柱前手性衍生化反相高效液相色谱法拆分地佐西平对映异构体的研究

用乙酰葡萄糖异硫氰酸酯(GITC)作柱前手性衍生化试剂,以反相高效液相色谱法成功地拆分了地佐西平对映异构体。在此基础上建立了地佐西平对映异构体纯度和血药浓度测定方法。已用于测定右旋地佐西平的光学纯度和小鼠血药浓度。     

Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML).

The important cell cycle regulatory gene p15(INK4b) has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelodysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15(INK4b) gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5' region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD.     

Acupuncture of specific points influences cortical auditory evoked potentials--a volunteer crossover study

Specificity of acupoints remains a crucial question in acupuncture research. The aim was to investigate whether acupuncture of specific points influences the Cortical Auditory Evoked Potentials (CAEP). Ten healthy volunteers were enrolled in this study according to inclusion criteria. One of 4 acupoints: TH3, GB43 (both claimed as specific for auditory system by Traditional Chinese Medicine) and non-specific points H7 and ST44, was stimulated during one session. Each volunteer received 4 sessions of acupuncture with an interval of 1 week between the sessions. The latencies and amplitudes of CAEP were registered before and after the acupuncture during each session. The mean peak latencies of P2 component decreased after stimulation of TH3 by 11 ms and GB43 by 14 ms whereas the peak latencies of N2 component increased after stimulation of TH3 by 9 ms and GB43 by 4 ms compared to baseline values (p<0.05). The stimulation of H7 and ST44 did not produce any changes. These findings confirm the specificity of acupuncture points TH3 and GB43 in relation to auditory system.     

Linking male use of the sex industry to controlling behaviors in violent relationships: an exploratory analysis

In an attempt to better understand the relationship between male use of the sex industry (i.e., pornography and strip clubs) and interpersonal violence (IPV), 2,135 female residents of an IPV shelter were surveyed regarding their batterer's use of both the sex industry and controlling behaviors in their relationship. Findings indicate that male domestic violence offenders who utilize the sex industry use more controlling behaviors than male domestic violence offenders who do not. Implications for policy, practice, and research are discussed.     

Interprothetische Frakturen am Femur

The treatment of interprosthetic fractures is challenging and the incidence is increasing as a result of increasing patient longevity and rising arthroplasty rates. Interprosthetic fractures occur between arthroplasty stems or any intramedullary implant that has been implanted for fracture fixation. Management of these fractures is a complex undertaking. The majority of fractures are localized at the femoral supracondylar level after knee resurfacing arthroplasty. The fixation status of the arthroplasty component determines the management strategies. As a result of clinical and biomechanical studies, loosening of the implant usually requires revision arthroplasty, whereas minimally invasive reduction and locked internal fixation is the treatment of choice for stable implants. Minimally invasive surgery is necessary to not further compromise local perfusion. As locked plating provides superior biomechanical stability, the use of cerclage cables should be carefully evaluated. Complex fracture configurations, inferior bone stock or an intramedullary canal that is already occupied by support structures might obviate the implantation of long revision stems and might require a more extensive approach (e.g., total femoral arthroplasty).     

Associations of metabolically healthy obesity with prevalence and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall Cohort Study

Background and aims

There is controversy on the potentially benign nature of metabolically healthy obesity (MHO), i.e., obese persons with few or no metabolic abnormalities. So far, associations between MHO and coronary artery calcification (CAC), a measure of subclinical atherosclerosis, have mainly been studied cross-sectionally in Asian populations. We assessed cross-sectional and longitudinal MHO CAC associations in a Caucasian population.

Impact of Age and Polytherapy on Fingolimod Induced Bradycardia: a Preclinical Study

Fingolimod is a an oral disease modifying drug for relapsing remitting multiple sclerosis (MS) preventing egress of B and T cells from lymph nodes. Relevant first dose adverse events include bradycardia and atrioventricular conduction slowing. Cardiac side effects of fingolimod and combinational pharmacotherapy including duloxetine and tolterodine were monitored in mice of different age using implantable ECG telemetric systems. Cardiac tissue was assessed for S1P-receptor subtype (1 and 3), and for GIRK1 expression. Fingolimod led to a significant heart rate reduction within 60 min, which returned to baseline values within 24 h. In older mice bradycardia was more pronounced compared to younger mice. Atrioventricular conduction was not affected. Older mice showed a higher S1PR3 expression in a naïve state and receptor expression was reduced after fingolimod administration. Combination with duloxetine or tolterodine alleviated fingolimod induced heart rate decrease. Our data provide preclinical evidence that negative chronotropic effects of fingolimod might be age dependent, possibly due to an altered expression and internalization of cardiac S1PR3 in older animals. This data could be relevant for future clinical monitoring and patient selection in the aging MS population. Combinational therapies of fingolimod and duloxetine or tolterodine are well tolerated and safe without an increased risk for pronounced bradycardia or arrhythmia.     

Umweltschadstoffe als Adjuvanzien und Co-Faktoren einer immunologischen Erkrankung

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Aufgabe des Immunsystems ist es, den Körper gegen eindringende Krankheitserreger zu schützen. Voraussetzung dafür...