Serum ALP Levels Research Articles

Silybum marianum promotes growth, hepatic antioxidative activity, and splenic immunity but does not influence the intestinal barrier function of Nile tilapia, Oreochromis niloticus

Alternative additives such as phytobiotics have been a research priority to promote chemotherapeutic-free and disease-resistant aquaculture. Hence, various Silybum marianum (SM) extract levels, including 1, 2, 3, and 4 g kg−1, were supplemented with a reference diet, and the reference diet containing no SM was considered a control. Each test diet was fed in triplicate to experimental fish for 60 days. The effects were observed on growth, liver, lymphoid organs (kidney and spleen), and intestinal health in relation to a panel of blood biochemical responses of Nile tilapia, Oreochromis niloticus. Better growth performance in Nile tilapia fed any supplementation levels of SM resulted from improved feed utilization and feed conversion ratio. Microscopic observations found normal kidney, liver, and spleen microstructure across all treatments. Of interest, the antioxidative capacity of the liver was stimulated by SM supplementation, supported by higher expression of CAT, SOD, and GPx genes coupled with higher levels of hepatic GST and T-AOC and lower levels of hepatic MDA concentrations. This was further aligned with lower levels of serum ALP, AST, and ALT relevant to liver function. Meanwhile, splenic immune relevant gene expression (IFN-γ1, LYZ, and hepcidin) increased significantly in all SM-treated fish compared to the control group. Also, hematological responses, including red blood cell indices (RBCs, Hb, HTC, PCV, MCV, MCH, and MCHC) and white blood cell indices (WBCs, lymphocytes, eosinophils, basophils, and heterophils), except monocytes, were improved by SM supplementation. Intestinal microstructures were normal, and their barrier functions were unchanged by dietary supplementation. Hence, SM extract could be used as a promising avenue for enhancing the functionality of aquadiet, leading to improving overall health performance. However, the mode of action of the bioactive ingredients present in SM extract is warranted to be further studied to consider SM as a functional additive for aquafeeds.

Akut pankreatitli hastalarda akut pankreatik ve peripankreatik sıvı gelişiminde prediktif faktörler

Aims: Acute fluid collections after acute pancreatitis carries risk of serious complications as infected pseudocyst and Wall off Necrose development. Hence, it is important to predict the development of acute fluid collections for treatment and management of acute pancreatitis. In this study, it is aimed to investigate predictive factors for development of acute fluid collections in patients with acute pancreatitis. 
 Methods: Total of 438 patients diagnosed with acute pancreatitis were screened. According to the Revised Atlanta Classification fluid development after acute pancreatitis was determined and the relationship between fluid development and the hematological/biochemical parameters of the patients at the time of admission was investigated. The best cut-off point of laboratory measurements for fluid development was determined by ROC analysis and the factors that may be most decisive in distinguishing between the patients with and without fluid development were determined by multivariate forward stepwise logistic regression analysis.
 Results: It is found that developing acute fluid collections after acute pancreatitis was higher in patients with younger age and male gender. Also the risk of developing acute fluid collections after acute pancreatitis was found to be 6.2 times higher in patients with CRP/Albumin ratio greater than 1.09; 2.5 times higher in patients with ALP below 199.5 U/L; 1.9 times higher in patients with WBC greater than 11,6 ×10⁹/L and 1.5 times higher in patients with PLR above 197.1. Also the risk of developing acute necrotic collections after acute pancreatitis was 3 times higher in patients with serum calcium level below 8,6 mg/dl.
 Conclusion: It has been determined that, presence of high CRP/albumin ratio, high NLR and low serum ALP level can be used as an indicator in predicting acute pancreatic and peripancreatic fluid development.

