Substance P regulates macrophage inflammatory protein 3alpha/chemokine C-C ligand 20 (CCL20) with heme oxygenase-1 in human periodontal ligament cells

Although substance P (SP), a potent proinflammatory peptide, is involved in inflammation and immune responses, the effect of SP on the expression of macrophage inflammatory protein 3alpha[MIP-3alpha, chemokine C-C ligand 20 (CCL20)] in periodontal ligament (PDL) cells is unknown. Equally enigmatic is the link between SP, the stress protein heme oxygenase-1 (HO-1), and CCL20 production. We investigated whether SP induces the release of chemokine CCL20 from immortalized PDL (IPDL) cells, and further clarify SP-mediated pathways. We also examined the relationship between HO-1 and CCL20 by treating PDL cells with SP. Incubating IPDL cells with SP increased expression of CCL20 mRNA and CCL20 protein in a dose-time-dependent manner. Highly selective p38 and extracellular-regulated kinase 1/2 (ERK1/2) inhibitors abrogated SP-induced expression of CCL20 in IPDL cells. SP is also responsible for initiating phosphorylation of IkappaB, degradation of IkappaB and activation of nuclear factor (NF)-kappaB. SP induced expression of HO-1 in both a concentration- and time-dependent manner, and CCL20 reflected similar patterns. The inductive effects of SP on HO-1 and CCL20 were enhanced by HO-1 inducer hemin and the membrane-permeable guanosine 3',5'-monophosphate (cGMP) analogue 8-bromo-cGMP. Conversely, this pathway was inhibited by the HO-1 inhibitor zinc protoporphyrin IX (ZnPP IX) and the selective inhibitor of guanylate cyclase, 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one (ODQ). We report herein the pathway that connects SP along with other modulators of neuroimmunoregulation to the induction of HO-1 and the inflammatory mediator macrophage inflammatory protein (MIP)-3alpha/CCL20 in IPDL cells, which play an important role in the development of periodontitis or inflammation during orthodontic tooth movement.     

A Mathematical Model and Experimental Verification of Optimal Nozzle Diameter in Needle-Free Injection

Needle-free injection (NFI), as an alternative drug delivery strategy, owns great potential. It is able to reduce complaints about needle phobia and avoid the occurring of accidental needle stick injuries. The nozzle diameter is inherently important in determining the injection dose, injection depth, and pain associated with NFIs. In this work, needle-free injectors with nozzle diameters of 0.17, 0.20, 0.30, 0.40, and 0.50 mm were studied in the simulation and experiment. This article optimizes the mathematical model for spring-powered NFI by considering the hydraulic loss due to the abrupt change in the nozzle exit area and the friction force between the piston and ampoule. We explore the dispersion pattern in gels with different nozzle diameters. Mice insulin injection was conducted to investigate the pharmacological effect of different injection methods. The experimental results show that there is the best dispersion effect and available injection depth while the nozzle diameter is 0.30 mm, which is in agreement with the result predicted by the mathematical model. Also, there is a satisfactory pharmacological effect on the mice insulin injection under the same injection condition. Undoubtedly, the mathematical model is capable of predicting the suitable nozzle diameter under the given conditions.     

Salty taste thresholds and preference in patients with chronic kidney disease according to disease stage: A cross‐sectional study

Aim

The present study was performed to evaluate the differences in salty taste thresholds among normal controls and non‐dialysis chronic kidney disease (CKD) patients according to disease stage and to evaluate the relationship between salty taste thresholds or preferences and mean spot urine sodium concentrations.

Methods

This cross‐sectional study enrolled 436 patients with non‐dialysis CKD and 74 normal controls. We evaluated detection and recognition thresholds, salty taste preferences and salt usage behaviours (through a questionnaire) in CKD patients and normal controls. We averaged the three most recent spot urine sodium concentrations and used this ‘mean spot urine sodium’ value to estimate sodium intake in CKD patients.

Results

Detection thresholds of stages 3 and 5 and recognition thresholds of stage 3 CKD patients were higher than those of normal controls. Salty taste preferences of stage 5 and salt usage behaviour scores of stages 4 and 5 CKD patients were lower than those of normal controls. Univariate analysis showed that estimated glomerular filtration rate (eGFR), salt usage behaviour score, salty taste preference, smoking, gender and zinc level were significantly associated with mean spot urine sodium in CKD patients. Multiple regression analysis showed that the eGFR and salty taste preference were independently correlated with mean spot urine sodium.

Conclusions

Education to change salty taste preferences and regular follow up are necessary to decrease salt intake in CKD patients.     

