Higher Alkaline Phosphatase Levels Research Articles

Incorporation of azithromycin into akermanite-monticellite nanocomposite scaffolds: Preparation, biological properties, and drug release characteristics

Bioceramics composed of calcium and magnesium silicates have garnered increasing attention for the development of porous scaffolds in bone tissue engineering (BTE). This heightened interest is primarily attributed to their remarkable bioactivity and their capacity to form strong bonds with hard tissue. Fabricating nanocomposite scaffolds is a recognized approach for improving the characteristics of scaffolds used in BTE. This research investigates the mechanical and biological properties, antibacterial activity, and drug-release characteristics of scaffolds composed of akermanite (AKT), monticellite (MON), and monticellite-akermanite (MON-AKT). These scaffolds were fabricated utilizing the space holder process. Additionally, the in vitro drug release profile and antimicrobial activity of Azithromycin (AZT)-loaded MON-AKT composite scaffolds were investigated. The findings showed that the Mon-15 wt% AKT nanocomposite scaffold had the highest density, the smallest grain and micropore sizes, and the lowest porosity. In contrast, integrating AKT into MON-based composite scaffolds resulted in materials characterized by high mechanical strength and stability within physiological environments. The MON-AKT nanocomposite scaffolds exhibited cytocompatibility and demonstrated a high level of alkaline phosphatase (ALP) activity in osteogenic studies. Furthermore, antimicrobial activity assessments revealed that the AZT-encapsulated MON-AKT composite scaffolds effectively inhibited the growth of both S. aureus and E. coli bacteria. The outcomes showed that the antibacterial efficacy of the scaffold depends on both the amount of AZT and the type of bacteria. Overall, MON-AKT/3AZT scaffolds exhibited significantly superior bacterial inhibition compared to other scaffolds, making it a promising option for treating bone tissue defects.

Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity

PurposeMetabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3–4 weeks of life in at-risk patients.MethodsA single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05.ResultsIn the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3–4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3–4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation.ConclusionsMBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

Novel TRPV6 variant linked with transient neonatal hyperparathyroidism

BackgroundHereditary transient neonatal hyperparathyroidism (TNHP) is a rare autosomal-recessive condition caused by variants in TRPV6 gene which encodes for a transient maternal–fetal calcium transport channel. This is characterized by interference with placental maternal–fetal calcium transport causing fetal calcium deficiency. It primarily manifests as defective bone mineralization, narrow and bell-shaped thorax, bone fractures and short bones at birth. The current study aimed to describe a novel TRPV6 variant linked with TNHP in an Indian family and the review of literature.Case presentationThe proband is a term female neonate with fetal growth restriction born to a third-degree consanguineous couple. She was noted to have diffuse defective bone mineralization, narrow and bell-shaped thoracic cavity, short bones and curved ribs without any bone fractures. The first pregnancy was affected with similar features in the fetus and had been terminated. Parental whole-exome sequencing suggested heterozygous missense variant in exon 12 of the TRPV6 gene (c.1585G > A, p.Asp529Asn) in both the parents. The proband required non-invasive respiratory support for ten days in neonatal intensive care unit. She had low calcium and high parathyroid hormone (PTH) and alkaline phosphatase (ALP) levels. She received calcium, phosphorus and vitamin D supplements for three months leading to normalization of serum PTH and ALP levels. Whole-exome sequencing of the proband suggested a homozygous missense variant in exon 12 of the TRPV6 gene (p.Asp529Asn; ENST00000359396.9) that results in the amino acid substitution of asparagine for aspartic acid at codon 529. To the best of author’s knowledge, this is the twelfth case of TNHP reported in literature. The novel variant of TRPV6 gene present in this family has not been reported earlier.ConclusionOur finding broadens the genotypic spectrum of TNHP.

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study

BackgroundTo assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.MethodsData of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence.ResultsAfter a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15–1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15–1.20), 1.20 (1.18–1.22), 1.69 (1.47–1.93), 1.06 (1.06–1.07), 1.08 (1.07–1.09), 1.81 (1.37–2.39), or 0.29 (0.18–0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43–5.48), 4.03 (2.69–6.03), 1.97 (1.40–2.77), 4.69 (2.98–7.37), 2.51 (1.75–3.59), 2.09 (1.51–2.89), or 2.22 (1.55–3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19–1.41).ConclusionsUnhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

Simple predictors for the completion of scheduled gemcitabine‑cisplatin regimens based on real‑world urothelial cancer data.

