Serum Total Alkaline Phosphatase Research Articles

Experimental model of non-alcoholic fatty liver disease in pregnant rats to evaluate the effectiveness of therapy

Background: The growing incidence of non-alcoholic fatty liver disease in the population contributes to the development of obstetric complications during pregnancy and demands searching effective methods of hepatoprotective therapy. Aim: The aim of this study was to evaluate the efficacy of therapy for non-alcoholic fatty liver disease in an experimental model in pregnant rats. Materials and methods: this experimental study was carried out on 19 female Wistar rats weighing 250–300 g, obtained from the laboratory animal nursery of SMK Stezar Ltd. (Vladimir, Russia). Using a high-fat diet, non-alcoholic fatty liver disease was simulated in the study groups as follows. Group 1 (n = 7) consisted of non-pregnant rats, group 2 comprised pregnant rats without therapy (n = 6), and group 3 included pregnant rats and intraperitoneal administration of 12 mg of the low-molecular sugar preparation from day 16 to day 20 of gestation (n = 6). During the experiment, the body weight of female rats was measured weekly. After the experiment was completed, we evaluated the blood serum levels of aspartate aminotransferase, alanine aminotransferase, ferritin, triglycerides, total cholesterol, total bilirubin, urea, total alkaline phosphatase, bile acids, glucose, C-reactive protein, cholinesterase, and malondialdehyde, as well as catalase activity. Histological examination of the rat liver was carried out using the standard method with hematoxylin and eosin staining. Results: This study showed that high-fat diet caused oxidative stress manifested by decreased the blood catalase level and increased malonovodialdehyde in both pregnant and non-pregnant females; the blood bile acids level also increased. In pregnant rats with non-alcoholic fatty liver disease, the serum C-reactive protein and total alkaline phosphatase levels increased, the cholinesterase level decreased, and the catalase activity decreased even more. In the study group using the low-molecular sugar preparation, biochemical parameters in non-alcoholic fatty liver disease improved, probably due to the effect on lipogenesis and oxidative stress in the liver. The histological pattern was characterized by the impaired structural characteristics of hepatocytes and the circulatory bed. With the use of the low-molecular-weight sugar preparation, we noted a tendency to restore the structure of the hepatic beam area and a decrease in the manifestations of steatosis. Conclusions: The use of the low-molecular-weight sugar preparation in the treatment of non-alcoholic fatty liver disease improves biochemical blood parameters and tends to restore the histological structure of the liver.

Development of Paget's disease of bone in adults inheriting SQSTM1 mutations: a long-term follow-up.

In a 2015 study of SQSTM1 mutation carriers who had initial negative bone scintigraphy, we found that the rate of development of Paget's disease of bone (PDB) over 5yr was low. We report here an additional 8-yr follow-up of this cohort, exploring the hypothesis that the rate of development of PDB would increase as the cohort aged. In the current study, 21 of 24 subjects from 2015 who had a negative bone scintiscan at baseline and at first follow-up, had a repeat scintiscan and measurement of total serum alkaline phosphatase activity. Two subjects with P392L mutations were identified as having PDB (monostotic in one case, 2 bones involved in the other), giving an incidence during this follow-up period of 1 per 87 patient years or 11.9 per 1000 patient years. This was contrary to our hypothesis, as the rate of development had decreased as the cohort aged. When we compared by survival analysis the age at presentation with symptomatic PDB in the older generation, we found that the age of onset was later and disease severity in the affected relatives was markedly less than in their clinically affected parents (p< .001). Our results are in keeping with other recently published studies and the general secular trend in PDB and support the idea that an important environmental-genetic interaction is involved with the development of PDB and that exposure to the putative environmental factor has substantially reduced.

Effect of a weight loss diet with or without Spirulina supplementation on serum lipids and antioxidant capacity of overweight dogs

