Serum Total Alkaline Phosphatase Research Articles

Effect of dietary alanyl-glutamine dipeptide against chronic ammonia stress induced hyperammonemia in the juvenile yellow catfish (Pelteobagrus fulvidraco)

Triplicate groups of juvenile yellow catfish (1.98 ± 0.01 g) were fed diets supplemented with 0% and 1% alanyl-glutamine dipeptide (AGD) for 56 days under three ammonia concentrations (0.01, 5.70 and 11.40 mg L−1 total ammonia nitrogen). The results showed that ammonia poisoning could induce growth (weight gain and specific growth rate) and survival reduction, live ammonia and serum malondialdehyde accumulation, and subsequently lead to blood deterioration (serum total protein, albumin, globulin, alkaline phosphatase and acid phosphatase reduced), oxidative stress (superoxide dismutase and glutathione peroxidase activities declined), and induce down-regulation of antioxidant enzymes (SOD, GPX and GRX) genes transcription. However, dietary supplemented with 1% AGD could mitigate the adverse effect of ammonia poisoning on fish growth performance.

Assessment of transport stress on cattle travelling a long distance (≈648 km), from Jessore (Indian border) to Chittagong, Bangladesh

The effect of long-distance transport on cattle health has not frequently been studied in Bangladesh. The current study investigated the health conditions, and the extent and pattern of cattle injuries,...

Feeding European sea bass with increasing dietary fibre levels: Impact on growth, blood biochemistry, gut histology, gut evacuation

Changing trends in fish feed formulation, with progressively higher inclusion levels of plant ingredients, are invariably introducing more fibre despite the fact that this component cannot be utilized by most fish. The effects of increasing insoluble dietary fibre level on growth, nutrient utilisation, blood parameters and gut health in European sea bass (Dicentrarchus labrax L.) were studied over a period of 117 days. Moreover, investigation on digesta transit time through gastrointestinal evacuation pattern and digesta characteristics (moisture of digesta) were studied. Five isoproteic diets were formulated to contain increasing insoluble fibre levels, neutral detergent fibre, NDF (7.2, 8.9, 11.5, 13.1 and 15.5%) derived by the inclusion of sunflower hulls and soybean hulls. No significant differences due to fibre inclusion levels were observed in final body weight, specific growth rate, feed intake, feed conversion rate, protein and lipid efficiency. No significant differences in serum total protein, glucose, triglycerides, alkaline phosphatase and inorganic phosphorous were found. All the histological sections showed normal intestinal architecture, and inflammatory and/or degenerative changes were not present in any histological section from all subjects examined. The investigation into gastrointestinal evacuation pattern revealed no significant differences between treatments, however higher dietary fibre levels seem to increase the time required to empty the stomach while the time required to empty 90% of the hindgut content was similar in all the treatments: around 46–47 h. No differences were found between diets in the moisture content of digesta along the digestive tracts. We can conclude that the different insoluble fibre levels tested in this trial have no effects on overall performances and feed efficiency in European sea bass. Results from blood biochemistry profile and histology confirm good nutritional and health status of fish under all feeding treatments. The inclusion of fibre had no influence on digesta transit time. In formulation of feed for the on-growing of European sea bass insoluble fibre derived from sunflower hulls and soybean hulls can be included at a level of up to 15.5%.

Effects of 1.8 GHz radiofrequency field on microstructure and bone metabolism of femur in mice

To investigate the effects of 1.8 GHz radiofrequency (RF) field on bone microstructure and metabolism of femur in mice, C57BL/6 mice (male, age 4 weeks) were whole-body exposed or sham exposed to 1.8 GHz RF field. Specific absorption rates of whole body and bone were approximately 2.70 and 1.14 W/kg (6 h/day for 28 days). After exposure, microstructure and morphology of femur were observed by microcomputed tomography (micro-CT), Hematoxylin and Eosin (HE) and Masson staining. Subsequently, bone parameters were calculated directly from the reconstructed images, including structure model index, bone mineral density, trabecular bone volume/total volume, connectivity density, trabecular number, trabecular thickness, and trabecular separation. Biomarkers that reflect bone metabolism, such as serum total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRACP-5b), were determined by biochemical assay methods. Micro-CT and histology results showed that there was no significant change in bone microstructure and the above parameters in RF group, compared with sham group. The activity of serum ALP and BALP increased 29.47% and 16.82%, respectively, in RF group, compared with sham group (P < 0.05). In addition, there were no significant differences in the activity of serum TRACP-5b between RF group and sham group. In brief, under present experimental conditions, we did not find support for an effect of 1.8 GHz RF field on bone microstructure; however, it might promote metabolic function of osteoblasts in mice. Bioelectromagnetics. 39:386-393, 2018. © 2018 Wiley Periodicals, Inc.

