scholarly journals Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Wang ◽  
J. Li ◽  
M. Song ◽  
P. Yan ◽  
X. Ju ◽  
...  

AbstractValproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A rs4244285 and CYP2C19*3 G636A rs4986893) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid were significantly higher in patients with CYP2C19 *1/*2 genotype (P < 0.01) or CYP2C19 *2/*3 genotype (P < 0.01) than in those with CYP2C12 *1/*1 genotype. The mean concentration/dose ratios of valproic acid were significantly higher in patients with 1 (P < 0.01) or 2 (P < 0.01) mutated alleles for CYP2C19 than in those without mutated alleles. And the post hoc analysis revealed that the result has acceptable statistical (power (1 – β) = 0.8486 at type I  level of 0.05) to support the observed significant associations for CYP2C19 SNPs and serum C/D ratios of valproic acid. The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population. The determination of the CYP2C19 genotypes may be useful for dosing adjustment in schizophrenia patients on valproic acid therapy.

2020 ◽  
Author(s):  
Shengdong WANG ◽  
Jing Li ◽  
Mingfen Song ◽  
Pan Yan ◽  
Xuan Ju ◽  
...  

Abstract Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A and CYP2C19*3 G636A) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid was significantly higher in patients with 1 (P = 0.029) or 2 (P = 0.007) mutated alleles for CYP2C19 than in those without mutated alleles. The mean concentration/dose ratios of valproic acid was significantly higher in patients with CYP2C19 *1/*2 genotype (P = 0.029) or CYP2C19 *2/*3 genotype (P = 0.014) than in those with CYP2C12 *1/*1 genotype. The findings of this study suggest that CYP2C19 genotypes play an important role in controlling steady-state serum concentrations of valproic acid in Chinese Han population.


2018 ◽  
Vol 74 (1) ◽  
pp. 6054-2018
Author(s):  
MAREK SZCZUBIAŁ ◽  
ROMAN DABROWSKI ◽  
WOJCIECH ŁOPUSZYŃSKI ◽  
MARIOLA BOCHNIARZ ◽  
MAGDALENA KRAWCZYK ◽  
...  

The aim of this study was the investigation of the circulating concentration of IGF-1 in female dogs with spontaneous mammary tumours. The study was performed on 34 female dogs undergoing surgery due to spontaneously occurring mammary gland tumours (24 malignant and 10 benign) and 10 clinically healthy fe-male dogs. The serum concentrations of IGF-1 were determined by specific ELISA Kit assay. The mean con-centrations of IGF-1 were significantly higher (P < 0.05) both in dogs with malignant (173.35 ± 120.45 ng/ml) and benign (130.58 ± 59.0 ng/ml) mammary tumours than in healthy controls (117.45±71.0 ng/ml). In the group of female dogs with mammary carcinomas, the mean concentration of IGF-1 gradually increased from 132.85 ± 65.64 ng/ml in dogs with grade 1 tumours to 317.74 ± 119.25 ng/ml in those with grade 3 tumours, and significant differences (P < 0.05) were found among dogs with various grade tumours. These findings suggest that circulating IGF-1 may play an important role in the pathogenesis of canine mammary tumour. Moreover, high IGF-1 levels may reflect tumour cell differentiation into a more aggressive phenotype. .


1978 ◽  
Vol 79 (3) ◽  
pp. 357-362 ◽  
Author(s):  
T. J. VISSER ◽  
L. M. KRIEGER-QUIST ◽  
R. DOCTER ◽  
G. HENNEMANN

The development of a highly sensitive and specific radioimmunoassay for 3,3′-di-iodothyronine (3,3′-T2) is described. The assay was applied to the measurement of 3,3′-T2 in unextracted human serum and used 8-anilino-l-naphthalene-sulphonic acid to inhibit the binding of 3,3′-T2 to serum transport proteins. The lower limit of detection of the assay was 2 fmol 3,3′-T2 per tube, which corresponded to 10 pmol 3,3′-T2/l serum. The mean concentration of 3,3′-T2 in normal serum was found to be 23 pmol/l, which is considerably lower than most values reported previously. Evidence is presented which suggests that the cross-reactivity of tri-iodothyronine with the antiserum to 3,3′-T2 is an important factor in the measurement of serum concentrations of 3,3′-T2 by radioimmunoassay.