Obesity is a major health issue in dogs associated with disturbances in lipid metabolism and oxidative stress. Spirulina has been shown to have hypolipidemic and antioxidant effects in various animal species. No such data regarding dogs are available, however. The present study aimed to investigate the effect of a therapeutic high-protein, high-fiber weight loss diet, with or without Spirulina supplementation, on biochemical parameters of overweight dogs, with particular reference to serum lipids and plasma antioxidant capacity. Thirty-two dogs completed a double-blind randomized placebo-controlled trial in which they received either Spirulina (S) or placebo (P) tablets in a body weight-dependent amount for 12 weeks; at the same time, both groups were fed the same calorie-restricted diet. Dogs were weighed weekly and calorie restriction was adjusted accordingly to ensure a 1% body weight loss per week. Blood samples were collected at baseline (T0), after 6 weeks (T1), and after 12 weeks (T2). No difference in body weight loss (S: -11.9 ± 0.8%, P: -10.6 ± 0.8%, p = 0.229) was detected between groups at T2. After 6 weeks and an average weight loss of around 6% (S: -6.7 ± 0.6%, P: -5.9 ± 0.6, p = 0.276), significant reductions of serum total cholesterol, glucose, alkaline phosphatase, paraxonase-1 (all p < 0.0001) and gamma-glutamyltransferase (p < 0.018) were observed in both groups, regardless of supplementation. Plasma antioxidant capacity increased significantly in both groups at T2 (p = 0.0003). Serum triglycerides decreased significantly from T0 to T1 in the Spirulina group (p < 0.0001) but not in the placebo group (p = 0.28); as for the difference between groups, a non-significant trend (p = 0.098) was detected. A significantly higher percentage of dogs (p = 0.028) in the Spirulina group achieved a serum triglycerides reduction > 15% compared to baseline at T1 and > 30% at T2. A treatment effect (p = 0.0416) was found for bilirubin, which decreased only in the Spirulina group. In conclusion, a weight loss of around 6% achieved with a high-protein, high-fiber hypocaloric diet is sufficient to induce significant positive metabolic effects and improve lipid, glucose, and liver enzyme values. Plasma antioxidant capacity was tested in dogs undergoing a weight loss program for the first time, demonstrating that overweight individuals are in a deficient status and that a weight loss of around 10% is able to restore values comparable to those of healthy individuals. The results of this study suggest that Spirulina may manifest a hypotriglyceridemic effect in dogs, even if further research is needed to infer causation. The role Spirulina that supplementation plays in bilirubin metabolism and its related beneficial effect is also worth exploring.

Study of Correlation of Apgar Score and Thompson Score with Hepatic Function in Perinatal Asphyxia Affected Neonates—A Prospective Observational Study

Background Perinatal asphyxia is one of the leading causes of neonatal morbidity and mortality in the country. It leads to multi-organ failure with brain involvement as the major organ of concern (hypoxic-ischemic encephalopathy). Hepatic dysfunction is also a feature of perinatal asphyxia. Objectives To detect hepatic dysfunction in birth asphyxia. To correlate the liver damage with increasing severity of birth asphyxia and hypoxic-ischemic encephalopathy through Apgar score and Thompson score. Methods In this prospective observational study, after ethical clearance and informed consent from the parents, babies of gestational age &gt;35 weeks weighing &gt;1.8 kg, Apgar score &lt;7 at 1 minute received in the newborn unit of a tertiary care hospital in West Bengal, India were enrolled. Thompson’s score was assessed every day. The liver function test of these patients was assessed on days 1, 3, 10, and 15. Ultrasonography of the whole abdomen was performed on days 1 and 14 of life to rule out other probable causes of hepatic injury. Results A total of 308 neonates were studied, of which Apgar score at 1 minute indicates that 99 (32.14%) of the newborns had severe birth asphyxia and the rest had moderate birth asphyxia. All the liver enzymes except total protein and albumin showed a significant rise on days 1 and 3 with increasing severity of asphyxia. This correlation was seen with Apgar score at 1 minute on day 1 with TSB (r = -0.256, P &lt; .001), AST (r = -0.209, P &lt; .01), ALT (r = -0.178, P &lt; .002), ALP (r = -0.174, P &lt; .002). As per Thompson score, total serum bilirubin, aspartate aminotransferase and alkaline phosphatase showed maximum correlation on days 1 (r = 0.253, P &lt; .001, r = 0.187, P &lt; .001 and r = 0.268, P &lt; .001, respectively) and on day 3 (r = 0.159, P &lt; .005, r = 0.231, P &lt; .001, and r = 0.190, P &lt; .002, respectively). Conclusion Thompson score and Apgar score can be correlated to perinatal asphyxia-related hepatic injury.

Determination of optimal dietary calcium levels under different sources of zinc in Jing tint 6 layer chicks from 15 to 42 d of age

