Elevated Serum Alkaline Phosphatase Research Articles

Biochemical changes associated with the administration of aqueous pulp extract of Irvingia gabonensis fruit on adult male Wistar rats

Biochemical changes associated with the administration of aqueous pulp extract of Irvingia gabonensis fruit on adult male Wistar rats

Critical Illness Cholangiopathy in COVID-19 Long-haulers

Critical Illness Cholangiopathy in COVID-19 Long-haulers

In pursuit of new anti-malarial candidates: novel synthesized and characterized pyrano-benzodioxepin analogues attenuated Plasmodium berghei replication in malaria-infected mice

Malaria, a parasitic disease, is one of the major causes of morbidity and mortality, particularly in the tropics. Following the increased resistance of the primary causative parasite, Plasmodium sp, to the mainstream drug, artemisinin combination therapies (ACTs), combating malaria incidences, morbidity and mortality have remained elusive. Novel pyrano-benzodioxepin derivatives (DHA-PABA and DHA-LEVO) were synthesized and characterized using Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopies. The compounds were subjected to standard in vivo antimalarial screening (using chloroquine-sensitive strain) in mice, and the toxicity was also determined using a standard assay. The observed elevation in serum alkaline phosphatase and acid phosphatase activity in the untreated and the group administered lower doses of DHA-LEVO is an indication of the hepatic stage of the parasite in the experimental animal, which is accompanied by significant perturbation in the membrane of the hepatocyte leading to leakage of this enzyme out of the liver cells. The semisynthetic pyrano-benzodioxepin derivatives act rapidly by clearing the parasite load from the blood. The novel pyrano-benzodioxepin candidates containing endoperoxide functionality hold promise in the pursuit of new monotherapy drug candidates against the virulent strain of the plasmodium.

Risk Analysis of Denosumab-Induced Hypocalcemia in Bone Metastasis Treatment: Renal Dysfunction Is Not a Risk Factor for Its Incidence in a Strict Denosumab Administration Management System with Calcium/Vitamin D Supplementation.

We have reported that a strict denosumab administration management system with oral calcium/vitamin D supplementation attenuates denosumab-induced hypocalcemia in 158 cancer patients with bone metastasis. In this report, 27.8% of the patients experienced hypocalcemia, including 0.6% with grade 2. So far, the risk factors for ≥grade 2 hypocalcemia incidence have been identified in denosumab-treated cancer patients, including patients without calcium/vitamin D supplementation. Therefore, the present study aimed to reveal the factors that affect all-grade hypocalcemia incidence with calcium/vitamin D supplementation and team medical care according to the management system. A receiver operating characteristic curve analysis suggested that the cutoff of baseline serum calcium level for all-grade hypocalcemia incidence was 9.3 mg/dL. Multivariate analysis revealed that age ≥65 years (odds ratio, 95% confidence interval: 2.57, 1.11-5.95, p = 0.03), grade 1 or higher serum alkaline phosphatase elevation (3.70, 1.71-8.00, p < 0.01), an adjusted serum calcium level of less than 9.3 mg/dL (3.21. 1.25-8.24, p = 0.02) at baseline, and co-administration of cytotoxic agents (2.33, 1.06-7.11, p = 0.03) are risk factors for the incidence of all-grade hypocalcemia. However, renal dysfunction, which has been suggested to be a risk factor in previous reports, was not a factor. In conclusion, we revealed the risk factors for all-grade hypocalcemia in calcium/vitamin D supplementation and awareness, as demonstrated by the management system. Moreover, renal dysfunction was not a risk factor in our strict denosumab administration management system. Our results support the value of early detection of hypocalcemia incidence to guide the selection of an appropriate management strategy.

Voriconazole-associated periostitis: Pathophysiology, risk factors, clinical manifestations, diagnosis, and management.

Voriconazole use has been associated with osteoarticular pain and periostitis, likely due to high fluoride content in the drug formulation. This phenomenon has been described primarily with high dosage or prolonged course of voriconazole therapy in immunocompromised and transplant patient populations. Patients typically present with diffuse bony pains associated with elevated serum alkaline phosphatase and plasma fluoride levels in conjunction with radiographic findings suggestive of periostitis. We provide a comprehensive review of the literature to highlight salient characteristics commonly associated with voriconazole-induced periostitis.

Clinical Features and Serological Markers Risk Model Predicts Overall Survival in Patients Undergoing Breast Cancer and Bone Metastasis Surgeries.