1979 ◽  
Vol 82 (3) ◽  
pp. 395-401 ◽  
Author(s):  
JAN SVENSSON ◽  
PETER ENEROTH ◽  
JAN-ÅKE GUSTAFSSON ◽  
MARTIN RITZÉN ◽  
ÅKE STENBERG

The reduction of 4-[1,2-3H]androstene-3,17-dione (androstenedione) in vitro by scrotal skin was measured in samples from nine men (16–34 years old) with hypospadias and from ten male control subjects. The reduction of androstenedione was also studied in axillary and upper arm skin of seven control subjects. Androstenedione was reduced to material with chromatographic characteristics of 5α-androstane-3,17-dione and to 3α- and 3β-hydroxy-5α-androstan-17-one. No difference in 5α-reductase activity (defined as the sum of these three metabolites formed) was found in scrotal skin from hypospadic and control men. The mean concentration of 5α-dihydrotestosterone in serum from men with hypospadias was lower than that in serum from control subjects (P< 0·01). The mean ratio of the serum concentrations of testosterone and 5α-dihydrotestosterone was higher in hypospadic men than in control subjects (P< 0·05). No differences between the two groups were found in the mean serum concentrations of LH, FSH, prolactin, dehydroepiandrosterone, androstenedione, testosterone or testosterone-binding globulin.


2019 ◽  
Vol 17 (4) ◽  
pp. 112-116
Author(s):  
Sher Zamir ◽  
Azhar Ijaz ◽  
Muhammad Umair ◽  
Rahat Jan Wazir ◽  
Mohammad Salman ◽  
...  

Background: Literature has reported thyroid functional abnormalities in diabetes mellitus. The objectives of this study were to determine and compare the serum concentrations of T3, T4 and TSH in alloxan-induced type 1 diabetic and control Wistar albino rats. Materials & Methods: It was an experimental animal study on 20 Wistar albino rats, extending over a period of eight weeks. Alloxan, a diabetogenic agent, was used to produce animal models of type 1 diabetes. Animals were divided equally into two groups: control and diabetic. The animals in the diabetic group were injected intraperitoneally with 150 mg/kg body weight of 10% alloxan to induce diabetes. After 72 hours, diabetes was confirmed with glucometer (glucose >350mg/dl). During the course of experiment, one rat in control group and 2 rats in diabetic group died. Blood was collected for estimation of serum concentrations of thyroid hormones, thyroid stimulating hormone at the end of experimental period. Serum T3, T4, and TSH were measured using ELISA kits. Results: At the end of eight weeks, the mean concentration of serum T3 was 0.69 ±0.29 ng/ml and 0.44±0.02 ng/ml in control and diabetic groups, respectively. The mean concentration of T4 was 3.78±1.16 μg/dl and 2.24±0.86 μg/dl in control and diabetic groups respectively. The mean concentration of TSH was 0.77±0.20 μU/ml and 1.41±0.23 μU/ml in control and diabetic groups respectively. The mean serum concentrations of T3 (p=.0025) and T4 (p=<.00001) were significantly lower in diabetic and that of TSH (p=<.00001) were significantly higher in diabetic than control group. Conclusion: This study concludes that the serum concentrations of both T3 and T4 are significantly lower and that of TSH is significantly higher in alloxan-induced type 1 diabetic as compared to control group in Wistar albino rats.


2012 ◽  
Vol 109 (10) ◽  
pp. 1873-1880 ◽  
Author(s):  
Yulan Lin ◽  
Alicja Wolk ◽  
Niclas Håkansson ◽  
Jose Luis Peñalvo ◽  
Jesper Lagergren ◽  
...  

