Elevated Serum Alkaline Phosphatase Research Articles

Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp-/- mice.

PWE-113 The liver biopsy in alcoholic hepatitis: data from the steroids or pentoxifylline in alcoholic hepatitis (stopah) clinical trial

Introduction The European Association for the Study of the Liver guidelines recommend the use of liver biopsy to confirm alcoholic steatohepatitis (ASH) in patients suspected to be suffering from alcoholic hepatitis and who are classified as high risk after prognostic assessment. Despite this it was only in 2014 that Altamirano et al published the first prognostic liver biopsy based scoring system for the evaluation of ASH (the Alcoholic Hepatitis Histological Score or AHHS). This work sought to validate their scoring system and further explore the utility of the liver biopsy in ASH. Method Two independent histopathologists, blinded to treatment and outcome, centrally reviewed liver biopsies of patients with clinically high-risk alcoholic hepatitis who had been recruited to the STOPAH trial. Results 93 (47%) of the 208 biopsies received were both adequate in quality and taken between admission and day 5 of trial treatment. 88% (82/93) had histological features diagnostic of ASH. 89% (32/36) of cases obtained as routine clinical practice were diagnostic of ASH compared to 79% (15/19) biopsied for diagnostic uncertainty. Clinically more severe liver disease was associated a higher rate of ASH diagnosis (82% of GAHS ≤8 vs. 97% of GAHS >8). 65% (53/82) of biopsy proven cases of ASH were classified as severe by AHHS. This group had a significantly higher 28 day mortality rate than those classified as mild/moderate (18% vs. 0%, Fisher’s exact p = 0.02). AHHS severity positively correlated with baseline Maddrey’s Discriminant Function and Glasgow Alcoholic Hepatitis Score (r = 0.2, p = 0.045 and r = 0.3, p = 0.01 respectively). Clinical markers of severe disease positively correlated with biopsy features of severe disease including: - serum bilirubin with bilirubinostasis (r = 0.5, p= - serum white cell and neutrophil count with lobular inflammation (r = 0.4, p = Elevation of serum alkaline phosphatase (ALP) and bilirubin are usually associated with more severe liver disease, however in this study they were seen to negatively correlate with certain biopsy features of more severe disease: - serum ALP negatively correlated with ductular changes (r = -0.2, p = 0.04) - serum bilirubin negatively correlated with Laennec fibrosis grading (r = -0.3, p = 0.01) Conclusion This work goes some way towards validating the AHHS classification. The work also highlights the parallels between clinical and histological parameters and documents negative correlations seen in other liver diseases but not previously noted in ASH. Disclosure of interest None Declared.

Methylene blue attenuates acute liver injury induced by paraquat in rats.

Paraquat (PQ) poisoning often leads to severe oxidative liver injury. Recent studies have reported that methylene blue (MB) can prevent oxidative stress-induced diseases. This study tested the hypothesis that MB treatment reduced acute liver injury induced by PQ in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: (1) normal group, (2) MB group (2mg/kg i.p.), (3) PQ group (35 mg/kg i.p.) and (4) PQ+MB group (MB 2mg/kg i.p. administrated 2h after PQ). We evaluated the changes of liver histopathology, serum liver enzymatic activities, oxidative stress, heme oxygenase-1 expression, and mitochondrial permeability transition. The rats were injected with PQ produced liver injury, evidenced by histological changes and elevated serum alkaline phosphatase and alanine transaminase levels; PQ also led to oxidative stress, an increase of malondialdehyde content and mitochondrial permeability transition pore opening. Pathological damage and all of the above mentioned markers were reversed in the animals treated with MB than in those who received PQ alone. Meanwhile, MB significantly increased the contents of superoxide dismutase, adenosine triphosphate and the expression of heme oxygenase-1. In conclusion, MB had a protective effect against PQ-induced hepatic damage in rats. The mechanisms of the protection seem to be the inhibition of mitochondrial permeability transition opening and the increase of heme oxygenase-1 expression.

