Influence Of UGT1A3 Gene Polymorphism In Pediatric Epileptics on Valproate: A Protocol (Preprint)

2020 ◽  
Author(s):  
Usha Adiga ◽  
Sachidanada Adiga ◽  
Nandit Banawalikar ◽  
Vijaya Shenoy

BACKGROUND Epilepsy is a chronic neurological disease characterized by recurrent unprovoked seizures. Therapeutic drug monitoring (TDM) has often been performed during the pharmacological treatment of epilepsy, but the plasma levels of some AEDs do not correlate well with the doses and/or the therapeutic or toxic effects of the drugs. OBJECTIVE Objective of the study is to evaluate the pattern of polymorphism in UGT1A3 in pediatric epileptics on valproate. It also aims to find the association between gene polymorphism and plasma concentration of valproate, its clinical effectiveness and its adverse effect profile. METHODS One hundred children aged 2-18 years with a diagnosis of epilepsy and treated with sodium valproate mono therapy will be included in the study. Their demographic profile, type of seizure, dose and frequency of sodium valproate will be recorded. Five ml of venous blood will be collected after 30 days of starting the regimen,3ml EDTA blood will be utilized for genotyping by PCR-RFLP method and for platelet count, 2 ml plain blood will be used for estimating serum drug concentration by HPLC and for biochemical tests. The patient will be followed up quarterly or more frequently (as deemed by the clinician) for clinical evaluation. Statistical analysis: Hardy-Weinberg equilibrium (HWE) analysis will be performed on UGT1A3 polymorphisms. ANOVA will be used to investigate the association between genotypes distribution and serum concentration of VPA. A p-value <0.05 was regarded as statistically significant. RESULTS The study is funded by Indian council of Medical research, sanction letter dated 19.08.2019 No.5/4-5/187/Neuro/2019-NCD-I. The university ethical approval was obtained, ref NU/CEC/2019/0223.A total of thirty samples are collected at the end of six months.PCR-RFLP and HPLC methods are standardized and results will be available on completion of the study. CONCLUSIONS Genetic polymorphisms of UGTs may influence VPA metabolism and hence the steady-state concentration of the drug in plasma may be altered. This may demand an increased or reduced dose of VPA in epileptics so as to maintain the therapeutic levels. The study may be useful in optimizing the anti-epileptic dosage. CLINICALTRIAL NOt applicable.

2018 ◽  
Vol 1 (2) ◽  
pp. 114
Author(s):  
Wahdaniah Wahdaniah ◽  
Sri Tumpuk

Abstract: Routine blood examination is the earliest blood test or screening test to determine the diagnosis of an abnormality. Blood easily froze if it is outside the body and can be prevented by the addition of anticoagulants, one of which Ethylene Diamine Tetra Acetate (EDTA). Currently available vacuum tubes containing EDTA anticoagulants in the form of K2EDTA and K3EDTA. K3EDTA is usually a salt that has better stability than other EDTA salts because it shows a pH approaching a blood pH of about 6.4. The purpose of this research is to know the difference of erythrocyte index results include MCH, MCV and MCHC using K3EDTA anticoagulant with K2EDTA. This research is a cross sectional design. This study used venous blood samples mixed with K2EDTA anticoagulant and venous blood mixed with K3EDTA anticoagulants, each of 30 samples. Data were collected and analyzed using paired different test. Based on data analysis that has been done on MCH examination, p value <0,05 then there is a significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value. Then on the examination of MCV and MCHC obtained p value <0.05 then there is no significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value.Abstrak: Pemeriksaan darah rutin merupakan pemeriksaan darah yang paling awal atau screening test untuk mengetahui diagnosis suatu kelainan. Darah mudah membeku jika berada diluar tubuh dan bisa dicegah dengan penambahan antikoagulan, salah satunya Ethylene Diamine Tetra Acetate (EDTA). Dewasa ini telah tersedia tabung vakum yang sudah berisi antikoagulan EDTA dalam bentuk  K2EDTA dan  K3EDTA. K3EDTA  biasanya berupa garam yang mempunyai stabilitas yang lebih baik dari garam EDTA yang lain karena menunjukkan pH yang mendekati pH darah yaitu sekitar 6,4. Tujuan dari penelitian ini adalah untuk mengetahui perbedaan hasil indeks eritrosit meliputi MCH, MCV dan MCHC menggunakan antikoagulan K3EDTA dengan K2EDTA. Penelitian ini merupakan penelitian dengan desain cross sectional. Penelitian ini menggunakan sampel darah vena yang dicampur dengan antikoagulan K2EDTA dan darah vena yang dicampur dengan antikoagulan K3EDTA, masing-masing sebanyak 30 sampel. Data dikumpulkan dan dianalisis menggunakan uji beda berpasangan. Berdasarkan analisis data yang telah dilakukan pada pemeriksaan MCH didapatkan nilai p < 0,05 maka ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit. Kemudian pada pemeriksaan MCV dan MCHC didapatkan nilai p < 0,05 maka tidak ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit.