Gemcitabine plus cisplatin (GC) is the standard first line of chemotherapy for urothelial carcinoma. However, it is often difficult to complete scheduled GC therapy because of real-world adverse events. Therefore, the reasons behind delays, scheduled cancelations and determined predictive factors for completing scheduled GC therapy were retrospectively analyzed. Patients diagnosed with locally advanced or metastatic urothelial carcinoma from 2009 to 2020 received a 4-week GC therapy schedule in Oita University Hospital. Information was retrospectively extracted from medical records and all cycles were divided into two groups: One wherein all treatments were administered and completed on schedule and the other wherein treatment was either delayed or canceled in during the treatment schedule. Predictive factors were then statistically extracted between the two groups. In total, 70 patients received 201 cycles of a 4-week scheduled GC therapy. Of the 201 cycles, a total of 68 (33.8%) completed all scheduled treatments, while 133 (66.1%) did not complete the treatment as scheduled. In the group where administration was not completed on schedule, the factors of male, ureteral cancer, lower stage, <90% of gemcitabine and cisplatin dosage, solitary kidney, high creatinine level, low estimated glomerular filtration rate level, low platelet count and high alkaline phosphatase level at the initiation of each cycle were more significant. Additionally, the lowest anticancer drug percentage administration was on day 15. From these results, predictive factors for patients with various backgrounds who completed the scheduled 4-week GC therapy based on real-world data were identified. This information can be useful for clinical physicians when deciding the course of treatment.

Calcium Homeostasis Abnormalities in Patients Taking Chronic Anticonvulsants Therapy – A Cross-sectional Study

Introduction: Epilepsy is a well-known disease entity that is responsible for a significant amount of morbidity. The purpose of this research is to determine the frequency of calcium homeostasis abnormalities in patients who are taking chronic anticonvulsant medication and to analyze the levels of Vitamin D in the serum of patients who are taking chronic anticonvulsant medication. Materials and Methods: The SVRRGGH general medicine department in Tirupati conducted this cross-sectional single-centered prevalence study. The study included outpatients, inpatients, and acute medical care (AMC) patients. After applying the inclusion and exclusion criteria, the study randomly selected 100 seizure disorder patients from the SVRRGH in Tirupati. Epilepsy patients who participated in the study were asked about medication, compliance, and seizure control. Anticonvulsant usage and duration were recorded. Serum calcium, Vitamin D, alkaline phosphatase (ALP), and parathormone were measured. Hypoalbuminemia caused calcium adjustments. Liver and renal function tests ruled out other major causes of hypovitaminosis D. Results: In this study, 36% were hypocalcemic and 64% were normocalcemic. There was a significant association between a number of drugs, duration of up to 12 months, normal Vitamin D levels, and good seizure levels with hypocalcemia ( P &lt; 0.001). Around 25% had high ALP levels and 75% had normal ALP levels. High ALP levels were significantly associated with hypocalcemia ( P &lt; 0.001). Conclusion: Chronic anticonvulsant therapy is associated with significant hypocalcemia and hypovitaminemia D, and our findings suggest that calcium and Vitamin D supplementation might be beneficial for patients experiencing these conditions.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Influence of Titanium Surface Residual Stresses on Osteoblastic Response and Bacteria Colonization.

Grit basting is the most common process applied to titanium dental implants to give them a roughness that favors bone colonization. There are numerous studies on the influence of roughness on osseointegration, but the influence of the compressive residual stress associated with this treatment on biological behavior has not been determined. For this purpose, four types of surfaces have been studied using 60 titanium discs: smooth, smooth with residual stress, rough without stress, and rough with residual stress. Roughness was studied by optic interferometry; wettability and surface energy (polar and dispersive components) by contact angle equipment using three solvents; and residual stresses by Bragg-Bentano X-ray diffraction. The adhesion and alkaline phosphatase (ALP) levels on the different surfaces were studied using Saos-2 osteoblastic cultures. The bacterial strains Streptococcus sanguinis and Lactobacillus salivarius were cultured on different surfaces, determining the adhesion. The results showed that residual stresses lead to increased hydrophilicity on the surfaces, as well as an increase in surface energy, especially on the polar component. From the culture results, higher adhesion and higher ALP levels were observed in the discs with residual stresses when compared between smooth and roughened discs. It was also found that roughness was the property that mostly influenced osteoblasts' response. Bacteria colonize rough surfaces better than smooth surfaces, but no changes are observed due to residual surface tension.