656 Elevated Serum Alkaline Phosphatase At Follow-Up Is Associated With Worse Outcomes in Primary Sclerosing Cholangitis

Background: Primary sclerosing cholangitis (PSC) is a progressive, chronic cholestatic liver disease characterized by inflammatory and fibrotic destruction of the intrahepatic and/or extrahepatic bile ducts. The pathogenesis of lesions in PSC are unknown. Bacterial components have been postulated to stimulate an aberrant immune response resulting in the perpetuation of the biliary inflammation seen in PSC. Alpha-hemolytic streptococci was associated with this disease in a previous study of bile samples from PSC patients, though more likely in those previously instrumented. Aims: To assess the microbial composition of bile collected via diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in patients with PSC compared to controls using culture and qPCR.Methods: Bile was collected prospectively during routine ERCPs. A catheter was passed through the scope and bile was carefully aspirated upon entry in order to minimize contamination. Bacterial culture was performed using serial 10 fold dilutions of the sample in phosphate buffered saline (PBS) to achieve dilutions ranging from 10-1 to 10-3. A 0.1mL aliquot of the original sample and each dilution was plated onto enrichment media. The tubes were examined daily for growth for up to 5 days. We also extracted DNA from the bile using the tissue protocol in QIAamp DNA Mini Kit. Participants: 18 patients with primary sclerosis cholangitis (7 were ERCP naive) and 7 non-PSC patients Results: Of the 18 patients with PSC, alpha hemolytic streptococci was identified in 10 of the samples alone or in combination with staphylococcus. This was not related to having had a prior ERCP (p=.36). Eight of the PSC samples had no growth. Of the 7 non-PSC patients, alpha-hemolytic strep was found in three patients but only in combination with multiple other organisms. Among the control samples there was no one dominating species.11/18 PSC patients had concurrent inflammatory bowel disease. All 7 non-IBD patients had growth while only 3 of the IBD patients had growth. Samples from those without IBD were more likely to have growth (p=0.0025). 7/18 PSC patients had received antibiotics prior to the ERCP. Bacteria growth was not related to antibiotic use prior to ERCP (p=0.27). qPCR was done to confirm these finding which correlated when compared to a standard E.Coli curve. Conclusion: Alpha-hemolytic Streptococcus may play a role in the pathogenesis of primary sclerosing cholangitis as this was the dominant species cultured from bile samples of PSC patients. . While validating previous work, in this study alpha hemolytic strep was found in both ERCP naive patients and not. Alpha-hemolytic strep was not regularly seen in the non-PSC bile samples, and if present was in combination with multiple other species. This finding suggests antibiotics targeting alpha hemolytic streptococcus may be a useful therapy for PSC.

Cholangioscopic diagnosis of iatrogenic recurrent choledocholithiasis

A 50-year-old woman was referred to our center for cholangioscopy for investigation of recurrent choledocholithiasis and a refractory biliary stricture. Ten years before this referral she had undergone a complicated cholecystectomy, which had started as a laparoscopic procedure but had to be converted to open surgery. Five years after cholecystectomy, she developed abdominal pain and elevated serum alkaline phosphatase levels.

Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9.

An increased risk of valproate-induced toxicity has been reported in children, particularly in those younger than 2 years of age. Significant variations in valproate pharmacokinetics and shifts in the metabolic pathways towards CYP2C9-dependent metabolism seem to play some role in the age-related differences in the incidence of adverse events. We present the case of a premature patient with moderate hemorrhage in the subependymal region (grade II — intraventricular hemorrhage without ventricular dilatation), several myoclonic episodes in her right upper arm (series of jerks lasting milliseconds), and epileptiform abnormalities on the EEG (localized spike-and-wave in the left frontal region with preserved background activity who was treated with valproate. Serious side effects, consisting of bone marrow depression, hyperammonemia, and serum alkaline phosphatase elevation, were observed seventeen days after the beginning of valproate therapy. The toxic symptoms were likely the consequence of a reduced ability to metabolize valproate. The patient was demonstrated to carry two loss-of-function mutations in CYP2C9 (CYP2C9*3/*3) resulting in exaggerated blood concentrations of valproate. The present case highlights the importance of assaying inborn errors in CYP2C9 gene in pediatric patients to avoid valproate-evoked serious side effects.

Central giant cell granuloma of posterior maxilla: first expression of primary hyperparathyroidism.