An experiment was conducted to investigate the optimal dietary calcium (Ca) levels in Jing Tint 6 layer chicks fed different sources of zinc (Zn). The diets were formulated using 2 different Zn sources: organic Zn (80 mg/kg Zn as HMZn) and inorganic Zn (80 mg/kg Zn as sulfate). For each Zn source, 5 diets were formulated to contain Ca levels of 0.80, 0.90, 1.03, 1.10, and 1.20%. Results showed that dietary Ca levels had a significant effect on body weight gain (BWG) and feed conversion ratio (FCR) (P < 0.05). In addition, BWG was significantly enhanced by the organic Zn diets (P < 0.05). Dietary Ca levels significantly affected tibia length (P < 0.05) and serum Ca and P contents (P < 0.05) but did not affect serum total protein (TP), albumin (ALB), or alkaline phosphatase (ALP) levels (P > 0.05). The apparent total tract retention coefficients (ATTRC) of Ca showed a quadratic trend (P < 0.05) with increasing Ca levels. Furthermore, organic Zn diets reduced excreta Ca output and enhanced the ATTRC of Ca in birds on d 42 compared with inorganic Zn diets. The optimal dietary Ca levels were estimated as 0.93, 0.94, and 0.96% for birds fed organic diets and 1.07, 0.99 and 0.94% for birds fed inorganic diets using nonlinear models based on the criteria of BWG, tibial length, and serum P, respectively. In general, organic Zn supplementation improved growth performance and reduced the calcium requirements of birds on d 42.

Comparison of serum alkaline phosphatase levels between two measurement methods in chronic hemodialysis patients in Japan: involvement of ABO blood group system and relationship with mortality risk.

Elevated serum alkaline phosphatase (ALP) levels are a risk factor for all-cause mortality in hemodialysis patients. Traditionally in Japan, ALP measurements were conducted using the JSCC method, which yields higher ALP measurement values than the IFCC method, mainly due to its increased sensitivity to intestinal ALP. Serum total ALP levels before and after switching the assay method from JSCC to IFCC were compared among different blood types in 521 hemodialysis patients (Study 1). The association between ALP levels measured by the JSCC method and 7-year mortality was analyzed, including blood types and liver function parameters as covariates, in 510 hemodialysis patients (Study 2). ALP levels measured by the JSCC method were approximately three times higher than those measured by the IFCC method, with significant elevation in patients with blood types B and O compared to those with blood types A and AB. Similarly, ALP levels measured by the IFCC method were significantly higher in patients with blood types B and O compared to those with blood types A and AB (Study 1). The highest tertile of ALP levels showed a significantly increased risk of all-cause mortality, even after adjusting for patient background. However, this significance disappeared when serum liver function-related or inflammatory markers were included as covariates (Study 2). ALP levels measured by the JSCC method are associated with life prognosis, but caution should be exercised due to their elevation in patients with blood types B and O and in those with hepatic dysfunction or inflammation.

Features of post-surgical menopause with concomitant primary hypothyroidism: A prospective single-stage clinical study

Background. In recent decades, the frequency of surgical interventions on reproductive system organs has been steadily increasing. In gynecological practice, preference is given to minimally invasive surgery and precision treatments, especially involving ovaries. Despite the modern approach, it is not always possible to preserve this endocrine organ, which leads to post-surgical menopause (PSM). The relatively high incidence of total hysterectomy-associated PSM and primary hypothyroidism in late reproductive age often leads to their combination. Clinical manifestations aggravating each other form an unfavorable vicious circle. Aim. To study the features of the PSM course with concomitant primary hypothyroidism. Materials and methods. A prospective clinical study included 130 women aged 45 to 55 years with a history of PSM. The main group consisted of 70 patients with PSM with subclinical primary hypothyroidism. A control group included 60 PSM patients without thyroid disorders. We assessed the effect of hypothyroidism on the PSM course by comparing several indicators in the main and control groups. Results. It was found that in the main group patients, severe 26.5% and moderate 38.8% menopausal syndrome prevailed, while in the control group patients, such forms were twice as common. In the women of the main group, the levels of triglycerides were higher than those in the control group by 1.3 times (2.6±0.86 mmol/L and 1.43±0.33 mmol/L, respectively). The total serum alkaline phosphatase activity in patients in the study groups was 29.8% higher than in healthy women. Conclusion. It can be concluded that the severity of menopausal disorders depends on the thyroid status, with more severe in patients of the main group with hypothyroidism. In addition, in patients of the main group with hypothyroidism, dyslipidemia is more pronounced, which predisposes them to severe diseases in the future, in particular cardiovascular disorders, the unfavorable course of metabolic syndrome, and the development of postmenopausal osteoporosis.

Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction, which can impact other solid organs. However, the profiles and consequences of hepatic injury resulting from PAH and CTEPH have not been well studied. Objectives: We aimed to identify underlying patterns of liver injury in a cohort of patients with PAH and CTEPH enrolled in 15 randomized clinical trials conducted between 1998 and 2014. Methods: We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity. Measurements and Main Results: Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin data. Using k-means clustering, we identified phenotypes with no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns. Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and the highest risk of mortality. The cholestatic injury group also experienced the greatest placebo-corrected treatment effect on 6-minute-walk distance. Randomization to the experimental arm transitioned patients to a healthier liver status. Conclusions: Liver injury was associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment had beneficial effects on liver health compared with placebo. The role of liver disease (often subclinical) in determining outcomes warrants prospective studies.