Juvenil İdiyopatik Artrit Tanılı Çocuklarda 25 Hidroksivitamin D Düzey Takibinin Önemi

Objective: In patients with juvenile idiopathic arthritis (JIA), bone metabolism may be negatively affected due to both the activity of the disease and the medications used. Our study aimed to investigate the necessity of evaluating 25 hydroxyvitamin D (25 (OH) Vit D), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) levels and possible related factors in the follow-up of patients diagnosed with JIA.&#x0D; Method: The records of 68 patients with JIA were retrospectively evaluated. Disease subtypes, medications used, and whether they were in remission or active disease were reviewed.&#x0D; Results: 25 OH Vit D levels were low in 14.7% of patients with JIA compared to the control group. 66.6% of the patients with systemic arthritis had high ALP levels. 25 OH Vit D level was low in 16.6% of steroid users, and Vitamin D level was low in 55.5% of the patients in the active disease group. It was determined that patients in the active disease group had the highest ALP and lowest vitamin D levels compared to patients in remission with and without medication.&#x0D; Conclusion: Bone metabolism in patients with JIA is negatively affected. Since vitamin D plays a crucial role in bone metabolism, it was emphasized that vitamin D levels should be evaluated especially during active disease and supplements should be provided for patients with low vitamin D levels.

Prevalence of high and low serum alkaline phosphatase levels and the associated factors in patients with rheumatoid arthritis: results from the IORRA cohort study.

Prevalence of high and low serum alkaline phosphatase levels and the associated factors in patients with rheumatoid arthritis: results from the IORRA cohort study.

Paget disease of bone in a southeastern Veteran population

BackgroundPaget disease of bone (PDB) is a disorder of accelerated bone remodeling resulting in bone overgrowth and impaired integrity that traditionally is described to be more frequent in individuals of European descent. Based on clinical observation, we hypothesized that among the US Southeastern Veteran population, the disease is more common among African American patients. Materials and methodsWe conducted a cross-sectional study using the Veterans Affairs’ Clinical Data Warehouse (CDW) and review of electronic medical records (EMR). Using the CDW, we identified patients from the Birmingham VA Medical Center (BVAMC) with an International Classification of Diseases code for PDB between January 2000 and December 2020. We extracted their self-reported race from the CDW and determined the proportion of African American patients, which we compared to the proportion of White patients. As a secondary goal, we extracted relevant clinical characteristics from the EMR. The statistical analysis was done using Stata/SE 14.2 for Mac. ResultsWe identified 285 individuals from the BVAMC with PDB between January 2000 and December 2020. The proportion of African American patients was significantly higher than White patients (0.51 vs. 0.4, p = 0.0036). African American patients presented at a younger age than their peers (mean[standard deviation] age at diagnosis: 64.6[11.6] vs. 70.1[10.7] years, p = 0.0009) but did not have higher alkaline phosphatase levels, higher proportion of polyostotic disease, or of symptoms and complications. ConclusionsIn the BVAMC population, PDB is more common among African American patients than White patients. Our findings and other publications hint at the existence of a cluster of PDB among the African American population in the US Southeast.

Pretreatment level of serum sialic acid predicts both qualitative and quantitative bone metastases of prostate cancer.

Recently, serum sialic acid (SA) has emerged as a distinct prognostic marker for prostate cancer (PCa) and bone metastases, warranting differential treatment and prognosis for low-volume (LVD) and high-volume disease (HVD). In clinical settings, evaluating bone metastases can prove advantageous. We aimed to establish the correlation between SA and both bone metastasis and HVD in newly diagnosed PCa patients. We conducted a retrospective analysis of 1202 patients who received a new diagnosis of PCa between November 2014 and February 2021. We compared pretreatment SA levels across multiple groups and investigated the associations between SA levels and the clinical parameters of patients. Additionally, we compared the differences between HVD and LVD. We utilized several statistical methods, including the non-parametric Mann-Whitney U test, Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression. The results indicate that SA may serve as a predictor of bone metastasis in patients with HVD. ROC curve analysis revealed a cut-off value of 56.15 mg/dL with an area under the curve of 0.767 (95% CI: 0.703-0.832, P < 0.001) for bone metastasis versus without bone metastasis and a cut-off value of 65.80 mg/dL with an area under the curve of 0.766 (95% CI: 0.644-0.888, P = 0.003) for HVD versus LVD. Notably, PCa patients with bone metastases exhibited significantly higher SA levels than those without bone metastases, and HVD patients had higher SA levels than LVD patients. In comparison to the non-metastatic and LVD cohorts, the cohort with HVD exhibited higher levels of alkaline phosphatase (AKP) (median, 122.00 U/L), fibrinogen (FIB) (median, 3.63 g/L), and prostate-specific antigen (PSA) (median, 215.70 ng/mL), as well as higher Gleason scores (> 7). Multivariate logistic regression analysis demonstrated that an SA level of > 56.15 mg/dL was independently associated with the presence of bone metastases in PCa patients (OR = 2.966, P = 0.018), while an SA level of > 65.80 mg/dL was independently associated with HVD (OR = 1.194, P = 0.048). The pretreatment serum SA level is positively correlated with the presence of bone metastases.

