Relating Observed Psychoactive Effects to the Plasma Concentrations of Delta-9-Tetrahydrocannabinol and Its Active Metabolite: An Effect-Compartment Modeling Approach

The medical use of marijuana is increasing, yet little is known about the exposure-response relationship for its psychoactive effects. It is well known that the plasma concentrations of the principal psychoactive component of marijuana, Δ⁹-tetrahydrocannabinol (THC), do not directly correlate to the observed psychoactive effects. The purpose of this research was to use an effect-compartment modeling approach to predict and relate the concentrations of the psychoactive components (THC and its active metabolite) in the “hypothetical” effect-site compartment to the observed psychoactive effects. A “hypothetical” effect-compartment model was developed using literature data to characterize the observed delay in peak “highness” ratings compared with plasma concentrations of the psychoactive agents following intravenous administration of THC. A direct relationship was established between the reported psychoactive effects (“highness” or intoxication) and the predicted effect-site concentrations of THC. The differences between estimated equilibration half-lives for THC and THC-OH in the effect-compartment model indicated the differential equilibration of parent drug and the active metabolite between plasma and the effect-site. These models contribute to the understanding of the pharmacokinetic-pharmacodynamic relationships associated with marijuana use and are important steps in the prediction of pharmacodynamic effects related to the psychoactive components in marijuana.     

Association of IL1B polymorphisms with gastric cancer in a Chinese population

OBJECTIVES: To investigate the association between IL1B polymorphisms and risk of gastric cancer in a Chinese population, seven SNPs in the IL1B gene were selected for this study. METHODS: A multiplex genotyping method, which is based on adapter ligation and allele-specific amplification, was established to type seven SNPs on the IL1B gene simultaneously. One hundred and forty-one non-cancer outpatients and 97 patients with gastric cancer were genotyped, and the relation between IL1B polymorphisms and gastric cancer was statistically analyzed. RESULTS: The seven SNPs were successfully typed and the results were consistent with those obtained by both Sanger's sequencing and PCR-RFLP. Handling with statistical analysis, we observed significantly different genotype frequencies of 0794C>T (chi(2)=6.11, P=0.05), 1274C>T (chi(2)=6.86, P=0.03) and 2143T>C (chi(2)=6.86, P=0.03) between patients and controls. CONCLUSION: ALM-ASA is a potential method for multiplex SNP typing with a low consumption of genomic DNA. SNPs 0794C>T, 1274C>T, and 2143T>C are associated with gastric cancer.     