Combined quercetin and simvastatin attenuate hepatic fibrosis in rats by modulating SphK1/NLRP3 pathways

Liver fibrosis involves several signalling pathways working in concert regulating the deposition of extracellular matrix. In this study, we evaluated the effect of quercetin and simvastatin alone and their combination on the treatment of experimentally induced hepatic fibrosis in rats. To decipher the potential mechanisms involved, liver fibrosis was induced in rats by administration of 40 % carbon tetrachloride (CCl4) (1 μl/g rat, i.p., twice weekly) for 6 weeks. Quercetin (50 mg/kg, orally), simvastatin (40 mg/kg, orally) either individually or combined were administered for another 4 weeks. The three treatment groups ameliorated hepatic dysfunction and altered parameters of sphingolipid and pyroptosis pathways. Yet, the combined group showed a more pronounced effect. Treatments lowered serum levels of GOT, GPT, ALP and elevated albumin and total protein levels. Histopathological and electron microscope examination of liver tissue revealed diminished fibrosis and inflammation. Protein expression levels of α-SMA, IL-1β, PPAR-γ, TGF-β1, caspase-1 and caspase-3 expression in liver tissues were reduced. Additionally, hepatic mRNA levels of SphK1 and NLRP3 decreased after treatment. Furthermore, the three groups lowered MDA levels and elevated total antioxidant capacity, GSH and Nrf2 expression levels. Treatments downregulated sphingolipid pathway and NLRP3-mediated pyroptosis and stimulated an anti-apoptotic, anti-proliferative and antioxidant activity. This suggests that targeting the SphK1/NLRP3 pathway could be a prospective therapeutic strategy against liver fibrosis.

The effect of Nigella sativa on serum levels of insulin-like growth factor and its binding proteins in postmenopausal women with low bone density: A triple-blind randomized controlled trial

Animal studies have shown that Nigella sativa (NS) seed oil can increase Insulin-like growth factor (IGF-1) serum levels. This study aimed to investigate the effect of oral capsule NS on serum levels of IGF-1 and its binding proteins (IGFBP-1, IGFBP-3) in postmenopausal women with bone loss density. Sixty postmenopausal women of 50 to 65 years with bone loss density randomly received a soft capsule of NS oil 1000 mg or placebo once daily for six months with a 1:1 allocation ratio. DEXA method was used to measure bone density. Serum concentrations of IGF-1, IGFBP-1 and-3, ALT, AST, ALP, Cr, and urea were measured at baseline and after the intervention. There were no significant differences in serum levels of IGF1, IGFBP-1, urea, Cr, ALT, AST, and ALP between the two groups at the end of six months. However, a significant increase has been shown in IGFBP-3 between groups after the intervention (Adjusted mean difference: 95% CI: 1.65: 0.36 to 2.97; p=0.013). We observed a significant increase in IGFBP-3 serum levels without any side effects. Additional research with an increased number of participants may be needed for further clarification of its beneficial anabolic effects on the GH system.

Assessment of Liver Enzymes among Gold Mining Workers in Alabedia Souk Nile River Sudan

This study aims to measure the liver enzymes among gold mining workers and compare them with a group of healthy subjects as a control sample. This cross-sectional study was conducted Alabedia market, Nile River, Sudan. The study included 70 people, the gold prospectors by mercury as a test group (50 people) and healthy (20 people) as a control group. The venous blood samples were collected from the two groups to measure the rates of Hg liver enzymes. Statistical analysis of the results reviled that, there was a significant increase in serum level of ALP in the test group (82.8 IU/L) when compared with the control group (70.25.1IU/L) with a P. value of 0.013, and an increase in serum level of ALT in the test group was (21.18 IU/L) when compared with a control group of (26.96.1IU/L) with P. value of 0.003. Statistical analysis of the results reviled that, there was no significant increase in serum level of AST when compared with a control group with a P-value of 0.071. The mean level of serum mercury in the test group was (62.17) and in the control group was (0.72) with P. value of <0.001. This study established that there is a significant increase in the levels of serum mercury compared to the control group. The new workers are more exposed to mercury than the older workers because the new workers have no experience in contact with gold mining extraction.