Long-term treatment of evocalcet in hemodialysis patients with secondary hyperparathyroidism: a five-year prospective cohort study in 147 Japanese patients

BackgroundCinacalcet hydrochloride (cinacalcet), an oral calcimimetics for secondary hyperparathyroidism (SHPT), has been widely used worldwide. In contrast, evocalcet, an improved derivative of cinacalcet, was approved only in Japan in 2018 and has not received approval overseas. Consequently, the available information on the long-term use of evocalcet relies solely on data from a 1-year dosing phase III clinical trial.MethodsThe cohort of 147 chronic hemodialysis patients on cinacalcet to manage SHPT was simultaneously switched to the lowest dose of evocalcet (1 mg/day) and prospectively followed for 5 years in real-world clinical settings.ResultsThe median evocalcet dose was 1 mg/day at 0.5 years, and it remained stable at 2 mg/day from 1 to 5 years after the prescription initiation. Additionally, serum parathyroid hormone, corrected calcium, phosphorus, and total alkaline phosphatase levels showed no significant changes compared with their levels at the time of the switch and remained stable over the 5-year period. Furthermore, no adverse events related to vital signs, serum biochemistries, or upper gastrointestinal symptoms were observed in patients during treatment with evocalcet.ConclusionsThese results suggest that only a small number of patients require higher evocalcet doses, and that SHPT can be effectively managed with low-dose evocalcet for 5 years. Additionally, the drug’s long-term safety has been confirmed.Trial registration: name of the registry: Prescription change from cinacalcet hydrochloride to evocalcet in hemodialysis patients. Trial registration number R000041815. Trial registration UMIN000036702. Registered 10 May 2019—retrospectively registered. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000041815.

Retrospective evaluation of cases of benign transient hyperphosphatasemia

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

Extrusion and chlorogenic acid treatment increase the ordered structure and resistant starch levels in rice starch with amelioration of gut lipid metabolism in obese rats.

Dietary interventions are receiving increasing attention for maintaining host health and diminishing disease risk. This study endeavored to elucidate the intervention effect of chlorogenic acid coupled with extruded rice starch (CGA-ES) in mitigating lipid metabolism disorders induced by a high-fat diet (HFD) in rats. First, a significant increase in resistant starch (RS) and a decrease in the predicted glycemic index (pGI) were observed in CGA-ES owing to the formation of an ordered structure (Dm, single helix, and V-type crystalline structure) and partly released CGA. Compared to a physical mixture of starch and chlorogenic acid (CGA + S), CGA-ES showed a more potent effect in alleviating lipid metabolism disorders, manifesting as reduced levels of blood glucose, serum total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (AKP), as well as body weight. It is correlated with an improvement in the gut microecology, featuring bacteria known for cholesterol reduction and butyrate production (Butyricicoccus, Bifidobacterium, Fusicatenibacter, Turicibacter, and Enterorhabdus), along with bile acid, butyrate and PG (PG (17:0/16:0) and PG (18:1/16:0)). The RS fraction of CGA-ES was found to be the main contributor. These findings would provide evidence for future studies to regulate lipid metabolism disorders, and even obesity using CGA-ES.

Receiver Operating Characteristic Analysis of Liver Function Tests in Patients with Chronic Viral Hepatitis B in Baghdad, Iraq

Hepatitis B virus (HBV) infection is a global health challenge, and clearance or persistence of HBV is mostly determined by host immune responses, Therefore, this study aimed to determine HBV effects in chronic HBV patients living in Baghdad receiver operating characteristic (ROC) analysis. The impact of HBV genotypes on liver-function parameters was explored A case-control study was conducted during June-October 2018 on 80 chronic HBV patients and 96 matched control. The results revealed that most patients were males 50 (62.5%), while female patients accounted for 30 (37.5%). The sera of patients were positive for anti-HBc (hepatitis B core antigen) IgG and -HbsAg (hepatitis B surface antigen) antibodies, while they were negative for anti-Hbc IgM antibody. Such profile is consistent with the interpretation of chronic HBV infection. Four liver-function tests (LFTs); total serum bilirubin (TSB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. Significantly increased levels of ALP, ALT and AST were observed in HBV patients compared to normal healthy control, while TSB showed no significant variation. However, in receiver operating characteristic (ROC) analysis, only ALP and AST occupied an excellent area under curve (AUC &gt; 0.90).

