Alkaline Phosphate Research Articles

Serum Alkaline Phosphate Level Associates with Metabolic Syndrome Components Regardless of Non-Alcoholic Fatty Liver; A Population-Based Study in Northern Iran.

Background: Serum alkaline phosphatase (ALP) is an indicator of hepatobiliary disorders, such as metabolic syndrome (MetS). To assess the association between serum ALP levels and MetS, with or without non-alcoholic fatty liver disease (NAFLD), in a cohort study in northern Iran. Methods: Data from approximately 5257 subjects aged more than 18 years participating in the Amol cohort were used. We extracted the required data and investigated the correlation between liver enzyme levels and MetS. Multiple logistic regression analyses based on the serum ALP quartiles were performed. Results: Of them, 2860 were male with a mean age of 42.11±16.1 years. A positive linear trend was observed between serum ALP levels and the number of MetS components in both sexes. In both sexes, systolic blood pressure, waist circumferences, and high-density lipoprotein (HDL) had a significant association with ALP. After adjusting for age, both sexes with NAFLD showed an increased risk of developing MetS. The risk of NAFLD increased in individuals with>2nd quartile of ALP. Furthermore, higher ALP levels were associated with an increased risk of MetS in males (1.1014 [0.782-1.315]) and females (1.441 [1.085-1.913]). Conclusion: There is a significant association between serum ALP levels and MetS, independent of fatty liver changes, suggesting that this marker can be considered as a feasible predictor of MetS.

Hepatoprotective and Nephroprotective Effects of Haronga (Harungana madagascariensis) in Combination with Antioxidant Compounds in Albino Spraque Dawley Rats

Aim: The aim of this study was to evaluate the effects of Harungana madagascariensis stem bark ethyl acetate extract with antioxidants on the liver and kidney in rats.
 Study Design: Experimental.
 Place and Duration of Study: Department of Veterinary Pharmacology and Toxicology, University of Ibadan (from January-February, 2020).
 Methodology: This was done using Albino rats (Wistar) grouped into 12 of 5 animals per group for protective studies,ethyl acetate extract (EHM) of the plant at 100mg/kg, 200mg/kg and 500mg/kg in combination with each of Ascorbic acid (200mg/kg), Selenium (1mg/kg) and/or Allopurinol (50mg/kg). Group I-III are control groups, IV-VI EHM/Ascorbic acid, groups VII-IX EHM/Se, and groups X-XII EHM/AL. The combination were administered for 8 days prior acetaminophen (800mg/kg) on day 9. Animals were sacrificed on day 10 and samples were collected for biochemical and histopathological evaluations.
 Results: The study showed that acetaminophen induced-stress on the liver and kidney causing increase in liver biomarkers such as the aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphate (ALP), creatinine, blood urea, total protein and gamma-glutamyl transferase (GGT). The combination of H. madagasacariensis Ethyl acetate extract with Ascorbic acid, Allopurinol and/or Selenium at different doses causes protective effects by reducing the release of biomarkers and stabilized the elevated enzymes level shown in acetaminophen group. The histopathology of the liver in the acetaminophen group showed moderate portal congestion with mild periportal cellular infiltration and a moderate to severe portal fibrosis, while the kidney showed severe diffuse tubular degeneration and necrosis.
 Conclusion: The EHM (500 mg/kg and 200 mg/kg) in combination with Ascorbic acid, Allopurinol or Selenium protected the liver and kidney from injury induced by Acetaminophen. The Ethyl acetate extract (EHM) of the plant showed synergy with Ascorbic acid, Selenium and Allopurinol to prevent injury on both organs.

Dietary phosphorus requirement of silver CARP (Hypophthalmichthys molitrix) fingerlings.

The aim of this study was to determine the optimal dietary phosphorus (P) requirement and its effects on growth performance, body composition, mineralizationand alkaline phosphate (ALP) activity in silver carp (Hypophthalmichthys molitrix). A total of 360 fish with an average initial weight of 7.0 ± 0.15 g were divided into 18 tanks (70 L capacity each) with a stocking density of 20 fish per tank in triplicate. The fish were fed diets containing six levels of P (3.3, 4.4, 5.5, 6.5, 7.5and 8.6 g/kg) up to satiation for 90 days twice daily at 09:00 and 16:00. The results showed that fish fed diets containing 6.5and 7.5 g/kg dietary P had significantly higher (p < 0.05) growth performance in terms of final weight gain, average weight gain (AWG), weight gain% (WG%), protein efficiency ratio (PER) and specific growth rate (SGR) than fish fed other diets. The best value of the feed conversion ratio (FCR) was observed in fish fed the 6.5 g/kg P diet, which was not significantly different from the 7.5 g/kg P diet. Increasing P supplementation above 6.5 g/kg significantly reduced (p < 0.05) the feed intake of silver carp. Whole-body composition analysis indicated that increasing P levels resulted in a decrease (p < 0.05) in crude fat (CF) and an increase (p < 0.05) in crude ash (CA) content, while crude protein (CP) and moisture content remained unaffected (p > 0.05). Fish fed diets containing ≥6.5 g/kg P had significantly higher (p < 0.05) Ca content in the whole body, bonesand scales compared to those fed diets containing ≤5.5 g/kg P. A similar trend was observed for P and Mg contents in the whole body, bonesand scales. The Zn content tended to decrease (p < 0.05) with increasing P supplementation in the whole body and bones, but fish fed diets containing ≥6.5 g/kg P had significantly higher (p < 0.05) Zn content compared to fish fed diets containing ≤5.5 g/kg P. The Ca/P ratio was significantly affected by P supplementation. Fish fed diets containing ≥6.5 g/kg P had significantly higher (p < 0.05) Ca and P contents in the serum than fish fed other diets. ALP activity increased (p < 0.05) with increasing P levels up to 6.5 g/kg P and decreased (p < 0.05) thereafter. In conclusion, supplementing P up to 6.35 g/kg is recommended for the optimal growth of silver carp.

Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals across Populations and Testing Platforms.

Harmonization in laboratory medicine is essential for consistent and accurate clinical decision-making. There is significant and unwarranted variation in reference intervals (RIs) used by laboratories for assays with established analytical traceability. The Canadian Society of Clinical Chemists (CSCC) Working Group on Reference Interval Harmonization (hRI-WG) aims to establish harmonized RIs (hRIs) for laboratory tests and support implementation. Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (a) analysis of big data from community laboratories across Canada; (b) statistical evaluation of age, sex, and analytical differences; (c) derivation of hRIs using the refineR method; and (d) verification of proposed hRIs across 9 laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults. Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived hRIs met proposed verification criterion across 9 laboratories and 5 manufacturers for alkaline phosphatase, albumin (bromocresol green), chloride, lactate dehydrogenase, magnesium, phosphate, potassium (serum), and total protein (serum). Further investigation is needed for some analytes due to failure to meet verification criteria in one or more laboratories (albumin [bromocresol purple], calcium, total carbon dioxide, total bilirubin, and sodium) or concern regarding excessively wide hRIs (alanine aminotransferase, creatinine, and thyroid stimulating hormone). We report a novel data-driven approach for RI harmonization. Findings support feasibility of RI harmonization for several analytes; however, some presented challenges, highlighting limitations that need to be considered in harmonization and big data analytics.

Characterization of phenyl propiolic acid from Proteus mirabilis DMTMMR-11 and Evaluation of its mode of action against Yersinia enterocolitica (MTCC-840) an in-Vitro and in-Vivo based approach

Foodborne illnesses are pervasive in raising public health concerns in both developed and developing nations. Yersinia enterocolitica a zoonotic bacterial species that causes food-transmitted infections, and gastroenteritis, is its most prevalent clinical manifestation. This study aims to investigate the differences, dependencies, and inhibitory mechanisms between the host and the microbiome. Proteus mirabilis DMTMMR-11, the bacterium found in the human gastrointestinal tract was used for the extraction of intracellular metabolite, because of its beneficial effects on the normal flora of the human gut. Phenyl propiolic acid was identified as the dominant compound in the metabolite after characterization using FT-IR, NMR, and LC-MS-MS. To assess its inhibitory mechanism against Yersinia enterocolitica, the pathogen was subjected to biological characterization by MBC and MIC, resulting in the rate of inhibition at 50 μg/ml. Anti-bacterial curve supports the inhibited growth of Y. enterocolitica. Mechanism of inhibition at its cellular level was indicated by the increase in alkaline phosphate content, which drastically reduced the cell membrane and cell wall potential expanding its permeability by intruding the membrane proteins, which was observed in SEM Imaging. Phenyl propiolic acid efficiently disrupts the biofilm formation by reducing the adherence and increasing the eradication property of the pathogen by exhibiting 65% of inhibition at the minimal duration of 12h. In-vivo study was carried out through host-pathogen interaction in C. elegans, an efficient model organism assessed for its life-span, physiological, and behavioral assays.

Heterogeneity in regional changes in body composition induced by androgen deprivation therapy in prostate cancer patients: potential impact on bone health-the BLADE study.

It is not clear whether changes in body composition induced by androgen deprivation therapy (ADT) in prostate cancer (PC) patients are uniform or vary in the different body districts and whether regional lean body mass (LBM) and fat body mass (FBM) could have an impact on bone health. To prospectively evaluate the regional changes in LBM and FBM in PC patients submitted to degarelix; to explore the relationship of regional body composition and bone mineral density (BMD) and bone turnover markers. 29 consecutive non metastatic PC patients enrolled from 2017 to 2019. FBM, LBM and bone mineral density (BMD) evaluated by dual-energy x-ray absorptiometry (DXA) at baseline and after 12-month of ADT. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) assessed at baseline, 6 and 12months. All patients underwent degarelix administration. T-test or sign test and Pearson or Spearman test for continuous variables were used when indicated. Median percent increase in FBM ranged from + 14.5% in trunk to + 25.4% in the left leg after degarelix. LBM changes varied from + 2% in the trunk to -4.9% in the right arm. LBM in both arms and legs and their variations after degarelix directly correlated with ALP and inversely correlated with CTX. Lean mass of limbs, trunk and legs significantly correlated with BMD of the hip, lean mass of the trunk significantly correlated with spine BMD. These are post-hoc analysis of a prospective study and this is the main limitation. an heterogeneous change in body composition among body district is observed after ADT and bone turnover is influenced by lean mass and its variation. A supervised physical activity is crucial to maintain general physical performance and preserving bone health.