BackgroundSurgical therapy of breast cancer and bone metastasis can effectively improve the prognosis of breast cancer. However, after the first operation, the relationship between preoperative indicators and outcomes in patients who underwent metastatic bone surgery remained to be studied. Purpose 1. Recognize clinical and laboratory prognosis factors available to clinical doctors before the operation for bone metastatic breast cancer patients. 2. Develop a risk prediction model for 3-year postoperative survival in patients with breast cancer bone metastasis.MethodsFrom 2014 to 2020, patients who suffered from breast cancer bone metastasis and received therapeutic procedures in our institution were included for analyses (n=145). For patients who underwent both breast cancer radical surgery and bone metastasis surgery, comprehensive datasets of the parameters of interest (clinical features, laboratory factors, and patient prognoses) were collected (n=69). We performed Multivariate Cox regression to identify factors that were associated with postoperative outcome. 3-year survival prediction model and nomograms were established by 100 bootstrapping. Its benefit was evaluated by calibration plot, C-index, and decision curve analysis. The Surveillance, Epidemiology, and End Results database was also used for external validation.ResultsRadiotherapy for primary cancer, pathological type of metastatic breast cancer, lymph node metastasis, elevated serum alkaline phosphatase, lactate dehydrogenase were associated with postoperative prognosis. Pathological types of metastatic breast cancer, multiple bone metastasis, organ metastases, and elevated serum lactate dehydrogenase were associated with 3-year survival. Then those significant variables and serum alkaline phosphatase counts were integrated to construct nomograms for 3-year survival. The C-statistic of the established predictive model was 0.83. The calibration plot presents a graphical representation of calibration. In the decision curve analysis, the benefits are higher than those of the extreme curve. The receiver operating characteristic of the external validation of the model was 0.82, indicating a favored fitting degree of the two models.ConclusionOur study suggests that several clinical features and serological markers can predict the overall survival among the patients who are about to receive bone metastasis surgery after breast cancer surgery. The model can guide the preoperative evaluation and clinical decision-making for patients. Level of evidence Level III, prognostic study.

The Combined Prognostic Significance of Alkaline Phosphatase and Intracranial Arterial Calcifications in Hemodialysis Patients

Introduction: The prevalence of intracranial arterial calcification (ICAC) in maintenance hemodialysis (MHD) patients is about 90%, and its severity is correlated with age, hemodialysis vintage, and mineral bone disease. Elevated concentrations of calcium and phosphorus are not sufficient for medial calcification because of inhibition by pyrophosphate. Alkaline phosphatase (ALP) promotes calcification by hydrolyzing extracellular pyrophosphate. Epigenetic mechanisms involving ALP inhibition by apabetalone were investigated as a potential target for preventing vascular calcifications (VCs). This study assessed the combined impact of VCs and elevated serum ALP on mortality among chronic HD patients. Methods: VCs represented by ICAC were measured simultaneously with mineral bone disease parameters including serum ALP of MHD patients who underwent noncontrast brain computed tomography from 2015 to 2018 in our institution. Results: This retrospective study included 150 MHD patients (mean age 71.3 ± 12.1 years, 60.1% male). Of the total cohort, 12 (7.8%) had no brain calcifications and 69 (45.1%) had multiple intracranial calcifications. Considering the patients with normal ALP and no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 4.6 (95% CI: 1.7–12.7) among patients with brain calcifications and normal ALP (p = 0.003) and odds ratios for all-cause mortality of 6.1 (95% CI: 2.1–17.7) among patients with brain calcifications and elevated ALP (p= 0.001). Conclusion: We found an independent association between ICAC and the risk of death among MHD patients. The combined effect of ICAC and elevated ALP was associated with a higher odds ratio for all-cause mortality in MHD patients and may contribute to the risk stratification of these patients.

Clear Cell Chondrosarcoma-Oncological Outcomes in an Asian Cohort.