Functional Assessment of MGO Nanoparticle Supplementation in an Acute Liver Injury Rat Model

Magnesium supplements have been effective for modulating process of bile resistance, decrease oxidative stress and systemic inflammation. Current study was designed to functionally evaluate the MgO nanoparticle supplementation in an acute liver injury rat model. The animals were randomly divided into five groups. All groups were administrated with CCl4 to induce hepatic injury except of negative control group which received only vehicle. CCl4 administration is followed by MgO nanoparticles in the concentration of 150 and 300 mg/kg in low dose and high dose treated group respectively except of standard control group. After 21 days of treatment, the animals were sacrificed to collect blood and liver samples. Serum levels of bilirubin, AST, ALT and ALP were determined. Liver sample was also subjected to RNA isolation by Trizol method followed by the cDNA synthesis and Real Time PCR. In addition, lipid profile was also assessed. The data obtained was analyzed by one way analysis of variance (ANOVA). The results showed that levels of bilirubin, AST, ALT and ALP were significantly elevated in positive control group while MgO treated groups, somehow, had normal ranges of these enzymes. Furthermore, the qPCR results showed that the expression of Farnesoid X receptor (FXR), transcriptional regulator of the bile salt export pump (BSEP) and sodium taurocholate cotransporting polypeptide (NTCP), is reduced in positive control group, while nanoparticles treated groups had normal expression of these genes. In conclusion, our data showed that MgO nanoparticles possess hepatoprotective activity against hepatic injury.

Age-specific reference intervals for liver function tests in healthy neonates, infants, and young children in Iran.

The reference intervals (RIs) for liver function tests (LFTs) were determined in Iranian children for the first time. A total of 344 healthy pediatrics aged 3 days to 30 months old were recruited. Serum levels of ALT, AST, ALP, direct bilirubin, and total bilirubin were measured. RIs were determined using CLSI Ep28-A3 guidelines. All analytes demonstrated age-specific differences except AST. ALT and ALP demonstrated significantly elevated levels in infants 0 to <5 months relative to the remainder of the age range. Direct and total bilirubin demonstrated markedly elevated levels in early life with mean of 0.28 mg/dL and 1.64 mg/dL observed for direct and total bilirubin, respectively, decreasing by ~50% in the adjacent partition. These novel data will help improve the clinical interpretation of biochemical test results in young Iranian neonates and children and can be of value to clinical laboratories with similar populations.

BDE-47 induces metabolic dysfunction-associated steatotic liver disease (MASLD) through CD36-mediated increased fatty acid uptake and PPARα-induced abnormal fatty acid oxidation in BALB/c mice

The widespread existence of 2,2′,4,4′-tetra-bromodiphenyl ether (BDE-47) in the environment has aroused great concern. BDE-47 induces the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanism has not been fully elucidated. Here, we further investigate the underlying mechanism using BALB/c mice. After BDE-47 exposure, the livers of mice enlarged, the serum levels of ALT, ALP, TG and TC enhanced, and hepatic steatosis occurred. Transcriptome sequencing identifies 2250 differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis reveals that down-regulated DEGs are mainly enriched in pathways associated with lipid metabolism, particularly in fatty acid (FA) degradation. And up-regulated DEGs are mainly enriched in pathways related to lipid and FA transport. The expression levels of AhR, Pparγ and Cd36 involved in FA uptake are up-regulated, and those of PPARα and target genes including Cpt1 and Cyp4a1 related to β and ω-oxidation are inhibited. These results reveal BDE-47 could lead to metabolic dysfunction-associated steatotic liver disease (MASLD) by promoting FA uptake via upregulating Cd36 and hindering oxidative utilization by downregulating PPARα.

