Decrease In Alkaline Phosphatase Levels Research Articles

6976 Early-Onset Paget's Disease- A Unique Presentation In A Young Female With Elevated Alkaline Phosphatase And Low Back Pain

Abstract Disclosure: F. El Sayed: None. Background Paget disease of bone is an age-related disorder characterized by abnormal growth in certain bones, leading to changes in size and shape. Commonly affecting the skull, spine, pelvis, and long bones, it is more prevalent in men, those over 55, with a family history, and of European ancestry. The prevalence of Paget's disease of bone is approximately 2-3% in individuals over 55 in the United States and Europe, with higher rates in those of European descent. Symptoms, such as pain and deformities, may arise from the condition itself or complications like arthritis. While Paget disease can cause visible abnormalities and fractures in affected bones, most individuals remain asymptomatic. Diagnosis often involves blood tests measuring alkaline phosphatase levels, bone scans, and x-rays. Case Presentation We present the case of a 34-year-old woman who sought evaluation due to persistently elevated alkaline phosphatase (ALP) levels in the thousands. The abnormality was discovered during routine blood work conducted during her pregnancy in 2020, and subsequent investigation revealed a chronic elevation for over three years. The patient reported chronic lower back pain but denied other neurological symptoms. Quantification of ALP Bone showed elevated levels at 629, with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as well as within-range calcium and gamma-glutamyl transferase (GGT). A whole-body bone scan revealed marked radio tracer uptake in the calvarium, raising concerns for Paget's disease. The patient received a one-time infusion of Zoledronic acid (5 mg), leading to a significant decrease in ALP levels to 182 after three months. Subsequent examination by an Ear, Nose, and Throat (ENT) specialist unveiled bilateral extra bone deposition and mild hearing loss in the right ear, adding a unique dimension to the patient's presentation. This case highlights the importance of a comprehensive approach to diagnose and manage Paget's disease, even in younger individuals with atypical symptoms. Discussion and conclusion Paget's disease presenting in young adults with back pain can be a diagnostic challenge due to its atypical occurrence in this age group. Although back pain is a common symptom, the underlying cause might not immediately be linked to Paget's disease, which typically affects older individuals. However, when encountering persistent back pain in young adults, especially when accompanied by elevated alkaline phosphatase levels, clinicians should consider Paget's disease as a potential differential diagnosis. Further investigation, including imaging studies and bone scans, becomes crucial to confirm the presence of Paget's disease and initiate appropriate management strategies to mitigate its impact on the patient's health and quality of life. Presentation: 6/2/2024

Association between 99mTc-PSMA SPECT/CT imaging and prostate-specific antigen (PSA) and alkaline phosphatase (ALP) levels post-endocrine therapy in patients with prostate cancer and bone metastases

AimTo investigate the association between positive lesions detected by 99mTc-PSMA SPECT/CT and blood levels of prostate-specific antigen (PSA) and alkaline phosphatase (ALP) in patients with prostate cancer (PCa) and bone metastasis undergoing endocrine therapy. MethodsA retrospective analysis was performed on 43 patients diagnosed with PCa bone metastasis who underwent endocrine therapy. PSA, ALP, whole body bone imaging and 99mTc-PSMA SPECT/CT imaging were collected from all patients (Among them, 17 cases were re-examined 99mTc-PSMA SPECT/CT imaging). According to the results of the first 99mTc-PSMA SPECT/CT imaging for detecting bone metastasis, all cases were divided into two groups: positive group and negative group. The relationship between 99mTc-PSMA imaging and PSA and ALP was analyzed by ROC curve. Fisher exact probability method was used to examine the changes in imaging radioactivity uptake, PSA, and ALP levels in 17 patients after treatment, and P < 0.05 was statistically significant. ResultsAll 43 patients had different degrees of radioactive concentrations on whole-body bone imaging. The first 99mTc-PSMA SPECT/CT imaging showed positive bone metastases in 31 cases and negative bone metastases in 12 cases. ROC curve analysis of PSA and ALP, AUC were 0.778 and 0.770, respectively. When PSA > 1.13 ng/mL, 99mTc-PSMA SPECT/CT imaging diagnostic sensitivity was 93.55%, and specificity was 66.67%. When ALP was >86U/L, the diagnostic sensitivity of 99mTc-PSMA SPECT/CT imaging was 64.52%, and the specificity was 83.33%. In 17 cases, the PSA level decreased in 7 and increased in 10. There were 10 cases of increased ALP and 7 cases of decreased ALP levels. In the second 99mTc-PSMA imaging lesion, there were 9 cases with decreased or no uptake, and 8 cases with increased uptake or number of lesions. The changes in 99mTc-PSMA uptake by Fisher’s exact probability method were statistically significant (P < 0.05, P = 0.006, and P = 0.006, respectively), and ALP level was not statistically significant (P = 0.563). Conclusion99mTc-PSMA SPECT/CT imaging can detect PCa bone metastases, which are related to PSA levels. When PSA > 1.13 ng/mL, the sensitivity of diagnosis and detection of positive bone metastases is higher, and when ALP is >86U/L, 99mTc-PSMA imaging has higher specificity.

Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence

ObjectiveTo investigate the association between liver enzymes and ovarian cancer (OC), and to validate their potential as biomarkers and their mechanisms in OC. MethodsGenome-wide association studies for OC and levels of enzymes such as Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase, and gamma-glutamyltransferase were analyzed. Univariate and multivariate Mendelian randomization (MR), complemented by the Steiger test, identified enzymes with a potential causal relationship to OC. Single-cell transcriptomics from the GSE130000 dataset pinpointed pivotal cellular clusters, enabling further examination of enzyme-encoding gene expression. Transcription factors (TFs) governing these genes were predicted to construct TF-mRNA networks. Additionally, liver enzyme levels were retrospectively analyzed in healthy individuals and OC patients, alongside the evaluation of correlations with cancer antigen 125 (CA125) and Human Epididymis Protein 4 (HE4).ResultsA total of 283 single nucleotide polymorphisms (SNPs) and 209 SNPs related to ALP and AST, respectively. Using the inverse-variance weighted method, univariate MR (UVMR) analysis revealed that ALP (P = 0.050, OR = 0.938) and AST (P = 0.017, OR = 0.906) were inversely associated with OC risk, suggesting their roles as protective factors. Multivariate MR (MVMR) confirmed the causal effect of ALP (P = 0.005, OR = 0.938) on OC without reverse causality. Key cellular clusters including T cells, ovarian cells, endothelial cells, macrophages, cancer-associated fibroblasts (CAFs), and epithelial cells were identified, with epithelial cells showing high expression of genes encoding AST and ALP. Notably, TFs such as TCE4 were implicated in the regulation of GOT2 and ALPL genes. OC patient samples exhibited decreased ALP levels in both blood and tumor tissues, with a negative correlation between ALP and CA125 levels observed.ConclusionThis study has established a causal link between AST and ALP with OC, identifying them as protective factors. The increased expression of the genes encoding these enzymes in epithelial cells provides a theoretical basis for developing novel disease markers and targeted therapies for OC.

THU457 Variable Presentations Of Hypophosphatasia In Two Patients In The Outpatient Setting

Abstract Disclosure: A. Elmaaz: None. S. Batool: None. P. Dandona: None. Introduction: Hypophosphatasia is a rare disorder characterized by defective mineralization of bone and teeth which is caused by an autosomal inherited mutation in the tissue nonspecific alkaline phosphatase (ALP) encoding genes. Here we present two cases of multiple dental and bony defects secondary to low ALP enzyme activity due to hypophosphatasia. Case 1: A 27-year-old female with history of mitochondrial disease, gastroparesis, malabsorption syndrome, and autonomic dysfunction was referred to Endocrinology clinic because of persistently low serum ALP levels associated with recurrent muscle, joint, and bone pain since the age of 13. She had history of multiple tooth extractions because of dental developmental abnormalities and fractures. She also reported history of fractures of three of her fingers in both hands during her childhood and teenage years. The patient was adopted and was unaware of any biological family history. Physical examination was remarkable for short-statured female, 4'8". Notably, the middle phalanges in little fingers bilaterally were shorter than the other fingers. Workup showed vitamin D level of 21 (30-80) ng/ml, despite being on 50,000 IU twice a week for 6 months with normal PTH and ionized calcium levels. The repeated serum level of ALP was 24 (31-125) U/L with bone and liver isoenzymes levels of 42% and 58 % respectively. Vitamin B6 level was 13.2 (2.1-21.7) ng/ml. Bone mineral density was unremarkable. Case 2: A 53-year-old female with history of congenital left hip dysplasia, hypertension, and dyslipidemia was seen by Endocrinology service for evaluation of decreased ALP levels. She denied any history of falls or fractures. However, she reported chronic bone pain, especially in bilateral hip joints with history of multiple surgeries in her left hip joint. She had required teeth braces and multiple dental surgeries during her childhood due to dental maldevelopment. Her height was 4'8". Laboratory workup was remarkable for low serum ALP level of 30 U/L with bone isoenzyme of 24 %. Vitamin B6 level was 206.7 (2.1-21.7) ng/ml. She had elevated serum phosphorus levels with normal calcium, PTH, and vitamin D levels. Pyridoxal-5- Phosphate level was high. Bone mineral density revealed osteopenia. Conclusion: Hypophosphatasia is a rare disease, hence it could be easily missed due to high variability in clinical presentations and severity of symptoms. Low serum levels of ALP with history of bone pain, recurrent fractures, premature loss of deciduous teeth, or loss of adult dentition should raise the suspicion of hypophosphatasia. Resistance to vitamin D supplementation is another clue to the diagnosis. A multidisciplinary approach is required for appropriate management. Presentation: Thursday, June 15, 2023