Microcystin-leucine-arginine impairs bone microstructure and biomechanics by activating osteoimmune response and inhibiting osteoblasts maturation in developing rats

Microcystin-LR (MC-LR) affects bone health in adult mice via osteo-immunomodulation. However, its effect on osteoblasts and bone development is unclear. This study investigated the effect of MC-LR on bone osteoimmune and osteoblasts in the developing period. 18 Four-week-old male Sprague Dawley rats were divided into two groups (n = 9 per group) and exposed to 0 (control) and 1 μg/kg b.w. MC-LR (exposure) by intraperitoneal injection for four weeks. The heart blood was collected for serological examination, and the femur for morphological, histopathological, and biomechanical analysis. MC-LR exposure significantly weakened bone microstructures (bone volume, bone volume/total volume, bone trabecular number, connectivity density) and biomechanics (maximum loads and maximum deflection) (P < 0.05). Besides, MC-LR decreased serum procollagen type І car-boxy-terminal propeptide, osteocalcin, bone morphogenetic protein-2, osteoprotegerin, and receptor activator of nuclear factor κB ligand, while elevating osteoclasts number, matrix metalloproteinase-9, β-catenin, Runt-related transcription factor 2, and osterix in bone, and bone alkaline phosphate, C-terminal cross-linked telopeptide of type-I collagen, tartrate-resistant acid phosphatase-5b in serum (P < 0.05). Moreover, MC-LR increased CD4+ T-cells, CD4+/CD8+, M1 and M2 macrophages, and cells apoptosis in the bone marrow, interleukin-6, interleukin-17, and tumor necrosis factor-α in serum, decreased serum interleukin-10 (P < 0.05). Overall, MC-LR can promote bone resorption by activating osteoclasts via osteoimmunology, which may involve macrophages besides lymphocytes. MC-LR may inhibit bone formation by stopping the osteoblasts at an immature stage. Thus, MC-LR weakened bone microstructure and biomechanics in developing period. Its risk on bone development needs further study.

Effect of Conventional and Conservation Agriculture Practices on Dissipation of Metribuzin and Clodinafop-Propargyl, Soil Enzymatic and Microbial Activities in Wheat in a Rice-Wheat System

ABSTRACT Soil enzymes and microbial activity are an indicator of soil quality for assessing the sustainability of agricultural ecosystems. The present study determined the persistence of metribuzin and clodinafop-propargyl and response of soil quality indicators to (1) conservation agriculture (continuous zero tillage and surface residue retention) and conventional agriculture (continuous tillage and removal/incorporation of residues) practices and (2) weed management practices in a wheat field under rice-wheat system. The shift from conventional to conservation agriculture practices increased the dissipation of metribuzin and clodinafop propargyl and significantly enhanced soil dehydrogenase (DHA) and urease activity. The residues of metribuzin and clodinafop in grain and straw samples from all treatment were below maximum residue limits (<0.01 µg g−1). Post-emergence application of clodinafop-propargyl plus metribuzin caused significant inhibition in DHA and urease activity at 7 days after treatment (DAT) compared to unsprayed control. However, from 31 DAT till crop harvest (115 DAT), herbicide treated plots had higher enzymatic activity than unsprayed plots. Intervention of one hoeing following herbicide application had greater stimulation in enzyme activity than sole herbicide. Conservation agriculture practices had higher colony development (CD) and ecophysiological (EP) indices than conventional agriculture practices for heterotrophic bacteria, fungi and actinomycetes. All tillage, residue and weed management practices had non-significant effect on alkaline phosphatase activity and phosphate solubilizers, in soil. Adoption of conservation agriculture practices along with integrated weed management seems to be the best way of sustaining the soil biological parameters and cycling of various important soil nutrients which may potentially alter vital soil processes resulting in increased agricultural sustainability.