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats.

Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD+). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions.

Circulating Levels of Total Cholesterol and Alkaline Phosphatase in Healthy Foals From Weaning to 18 months of Age Vary Significantly in Relation to Growth Stage

In view of the peculiar nutritional demands of the growing foal, the concentration of selected circulating parameters may display to mirror the metabolic activity of developing tissues across growth stages, following yields of mass and size, over time. This study aimed to evaluate the possible change of selected serum biochemical parameters in foals at different growth stages and to target these parameters as potential biomarkers of body development. Twelve Anglo-Arab spring-born foals were screened from weaning to 18 months of age. Live weight and gains were analyzed according to respective growth stage and correlated with biochemical parameters. Individual double whole blood samples were collected before and after weaning and when the foals were 12 and 18 months old. Body mass and wither heights (WH of yearlings) were concomitantly recorded. Foals appeared healthy throughout the trial and showed significantly different (P < .001) levels of total serum cholesterol (TC) and alkaline phosphatase (ALP) in relation to growth stages. Both those metabolites showed peaks in weanlings to progressively decrease in 18 months olds. On each sampling, ALP constantly displayed to set above the upper limit of the physiological range for the adult healthy horse. Results highlighted marked statistical significance across growth stages and point to ALP and TC as biomarkers of growth stage. These findings pave the way to the interpretation of circulating metabolites associated with growth stage and encourage further experiments to validate ALP and TC as potential biomarkers for body development assessment of foals.

Anti-Diabetic Effects of Amygdalus Lycioides Spach in Streptozocin-Induced Diabetic Rats.

Diabetes mellitus is a group of metabolic disorders characterized by elevated blood sugar and abnormalities in insulin secretion and action. There are many anti-diabetic plants, which might supply useful sources for developing new medicines that can be used in treatment of diabetes mellitus. The primary objective of the present investigation is to evaluate the anti-diabetic properties of the aerial parts of Amygdalus lycioides in streptozocin-induced diabetic rats. Sixty rats were divided into 6 groups: streptozocin-induced diabetic control, insulin-treated diabetic group, and four Amygdalus lycioides-treated diabetic groups (125, 250, 500, and 1000 mg/kg/day). After 2 weeks of plant extract administration, the effects of extracts on blood glucose, body weight, BUN, creatinine, total cholesterol, LDL, HDL, triglyceride, total protein, Na, K, and plasma enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) were analyzed. The pancreas of rats was also stained for stereological studies. Phytochemical evaluation of this extract showed the presence of flavonoids and tannins compounds. Glucose serum levels and glucose tolerance test showed a decrease in treatment with Amygdalus lycioides (1000 mg/kg). Serum total cholesterol, LDL, triglyceride, creatinine and alkaline phosphatase levels were decreased significantly by the extract but aspartate aminotransferase found to be increased after treatment. The total number and numerical density of beta cells increased in the Amygdalus lycioides group (1000 mg/kg). It seems that Amygdalus lycioides may act as a potential drug to treat diabetes and its complications. However, more investigations should be done to more clarify these results.

Indirect Effect of Smoking on Liver Function: A Comparative Study among Iraqi Students in Baghdad City

Smoking is a process in which a substance like tobacco is burned to produce smoke that inhales and absorbed into the bloodstream. The cigarette smoking is one of the greatest causes of illness, such as lung cancer, and premature death. The present study was constructed to evaluate the effect of cigarette smoking on the liver biochemical state. The study includes 50 smokers as patient group and 50 (age and sex matched) non-smokers as control group. The liver functions tests; aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein and alkaline phosphatase (ALP) were estimated spectrophotometrically. The results revealed that there was a signifcant reduction in the levels of AST, ALT, serum total protein and ALP of smokers in comparison with the healthy control (non-smokers) group. Also the results revealed the presence of a positive correlation between ALT and AST. To conclude, alterations in liver parameters levels could be attached to the oxidative stress created through the accumulative effect of inhaled smoke as well as the interaction of absorbed toxic chemicals like nicotine. Therefore, the association between smoking attitude and liver functions tests should be carefully analyzed.