Evaluation of Omega-3 Effect as Adjuvant Therapy to Methotrexate on Alkaline Phosphatase Level in Iraqi Patients with Active Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common inflammatory disease associated with many extraarticularfeatures. The aim: of the current study is to assess the influence of omega-3 fatty acids(EPA, DHA) on serum alkaline phosphatase in patients with active RA. A single blinded placebocontrolled clinical trial with 12 weeks follow up period at which 50 patients with active RAusing methotrexate were randomized into 2 groups to receive either omega-3 (1000 mg) capsulethree times daily or capsules prefilled with glucose as placebo and were evaluated at zero time(baseline) and after 12 weeks for alkaline phosphatase level in serum. In addition to twenty fivehealthy subjects as control group. The age of RA patients in omega-3 group ranged from 25-80years (50.36±2.46), whereas the age of RA patients in placebo group ranged from 35-68 years(50.08±1.84 ), while the age of apparently healthy subjects in control group where ranged from40-60 years (94.20±1.12). The RA disease activity was measured using disease activity score of28 joints(DAS28-ESR) and clinical disease activity index (CDAI). After 12 weeks of startingadjuvant treatment with either omega-3 or placebo, the results showed that there were nosignificant difference between the effect of omega- 3 and placebo on alkaline phosphatase level.In Conclusion, omega-3 significantly decreased alkaline phosphatase level in patient with activerheumatoid arthritis

Thyrotropin inhibits osteogenic differentiation of human periodontal ligament stem cells.

Periodontal ligament stem cells (PDLSCs) are derived from the periodontal ligament and have the characteristics of pluripotent differentiation, including osteogenesis, and are one of the important seed cells in oral tissue engineering. Thyrotropin (TSH) has been shown to regulate bone metabolism independently of thyroid hormone, including the fate of osteoblasts and osteoclasts, but whether it affects osteogenic differentiation of PDLSCs is unknown. PDLSCs were isolated and cultured from human periodontal ligament and grown in osteogenic medium (containing sodium β-glycerophosphate, ascorbic acid, and dexamethasone). Recombinant human TSH was added to the culture medium. Osteogenic differentiation of PDLSCs was assessed after 14 days by staining with alkaline phosphatase and alizarin red and by detection of osteogenic differentiation genes. Differentially expressed genes (DEGs) in PDLSCs under TSH were detected by high-throughput sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the biological functions and signaling pathways involved in DEGs. We found that osteogenic differentiation of PDLSCs was significantly inhibited in the presence of TSH: including decreased calcium nodule formation, decreased alkaline phosphatase levels, and decreased collagen synthesis. Using high-throughput sequencing, we found changes in the expression of some osteogenesis-related genes, which may be the reason that TSH inhibits osteogenic differentiation of PDLSCs. Unless TSH is ≥10mU/L, patients with subclinical hypothyroidism usually do not undergo thyroxine supplementation therapy. However, in this work, we found that elevated TSH inhibited the osteogenic differentiation of PDLSCs. Therefore, correction of TSH levels in patients with subclinical hypothyroidism may be beneficial to improve orthodontic, implant, and periodontitis outcomes in these patients.