膝骨性关节炎患者平衡功能障碍及其影响因素分析

目的 探讨膝骨性关节炎（KOA）患者平衡功能及其相关影响因素。方法 选取2014年12月至2017年9月合肥市第二人民医院骨科收治的单膝受累30例KOA患者为观察对象,采用平衡测试仪对患者进行平衡功能检测,比较健、患侧测试完成耗时及平均轨迹误差,收集患者体质量指数、K-L分级、疼痛指数、美国膝关节协会评分（KSS）等指标,利用多元回归分析上述指标对患者平衡功能的影响。结果 患者健、患侧平衡指标比较,患侧平均轨迹误差值（46.63±25.30）%大于健侧值（40.77±23.85）%,差异有统计学意义（t=-2.299,P<0.05）;多元回归分析示：KSS临床评分对睁眼时前-后平均运动速度（t=-2.593,P<0.05）及重心摆动轨迹长度（t=-2.178,P<0.05）的影响具有统计学意义,对两者变异的解释比例分别为19%、15%,而疼痛指数对闭眼轨迹长度/睁眼轨迹长度比（Romberg值长度比）的影响具有统计学意义（t=-2.641,P<0.05）,解释比例为20%。结论 KOA患者存在平衡功能障碍;膝关节疼痛指数及KSS临床评分对于评估KOA患者平衡功能障碍具有重要意义。     

Safety and efficacy of propofol anesthesia for pediatric target-controlled infusion in children below 3 years of age: a retrospective observational study

Background: Although the requirement of propofol in children is increasing, propofol for induction and maintenance of anesthesia below 3 years old has not been approved in Korea. This study can provide a clinical evidence to increase the range of approval.

Research design and methods: We reviewed the medical records of patients below 3 years of age who underwent surgery between September 2013 and December 2016. Safety was evaluated on the basis of vital signs, and laboratory findings and efficacy were evaluated on the basis of the bispectral index (BIS). Adverse events were examined.

Results: A total of 109 patients anesthetized with propofol (propofol group) were compared with 109 patients with volatile anesthetics (volatile group) after propensity score matching. There was a difference in the proportion of patients showing decreased systolic pressure (P < 0.001) and heart rate (P = 0.03), but there was no difference in diastolic pressure (P = 0.238), mean arterial pressure (P = 0.175) during surgery. After surgery, there was no difference in all vital signs and the proportion patients who experienced adverse events of two groups.

Conclusions: Propofol anesthesia by target-controlled infusion was effective and didn’t show serious propofol-related perioperative adverse events.     

Evaluation of biomarkers for treatment selection using individual participant data from multiple clinical trials

Biomarkers that predict treatment effects may be used to guide treatment decisions, thus improving patient outcomes. A meta‐analysis of individual participant data (IPD) is potentially more powerful than a single‐study data analysis in evaluating markers for treatment selection. Our study was motivated by the IPD that were collected from 2 randomized controlled trials of hypertension and preeclampsia among pregnant women to evaluate the effect of labor induction over expectant management of the pregnancy in preventing progression to severe maternal disease. The existing literature on statistical methods for biomarker evaluation in IPD meta‐analysis have evaluated a marker's performance in terms of its ability to predict risk of disease outcome, which do not directly apply to the treatment selection problem. In this study, we propose a statistical framework for evaluating a marker for treatment selection given IPD from a small number of individual clinical trials. We derive marker‐based treatment rules by minimizing the average expected outcome across studies. The application of the proposed methods to the IPD from 2 studies in women with hypertension in pregnancy is presented.     

Association of long-term adherence to the mind diet with cognitive function and cognitive decline in American women

Objectives

There is increasing attention for dietary patterns as a potential strategy to prevent cognitive decline. We examined the association between adherence to a recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function and cognitive decline, taking into account the interaction between the apolipoprotein E ε4 genotype and the MIND diet.

Design

Population-based prospective cohort study.

Participants

A total of 16,058 older women aged 70 and over from the Nurses’ Health Study.

Measurements

Dietary intake was assessed five times between 1984 and 1998 with a 116-item Food Frequency Questionnaire. The MIND score includes ten brain-healthy foods and five unhealthy foods. Cognition was assessed four times by telephone from 1995 to 2001 (baseline) with the Telephone Interview for Cognitive Status (TICS) and by calculating composite scores of verbal memory and global cognition. Linear regression modelling and linear mixed modelling were used to examine the associations of adherence to the MIND diet with average cognitive function and cognitive change over six years, respectively.

Results

Greater long-term adherence to the MIND diet was associated with a better verbal memory score (multivariable-adjusted mean differences between extreme MIND quintiles=0.04 (95%CI 0.01-0.07), p-trend=0.006), but not with cognitive decline over 6 years in global cognition, verbal memory or TICS.

Conclusion

Long-term adherence to the MIND diet was moderately associated with better verbal memory in later life. Future studies should address this association within populations at greater risk of cognitive decline.

     

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.