Author(s):  
Mariam Raafat ◽  
Soha H. Talaat ◽  
Salma M. Abdelghaffar ◽  
Engy A. Ali

Abstract Background Endometriosis is a common gynecologic disorder characterized by the implantation of the endometrial tissue ectopically outside the endometrial cavity. It affects about 10% of females at the childbearing period and is estimated to be present up to 20–50% in women complaining of infertility. While laparoscopy is considered the mainstay for diagnosis, magnetic resonance imaging (MRI) is recognized as a useful tool for definitive diagnosis, pre-surgical planning, and determining whether the patient will require multi-specialty involvement. The aim of this study is to evaluate the performance of MRI with the addition of diffusion-weighted imaging (DWI) and T2 star (T2*) to conventional MRI, for the accurate assessment of ectopic endometrium. Results Endometriotic lesions that showed diffusion restriction on DWI were 80.7%, and 96.1% of the endometriotic lesions had signal voids on the T2*W sequence, whereas only 65.4% of the lesions had typical signal intensities on T1WI and T2WI. Diagnostic performance of the MRI examination was improved by the use of the diffusion sequence and better improved by the T2* sequence, compared to the conventional MR protocol sensitivity (SE) = 96.12% and specificity (SP) = 85.7% in T2*-weighted images, SE = 80.7% and SP = 71.4% in DWI, and SE = 65.4% and SP = 71.4% in conventional MRI. P value for conventional MRI was 0.1, which is of no statistical significance (p < 0.05). P value for DWI was 0.016, which is statistically significant (p < 0.05). P value for T2*WI was 0.001, which is more statistically significant (p < 0.05) and could be adequately correlated with laparoscopy. Conclusion DWI and T2* significantly increase MRI diagnostic accuracy by allowing the detection of the hemorrhagic character of the endometriotic lesions. Studies with a large sample size are needed to confirm that they can replace invasive laparoscopy for the diagnosis of endometriosis.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Pasant Mohamed Abo-Elhoda Darwish Mohamed Abo-Elhoda ◽  
Hesham Mahmoud Ahmed Mansour ◽  
Yosra Abdelzaher Abdullah ◽  
Eman Ahmed Fouad Darwish

Abstract Background Susceptibility weighted imaging (SWI) is a 3D gradient-echo MR technique that is based on blood oxygen level dependent (BOLD) induced phase effects between the venous blood and the surrounding brain parenchyma. SW-MR imaging allows for noninvasive visualization of small veins at submillimeter resolution and, therefore, is used to depict venous architecture in brain lesions. The extreme sensitivity of SWI for the detection of neovascularity (venous blood), haemorrhage, and calcification has been an indispensable tool for characterization of the internal architecture of brain tumours. Objectives Is to evaluate the role of Susceptibility weighted imaging in assessment of adults Intra axial brain Neoplasms, and its ability to characterize them into high and low grade lesions in comparison to histopathology which will be used as gold standard. Methods A cross sectional study including 31 patients suspecting intracranial brain neoplasm radiologically and clinically, conducted at Private center, the patients were investigated using Siemens machine Magnetom Skyra 3T, the period was between January 2018 till the end of June 2019 . Results Our study included 31 patients. Including 15 female and 16 male patients, with the patient’s age ranging from 20 to 68 years old with median 48 years old ranging from 35.75 (25% percentile) to 58.75 (75% percentile). Among total cases, there were 8 patients with grade 2 glioma, 10 patients with grade 3 glioma and 6 patients with grade 4 glioma, 2 patients with lymphoma and 5 patients with brain metastasis (1 lung cancer and 4 breast cancer). All the patients were evaluated with MRI including SWI sequence with special comment on the number of the intratumoral susceptibility signal (ITSS), the size of the ITSS, its morphology as well as the ratio of the ITSS to the tumor size, which were then correlated with the patient histopathological results obtained later. The study revealed that the best parameter to accurately grade the tumor is the number of ITSS within the lesion with P value 0.001, followed by the size of the ITSS with P value 0.002 and Pearson Chi-Square value equals 20.6, while the lowest one was the ratio of the ITSS to the tumor size with P value 0.002 Pearson Chi-Square value equals 17.3. Our study showed that the morphology alone was not able to accurately grade the tumor with P value 0.007 ( Not significant) Conclusion SWI using 3T MR system provides quite useful information for preoperative tumor grading. There seems to be a strong correlation between pathological grading and that assessed with SWI.