Effect of replacing inorganic zinc with a lower level of organic zinc (zinc propionate) on performance, biochemical constituents, antioxidant, immune and mineral status in buffalo calves

An experiment of 120 days was carried out to investigate the effects of replacing inorganic zinc (ZnSO4; 80 ppm) with lower level (75% of inorganic levels; 60 ppm) of organic zinc (Zn propionate; Zn-Prop) on growth, serum biochemical constituents, immune response, mineral and antioxidant status in buffalo calves. Twelve buffalo calves (193.3±19.63kg; 14-24 months) were randomly allotted to a control (80 ppm Zn) and experimental (60 ppm Zn) diets. All calves were weighed at fortnight interval. Animals were immunized against Brucella abortus (BA) and chicken RBC (CRBC) antigens on day 90 with a booster dose of 15 days interval and serum was collected on 7, 14, 21 and 28 d of post sensitization (PS) to study the antibody titres. Blood was collected on 114 d of experiment to prepare serum and haemolysate. Cell mediated immune response (CMIR) was determined against phytohemagglutinin-P (PHA-P) on day 118. The fortnightly body weights, average daily gain, dry matter intake, feed conversion ratio were comparable between the dietary groups. Similarly, serum albumin, globulin, creatinine and mineral (Zn, Cu, Mn, Fe) levels were comparable while higher (P less than 0.05) serum total protein and alkaline phosphatase activities were observed in organic Zn supplemented calves. After 7 d of PS, serum antibody titres (log2) against BA were higher (P less than 0.05) with Zn-Prop supplementation, while the titres against CRBC were not affected by Zn source and dose. Lipid peroxidation and antioxidant enzyme activities (glutathione reductase, RBC catalase and superoxide dismutase) estimated in haemolysate were comparable between groups, while glutathione peroxidase (P less than 0.05) activity increased with Zn-prop supplementation compared to ZnSO4. The CMIR was higher (P less than 0.05) with organic Zn. It can be concluded that the growth performance, antioxidant status, and immune response in calves fed lower levels of organic Zn (Zn-Propionate) (75% of inorganic mineral supplementation) was comparable to those fed 100% of inorganic zinc and the CMI response was higher in organic Zn supplemented calves.

Teriparatide treatment in an adult patient with hypophosphatasia exposed to bisphosphonate and revealed by bilateral atypical fractures

Atypical femoral fractures are defined as atraumatic fractures located in the subtrochanteric region or femoral shaft. They have been mainly reported in patients taking bisphosphonates. We report the case of a 67-year-old female with osteoporosis treated by alendronate during ten years. Radiographies showed atypical femoral fractures. Serum levels of total and bone-specific alkaline phosphatase were low. In order to accelerate bone healing, teriparatide was introduced. After one year of teriparatide treatment, pain and functional difficulty have decreased, and alkaline phosphatase levels were normalized. In view of this history of recurrent fractures, of atypical femoral fractures, of early spontaneous loss of teeth, and of low serum total and bone-specific alkaline phosphatase levels, the diagnosis of hypophosphatasia has been considered and confirmed by genetic research. Other conditions than exposure to anti-resorptive therapies may promote atypical femoral fractures, such as in conditions associated with abnormal bone structures, as hypophosphatasia, a rare inherited bone metabolism disorder. A few case reports have reported adult hypophosphatasia treated by teriparatide with a good efficacy on bone pain and consolidation but with mixed results on biological markers. Teriparatide may be therefore a treatment option in adult hypophosphatasia. ALP levels should be carefully checked among osteoporotic patients and specially before introducing a bone resorption inhibitor. Low alkaline phosphatase levels have to be taken into account and an evocative history of hypophosphatasia has to be sought because this condition may expose patients to develop atypical femoral fractures during bisphosphonate treatment.