Clear cell chondrosarcoma is a rare subtype of chondrosarcoma, included in the category of low-grade (grade 1) sarcomas of the bone. We evaluated the results of treatment of these rare tumours at our institute and documented their outcomes in a hitherto unreported ethnic (Asian) cohort. Of the 480 extremity and pelvic chondrosarcomas diagnosed between January 2006 and December 2017 at our institute, 12 (2.5%) were clear cell chondrosarcoma. There were 11 male patients and one female patient. The mean age was 35years (range 24-51years). Mean duration of symptoms was 6months and all cases were in the long bones; 8 cases in the femur, 2 in the humerus, and 1 each in the tibia and fibula. All cases were non metastatic at presentation Three patients were excluded from final analysis as they did not seek treatment at our hospital after initial presentation. Seven of nine cases had elevated alkaline phosphatase levels (mean value of 342 and range of 94-1353). Eight cases underwent wide excision while one case who had curettage elsewhere and presented to us with no evidence of residual disease was managed with watchful observation. None of the patients received adjuvant chemotherapy or radiotherapy. There were no local or distant recurrences at a median follow-up of 73months (range 43-244months). Seven of nine cases had elevated alkaline phosphatase levels (mean value of 342 and range of 94-1353). Eight patients were alive and disease free at last follow-up while one had died due to an unrelated cause at 76months after index surgery. Clear cell chondrosarcomas comprised only 2.5% (12 of 480) of all chondrosarcomas in our study. Elevated serum alkaline phosphatase levels may serve as a surrogate marker to help in diagnosis. Wide excision in clear cell chondrosarcomas is recommended and provides excellent oncological outcomes.

Transient Hyperphosphatasemia Following Pediatric Kidney Transplant.

IntroductionTransient hyperphosphatasemia (TH) is a rare benign condition of elevated serum alkaline phosphatase (AP) levels seen in healthy children. TH has been reported to occur in pediatric solid organ transplants, including kidney transplant patients. Little is known about TH in pediatric kidney transplant patients.ObjectiveTo evaluate the incidence and natural history of TH in pediatric kidney transplant patients.MethodsA retrospective chart review of patients < 18 years of age who underwent kidney transplantation at the University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between 2008 and 2019 was performed to identify patients with TH, defined as an AP level greater than 1,000 IU/L. Exclusion criteria included repeat kidney transplants or kidney transplant as part of a multiorgan transplant.ResultsOne hundred seventy-six patients underwent a solitary kidney transplant, of which 87 were less than 12 years of age. Eleven patients (6.5%) were found to have TH, all of whom were < 12 years of age (12.8%) (median age: 5 years; range: 1 - 11 years). The median AP level prior to transplant was 183 IU/L (range: 104 - 309 IU/L) and the median peak AP was > 2,300 IU/L (range: 1,227 - 4,912 IU/L). The median time from a kidney transplant to the diagnosis of TH was 0.6 years (range: 0.3 to 7.7 years). The median length of time that TH persisted was 0.5 years (range: 0.2 to 0.9 years). The median estimated glomerular filtration rate (GFR) at the time of diagnosis of TH was 84 mL/min/1.73m2 per the bedside Schwartz equation (range: 45 to 152 mL/min/1.73m2). One patient had variable AP levels over nine months prior to resolution; the other 10 patients had a solitary peak of AP prior to resolution. No patient required treatment of elevated AP levels and the TH resolved spontaneously without intervention. No patients had significant abnormalities of markers of metabolic bone disease or were on active vitamin D, calcium, or phosphorus supplements. Two patients reported bone pain, and one patient was found to have avascular necrosis of the hip.ConclusionsTH is a relatively common finding following a pediatric kidney transplant in pre-pubertal children less than 12 years of age. It primarily occurs in the first year following a kidney transplant and usually resolves without recurrence within one year of onset.

Factor analysis of Traditional Chinese Medicine syndromes and clinical characteristics of patients with secondary hyperparathyroidism maintained by hemodialysis: A cross-sectional study