Profile of Amoebic vs Pyogenic Liver Abscess and Comparison of Demographical, Clinical, and Laboratory Profiles of these Patients From a Tertiary Care Center in Northern India

Amoebic liver abscess (ALA) and pyogenic liver abscesses (PLA) are the most common causes of liver abscess in developing and developed countries, respectively. Although incidence of liver abscess is low, but mortality is high amongst the patients due to delayed diagnosis. The study was done to find out the prevalence of amoebic and PLA among patients of liver abscess. The clinical, personal, and demographical details were also evaluated to find out the risk factor(s) associated with ALA and PLA, respectively. A retrospective study was conducted to find the prevalence of amoebic and PLA. Clinical, demographic, personal details were evaluated from hospital records. Laboratory parameters such as total leucocyte count, platelets, bilirubin, ESR (Erythrocyte Sedimentation Rate), hemoglobin, glycosylated hemoglobin (HbA1c), alkaline phosphate (ALP), Aspartate aminotransferase (SGOT/AST), Alanine aminotransferase (SGPT/ALT), serum albumin, bilirubin levels, and procalcitonin were recorded. The Ultrasonography (USG) findings regarding the size, location, volume, and number of abscesses were also analyzed. Total of 107 patients of liver abscess were evaluated, and 61.6% of patients were of amoebic etiology, and 25.3% were of pyogenic etiology. Males of 20-60 years of age were predominantly affected with right upper quadrant pain and fever as the most common presentations. ALA patients were found to have solitary abscess in the right lobe involving 6th and 7th segments, with decreased hemoglobin, hyperbilirubinemia, elevated ALP and SGOT, with normal SGPT, and addiction to alcohol. PLA patients had increased HbA1c, increased PCT values, low serum albumin levels, and low platelet-to-white blood cellvalues. The most common bacteria causing PLA was Escherichia coli (n= 8) followed by Enterobacter cloacae (n= 5). Mortality was seen in 6 patients. Liver abscess is found to have relatively high mortality and morbidity. Therefore, early diagnosis is the only method to prevent mortality and morbidity in these patients. Since the presentation is very nonspecific, evaluation of certain risk factors and laboratory parameters can aid in the diagnosis.

Coating 3D-printed bioceramics with histatin promotes adhesion and osteogenesis of stem cells.

Mesenchymal stem cell and 3D printing-based bone tissue engineering present a promising technique to repair large-volume bone defects. Its success is highly dependent on cell attachment, spreading, osteogenic differentiation and in-vivo survival of stem cells on 3D printed scaffolds. In this study, we adopted a human salivary histatin-1 (Hst1) as a cell-targeting strategy to enhance the interactions of human adipose-derived stem cells (hASCs) on 3D printed β-tricalcium phosphate (β-TCP) scaffolds. Fluorescent images showed that Hst1 significantly enhanced the total numbers and surface area of hASCs on both bio-inert glass and 3D printed β-TCP scaffold. In addition, Hst1 was associated with significantly higher proliferation, alkaline phosphate staining on 3D printed β-TCP scaffolds than the control. Subsequently, the small animal imaging showed that the fluorescent densities of the Hst1-treated hASC/3D printed TCP constructs were always significantly higher than those of the control. The specific inhibitors of ERK and p38 but not JNK signaling significantly inhibited the adhesion of hASCs. Hst1 promoted total fluorescent intensities of talin, vinculin and paxillin per cell. In conclusion, Hst1 could significantly promote the adhesion, spreading, osteogenic differentiation and in-vivo survival of hASCs on 3D printed β-TCP scaffolds, bearing a promising application potential in stem cell/3D printing-based bone tissue engineering.

Beyond blood sugar: Unraveling the complexities of liver and kidney health in type 2 diabetes mellitus

ABSTRACT Background: Diabetes mellitus (DM) poses a formidable global health challenge, particularly with the alarming rise of type 2 diabetes. Projections indicate that by 2030, around 440 million individuals will grapple with type 2 diabetes, attributing this surge to urbanization, sedentary lifestyles, and obesity. The intricate relationship between diabetes, liver, and renal functions plays a crucial role in the disease’s progression and complications. Aims and Objectives: This study aims to explore the complex interplay between type 2 diabetes mellitus (T2DM), liver function, and renal health. Specific objectives include assessing abnormal liver function, evaluating kidney profile parameters, and examining the prevalence of anemia in T2DM patients. The study seeks to contribute insights that inform proactive management strategies for diabetes-related complications. Material and Methods: Conducted as a facility-based cross-sectional study from March to June 2022, 120 individuals with T2DM participated. The study focused on patients attending routine follow-ups at the Outpatient Department of general medicine in Santosh Hospital, SMCH, SDTU Ghaziabad. Rigorous assessments and statistical analyses were employed to examine gender distribution, liver and kidney profile parameters, and other relevant factors. Results: Among the notable findings, Table 1 reveals a significant gender distribution, with 51.8% males in the diabetes group. Liver profile parameters, including alkaline phosphates and albumin, exhibited statistically significant differences between diabetes and control groups. Kidney profile parameters also showed significant variations, emphasizing the intricate relationship between diabetes and renal complications. The study further explored differences between male and female patients in the control group, revealing significant variations in hemoglobin levels. Conclusion: This study sheds light on the prevalence of abnormal liver function in T2DM individuals, emphasizing the significance of early detection and tailored interventions. Kidney disorders and the often-overlooked complication of anemia further contribute to the complexity of health challenges faced by those with diabetes. The findings underscore the need for vigilant monitoring and comprehensive management strategies to enhance patient care in the face of this multifaceted health challenge.