距下关节镜辅助下经皮撬拨复位内固定治疗合并糖尿病的跟骨骨折

目的:探讨距下关节镜辅助下经皮撬拨复位内固定治疗合并糖尿病的跟骨骨折的临床疗效和安全性。方法:2016年3月至2019年7月收治22例闭合性跟骨骨折患者。男14例,女8例。年龄36~65岁,中位数48.5岁。根据Essex-Lopresti分型,舌型骨折6例、关节压缩型骨折16例。根据Sanders分型,Ⅱ型14例(ⅡA型5例、ⅡB型7例、ⅡC型2例)、Ⅲ型8例(ⅢAC型4例、ⅢAB型3例、ⅢBC型1例)。所有患者均合并2型糖尿病,1例合并同侧闭塞性下肢动脉硬化,2例合并下肢周围神经病变。均采用距下关节镜辅助下经皮撬拨复位内固定治疗。在X线片上测量患者的跟骨高度、宽度、长度、B-hler角、Gissane角,采用Burwell-Charnley骨折复位放射学标准评定复位情况,采用美国足与踝关节协会(American Orthopedic Foot and Ankle Society,AOFAS)踝与后足功能评分标准评定总体疗效。观察记录治疗及随访期间的并发症发生情况。结果:所有患者均获得随访,随访时间11~37个月,中位数13个月。术后3d拍摄的X线片显示,患侧的跟骨长度、跟骨高度、B-hler角、Gissane角均较术前增大[(73.41±4.51)mm,(81.21±2.20)mm,t=2.121,P=0.031;(32.34±3.60)mm,(41.21±3.20)mm,t=1.945,P=0.021;8.3°±2.1°,24.8°±3.2°,t=3.931,P=0.008;91.1°±4.7°,112.2°±1.4°,t=2.224,P=0.040],跟骨宽度较术前减小[(44.25±2.50)mm,(34.21±2.10)mm,t=-3.112,P=0.011]。术后1周时,按照Burwell-Charnley骨折复位放射学标准评定,解剖复位16例(SandersⅡ型13例、Ⅲ型3例),复位一般5例(SandersⅡ型1例、Ⅲ型4例),复位差1例(SandersⅢ型);复位评定为差的患者,随访期间未出现骨关节炎表现,未进行处理。末次随访时所有骨折均达到临床愈合标准;AOFAS踝与后足功能评分为(90.00±2.18)分;20例糖化血红蛋白<7%,2例糖化血红蛋白>7%,但均无糖尿病足表现。所有手术切口均愈合,其中21例3周内甲级愈合,1例术后6周时乙级愈合。所有患者均未发生跟骨骨髓炎、跟腱挛缩、创伤性马蹄内翻足、踝关节僵硬等并发症。结论:采用距下关节镜辅助下经皮撬拨复位内固定治疗合并糖尿病的跟骨骨折,可实现骨折的精准复位和有效固定,术后关节功能恢复好,并发症少。     

线粒体复合体在肾脏疾病中的研究进展

肾脏是富含线粒体的器官之一,其正常运行依赖于线粒体氧化磷酸化(oxidative phosphorylation,OXPHOS)为细胞供能.线粒体复合体(mitochondrial complex,MC)构成了线粒体呼吸链(mitochondrial respiratory chain,MRC),具有电子传递和质子转移的功能,参与OXPHOS的过程.近年的研究表明,MC参与了肾脏疾病的发生发展,MC在不同的肾脏疾病中作用不尽相同.本文旨在系统综述MC的功能,总结其在急性肾损伤(acute kidney injury,AKI)、以糖尿病肾病(diabetic kidney disease,DKD)为主的慢性肾脏病(chronic kidney disease,CKD)、肾脏肿瘤、线粒体DNA(mtDNA)疾病等不同肾脏病领域中的作用,分析探讨MC作为新的靶点在肾脏疾病诊治中的潜在价值.     

用双位点单抗免疫酶法测定CK—MB质量

应用免疫单抗ＥＬＩＳＡ法测定ＣＫ－ＭＢ的质量，与免疫抑制法及电泳法进行了比较，其准确性和精密性均符合临床要求。急性心肌梗塞（ＡＭＩ）２５份血标本测定结果与免疫抑制法相关方程为Ｙ＝１．０７７Ｘ－４．３，ｒ＝０．９９６，免疫酶法比免疫抑制法更具有特异性。     

Urinary stone analysis on 12,846 patients: a report from a single center in China

We reported a retrospective review of the urinary stone compositions in 12,846 patients. Data on urinary stone compositions analyzed between January 2003 and December 2012 in our center were collected. Infrared spectroscopy was used for stone analysis. Predominant stone component was recorded. Patients were divided into four age groups: 0–18, 19–40, 41–60, and 61–92, and five categories by components. In order to determine the change of stone characteristics with respect to time, data were also divided into two periods, 2003–2007 and 2008–2012. A total of 12,846 stones were included in this study. The age of the patients ranged from 1 to 92 years with 7,736 males and 5,110 females. Stone made of single component was rare, 2.61 %. Calcium oxalate stone was the most common component at 82.56 %. Calcium oxalate and uric acid stones were more common in male than in female. The incidence of calcium phosphate stones and uric acid stones had increased during the past 5 years, while calcium oxalate stones decreased. We found the highest incidence of stone disease in the 41–60 years old group and the lowest in the 1–18 years old for both genders. Calcium oxalate was the dominant component in every group but was more prevalent in 19–40 years group. The percentage of magnesium ammonium phosphate stone and uric acid stone increased with age.     

