoma cells in their transdifferentiation to small cell prostate cancer cells. Moreover, one of them was recently shown to silence AR expression. Therefore we conclude that two circulating miRs may serve to monitor adaptive responses and identify virulent subsets of prostate cancer, thus serving to guide therapy and selection of patients for clinical trials. Validation of these findings is ongoing in a larger cohort of patients. Citation Format: Ana M. Aparicio, Emily Gallichotte, Heather Cheng, Suk-Young Yoo, Sankar Maity, Christopher Logothetis, Muneesh Tewari. Circulating micro-RNAs can detect adaptive response to therapy and aggressive subset of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1205. doi:10.1158/1538-7445.AM2013-1205

595 ALKALINE PHOSPHATASE IS A PROTECTIVE ENZYME DURING LIVER FIBROGENESIS

Background and Aim: Serum alkaline phosphatase (AP) levels serve as a marker for many liver diseases. Recent studies indicate that AP may act as a protective enzyme by dephosphorylation of LPS because dephosphorylation blocks toxicity of this product. Gut-derived LPS is known to aggravate liver damage and fibrosis and we hypothesized that higher levels of AP may represent a physiological response upon higher levels of this toxin during fibrosis. We therefore studied hepatic expression levels and effects of intestinal AP during fibrogenesis. Methods: Intestinal AP knock-out C57BL/6 mice (iAP KO) were examined at 6 weeks of age and compared to age-matched wildtype. Liver fibrogenesis was induced by CCl4 administration to Balb/c mice for 1 day (acute studies) or 8 weeks (chronic studies). The latter group received saline or calf-intestinal AP (5 units, i.v.), from week 6 to 8 (3x/week, n = 6/group). Results: iAP KO mice displayed higher intrahepatic expression levels of fibrogenic markers (PAR-1, Collagen I) paralleled by an increase in macrophages of the pro-fibrotic M2 phenotype relative to WT. So, lack of intestinal AP stimulates fibrogenesis within the liver. We subsequently examined intrahepatic AP expression in normal mice, after CCl4-induced acute liver damage and after chronic CCL4 administration, characterized by liver fibrosis. Results show a gradual increase in intrahepatic AP-activity from normal to fibrotic animals. Histochemical analysis revealed that this APactivity is able to dephosphorylate the lipid A moiety of LPS. We further explored the role of AP by injecting iAP to mice with CCL4-induced fibrosis. Data show a reduced hepatic AP activity, paralleled by significant lower expression levels of desmin and significant lower accumulation of M2 macrophages in iAP-treated mice compared to control. Conclusions: Based on the increased hepatic fibrogenic activity in intestinal AP-KO mice, and the attenuated fibrogenesis in fibrotic mice receiving intestinal AP, we conclude that iAP attenuates fibrosis. The enhanced expression of AP in fibrotic livers and the demonstration that this AP activity is able to dephosphorylate LPS, suggests that endogenous AP serves as a protective enzyme after liver damage. Enhanced AP activity during disease may therefore reflect a physiological response to LPS.

Intrahepatic cholangiocarcinoma: a clinicopathologic study of 37 resected cases.

This study aimed to evaluate prognostic factors for intrahepatic cholangiocarcinoma (ICC) patients who underwent surgical procedure. A total of 37 ICC patients who underwent curative hepatic resection in our department from November 2006 to June 2009 were recruited in this study. Eighteen clinicopathological factors that might influence survival were selected. Survival rates of patients were calculated using the Kaplan-Meier method and the prognostic factors were selected by the Cox proportional hazard model. The overall 1-, 3- and 5- year survival rates were 37.1%, 17.1% and 11.4%, respectively. Univariate analysis showed that tumor thrombus, intrahepatic bile duct dilatation, hepatolithiasis, high serum levels of carbohydrate antigen 19-9 (CA19-9), high serum levels of total bilirubin (TB), low serum levels of prealbumin, high serum levels of γ-glutamyltransferase (γ-GT), high serum levels of alkaline phosphatase (ALP), transfusion, lymph node metastases, advanced UICC stages were significant risk factors for survival. Multivariate analysis identified CA19-9, prealbumin as independent risk factors for postoperative survival. This study suggested serum prealbumin levels could effectively predict the survival of the ICC patients with the treatment of operation. High serum CA19-9 level was associated with poor survival of ICC patients who underwent operation.

