Increased Serum Alkaline Phosphatase Research Articles

Statin Induced Changes in Rat Pancreatic Tissue: A Histological and Biochemical Perspective

Objective: This study aimed to elucidate the effects of simvastatin on pancreatic histomorphology and biochemical profile in a rat model. Method: Forty male Sprague-Dawley rats weighing 250 g were divided into two equal groups: a control group (A) and an experimental group (B) treated with simvastatin 60 mg/kg/day for 12 weeks. At the end of the experiment, the rats were euthanized, and their pancreas was collected for analysis and examined using gold-standard histological parameters including inflammation and fatty infiltration. Biochemical parameters i.e. serum amylase and alkaline phosphatase were also analysed. Statistical Package for the Social Sciences (SPSS) software version 23 was employed for data analysis. Mean ± SD was employed to express quantitative variables. Qualitative variables were expressed as frequencies and percentages. Chi-square tests compared qualitative variables while independent sample t-tests compared quantitative variables between groups, with P < 0.05 defining statistical significance. Results: The administration of Simvastatin resulted in a substantial induction of pancreatic inflammation and fatty infiltration, accompanied by notable alterations in the biochemical profile. Specifically, there was a significant reduction in serum amylase levels and a concomitant increase in serum alkaline phosphatase (ALP) levels, as compared to the control group. Conclusion: This study demonstrates that simvastatin profoundly alters pancreatic histomorphology in rats, resulting in marked inflammation, necrosis, fatty infiltration, and interstitial fibrosis. These novel findings provide unique insights into simvastatin's effects on pancreatic morphology using a robust animal model. Keywords: Simvastatin; Sprague-Dawley rats; pancreatic histomorphology, Amylase, Alkaline phosphatase.

Potential for the development of Taraxacum mongolicum aqueous extract as a phytogenic feed additive for poultry.

Taraxacum mongolicum (TM) is a kind of medicinal and edible homologous plant which is included in the catalogue of feed raw materials in China. It is rich in polyphenols, flavonoids, polysaccharides and other active substances, and shows many benefits to livestock, poultry and aquatic products. The study aimed to assess the potential of TM aqueous extract (TMAE) as a substitute for poultry AGPs. A total of 240 one-day-old Arbor Acker broilers were randomly assigned to four groups and fed a basal diet (Con) supplemented with 500, 1000, and 2000 mg/kg TMAE (Low, Medium, and High groups). The growth performance of the broilers was measured on day 21 and day 42. At the end of the trial, the researchers measured slaughter performance and collected serum, liver, spleen, ileum, and intestinal contents to investigate the effects of TMAE on serum biochemistry, antioxidant capacity, immune function, organ coefficient, intestinal morphology, flora composition, and short-chain fatty acids (SCFAs). The results showed that broilers treated with TMAE had a significantly higher average daily gain from 22 to 42 days old compared to the Con group. Various doses of TMAE resulted in different levels of improvement in serum chemistry. High doses increased serum alkaline phosphatase and decreased creatinine. TMAE also increased the antioxidant capacity of serum, liver, and ileum in broilers. Additionally, middle and high doses of TMAE enhanced the innate immune function of the liver (IL-10) and ileum (Occludin) in broilers. Compared to the control group, the TMAE treatment group exhibited an increase in the ratio of villi length to villi crypt in the duodenum. TMAE increased the abundance of beneficial bacteria, such as Alistipes and Lactobacillus, while reducing the accumulation of harmful bacteria, such as Colidextracter and Sellimonas. The cecum's SCFAs content increased with a medium dose of TMAE. Supplementing broiler diets with TMAE at varying doses enhanced growth performance and overall health. The most significant benefits were observed at a dose of 1000 mg/kg, including improved serum biochemical parameters, intestinal morphology, antioxidant capacity of the liver and ileum, immune function of the liver and ileum, and increased SCFAs content. Lactobacillus aviarius, norank_f_norank_o__Clostridia_UCG-014, and Flavonifractor are potentially dominant members of the intestinal microflora. In conclusion, TMAE is a promising poultry feed additive and 1000 mg/kg is an effective reference dose.