The relationship between spinopelvic parameters and clinical symptoms of severe isthmic spondylolisthesis: a prospective study of 64 patients

Purpose

To investigate the relationship between spinopelvic parameters and clinical symptoms for patients with severe isthmic spondylolisthesis.

Methods

A series of spinopelvic parameters were measured in 64 patients with L5 severe isthmic spondylolisthesis. The patients were divided into two groups according to Oswestry score obtained preoperatively, i.e. mild or severe low back pain group. T test was used to compare parameters between two groups, and multiple linear regression analysis was employed to investigate the association between parameters and Oswestry score.

Results

Compared with two group patients, parameters of spondylolisthesis grade, pelvic tilt (PT), lumbar lordosis (LL), T9 tilting angle (T9TA), sacro-femoral horizontal distance (SFHD), distance between perpendicular line through C7 and sacrum (SC7D), pelvic tilt/sacral slope (PT/SS), sacro-femoral horizontal distance/vertical distance (SFHD/SFVD), and lumbar lordosis/thoracic kyphosis (LL/TK) were significantly increased in severe low back pain group, while SS and SFVD were significantly decreased, and no significant difference was found for pelvic incidence (PI) and TK. The statistical analysis showed that spondylolisthesis grade, PT, SC7D, LL, SFHD, PT/SS, SFHD/SFVD, and LL/TK had a significant positive correlation with Oswestry score, with an order of spondylolisthesis grade > PT/SS > SC7D > PT > SFHD/SFVD > SFHD > LL/TK > LL. No significant correlation was found for PI, TK, T9TA with Oswestry score, while SS and SFVD had a significant negative correlation with Oswestry score, with an order of SS > SFVD.

Conclusions

The spinopelvic parameters (spondylolisthesis grade, SS, PT, SC7D, LL, SFVD, SFHD, PT/SS, SFHD/SFVD, LL/TK) are significantly correlated with clinical symptoms of severe isthmic spondylolisthesis in patients. The association of the exacerbation of low back pain with SS (correlation coefficient −0.981, strong) and SFVD (correlation coefficient −0.802, strong) is the most significant correlation.     

The effects of urokinase-type plasminogen activator (uPA) on cell proliferation and phenotypic transformation of rat mesangial cells induced by high glucose

Aims

To investigate the effects of urokinase-type plasminogen activator (uPA) on proliferation and phenotypic transformation of rat mesangial cells (MCs) under high glucose conditions and its possible signal transduction pathway.

Methods

Rat MC were divided into 4 groups: the control group, the high glucose group, the high glucose and wortmannin group, and the high glucose and uPA group. MC proliferation in all groups was detected by the 3-(4,5-dimethylthiazol-)-2,5-diphenyltetrazolium bromide (MTT) method. MC cell cycle was analyzed by flow cytometry. Expression of cyclin dependent kinase 2 (CDK2), and activity of the signaling protein Akt in MC were detected by Western blot. Expression pattern and quantity of α-smooth muscle actin (α-SMA) in MC were examined using laser confocal microscopy. The expression of plasminogen activator inhibitor-1 (PAI-1), and collagen IV in renal tissues in rats was tested with immunohistochemistry and Western blotting methods.

Results

Activation of Akt induced by high glucose can be reduced significantly by wortmannin and uPA. There was no obvious change in CDK2 protein expression in different groups (P > 0.05). Expression of α-SMA in MC cytoplasm increased dramatically (P < 0.01). Expression of α-SMA decreased significantly in the high glucose and wortmannin group and the high glucose and uPA group compared with that of the high glucose group (P < 0.01). In diabetic rats, uPA down-regulated PAI-1 and collagen IV expression in mesangial matrix (P < 0.05).

Conclusion

uPA antagonizes cell proliferation and phenotypic transformation of MCs induced by high glucose through inhibiting Akt signaling pathway.