Dietary Theobroma cocao Prevents Hepatotoxicity Secondary to Myocardial Injury

Dietary products like cocoa with high flavonoids may play a role to boost the integrity of the liver against insults resulting from myocardial injury. Twenty-four male Wistar rats, divided into four groups of 6 rats were used for the study. Group 1 was control and received 0.9% normal saline via oral gavage. Group 2 was the acute myocardial injury group, and received two doses of subcutaneous injection of isoproterenol (100 mg/kg body weight) at an interval of 24 hours between doses. Group 3 was administered Theobroma cacao (100 mg/kg body weight orally) only for 2 weeks. Group 4 was pretreated with Theobroma cacao for 2 weeks and then followed by injection of isoproterenol (100 mg/kg body weight) on day 15 and 16. At the end of the experimental period, the rats were euthanized and serum collected for laboratory investigations of lactate dehydrogenase, troponin, alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. Administration of isoproterenol resulted in a significant (p&lt;0.001) elevation in the serum concentrations of the cardiac biomarkers, troponins and LDH when compared with the control group. Pretreatment with Theobroma cacao before myocardial infarction caused a significant (p&lt;0.01) reduction in the concentrations of LDH and troponins with values similar to the control group. The serum liver enzymes AST, ALT, and ALP levels were also significantly (p&lt;0.01) but were reversed in the Theobroma cacao cocoa treatment groups. It is concluded that Theobroma cacao prevents hepatic and heart damage thus providing a support for the prophylactic use of dietary Theobroma cacao against hepatotoxicity.

Health status outcome among cannabis addicts after treatment of addiction.

The abuse of Cannabis is a widespread issue in the Asir region. It has a lot of legal and occupational repercussions. The purpose of this study was to evaluate the health status of cannabis addicts at admission and after treatment using body mass index, glycemic status, liver function, renal function, and oxidative stress. A cross-sectional study was conducted with 120 participants. The study was conducted at Al Amal Hospital for Mental Health in Asir region of Saudi Arabia, with 100 hospitalized patients receiving addiction treatment and 20 healthy volunteers. The participants were divided into two groups: group I, the control group, and group II, the cannabis addicts. The socio-demographic data were gathered. The level of cannabis in the urine and the CWAS [Cannabis Withdrawal Assessment Scale] were determined. In addition, the Body Mass Index [BMI], vital signs [temperature, heart rate, systolic blood pressure, diastolic blood pressure, and respiratory rate], serum levels of albumin, total bilirubin, direct bilirubin, AST, ALT, and ALP, urea, creatinine, Thiobarbituric acid-reactive substances [TBARS], superoxide dismutase [SOD], reduced glutathione [GSH], and catalase [CAT] were analyzed on the first day of admission and after treatment. According to the results, there was no significant change in the body mass index. The vital signs in the cannabis user group were significantly lower than the corresponding admission values. Regarding renal function tests such as urea and creatinine, we found that after treatment, the mean urea and creatinine values in the cannabis user group did not differ significantly from the corresponding admission values. However, after treatment, the mean values of fasting blood glucose levels in the cannabis user group were significantly lower than at admission. Also, the mean values of liver function tests such as albumin, total bilirubin, direct bilirubin, AST, ALT, and ALP in the cannabis user group were significantly lower than the corresponding admission values after treatment. In assessing the antioxidant system, we found that the mean values of TBARS, SOD, GSH, and CAT in the cannabis user group did not differ significantly from the corresponding admission values after treatment. The current findings have revealed that cannabis addiction harms the various body systems and has significant implications for the addict's state of health. The values of oxidative stress biomarkers did not change in this study, but other measured parameters improved after treatment.

Total flavonoids extracted from Penthorum chinense Pursh mitigates CCl4-induced hepatic fibrosis in rats via inactivation of TLR4-MyD88-mediated NF-κB pathways and regulation of liver metabolism

Background:Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear.Methods: The chemical composition of TFPCP was determined using UHPLC–Q-Orbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl4)-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg∙day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg∙day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%–20% CCl4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics.Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl4-treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1β); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-β1, TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites.Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88-mediated NF-κB pathway and the regulation of liver metabolism.