The Clinical Utility of the Saliva Proteome in Rare Diseases: A Pilot Study for Biomarker Discovery in Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to comprehensively screen for novel biomarkers. Saliva samples of PSC patients and healthy controls were processed and subsequently analyzed using a liquid chromatography-tandem mass spectrometry technique. A bioinformatic approach was applied to detect the differentially expressed proteins, their related biological functions and pathways, and the correlation with the clinical evidence in order to identify a possible marker for the PSC group. We identified 25 differentially expressed proteins in PSC patients when compared to the healthy control group. Among them, eight proteins exhibited area under the curve values up to 0.800, suggesting these saliva proteins as good discriminators between the two groups. Multiple positive correlations were also identified between the dysregulated salivary proteins and increased serum alkaline phosphatase levels and the presence of ulcerative colitis. Pathway analysis revealed significant enrichments in the immune system, neutrophil degranulation, and in the interleukine-17 signaling pathway. We demonstrated the potentiality of saliva as a useful biofluid to obtain a fingerprint of the pathology, suggesting disulfide-isomerase A3 and peroxiredoxin-5 as the better discriminating proteins in PSC patients. Hence, analysis of saliva proteins could become, in future, a useful tool in the screening of patients with suspected PSC.

Low dietary oyster mushroom spent substrate limitedly ameliorates detrimental effects of feeding combined marula seed cake and mucuna seed meal as soya bean replacements in broiler chickens

This study investigated ameliorative effects of dietary oyster mushroom (Pleurotus ostreatus) spent substrate (OMSS) in broiler chickens fed diets supplemented with combined marula seed cake (MSC) and mucuna seed meal (MSM) replacing soya bean meal (SBM). In a completely randomised design (CRD), 400 day-old Ross 308 chicks were randomly allocated to 5 iso-nitrogenous-energetic diets (control with 100% SBM, control with 60% MSC and 40% MSM replacing SBM (MSC + MSM), MSC + MSM with 1.25% OMSS, MSC + MSM with 2.5% OMSS, and MSC + MSM with 5% OMSS) each with 8 replicate pens of 10 during starter, grower and finisher phases. Dietary MSC + MSM decreased (P < 0.001) feed intake (FI), body weight gain (BWG), and feed conversion efficiency (FCE); slaughter weight, hot carcass weight (HCW), cold carcass weight (CCW), breast weight, and back lengths (P < 0.001); serum SDMA and alanine transaminase (P < 0.05). In contrast, it increased the weights of the thigh (P < 0.001), wing (P < 0.01), liver (P < 0.001), proventriculus (P < 0.001), gizzard (P < 0.001), duodenum (P < 0.001), jejunum (P < 0.001), ileum (P < 0.001), and caecum (P < 0.01) and serum alkaline phosphatase (P < 0.05) and cholesterol (P < 0.01). Further, it increased meat redness and decreased its hue angle at 45 min post-slaughter (P < 0.01) whilst it decreased its pH (P < 0.01) and increased its shear force (P < 0.05) at 24 h post-slaughter. Compared to higher levels, low (1.25%) dietary OMSS improved, though limitedly, FI, BWG, and FCE at grower and finisher phases only (P < 0.001) whilst it reversed MSC plus MSM-induced deleterious effects on slaughter weight, HCW, and CCW (P < 0.001) and increases in gizzard weight (P < 0.001) and meat shear force at 24 h post-slaughter (P < 0.05). Otherwise, OMSS generally decreased (P < 0.05) serum SDMA and alanine transaminase whilst it abrogated and augmented increases in serum alkaline phosphatase (P < 0.05) and cholesterol (P < 0.01), respectively, and reversed the increase and decrease in meat redness (P < 0.01) and hue angle (P < 0.05), respectively. In conclusion, dietary replacement of SBM with combined MSC plus MSM induced deleterious effects in broiler chickens that were limitedly abrogated by low (1.25%) inclusion level of OMSS.