A case of 19-year-old male patient reported with the chief complaint of slowly growing diffuse painless swelling over the right part of the face from last 6 months. Intraoral examination revealed a swelling on right side of palate in relation to molar region with buccal cortical plate expansion. Radiographic examination (orthopantograph and 3DCT) showed large multilocular radiolucency in right maxilla with generalized loss of lamina dura. Incisional biopsy was done and specimen was sent for histopathological examination which showed multinucleated giant cells containing 15–30 nuclei. Based on clinical, radiological, and histopathological findings provisional diagnosis of central giant cell granuloma was made. Blood tests after histopathology demonstrated elevated serum calcium level and alkaline phosphatase level. Immunoassay of parathyroid hormone (PTH) level was found to be highly elevated. Radiographic examination of long bones like humerus and femur, mandible, and skull was also done which showed osteoclastic lesions. Considering the clinical, radiographic, histopathological, and blood investigation findings, final diagnosis of brown tumour of maxilla was made. The patient underwent partial parathyroidectomy under general anaesthesia to control primary hyperparathyroidism. Surgical removal of the bony lesion was done by curettage. The patient has been followed up for 1 year with no postoperative complications and the lesion healed uneventfully.

A rare case of peripheral osteoma of the zygoma.

A rare case of peripheral osteoma of the zygoma.

Elevation of serum alkaline phosphatase (ALP) level in postmenopausal women is caused by high bone turnover.

Most of the alkaline phosphatase (ALP) isoenzymes are derived from the bones and liver. High levels of ALP are often encountered during routine blood investigation in elderly patients. However, because ALP includes various isoenzymes from other tissues, an accurate diagnosis is usually not possible on the basis of elevated ALP alone. To identify the cause of increased ALP in postmenopausal women. We measured serum ALP in a group of 626 postmenopausal osteoporotic women before and after treatment with a bisphosphonate (either alendronate or risedronate). We analyzed the correlations between ALP levels and bone metabolic markers or hepatic function markers. The ALP and BAP levels of people in their 80s were significantly higher than those of people in their 60s. With bisphosphonate therapy, the BAP decreased, and the elevated ALP decreased to normal range levels. ALP was highly and significantly correlated with BAP both before and after treatment. The changes in levels of ALP correlated well with the changes in BAP levels before and after bisphosphonate therapy. Markers of liver function correlated with total ALP (p<0.01), but the correlation was much smaller than that between ALP and BAP. Bisphosphonate treatment lowered ALP levels, and this decrease was strongly correlated with a decrease in BAP. Among blood test data, the decrease in BAP had the strongest correlation with the ALP decrease. For treatment of osteoporosis, ALP is an acceptable alternative to BAP. Elevated ALP in postmenopausal women is mainly caused by high bone turnover.

Skeletal Metastasis in Gallbladder Cancer from a High-Volume Tertiary Care Center of North India: a Series of Rare Occurrence

Gallbladder carcinoma is usually characterized by late diagnosis and poor prognosis. Skeletal metastases in gallbladder cancer have been rarely reported in literature. In this study, we evaluated the incidence of skeletal metastasis in gallbladder cancer at our high-volume center and their clinical presentation, radiological imaging, treatment received, outcome, and survival. Records of all gallbladder carcinoma patients registered in our department from October 2007-October 2012 were retrospectively reviewed to identify gallbladder cancer patients with skeletal metastasis and their data was collected and analyzed. Out of 340 cases of gallbladder carcinoma, 189 (55.58 %) were having stage IV disease. Of these, seven (2.1 %) patients had cytologically proven skeletal metastasis. All seven patients had advanced loco-regional abdominal disease with coexistent liver metastasis. Presenting symptoms were predominantly weight loss and back pain with markedly elevated serum alkaline phosphatase (median = 1231 IU/ml). Dorsolumbar vertebral metastasis was the most common site of skeletal metastasis in our series (5/7), followed by pelvic bone (2/7) while skull and sternal metastasis were present in one patient each. All these patients had short median survival (median = 30 days, range = 15-60 days). Incidence of skeletal metastasis in gallbladder cancer is very low (2.1 %). Axial skeleton was the most common site of bone metastasis. Gallbladder cancer with skeletal metastasis portends poor prognosis with rapidly fatal course.