IntroductionSecondary hyperparathyroidism (SHPT) causes damage to skeletal, cardiovascular, and nervous systems and is common in the maintenance of hemodialysis (MHD) patients. This study explored association between the clinical characteristics of traditional Chinese medicine (TCM) syndromes in MHD patients with SHPT. MethodsEligible patients were identified from two hemodialysis centers in Wuhan, Hubei, China between June 2019 and December 2019. All participants were requested to complete questionnaires containing demographic and clinical information. TCM syndrome was defined by the physicians. Laboratory parameters were abstracted by medical records review. Multivariate logistic regression and ridge regression were applied to identify factors associated with SHPT.Sensitivity analysis was adopted to test robustness of results. ResultsA total of 177 MHD patients were recruited. Multivariate logistic regression indicated Yang deficiency of the spleen and kidney syndrome (OR 2.768; 95%CI 1.074-7.134); male (OR 2.525; 95%CI 1.110-5.744); hypocalcemia (OR 0.158; 95%CI 0.028-0.897); the elevation of serum creatinine (OR 1.003; 95%CI 1.002-1.005), alkaline phosphatase (OR 1.018; 95%CI 1.008-1.029) and neutrophil to lymphocyte ratio (OR 2.101; 95%CI 1.462-3.020) level appeared to be factors associated with SHPT in MHD patients. Ridge regression suggested dialysis duration was one of the factors of SHPT, others were the same as logistic regression results. Sensitivity analysis showed the association between gender and SHPT was not significant. ConclusionYang deficiency of the spleen and kidney syndrome, systemic inflammation, hypocalcemia, elevated serum creatinine and alkaline phosphatase level appeared to be associated with SHPT in MHD patients. These results demonstrate an integrated traditional Chinese and western medicine perspective.

Adjunct Fenofibrate Up-regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis.

Accumulation of cytotoxic bile acids (BAs) during cholestasis can result in liver failure. Glucuronidation, a phase II metabolism pathway responsible for BA detoxification, is regulated by peroxisome proliferator–activated receptor alpha (PPARα). This study investigates the efficacy of adjunct fenofibrate therapy to up‐regulate BA‐glucuronidation and reduce serum BA toxicity during cholestasis. Adult patients with primary biliary cholangitis (PBC, n = 32) and primary sclerosing cholangitis (PSC, n = 23), who experienced an incomplete response while receiving ursodiol monotherapy (13‐15 mg/kg/day), defined as serum alkaline phosphatase (ALP) ≥ 1.5 times the upper limit of normal, received additional fenofibrate (145‐160 mg/day) as standard of care. Serum BA and BA‐glucuronide concentrations were measured by liquid chromatography–mass spectrometry. Combination therapy with fenofibrate significantly decreased elevated serum ALP (−76%, P < 0.001), aspartate transaminase, alanine aminotransferase, bilirubin, total serum BAs (−54%), and increased serum BA‐glucuronides (+2.1‐fold, P < 0.01) versus ursodiol monotherapy. The major serum BA‐glucuronides that were favorably altered following adjunct fenofibrate include hyodeoxycholic acid–6G (+3.7‐fold, P < 0.01), hyocholic acid–6G (+2.6‐fold, P < 0.05), chenodeoxycholic acid (CDCA)–3G (−36%), and lithocholic acid (LCA)–3G (−42%) versus ursodiol monotherapy. Fenofibrate also up‐regulated the expression of uridine 5′‐diphospho‐glucuronosyltransferases and multidrug resistance–associated protein 3 messenger RNA in primary human hepatocytes. Pearson’s correlation coefficients identified strong associations between serum ALP and metabolic ratios of CDCA‐3G (r2 = 0.62, P < 0.0001), deoxycholic acid (DCA)‐3G (r2 = 0.48, P < 0.0001), and LCA‐3G (r2 = 0.40, P < 0.001), in ursodiol monotherapy versus control. Receiver operating characteristic analysis identified serum BA‐glucuronides as measures of response to therapy. Conclusion: Fenofibrate favorably alters major serum BA‐glucuronides, which correlate with reduced serum ALP levels and improved outcomes. A PPARα‐mediated anti‐cholestatic mechanism is involved in detoxifying serum BAs in patients with PBC and PSC who have an incomplete response on ursodiol monotherapy and receive adjunct fenofibrate. Serum BA‐glucuronides may serve as a noninvasive measure of treatment response in PBC and PSC.

Jaundice in patients with COVID-19.