A Systematic Review and Meta Analysis of Non-Randomized Interventional Studies on the Pamidronate Treatment Efficacy for Patients with Bone Fibrous Dysplasia

Objective: Pamidronate is one of the main therapies for Fibrous Dysplasia (FD), with documented enhancements in patients' clinical characteristics. Nevertheless, its usage has yielded inconclusive results. Therefore, this review aimed to investigate pamidronate’s impact on several clinical and biochemical outcomes in FD patients. Materials and Methods: This review was conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, ProQuest, Wiley, and EBSCO search databases were used to search the literature. Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) was applied for quality assessment of the included studies and Review Manager (RevMan) 5.4 was employed in performing the meta-analysis. Results: There are eight and seven studies used in the meta-analysis and systematic review, respectively. The results showed there are two studies with a low risk of bias and six with a moderate category. All papers included in this meta-analysis showed significant differences in the reduction of bone pain (p&lt;0.00001) and serum alkaline phosphatase (SAP) (p=0.04) after pamidronate treatment compared to the before-treatment groups. Conclusion: The findings of this study indicated that pamidronate therapy had been proven to significantly reduce bone pain and increase SAP in FD patients. However, trials with more age-specific samples and a lower risk of bias should be carried out to determine the statistical significance of overall results.

Hepatic Response and Progression Criteria in Light Chain Amyloidosis: A Multicenter Validation Study

Background: Liver involvement in light chain amyloidosis (AL) is seen in up to 20% of patients and is typically encountered as part of multi-organ involvement. Liver involvement is associated with a poor prognosis. The goal of this study was to assess the prognostic impact of the hepatic response criteria, which were published in 2005 and were not broadly assessed for their prognostic value. Patients and methods: Ten centers across the USA and Europe participated in this study.AL amyloidosis patients who were diagnosed between 2010 and 2015, had liver involvement with serum alkaline phosphatase (AP) &amp;gt;1.5 upper reference limit (URL), and achieved hematologic response to therapy were included in this study. Hepatic response was assessed at 6, 12, and 24 months from therapy initiation and at best response. Based on a receiver operation characteristic analysis, a 50% reduction in AP was set as the optimal cut point for discrimination of 5-year overall survival (OS) in the 12-months response assessment landmark (area under the curve 0.67). Therefore, hepatic response was defined as a reduction in AP &amp;gt;50% from baseline value in addition to AP normalization, regardless of AP percentage reduction. Hepatic progression was defined as &amp;gt;50% increase in serum AP. OS was assessed from therapy initiation until death or last follow-up and was plotted using the Kaplan-Meier method. The log-rank test used to compare survival between groups. For fixed-time point survival analysis, patients who died before the landmark were excluded. Hepatic response at a fixed time points, when missing, was imputed based on available data from adjacent time points (imputation of hepatic response was performed in 15%, 23%, and 22% of evaluable patients at 6-, 12-, and 24-month landmarks, respectively). Multivariate Cox proportional models were set to determine independent prognostic factors for OS using variables with p-value &amp;lt;0.1 in a univariate analysis. P-values &amp;lt;0.05 were considered significant. Results: One hundred and sixteen patients (n=116) are included. The median age was 60 years, and the median serum AP was X2.6 URL. Concomitant kidney involvement was present in 63.8% of patients, while coexisting heart involvement was seen in 56% of patients. Hematologic VGPR or better was achieved in 69% of patients. AP decrease deepened with time, with a median reduction at 6-, 12-, 24-months and best response being 22%, 34%, 53%, and 56%, respectively. Overall, 65% of patients (n=75) achieved hepatic response, of whom 71 patients based on reduction in AP &amp;gt;50% and 4 patients for reaching AP within normal reference but not meeting &amp;gt;50% reduction in AP (40- 46% reduction in AP). The median time to hepatic response was 13.8 months, longer for patients undergoing autologous stem cell transplantation (ASCT) as their primary therapy compared to non-transplant therapies (24 vs 12.6 months, P=0.1). With a median follow-up of 105 months, 42 patients died (36.2% of the study cohort). The 2-, 5- and 10-year OS rates were 83%, 67%, and 61%, respectively. Achievement of hepatic response as early as 12 months and at best response was associated with a longer survival (Figure). Hepatic response was an independent prognostic factor in a multivariate analysis, after adjusting for other known prognostic factors (age, cardiac stage, hematologic response, and primary therapy). Predictors of hepatic response include higher baseline AP level, lower total bilirubin, hematologic ≥VGPR, and cardiac and renal responses, when applicable. Hepatic progression was borderline associated with inferior OS (5-year OS 47% vs 70% among non-progressors, P=0.08). Conclusions: Hepatic response and progression measured by the change in alkaline phosphatase are prognostic in AL amyloidosis. These criteria are independent of other prognostic markers, and thus may have clinical implications for patients' care.