Abstract 17213: Serum Alkaline Phosphatase Elevation is an Independent Predicting Factor of Worsening Renal Function in the Patients with Acute Heart Failure

Background: Worsening renal function (WRF) has been associated with poor outcome in the patients with acute heart failure (AHF). Recently, venous congestion had been paid attention to the important predictor of WRF in AHF. Abnormal serum alkaline phosphatase (ALP) was reported as a biological marker of liver congestion and of the extent of right sided filling pressure in AHF. In this study, we evaluated the relationship between ALP and development of WRF in AHF. Method: We enrolled consecutive patients hospitalized due to AHF in cardiovascular center of St Luke’s International Hospital, Tokyo, Japan from January, 2004 to December, 2013. We excluded the patients either on dialysis, estimated glomerular filtration rate (eGFR) under 15 ml/min/m2, or primary liver disease. We defined WRF as elevation of serum creatinine of 0.3 mg/dl or above raised from admission to discharge. We classified patients into tertiles by baseline measurements of ALP. We performed multivariate analysis to make the prediction model of WRF. Result: Total 1245 patients (age 76.4±12.9 years old, male 54.8%) were enrolled. During hospitalization, 166 (13.3%) patients developed WRF. Patients were classified into tertiles (&lt;77, 77 to 203, &gt;203 IU/L). Compared with the lowest ALP tertile, middle and the highest ALP tertile groups developed WRF more frequently (8.4% vs 15.5% vs 16.8%, P=0.003). In multivariate logistic regression, after adjustment of age, gender, and other risk factors, we found eGFR (Odds ratio (OR) 0.978, 95%Confidence Interval (CI) 0.967 to 0.987, P&lt;0.001), diabetes mellitus (OR 1.83, CI 1.19 to 2.80, P=0.005), norepinephrine use (OR 1.65, CI 1.04 to 2.61, P=0.03), albumin (OR 0.507, CI 0.337 to 0.764, P=0.001), middle tertile ALP (OR 1.81, CI 1.07 to 3.06, P=0.02), and highest tertile ALP (OR 2.08, CI 1.24 to 3.48, P=0.005) compared with lowest tertile were independent variable to predict WRF. Conclusion: Our study showed that elevated serum ALP is an independent predicting factor for WRF in the patients with AHF.

Palliative prognostic tools for the terminally ill patients with gastric cancer.

120 Background: Terminally ill patients with gastric cancer have specific gastrointestional symptoms and signs related with cancer progression. To estimate accurate survival expectancy of gastric cancer patients is important for timely decision making of their end of life issues. Methods: We reviewed the 276 patients with terminally ill gastric cancer who were treated at Yonsei Cancer Center between January 2007 and December 2011 and eventually were died. Retrospectively, we conducted the data of clinical signs, symptoms, and laboratory results at the time of cessation of the active treatment. Then, we established the palliative survival estimation model by stratification of risk group. Results: Median palliative survival time from the decision to stop further treatment to death was 42days. In the multivariate Cox regression analysis, 5 parameters were identified as prognostically significant factors: anorexia, dyspnea, hypoalbuminemia, elevated blood urea nitrogen, and elevated serum alkaline phosphatase. We scored each variables as 1-3 for symptom(1:asymptomatic, 2:symptomatic, 3:symptomatic requiring intervention) and 1-2 for lab results(1:normal, 2:abnormal) and summed up each scores. Using the total score, patients were divided into 3 risk groups: low-risk(5-7points), intermediate-risk(8-11points), and poor-risk patients(12point). As a result, median palliative survival for low-risk group(n=110) was 87.0±7.4days, intermediate-risk group(n=158) and poor-risk group(n=8) were 31.0±2.1days and 6.0±2.1days, respectively (p&lt;0.0001). Conclusions: Using multivariate analysis and summation of each prognostic factor score, 3 risk groups were determined. After validation by prospective multicenter trial, this palliative survival time estimation tool will be helpful to inform the accurate survival for terminally ill gastric cancer patients.

Effect of Thymoquinone and Omega-3 on Intestinal Ischemia/Reperfusion Induced Hepatic Dysfunction in Rats

Intestinal Ischemia-Reperfusion (I/R) is a complex phenomenon causing local and remote tissue destruction and multiple-organ dysfunction. The present study investigates the effect of thymoquinone and omega-3 on intestinal I/R-induced hepatic dysfunction. Sixty four Wistar albino rats were randomly allocated into four experimental groups: sham control, intestinal I/R control, thymoquinone (10 mg/kg) and omega-3 (300 mg/kg) pre-treated groups respectively. Intestinal I/R model were established by clamping the superior mesenteric artery for 30 min followed by 60 min reperfusion. Serum levels of aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) were measured. Hepatic tissue contents of Malondialdehyde (MDA), reduced Glutathione (GSH), Myeloperoxidase (MPO) and Tumor Necrosis Factor alpha (TNF-α) and Superoxide Dismutase (SOD) activity were measured. Apoptosis in hepatic tissue cells was determined by immunities to chemical analysis of caspase-3. Hepatic histopathological examination was carried out. Intestinal I/R elevated serum AST, ALT and ALP levels. In-addition, hepatic tissue SOD activity and GSH content were decreased, while MDA, MPO and TNF-&alpha contents were increased. Pre-treatment with thymoquinone or omega-3 corrected the histopathological changes and serum AST, ALT, ALP levels as well as hepatic tissue activity of SOD and GSH contents. In-addition, hepatic tissue contents of MDA and MPO were decreased. Furthermore, immunohistochemical examination showed remarkable activation of caspase-3 activity in hepatic tissue after intestinal I/R, which were corrected by thymoquinone or omega-3 pre-treatment. The protective potential of thymoquinone and omega-3 on hepatic dysfunction could be attributed to the known antioxidant, antiapoptotic and anti-inflammatory effects of test drugs.