Chitosan nanoparticle encapsulation increased the prophylactic efficacy of Lactobacillus plantarum RM1 against AFM1-induced hepatorenal toxicity in rats

Aflatoxin M1 (AFM1) is a significant contaminant of food, particularly dairy products and can resist various industrial processes. Several probiotic strains like Lactobacillus plantarum are known to reduce aflatoxin availability in synthetic media and some food products. The current work investigated the possible chitosan coating prophylactic efficacy of Lactobacillus plantarum RM1 nanoemulsion (CS-RM1) against AFM1-induced hepatorenal toxicity in rats. Twenty-eight male Wistar rats were divided into four groups (n = 7) as follows: group 1 received normal saline, group 2 received CS-RM1 (1mL contains 6.7 × 1010 CFU), group 3 received AFM1 (60 µg/kg bwt), and group 4 received both CS-RM1(1 mL contains 6.7 × 1010 CFU) and AFM1 (60 µg/kg bwt). All receiving materials were given to rats daily via oral gavage for 28 days. AFM1 caused a significant elevation in serum levels of ALT, AST, ALP, uric acid, urea, and creatinine with marked alterations in protein and lipid profiles. Additionally, AFM1 caused marked pathological changes in the liver and kidneys, such as cellular necrosis, vascular congestion, and interstitial inflammation. AFM1 also increased the MDA levels and decreased several enzymatic and non-enzymatic antioxidants. Liver and kidney sections of the AFM1 group displayed strong caspase-3, TNF-α, and iNOS immunopositivity. Co-treatment of CS-RM1 with AFM1 significantly lowered the investigated toxicological parameter changes and markedly improved the microscopic appearance of liver and kidneys. In conclusion, AFM1 induces hepatorenal oxidative stress damage via ROS overgeneration, which induces mitochondrial caspase-3-dependent apoptosis and inflammation. Furthermore, CS-RM1 can reduce AFM1 toxicity in both the liver and kidneys. The study recommends adding CS-RM1 to milk and milk products for AFM1-elimination.

Role of serum alkaline phosphatase as a potential biomarker of severity and prognosis in intracerebral hemorrhage

ObjectivesAlkaline phosphatase (ALP) catalyzes the hydrolysis of pyrophosphate and facilitates vascular calcification. We aimed at investigating serum ALP levels in intracerebral hemorrhage (ICH) patients and ascertaining its relationship to severity and prognosis. MethodsSerum ALP levels from 148 patients and 148 healthy controls were detected. Glasgow coma scale (GCS) score and hematoma volume at admission were recorded to evaluate hemorrhagic severity. Modified Rankin Scale (mRS) score > 2 at 90 days after onset was judged as a poor prognosis. ResultsSerum ALP levels in patients with ICH were substantially elevated compared with healthy controls, and were significantly related to hematoma volume and GCS score. Serum ALP levels significantly distinguished ICH patients at risk for unfavorable prognosis. Serum ALP levels > 78.5 U/L in ICH patients may indicated a unfavorable prognosis with 69.1 % sensitivity and 83.6 % specificity, and served as an independent predictor for unfavorable prognosis. ConlusionsElevated serum ALP levels were intimately connected with increased severity and 90-day unfavorable prognosis in patients with ICH. Serum ALP could be a potential biomarker for severity and prognosis of ICH.

Reduced liver damage and fibrosis with combined SCD Probiotics and intermittent fasting in aged rat.

This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30-day intermittent fasting (IF) program in 24-month-old male Sprague-Dawley rats. Rats underwent 18-h daily fasting and received 1 × 108 CFU of SCD Probiotics daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, and SVM techniques, while histopathological evaluations used Haematoxylin and eosin and Masson trichrome-stained tissues. Blood samples were collected for biochemical analysis. Gross alterations in the quantity of biomolecules were observed with individual or combined treatments. LDA and SVM analyses demonstrated a high accuracy in differentiating control and treated groups. The combination treatments led to the most significant reduction in cholesterol ester (1740 cm-1 ) and improved protein phosphorylation (A1239 /A2955 and A1080 /A1545 ) and carbonylation (A1740 /A1545 ). Individually, IF and SCD Probiotics were more effective in enhancing membrane dynamics (Bw2922 /Bw2955 ). In treated groups, histological evaluations showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis and fibrosis. Serum ALP, LDH and albumin levels significantly increased in the SCD Probiotics and combined treatment groups. This study offers valuable insights into the potential mechanisms behind the beneficial effects of IF and SCD Probiotics on liver biomolecule content, contributing to the development of personalized nutrition and health strategies.