Transient decrease in alkaline phosphatase level in a boy with neck swelling: a case report of Kikuchi-Fujimoto disease

Transient decrease in alkaline phosphatase level in a boy with neck swelling: a case report of Kikuchi-Fujimoto disease

THE EFFECT OF GIVING ALOE VERA GEL ON RATS WITH BACTERIA-INDUCED PERIODONTITIS

Background: Aloe vera (AV) contains a variety of characteristic antibiotic and anti-inflammatory components that have potential advantages for periodontal disease therapy. Diagnostic and prognostic markers of periodontal disease through the activity of alkaline phosphatase (ALP) in gingival crevicular fluid. This study was conducted to evaluate the effect of giving AV gel on alkaline phosphatase levels in rats with bacteria-induced periodontitis Method: Thirty-six male Sprague dawley were healthy and active, weighing 170-200 grams, aged 2 months were distinguished into two groups: the control group of periodontitis given therapy Gel Metronidazole plus 25% and AV gel 99.03% as a treatment group. Aloe vera gel is administered topically in gingival sulcus at a dose of 300 mg/kg of rat weight. Samples were taken from gingival sulcus liquid on days 1, 2 and 3 using periopaper paper. Alkaline phosphatase levels are measured using a UV/Vis Spectrophotometer with a wavelength of 405 nm. Variant analysis is used to compare ALP levels in different groups Result: There was significant difference in alkaline phosphatase levels between the control group and the treatment group (p&gt;0.05). In Sprague dawley rats with periodontitis, there was a significant decrease in ALP levels on days 1, 2 and 3 given Metronidazole gel plus 25% therapy and AV gel 99.03%. But the treatment group showed lower ALP levels than the control group Conclusion: This study revealed that the use of AV gel locally has an effect and can be as an adjunct therapy for periodontitis

Oral versus intramuscular cholecalciferol replacement in hemodialysis patients with vitamin D deficiency

Introduction: Low 25-hydroxyvitamin D (25(OH)D) level in hemodialysis (HD) patients is associated with high bone turnover, secondary hyperparathyroidism, and decreased bone mineral density (BMD). Objective: To investigate the efficacy of equivalent doses of pulse oral cholecalciferol versus intramuscular (IM) cholecalciferol in correcting serum 25(OH)D levels in HD patients with vitamin D deficiency. Patients and Methods: In a prospective randomized open-label clinical trial, 80 HD patients with 25(OH)D level &lt;20 ng/mL and serum intact parathyroid hormone (iPTH) level &gt;100 pg/mL were enrolled in the study. Patients were divided into two groups. Group I: 40 HD patients received oral cholecalciferol 25 000 IU weekly for 12 weeks. Group II: 40 HD patients received a single dose of IM cholecalciferol 300 000 IU. Patients were maintained on their regular medications as alfacalcidol or phosphate binders. Serum calcium, phosphorus, 25(OH)D, alkaline phosphatase and iPTH were monitored at 0, 6th, and 12th week of intervention. Results: Significant increase in serum 25(OH)D level in group II patients who received IM (intramuscular) cholecalciferol, with delta mean a change of vitamin D level was 2.92 ±7.29 ng/mL over three months in comparison to the insignificant change in oral cholecalciferol group. Additionally there was a significant increase in the mean of serum calcium in comparison to oral cholecalciferol group, while we found a statistically significant decrease in alkaline phosphatase level in both groups too (P&lt;0.05). The mean of iPTH levels was reduced significantly with IM cholecalciferol dose (1064.00 ± 787.60 to 609.9 ± 551.41 pg/mL; P&lt;0.05). Conclusion: Intramuscular cholecalciferol dose is more effective at increasing 25(OH) D levels in dialysis patients than oral supplementation, achieves more increase in serum calcium and reduce iPTH levels. However, the longer duration of treatment is required to achieve recommended levels of vitamin D and suppress high iPTH levels.

Diagnosis of Hypophosphatasia in Adults Presenting With Metatarsal Stress Fracture: Proof-of-Concept for a Case-Finding Strategy.