Cytoreductive nephrectomy and its effect on prognosis in patients with disseminated renal cell carcinoma receiving treatment in wide clinical practice

Aim. To evaluate the effect of cytoreductive nephrectomy (CN) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to identify a group of patients who are candidates for cytoreductive surgical treatment.Materials and methods. We retrospectively analyzed a database of 403 patients with mRCC treated at the Moscow City Oncological Hospital No. 62 and the City Clinical Oncological Dispensary (Saint Petersburg) between 2006 and 2022. In total, 330 (81.9 %) patients underwent CN. All patients received systemic anti-tumor therapy: targeted anti-angiogenic therapy - 317 (78.6 %), cytokines - 61 (15.1 %), checkpoint inhibitors - 25 (6.2 %). The groups of operated and non-operated patients were unbalanced: CN was more often not performed in patients with multiple metastases, bone and liver lesions, laboratory abnormalities (anemia, increased serum alkaline phosphatase and lactate dehydrogenase) and unfavorable prognosis per IMDC (International mRCC Database Consortium) classification (p &gt;0.05 for all). Results. CN was associated with a significant increase in OS compared with primary tumor preservation in situ: median OS was 36 months with 95 % confidence interval 29.1-37.1, and 11 months with 95 % confidence interval 8.1-21.3, respectively (p &lt;0.0001). The benefit for OS in the CN group was also observed in clear-cell mRCC (p &lt;0.0001), grade G3 (p &lt;0.0001), multiple metastases (p &lt;0.0001) groups, and in the IMDC poor prognosis group (p &lt;0.0001). Conclusion. CN in selected mRCC patients results in a significant increase in OS. Further research is needed to determine selection criteria for surgical treatment candidates.

Risk factors for the comorbidity of osteoporosis/osteopenia and kidney stones: a cross-sectional study.

To evaluate whether low femoral neck bone mineral density (BMD) was associated with a higher risk of kidney stones, and identify risk factors for the comorbidity of osteoporosis/osteopenia and kidney stones. We analyzed individuals aged ≥ 20 years from National Health and Nutrition Examination Survey 2007-2020 data. Osteoporosis/osteopenia is defined as any T-score < -1.0 of femoral neck, total femoral, and mean lumbar spine (L1-L4) BMD. Dietary intakes (sodium, potassium, magnesium, calcium, phosphorus, calcium/phosphorus, vitamin D (25OHD2+25OHD3)) and serum parameters (sodium, potassium, calcium, phosphorus, bicarbonate, vitamin D, alkaline phosphatase (ALP)) were screened for identifying risk factors for the comorbidity. The prevalence of comorbidity of osteoporosis/osteopenia and kidney stones was 4.82%. Femoral neck BMD T-score was negatively associated with the prevalence of kidney stones (n=11,864). Dietary magnesium intake, serum phosphorus, and bicarbonate were negatively associated with the comorbidity prevalence, and serum ALP was positively associated with the comorbidity prevalence (n=6978). Additionally, there remain significant associations of dietary magnesium intake, serum ALP, and bicarbonate with not only femoral neck BMD T-score (n=11331), but also the prevalence of kidney stones (n=23,111) in general population. Furthermore, dietary magnesium intake was positively correlated to femoral neck BMD T-score in stone formers (SFs), while serum ALP was negatively correlated to femoral neck BMD T-score in SFs (n=1163). Low femoral neck BMD was closely associated with an increased risk of kidney stones. Low magnesium intake and increased serum ALP were associated with the increased risk of the comorbidity, as well as indicative of low femoral neck BMD T-score in SFs, which offered a clue to further clarify the mechanism leading to paradoxical calcification of bone resorption and kidney stones, and had the potential to perform personalized diagnostic workup for low BMD in SFs.