Serum alkaline phosphatase can be elevated in patients with hypophosphatasia due to liver disease

BackgroundHypophosphatasia (HPP) is a rare inherited disorder caused by pathogenic loss-of-function variants in the ALPL gene, encoding the tissue-nonspecific isoenzym of alkaline phosphatase (ALP; TNSALP). Low serum ALP is the biochemical hallmark of HPP, but it is unknown whether ALP levels can increase due to concurring liver disease, which may lead to a missed diagnose of HPP. We present a patient with genetically confirmed HPP, who showed a transient increase of serum ALP levels due to alcohol-induced hepatitis. Clinical reportA 71-year old man was seen at our Bone Center for surveillance of HPP. Serum ALP was always low (23 U/L; reference value: <115 U/L). During follow-up, his serum ALP increased (156 U/L, further rising to 204 U/L), with concomitantly elevated serum gamma-glutamyl transferase and transaminases, and a rise in bone specific ALP (18.7 μg/L; reference value: 5.7–32.9 μg/L). This was attributed to alcohol-induced hepatitis. After refraining from alcohol intake, both serum ALP and bone specific ALP levels returned to initial low levels (30 U/L and 4.3 μg/L respectively). ConclusionsWe demonstrated the history of a 71-year old patient with HPP, presenting during routine follow-up with an elevated serum ALP level up to 204 U/L due to alcohol-induced hepatitis. This case illustrates that the diagnosis of HPP can potentially be missed when ALP levels are normal or elevated due to a concomitant liver disease.

THU458 Demineralization Zebras: A Rare Case Of Hypophosphatasia In An Adult Presenting With Osteopenia

Abstract Disclosure: B.P. Ramchandani: None. A. Khan: None. H. Aftab: None. Introduction: Hypophosphatasia (HPP) is a rare genetic bone disease with only 500-600 cases reported in the United States. It is characterized by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, leading to impaired bone mineralization. HPP presenting in the perinatal period is fatal. During infancy, rachitic deformities develop by age 6 months. Children present with early loss of deciduous teeth and delayed milestones while in adulthood, HPP is characterized by recurrent fractures, osteoporosis, and muscle weakness. We describe a case of HPP diagnosed in a patient after low ALP was discovered on laboratory testing. Case: A 69-year-old female presented for the evaluation of osteopenia. She had a history of fracture of the right knee as well as fracture of the base of the right 5th metatarsal and lateral aspect cuboid, which healed well with conservative management. Dental history was significant for 5 implants over the last 15 years. She was on vitamin D supplements and had also taken risedronate for osteopenia for 14 years which was discontinued at her first visit with us. Family history was significant for osteoporosis in her mother. Initial lab studies were significant for an ALP of 29 U/L (ref range 39-113 U/L), phosphate of 4.9 mg/d (ref range 2.4-4.8 mg/dl), pyridoxal 5’-phosphate level (vitamin B6) of 308 nmol/L (ref range 20-125 nmol/l), a vitamin D 25-OH level of 20 ng/mL (ref range &amp;gt;30 ng/ml) and PTH of 49 pg/dl (ref range 15-88 pg/ml). Repeat lab testing done 6 months after stopping risedronate showed consistent similar results with an ALP of 32 U/L, phosphate level of 5.1 mg/dl, vitamin B6 level of 349 nmol/L, and vitamin D 25OH level of 26 ng/mL. Bone density scan revealed a lumbar spine BMD of 1.503 g/cm2 (T-score 2.5) and a mean total hip BMD of -0.3 consistent with osteoporosis of spine and osteopenia of hip. Genetic testing and counseling were offered to the patient, however she declined. Discussion: Our patient presented with recurrent fractures and loss of dentition requiring multiple dental implants in the background of osteopenia. Given persistently low serum ALP and elevated serum vitamin B6 levels her presentation suggested a diagnosis of HPP. Management includes supportive treatment with prompt treatment of fractures, and routine dental care. Although there is no approved medication for adults, enzyme therapy replacement with asfotase-alfa (a recombinant human ALP) is FDA-approved for pediatric-onset HPP which improves bone mineralization and muscle strength, however discontinuation of therapy leads to reappearance of bone hypomineralization. Once the diagnosis is made, genetic testing and counseling should be offered to prevent complications in future pregnancies. Presentation: Thursday, June 15, 2023