2019 ◽  
Vol 13 (2) ◽  
pp. 72-86
Author(s):  
Depi Lukitasari

Background. During hospitalization large number of invasive procedure recived by patient and preceived as threatening and anxiety experience. One of the invasive procedures that commonly done is the venous blood extraction. The children in preschool age preceived venous blood extraction as something that endanger the integrity of the body and lead to anxiety experience. To reduce the anxiety during the venous blood extraction, a nurse could perform a clay theraphy. The aim of this research is to ascertain the effect of clay therapy toward scoreof anxiety in preschool age children that undergoing venous blood extraction in RSUD Al-Ihsan.Methode. The study was quasi-experiment with nonequivalent control group posttest only. A total of 34 children who recieve venous blood extraction was assigned into 2 group, 17 children in control and 17 children in intevention. The children anxiety level measured using anxiety observation sheet before the procedure complete. Data were analyzed used independent t test for bivariate and logistik regresion for multivariate. Result Findings. The results  show a significat difference in anxiety score between control group and intervention group with p-value 0,001 < α 0.05 which means there is impact of clay therapy to level anxiety in preschool age children undergoing invasive procedure in RSUD Al-Ihsan. Conclusion. This research indicate that clay therapy may be used to reduce anxiety in children that undergoing venous blood extraction.


2017 ◽  
Vol 26 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Shorifa Shahjadi ◽  
Arif Salam Khan ◽  
Mesbah Uddin Ahmed

Background: Mitochondrial dysfunction and abnormal brain bioenergetics can cause autism.Cellular function impairment due to mitochondrial dysfunction may cause cognitive impairment, language deficits and abnormal energy metabolism in autism.Objective: The aim of this study was to evaluate biochemical evidence of the mitochondrial dysfunction by measuring blood ammonia, serum lactate, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine kinase (CK) in autism spectrum disorder children.Methods: This observational type of analytical study with case-control design was conducted in the Department of Physiology of Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka. For this study, a total number of 20 Subjects were randomly selected, among which 10 were apparently healthy subjects (control group-A) for comparison and 10 were diagnosed children with autism spectrum disorder (study group-B). 5ml venous blood was collected from both groups for analysis serum CK, AST, ALT, lactate and blood ammonia. Blood ammonia, serum lactate, AST, ALT and CK level were estimated in all children by standard laboratory method. Independent sample‘t’ test was used for statistical analysis. P value <0.05 was accepted as significant. The mean of all the measured biochemical variables in normal children were within normal ranges.Result: Blood ammonia, serum lactate, AST, CK were found significantly higher in autism spectrum disorder children in comparison to control Conclusion: From the result of this study it may be concluded that mitochondrial dysfunction occur in autistic spectrum disorder children .J Dhaka Medical College, Vol. 26, No.1, April, 2017, Page 43-47


2015 ◽  
Vol 101 (1) ◽  
pp. e1.10-e1 ◽  
Author(s):  
J. Samardžić ◽  
A. Smits ◽  
V. Cossey ◽  
I. Soldatović ◽  
M. Bajčetić ◽  
...  

