Increased Serum Alkaline Phosphatase Research Articles

Monthly Administration of a Novel PTH-Collagen Binding Domain Fusion Protein is Anabolic in Mice

We synthesized fusion proteins of parathyroid hormone (PTH) (1-33) and the collagen binding domain of ColH (CBD) and tested them for anabolic bone activity in mice. Two fusion proteins were synthesized, linking the carboxy terminus of PTH(1-33) either directly to the amino terminal of the CBD or to the CBD through an adjacent ColH domain (PTH-PKD-CBD). Both PTH-CBD and PTH-PKD-CBD increased cAMP accumulation in cells stably transfected with the PTH/PTHrP receptor, and both peptides bound to type 1 collagen in flow-through assays. Distribution studies indicated that the PTH-CBD was concentrated in the bone and skin, tissues with abundant collagen and blood flow. Administration of 320 μg/kg PTH-CBD either weekly (for 8 weeks) or monthly (for 6 months) to 7-week-old C57BL/6J mice resulted in a sustained increase in bone mineral density (BMD) (15% for weekly studies, 13% for monthly studies; P < 0.05). PTH-PKD-CBD showed only 5% increases in BMD after weekly administration, and, as expected, neither weekly nor monthly PTH(1-34) affected BMD. PTH-CBD increased serum alkaline phosphatase levels. Importantly, there were no significant increases in serum calcium observed. Collectively, the data suggest that PTH-CBD has a sustained anabolic effect in bone with either weekly or monthly administration. This approach of targeted delivery of PTH to bone may show promise for the treatment of disorders of low bone mass, such as postmenopausal osteoporosis.

Increased serum alkaline phosphatase as a predictor of long-term mortality after stroke

Although the critical role of alkaline phosphatase in bone mineralization is clearly understood, the potentially adverse effect of high alkaline phosphatase levels on the cardiovascular system was only recently suggested. In this study, we hypothesized that increased levels of serum alkaline phosphatase may be associated with poor outcome after stroke in terms of mortality. We prospectively included patients with acute stroke admitted consecutively to our hospital, from October 2002 to September 2008. A total of 2,029 patients were selected for the analyses. In the analyses of mortality, the patients were divided by baseline measurements into quintiles of alkaline phosphatase levels (<57, 57-69, 70-81, 82-97, >97 IU/L). In the Cox proportional hazard models, compared with the first alkaline phosphatase quintile, adjusted hazard ratios of the third, fourth, and fifth quintiles for all-cause death were 1.67 (95% confidence interval 1.12-2.49), 1.79 (1.20-2.67), and 2.83 (1.95-4.10). When we divided the patients into ischemic and hemorrhagic stroke, the association was also significant for both subtypes of stroke. In terms of vascular death, compared to the first alkaline phosphatase quintile, the adjusted hazard ratios of the fourth and fifth quintiles of alkaline phosphatase were 1.81 (95% confidence interval 1.14-2.86) and 2.78 (1.87-4.15). Our study demonstrated that increased serum levels of alkaline phosphatase are an independent predictor of all-cause and vascular death after either ischemic or hemorrhagic stroke.

Bone Mineral Content Measured by DEXA Scan in Preterm Neonates Receiving Total Parentral Nutrition with and without Phosphorus Supplementation

Intravenous phosphorus preparation was not available in Egypt till recently. So we aimed to prove the positive effect of adding intravenous phosphorus to total parentral nutrition (TPN) on calcium (Ca) and phosphorus (PO4) metabolism ofpreterm neonates by measuring bone mineral content (BMC) using DEXA scan. A case-control study was conducted in NICU of Obstetric and Gynecology Hospital of Ain Shams University which is a tertiary care unit in Cairo. Thirty preterm infants were prospectively enrolled in the study divided into 2 groups; 15 preterm infants received TPN with phosphorus supplementation (group 1) and 15 preterm received TPN without phosphorus supplementation (group 2). Serum Ca, PO4 and alkaline phosphatase (ALP) assay were done together with urinary calcium/creatinine (Ca/Cr) ratio, abdominal ultrasound and DEXA scan. There were no significant difference regarding serum Ca and PO4 between group 1 and 2. Yet there were highly significant increase in serum ALP and urinary Ca/Cr ratio in group 2 compared to group 1 (p = 0.001). Also group 1 had significantly higher BMC compared to group 2 even with TPN duration less than 15 days (p = 0.001). BMC was significantly positively correlated with G.A and B.W in both groups and was significantly negatively correlated with serum ALP in group 2 and with urinary calcium/creatinine ratio in group 1. Duration of TPN as short as 2 weeks can affect negatively the BMC as documented by DEXA scan in preterm infants receiving TPN without phosphorus supplementation.