Cholestatic Jaundice Due to Renal Cell Carcinoma: A Variant of Stauffer’s Syndrome

Introduction: Renal cell carcinoma is associated with a wide spectrum of para-neoplastic syndromes, which may be precursors of primary or recurrent disease. Non-metastatic hepatic dysfunction in patients suffering from renal cell carcinoma is known as Stauffer’s syndrome, first described by Stauffer in 1961. Hepatic dysfunction without jaundice is commonly described in the literature, but paraneoplastic cholestatic jaundice is rare. A 65-year-old male with past medical history significant for end-stage renal disease on hemodialysis, diabetes, coronary artery disease, and congestive heart failure presented to the hospital with jaundice, malaise, fatigue, poor appetite and abdominal discomfort for the last 2 weeks. The patient was a non-smoker and non-alcoholic with no family history of malignancy or liver diseases. Vitals were unremarkable on initial presentation. Physical examination was significant for mild tenderness in the right upper quadrant. Blood work demonstrated blood glucose 240 mg/dL, BUN-28 mg/dL, creatinine 1.91 mg/dL, total bilirubin 8 mg/dL, direct bilirubin-4.5 mg/dL, alkaline phosphatase-353 U/L, AST-45 U/L, and ALT-26 U/L. Complete blood count revealed white count-6.0 K/uL, hemoglobin-11.7 mg/dL, hematocrit-34%, and platelets-182000 /μL. Initial urinalysis was significant for protein, glucose, trace ketones, 4+ urobilinogen, a large amount of bilirubin, and a small amount of blood. Ultrasound of the liver demonstrated thick-walled gallbladder with cholelithiasis and intraluminal sludge. Computed tomography of the abdomen with oral contrast demonstrated a 1.5-cm enhancing exophytic lesion in the lower pole of the right kidney (Figure 1). Thus, the radiological evaluation confirmed the diagnosis of renal cell cancer. The patient underwent surgery for RCC that resolved the hepatic dysfunction in 2-3 weeks post-surgery. Stauffer’s syndrome is associated with the production of cytokines by the tumor and several biochemical abnormalities, including elevated serum alkaline phosphatase. Hepatic dysfunction, in the absence of liver metastases, occurs in 10-15% of RCC and is attributed to the production of cytokines from the tumor, including interleukin-6. It is associated with fever, weight loss, and an unfavorable prognosis.Figure 1: CT abdomen demonstrated a 1.5-cm enhancing exophytic lesion in the lower pole of the right kidney (marked by an arrow).

The natural history of main duct-involved, mixed-type intraductal papillary mucinous neoplasm: parameters predictive of progression.

As such, the natural history of MPD-involved IPMN is poorly understood. The high-risk of malignancy associated with main pancreatic duct (MPD)-involved intraductal papillary mucinous neoplasm (IPMN) has been established by surgical series. The International Consensus Guidelines recommend surgical resection of MPD-involved IPMN in fit patients. A review of a prospectively collected database (1992-2012) of patients with IPMN undergoing primary surveillance was performed. Invasive progression was defined as invasive carcinoma on pathology and/or positive cytopathology. Analyses included univariate, logistic regression, and receiver operating characteristic curve analyses. A total of 503 patients with IPMN underwent primary surveillance, 70 for MPD-involved, mixed-type IPMN. Indications for intensive surveillance of these 70 high-risk patients were comorbidities, patient choice, and early/borderline MPD dilation (42%, 51%, and 7%, respectively). Mean follow-up was 4.7 years. Nine patients (13%) progressed at a mean of 3.5 (range, 1-9) years during follow-up. Univariate analyses yielded weight loss, interval (from isolated branch-duct IPMN) to MPD involvement, diffuse MPD dilation, increase of MPD diameter, absence of extra pancreatic cysts, elevated serum CA19-9 levels, and elevated serum alkaline phosphatase levels as significant. Maximum MPD and/or branch-duct diameter were not significant. In logistic regression, diffuse MPD dilation, serum CA19-9 and serum alkaline phosphatase levels, and absence of extra pancreatic cysts were predictors of invasiveness. The receiver operating characteristic curve indicated that the combination of these 4 factors achieved an accuracy of 98% in predicting progression. Primary surveillance of mixed-type IPMN may be a reasonable strategy in select patients. Diffuse MPD dilation, serum CA19-9, serum alkaline phosphatase, and absence of extrapancreatic cysts predict patients likely to progress during primary surveillance.