Euphorbia royleana Boiss Derived Silver Nanoparticles and Their Applications as a Nanotherapeutic Agent to Control Microbial and Oxidative Stress-Originated Diseases.

Nanotechnology is one of the most advance and multidisciplinary fields. Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. The use of plants and their extracts is one of the most valuable methods towards rapid and single-step protocol preparation for various nanoparticles, keeping intact "the green principles" over the conventional ones and proving their dominance for medicinal importance. A facile and eco-friendly technique for synthesizing silver nanoparticles has been developed by using the latex of Euphorbia royleana as a bio-reductant for reducing Ag+ ions in an aqueous solution. Various characterization techniques were employed to validate the morphology, structure, and size of nanoparticles via UV-Vis spectroscopy, XRD, SEM, and EDS. FTIR spectroscopy validates different functional groups associated with biomolecules stabilizing/capping the silver nanoparticles, while SEM and XRD revealed spherical nanocrystals with FCC geometry. The results revealed that latex extract-mediated silver nanoparticles (LER-AgNPs) exhibited promising antibacterial activity against both gram-positive and -negative bacterial strains (Bacillus pumilus, Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, and Streptococcus viridians). Both latex of E. royleana and LER-AgNPs were found to be potent in scavenging DPPH free radicals with respective EC50s and EC70s as 0.267% and 0.518% and 0.287% and 0.686%. ROSs produced in the body damage tissue and cause inflammation in oxidative stress-originated diseases. H2O2 and OH* scavenging activity increased with increasing concentrations (20-100 μg/mL) of LER-AgNPs. Significant reestablishment of ALT, AST, ALP, and bilirubin serum levels was observed in mice intoxicated with acetaminophen (PCM), revealing promising hepatoprotective efficacy of LER-AgNPs in a dose-dependent manner.

Combination of osteogenesis imperfecta and hypophosphatasia in three children with multiple fractures, low bone mass and severe osteomalacia, a challenge for therapeutic management

Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and tissue-non-specific isoenzyme of alkaline phosphatase (ALPL), respectively. Both conditions result in skeletal deformities and bone fragility although bone tissue abnormalities differ considerably. Children with OI have low bone mass and hypermineralized matrix, whereas HPP children develop rickets and osteomalacia.We report a family, father and three children, affected with growth retardation, low bone mass and recurrent fractures. None of them had rickets, blue sclera or dentinogenesis imperfecta. ALP serum levels were low and genetics revealed in the four probands heterozygous pathogenic mutations in COL1A2 c.838G > A (p.Gly280Ser) and in ALPL c.1333T > C (p.Ser445Pro). After multidisciplinary meeting, a diagnostic transiliac bone biopsy was indicated for each sibling for therapeutic decision.Bone histology and histomorphometry, as compared to reference values of children with OI type I as well as, to a control pediatric patient harboring the same COL1A2 mutation, revealed similarly decreased trabecular bone volume, increased osteocyte lacunae, but additionally severe osteomalacia. Quantitative backscattered electron imaging demonstrated that bone matrix mineralization was not as decreased as expected for osteomalacia.In summary, we observed within each biopsy samples classical features of OI and classical features of HPP. The apparent nearly normal bone mineralization density distribution results presumably from divergent effects of OI and HPP on matrix mineralization. A combination therapy was initiated with ALP enzyme-replacement and one month later with bisphosphonates. The ongoing treatment led to improved skeletal growth, increased BMD and markedly reduced fracture incidence.