Benefits of Sevelamer on Markers of Bone Turnover in Taiwanese Hemodialysis Patients

Sevelamer hydrochloride is a recently developed phosphate binder, which is a quaternary amine anion exchanger without calcium or aluminum. Sevelamer is effective in controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis (HD) patients. We investigated whether sevelamer restored bone metabolism in chronic HD patients. An 8-week, prospective, open-label, randomized study was conducted after a 2-week washout period in chronic hyperphosphatemic HD patients. This study compared the effect of sevelamer on markers of bone turnover with that of calcium acetate, as stratified by baseline serum intact parathyroid hormone (iPTH) level. There was no difference in the changes of serum phosphorus, calcium-phosphorus product and serum iPTH between the sevelamer and the calcium acetate groups. However, more hypercalcemic events (12%) were documented under calcium acetate treatment. In patients with hypoparathyroidism, calcium acetate treatment decreased serum iPTH at the end of the study, while sevelamer did not. Increased serum alkaline phosphatase levels were found among patients receiving sevelamer treatment compared with those who received calcium acetate treatment. In those patients receiving sevelamer, the serum alkaline phosphatase level was also positively correlated to the sevelamer dosage (r = 0.246, p = 0.013). Sevelamer effectively reduces serum phosphorus with a lower incidence of hypercalcemic effects in HD patients. Sevelamer is an effective means of treatment for chronic hyperphosphatemic HD patients, especially those with hypoparathyroidism.

Anti-oxidative status and hepatic enzymes following acute administration of diethyl phthalate in olive flounder Paralichthys olivaceus, a marine culture fish

Although diethyl phthalate (DEP) is one of the most frequently used phthalates in solvents and fixatives for numerous industrial products, almost no research has been done on its biochemical toxicity in aquatic animals. Olive flounder (Paralichthys olivaceus), an important culture fish in far eastern Asian countries, were treated with intraperitoneal DEP at 0, 100, 300 or 900mg/kg for three consecutive days and biochemical effects were assessed in the liver, kidney and serum 24h after the final dosing. Measured parameters were mostly restricted to oxidative status and toxicity of the organs. In the hepatic tissue, there were significant increases in lipid peroxide (LPO) at 100mg/kg and above. Other hepatic parameters, which were examined, changed only after 900mg/kg: reduced glutathione content (GSH), glutathione reductase activity (GR), glutathione peroxidase (GPx) activity increased; catalase (CAT) activity decreased. DEP also induced elevation in LPO levels at above 100mg/kg in renal tissues; however, there was only a decrease in GR and glutathione S-transferase (GST) activities with DEP 900mg/kg in contrast to the liver. Enzyme activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in hepatic tissues decreased in a dose-dependent manner in response to DEP at above 300mg/kg. DEP at 300–900mg/kg, although not uniform among parameters, caused increases in serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), AST, ALT activities and osmolality value, suggesting that DEP at these doses induced hepatic cell damage. The results indicate that 100–900mg/kg DEP induced oxidative stress and the fish seemed to activate compensatory anti-oxidant systems to cope with the imposed substance on the liver. Such compensatory activation was not evident in the kidney. Overall, DEP was only weakly toxic to olive flounder in terms of oxidative and hepatic damage.

Appropriate diagnosis of biliary cystic tumors: comparison with atypical hepatic simple cysts

Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are often confused with other intrahepatic cystic diseases. The aims of this study were to investigate predictive factors of biliary cystic tumor (BCT) and clinical characteristic of BCAC. We retrospectively reviewed preoperative diagnoses, overall characteristics and postoperative outcome of 20 BCTs and 19 cystadenoma-mimicking simple cysts that were pathologically confirmed. Comparing with atypical simple cysts, symptoms, left-lobe cyst, thick wall, septation, mural nodule, bile duct dilatation and an increase of serum alkaline phosphatase were associated with BCTs. However, on multivariate analysis, mural nodule, left-lobe cyst, and an increase of serum alkaline phosphatase were significantly frequent in BCTs with odds ratios of 75.5, 13.8, and 33.0, respectively. Among the 20 BCTs, seven BCACs were diagnosed. The characteristics of BCACs were mural nodule (P<0.01), intrahepatic cyst debris (P<0.01), and bile duct dilation (P=0.04). Cystic fluid analysis provided no significant differences between BCT and simple cyst. After fine needle aspiration cytology of BCTs, all except one BCAC with atypical cell showed nonspecific findings. After complete surgical excision (97.4% of patients), only one patient with BCAC had recurrence during 29 months of follow-up period. In hepatic cysts with mural nodule, left-lobe cyst or increment of serum alkaline phosphatase seem to be indicative of BCTs in the diagnosis of suspicious hepatic cyst. Intracystic debris, bile duct dilation, and mural nodule may be suggestive clinical features of malignancy in BCTs.

腎不全患者の好中球減少症に対するrhG-CSF(KRN8601)の薬物動態と有用性の検討

rhG-CSF (recombinant human granulocyte colony stimulating factor) promotes production and release of neutrophil from bone marrow, and it enhances neutrophil function. In this study, the pharmacokinetics, effects on neutrophil and immune functions and efficacy and safety of rhG-CSF were studied in patients with end-stage renal failure (CRF). To 9 patients with CRF; 2 patients on conservative therapy and 7 patients under regular hemodialysis, 50 micrograms/m2 rhG-CSF were administered intravenously under the schedule of single or 2 week consecutive injection. In single injection study, serial changes in plasma rhG-CSF concentration and peripheral blood cell count were examined following the administration. In consecutive injection study, plasma rhG-CSF concentration, anti-rhG-CSF antibody, peripheral blood cell counts, blood chemistry and coagulation factors, and neutrophil and immune functions were examined. As the results, 1) Half life of rhG-CSF, 2.87 +/- 0.65 hr, was about 2 times longer than that in healthy subjects, and it was not affected by hemodialysis treatment. 2) Marked increase in leukocyte and neutrophil counts and mild increase in lymphocyte count were observed during single and consecutive administration of rhG-CSF. There was no significant change in other leukocyte differentiations, RBC, or platelet count. 3) Neutrophil alkaline phosphatase score increased significantly during single and consecutive administration, and other neutrophil function also improved in several patients with impaired neutrophil function. 4) Slight bone pain and increase in serum alkaline phosphatase were observed in about a half of patients during consecutive injection study. Neither antibody nor accumulation of rhG-CSF was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicity of crude oil products and detergent on serum alkaline phosphatase concentration of Clarias gariepinus juveniles

The comparative effect of exposing Clarias gariepinus juveniles (100.20 + 0.8g) to diferent concentrations of crude oil products and detergent were studied. Bonny Light Crude oil (BLCO), Premium motor spirit (PMS), Dual purpose kerosene (DPK) and Ariel Enzymax Detergent (AED) were respectively applied at three concentratons, 2.00, 4.00and 6.00mi/L as well as a control experiment 0.00ml/L with no toxicant for two hours (2 hours) toxicity period. Increased serum alkaline phosphatase and low degree of toxicity were recorded in the fish samples exposed to the various pollutants than in the fish control. The comparatively low toxicity noticed within the sample fish was attributed to the reduced length o exposure to the pollutants this probably lowered the pressure of the toxicant on organs of the fish. Keywords: Clarias gariepinus , Serum alkaline phosphatase, Bonny light crude oil, Premium motor spirit, Dual purpose kerosene, Ariel enzymax detergent

ONCOGENIC OSTEOMALACIA, YOU SAY' BETTER START LOOKING THEN-A CASE REPORT

Tumour-induced or oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome characterized by bone pain and muscle weakness. A biochemical profile consisting of normocalcaemia,hypophosphataemia, phosphaturia, increased serum alkaline phosphatase and inappropriately low serum levels of 1, 25-dihydroxyvitamin-D is diagnostic. OOM is usually caused by an osseousor soft-tissue tumour of mesenchymal origin that secretes phosphaturic substances leading to increased urinary phosphate wasting. These tumours are small and slow growing. The diagnosis continues to be easily missed and when eventually made, localization of the tumour can be difficult. We describe the case of a young man who presented with severe generalized pain associated with muscle weakness. He was extensively investigated and eventually diagnosed to have OOM 3 years after initial presentation. Specialized investigations were necessary to localize the offending tumour.

