Population pharmacokinetics of theophylline in adult Chinese patients with asthma and chronic obstructive pulmonary disease

Background Theophylline has a narrow therapeutic range and large interindividual variability in blood levels, so a thorough understanding of its pharmacokinetic characteristics is essential. Population pharmacokinetic (PPK) approaches could achieve it and many PPK studies of theophylline have been reported in infants. However, none was conducted in Chinese adults and none has explored the effect of CYP1A2 genotypes on the PPK characteristics of theophylline in adults. Objective To evaluate the PPK characteristics of theophylline and to assess the possible influence of covariates, including CYP1A2 genotypes, on theophylline clearance in Chinese adult patients. Setting The study is conducted at the department of respiration in Zhujiang Hospital, Guangzhou, China. Methods Theophylline concentrations were obtained from eligible patients and were measured by high performance liquid chromatography. The polymorphisms of ??3860G?>?A, ??163C?>?A, C5347T (CYP1A2*1B) and G-3113A were genotyped using a direct sequencing method. Then, CYP1A2 genotypes, age, fat-free mass (FFM) and other covariates were used to develop a PPK model by NONMEM software. Bootstrap analysis was used to asses the accuracy and prediction of the PPK model. Main outcome measure The concentration and clearance of theophylline. Results A total of 134 theophylline concentrations from 95 patients were obtained. The final model was as follows: CL/F(L/h)?=?4.530?×?(FFM/56.1)^0.75 ×?0.713^CYP1A2*1B, the inter-individual variability in clearance/bioavailability (CL/F) was 44.0%, and the residual variability was 9.8%. The final model was proved to be reliable by bootstrap analysis. Conclusion Theophylline clearance was significantly associated with FFM and CYP1A2*1B genotypes in Chinese adult patients.     

中医辨证治疗高血压的效果分析

目的:分析中医辨证治疗高血压的效果.方法:随机抽取2015年3月～2016年9月128例高血压患者,分为对照组(n=64)与观察组(n=64),对照组予以西医的治疗方法,即服用常规的降血压药物;观察组予以中医辨证治疗的方法,即依据不同的症状服用不同的中药药剂,观察两组临床效果、治疗后的血压与不良反应.结果:观察组临床有效率为89.06％,明显高于对照组的70.31％(P<0.05);同时两组血压变化明显,并且两组均未出现不良反应.结论:采取中医辨证治疗高血压,可获得良好的治疗效果,提升康复率,值得临床推广.     

Peripheral blood leukocyte telomere length is associated with age but not renal function: A cross-sectional follow-up study

Objectives

We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese.

Methods

The telomere restriction fragment (TRF) length of leukocytes in the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed.

Results

Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function.

Conclusion

The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.

     

A multi-group path analysis of the relationship between perceived racial discrimination and self-rated stress: how does it vary across racial/ethnic groups?

Objective: The objective of this study was to answer three questions: (1) Is perceived discrimination adversely related to self-rated stress via the social capital and health care system distrust pathways? (2) Does the relationship between perceived discrimination and self-rated stress vary across race/ethnicity groups? and (3) Do the two pathways differ by one’s race/ethnicity background?

Design: Using the Philadelphia Health Management Corporation’s Southeastern Pennsylvania Household Survey, we classified 9831 respondents into 4 race/ethnicity groups: non-Hispanic White (n?=?6621), non-Hispanic Black (n?=?2359), Hispanic (n?=?505), and non-Hispanic other races (n?=?346). Structural equation modeling was employed to simultaneously estimate five sets of equations, including the confirmatory factor analysis for both social capital and health care distrust and both direct and indirect effects from perceived discrimination to self-rated stress.

Results: The key findings drawn from the analysis include the following: (1) in general, people who experienced racial discrimination have higher distrust and weaker social capital than those without perceived discrimination and both distrust and social capital are ultimately related to self-rated stress. (2) The direct relationship between perceived discrimination and self-rated stress is found for all race/ethnicity groups (except non-Hispanic other races) and it does not vary across groups. (3) The two pathways can be applied to non-Hispanic White and Black, but for Hispanic and non-Hispanic other races, we found little evidence for the social capital pathway.