ABSTRACTHypophosphatasia (HPP) is caused by loss‐of‐function mutations in ALPL resulting in decreased alkaline phosphatase (ALP) activity. Metatarsal stress fracture (MSF) is a common clinical feature of hypophosphatasia in adults. In this study, the primary objectives were to determine whether new cases of ALPL variants could be identified in patients with MSF and who also had serum ALP concentration below the reference range and to phenotype their clinical course. Electronic health records were queried for adult patients with MSF using International Classification of Disease codes (ICD‐9, ICD‐10CM) and ALP measurements. Patients with ALP levels below the normal limit were invited to receive mutational analysis of ALPL and to complete the following surveys: the Short Form 36 version 2 (SF36v2), the Brief Pain Inventory‐Short Form (BPI), and the Health Assessment Questionnaire Disability Index (HAQ‐DI). Cases with and controls without ALPL pathogenic variants were compared by survey scores and clinical variables relevant to fracture. In 1611 patients with MSF presenting to a podiatry clinic (10/1/2011–10/1/2017), 937 had ALP measurement, of whom 13 (1.4%) had ALP levels below the lower normal limit. In eight patients consenting to participate, two had heterozygous pathogenic ALPL variants. ALPL variants were found in 2 of 1611 patients (0.12%) with MSF, 2 patients of 937 (0.21%) in those with MSF and any ALP measurement, and 2 of 13 patients (15%) in MSF and decreased ALP level. Cases versus controls rated lower scores on eight of eight SF36v2 scales (range, 0–100); higher scores for worst pain (8.0 vs. 0.8) and average pain (6.0 vs. 0.7) on the BPI (range, 0–10); and higher standard disability score (1.4 vs. 0) on the HAQ‐DI (range, 0–3). These data provide proof‐of‐concept for HPP case identification in patients presenting to a podiatry clinic with MSF, suggesting a search for historically low ALP levels may be a useful step for consideration of HPP diagnosis, and supports a prospective study to determine an optimal case‐finding strategy. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

THERAPEUTIC PLASMAPHERESIS IN A COMPLEX TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS

The aim: To determine the pathogenetic expediency, efficiency and the place of therapeutic plasmapheresis in a complex treatment of patients with chronic hepatitis. Materials and methods: It was carried out the analysis of case histories of 77 patients. In the course of treatment, the patients were diagnosed with chronic toxic hepatitis (K.71). Diagnosis was exposed in accordance with the official documentation introduced by the Gastroenterological department of Sumy Regional Clinical Hospital CH"SRCH", Sumy Regional Infectious Diseases Clinical Hospital named after Krasovytsky ZY and Sumy Regional Center of Blood Service. Results: It was found that total protein indicator is the normal range and albumin after plasmapheresis and during conservative treatment. Markers of cytolysis and cholestasis are have great value may. The most significant changes were observed in rates indicating lesion of the hepatic parenchyma, including ALT, AsAT and alkaline phosphatase. In conservative treatment, the percentageof the alkaline phosphatase level improved by 31%, after the course of plasmapheresis - by 58%. The obtained figures of cholestasis indexes indicate the effectiveness of both methods of treatment, but treatment with plasmapheresis has a more expressed effect on the decrease of alkaline phosphatase level. The level of bilirubin improve on 38,8% after plasmapheresis and 65% in the comparison group. Conclusion: Inclusion in the complex therapy of chronic hepatitis plasmapheresis reduces the severity of cytolysis and cholestasis, increases remission and significantly improves clinical manifestations.

Serum Alkaline Phosphatase Level is Associated with Angiographic Vasospasm, Delayed Cerebral Ischemia-Caused Clinical Deterioration, and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

Alkaline phosphatase (ALP) has been implicated to be associated with poor outcome in ischemic stroke patients, yet its role in aneurysmal subarachnoid hemorrhage (aSAH) patients is unknown. The current study aimed to investigate the on-admission and short-term variation trend of ALP levels in aSAH patients as well as its associations with vasospasm, delayed cerebral ischemia (DCI), and outcome after aSAH. Between January 2014 and May 2018, all consecutive aSAH patients were prospectively enrolled. Blood samples from patients and 78 healthy individuals were obtained. Baseline information, clinical data, and radiologic data were collected, and serum ALP levels during hospitalization were measured. Patients were followed up for 6months. One hundred and ninety-six aSAH patients were included. The serum ALP levels in aSAH patients were significantly higher compared to controls (71 vs. 61U/L, p = 0.0002), yet did not differ significantly between patients with severe (WFNS 4-5) and mild clinical condition (72 vs. 63U/L, p = 0.3362). However, ALP was significantly higher in patients with severe radiologic status (modified Fisher 3-4) compared to those with mild radiologic status (77 vs. 61.5U/L, p = 0.0005). A significant correlation emerged between modified Fisher score and ALP level (r = 0.246, p = 0.001). Multivariable analysis found that higher ALP level was associated with angiographic vasospasm (OR 1.019, 95%CI 1.002-1.036, p = 0.026) and DCI-caused clinical deterioration (OR 1.019, 95%CI 1.001-1.037, p = 0.037), while higher WFNS score, modified Fisher score, and ALP level were independently associated with unfavorable outcome (serum ALP level, OR 1.083, 95%CI 1.041-1.127, p < 0.001). Trend analysis of ALP level based on 103 patients' data revealed a significant decrease in ALP level on post-admission day 7-9 (median; on-admission day vs. post-admission day 7-9, 72 vs. 60U/L, p = 0.0012; post-admission day 3-5 vs. day 7-9, 70 vs. 60U/L, p = 0.0052) and subsequent increase in ALP level on post-admission day 12-14 (median, 84U/L, p < 0.0001). Higher ALP levels were observed in patients with unfavorable outcome on on-admission day, post-admission day 3-5, and 12-14 (median; unfavorable vs. favorable; on-admission day, 86 vs. 67U/L, p = 0.0122; post-admission day 3-5, 80 vs. 64U/L, p = 0.0044; post-admission day 7-9, 75 vs. 53.5U/L, p < 0.0001) but not on post-admission day 12-14. Elevated serum ALP level is associated with vasospasm, DCI-caused clinical deterioration, and functional outcome after aSAH. Further studies are required to examine the potential role of serum ALP as an outcome predictor for aSAH patients.