Genistein and a Soy Extract Differentially Affect Three-Dimensional Bone Parameters and Bone-Specific Gene Expression in Ovariectomized Mice

Soy isoflavone preparations, such as purified genistein and a soy extract (Novasoy), were reported previously to exert beneficial effects on bones. Our purpose in this study was to compare the effects of genistein and Novasoy on 3-dimensional trabecular bone parameters and the expression of bone-specific genes in ovariectomized (OVX) mice. The sham-operated mice were fed the control diet and OVX mice were fed diets containing genistein or Novasoy or the control diet, with or without 17β-estradiol treatment, for 5 wk. Trabecular bone parameters of tibias were measured by microcomputed tomography and gene expression was assayed by real-time PCR. Consumption of diets containing genistein or Novasoy partially prevented the ovariectomy-induced increase in body weight but did not alter the uterus weight of the OVX mice. Novasoy, but not purified genistein, significantly preserved trabecular bone mass, bone volume, and trabecular bone separation in the proximal tibial metaphysis. Purified genistein decreased mRNA expression of receptor activator of nuclear factor-кB ligand (RANKL), carbonic anhydrase II, and cathepsin K and enhanced the ratio of osteoprotegrin:RANKL mRNA expression in the tibial head of the OVX mice. In contrast, the diet containing Novasoy suppressed the OVX-induced increase in serum alkaline phosphatase but did not alter bone-specific gene expression of tibia. Our study demonstrated that a soy extract containing a similar level of genistein in the form of Novasoy is more effective than purified genistein in improving tibial trabecular bone quality in OVX mice, but the mechanism of action might be distinct from that of genistein.

Toxicological implications of aqueous extract of Bambusa vulgaris leaves in pregnant Dutch rabbits

Aqueous extract of Bambusa vulgaris L. leaves at 250 and 500 mg/kg body weight was investigated for toxic effects in pregnant rabbits. Apparently healthy, female rabbits (Dutch) weighing between 1.62 and 1.70 kg as previously used in our abortifacient study were paired overnight with male rabbits in ratio 2:1 and those that became pregnant were completely randomized into three groups (A-C). Group A (the control), received orally 1.85 mL/kg body weight (3 mL) of distilled water thrice daily on days 1-9 of pregnancy while groups B and C were treated orally with the same volume corresponding to 250 and 500 mg/kg body weight of the extract. Clinical signs of toxicity were not observed in all the animals during the study. The extract did not significantly alter (p > .05) the serum follicle stimulating hormone and total protein content of the pregnant rabbits throughout the exposure period whereas, the concentrations of luteinizing hormone, progesterone, albumin, globulin, urea and calcium decreased in the serum of the rabbits. At 250 mg/kg body weight, the extract increased kidney alkaline phosphatase (ALP) activity whereas at 500 mg/kg body weight of the extract, the ALP level was similar to the control group. Liver ALP at all doses, as well as the activity of gamma glutamyl transferase (GGT) at 500 mg/kg body weight was reduced. This reduction was accompanied by an increase in serum ALP and GGT at these doses. At 250 mg/kg, the extract increased kidney GGT. Conversely, at 500 mg/ kg, kidney GGT activity decreased. Liver and serum GGT were not altered by the 250 mg/kg. The extract also increased the serum levels of creatinine, uric acid, sodium, potassium and bicarbonate ions as well as total and conjugated bilirubin. In the hepatocytes of extract-treated animals, there was no evidence of necrosis, inflammation, fibrosis and degenerative changes in the central vein and radiating hepatic cords, while the glomerulus and the tubules of the nephrons also remained intact. The alterations in biochemical parameters by the aqueous extract of B. vulgaris leaves suggests adverse effect on the synthetic, secretory, reabsorptive and excretory functions of liver and kidney of the animals. Therefore, the absence of histopathological lesions in the hepatocytes and nephrons implies that histopathological changes are not a sensitive assay for the assessment of tissue damage by the extract.