Conclusions: For non-Hispanic White, non-Hispanic Black, and Hispanic, perceived discrimination is negatively related to self-rated stress. This finding highlights the importance of reducing interpersonal discriminatory behavior even for non-Hispanic White. The health care system distrust pathway can be used to address the racial health disparity in stress as it holds true for all four race/ethnicity groups. On the other hand, the social capital pathway seems to better help non-Hispanic White and Black to mediate the adverse effect of perceived discrimination on stress.     

Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β = 4.6, 95% CI 0.5, 8.7) and BDE-153 (β = 4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.     

Parent–child separation: the relationship between separation and psychological adjustment among Chinese rural children

Purpose

The current study aimed to explore the characteristics of psychological adjustment among Chinese left-behind children (LBC) in rural areas, and to examine the association between separation duration from parent/parents (SDP) and children’s psychological adjustment and the extent to which personality mediates this hypothesized link.

Methods

We surveyed 534 rural children and adolescents aged 10–17 years at school (440 LBC and 94 non-LBC) in 2013, who were selected for participation using stratified cluster sampling from two counties in Chongqing, China. Measures used included socio-demographic variables, age at the commencement and end of the separation from parents, the revised Chinese Juvenile Eysenck Personality Questionnaire, and the Adolescent Psychological Adaptability Scale.

Results

Most children (82.4%) had experienced separation from parents. t test results showed a marginally significant difference (p?=?.08) in psychological adjustment between LBC (mean?=?64.44, SD?=?8.62) and non-LBC (mean?=?66.16, SD?=?9.26). LBC’s mean SDP was 5.64 years (SD?=?3.90). Correlation analysis showed that children’s SDP was negatively associated with psychological adjustment. Structural equation modeling showed that neuroticism, but not extraversion or psychoticism, fully mediated the link between children’s SDP and psychological adjustment.

Conclusion

Personality (neuroticism) is one of the mediating pathways through which long-term SDP may predict poor psychological adjustment among children. Given the detrimental impact of long-term SDP, interventions should target the mediating pathway to buffer against the negative impact of parental separation on the affected rural children and to improve their mental health.

     

Effects of systemic fluoride and in vitro fluoride treatment on enamel crystals

Systemically administered fluoride at a concentration of 75 ppm increases the surface roughness of developing enamel crystals in rats, which may be significant in advancing our understanding of the biological mechanism of fluorosis. Thus, the aim of this study was to investigate whether the increased surface roughness may be a result of surface restructuring by the direct action of fluoride at the crystal surface. We examined the fluoride dose-dependent roughening of enamel crystal surfaces in vivo, in the rat, and whether this roughening could be mimicked by the in vitro treatment of rat enamel crystals with neutral pH fluoride solutions. Our results showed that enamel crystal surface roughness increased after treatment with increasing fluoride ion concentrations, whether applied in vitro or administered systemically. This suggests a mechanism, alongside others, for the increased surface roughness of crystals in fluorotic enamel.     

Effect of occlusal trauma on healing of periapical pathoses: report of two cases

AIM: To present two clinical cases and demonstrate that occlusal trauma may affect healing of periapical pathoses. SUMMARY: Two teeth with periradicular disease did not respond successfully to conventional root canal treatment or endodontic surgery. Occlusal adjustment was finally performed on both cases. After occlusal adjustment, uncomplicated healing and periapical repair occurred in both cases. The findings in these two cases suggest that occlusal trauma may play a role in the healing of periapical pathoses. KEY LEARNING POINTS: Occlusal trauma is positively correlated with changes in periodontal tissues. Although experiments in animals have shown that application of forces to teeth will not induce further periodontal destruction, we believe that some failures of root canal treatment may be due to the presence of occlusal trauma modulating the responses of inflamed periapical tissues or apical pathoses with persistent infection.