Background and AimWhile many studies have reported on liver injury in patients with coronavirus disease 2019 (COVID‐19), none have specifically addressed the significance of hepatic jaundice. We aimed to determine the clinical consequences and etiologies of jaundice in patients with COVID‐19.MethodsWe retrospectively analyzed clinical features, laboratory abnormalities, and rates of survival and intensive care unit admission in 551 patients with COVID‐19, hospitalized between 1 March 2020, and 31 May 2020 at a tertiary care academic medical center. Hepatic jaundice was defined as a serum total bilirubin concentration >2.5 mg/dL and a direct bilirubin concentration >0.3 mg/dL that was >25% of the total. Liver injury was characterized as cholestatic, mixed, or hepatocellular at the time of peak serum total bilirubin concentration by calculating the R factor.ResultsHepatic jaundice was present in 49 (8.9%) patients and associated with a mortality rate of 40.8% and intensive care unit admission rate of 69.4%, both significantly higher than for patients without jaundice. Jaundiced patients had an increased frequency of fever, leukopenia, leukocytosis, thrombocytopenia, hypotension, hypoxemia, elevated serum creatinine concentration, elevated serum procalcitonin concentration, and sepsis. Nine jaundiced patients had isolated hyperbilirubinemia. Of the 40 patients with abnormally elevated serum alanine aminotransferase or alkaline phosphatase activities, 62.5% had a cholestatic, 20.0% mixed, and 17.5% hepatocellular pattern of liver injury.ConclusionHepatic jaundice in patients with COVID‐19 is associated with high mortality. The main etiologies of liver dysfunction leading to jaundice appear to be sepsis, severe systemic inflammation, and hypoxic/ischemic hepatitis.

Incidental Finding of Extreme Elevation of Serum Alkaline Phosphatase in Pregnancy

Increased levels of alkaline phosphatase (ALP) should alert us to changes in the liver, kidney, bone and malignancy. However, there is a physiological increase in pregnancy up to twice the upper limit. There has been a paucity of cases reporting extreme elevations of ALP in pregnancy. This is a case of an incidental pregnancy finding of a 24-fold increase in ALP in the third trimester (2877 U/L). The patient was kept under surveillance and ALP levels were monitored during the postpartum period.Literature suggests a correlation between ALP elevation and several perinatal complications, proposing it could represent an important tool in monitoring high-risk pregnancies and underlying placental damage. We report a case with no perinatal complications and normal labor at term, with a placenta showing lesions of chronic villitis. We should not rely exclusively on an isolated, marked rise in ALP to dictate the approach in the absence of other fetomaternal considerations.

Early histopathologic changes in primary biliary cholangitis: does 'minimal change' primary biliary cholangitis exist? A pathologist's view.

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is an autoimmune, slowly progressive, cholestatic liver disease characterized by nonsuppurative destructive cholangitis, and interlobular bile duct destruction. Necroinflammatory activities of the hepatic parenchyma and limiting plates of milder form along with late liver fibrosis may develop. Serum liver tests include elevated serum alkaline phosphatase along with a positive antimitochondrial antibody (AMA) in nearly 95% of patients. Liver biopsies are an important confirmatory and staging tool and are additionally very helpful when AMA is negative. More specifically, the earliest changes in liver biopsy suspicious for PBC can be detected, namely loss of the canals of Hering (CoH), as proposed by various authors recently. CoH loss has been described as an early feature of PBC. We focus on early histologic features of PBC, investigating through the literature the possible role of 'minimal change' supporting the clinical diagnosis of PBC, even in the absence of characteristic granulomatous duct destructive lesions.

Serum uric acid, lipid profile and alkaline phosphatase levels in ischemic cerebrovascular accident patients

Background: Stroke or cerebrovascular accident (CVA) is noted as the second cause of mortality, especially in the elderly population. Recent studies indicated that higher concentrations of uric acid are involved in various vascular diseases. The findings of previous investigations suggest that, elevated serum alkaline phosphatase (ALP) levels may have a pathophysiological character in the occurrence of atherosclerotic vascular disease (AVD) of the heart and brain. This study evaluated the association between serum uric acid (SUA) levels, serum lipid levels, serum alkaline phosphatase (ALP) levels, and changes in ischemic cerebrovascular accident patients.Methods: All patients with Ischemic cerebrovascular accident age &gt;50 years were included based on their clinical, laboratory, and radiological findings (including computed tomography (CT)/magnetic resonance imaging (MRI)) those admitted in our hospital. As control group 200 healthy individuals matched for sex and age were recruited from the same demographic area.Result: Multiple logistic regression analysis findings proposed four components as significant predictors in ischemic cerebrovascular accident (serum uric acid, serum ALP, LDL and HDL. In this study, it was found, that patients with ischemic cerebrovascular accident had significant difference (p&lt;0.001) in serum uric acid and serum ALP than normal patients (non-ischemic cerebrovascular accident patients).Conclusions: Patients with ischemic cerebrovascular accident had significant difference (p&lt;0.001) in SUA and serum ALP than normal patients (non-ischemic cerebrovascular accident patients). High SUA levels were observed to be associated significantly with ischemic stroke. On the basis of our study design, we cannot clarify that the elevated levels are the risk of ischemic stroke and it requires further studies.