The Relationship between Alkaline phosphates level, liver diseases and gallstone

The Relationship between Alkaline phosphates level, liver diseases and gallstone

Phytochemical screening and effects of aqueous extracts of Cymbopogon citratus(DC) Staptand Origanum vulgare (LINN) on the biochemical and haematological profileof Wistar strain albino rats

Medicinal plants have played a major role in the field of medicine as alternative therapy to orthodox drugs. This present study aimed to evaluate the acute toxicity of Cymbopogon citratus and Origanum vulgare aqueous extracts on albino rats.The qualitative phytochemical analyses of the was done using standard procedures. The LD50 was determined using modified Lorke’s method, while the biochemical and haematological analysis were done by automated methods. Results from phytochemical analysis reveals the presence of Alkaloids, Flavanoids, Phenols and tannins, Steroids and sterols, Carbohydrates, Saponins, Protein and amino acid and Anthraquininein the two extracts. Furthermore, the electrolytes(urea and creatinine) were within the normal range in rats of the control and the orally administered aqueous extracts of Cymbopogon citratus and Origanum vulgare (100 mg/kg, 200 mg/kg and 400 mg/kg). Total protein, alkaline phosphate, total bilirubin, conjugate bilirubin, alanine aminotransferase, albumin and Aspartate aminotransferase were also within the normal range in both control and groups treated with 100mg/kg and 200mg/kg and 400mg/kg. White blood celland platelet followed same trend of falling within the normal range while Packed cell volume, Haemoglobin values were higher than the normal range across the control and test groups. Aqueous crude extracts ofC. Citratusand O. vulgarecontain primary and secondary metabolites thus with potential medicinal properties as anti-inflammatory, anti- malaria, anti- viral, anti- bacteria and anti-fungal agents. Orally administered aqueous crude extracts C. citratus and O. vulgare (100mg/kg, 200mg/kg and 400mg/kg)have no toxicological/pathological effect on wistar strain albino rats and as such, indigenous plants safe for consumption.

Repurpose of Mefloquine-Cotrimoxazole Combination as Anti-Plasmodial Agents in Mice Infected with Pasmodium Berghei

The keystone for the treatment of malaria is artemisininbased combination therapy (ACT). The vulnerability of parasites to ACT has, regrettably, declined. Determining new medications or drug combinations that would mitigate parasite resistance is therefore pertinent. Thisstudy assessed the antimalarial property of mefloquinecotrimoxazole in parasitized mice. Thirty adult Swiss albino mice of (18-30g) were grouped into five of 6 mice each. All the mice were inoculated with Plasmodium berghei and orally treated. Group 1 was not treated while groups 2,3, 4 and 5 were treated with chloroquine (10mg/ kg), mefloquine (10mg/kg), cotrimoxazole (10mg/kg) and a combination of mefloquine/cotrimoxazole (10mg/ kg) respectively for five (5) days. The mean survival timewas determined and blood samples were collected and evaluated for percentage parasitemia, hematological and biochemical markers. The results showed that mefloquine/cotrimoxazole combination significantly (p&lt;0.05) reduced percentage parasitemia when compared with single doses of cotrimoxazole and mefloquine. Curatively, cotrimoxazole, mefloquine and mefloquine /cotrimoxazole combination produced 84.90%, 98.95% and 96.96% respectively, whencontrasted with the 90.84% delivered by chloroquine. Suppressively, cotrimoxazole, mefloquine, mefloquine /cotrimoxazole combination, delivered 84.62%, 90.20% and 97.55% respectively. The prophylactic test delivered cotrimoxazole (61.04%), mefloquine (75.23%), mefloquine /cotrimoxazole combination (89.94%) parasitamia inhibition for day 4. When compared to the individual doses of cotrimoxazole and mefloquine,the mefloquine/cotrimoxazole combo significantly (p&lt;0.05) prolonged the mean survival time in the curative,prophylactic, and suppressive tests. The combination also produced significant (p&lt;0.05) reduction in anemia characterized by increased packed cell volume, hemoglobin,red blood cells and decrease in white blood cells, neutrophils lymphocytes and monocytes when compared with single doses of cotrimoxazole and mefloquine respectively. Theresult showed that the levels of aspertate transferase,alanine alanine transferase, alkaline phosphate total protein, total bilirubin, urea, creatinine and uric acid that were slightly altered was curtailed by mefloquine/cotrimoxazole. The study showed that cotrimoxazole can be utilized as an accomplice drug with mefloquine for the management of malaria.