A Case of Renal Osteodystrophy with Unexpected Serum Intact Parathyroid Hormone Concentrations

A 64-year-old female with long-standing end-stage renal disease (ESRD),1 status post 2 failed renal transplants, was evaluated for management of renal osteodystrophy with particular concern for adynamic bone disease (ABD). ABD was suspected because of low normal serum intact parathyroid hormone (PTH) concentrations (range 2.5–54 ng/L, reference range 10–65 ng/L), intermittently increased serum calcium concentrations (range 88–107 mg/L, reference range 84–105 mg/L), and severe osteoporosis. However, her mildly increased serum alkaline phosphatase activities (range 149–196 U/L, reference range 30–120 U/L) were inconsistent with the low bone turnover observed in ABD. This discrepant clinical profile prompted investigation into the PTH assay used at our institution. Simultaneous samples were analyzed for intact PTH on our Roche Elecsys 2010 immunoassay analyzer and at a reference laboratory (Quest Diagnostics) on the Siemens Immulite 2000 immunoassay analyzer. Discrepant values of 48 and 786 ng/L were obtained, respectively. Parathyroid hormone functions to maintain serum calcium concentrations within a tight physiologic range. Patients with chronic renal failure develop secondary hyperparathyroidism owing to decreased renal production of 1,25-dihydroxyvitamin D and hyperphosphatemia, both of which result in hypocalcemia. These derangements in mineral metabolism stimulate PTH production to raise serum calcium and promote phosphorus excretion. Increased serum PTH leads to excessive bone resorption through stimulation of osteoblasts and osteoclasts. The combination of secondary hyperparathyroidism and mineralization defects (osteomalacia) represents the most common form of renal osteodystrophy (ROD). In contrast, a subtype of ROD known as adynamic bone disease can be observed in the setting of prolonged peritoneal or hemodialysis, oversuppression of PTH with calcitriol or calcium-based phosphate binders, or the use of bisphosphonates for osteoporosis treatment (1). ABD is characterized by marked suppression of bone remodeling that leads to fracture. Common biochemical hallmarks of ABD include hypercalcemia, low or inappropriately normal PTH concentrations, and reduced markers of bone turnover …

Introduction of a Phe377del Mutation in ANK Creates a Mouse Model for Craniometaphyseal Dysplasia

Craniometaphyseal dysplasia (CMD) is a monogenic human disorder characterized by thickening of craniofacial bones and flaring metaphyses of long bones. Mutations for autosomal dominant CMD have been identified in the progressive ankylosis gene ANKH. Previous studies of Ank loss-of-function models, Ank(null/null) and Ank(ank/ank) mice, suggest that Ank plays a role in the regulation of bone mineralization. However, the mechanism for Ank mutations leading to CMD remains unknown. We generated the first knockin (KI) mouse model for CMD expressing a human mutation (Phe377 deletion) in ANK. Homozygous Ank knockin mice (Ank(KI/KI)) replicate many typical features of human CMD including hyperostosis of craniofacial bones, massive jawbones, decreased diameters of cranial foramina, obliteration of nasal sinuses, fusion of middle ear bones, and club-shaped femurs. In addition, Ank(KI/KI) mice have increased serum alkaline phosphatase and TRACP5b, as reported in CMD patients. Biochemical markers of bone formation and bone resorption, N-terminal propeptide of type I procollagen and type I collagen cross-linked C-terminal telopeptide, are significantly increased in Ank(KI/KI) mice, suggesting increased bone turnover. Interestingly, Ank(KI/KI) bone marrow-derived macrophage cultures show decreased osteoclastogenesis. Despite the hyperostotic phenotype, bone matrix in Ank(KI/KI) mice is hypomineralized and less mature, indicating that biomechanical properties of bones may be compromised by the Ank mutation. We believe this new mouse model will facilitate studies of skeletal abnormalities in CMD at cellular and molecular levels.

EASL Clinical Practice Guidelines: Management of cholestatic liver diseases

EASL Clinical Practice Guidelines (CPG) on the management of cholestatic liver diseases define the use of diagnostic, therapeutic and preventive modalities, including non-invasive and invasive procedures, in the management of patients with cholestatic liver diseases. They are intended to assist physicians and other healthcare providers as well as patients and interested individuals in the clinical decision-making process by describing a range of generally accepted approaches for the diagnosis, treatment and prevention of specific cholestatic liver diseases. The clinical care for patients with cholestatic liver diseases has advanced considerably during recent decades thanks to growing insight into pathophysiological mechanisms and remarkable methodological and technical developments in diagnostic procedures as well as therapeutic and preventive approaches. Still, various aspects in the care of patients with cholestatic disorders remain incompletely resolved. The EASL CPG on the management of cholestatic liver diseases aim to provide current recommendations on the following issues:

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

Recent in vitro studies have shown a link between alkaline phosphatase and vascular calcification in patients with chronic kidney disease (CKD). High serum levels of alkaline phosphatase are associated with increased death risk in epidemiologic studies of maintenance hemodialysis (MHD) patients. We hypothesized that coronary artery calcification is independently associated with increased serum alkaline phosphatase levels in MHD patients. We examined the association of coronary artery calcification score (CACS) and alkaline phosphatase in 137 randomly selected MHD patients for whom markers of malnutrition, inflammation, and bone and mineral disorders were also measured. Serum alkaline phosphatase was the only measure with significant and robust association with CACS (P < 0.003), whereas either other biochemical markers had no association with CACS or their association was eliminated after controlling for case-mix variables. Serum alkaline phosphatase >120 IU/L was a robust predictor of higher CACS and was particularly associated with the likelihood of CACS >400 (multivariate odds ratio 5.0 95% confidence interval 1.6 to 16.3; P = 0.007). Serum alkaline phosphatase of approximately 85 IU/L seemed to be associated with the lowest likelihood of severe coronary artery calcification, but in the lowest tertile of alkaline phosphatase, the CACS predictability was not statistically significant. An association between serum alkaline phosphatase level and CACS exists in MHD patients. Given the high burden of vascular calcification in patients with CKD, examining potential therapeutic interventions to modulate the alkaline phosphatase pathway may be warranted.

Effect of Quinalphos on Testicular Steroidogenesis in Rats

The effect of quinalphos (250 micrograms/kg i.p.) an organophosphorus insecticide treatment for 13 and 26-days on the testicular steroidogenic enzymes viz. 3 beta-Hydroxysteroid Dehydrogenase and 17 beta-Hydroxysteroid Dehydrogenase, as well as cholesterol content and histology of the testes of the Wistar strain rats was studied. The time duration of 13 days is approximately equivalent to one cycle of the seminiferous epithelium in Wistar strain rats. Treatment of quinalphos for 13 days failed to produce any effect on the relative weights of the testes and accessory sex glands. However, significant inhibition of 3 beta-HSD activity and increased cholesterol level in testis were observed. The rats treated for 26 days similarly showed a highly significant inhibition of the activity of both 3 beta-HSD and 17 beta-HSD. The relative weights of the testes and accessory sex glands were also significantly reduced. Histological examination of the testis revealed that quinalphos treatment produced detrimental changes in the seminiferous epithelium. Treatment with quinalphos for 13-days produced no toxic effect with the exception of a significant increase in serum alkaline phosphatase. However, after 26-days of treatment toxicity was significantly increased as reflected on serum transaminases, phosphatases and blood urea levels of rat. Present study indicated that quinalphos impairs testicular functions in rats.

Endoscopic treatment for biliary stricture after adult living donor liver transplantation

Endoscopic intervention is considered to be the primary treatment for biliary stricture after adult living donor liver transplantation (LDLT) with duct-to-duct biliary reconstruction. The aim of this study was to investigate the risk factors of biliary stricture and the clinical outcomes and predictors of failure after endoscopic retrograde cholangiography with balloon dilation (ERC-D). We enrolled 239 adult patients who underwent LDLT between 2000 and 2006. Sixty-eight patients (28.4%) developed biliary stricture. Twenty-nine patients with anastomotic biliary stricture were treated with ERC-D and stenting. We retrospectively analyzed the risk factors of biliary stricture and the clinical outcomes of ERC-D. The median follow-up period was 31 months. The risk factors of biliary stricture on multiple logistic regression analysis were a graft with multiple bile ducts, a previous history of bile leakage, and hepatic artery stenosis. The overall success rate of ERC-D was 64.5%. On simple logistic regression, the failure of primary ERC-D was associated with late biliary stricture over 24 weeks and more than 8 weeks between a 2-fold increase of serum alkaline phosphatase from the stable level and ERC-D, even though these were not statistically significant on multiple logistic regression. The relapse rate of stricture after successful ERC-D was 30%. The duration of stenting in the recurrence group was shorter than that in the nonrecurrence group (11.8 +/- 5.03 versus 29.0 +/- 11.6 weeks, P = 0.004). ERC-D is effective for the management of anastomotic biliary stricture. However, the failure rate of primary ERC-D may be high in patients with late onset and delayed diagnosis of biliary stricture. The recurrence seems to occur frequently in patients with a short duration of stenting.