The Effect of Vitamin D Supplementation on Bone Metabolic Markers in Chronic Kidney Disease.

Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo-controlled trial investigating the effect of cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3-G4 and vitamin D ≤20 ng/mL (Clinical Trials Registry of India: CTRI/2013/05/003648). Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At 16 weeks, the serum 25(OH)D and 1,25(OH)2 D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change: 23.40 ng/mL; 95% CI, 19.76 to 27.06; p < 0.001, and 14.98 pg/mL; 95% CI, 4.48 to 27.18; p = 0.007, respectively). Intact parathyroid hormone (iPTH) decreased in the cholecalciferol group (between-group difference in mean change -100.73 pg/mL (95% CI, -150.50 to -50.95; p < 0.001). Serum total and bone-specific alkaline phosphatase (SAP, BAP) and serum C-terminal cross-linked collagen type I telopeptides (CTX-1) were significantly reduced in cholecalciferol group (between group difference for change in mean: -20.25 U/L; 95% CI, -35.14 to -5.38 U/L; p = 0.008 for SAP; -12.54 U/L; 95% CI, -22.09 to -2.98 U/L; p = 0.013 for BAP; and -0.21 ng/mL; 95% CI, -0.38 to -0.05 ng/mL; p = 0.05 for CTX-1). Correlation analysis showed significant correlation of Δ25(OH)D with ΔiPTH (r = -0.409, p < 0.0001), Δ1,25(OH)2 D (r = 0.305, p = 0.001), ΔSAP (r = -0.301, p = 0.002), ΔBAP (r = -0.264, p = 0.004), and ΔCTX-1 (r = -0.210, p = 0.0230). Cholecalciferol supplementation corrects vitamin D deficiency and is effective in lowering serum intact parathyroid hormone and bone turnover markers in early stages of CKD. © 2017 American Society for Bone and Mineral Research.

Cocos nucifera water improves metabolic functions in offspring of high fat diet fed Wistar rats.

Maternal high fat diet has been implicated in the aetiology of metabolic diseases in their offspring. The hypolipidaemic actions of Cocos nucifera water improve metabolic indices of dams consuming a high fat diet during gestation. This study investigated the effects of C. nucifera water on metabolism of offspring of dams exposed to high fat diet during gestation. Four groups of pregnant Wistar rat dams (n=6) were treated orally from Gestation Day (GD) 1 to GD 21 as follows: standard rodent feed+10 mL/kg distilled water (Control), standard rodent feed+10 mL/kg C. nucifera water, high fat feed+10 mL/kg distilled water (high fat diet), and high fat feed+10 mL/kg C. nucifera water (high fat diet+C. nucifera water). The feeds were given ad libitum and all dams received standard rodent feed after parturition. Fasting blood glucose was measured in offspring before being euthanized on Postnatal Day (PND) 120. Serum insulin, leptin, lipid profile and liver enzymes were measured. Serum total cholesterol (TC), insulin, alanine transaminase (ALT) and alkaline phosphatase levels were significantly increased (p<0.05) in high fat diet offspring compared with controls. Similar changes were not observed in high fat diet+C. nucifera water offspring. Results suggest that the adverse effects of maternal high fat diet on offspring's metabolism can be ameliorated by C. nucifera water.

CD14/-159 and TNFα/-308 Promoter Polymorphisms are not associated with Development of Idiopathic Neonatal Hepatitis among Filipinos

Objective. To determine if the CD14/-159 and the TNFα/-308 single nucleotide polymorphisms (SNPs) are associated with the development of Idiopathic Neonatal Hepatitis (INH) in Filipino children. Methods. Genomic DNA from 33 patients diagnosed with INH and 33 age- and sex-matched controls, children without any liver disease, were recruited. Baseline serum total bilirubin (TB), direct bilirubin (DB), and alkaline phosphatase (ALP) of the patients were obtained from their medical records. Genotypes for CD14/159 and TNFα/-308 were determined via PCR and direct sequencing. Results. No significant difference was seen between the frequency of the CD14/-159 T allele (p=0.86) nor the TNFα/-308 A allele (p=0.62) between INH patients and controls. There was also no significant difference between the genotypic distribution of the INH and control populations for both CD14/-159 (p=0.54) and TNFα/-308 (p=0.62). There were also no significant differences noted between the different genotypes of CD14/159 and TNFα/-308 and levels of alkaline phosphatase (p=0.65, p=0.91), total bilirubin (p=0.89, p=0.75), and direct bilirubin (p=0.93, p=0.68). Conclusion. In this preliminary study, CD14/-159 and TNFα/-308 showed no association with the development of INH among Filipinos.