Nutritional Composition and Anti-Type 2 Diabetes Mellitus Potential of Femur Bone Extracts from Bovine, Chicken, Sheep, and Goat: Phytochemical and In Vivo Studies.

Nutritional deficits in one's diet have been established as the key risk factor for T2DM in recent years. Nutritional therapy has been demonstrated to be useful in treating T2DM. The current study was carried out to assess the nutritional composition of bovine (12 months), chicken (4 months), sheep (13 months), and goat (9 months) femur bone extracts, as well as their potential therapeutic effects on T2DM regression in a Wistar albino rat model (500 mg/kg b.wt.). The proximate composition of the different extracts, their fatty acid composition, their amino acids, and their mineral contents were identified. In vivo data indicated considerably improved T2DM rats, as seen by lower serum levels of TL, TG, TC, ALT, AST, ALP, bilirubin, creatinine, urea, IL-6, TNF-α, sICAM-1, sVCAM-1, and MDA. Low levels of HDL-C, GSH, and total proteins were restored during this study. Histological investigations of liver and pancreatic tissue revealed that the distribution of collagen fibers was nearly normal. The bovine extract, on the other hand, was the most active, followed by the sheep, goat, and finally chicken extract. This research could result in the creation of a simple, noninvasive, low-cost, and reliable method for T2DM control, paving the way for potential early therapeutic applications in T2DM control.

CARDIOPROTECTIVE ACTIVITY OF CALLIANDRA PORTORICENSIS LEAF ETHANOL EXTRACT AGAINST KEROSENE VAPOUR INDUCED CARDIOTOXICITY IN MALE ALBINO RATS

Aim and objective: This study investigated the cardioprotective activities of Calliandra portoricensis leaf ethanol extract (CPLEE) on kerosene vapour–induced cardiotoxic male albino rats. Methods: Twenty-five male albino rats (120-150 g) were grouped into five groups (n=5). Group 1 received distilled water (normal control), while CPLEE constituted doses of 25 and 50 mg/kg b.wt p.o were administered once daily for the last 4 weeks to animals in group 4 and 5 respectively. Group 2 received kerosene vapour1.0 mL/kg body wt by inhalation for 4 weeks to induce toxicity, while group 3 received vitamin C 200 mg/kg p.o. Serum and cardiac samples were collected and used for the biochemical analyses. Results: Qualitative phytochemical analysis of CPLEE revealed the presence of different phytochemicals including flavonoids, tannin, saponin, alkaloids, cardiac-glycosides, etc. CPLEE caused a significant reduction (p&lt;0.05) in the serum levels of ALT, AST, ALP and LDH in the treated kerosene vapour groups in contrast to the untreated kerosene vapour induced cardiotoxic group. CPLEE showed potentials to mop-up free radicals generated by kerosene, by significantly reducing (p&lt;0.05) lipid peroxidative-product (malondialdehyde, MDA) levels and increasing antioxidant activities of superoxide dismutase, catalase and reduced glutathione (GSH) in dose dependent manner in the treated kerosene vapour groups compared to the untreated kerosene vapor-induced cardiotoxic group. Conclusion: The findings suggests that the CPLEE have the capacity to improving cardiac functions at safe doses possibly due to its abundant phytochemicals and antioxidants that offers protections against kerosene vapour-induced oxidative-damage. Peer Review History: Received: 15 June 2023; Revised: 20 July; Accepted: 23 August, Available online: 15 September 2023 Academic Editor: Dr. Iman Muhammad Higazy, National Research Center, Egypt, imane.higazy@hotmail.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Prof. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, alialkaf21@gmail.com