Comparative effects of Venlafaxine and Alendronate on Biochemical, Bone mechanical and Anti-inflammatory properties in ovariectomized rats

The drug of choice in the treatment of postmenopausal osteoporosis is alendronate. Antidepressive agents are currently used in combination with alendronate to protect against depression and may affect the condition of osteoporosis. The aim is to study the comparative effects of venlafaxine and alendronate on biochemical, bone mechanical and anti-inflammatory properties in osteoporotic induced rats. 36 female Wistar albino rats were included (6 rats/group). Treated groups were ovariectomized bilaterally to induce osteoporosis. Rats were treated orally with alendronate (3mg/kg/day) and venlafaxine (20mg/kg/day) and combined alendronate and venlafaxine for 28 days. Body weight, serum alkaline phosphates, serum calcium, three point bending test, bone mineral mass and inflammatory cytokines The induction of osteoporosis showed significant elevated serum alkaline phosphatase, decreased serum calcium, body weight, bone mineral mass and inflammatory cytokines. Venlafaxine treatment did not ameliorate the changes in tested parameters, where at end of the experiment alendronate has significant improved with serum alkaline phosphatase, serum calcium, bone mineral mass, bone mineral density. The improvement was not affected by combining venlafaxine with alendronate whereas the venlafaxine treatment alone caused a significant deterioration of tested parameters. Venlafaxine is an anti-depressive agent that inhibits brain serotonin which leads to decrease in bone formation. Hence, from the above findings the combination of alendronate and venlafaxine showed worsen the condition of osteoporosis rats.

Further delineation of PIGB-related early infantile epileptic encephalopathy

Pathogenic variants in phosphatidylinositol glycan anchor biosynthesis class B (PIGB) gene have been first described as the cause of early infantile epileptic encephalopathy 80 (EIEE-80) in 2019. This disorder, an inherited glycosylphosphatidylinositol deficiency, is associated with a complex neurologic phenotype, including developmental delay, early-onset epilepsy and peripheral neuropathy. We report on a 5 year-old girl born from consanguineous parents, manifesting severe global developmental delay with absent speech, mixed peripheral polyneuropathy, hypotonia, bilateral equino-varo-supinated-cavus foot, early-onset scoliosis, elevated serum alkaline phosphatase and a single episode of febrile status epilepticus. Hypomyelination was documented on brain MRI. Whole-exome sequencing (WES) disclosed the likely pathogenic biallelic PIGB NM_004855.4: c.463G > C, p.(Asp155His) missense variant. In our patient, while other characteristic clinical, neuroimaging and laboratory findings (as described in the first research paper) were present, seizures were not a major clinical issue, thus contributing to our knowledge on this ultra-rare disorder.

Lactobacillus acidophilus LA14 Alleviates Liver Injury.

ABSTRACTAlthough the probiotic Lactobacillus acidophilus LA14 is used worldwide, its effect on liver diseases remains unelucidated. Here, 32 rats were divided into four groups, gavaged with L. acidophilus LA14 (3 × 109 CFU) or phosphate-buffered saline for 7 days, and then intraperitoneally injected with d-galactosamine or saline. After 24 h, blood, liver, ileum, and feces samples were collected for liver injury, inflammation, intestinal barrier, gut microbiota, metabolome, and transcriptome analyses. Pretreatment with L. acidophilus LA14 alleviated the d-galactosamine-induced elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bile acids; mitigated the histological injury to the liver and gut; and suppressed the inflammatory cytokines macrophage inflammatory protein 1α (MIP-1α), MIP-3α, and MCP-1. L. acidophilus LA14 also ameliorated the d-galactosamine-induced dysbiosis of the gut microbiota and metabolism, such as the enrichment of Bacteroides sp. strain dnLKV3 and the depletion of Streptococcus, butanoic acid, and N-acetyl-d-glucosamine. The underlying mechanism of L. acidophilus LA14 included prevention of not only the d-galactosamine-induced upregulation of infection- and tumor-related pathways but also the d-galactosamine-induced downregulation of antioxidation-related pathways during this process, as reflected by the liver transcriptome and proteome analyses. Furthermore, the administration of L. acidophilus LA14 to healthy rats did not alter the tested liver indicators but significantly enriched the beneficial Lactobacillus and Bifidobacterium species, promoted metabolism and regulated pathways to improve immunity. The ability of L. acidophilus LA14 to alleviate liver injury was further confirmed with an acetaminophen-induced mouse model. These results might provide a reference for future studies on the application of L. acidophilus LA14 for the prevention of liver injury.IMPORTANCE The probiotic Lactobacillus acidophilus LA14 is widely used, but its effect on liver diseases has not been elucidated. We explored the protective effect of L. acidophilus LA14 on the liver using rats with d-galactosamine-induced liver injury. Pretreatment with L. acidophilus LA14 alleviated the d-galactosamine-induced elevation of serum ALT, AST, ALP, and bile acids, mitigated the histological injury to the liver and gut, and suppressed the inflammatory cytokines MIP-1α, MIP-3α, and MCP-1. These effects were correlated with the modulations of the gut microbiome, metabolome, and hepatic gene expression induced by L. acidophilus LA14. Moreover, the ability of L. acidophilus LA14 to alleviate liver injury was further confirmed with an acetaminophen-induced mouse model. These results might provide a reference for future studies on the application of L. acidophilus LA14 for the prevention of liver injury.