BROWN TUMOR OF PRIMARY HYPERPARATHYROIDISM ASSOCIATED WITH ECTOPIC PARATHYROID TISSUE

This study presents an unusual case of primary hyperparathyroidism with a brown tumor caused by ectopic parathyroid tissue within the mediastinum. A 48-year-old male was admitted, complaining of a painful and hemorrhagic swelling in the anterior mandible, of unknown duration. The patient's medical history was uneventful. Spiral computed tomography revealed well-defined multilocular radiolucencies located within the anterior and body of the mandible, bilateral mastoid processes, and temporal bone, causing significant cortical expansion and thinning. An incisional biopsy of the anterior mandible showed a central giant cell lesion, and laboratory exams detected high values of parathormone, alkaline phosphate, and calcium. Further sestamibi-SPECT parathyroid scintigraphy was carried out and hyperfunctioning ectopic parathyroid tissue within the mediastinum region was detected. The patient was referred to an endocrinologist and is being prepared for thoracic surgery for analysis of the ectopic parathyroid tissue. This study presents an unusual case of primary hyperparathyroidism with a brown tumor caused by ectopic parathyroid tissue within the mediastinum. A 48-year-old male was admitted, complaining of a painful and hemorrhagic swelling in the anterior mandible, of unknown duration. The patient's medical history was uneventful. Spiral computed tomography revealed well-defined multilocular radiolucencies located within the anterior and body of the mandible, bilateral mastoid processes, and temporal bone, causing significant cortical expansion and thinning. An incisional biopsy of the anterior mandible showed a central giant cell lesion, and laboratory exams detected high values of parathormone, alkaline phosphate, and calcium. Further sestamibi-SPECT parathyroid scintigraphy was carried out and hyperfunctioning ectopic parathyroid tissue within the mediastinum region was detected. The patient was referred to an endocrinologist and is being prepared for thoracic surgery for analysis of the ectopic parathyroid tissue.

#3986 THE ROLE AND MECHANISM OF EZH2 IN VASCULAR CALCIFICATION ASSOCIATED WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Vascular calcification (VC) is a prevalent complication in chronic kidney disease and contributes to increased cardiovascular morbidity and mortality. EZH2 (Enhancer of zeste 2 homolog-2) is reported as a key epigenetic regulator involved in various kidney diseases such as acute kidney injury, renal fibrosis, diabetic nephropathy, and lupus nephritis. In this study, we aimed to investigated the role of EZH2 in chronic kidney disease associated vascular calcification. Method 1. Patients and Radial Artery Analysis Radial arteries with or without calcification from patients with end-stage renal disease that underwent arterial venous fistular surgery were collected for Von Kossa staining and immunohistochemical (IHC) staining. 2. Animal model of Chronic renal failure-Vascular Calcification (CRF-VC) (in vivo) An adenine and phosphate (1.2%) diet-induced CRF mouse model was designed following an 8-week program. The thoracoabdominal arteries of mice and rats were dissected to assay Ca deposition and histological analysis. Plasma levels of Alkaline phosphate (ALP), and phosphate (Pi) were measured. The transcription level of EZH2 and Runt-related transcription factor 2 (Runx2) were measured by real-time PCR and IHC staining. 3. Aortic ring calcification (ex vivo) Thoracic aortas were dissected from SD rat. To induce calcification, Pi (NaH2PO4/Na2HPO4 [pH = 7.4]) was added to HG-DMEM at a final concentration of 2.6 mmol/l. After the indicated incubation periods (3, 5, 7 days), samples were taken for Calcium deposition assay, Western blotting and histological analysis. 4. Cell culture and treatment (in vitro) Calcification of rat smooth muscle embryonic thoracic aorta cell line A7r5 (VSMC) was induced by incubation in calcifying media. 3-deazaneplanocin A (3-DZNeP), a carbocyclic analog of adenosine was added right after Pi to block EZH2 activation. After the indicated incubation periods, samples were collected for Calcium deposition assay and Western blotting analysis. Results 1. In vivo, EZH2 protein level was increased in calcified radial arteries from patients with end-stage renal disease that underwent arterial venous fistular operation. In CRF-VC mice model, the aortic calcium deposition markedly aggravated in the group induced by adenine diet. Severe vascular calcification was also induced as shown by increased intensity of von Kossa. Moreover, IHC and q-PCR results showed that the protein and transcriptional levels of EZH2 expression were upregulated in calcified aortas of CRF mice, in paralleled with the increased expression Runx2 in protein and transcriptional levels. 2. Ex vivo, histological analysis revealed significant medial vascular calcification in the aortic ring culture with this calcifying medium for 7 days. Similarly, WB results showed that the expression of EZH2 and its downstream, methylation of Histone H3 at lysine 27 (H3K27me3), were significantly enhanced after high Pi medium stimulation while the osteogenic markers Runx2, Osteopontin (OPN) and Msh homeobox 2 (Msx2) protein levels were upregulated and the expression of VSMC differentiation markers α-Smooth muscle actin (α-SMA), Calponin (CNN) and Smooth muscle protein 22 (SM22) were downregulated. 3. In vitro, the osteogenic markers Runx2, OPN and Msx2 were significantly upregulated in high Pi treated VSMCs compared to control VSMCs. Moreover, the epigenetic markers EZH2 and H3K27me3a were markedly repressed in calcifying VSMCs by time. 4. 3-DZNep treatment reduced the calcium deposition in a concentration dependent manner. Western blotting showed that 3-DZNep treatment blocked the increased expression of osteogenic markers Runx2, Bone morphogenetic protein 2 (BMP2) as well as epigenetic markers EZH2 and H3K27me3a by high Pi treatment, indicating that inhibition of EZH2 attenuates VSMCs Calcification. Conclusion Our study revealed that EZH2 is highly expressed in calcified vascular tissues of CRF patients and CRF mice, rat aorta culture and VSMCs calcification models, and EZH2 inhibitor 3-DZNep attenuated calcification of VSMCs. EZH2 could be a promising target for treatment of vascular calcification in CRF patients.