Quantification of circulating tumour cells over time in dogs with appendicular osteosarcoma.

Enumeration of circulating tumour cells (CTC) has shown promise for prognostication and guidance of therapeutic decisions in human cancers. The objective of this study was to enumerate CTC over time in dogs with naturally occurring osteosarcoma (OSA), and to determine correlation with patient outcome. Twenty-six dogs with OSA and no evidence of metastatic disease at the time of amputation were enrolled. Dogs were assessed for lung metastases and CTC prior to and following amputation, and at each chemotherapy visit. Twenty-one dogs completed the study. Nineteen dogs were euthanized and two were alive and free of metastases. Overall survival time ranged from 88 to 1058 days (median survival time (MST) 374 days). Increased serum alkaline phosphatase activity, advanced age, and higher body weight were significantly associated with lower MST. Dogs with OSA had a mean of 356 (0 to 4443) CTC/106 leukocytes. In 12 of 15 dogs that developed radiographic evidence of metastasis, a pre-metastatic CTC spike was retrospectively detectable on average 36.5 (1-100 days) days prior to metastasis and was associated with significantly shorter MST (301 ± 64 vs. 626 ± 55 days; p = .0107). In a multivariable analysis, dogs with a CTC spike were 10× more likely to die compared with those without. These results suggest that a spike in CTC frequency precedes detection of metastasis in dogs with OSA and is associated with shorter survival. More frequent enumeration of CTC in a larger cohort of dogs with OSA may be warranted.

Benign transient hyperphosphatasemia in infants and children: a retrospective database study.

Benign transient hyperphosphatasemia seems to be a disorder described among otherwise healthy infants and children, which resolves spontaneously. Other known causes of markedly elevated serum ALP should be excluded, especially bone and liver disease. Higher awareness and recognition of this benign condition are important in order to avoid unnecessary tests and parental anxiety. • Benign transient hyperphosphatasemia is a benign condition characterized by greatly increased serum alkaline phosphatase without laboratory or clinical evidence of underlying bone or liver disease, which usually resolves spontaneously, with no intervention. • In the case of an incidental finding of high serum alkaline phosphatase in an otherwise healthy infant or child with no other clinical or laboratory suspicion of bone or liver disease, we recommend repeating the alkaline phosphatase level within a few months in order to confirm the resolution of this condition. • When benign transient hyperphosphatasemia is suspected, a "wait and see" approach is optimal in order to avoid unnecessary investigations and parental anxiety.

TOXICITY PROFILES OF METHANOL EXTRACT OF CROSSOPTERYX FEBRIFUGA LEAF (AFZEL. EX G. DON) BENTH

Crossopteryx febrifuga is one of the plants used for the local treatment of some disease conditions by the people of Nigeria via its leaf, root and bark without knowing the toxic nature of the plant recipes. This research was designed to ascertain the toxicity profiles of the plant leaf. Acute toxicity was determined in two phases using rats. In sub-acute toxicity studies, haematology, histopathology and evaluation of liver function indices were conducted. In the first phase of the toxicity study, the mice showed no observable toxic effects as high as at 1000 mg/kg. However, it caused sluggishness, respiratory distress at higher doses in the second phase. On haematological indices, white blood cell, lymphocyte, erythrocytes, haemoglobin, haematocrit rose significantly across the doses administered. The liver function test revealed significant increase in serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), albumin, total protein and conjugated bilirubin while 800 mg/kg extract reduced the aspartate transaminase. On histopathology, liver revealed normal hepatocytes but dilated central vein while in kidney, renal corpuscle, glomeruli and tubule were normal. On heart, revealed was active vascular congestion with normal bundle of myocardial fibres and coronary artery while in aorta, it revealed normal architecture. With the nature of the toxicity profile revealed especially at doses less than 500 mg/kg of C. febrifuga extract, the plant could be considered to be relatively safe. This study is significant as it provides information that may suggest some safe doses out of the doses used for clinical trial and application