The Effect of Potato (Solanum tuberosum L.) Skin Extract on Alkaline Phosphatase Level in Periodontitis

Periodontitis is a chronic inflammation on tooth supporting tissues leads to alveolar bone resorption and tooth loss. Increase of alkaline phosphatase (ALP) level is found in periodontitis condition. Potato skin extract is known for its antioxidant and antiinflammation compounds therefore presumably potential as adjuvant therapy for periodontitis. This study aim was to know the effect of oral intake of potato skin extract on alveolar bone ALP and serum ALP level in model periodontitis Sprague dawley rats. Type of the study was experimental with posttest-only control group design. Thirty-five male Sprague dawley rats were divided into five groups: healthy control, negative control (aquadest-treated periodontitis), and potato skin extract- treated periodontitis in three different concentrations (25%, 50%, 75%). After 14-day treatments, ALP level on alveolar bone and blood serum samples from each group were measured using UV-Vis spectrophotometer. The results showed both alveolar bone ALP and serum ALP level were lower in potato skin extract-treated periodontitis groups in comparison to negative control group. Statistic analysis using One-way Anova showed significant difference of ALP level amongst groups (p<0.05). Post-hoc LSD test showed significant differences of ALP level between each treated and control groups (p<0.05). This study concluded potato skin extract decreased ALP level, with concentration 75% showed lowest both ALP levels of alveolar bone and serum samples, indicated alveolar bone remodeling. Moreover, it is suggested that ALP level in serum can represent ALP level on alveolar bone tissues in periodontitis condition.

Features of the structural and functional parameters of the liver in experimental steatohepatitis and its correction in obese rats

The improvement of the pharmacological strategy of non-alcoholic fatty liver disease is based on the study of the effect of pharmaceutical preparations on the structure and function of the liver. The pathogenesis of steatohepatitis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. The purpose of the study was to characterize the structural and functional parameters of the liver when using the biologically active compound Angiolin for the correction of experimental steatohepatitis. An experimental study was performed on 110 sexually mature white male rats weighing 180-220 grams, which were kept on a standard diet of vivarium. All animals were divided into two groups: control (30 intact animals) and experimental (80 animals). A model of non-alcoholic steatohepatitis was created for all animals of the experimental group. They were kept on a hypercaloric diet with a high fat and high cholesterol content for 8 weeks. After that, part of the animals (10 rats) was withdrawn from the experiment by intrapleural administration of sodium thiopental (50 mg/kg) and the necessary biochemical and morphological studies were performed. Part of the animals (30 rats) was continued to be kept on a high-fat diet for 4 weeks and the biologically active compound Angiolin was administered (20 rats), and Rings-Locke solutions were administered to 10 rats. After the creation of the model, the other animals of the experimental group (40 rats) were transferred to a full-fledged standard semi-synthetic starch-casein diet, and the biologically active compound Angiolin was administered for 20 rats and Ringer-Locke solution for another 20 rats for 4 weeks. Macroscopic evaluation and description of the liver of animals was carried out after withdrawal under thiopental anesthesia. Statistical analysis of the results was carried out using the program “STATISTICA 8” using parametric and non-parametric methods for assessing the results. It was found that the use of the biologically active compound Angiolin once a day for 30 days can reduce cytolysis syndrome (reduce biochemical parameters such as ALT, AST, gamma-glutamyl transpeptidase), reduce cholestasis syndrome (decrease in alkaline phosphatase level), and normalize liver function, improves the morphological state of hepatocytes, which indicates the normalization of the structural and functional state of the liver.