Percutaneous Biliary Balloon Dilation: Impact of an Institutional Three-Session Protocol on Patients with Benign Anastomotic Strictures of Hepatojejunostomy

Background: Percutaneous biliary balloon dilation (PBBD) stands as a safe, useful, and inexpensive treatment procedure performed on patients with benign anastomotic stricture of Roux-en-Y hepatojejunostomy (BASH). However, the optimal mode of application is still under discussion. Methods: A retrospective cohort study was conducted including patients admitted between 2008 and 2015 with diagnosis of BASH. Patients were divided into 2 groups: group I (n = 22), included patients treated after the implementation of an institutional protocol of 3 PBBD sessions within a fixed time interval and group II (n = 24) consisted of our historical control of patients who underwent one or 2 dilation sessions. Patency at one-year post procedure was assessed with the classification proposed by Schweizer. Symptomatic response to treatment was analyzed using the Terblanche classification. Results: Patients in group I exhibited more excellent/good results (90 vs. 50%, p = 0.003) and less poor results (5 vs. 42%, p = 0.005) according to the Schweizer classification and more grade I/excellent results according to Terblanche classification (p = 0.003). Additionally, group I showed lower serum total bilirubin (p = 0.001), direct bilirubin (p = 0.002), alkaline phosphatase (p = 0.322), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.006). Conclusion: A protocol of 3 consecutive PBBD sessions within a fixed time interval may yield a high rate of patency, with a positive clinical, biochemical, and radiological impact on patients with BASH.

ALKALINE PHOSPHATASE;

Background: This study was carried out to determine the role of total serumalkaline Phosphatase in bone metastasis among patients of breast cancer. Setting; Departmentof Surgery, Nishtar Medical University, Multan in collaboration with breast clinic MINAR. StudyDuration; January 2016 to June 2017 Subjects and methods; It was a retrospective studycarried out at breast clinic MINAR, Multan. The medical record of the female patients havingbreast cancer aged 25 to 70 years (who presented from January 2016 to June 2017) wasscrutinized. All the registered patients during above mentioned period having breast carcinomawith metastatic bone disease, as depicted on bone scan, were taken as index cases. All thecases underwent total serum alkaline Phosphatase estimation. We collected 86 cases for thisresearch study. Primary bone tumours, lymphomas, sarcomas and bone metastasis due toother primary visceral malignancies were excluded. All the required data were entered andanalyzed using computer program SPSS version 20.0. Results; The mean age of the breastcancer patients was 46.51 ± 11.11 years (ranging from 25 – 70 years). Eighty four (97.7%) weremarried. All the patients presented with lump breast. Only 3 (3.5%) of the cases gave familyhistory of breast cancer and history of contraceptive pills was positive in 4 (3.7%) of the cases.History of breast feeding was positive in 63 (73.3%) of the cases. Mean age at menarche was13.21± 0.896 years in our study cases. Mean age at menopause in our study was 46.86 ±5.66 years. Total serum alkaline Phosphatase was raised in 27 (31.4%) cases. Only 6 (6.9%) ofthe cases showed its level more than 500 IU/L. Conclusion; Our study results don’t favor totalserum alkaline Phosphatase estimation as biological marker of bone metastasis among breastcancer patients. Bone scan is more reliable and hence be employed for detection of bonemetastasis. Further studies on bone ALP and total ALP estimation are required to generatefurther evidence on this subject.