Selected osteointegration markers in different timeframes after dental implantation: findings and prognostic value.

The study aimed to determine the osteointegration markers after dental implantation and evaluate their predictive value. The study was performed on 60 practically healthy persons who needed teeth rehabilitation using dental implants. The conical-shaped implants (CI) and hexagonal implants (HI) were used. The content of Osteopontin (OPN), Osteocalcin (OC), Alkaline Phosphatase (ALP), Osteoprotegerin (OPG), and nitric oxide (NO) was determined in patients' gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF), collected 1, 3, and 6months after implantation. During the 3-6months of observation level of OPN increased in patients with CIs (<50years > 50years) and HIs (<50years) (CI: <50years F = 36.457, p < 0.001; >50years F = 30.104, p < 0.001; HI < 50years F = 2.246, p < 0.001), ALP increased in patients with CIs (<50years: F = 19.58, p < 0.001; >50years: F = 12.01; p = 0.001) and HIs (<50years) (F = 18.51, p < 0.001), OC increased in patients <50years (CI: F = 33.72, p < 0.001; HI: F = 55.57, p < 0.001), but in patients >50years - on the 3days month (CI: F = 18.82, p < 0.001; HI: F = 26.26, p < 0.001), but sharply decreased at the end of sixth month. OPG increased during 1-3months of the observation in patients <50years (CI: F = 4.63, p = 0.037; HI: F = 2.8927, p = 0.046), but at the end of the sixth month returned to the initial level; NO content in PISF increased in patients with CI (>50years) during 1-6months of the observation (F = 27.657, p < 0.001). During the post-implantation period, age-related differences in osteointegration were observed. Patients <50years old had relatively high levels of OPN, ALP, OC, and OPG in PISF, resulting in less alveolar bone destruction around dental implants and more intensive osteointegration. These indicators may be used as biological markers for monitoring implant healing. The process of osseointegration was more intense in CIs due to their comparatively high mechanical loading.

Time Course of Biochemical and Metabolic Parameters During and After COVID-19.

Long COVID is characterized by the persistence of symptoms among individuals who are infected with the SARS-CoV-2 virus. The enduring impact of these long-term effects on the health and well-being of those affected cannot be denied. About 470 patients with SARS-CoV-2 were consecutively recruited in this longitudinal study. The participants were entered into moderate, severe, and critical groups. 235 out of 470 participants were female. The levels of fasting blood sugar (FBS), alanine transaminase (SGPT), aspartate aminotransferase (SGOT), alkaline phosphatase (ALP), creatinine (Cr), urea, uric acid (UA), and total protein (TP) were measured during hospitalization and again at one and three months after infection. The levels of Zn and hemoglobin A1c (HbA1c) were also measured only during hospitalization. COVID-19 severity was associated with high levels of glucose, urea, Cr, ALT, AST, ALP, and HbA1c, and low levels of Zn, UA, and TP. There were significant sex differences for these markers at all three-time points. Glucose, urea, Cr, ALT, AST, and ALP all decreased three months after infection, whereas the levels of UA and TP returned towards normal. COVID-19 infection affects the levels of multiple biochemical factors in a gender-dependent manner. The biochemical changes become more tangible with increasing disease severity, and several of these predict mortality. Levels begin to return to normal after the acute phase of the disease, but in some individuals, at three months, several markers were still not within the normal range. Whether the trajectory of these changes can predict long COVID requires further testing.

Lower pretreatment serum testosterone level predicts poor prognosis in the patients with metastatic hormone-sensitive prostate cancer undergoing androgen deprivation therapy.