*presenting author, supported by ERAWEB II scholarship for postdoctoral program at the KU Leuven, Belgium (2014–2015)IntroductionVancomycin, a glycopeptide antibiotic, is frequently used for late onset sepsis (LOS) and catheter-related infection. Larger inter- and intra-patient variability, combined with a narrow therapeutic index, warrants therapeutic drug monitoring (TDM). However, large inter-individual variability in PK parameters in neonates is documented, only partly explained by covariates such as weight, age or serum creatinine (1,2). In the current study, we focus on the potential impact of between assay differences for vancomycin (3) on the variability in its concentration in a single neonatal intensive care unit (NICU).MethodsVancomycin TDM observations of neonates and young infants treated with intravenous vancomycin, mainly for (suspected) LOS (ie, >72 hours after birth), in the Leuven NICU, Belgium, between June 2011 and December 2014. Our patient population, consists of (pre)term neonates, inborn or transferred, in need of specialized care related to prematurity, infections, perinatal asphyxia, congenital diseases (eg, surgery for cardiopathy, congenital diaphragmatic hernia, or esophageal atresia), or other diseases. Clinical characteristics at birth, as well as characteristics at the moment of TDM were extracted from the patient files. We aimed to document early vancomycin exposure, therefore only first trough levels were included. Serum vancomycin assay was performed either with a particle-enhanced turbidimetric inhibitionimmunoassay method (Siemens Dimension; Dade Behring, Deerfield, Illinois–PETINIA) or with an enzyme multiplied immunoassay technique (Cobas c702; Roche Diagnostics, Basel, Germany–COBAS). The data were analyzed by Chi-square test, t test and Mann-Whitney U test. Linear Mix Model was used to assess significant differences between groups, when adjusting for confounding factors. Data were analyzed in SPSS 20.0 (IBM corp.), p-value <0.05 was significant.ResultsIn total, 564 vancomycin TDM observations, 311 assayed with PETINIA and 253 with COBAS, were included. Both cohorts had comparable clinical characteristics (median [min-max] current weight 2150 [420–5000] grams for PETINIA vs. 2120 [500–5840] grams for COBAS, and median postmenstrual age 35 [25–58] weeks for PETINIA vs. 35 [25–51] weeks for COBAS). We determined the significant difference between the vancomycin concentrations using two different immunoassays: PETINIA vs. COBAS (F=17.971; p<0.001). When adjusting for current body weight and postmenstrual age, the major covariates associated with vancomycin serum trough levels in neonates, the difference in vancomycin concentration between cohorts was statistically significant (F=17.076, p<0.001, F=18.951, p<0.001, respectively). Overall, immunoassays PETINIA and COBAS significantly differed by vancomycin concentrations when adjusting for covariates, and the mean difference for vancomycin concentration was 2.167 mg/l.ConclusionThe present study confirms the impact of assays on the variability in vancomycin concentration in neonates in a single NICU. Comparison between these two immunoassays showed a mean proportional differences >20%. Therefore, it is important to know how the vancomycin is measured when interpreting results, and particularly the transferability of vancomycin results between the laboratories has to be interpreted with caution.


2020 ◽  
Author(s):  
Benedicto Crespo-Facorro ◽  
Miguel Ruiz-Veguilla ◽  
Javier Vazquez-Bourgon ◽  
Ana C. Sanchez-Hidalgo ◽  
Nathalia Garrido-Torres ◽  
...  

Background: Antipsychotics suppress expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID versus COVID RNA-Seq samples (CRA002390 project in GSA database) and drug-naive patients with psychosis at baseline and after three months of aripiprazole treatment was identified. An integrative analysis between COVID and aripiprazole immunomodulatory antagonist effects was performed. Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher's Exact Test, two tail; P value=3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated schizophrenia patients (P adj<0.05). The most significant pathways were associated to the immune system such as the inflammatory bowel disease (IBD) (the most significant pathway with a P adj of 0.00021), Th1 and Th2 cell differentiation and B cell receptor signaling pathway, all three related to the defense against infections. Interpretation: This exploratory investigation may provide further support to the notion that protective effect is exerted by phenylpiperazine by modulating the immunological dysregulation associated to COVID-19. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.