Serum Alkaline Phosphatase Levels and Increased Risk of Brain Hemorrhage in Hemodialysis Patients: The Q-Cohort Study.

Aim: Elevated serum alkaline phosphatase (ALP) levels have been associated with increased risks of all-cause and cardiovascular mortality in patients receiving hemodialysis. However, little is known about the impact of serum ALP levels on the development of stroke, such as brain hemorrhage and infarction. Methods: A total of 3,497 patients receiving maintenance hemodialysis registered in the multicenter observational Q-Cohort Study were analyzed. The primary outcomes were the incidences of brain hemorrhage and infarction. The covariate of interest was serum ALP levels. Patients were divided into tertiles based on their serum ALP levels (U/L) at baseline (T1, ＜69.3; T2, 69.3–98.4; T3, ＞98.4). The risks of brain hemorrhage, brain infarction, and composite stroke were estimated using Cox proportional hazards models and competing risk models with all-cause death as a competing risk. Results: A total of 89 patients developed brain hemorrhage and 195 patients developed brain infarction during the 4-year follow-up period. The risk of brain hemorrhage in the highest tertile (T3) was significantly higher than that in the lowest tertile (T1) (multivariable-adjusted hazard ratio [95% confidence interval], 1.93 [1.12–3.35], subdistribution hazard ratio, 1.91 [1.10–3.30]). However, there was no significant association between serum ALP levels and the risk of brain infarction or composite stroke. Conclusions: Higher serum ALP levels are associated with an increased risk of brain hemorrhage, but not brain infarction, in patients receiving maintenance hemodialysis. High serum ALP level is thus an important risk factor for brain hemorrhage in hemodialysis patients.

Transient hyperphosphatasemia: Possible association with pediatric acute respiratory infection.

ABSTRACTImportanceAcute respiratory infections are quite prevalent in children. Transient hyperphosphatasemia (TH) is defined as the transient elevation of serum alkaline phosphatase (ALP) level, which occurs mainly in infants and children without liver or bone disorders. Although no apparent cause has been identified, a possible association of respiratory infections with TH has been reported in the literature.ObjectiveIn this study, we aimed to investigate the association between TH and respiratory infectious diseases.MethodsWe collected the results of biochemical investigations, including ALP level, for a period of 5 years in our hospital. We then examined the patients with transiently elevated ALP levels of > 2000 U/L.ResultsDuring the observation period, 1501 blood samples were collected from 1097 patients. Marked elevation of serum ALP level was observed in 12 patients. All patients with hyperphosphatasemia, except for one with Fanconi syndrome attributable to the underlying Wilson’s disease, were aged < 5 years and were diagnosed with TH. Ten of these 11 patients with TH had acute respiratory infections. Marked ALP elevation was not found in any patients with non‐inflammatory diseases. ALP isoenzyme profiles showed a characteristic pattern in all six patients in whom the ALP isoenzyme test was conducted.InterpretationOur results suggest an association between respiratory infections and TH. The consideration of TH in patients with acute respiratory infections may lead to earlier and accurate diagnosis of this condition, thereby avoiding unnecessary medical interventions.