Pattern of Elevated Serum Alkaline Phosphatase (ALP) Levels in Hospitalized Patients: A Single Centre Study

Background: Persistent elevation of serum ALP is frequently encountered and can pose a diagnostic dilemma due to its association with a wide range of clinical conditions. However, the significance of ALP in these clinical conditions in routine practice is often underestimated or overrated. Objectives: This study was determined to assess the pattern of ALP with an aim to elucidate its clinical utility among hospitalized patients. Method &amp; materials: The inpatients with high ALP level were enlisted &amp; analysed between January to December 2012 excluding cases of (a) patients who have bone involvements with malignancies and (b) HIV-seropositive patients attending a tertiary care Hospital at Dhaka. Extremely high levels of ALP were defined as being more than 1000 U/L. These patients were divided into different groups according to their final diagnosis. Results: A total of 154 hospitalized patients with eligible medical records were identified (98 male and 56 female, mean age 36 years). Their ALP levels are ranging from 1,006 to 3,067 IU/L; very extreme values of &gt; 3000 IU/L being rarely (only about 2%) documented. Patients with sepsis can have an extremely high alkaline phosphatase level (1,648.2 ± 328.4 IU/L) and a normal bilirubin. Conclusion: High serum ALP levels in hospitalized patients were commonly found in three major groups having obstructive biliary diseases, infiltrative liver disease and sepsis. A variety of other causes were also noted. This routine laboratory test should receive more attention in clinical decision-making than has previously been given. DOI: http://dx.doi.org/10.3329/pulse.v6i1-2.20329 Pulse Vol.6 January-December 2013 p.20-26

Animal models in primary biliary cirrhosis and primary sclerosing cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated cholangiopathies with enigmatic etiology and pathogenesis. They have distinct clinical, laboratory, immunological, and histomorphological characteristics. Well-characterized animal models for PBC and PSC are utterly needed to develop novel pathogenetic concepts and to study innovative treatment strategies. The aim of the current paper is to outline the characteristics of ideal PBC and PSC animal models and to contrast this with a real-life up-to-date overview of currently available mouse models. Although some of this models show several individual characteristics of PBC and PSC, it is obvious that all of them have substantial and important limitations. Nevertheless, some may be beneficial to study certain pathophysiological aspects. Potential cholangiopathy animal models should be systematically investigated in regard to elevated serum alkaline phosphatase, bilirubin, and bile acid levels; immunological abnormalities; and longitudinal studies in regard to their liver phenotype. We herein propose a common systematic workup for potential models based on the fact that there are some intriguing disease combinations in specific genetically modified mice and recommend a stepwise process in regard to model characterization with methodical harvesting and screening of numerous organs for potential concomitant diseases. Due to the complex nature of both cholangiopathies, it seems to be very likely that no single perfect PBC or PSC model will ever be generated. The models outlined herein will certainly help to clarify specific pathogenetic aspects and even more important may turn out to be suitable to test potential drugs for treatment.