HEPATOPROTECTIVE ACTIVITY OF FRUIT AND LEAF EXTRACTS OF FICUS CARICA AND FICUS BENGHALENSIS IN EXPERIMENTAL RATS

Ficus plants have traditionally been used as potential remedies for treating various diseases. Hepatotoxicity is one of the severe threats to human health which must be adequately cured. The study was planned to investigate the hepato-protective potential of methanolic extracts of fruit and leaves of Ficus carica and Ficus benghalensis against carbon tetrachloride (CCl4)-induced hepatotoxicity in an experimental rat model. The study was planned using a randomized control design (RCD). The study included 6 groups of animals (n= 5 per group) having average body weight (230±20 g), out of which 5 groups were treated with CCl4 (15 µL kg-1 body weight), and the remaining one was left as healthy control. Four of the five CCl4-treated groups were administered individually with fruit and leaf extracts (25 mg kg-1 body weight) of F. carica and F. benghalensis, while the fifth was left as CCl4-treated control. The total serum bilirubin (TSB), total serum protein (TSP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels of the control group during the treatment period ranged from 0.54±0.16 to 0.59±0.15 mgdL-1, 8.56±0.73 to 8.66±0.75 gdL-1, 46.00±21.41 to 49.41±22.68 UL-1, 41.6±13.99 to 44.41±13.16 UL-1, and 139.80±28.72 to 145.62±28.82 UL-1, respectively. CCl4 administration significantly (p&lt;0.05) increased the TSB, ALT, AST, and ALP levels in the range of 1.48±0.30-2.30±0.19 mgdL-1, 147.6±34.22 to 233.81±14.94 UL-1, 118.8±15.88 to 167.8±16.4143 UL-1, and 213.8±21.46 to 260±26.664 UL-1, respectively. The elevated TSB, ALT, AST, and ALP levels were significantly (p&lt;0.05) decreased after F. carica and F. benghalens extract treatment to 1.06±0.15-1.70±0.21 mgdL-1, 115.00±28.19-190.21±25.68 UL-1, 89.8±16.29-111.8±23.81 UL-1, and 195.38±42.29-218.4±35.02 UL-1 respectively. Moreover, TSP level was significantly decreased after CCl4 administration and improved after extract treatment. It was concluded that methanolic extract from the leaf and fruit of both F. benghalensis and F. carica protects against CCl4-induced hepatotoxicity in rats. Keywords: Hepatoprotective potential, Ficus carica, Ficus benghalensis, Hepatic damage, Experimental rat model

Unraveling the interaction between lead and calcium in occupationally exposed males: an exploratory observation study.

The systemic illnesses associated with chronic lead exposure are partially explained by the interaction between lead and calcium metabolism. Lead exposure is posited to alter calcium levels either by altering calcium homeostasis markers or altering bone remodeling. The present study investigated the interaction between blood lead levels and calcium homeostasis markers and bone remodeling markers among lead-smelting plant workers. Adult male workers employed at the lead-smelting plant were clinically investigated as part of their regular occupational health assessment program. Additionally, control participants without occupational lead exposure, employed in administrative and white-collar jobs were invited to participate in the study. Sociodemographic and occupational details were collected by pre-standardized semi-structured questionnaires from all consenting participants, followed by clinical examination and blood collection. Blood lead levels were estimated using microwave-assisted acid digestion and the inductively coupled plasma mass spectrometry technique. Serum calcium and total protein and alkaline phosphatase levels were estimated as per standard biochemical techniques. 25-hydroxy vitamin-D3, calcitriol, and osteocalcin were estimated using the enzyme-linked immunosorbent assay. In addition to comparative analysis for comparing the two groups, independent linear regression models were explored to investigate the associations between serum calcium and blood lead and osteocalcin levels. A total of 189 lead-exposed men employed at the lead-smelting plant and 25 male control participants consented to participate. The two groups were similar in age, diet, and body mass index. Occupationally exposed individuals exhibited significantly lower serum calcium and higher bone remodeling markers (osteocalcin and alkaline phosphatase) as compared to controls. However, the serum 25-hydroxy vitamin-D3 and calcitriol levels were not significantly different between the two groups. Lastly, the serum lead and osteocalcin were weakly but significantly associated with serum calcium levels after controlling for variations in total protein, diet, 25-hydroxy vitamin-D3, calcitriol, and alkaline phosphatase in the study participants. Current observations reinforce the adverse role of lead exposure on calcium metabolism. Although lead exposure is posited to affect calcium metabolism by multiple pathways, current study observations favor the bone remodeling pathway. The observations recommend periodic screening for calcium and bone health among lead-exposed adults.