Neurological and Neurosurgical Aspects of Hypophosphatasia

Hypophosphatasia is a rare hereditary progressive disease caused by a mutation in ALPL gene and characterized by low activity of alkaline phosphatase. Due to the disruption of the bone mineralization process, ricket-like deformations of the skeleton occur in the clinic picture more frequently but other systemic manifestations can be also observed as respiratory insufficiency, urinary tract damage, and neurological disorders. Seizures, delayed physical and psychomotor development, attention deficit disorder, muscle weakness, fatigue, intracranial hypertension associated with the development of craniosynostosis are revealed in these patients. The severity of the disease depends on age: the highest mortality is reported in younger patients, in perinatal and infantile forms of hypophosphatasia. Diagnosis is based on the identification of specific clinical manifestations: retardation of growth and development, skeletal deformities, pain in muscles and joints, premature tooth loss. In laboratory tests, a steady decrease in alkaline phosphatase level is detected taking into account age and sex specification. If possible, alkaline phosphatase substrates are measured: levels of pyridoxal-5-phosphate in the blood and phosphoethanolamine in urine are higher at low enzyme activity. Radiographs of long bones typically reveal characteristic ‘tongues’ of lucency projecting from growth plates into metaphyses, hypomineralization, osteopenia, various kinds of deformation. All patients with suspected hypophosphatasia should be consulted by a clinical geneticist and evaluated to identify possible mutation in the ALPL gene.

HYPOPHOSPHATASIA IN ADULTS: CLINICAL CASES AND LITERATURE REVIEW

Hypophosphatasia is a rare inborn error of metabolism caused by mutations in the gene encoding tissue-nonspecific isoenzyme of alkaline phosphatase. Inexpressive clinical picture of the disease in adults is often difficult to diagnose. We present two clinical observations: in one case, the patient was treated for a long time with alfacalcidol and calcium supplementation due to misdiagnosis of systemic osteoporosis with pathologic fractures of the vertebras, although at the presentation the patient had a typical for hypophosphatasia decrease of alkaline phosphatase. In another case, a patient with diagnosis of aseptic necrosis of the femoral head had a sharp decrease in alkaline phosphatase levels at presurgical evaluation. In both cases, the diagnosis was confirmed by genetic testing. For patients with aseptic necrosis the confirmation of the diagnosis of hypophosphatasia determines the need for treatment with asfotase alfa in the postoperative period to preserve the stability of the endoprosthesis.

Effects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products

IntroductionProangiogenic prolyl hydroxylase (PHD) inhibitors represent a novel approach to stimulate tissue regeneration. Diabetes mellitus involves the accumulation of advanced glycation end products (AGEs). Here we evaluated the impact of AGEs on the response of human pulp tissue to the PHD inhibitor L-mimosine (L-MIM) in monolayer cultures of dental pulp–derived cells (DPCs) and tooth slice organ cultures. MethodsIn monolayer cultures, DPCs were incubated with L-MIM and AGEs. Viability was assessed based on formazan formation, live-dead staining, annexin V/propidium iodide, and trypan blue exclusion assay. Vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 production was evaluated by quantitative polymerase chain reaction and immunoassays. Furthermore, expression levels of odontoblast markers were assessed, and alizarin red staining was performed. Tooth slice organ cultures were performed, and VEGF, IL-6, and IL8 levels in their supernatants were measured by immunoassays. Pulp tissue vitality and morphology were assessed by MTT assay and histology. ResultsIn monolayer cultures of DPCs, L-MIM at nontoxic concentrations increased the production of VEGF and IL-8 in the presence of AGEs. Stimulation with L-MIM decreased alkaline phosphatase levels and matrix mineralization also in the presence of AGEs, whereas no significant changes in dentin matrix protein 1 and dentin sialophosphoprotein expression were observed. In tooth slice organ cultures, L-MIM increased VEGF but not IL-6 and IL-8 production in the presence of AGEs. The pulp tissue was vital, and no signs of apoptosis or necrosis were observed. ConclusionsOverall, in the presence of AGEs, L-MIM increases the proangiogenic capacity, but decreases alkaline phosphatase expression and matrix mineralization.