Assessment of Liver Enzymes Activity in Patients with Rheumatoid Arthritis in Nineveh province

Aim of the study: to determine the effect of Rheumatoid Arthritis(RA) on liver enzymes level. Methods: 75 subjects were enrolled in this study (40 patients with Rheumatoid arthritis (RA) and 35 healthy subjects as control group), at Mosul city, Northern of Iraq, aged 20-70 years. The biochemical parameters measured were some of liver function tests which include measurement of the liver enzymes activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT). Results: There was a significant increase in liver enzymes activity in patients when compared to control. There was also significant increase in serum AST level at age group 40-50 years when compared to other age group in patients, in addition, there was a significant increase in serum ALP in female patients when compared to male patients. There was non-significant change in liver enzymes activity when compared according to residence, according to family history, and according to rheumatoid factor in patients. Conclusion: The results of the present study indicated no deterioration in liver functions in patients with rheumatoid arthritis regarding serum enzymes (aspartate transaminase, alanin transaminase, gamma glutamyl transferase and alkaline phosphatase), although subclinical alteration in liver functions could be expected in those patients, so that measurement of other early markers of liver dysfunction is occasionally recommended.

The Effect of Dietary Humic Substances on Cellular Immunity and Blood Characteristics in Piglets

This study’s objective was to determine the impact of dietary humic substances on immune response and blood profiles in piglets. A total of 24 crossbred piglets (Slovakian White × Landrace; 35 days old; average body weight of 11.67 kg) were allotted to two dietary groups with (experimental; 5 g·kg−1) or without (control; 0 g·kg−1) natural humic substances supplementation. In this study, we observed a significant increase of the proportion of CD4+CD8- lymphocytes (p &lt; 0.001) in the experimental group. The results also showed a tendency for an increase of the phagocytic activity and the engulfing capacity of phagocytes and the numbers of the other monitored lymphocyte subpopulations (CD3+, CD21+, CD4-D8+, CD4+CD8+, CD4+CD25+) in piglets in the experimental group compared to the control group. Supplementation of humic substances increased serum alkaline phosphatase compared to the control group (p &lt; 0.05). Other monitored blood parameters were not significantly affected by dietary treatment. It concluded that inclusion of humic substances in the diet of piglets could have a stimulating effect on cellular immunity, without a negative effect on haematological and biochemical parameters.

Cholestatic liver injury: A rare but fatal complication during and after COVID-19 infection.

The 2019 coronavirus disease (COVID-19), resulting from the severe acute respiratory syndrome 2 virus, has transformed our globe and provided a new perspective on respiratory tract infections. However, COVID-19 would not be recognized as a condition restricted to only pneumonia. This narrative review was conducted by searching manuscripts in several databases, including PubMed/ MEDLINE, Web of Science, and Reference Citation Analysis, from December 2019 to July 2022. Many studies have revealed a broad spectrum of potential systemic symptoms, including biliary complications. Although biliary injury has been observed in a very low proportion of COVID-19 patients, it is associated with increased mortalities and long-term morbidities. We identify a cholangiopathy condition in individuals during infection and after recovering from severe COVID-19, defined by a significant increase in serum alkaline phosphatase and signs of bile duct injury. Understanding the pathogeneses behind this condition would help us develop new techniques to prevent these complications. This review thoroughly discusses and summarizes the current information regarding COVID-19-associated cholangiopathy. In addition, the possible explanations for COVID-19-associated cholangiopathy are presented. Since the exact pathogenesis may not be concluded, this review could provide relevant information to encourage additional investigations shortly.

Effects of new antiseizure medication on bone metabolism and bone mineral density in children: A meta-analysis.