Aryl hydrocarbon receptor attenuates cholestatic liver injury by regulating bile acid metabolism

Cholestatic liver disease is defined as the bile acids (BAs) accumulation in the liver caused by impaired synthesis, and secretion, together with excretion of BAs due to a variety of factors, which, if left untreated, can result in hepatic fibrosis, cholestatic cholangitis, cholestatic cirrhosis, eventually, end-stage liver disease. Currently, modulation of BA metabolism is still a prospective therapeutic strategy for treating the cholestatic diseases. Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with far-reaching effects on the chronic liver disease. However, its role and mechanism in cholestatic liver damage is still unknown. Therefore, in this work, we explored the impact of AHR on the cholestatic liver injury using AHR overexpression mediated by adeno-associated viral (AAV) vectors. We found that AHR is differentially expressed in different stages of cholestatic liver disease, showing either down-regulation or an increase in protective effects. Overexpression of AHR increased body weight, decreased serum total bilirubin (TBil) and alkaline phosphatase (ALP), reduced porphyrin accumulation in liver tissue, and regulated the bile acid pool in the cholestatic mouse model induced by DDC diet. Overall, our data indicate that AHR attenuated cholestatic liver injury. AHR function indicates that it may have an action in the clinical management of cholestasis.

Bovine Viral Diarrhea Virus Infection in Cattle - Antioxidant Status and Some Biochemical Parameters

Background: Bovine viral diarrhea virus (BVDV) infections in cattle result in significant economic losses due to reproductive performance deficiencies caused by gastrointestinal, respiratory system infections, and transplacental infections. BVDV is one of the most important and widespread pathogens in cattle worldwide, including Turkey. Methods such as virus neutralization, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase and polymerase chain reaction (RT-PCR) are used for the detection of the disease. The diagnosis of the disease in its subclinical form is challenging due to the lengthy and costly procedures involved. Investigating oxidative stress parameters in ruminants with various diseases contributes significantly to diagnosis and prognosis. This study aimed to investigate some oxidative stress and biochemical parameters in cattle infected with BVDV. Materials, Methods &amp; Results: In the study, blood samples were collected from 80 Simmental breed cows aged between approximately 4 and 8 years to determine the presence of BVDV antibodies using the ELISA method. Based on the results obtained, study groups were organized. The study included a group of 10 animals with positive antibody levels as the infected group, and a group of 10 animals with negative antibody levels as the healthy group. Blood samples were taken from the animals, and serum separation was ensured. In the obtained serum samples, levels of vitamin E, vitamin A, β-Carotene, catalase, GSH-Px, and MDA were determined using spectrophotometric methods. In addition, serum total protein, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), calcium (Ca), and phosphorus (P) were measured using commercial test kits and an autoanalyzer. In the study, it was observed that the differences in serum MDA, vitamin E, vitamin A, β-carotene, and catalase levels were statistically significant between the healthy and BVDV-infected groups (P &lt; 0.001). The activity of GSH-Px was also found to be statistically different between the groups (P &lt; 0.01). Among the biochemical parameters, HDL, LDL, and AST levels were found to be statistically significant between the healthy and BVDV-infected groups (P &lt; 0.001). Additionally, ALP and glucose levels were found to be statistically significant (P &lt; 0.01). However, although there were differences in the levels of total protein, albumin, Ca, and P between the groups, these results were not statistically significant.Discussion: Although the diagnosis of the disease was partially made based on clinical observations in BVDV infections, the ELISA method was used for accurate diagnosis. Furthermore, it was found that there was a significant difference in MDA concentration between the healthy and infected groups, indicating oxidative damage caused by the virus. Similarly,significant differences in vitamin E, vitamin A, β-carotene, GSH-Px, and catalase levels were observed between the groups, indicating a decrease in antioxidant values due to the infection. In addition, differences in ALP, AST, glucose, LDL, and HDL levels were found between the groups. This difference is thought to be related to the effects of the disease agent on the liver and systemically. This study demonstrates that, in addition to the viral pathogen, antioxidant and biochemical values are important criteria in the detection of the disease. Keywords: antioxidant, bovine, BVDV, MDA, serum biochemistry.