2019 ◽  
Vol 16 (3) ◽  
pp. 20-26
Author(s):  
L.V. Natrus ◽  
L.V. Gayova ◽  
O.O. Gorkunenko ◽  
P.A. Chernovol ◽  
M.V. Zelinska

Relevance. Investigation of polymorphism in a locus of CYP2E1 as the prognostic factor of drug-induced hepatotoxicity at anti-TB therapy is significant due to the influence of CYP2E1 on drug metabolism. The objective of the investigation is to analyze the association of rs2070676 СYP2E1 gene polymorphism with drug-induced hepatotoxicity by means of the clinical-laboratory values of serum transaminases at anti-TB treatment. Materials and methods. The study involved 47 patients with drug-susceptible tuberculosis first time discovered. 58 healthy volunteers comprised a control group. Laboratory indices were determined in venous blood three times: before the treatment as baseline; in 2 months of intensive therapy (isoniazid, rifampicin, ethambutol, pyrazinamide), then in 4 months of maintenance therapy (isoniazid, rifampicin). Serum activities of enzymes ALT, AST, and GGT were measured by standard algorithm on automatic analyzer BS-300. Analysis of rs2070676 polymorphism of CYP2E1 gene was performed by polymerase chain reaction using standard PureLink® Genomic DNA Kit for Purification of Genomic DNA; Manufacturer of INVITROGEN (USA). For statistical processing, IBM SPSS Statistics 23 was applied. Results. Investigation of serum ALT and AST in patients with major genotype CYP2E1 (C/C) showed the lower baseline ALT and AST levels comparing to the control group, which might be caused by suppression of hepatocytes functions at the development of the disease. Anti-TB treatment caused an increase in ALT and AST levels comparing to the baseline in patients with major CYP2E1 (C/C) genotype. In the group with C/G polymorphism, the baseline ALT level didn’t differ much from the baseline of the control group; it showed a decrease after intensive therapy and returned back to the initial level at maintenance therapy. This might be related to the certain protective property of СYP2E1 gene polymorphism. The AST level was increased after intensive therapy (to a smaller extent than for the patients with major C/C genotype) and remained on the same level at maintenance therapy. A study of GGT showed a gradual increase regardless of genotype. Conclusion. According to the data of the experiment, the status of hepatocytes in patients with tuberculosis at baseline and during treatment was different depending on the CYP2E1 genotype. The results of the experiment indicate that the CYP2E1 gene polymorphism has a certain protecting role. It reduces the level of drug metabolites and hepatotoxicity which causes mitochondrial dysfunction.


2017 ◽  
Vol 4 (2) ◽  
pp. 457
Author(s):  
Sujatha G. ◽  
Vindhya P. ◽  
Kalyan Kumar K.

Background: Approximately one million patients develop pleural effusion every year. It is a common clinical disorder and is either a manifestation or a complication of one or other respiratory or non-respiratory disorders. It leads to serious prognosis, if not diagnosed and treated properly. To calculate SEAG and Light’s criteria and to compare SEAG with Light’s criteria in analyzing pleural effusions.Methods: A total of hundred patients were selected for the study. Pleural fluid of patients who met the inclusion and exclusion criteria were collected, when pleural fluid is being tapped for diagnostic thoracocentesis. Venous blood sample was collected along with diagnostic thoracocentesis or within 24 hours of thoracocentesis.  Written informed consent was obtained from them for thoracocentesis.Results: In our study we compared the clinical outcome with outcome as per Pleural fluid/Serum protein ratio (p value of <0.0001), pleural fluid/serum LDH (p value of <0.0001) and pleural fluid LDH (p value of <0.0001) separately and the p values were statistically significant. The sensitivity, specificity, PPV and NPV of Light’s criteria were 77.2%, 100%, 100%, 93.9% respectively. We compared Light’s criteria outcome with clinical outcome and the difference was statistically significant (p value of <0.0001). SEAG showed 100% sensitivity, 97.43% specificity, 91.6% PPV and is 91.66% and NPV is 100%. We compared the clinical outcome with SEAG and there was statistically significant difference (p value of <0.0001). We compared SEAG with Light’s criteria and the difference was statistically significant (p <0.0001). We compared Light’s plus pleural fluid protein gradient with SEAG and the difference is statistically significant (p value of <0.0001).Conclusions: SEAG is more sensitive for classifying transudates and more specific for exudates than Light’s criteria.


2019 ◽  
Author(s):  
Jinfang Song ◽  
Mingzhu Zhang ◽  
Jiang Ni ◽  
Tao Wang ◽  
Yi-Qing Zhao

Abstract Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment. Results: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a reduction in fasting plasma glucose (FPG) levels with an increase in homeostasis model assessment for β cell HOMA-β in the carriers of genotype CG + GG at rs10830963, when compared with the wild-type CC (P <0.05). Conclusion: Thus, it was found that the MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers. Trial registration: This study was registered in the Chinese Clinical Trial Register (No. ChiCTR-CCC13003536).


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