Alkaline Phosphatase, Serum Phosphate, and Incident Cardiovascular Disease and Total Mortality in Older Men

We have examined the association between serum phosphate and alkaline phosphatase (ALP) with incident cardiovascular disease (CVD) outcomes and total mortality in older men. A prospective study of 3381 men, aged 60 to 79 years, without a history of myocardial infarction or stroke followed up for an average 11 years during which there were 605 major CVD events (fatal coronary heart disease and nonfatal myocardial infarction, stroke, and CVD death) and 984 total deaths. ALP but not serum phosphate was associated with increased risk of coronary heart disease and overall CVD events which persisted after adjustment for CVD risk factors and markers of inflammation and after exclusion of men with chronic kidney disease (adjusted hazard ratio per SD, 1.19 [1.05, 1.34]; P=0.007 and 1.10 [1.01, 1.21]; P=0.04). In contrast, serum phosphate was only associated with increased CVD mortality owing to noncoronary heart disease or stroke causes (adjusted hazard ratio per SD, 1.35 [1.01, 1.83]; P=0.04). Both raised phosphate and ALP were associated with significantly increased total mortality after full adjustment and exclusion of men with chronic kidney disease. ALP but not serum phosphate is associated with coronary heart disease risk in elderly men. High levels of ALP and serum phosphate are both associated with increased total mortality.

Biological characteristics of wharton's jelly derived mesenchymal stem cells after cryopreservation

Aim of this study was to explore the effects of cryopreservation on biological characteristics of wharton's jelly derived mesenchymal stem cells (WJ-MSC), and to provide experimental evidence for clinical applications and the establishment of WJ-MSC bank. Primary WJ-MSC were produced by umbilical cord tissue culture in vitro. Fifth passage of WJ-MSC acquired by continuous cell culture were mixed with cryoprotectants, frozen in -80°C refrigerator and stored in liquid nitrogen. After the cryopreserved WJ-MSC were thawed, the first passage of WJ-MSC was obtained through cell culture and was taken as the 1st preserved passage (PP1). Thus, PP2-PP15 WJ-MSC were obtained by continuous cell subculture. The 1st control passage (CP1) to 15th passage (CP15) represented the 6th passage to 21st passage WJ-MSC acquired by subculturing in non-cryopreserved group. The biological characteristics of WJ-MSC from cryopreserved and control group, including the recovery rate of nucleated cells, trypan blue exclusion, CCK-8 activity, cell apoptosis, cell adherence, proliferation index, cell surface antigen, cell cycle and the capacities of induced differentiation into adipocyte, osteoblast and neuron, were detected and compared. The results indicated that the recovery rate of nucleated cells of cryopreserved WJ-MSC was 98.2%, trypan blue exclusion rate was 94.3%, CCK-8 activity was 91.4%, apoptotic rate was 3.9%, and the adherence rate was 92.6%. There was a statistically significant difference in proliferation index between PP1 and CP1 (P < 0.05), but there were no statistically significant differences between PP2-PP15 and their corresponding controls. The subculture cells highly expressed CD29, CD44, CD71, CD73, CD90, CD105, CD166 and HLA-ABC, and lowly expressed CD34, CD45 and HLA-DR. The expressions of above-mentioned surface antigens were not different statistically between two groups. The proliferation latency and logarithm proliferation of the subculture cells between two groups were also not different. After induced differentiation into adipocyte, osteoblast and neuron, the staining with oil red O, alkaline phosphatase and neuron-specific enolase was performed respectively, and the positive degrees were not clearly different macroscopically between two groups. Relatively high levels of triglyceride, alkaline phosphatase, and neuron-specific enolase in relevant cells could be detected, but had no significant differences between two groups. It is concluded that some WJ-MSC (< 10%) are damaged after cryopreservation, and the biological characteristics of WJ-MSC in cryopreservation group keep constant, as compared with that in non-cryopreservation group.

Detection of circulating tumor cells in different stages of prostate cancer

To explore circulating tumor cell (CTCs) counts in different stages of prostate cancer (PC) in association with tumor burden, metastatic pattern and conventional serum biomarkers. Overall survival (OS) analyses were conducted with respect to optimized CTC cutoff levels. Circulating tumor cell counts were assessed in healthy controls (n = 15) as well as in locally advanced high risk (LAPC, n = 20), metastatic castration resistant (mCRPC, n = 40) and taxane-refractory (mTRPC, n = 15) PC patients. CTCs were detected using the CellSearch System. In metastatic PC (mPC), CTC counts were significantly increased compared to LAPC (p < 0.001). In LAPC, CTCs were at control level (p = 0.66). Patients with both bone and visceral lesions revealed the highest median CTC count (p = 0.004), whereas patients with sole soft tissue metastases displayed CTC counts comparable to controls (p = 0.16). No correlation was observed between CTC counts and osseous tumor burden assessed by bone lesion count (p = 0.54) or bone scan index (p = 0.81). CTC counts revealed a positive correlation with alkaline phosphatase (p < 0.001) and lactate dehydrogenase (p < 0.001) as well as a negative association with hemoglobin (p = 0.004) and PSA-doubling time (p = 0.01). Kaplan-Meier analyses demonstrated a cohort adjusted cutoff level of 3 CTCs with a shorter OS in case of ≥3 CTCs compared to <3 CTCs (p = 0.001), a cutoff level applicable in mCRPC (p = 0.003) but not in mTRPC patients (p = 0.054). Circulating tumor cell counts are applicable as a prognostic molecular marker, especially in mCRPC patients harboring bone metastases with or without visceral metastases. For clinical practice, mPC patients with elevated CTC counts in combination with short PSA-DT, high alkaline phosphatase and lactate dehydrogenase levels as well as low hemoglobin levels are at high risk of disease progression and limited OS.