English

Background: This study was carried out to determine the role of total serumalkaline Phosphatase in bone metastasis among patients of breast cancer. Setting; Departmentof Surgery, Nishtar Medical University, Multan in collaboration with breast clinic MINAR. StudyDuration; January 2016 to June 2017 Subjects and methods; It was a retrospective studycarried out at breast clinic MINAR, Multan. The medical record of the female patients havingbreast cancer aged 25 to 70 years (who presented from January 2016 to June 2017) wasscrutinized. All the registered patients during above mentioned period having breast carcinomawith metastatic bone disease, as depicted on bone scan, were taken as index cases. All thecases underwent total serum alkaline Phosphatase estimation. We collected 86 cases for thisresearch study. Primary bone tumours, lymphomas, sarcomas and bone metastasis due toother primary visceral malignancies were excluded. All the required data were entered andanalyzed using computer program SPSS version 20.0. Results; The mean age of the breastcancer patients was 46.51 ± 11.11 years (ranging from 25 – 70 years). Eighty four (97.7%) weremarried. All the patients presented with lump breast. Only 3 (3.5%) of the cases gave familyhistory of breast cancer and history of contraceptive pills was positive in 4 (3.7%) of the cases.History of breast feeding was positive in 63 (73.3%) of the cases. Mean age at menarche was13.21± 0.896 years in our study cases. Mean age at menopause in our study was 46.86 ±5.66 years. Total serum alkaline Phosphatase was raised in 27 (31.4%) cases. Only 6 (6.9%) ofthe cases showed its level more than 500 IU/L. Conclusion; Our study results don’t favor totalserum alkaline Phosphatase estimation as biological marker of bone metastasis among breastcancer patients. Bone scan is more reliable and hence be employed for detection of bonemetastasis. Further studies on bone ALP and total ALP estimation are required to generatefurther evidence on this subject.

Profile of chronic kidney disease related-mineral bone disorders in newly diagnosed advanced predialysis diabetic kidney disease patients: A hospital based cross-sectional study

AimChronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD population. There are limited data on the pattern of these disturbances in diabetic CKD patients. Therefore, a study was conducted to find out the profile of mineral bone disorders in T2DM patients with pre-dialysis CKD. MethodsIn this cross-sectional design, diabetic patients with newly-diagnosed stage 4 and 5 CKD were evaluated. Serum levels of calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D and total alkaline phosphatase (ALP) were measured in all patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). ResultsA total of 72 eligible patients participated (44 males, 28 females; age 54.2±11.7). Patients with CKD Stage 5 had a lower level of corrected serum calcium and significantly higher level of inorganic phosphorus, total ALP and iPTH as compared to stage 4 patients. Overall, 38.5% were hypocalcemic, 31.43% were hyperphosphatemic. 24.2% of CKD subjects were vitamin D deficient (<10ng/ml) and 41.4% having vitamin D insufficiency (10–20ng/ml). In stage 4, hyperparathyroidism (iPTH>110pg/ml) was detected in nearly 43% of patients. In stage 5, only 32% patients was found to have hyperparathyroidism (iPTH>300pg/ml).There was a good correlation between iPTH and total ALP (r=0.5, p=0.0001) in this cohort. 25 (OH) vitamin D was inversely correlated with ALP (r=−0.39, P=0.001) and showed negative correlation with urine ACR (r=−0.37, P=0.002). As a group, the osteoporotic CKD subjects exhibited higher iPTH (220.1±153.8 vs. 119±108pg/ml, p<0.05) as compared to those who were osteopenic or had normal bone density. There was significant correlation between BMD and iPTH (adjusted r=−0.436; P=0.001). In the multivariate regression model, we found intact PTH to predict BMD even after adjustment of all the confounders. ConclusionThe current study showed that adynamic bone disease is prevalent even in pre-dialysis CKD population. High bone turnover disease may not be the most prevalent type in diabetic CKD. However, it could contribute to the development of osteoporosis in CKD subjects. Serum total ALP can serve as a biochemical marker to identify pattern of bone turnover where intact PTH is not available.

Prevalence and risk factors for nonvertebral bone fractures in kidney transplant recipients - a single-center retrospective analysis.