Effects of Fusarium mycotoxins with yeast cell wall absorbent on hematology, serum biochemistry, and oxidative stress in broiler chickens

The objectives of the present study were to investigate the toxicity of feed-borne Fusarium mycotoxins on hematology, serum biochemistry, and oxidative stress of broiler chickens, and to evaluate the efficacy of yeast cell wall adsorbent (YCW) in preventing mycotoxins-induced adverse effects. A total of 300 one-day-old Arbor Acres broiler chickens (mixed sex) were randomly divided into 3 groups and received different treatments (5 repetitions per treatment). Treatments were control, naturally contaminated diet (NCD; aflatoxin, 102.08 mg/kg; zearalenone, 281.92 mg/kg; fumonisin, 5,874.38 mg/kg; deoxynivalenol, 2,038.96 mg/kg), and NCD + 2 g/kg of YCW. Broilers fed NCD showed elevated serum alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyl transferase (GGT), and malondialdehyde (MDA) at 21 d, and alanine transaminase, GGT, creatine kinase, and MDA at 42 d. Higher white blood cell, lymphocyte (LYM), platelet, red blood cell, hemoglobin, hematocrit, and mean corpuscular hemoglobin counts at 21 d, as well as LYM in whole blood and hepatic mRNA expression of heat shock protein 70 at 42 d were also observed in broilers fed with NCD compared with the control diet. However, lower mean corpuscular volume at 42 d and total superoxide dismutase (T-SOD) at both 21 and 42 d were observed in broilers with the NCD treatment when compared with those with the control treatment. Dietary addition of YCW at the level of 2 g/kg in addition to the NCD treatment showed a positive protective effect on GGT, T-SOD in serum, white blood cells, LYM, platelets, and hemoglobin in whole blood at 21 d, and T-SOD, MDA in serum, LYM, mean corpuscular volume in whole blood, and hepatic mRNA expression of heat-shock protein 70 at 42 d. It is suggested that feeding NCD for 42 d might result in a deleterious effect on broiler chickens, and addition of 2 g/kg of YCW can partly attenuate the detrimental effects of the NCD feeding.

Chronic pancreatitis with benign biliary obstruction: management issues.

Benign biliary obstruction (BBO) is an important complication in patients with advanced chronic pancreatitis (CP). Its presentation varies from an incidental finding to overt jaundice. Thus it presents certain management issues. The present study was therefore performed to analyze the clinical presentation and management of biliary obstruction in patients with CP. Retrospective analysis was performed from a prospectively collected database of 155 CP patients managed at our institute from October 2003 to June 2012. Among 43 (28 %) CP patients with biliary obstruction, 3 patients had evidence of malignancy on follow-up examination and were excluded from the final analysis. The various presentations include chronic nonprogressive elevation of serum alkaline phosphatase (SAP) (n = 15), a progressive increase in SAP with episodes of jaundice (n = 17), and persistent jaundice (n = 8). Of 15 patients with chronic nonprogressive elevation of SAP, 5 were managed conservatively, and the remaining 10 underwent only a pancreatic drainage procedure. During a median follow-up of 41 months (range 11-90 months), none of the 15 patients developed complications related to biliary obstruction. All patients with progressive increase in SAP levels and persistent jaundice underwent the biliary drainage procedure [choledochojejunostomy (CDJ, n = 20) and choledochoduodenostomy (CDD, n = 3)]. During a median follow-up of 30 months (range 10-89 months), two patients died of unrelated causes and two patients had an asymptomatic elevation of SAP. BBO is common in patients with CP; however, biliary drainage is not indicated for chronic nonprogressive elevation of SAP. In patients with a progressive increase in SAP or persistent jaundice, both CDJ and CDD provide effective biliary drainage.

Towards the revival of alkaline phosphatase for the management of bone disease, mortality and hip fractures

The story of alkaline phosphatase in the management of mineral and bone disorder (MBD) in patients with chronic kidney disease (CKD) is an interesting and educational part of the history of nephrology. Circulating alkaline phosphatase, a marker of bone turnover, was among the first bone markers used for the detection and management of ‘renal osteodystrophy’, a term previously used by clinicians and researchers since the 1970s. However, by the mid-1990s and early 2000s alkaline phosphatase fell out of favor, when commercial parathyroid hormone (PTH) assays become available. At the same time, the first Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines on CKD–MBD chose not to mention alkaline phosphatase, as target ranges were uncertain [1]. A rise in serum alkaline phosphatase, known as hyperphosphatasemia or hyperphosphatasia, is an expected finding in progressive CKD with worsening kidney function [2]. Elevated serum alkaline phosphatase concentrations in CKD patients with otherwise intact liver and biliary systems usually result from excess of the bone isoforms of the enzyme [3–5]. Specific detection of the bone isoform may not have clinical utility, since it was found not to correlate with inflammation or mortality risk [6]. The recent data suggest that a rise in alkaline phosphatase in dialysis patients is associated with worsening bone mineral density [7], and worse responsiveness to erythropoiesis stimulating agents [8].