Correlates of parathyroid hormone concentration in hemodialysis patients

The implications of chemical hyperparathyroidism on bone and mineral metabolism measures in maintenance hemodialysis (MHD) are not well known. We hypothesized that a higher serum intact parathyroid hormone (iPTH) level is associated with the higher likelihood of hyperphosphatemia, hyperphosphatasemia [high serum alkaline phosphatase (ALP) levels] and hypercalcemia. Over an 8-year period (July 2001-June 2009), we identified 106 760 MHD patients with iPTH and calcium (Ca), phosphorous (P) and ALP data from a large dialysis clinic. Logistic regression models were examined to assess the association between serum iPTH increments and the likelihood of hyperphosphatemia (P ≥5.5 mg/dL), hypercalcemia (Ca ≥10.2 mg/dL) and hyperphosphatasemia (ALP ≥120 U/L). Patients were 61 ± 16 years old and included 45% women, 59% diabetics and 33% Blacks. Compared with an iPTH level of 100 to <200 pg/mL, patients with an iPTH level of 600-700, 700 to <800 and ≥800 pg/mL had 122% (OR: 2.22, 95% CI: 2.04-2.41), 153% (OR: 2.53, 95% CI: 2.29-2.80) and 243% (OR: 3.43, 95% CI: 3.22-3.66) higher risk of hyperphosphatemia, respectively, and had 109% (OR: 2.09, 95% CI: 1.93-2.26), 130% (OR: 2.30, 95% CI: 2.10-2.52) and 376% (OR: 4.76, 95% CI: 4.50-5.04) higher risk of hyperphosphatasemia, respectively. Compared with an iPTH level of 100 to <200 pg/mL, both the low iPTH (<100 pg/mL, OR: 2.45, 95% CI: 2.27-2.64) and the high iPTH (≥800 pg/mL: OR: 2.13, 95% CI: 1.95-2.33) levels were associated with hypercalcemia. Higher levels of iPTH are incremental correlates of hyperphosphatemia and hyperphosphatasemia, whereas both very low and high PTH levels are linked to hypercalcemia. If these associations are causal, correction of hyperparathyroidism may have overarching implications on bone and mineral disorders in MHD patients.

Osteo mineralization of fibrin-decorated graphene oxide

Surface functionalized graphene oxide (GO) was synthesized by coating fibrin on its surface. The fibrin coated graphene oxide (FGO) was characterized for its physiochemical properties and its potential as an osteoinductive material was evaluated using osteoblast like cell line MG-63 and normal cell line NIH 3T3. The scanning electron microscopy (SEM) has confirmed the coating of fibrin on GO and the transmission electron microscopy (TEM) revealed both spherical and cubical nature of GO nanoparticles and FGO. In in vitro studies, FGO exhibited higher levels of alkaline phosphatase and calcium ion release which confirmed the osteoinductive nature of FGO. The 3-(4,5-dimethylthiazol-2-Y)-2,5-diphenyltetrazolium bromide (MTT) assay proved FGO as a biocompatible material. The results have suggested that FGO might be a promising scaffold for bone tissue engineering applications.

A study of bone mineral density and its determinants in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) has been inconsistently associated with low bone mineral density (BMD) and increased fracture risk. 86 consecutive T1DM cases and 140 unrelated age and sex matched healthy nondiabetic controls were included in the study. After history and examination, BMD and body composition were assessed by dual energy X-ray absorptiometry (DXA). Serum samples were analyzed for calcium, phosphorus, albumin, creatinine, alkaline phosphatase, 25 (OH) vitamin D3, intact parathormone (PTH) levels (both cases and controls) and HbA1c, antimicrosomal and IgA tissue transglutaminase (IgA TTG) antibodies, cortisol, follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG), tetraiodothyronine (T4), thyroid stimulating hormone (TSH), growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP3) (cases only). T1DM cases had a lower BMD as compared to controls at both total body (TB) and lumbar spine (LS) (P < 0.05). Patients with celiac autoimmunity (CA) had significantly, lower BMD as compared to age, sex, and body mass index (BMI) matched T1DM controls. Linear regression analysis showed that low BMD in T1DM patients was associated with poor glycaemic control, lower IGF-1 levels, less physical activity (in total population as well as in male and female subgroups), and lower body fat percentage (in females) and higher alkaline phosphatase level (in males) (P < 0.05).