Complex and longstanding bone disease superimposed by harmful influences of immunosuppression is the reason for increased risk of bone fracture in kidney transplant recipients. The aim of our study was to analyze the incidence and prevalence of nonvertebral bone fractures and early (in the first post-transplant year) clinical and laboratory risk factors for suffering bone fracture in the long-term post-transplant period. Clinical and laboratory data as well as bone mineral density (BMD) measurements of 507 first kidney transplant recipients who were transplanted in the period from 1976 to 2011 were analyzed. The mean age of included patients was 54.3±12.0 years, there were 45% females, and mean time on renal replacement treatment prior to transplantation was 63.4±43.6months. The average observation time post-transplant was 9.7years (1.4-36.3 years). Post-transplant, 64 (12.6%) patients suffered 89 nonvertebral fractures (44 patients suffered 1 fracture, 15 patients 2 fractures, and 5 patients 3 fractures). Patients with fractures had significantly lower late BMD of femoral neck in the period of 1 - 10years post-transplant, had osteopenia and osteoporosis more frequently in the same time period, and higher serum alkaline phosphatase in the first year post-transplant. 13 patients (13/64, 20.3%) had major fractures. Patients with major fractures were significantly older than patients with no major fractures and had lower serum albumin. Frequency of treatment with bisphosphonate, calcium, or phosphate did not differ between the groups. Vitamin D supplement (active form in 98% of cases) was prescribed more frequently in the group without fractures, but this was not statistically significant. Fracture rate in our transplant patient population was comparable to that reported in the literature. Except for a higher level of serum total alkaline phosphatase in the fracture group, we found no other early laboratory risk factors for bone fractures. BMD at the femoral region 1 - 10 years after kidney transplantation but not BMD at the time of transplantation was a risk factor for nonvertebral fractures. Osteopenia and osteoporosis in the post-transplant period were found to be a fracture risk factor. .

Dietary calcium intake and rate of bone loss in men.

A high Ca intake has been recommended for osteoporosis prevention; however, little research has examined the relationship between dietary Ca and bone health in men. We examined associations between dietary Ca intake, bone mineral density (BMD) and change in BMD at the total body, hip and spine over 2 years in a cohort of men (mean age 57 years, BMI 26 kg/m2) from a trial. Data from the total cohort (n 323) were used in the analysis of Ca intake and BMD at baseline, and data from the placebo group (n 99) were used in the longitudinal analysis of Ca intake and change in BMD. Parathyroid hormone (PTH) and the markers of bone turnover serum total alkaline phosphatase activity, serum C-telopeptide and serum procollagen type-1 N-terminal propeptide were measured in a subset of participants at baseline (n 150), and associations with dietary Ca at baseline were examined. Mean Ca intake was 870 mg/d. Baseline BMD was not related to dietary Ca intake at any site, before or after adjustment for covariables. Similarly, bone loss over 2 years was not related to Ca intake at any site, before or after adjustment. Dietary Ca intake was inversely correlated with PTH at baseline (r -0·19, P=0·02), but was not associated with the markers of bone turnover. BMD and rates of bone loss were unrelated to Ca intake in these men. This suggests that strategies to increase Ca intake are unlikely to impact on the prevalence of and morbidity from male osteoporosis.

Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats

Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis. The aims of this study were to determine whether Sirt1/FXR signaling pathway plays a critical role in TP-induced hepatotoxicity. Our study revealed that the intragastric administration of TP (400 μg/kg body weight) for 28 consecutive days increased bile acid accumulation, suppressed hepatic gluconeogenesis in rats. The expression of bile acid transporter BSEP was significantly reduced and cholesterol 7α-hydroxylase (CYP7A1) was markedly increased in the TP-treated group, whereas the genes responsible for hepatic gluconeogenesis were suppressed in the TP-treated group. TP also modulated the FXR and Sirt1 by decreasing its expression both in vitro and in vivo. The Sirt1 agonist SRT1720 and the FXR agonist obeticholic acid (OCA) were used both in vivo and in vitro. The remarkable liver damage induced by TP was attenuated by treatment with either SRT1720 or OCA, as reflected by decreased levels of serum total bile acids and alkaline phosphatase and increased glucose levels. Meanwhile, SRT1720 significantly alleviated TP-induced FXR suppression and FXR-targets involved in hepatic lipid and glucose metabolism. Based on these results, we conclude that Sirt1/FXR inactivation plays a critical role in TP-induced hepatotoxicity. Moreover, Sirt1/FXR axis represents a novel therapeutic target that could potentially ameliorate TP-induced hepatotoxicity.