#5571 THERAPY WITH BUROSUMAB IN ADULT PATIENTS WITH X-LINKED HYPOPHOSPHATEMIA: A YEAR OF FOLLOW-UP

Abstract Background and Aims X-linked hypophosphatemic rickets (XLH) is a genetic disorder secondary to the mutation of the PHEX gene that results in increased circulating levels of FGF23. Increased FGF23 causes hypophosphatemia secondary to renal phosphate loss. Clinically, the disease is characterized by reduced growth, bone alterations, weakness, chronic pain and reduced mobility. From a biochemical point of view, patients have hypophosphatemia, increased values of alkaline phosphatase, increased fraction excretion of phosphate (FEP). Recently, therapy with Burosumab, a monoclonal antibody against FGF23, has been introduced. Burosumab by reducing the receptor availability of circulating FGF23 reduces its activity. This leads to a normalization of serum phosphate and in paediatric patients an improvement of the clinical phenotype. In adult patients, the effectiveness of therapy in improving the clinical outcome and quality of life is being investigated. The purpose of the study was to evaluate the efficacy in improving the biochemical, bone and clinical picture of adult patients with XLH in therapy with Burosumab for one year. Method We enrolled patients with XLH naive for Burosumab therapy. In all we evaluated the biochemical aspects (phospahatemia, alkaline phosphatase, FEP), bone Radiographic Global Impression of Change score and clinical improvements (six-minute walk test, UP and go timed test, WOMAC Index) pre therapy and after a year of therapy. Burosumab was administered monthly at a dose of 1 mg/Kg. Results We enrolled 5 patients (45 ± 10 year old, weight 60 ± 10 Kg, Burosumab dose 60 ±10 mg) with genetic diagnosis of XLH. The comparison between pre therapy and post-one-year therapy showed in all patients: increase in average phosphatemia (pre 1.9± 0.5 mg/dl vs post 3.4 ±0.6 mg/dl p = 0.003), reduction in FEP (pre 50 ±15% vs 20 ±10% p = 0.004), reduction of UP and go timed test (pre 20± 5 sec vs post 11 ±5 sec p = 0.005) increase of the distance in the six minutes’ walk test (pre 150 ± 30 meters vs post 250 ± 50 meters p = 0.01), improvement of the WOMAC test (pre 15± 3 vs post 5± 2; p = 0.008) and reduction of the Radiographic Global Impression of Change score (pre -2 ±0.5 and post 2± 0.4; p = 0.001). The serum value of alkaline phosphate was high and it did not change with the Burosumab therapy (pre 200±50 UI/L vs post 220±60 UI/L; p: n.s. n.v. 33–98 UI/L). No patients had significant complications during the first year of treatment. Conclusion The therapy with Burosumab was well tolerated by patients. It resulted in a marked improvement in the biochemical picture associated with a better quality of life identified by increased strength (improved walk test and UP and go timed test) reduction of pain (best WOMAC test) and bone damage score. In conclusion, Burosumab may be a good and safe therapy option for adults’ patients with XLH.

#6287 EFFECT OF REMOTE ISCHEMIC PRECONDITIONING ON NUTRITIONAL STATUS, COGNITIVE FUNCTION, AND BONE IN HEMODIALYSIS PATIENTS: A RANDOMIZED CONTROLLED TRIAL