To explore the effect of new antiseizure medication on bone metabolism and bone mineral density in children. The Chinese and English databases (PubMed, EMBASE, Cochrane Library, CNKI, Wanfang and VIP) were systematically searched for observational studies evaluating the effects of new antiseizure medication on bone metabolism and bone mineral density in children with epilepsy. The effects of new antiseizure medication on serum calcium, phosphorus, alkaline phosphatase, bone alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone mineral density in children were systematically evaluated. After systematic retrieval and screening, 12 studies with high literature quality (including 629 epileptic children and 627 control subjects) were included in the systematic evaluation. Meta-analysis showed that new antiseizure medication decreased bone mineral density (MD: -0.05, 95%CI, -0.09, -0.02; P = 0.004). From different kinds of antiseizure medication, levetiracetam can reduce blood phosphorus concentration in children (MD: -0.04; 95%CI, -0.07, -0.01). Oxcarbazepine increased serum alkaline phosphatase in children (MD:17.98; 95%CI, 10.43,25.53; P < 0.00001), and the increase intensity was significantly higher than that of levetiracetam (MD: 7.66; 95%CI, 0.29, 15.02; P = 0.04). In addition, oxcarbazepine can cause a significant increase in parathyroid hormone in children (MD: 7.52; 95%CI, 3.37,11.66; P = 0.0004), and 25 - hydroxyvitamin D was reduced, and the difference was statistically significant (MD:-2.18; 95%CI, -3.23, -1.13; P = 0.00006). However, the effects of new antiseizure medication on serum calcium and bone alkaline phosphatase in children were not statistically significant. New antiseizure medication have different effects on bone metabolism and bone mineral density in children with epilepsy, and the effects of different types of new antiseizure medication are different.

Zinc Chloride Enhances the Antioxidant Status, Improving the Functional and Structural Organic Disturbances in Streptozotocin-Induced Diabetes in Rats.

Background and Objectives: Diabetes mellitus (DM) is a complex disease affecting the whole metabolic balance of the body and resulting in multiple organ complications: cardiovascular, neuronal, renal, etc. Our study focuses on investigating the effect of zinc chloride (Zn) on certain blood parameters suggestive for assessing the metabolic disturbances, the liver and kidney function, the oxidative stress and the immune defense capacity in experimental-induced DM with streptozotocin (STZ) and cholesterol in rats. Materials and Methods: The animals were assigned to three groups, as follows: Group 1 (Control): buffer citrate solution 0.1 mL/100 g body; Group 2 (STZ): 20 mg/kg body STZ and fat diet (10 g cholesterol/100 g diet); Group 3 (STZ+Zn): 20 mg/kg body STZ + 5 mg/kg body Zn chloride and the same fat diet. DM was induced by administering STZ in a single take daily, for three consecutive days, Zn and citrate buffer were administered orally for a month. The protocol was approved by the Ethics Committee of the University 'Grigore T Popa' Iasi, in agreement with the International Regulations about the handling of laboratory animals. Results: The use of STZ in rats fed with cholesterol was correlated with important weight gain, hyperglycemia, the intensification of the transaminases activity and the increase in serum alkaline phosphatase, cholesterol, triglyceride, urea, creatinine and in malondialdehyde. Conclusions: The treatment with Zn resulted in weight loss and a decrease in blood sugar in diabetic rats. Supplementation with Zn notably reduced oxidative stress, preserved the pancreatic architecture and restored the liver and kidney function and structure in STZ-induced DM in rats.

Clinical characteristics and long-term outcomes of 12 children with vitamin D-dependent rickets type 1A: A retrospective study.

Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by deficiency of the CYP27B1 gene. This study aims to investigate the phenotypic and genotypic features of VDDR1A children in southern China and evaluate the long-term therapeutic effects. Twelve children from southern China with VDDR1A were enrolled in this study. Their clinical, radiological, biochemical, and molecular findings were analyzed retrospectively. The rickets severity score (RSS), biochemical parameters, and height standard deviation score (HtSDS) were used to evaluate clinical outcomes. Six males and six females were included in this VDDR1A cohort. The age of onset was from 6 months to 1.8 years, and the age at diagnosis was 2.1 ± 0.8 years. The most common clinical symptoms at diagnosis were delayed walking (10/12) and severe growth retardation (9/12). HtSDS at diagnosis was negatively associated with age (p < 0.05). All patients presented with hypocalcemia, hypophosphatemia, increased serum alkaline phosphatase and parathyroid hormone, and high RSS at diagnosis. Two allelic variants of the CYP27B1 gene were identified in all patients, including nine different variants, four known and five novel, with c.1319_1325dupCCCACCC(p.Phe443Profs*24) being the most frequent. All patients were treated with calcitriol and calcium after diagnosis, and all patients but one were followed-up from 6 months to 15.6 years. HtSDS, RSS, and biochemical parameters were found to be improved during the first few years of the treatment. However, only five patients had good compliance. Although RSS and biochemical parameters were significantly improved, the HtSDS change was not significant from the time of diagnosis to the last visit, and seven patients remained of a short stature (HtSDS < -2). Our study extends the mutational spectrum of VDDR1A and finds a hotspot variant of the CYP27B1 gene in southern China. The results reconfirm the importance of early diagnosis and treatment compliance and reveal the challenge of height improvement in VDDR1A patients.

Updates on Paget's Disease of Bone.

Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.

Toxicity, genotoxicity, and carcinogenicity of 2-methylfuran in a 90-day comprehensive toxicity study in gpt delta rats.

2-Methylfuran (2-MF) exists naturally in foods and is used as a flavoring agent. Furan, the core structure of 2-MF, possesses hepatocarcinogenicity in rodents. Accumulation of toxicological information on furan derivatives is needed to elucidate their carcinogenic mode of action. In the current study, we examined the comprehensive toxicological studies of 2-MF using gpt delta rats. 2-MF was intragastrically administered to groups of 10 male and 10 female Sprague-Dawley gpt delta rats at a dose of 0, 1.2, 6, or 30mg/kg/day for 13 weeks. Effects of 2-MF on the hepatobiliary system including an increase in serum alkaline phosphatase were observed in the 6 and 30mg/kg groups, and cholangiofibrosis was found in the 30mg/kg group. The no observed adverse effect level was set at 1.2mg/kg/day for both sexes and 1.14mg/kg/day was determined as the benchmark dose low. The acceptable daily intake was calculated to be 11.4μg/kg/day. Increases in the number and areas of glutathione S-transferase placental form-positive foci in the 30mg/kg group were apparent, suggesting the hepatocarcinogenicity of 2-MF in rats. By contrast, the lack of increase in in vivo mutagenicity in the liver implied that 2-MF hepatocarcinogenesis may not involve genotoxic mechanisms.

Research on the Mechanism of Liuwei Dihuang Decoction for Osteoporosis Based on Systematic Biological Strategies.

Background Osteoporosis is an important health problem worldwide. Liuwei Dihuang Decoction (LDD) and its main ingredients may have a good clinical effect on osteoporosis. Meanwhile, its mechanism for treating osteoporosis needs to be further revealed in order to provide a basis for future drug development. Methods A systematic biological methodology was utilized to construct and analyze the LDD-osteoporosis network. After that, the human transcription data of LDD intervention in patients with osteoporosis and protein arrays data of LDD intervention in osteoporosis rats were collected. The human transcription data analysis, protein arrays data analysis, and molecular docking were performed to validate the findings of the prediction network (LDD-osteoporosis PPI network). Finally, animal experiments were conducted to verify the prediction results of systematic pharmacology. Results (1) LDD-osteoporosis PPI network shows the potential compounds, potential targets (such as ALB, IGF1, SRC, and ESR1), clusters, biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and signaling and Reactome pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) of LDD intervention in osteoporosis. (2) Human transcriptomics data and protein arrays data validated the findings of the LDD-osteoporosis PPI network. (3) The animal experiments showed that LDD can improve bone mineral density (BMD), increase serum estradiol (E2) and alkaline phosphatase (ALP) levels, and upregulate Wnt3a and β-catenin mRNA expression (P < 0.05). (4) Molecular docking results showed that alisol A, dioscin, loganin, oleanolic acid, pachymic acid, and ursolic acid may stably bind to JAK2, ESR1, and CTNNB1. Conclusion LDD may have a therapeutic effect on osteoporosis through regulating the targets (such as ALB, IGF1, SRC, and ESR1), biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) found in this research.