Impact of MDR1 and UGT Gene Polymorphisms on Sodium Valproate Plasma Concentration in Patients with Epilepsy.

BACKGROUND: This study aimed to identify the effects of multidrug resistance gene 1 (MDR1) and UGT gene polymorphisms on the plasma concentration of VPA in subjects with epilepsy and provide a reference for individualized medicine of patients with epilepsy. METHODS: One hundred subjects with epilepsy who were treated with sustained release VPA monotherapy were enrolled. Sanger sequencing was used to detect the genotypes of MDR1_G1199A, MDR1_G2677T/A, UGT1A6_A 552C, T19G and UGT2B7_C161T. By adjusting the plasma concentrations of VPA with body weight and a total daily dose of VPA, the concentration-to-dose ratio of VPA (CDRV) was obtained. Data were analyzed using SPSS17.0. RESULTS: No mutation of MDR1_G1199A gene was detected. MDR1_G2677T/A site T allele frequency is 43.5%, A is 14%. The genetic frequencies of UGT1A6_A552C, T19G, and UGT2B7_C161T were 29.5%, 25.5%, and 36%, respectively. Significant differences in CDRV were observed between carriers of TT, TG, and GG genotypes in the UGT1A6_T19G polymorphism (p = 0.021, p < 0.05). The CDRV was significantly lower in patients carry UGT1A6_T19G GG genotype compared to TG ((3.40 ± 1.61) µg.kg/mL.mg) and TT ((4.33 ± 1.97) µg.kg/mL.mg) genotype. While the MDR1_G2677T/A, UGT1A6_A552C and UGT2B7_C161T gene polymorphisms had no effect on the plasma concentration of VPA (p > 0.05). CONCLUSIONS: The genetic polymorphisms of UGT1A6_T19G significantly affect the plasma concentration of VPA in patients with epilepsy and the mutation of this locus can decrease the blood concentration of VPA. The MDR1_G2677T/A, UGT1A6_A552C and UGT2B7_C161T gene polymorphisms did not affect the plasma VPA concentration in Han patients with epilepsy.

Prognostic impact of prognostic nutritional index on renal cell carcinoma: A meta-analysis of 7,629 patients.

BACKGROUND: Prognostic nutritional index (PNI) is a parameter which reflects nutritional and inflammatory status. The prognostic value of PNI in renal cell carcinoma (RCC) remains in debate. The aim of this study is to evaluate the prognostic value and clinicopathological features of PNI in RCC. METHODS: A literature search was performed in the databases of PubMed, Embase, Web of Science, and Cochrane Library. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were extracted for meta-analysis. The association between PNI and overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), progression-free survival (PFS), recurrence-free survival (RFS), and clinicopathological factors were evaluated. RESULTS: Eleven studies involving 7,629 patients were included for meta-analysis. A decreased PNI was shown to be a significant predictor of worse OS (HR = 2.00, 95%CI = 1.64-2.42, p<0.001), CSS (HR = 2.54, 95%CI = 1.61-4.00, p<0.001), and DFS/PFS/RFS (HR = 2.12, 95%CI = 1.82-2.46, p<0.001) in RCC. Furthermore, a low PNI was correlated with Fuhrman grade III-IV (OR = 1.96, 95%CI = 1.27-3.02, p = 0.002), T stage T3-T4 (OR = 2.21, 95%CI = 1.27-3.87, p = 0.005), presence of sarcomatoid differentiation (OR = 5.00, 95%CI = 2.52-9.92, p<0.001), and presence of tumor necrosis (OR = 3.63, 95%CI = 2.54-5.19, p<0.001). CONCLUSION: PNI is an independent prognostic indicator of survival and associated with Fuhrman grade, T stage, sarcomatoid differentiation, and tumor necrosis in patients with RCC.

Febuxostat is superior to allopurinol in delaying the progression of renal impairment in patients with chronic kidney disease and hyperuricemia.

PURPOSE: This study aimed to compare efficacy of renal-protective function between febuxostat and allopurinol in patients with chronic kidney disease (CKD) and hyperuricemia (HUA). METHODS: Totally 152 CKD stage 2-3 patients complicated with HUA were recruited. According to their uric acid-lowering therapy, there were 67 patients included in febuxostat group and 85 in allopurinol group, respectively. Estimated glomerular filtration rate (eGFR), serum creatinine (Scr), 24-h proteinuria, serum uric acid (SUA) were measured at M0, M1, M3 and M6 after the treatment. Primary outcome was proportion of patients showing ≥ 10% decline in eGFR from baseline at M6. RESULTS: The eGFR at M6 was numerically higher at M6 and eGFR change (M6-M0) was increased in febuxostat group compared with allopurinol group. Most importantly, the proportion of patients showing a ≥ 10% decline in eGFR from baseline at M6 was reduced in febuxostat group compared with allopurinol group. Multivariate logistic regression analyses further validated that febuxostat vs. allopurinol was an independent predictor for reduced risk of eGFR decline ≥ 10% from baseline. Besides, SUA change (M6-M0) was decreased, but Scr change (M6-M0) and 24-h proteinuria change (M6-M0) were similar in febuxostat group compared with allopurinol group. CONCLUSIONS: Febuxostat presents a superior effect in delaying renal impairment progression compared with allopurinol in CKD patients complicated with HUA.

Effects of lanthanum carbonate on vascular calcification in elderly maintenance hemodialysis patients.

The effect of lanthanum carbonate on abdominal aortic calcification (AAC) in the elderly maintenance hemodialysis (MHD) patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group (n=28) and control group (n=26). The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone (iPTH) levels and AAC scores at third month after treatments were compared between the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen (BUN), serum creatinine (Scr), uric acid, albumin, hemoglobin, C reactive protein (CRP), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, total cholesterol between case group and control group (P>0.05 for all). There was also no significant difference in the baseline itching scores between the case group and the control group (P>0.05). At 1st and 3rd month after treatment, the itching scores in the case group were 14.2 ± 3.2 and 10.5 ± 2.3, respectively, which were significantly lower than the baseline and those in the control group (P<0.05 for all). At 1st and 3rd month after treatment, the itching scores in the control group were 23.6 ± 5.9 and 24.8 ± 6.3, respectively, which were significantly higher than the baseline (P<0.05). There was no significant difference in the baseline of serum calcium, phosphorus, calcium-phosphorus products, iPTH levels between the case group and control group (P>0.05). At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline (P<0.05), and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group (P<0.05). The AAC scores showed statistically significant difference between the case group and the control group (P<0.05). The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbonate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phosphorus and iPTH levels, resulting in the attenuation of vascular calcification.

Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands.

Design, syntheses and structure-activity relationships of N-acetylated piperazine privileged structures containing MC4R agonist compounds were described. The most potent derivatives were low nM MC4R selective full agonists. Several compounds from the series had modest pharmacokinetic properties.