Abstract Background and Aims Remote ischemic preconditioning (RIPC) is a process in which a brief period of ischemia is induced in one part of the body to protect another part from damage due to subsequent periods of more severe ischemia. Hemodialysis sessions are considered an ischemic process because it involves reducing blood flow to certain parts of the body, which can lead to tissue damage .Malnutrition, deterioration of cognitive function, bone disorders, cardiovascular disease, and hemodynamic instability can result from ischemia induced by hemodialysis sessions. These adverse effects increase mortality in HD patients. RIPC has been studied as a potential therapeutic strategy to reduce the risk of cardiovascular events in hemodialysis patients; however, the effect of RIPC on cognitive function, nutritional status, and bone disorder among hemodialysis patients has not been enough studied. Aim: to assess the effect of remote ischemic preconditioning on nutritional status, bone disorders, and cognitive function in hemodialysis patients at the urology and nephrology center, Mansoura University. Method Fifty patients who received regular hemodialysis for more than one year in our dialysis unit were included. The patients were randomized (single-blind) into two groups a control group (20 patients) and an intervention group (30 patients). Before each HD session, sphygmomanometer cuffs was placed around the non-vascular access arm. Three cycles of ischemia for five minutes were performed followed by reperfusion for five minutes. Ischemia was induced by inflating the sphygmomanometer cuffs to 200 mmHg. This maneuver was done before each HD session for 12 weeks. The Montreal Cognitive Assessment (MOCA) was used to assess cognitive function. The nutritional state was assessed by anthropometric measurement (body weight, BMI), laboratory (serum albumin and serum cholesterol), and Subjective Global Assessment Form (SGA). Serum calcium (s.Ca) and serum phosphorus (s.po), serum alkaline phosphate (s. ALP) and intact parathyroid hormone (iPTH) were used as indices for bone profile. Results The intervention group include 30 patient with mean age (36+/-10), 19 male (63.3%) and 11 females (36.7%). The control group include 20 patient with mean age (46+/-9), 12 male (60%) and eight female (40%). None of these patients’ demographic data (age, sex, original kidney disease, and duration of dialysis) were significantly different between the study groups (P&amp;gt;0.05). MOCA test score at baseline was (24.5 +/-2.6) at intervention group and (24.4+/-3.2) at control group, and after 12 weeks intervention was (24.8 +/-2.2) at intervention group and (24.4+/-2.8) at control group. there were no statistical significance regarding cognitive function between the two group over time (p = 0.4). NO significant Statistical changes in anthropometric measurements (Body weight (p = 0.3) and BMI (P = 0.6) were found between the two groups. Additionally, no significant changes (serum albumin and cholesterol) were detected. SGA score at baseline was at intervention group (1.2+/-0.4) and control group (1.1 +/- 0.3), and after 12 week was at the intervention group (1.4 +/-0.5) and control group (1.6 +/-0.5). SGA showed no statistical significance between the two groups over time (p = 0.2). No significant statistical changes regarding bone profile (s.ca (p = 0.5), s.PO (p = 0.2), s.ALP (p = 0.7) and iPTH (p = 0.5)). Conclusion Although some studies showed a beneficial effect of RIBC on reduction of cardiovascular risk, our study found no significant effect on cognitive function, nutritional status, and bone disorders among hemodialysis patients.

Evaluation of the Level of Histamine 1 and 2 Receptors with Some Biochemical Variables in Patients with Hepatitis C Virus Infection

The current study was carried out at Ibn - Sina Hospital in Nineveh Governorate, where the relationship between histamine receptors1&amp;2, liver enzyme functions, Albumin, and Alkaline phosphate was studied in patients with hepatitis C virus type. Samples were taken from patients diagnosed with hepatitis C, 60 of whom were compared with 30 controls. Take 5ml of blood, separate it with a centrifuge, and test the serum. The sample size was equal for Men and Women, and the age range was 18 to 78 years. ALT (GPT), Albumin, Alkaline phosphates, and histamine-2 receptor levels were statistically significant, while AST (GOT) and histamine-1 receptor levels were not statistically significant.

Host defense peptides combined with MTA extract increase the repair in dental pulp cells: in vitro and ex vivo study

Host Defense Peptides (HDPs) have, in previous studies, been demonstrating antimicrobial, anti-inflammatory, and immunomodulatory capacity, important factors in the repair process. Knowing these characteristics, this article aims to evaluate the potential of HDPs IDR1018 and DJK-6 associated with MTA extract in the repair process of human pulp cells. Antibacterial activity of HDPs, MTA and HDPs combined with MTA in Streptococcus mutans planktonic bacteria and antibiofilm activity was evaluated. Cell toxicity was assayed with MTT and cell morphology was observed by scanning electron microscopy (SEM). Proliferation and migration of pulp cells were evaluated by trypan blue and wound healing assay. Inflammatory and mineralization related genes were evaluated by qPCR (IL-6, TNFRSF, DSPP, TGF-β). Alkaline phosphatase, phosphate quantification and alizarin red staining were also verified. The assays were performed in technical and biological triplicate (n = 9). Results were submitted for the calculation of the mean and standard deviation. Then, normality verification by Kolmogorov Smirnov test, analyzing one-way ANOVA. Analyses were considered at a 95% significance level, with a p-value < 0.05. Our study demonstrated that HDPs combined with MTA were able to reduce biofilms performed in 24 h and biofilm performed over 7 days S. mutans biofilm (p < 0.05). IDR1018 and MTA, as well as their combination, down-regulated IL-6 expression (p < 0.05). Tested materials were not cytotoxic to pulp cells. IDR1018 induced high cell proliferation and combined with MTA induced high cellular migration rates in 48 h (p < 0.05). Furthermore, the combination of IDR1018 and MTA also induced high expression levels of DSPP, ALP activity, and the production of calcification nodules. So, IDR-1018 and its combination with MTA could assist in pulp-dentine complex repair process in vitro.