The validity of using FFQ to assess dietary lignans is uncertain. We aimed to validate the use of FFQ for the assessment of dietary intake of lignans compared to the serum biomarker enterolactone, the main product of dietary lignans' metabolism in human subjects. A random sample of women, aged 55–75 years, from the Swedish Mammography Cohort was selected. Information from two FFQ, the FFQ-87 (sixty-seven food items) and the FFQ-97 (ninety-three food items), and blood samples were collected. Dietary intake of lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol and syringaresinol) was assessed by the FFQ. Serum concentrations of enterolactone were analysed by time-resolved fluoroimmunoassay. The correlation coefficient between energy-adjusted lignan intake and serum enterolactone was estimated in crude and multivariable-adjusted models, taking into account the factors potentially influencing the serum enterolactone. Among the 135 participants aged 55–75 years, with a mean BMI of 26·7 kg/m2, the average energy-adjusted intake of total lignans was 1616 (sd 424) and 1516 (sd 409) μg/d according to the FFQ-87 (forty-five food items containing lignans) and the FFQ-97 (sixty-five food items containing lignans), respectively. The mean concentration of serum enterolactone was 23·2 (sd 15·4) nmol/l. The adjusted Pearson's correlation between dietary intake of lignans assessed by the FFQ-97 and serum enterolactone was statistically significant (r 0·22, P= 0·01). No significant correlation was observed for the FFQ-87 (r 0·09, P= 0·30). The present study indicates that the FFQ-97 might be better than the FFQ-87 for assessing dietary intake of lignans, although the correlation was low.


2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Reham A.M. Ellisy ◽  
Ali Helmi Bakri ◽  
Safwat A. Mangoura ◽  
Mahmoud H. Abdelraheem ◽  
Hanan S.M. Farghaly

2016 ◽  
Vol 85 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Csilla Tóthová ◽  
Oskar Nagy ◽  
Veronika Nagyová ◽  
Gabriel Kováč

This study was aimed at the evaluation of changes in the concentrations of selected blood serum proteins in calves during the first three months of life, including precolostral, colostral, milk, transitional and solid feeding period. Nine clinically healthy calves were used in this study. The first blood sampling was performed before the colostrum intake (day 0) and then at 1, 2, 7, 14, 30, 60, and 90 days of age. Blood serum was analyzed for the concentrations of α1-fetoprotein, prealbumin, transferrin, and lactoferrin. The results showed significant changes in the serum concentrations of all the evaluated proteins in calves during the first three months of life (P< 0.01 andP< 0.001). At birth, the mean concentration of α1-fetoprotein was low and increased more than × 8 at one day after colostrum intake, then a gradual decrease was found up to day 30 of life. Similar tendency was observed in the concentrations of prealbumin and lactoferrin. While the concentrations of prealbumin increased approximately × 3.5 at one day after colostrum intake, the serum lactoferrin values showed approximately 1.5-fold increase. A subsequent gradual decrease from the 2ndday of life was found for both prealbumin and lactoferrin. In the concentrations of transferrin, a significant increase was observed on day 7 (P< 0.05). The highest values were found at the age of 14 and 30 days. These results suggest that concentrations of these proteins in calves are markedly altered during the postnatal period, which should be taken into consideration for their precise interpretation in young animals.


1977 ◽  
Vol 86 (1) ◽  
pp. 140-145 ◽  
Author(s):  
Jan Fahrenkrug ◽  
Ove B. Schaffalitzky de Muckadell ◽  
Jens F. Rehfeld

ABSTRACT The serum concentrations of immunoreactive gastrin and immunoreactive calcitonin were measured in 13 fasting patients with achlorhydria and pernicious anaemia and in 10 age- and sex-matched fasting control subjects. All patients had highly elevated concentrations of gastrin in serum (1486 ± 336 pg/ml, mean ± sem). The mean concentration in the controls was 35.2 ± 6.4 pg/ml. No difference in the concentration of calcitonin was found between the pernicious anaemia patients and the controls, the levels being 0.93 ± 0.08 and 0.89 ± 0.03 ng/ml, respectively. Suppression of endogenous gastrin secretion in 5 of the patients by intragastric acid administration was not accompanied by any decrease in calcitonin concentration in serum. The findings suggest that chronically elevated endogenous gastrin is without influence on calcitonin secretion.


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