Stereological study of the effect of black olive hydroalcoholic extract on osteoporosis in vertebra and tibia in ovariectomized rats.

A cocktail of many different antioxidants might be more effective than supplementation with a single molecule, and it closely resembles the natural environment in which active compounds were found. This is the first study well-grounded in stereological examination that showed that black olive extract effectively can ameliorate the quantitative changes of the bone structure and prevented bone loss in this osteoporosis animal model. The aim of this study was to quantitatively evaluate the effects of black olive extract consumption on treatment of ovariectomized (OVX) induced osteoporosis in rats. This is the first study well-grounded in stereological examination. Ninety adult rats were allocated to control, sham-operated, OVX, and olive-supplemented OVX groups (received 250-, 500-, and 750-mg/kg body weight black olive hydroalcoholic extract orally) for 16 weeks. At the end of the experiment, blood samples were collected, and plasma levels of calcium, phosphorus, and alkaline phosphatase were assayed. Then, the specimens from both the tibia and fifth lumbar vertebra (L5) bones were processed, and stereological analysis was performed. Administration of extract resulted in decrease of alkaline phosphatase level during the treatment. After treatment of OVX rats with three doses of extract, the total number of the osteocytes revealed an increment in 500- and 750-mg/kg treated groups in comparison to the OVX group. This increment was significant only in L5. Compared to the OVX group, a significant increase was observed in the number of osteoblastsin L5 vertebra in three doses of extract-treated groups. However, this increment in tibia was statistically significant only in 750-mg/kg black olive hydroalcoholic extract-treated group. Moreover, the number of osteoclast cells were significantly decreased in vertebra and tibia in the treated groups compared to the OVX group (P < 0.05). Black olive hydroalcoholic extract effectively can ameliorate the quantitative changes of the bone structure and prevented bone loss in this osteoporosis animal model. Thus, it can be a promising candidate for treatment of accelerated bone loss especially in postmenopausal osteoporosis.

The effects of cystatin C and alkaline phosphatase changes on cognitive function 12-months after bariatric surgery

BackgroundThe mechanisms for improved cognitive function post-bariatric surgery are not well understood. Markers of kidney and liver function (i.e., cystatin C and alkaline phosphatase (ALP)) are elevated in obese individuals and associated with poor neurocognitive outcomes in other samples. Bariatric surgery can improve cystatin C and ALP levels, but no study has examined whether such changes correspond to post-operative cognitive benefits. Methods78 bariatric surgery patients completed a computerized cognitive test battery prior to and 12-months after surgery. All participants underwent an eight-hour fasting blood draw to quantify cystatin C and ALP concentrations. ResultsCognitive function improved after surgery. Cystatin C levels decreased at the 12-month follow-up; however, no changes were found in ALP concentrations. At baseline, higher cystatin C levels predicted worse attention/executive function, but no such effects emerged for ALP. Regression analyses controlling for possible medical and demographic confounds and baseline factors revealed that decreased ALP levels following surgery predicted better attention/executive function and memory abilities. Post-surgery changes in cystatin C did not correspond to cognitive improvements. ConclusionsDecreased ALP levels predicted better cognition following bariatric surgery, suggesting improved liver function as a possible mechanism of post-operative cognitive benefits. Future studies with neuroimaging and longer follow-up periods are needed to determine whether bariatric surgery can decrease risk for adverse brain changes and dementia in severely obese persons via improved metabolic function.

Vitamin D Provision in High-Yield Dairy Cows During the Winter Housing Period

Aim. To investigate the vitamin D status in highly productive cows during winter housing period and effect of cholecalciferol by various ways of vitamin D 3 injection to cows in last days of gestation and after calving. Methods. Enzyme-linked immunoassay, spectrophotometry. Results. It has been stated that intramuscular injection of cholecalciferol into cows caused increase of the vitamin D 3 active metabolite – 25-OHD 3 , calcium, phosphorus and magnesium levels together with decrease of alkaline phosphatase level in pre- and post-natal periods. Oral supplementation makes little infl uence on the studied blood parameters of cows. Conclusions. Extrabuccal administration and oral supplementation of cholecalciferol in winter housing period to high-yield cows in the last days of gestation and after calving is accompanied by increased levels of its metabolites and their effect on mineral metabolism in the postnatal period. The nature of these changes depends on the mode of vitamin D administration and the physiological state of the cows.