This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy. A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals. During a median follow-up of 41.7months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n=37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n=54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P=0.021 and P<0.001, respectively). Multivariate analysis identified testosterone level of <450ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P=0.007), along with high-volume disease and Gleason score 9-10. Similarly, testosterone level of <450ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P=0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level. Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.

Impairment of adenosine signaling disrupts early embryo development: unveiling the underlying mechanisms.

Purinergic signaling has been implicated in many biological functions, including development. In this study, we investigate the functions of extracellular adenosine and adenosine receptors using a mouse embryonic stem cell (ESC) line and morula stages isolated from mouse embryos. Feeder-free mouse ESC was investigated in the absence and presence of the leukemia inhibitory factor (LIF), configuring undifferentiated cells and cells undergoing spontaneous differentiation. High alkaline phosphatase (ALPL) and low CD73 levels resulting in low adenosine (eADO) levels were characteristic for pluripotent cells in the presence of the LIF, while LIF deprivation resulted in augmented adenosine levels and reduced pluripotency marker expression, which indicated differentiation. Tracing ESC proliferation by BrdU labeling revealed that the inhibition of ALPL by levamisole resulted in a decrease in proliferation due to less eADO accumulation. Furthermore, caffeine and levamisole treatment, inhibiting adenosine receptor and eADO accumulation, respectively, reduced ESC migration, similar to that observed in the absence of the LIF. Pharmacological approaches of selective adenosine receptor subtype inhibition triggered specific adenosine receptor activities, thus triggering calcium or MAP kinase pathways leading to differentiation. In line with the in vitro data, mouse embryos at the morula stage were sensitive to treatments with A1 and A3 receptor antagonists, leading to the conclusion that A1 receptor and A3 receptor inhibition impairs proliferation and self-renewal and triggers inappropriate differentiation, respectively. The findings herein define the functions of eADO signaling in early development with implications for developmental disorders, in which adenosine receptors or ectonucleotidase dysfunctions are involved, and which could lead to malformations and miscarriages, due to exposure to caffeine.

Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS

BackgroundSecondary hyperparathyroidism increases the risk of fractures and cardiovascular (CV) disease in hemodialysis (HD) patients. The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO guideline suggests monitoring total alkaline phosphatase (ALP), but the role of ALP versus PTH in the management of mineral and bone disorder is not clear. MethodsThe analysis included 28,888 HD patients in 9 countries in DOPPS phase 3-7 (2005-2021). The primary exposures of interest were normalized ALP and PTH – raw values divided by facility upper normal limit – measured at study enrollment. Cox models were used to estimate hazard ratios of all-cause/CV mortality and any/hip fracture adjusted for potential confounders. Linear mixed models, adjusted for potential confounders, were employed to investigate the relationship between normalized ALP levels and patient characteristics. ResultsNormalized PTH showed a J-shaped association with all-cause/CV mortality, and a weak linear association with fracture. In contrast, normalized ALP showed a strong association with all outcomes. Factors associated with higher ALP levels after controlling for PTH included Black race, longer dialysis vintage, diabetes mellitus, hypocalcemia, hypophosphatemia, elevated C-reactive protein, and the use of cinacalcet. ConclusionsTotal ALP is a more robust exposure of adverse outcomes than PTH in HD patients. PTH responsiveness is affected by race, primary renal disease, comorbidities, and mineral metabolism and therapy. Our results indicate that it may be useful to evaluate target organ response, rather than PTH alone when considering the consequences of secondary hyperparathyroidism.

Bone mineral density and related clinical and laboratory factors in peritoneal dialysis patients: Implications for bone health management.

End-stage renal disease (ESRD) patients often experience accelerated bone turnover, leading to osteoporosis and osteopenia. This study aimed to determine the prevalence of osteoporosis in Peritoneal Dialysis (PD) patients using bone mineral density (BMD) measurements obtained through dual-energy X-ray absorptiometry (DEXA) scan and to explore any possible associations with clinical and biochemical factors. In this cross-sectional study, we enrolled 76 peritoneal dialysis patients from the dialysis center at An-Najah National University Hospital in Nablus, Palestine. We used the DEXA scan to measure BMD at the lumbar spine and hip, with values expressed as T-scores. We conducted a multivariate analysis to explore the relationship between BMD and clinical and biochemical parameters. Over half (52.6%) of the PD patients had osteoporosis, with a higher prevalence observed among patients with lower BMI (p<0.001). Higher alkaline phosphatase levels were found among osteoporotic patients compared to non-osteoporotic patients (p = 0.045). Vitamin D deficiency was also prevalent in this population, affecting 86.6% of patients. No significant correlation was found between 25 vitamin D levels and BMD. No significant correlation was found between Parathyroid hormone (PTH) levels and BMD. A notable proportion of PD patients experience reduced BMD. Our study found no correlation between vitamin D levels and BMD, but it highlighted the significant vitamin D deficiency in this population. Furthermore, our analysis indicated a positive correlation between BMI and BMD, especially in the femoral neck area. This underscores the significance of addressing bone health in PD patients to mitigate the risk of fractures and improve their overall well-being.