Oxidized dietary fat, alkaline phosphatase concentrations and performance in racing greyhounds

Racing dogs are often fed raw meat. Raw meat may become oxidized because it contains no preservatives but few studies have examined the effect of feeding oxidized food to dogs. This study was originally designed to determine the effect of different concentrations of dietary fat on greyhound performance. After the experiment had been completed, however, it was discovered that the peroxide values (PV) of both diets were elevated indicating that fat oxidation had been present. This study was considered to have value, therefore, because it compared performance and blood parameters in eight trained Greyhounds fed either a high fat moderately oxidized (HFMO) diet (43%ME fat with PV of 44 mEq/kg) or a medium fat highly oxidized (MFHO) diet (31%ME fat with PV of 211 mEq/kg) for 8 weeks per diet in a randomized cross-over design. Dogs were raced over 500 m twice weekly. Race times over the last 4 weeks of each diet period and blood parameters before racing during the last week of each diet period were compared. Dogs fed the MFHO food ran 0.04 m/s slower (p = 0.06) and serum alkaline phosphatase concentrations were higher (149 vs. 56 U/L; p < 0.0001) than in dogs fed the HFMO diet. Further evaluation is needed to determine whether lower dietary fat or increased oxidation was responsible for the altered performance but oxidation of the food should be considered as one possible explanation for an increase in serum alkaline phosphatase during a diet trial.

Description of dogs naturally infected with Hepatozoon canis in the Aegean region of Turkey

Clinical and laboratory findings recorded in 10 dogs naturally infected with Hepatozoon canis in the Aegean region of Turkey were reported. The diagnosis was made by finding H. canis gamonts within leucocytes in Giemsa-stained blood smears. H. canis parasitaemia level was calculated manually by counting 500 neutrophils in blood smears. Parasitaemia varied from 1% to 23% of the circulating neutrophils. Anorexia, fever, depression, weight loss, and lymphadenopathy are the main clinical signs in infected dogs. All dogs had microcytic normochromic anaemia; however, 7 of the dogs had neutrophilia, 1 had lymphopenia, 2 had monocytosis, 1 had eosinophilia, and 9 had thrombocytopenia. Abnormal serum biochemical values were hyperproteinaemia (7 of 10 dogs), hypoalbuminaemia (9 of 10 dogs), hyperglobulinaemia (7 of 10 dogs), increased serum alkaline phosphatase activity (2 of 10 dogs), and increased serum creatinine kinase activity (8 of 10 dogs). Concurrent infections such as Ehrlichia canis, Anaplasma phagocytophilum, and Anaplasma platys were detected with a polymerase chain reaction test and 8 dogs had 2 or 3 of these concurrent infections.

Tenofovir use is Associated with an Increase in Serum Alkaline Phosphatase in the Swiss HIV Cohort Study

Tenofovir (TDF) use has been associated with proximal renal tubulopathy, reduced calculated glomerular filtration rates (cGFR) and losses in bone mineral density. Bone resorption could result in a compensatory osteoblast activation indicated by an increase in serum alkaline phosphatase (sAP). A few small studies have reported a positive correlation between renal phosphate losses, increased bone turnover and sAP. We analysed sAP dynamics in patients initiating (n = 657), reinitiating (n = 361) and discontinuing (n = 73) combined antiretroviral therapy with and without TDF and assessed correlations with clinical and epidemiological parameters. TDF use was associated with a significant increase of sAP from a median of 74 U/I (interquartile range 60-98) to a plateau of 99 U/I (82-123) after 6 months (P < 0.0001), with a prompt return to baseline upon TDF discontinuation. No change occurred in TDF-sparing regimes. Univariable and multivariable linear regression analyses revealed a positive correlation between sAP and TDF use (P < or = 0.003), but no correlation with baseline cGFR, TDF-related cGFR reduction, changes in serum alanine aminotransferase (sALT) or active hepatitis C. We document a highly significant association between TDF use and increased sAP in a large observational cohort. The lack of correlation between TDF use and sALT suggests that the increase in sAP is because of the bone isoenzyme and indicates stimulated bone turnover. This finding, together with published data on TDF-related renal phosphate losses, this finding raises concerns that TDF use could result in osteomalacia with a loss in bone mineral density at least in a subset of patients. This potentially severe long-term toxicity should be addressed in future studies.