#3724 CHANGES IN CARDIOVASCULAR CALCIFICATION AFTER PARATHYROIDECTOMY IN DIALYSIS-DEPENDENT PATIENTS

Abstract Background and Aims Vascular calcification (VC) is common in patients with end stage kidney disease on dialysis and with secondary hyperparathyroidism (SHPT). There is a lack of knowledge regarding dynamics of VC after surgical treatment of SHPT. We aimed to evaluate evolution of coronary artery calcification (CAC) and abdominal aortic calcification (AAC) after parathyroidectomy (PTx) in dialysis patients with SHPT. Method The prospective cohort study included 33 dialysis-dependent patients (mean age of 50±13 years) with severe SHPT who underwent subtotal (n = 16) or total PTx with autotransplantation of parathyroid tissue (n = 17). Cardiac computed tomography scan (quantification of coronary calcium by Agatston method) and lateral lumbar X-ray (semi-quantitative Kauppila score) were used to assess prevalence of VC before and 18 months after surgery. Levels of serum total calcium, phosphorus, parathyroid hormone (PTH), and alkaline phosphatase (AP) before and 18 months after surgery were also evaluated. Results In our cohort median dialysis vintage before surgery was 71 [Q1-Q3: 29; 136] months, total serum Ca was 2.47±0.23 mmol/l, median PTH was 139 [Q1-Q3: 90; 161] pg/ml. Prevalence of CAC before PTx was 79% (n = 26), and 61% (n = 20) of patients had AAC. Of note, 54.5% of the patients had severe coronary calcification (&amp;gt;400 AU), while only 12% were considered to have severe calcification using Kauppila score (&amp;gt;12). We observed moderate positive correlation between CAC and AAC scores (Spearman's ρ = 0.699 [95% CI: 0.48; 0.84], р&amp;lt;0.0001). Both CAC and AAC scores correlated moderately with age of the patients (ρ = 0.57 [95% CI: 0.3; 0.76], р = 0.0002, and ρ = 0.64 [95% CI: 0.39; 0.8], р&amp;lt;0.0001, respectively), AAC had weak correlation with their dialysis vintage (ρ = 0.45 [95% CI: 0.14; 0.68], р = 0.005. Median of baseline CAC was 458 [Q1-Q3: 23; 1585] AU, after 18 months - 491 [Q1-Q3: 58; 1956] AU, no statistically significant differences were observed (p = 0.91, Wilcoxon test). We did not find statistically significant differences between median of Kauppila scores before and after PTx as well: 3 [Q1-Q3: 0; 10] and 2 [Q1-Q3: 0; 10], correspondingly, p = 0.17 (Wilcoxon test) – Fig. 1. As it can be seen from Fig. 1, dynamics of both CAC and AAC values before and after PTx varied markedly across subjects. To investigate the factors that can promote VC we divided patients into 2 groups based on dynamics of САС (as the most accurate assessment method) 18 months after surgery: group 1 with CAC progression of more than 50 AU (n = 9) and group 2 with regression or progression less than 50 AU (n = 24). Patients who had progression of coronary calcification by the end of the follow-up had higher age (59±11 vs 46±12 years in 2nd group, p = 0.0128) higher serum calcium levels (2.57±0.24 vs 2.29±0.32 mmol/l in 2nd group, p = 0.0267), and higher AP levels at follow-up (69.8 [Q1-Q3: 62.8, 96.0] vs 51.7 [Q1-Q3: 41.4; 57.1] U/ml in 2nd group, p = 0.003). Univariate analysis showed no significant differences between groups comparing dialysis vintage (p = 0.53), phosphate levels (p = 0.54), PTH levels (p = 0.32). In addition, CAC progression risk was not associated with type of surgery (total vs subtotal PTx RR = 1.11 [95% CI: 0.71; 1.8], OR = 1.48 [95% CI: 0.3; 5.7], p = 0.708). Conclusion Prevalence of vascular calcification in dialysis-dependent patients with severe SHPT is high. Progression of CAC by 18 months after PTx was associated with higher age of the patients, higher follow-up levels of serum total Ca and AP.

The Preclinical Benefit of Glutamine in bisphenol A-induced Hepatotoxicity in Wistar Rats

Background: Oxidative stress may be a causative factor for bisphenol A (BPA) -induced hepatotoxicity. Glutamine (GM) is an amino acid with the ability to inhibit oxidative stress. Objective: This study evaluated the ability of GM to prevent BPA-induced hepatotoxicity in rats. Methods: Adult Wistar rats of both sexes (n=30) were used. The rats were randomly grouped into six of five rats each. Groups A (Control), B, and C were treated with normal saline (0.2 mL), GM (80 mg/kg), and BPA (50 mg/kg), respectively for 60 days. Groups D-F were treated with GM (20 mg/kg)+BPA (50 mg/kg), GM (40 mg/kg)+BPA (50 mg/kg), and GM (80 mg/kg)+BPA (50 mg/kg), respectively for 60 days. After treatment, blood and liver samples were obtained for biochemical and histological assessments, respectively. Results: Significantly (P&lt;0.01) decreased body weight and significantly (P&lt;0.01) increased liver weight occurred in the BPA-administered group when compared to the control group. The BPA-administered group showed significantly (P&lt;0.001) elevated serum total bilirubin, lactate dehydrogenase, aminotransferases, conjugated bilirubin, gamma-glutamyl transferase, alkaline phosphatase, and liver malondialdehyde concentrations when compared to the control group. Significantly (P&lt;0.001) decreased liver superoxide dismutase, glutathione peroxidase, catalase, and glutathione levels occurred in the PBA-administered group when compared to the control group. BPA caused hepatocyte necrosis, sinusoids, and central vein congestion. BPA-induced hepatotoxicity was reversed by GM; 20 mg/kg (P&lt;0.05), 40 mg/kg (P&lt;0.01), and 80 mg/kg (P&lt;0.001) in a dose-related fashion when compared to BPA. Conclusion: GM may be effective against BPA-associated hepatotoxicity.