Brucellar arthritis and sacroiliitis: an 8-year retrospective comparative analysis of demographic, clinical, and paraclinical features.

Brucellosis is a common global zoonotic disease with a wide range of complex and nonspecific clinical manifestations that may lead to misdiagnosis and delayed treatment. Osteoarticular involvement is the most common complaint in brucellosis. This present study aims to describe the clinical and laboratory characteristics and treatment of brucellosis patients with arthritis and sacroiliitis. This retrospective descriptive study was performed on patients presenting to a teaching hospital in Kermanshah, Iran with a diagnosis of brucellosis from 2011 to 2019. The demographic and clinical characteristics, complications, laboratory findings, and treatment were recorded during the study period. Then, the difference in the collected data was investigated between brucellosis patients with and without arthritis or sacroiliitis. Of 425 patients studied, 130 (30.58%) had osteoarticular involvement. Among them, 41 (9.64%) and 58 (13.6%) patients were diagnosed with arthritis and sacroiliitis, respectively. There were no significant demographic differences between patients with and without brucellar arthritis or sacroiliitis (p > 0.05). The patients with Brucella arthritis had a significantly higher frequency of arthralgia and radiculopathy (p ⩽ 0.05). Sacroiliitis was significantly more common in patients with arthralgia, neck pain, and low back pain, positive flexion-abduction-external rotation (FABER) test, radiculopathy, and vertebral tenderness compared to patients without sacroiliitis (p ⩽ 0.05), while fever and headache were significantly more common in patients without sacroiliitis (p ⩽ 0.05). The median Wright and 2-Mercapto Ethanol titers were higher in brucellosis patients with arthritis or sacroiliitis versus patients without arthritis or sacroiliitis, but the difference was not significant (p > 0.05). Synovial fluid had been analyzed in 20 cases. The mean white blood cell count, glucose, and protein level were 3461 ± 2.70 cells/mm3, 58.54 ± 31.43 mg/dL, and 8.6 ± 11.85 g/dL, respectively. In 80% of the subjects, neutrophil cells were predominant. There were no significant laboratory differences between patients with and without brucellar arthritis or sacroiliitis, except for a higher median platelet count in patients with arthritis and higher median levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in patients with sacroiliitis. Most cases of arthritis and sacroiliitis were diagnosed with ultrasound (31.8%) and FABER test (79.3%), respectively. Arthritis and sacroiliitis were the two most important and common manifestations of brucellar osteoarthritis with a frequency of 9.64% and 13.6%, respectively. Any complaints of low back pain and radiculopathy as well as the presence of spondylitis in patients should raise suspicion of sacroiliitis. High levels of AST and ALP and a high platelet count may be associated with brucellar sacroiliitis and arthritis, respectively. The use of imaging methods such as MRI and bone scan seems necessary for the diagnosis of sacroiliitis.

Retrospective evaluation of cases of benign transient hyperphosphatasemia

This study aimed to evaluate the demographic, clinical, and laboratory characteristics of children with benign transient hyperphosphatasemia (BTH) and to increase awareness of BTH. Children with BTH followed up in a tertiary pediatric endocrinology outpatient clinic were included in this retrospective study. Children who were aged under 5 years, who had no evidence of liver, kidney, or bone disease, who had serum total alkaline phosphatase (ALP) levels above 1000 IU/L, and whose ALP values resolved within 4 months, were included in the study. The study included 10 infants and children (4 females) with BTH who were referred to our clinic during 1 year for high ALP levels. The mean age was 2.4±0.5 years. The mean weight SDS was -0.24±1.27 and the mean height SDS was -0.51±0.67. The mean ALP level was 2.395±934 IU/L. The mean normalization time for serum ALP was 2.4±1.1 months. Benign transient hyperphosphatasemia is an entity that occurs in healthy infants and children without evidence of liver or bone disease and resolves without intervention.