Hepatoprotective Activity of 6-Heptadecylcyclohex -3-ene-1 Carboxylic Acid Isolated from the Methanol Extract of Dichrostachys cinerea Wight &amp; Arn. Stem Bark

Aim of the Study: The phytoconstituent 6-heptadecylcyclohex 3-ene-1 carboxylic acid isolated from the methanol extract of Dichrotachys cinerea Wight. stem bark was evaluated for hepatoprotective activity against CCl4 induced toxicity.&#x0D; Materials and Methods: The constituent 6-heptadecylcyclohex 3-ene-1 carboxylic acid isolated from the methanolic extract of D. cinerea and the structure was confirmed by spectroscopic studies. Hepatoprotective property was screened in male wistar strain rats. The parameters studied were estimation of liver function serum markers such as serum total bilirubin, total protein, alanine transaminase, aspartate transaminase, alkaline phosphatase and histological profile of the liver tissue.&#x0D; Results: The LD50 of methanolic extract and constituent, 6-Heptadecylcyclohex -3-ene-1 carboxylic acid were evaluated and found to be 500 and 100 mg/kg body weight respectively. The hepatoprotective activity of constituent was more significant as similar to the standard hepatoprotective drug silymarin. The histological profile of the liver tissue showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the controls.&#x0D; Conclusion: The methanolic extract of D. cinerea stem bark and the phytoconstituent 6-heptadecylcyclohex-3-ene-1 carboxylic acid showed significant protection from CCl4 induced liver damage.

Molecular test of Paget's disease of bone in families not linked to SQSTM1 gene mutations

PurposePaget's disease of bone (PDB) is a focal metabolic bone disorder characterized by an increased bone remodeling. Fifteen to 40 % of PDB patients have a familial form with an autosomal dominant inheritance. Disease-causing mutations of the SQSTM1 gene have been linked to PDB in about 40 % of families whereas genes linked to the remaining families are unknown. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in unrelated patient non-carriers of a SQSTM1 mutation. The current clinical practice guidelines still recommend the measure of serum total alkaline phosphatase (sALP) for PDB screening. In unrelated individual non-carriers of SQSTM1 mutations, we previously developed a genetic test combining male sex with five genetic markers (rs499345, rs5742915, rs2458413, rs3018362, rs2234968), giving rise to an area under the curve (AUC) for PDB phenotype of 0.73 (0.69; 0.77). A combination of male sex with total calcium corrected for albumin and Procollagen type I N-terminal propeptide (P1NP), had an AUC of 0.82 (0.73; 0.92). Combining both genetic and biochemical tests increased the AUC to 0.89 (0.83; 0.95). ObjectiveThis study aimed at estimating the performance of our previous test of PDB, in families not linked to SQSTM1 mutations with disease-causing genes yet unknown, and at developing a new algorithm if the performance is not satisfactory. MethodsWe genotyped the five SNPs cited above, and measured calcium corrected for albumin and P1NP in 181 relatives, with PDB or not, from 19 PDB families not linked to SQSTM1 mutations. Bivariate and multivariate logistic regression models including male sex were fitted to search for a molecular test that could best detect PDB in these families. A receiving operating characteristics analysis was done to establish a cut-off point for continuous variables. ResultsLogistic regression estimates of our previous molecular test gave rise to a high sensitivity of 78 %, 97 % and 88 % for the genetic, biochemical, and combined test but the specificity was very low, 35 %, 11 % and 21 %, respectively. This poor specificity persisted even when the cut-off point was changed. We then generated in these families, new logistic regression estimates but on the same parameters as mentioned above, giving rise to an AUC of 0.65 (0.55; 0.75) for the genetic test, of 0.84 (0.74; 0.94) for the biochemical test, and 0.89 (0.82; 0.96) for the combination test, the latter having a sensitivity of 96 % and specificity of 57 %. By comparison serum P1NP alone gave rise to an AUC of 0.84 (0.73; 0.94), with a sensitivity of 71 % and a specificity of 79 %. ConclusionIn PDB families not linked to SQSTM1 mutations, the estimates of our previous molecular test gave rise to a poor specificity. Using new estimates, the biochemical and combined tests have similar predictive abilities than our former test. Serum P1NP is a bone marker of interest for the screening for PDB in families not linked to SQSTM1 mutations.