In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

Functional beta-cells derived from umbilical cord blood mesenchymal stem cells for curing rats with streptozotocin-induced diabetes mellitus

INTRODUCTIONThis study aimed to investigate the therapeutic response to injected human umbilical cord blood mesenchymal stem cells (UCBMSCs) among albino rats with streptozotocin (STZ)-induced diabetes mellitus.METHODSControl group (GI; n = 25) rats were fed with standard rat diet. Rats with STZ-induced diabetes mellitus without (GII; n = 25) and with (GIII; n = 25) differentiated human UCBMSCs implantation were the test groups. Rats were sacrificed in Week 11 following implantation. Liver biopsies were sectioned and stained in order to highlight both the presence and function of impregnated cells in the liver tissue.RESULTSHaematoxylin and eosin-stained sections in GI and GII rats showed normal liver architecture while GIII rats showed presence of cell clusters inside the liver tissue and around the central veins. Cell clusters with blue cytoplasm were present in sections in GIII rats but absent in GI and GII rats, indicating the presence of injected differentiated human UCBMSCs. The anti-human insulin immunostaining of GIII rats showed clusters of cells within the liver parenchyma and around central veins, indicating that these cells were active and secreting insulin.CONCLUSIONUCBMSCs are proficient in differentiating into insulin-producing cells in vivo under specific conditions and, when transplanted into the liver of albino rats with STZ-induced diabetes mellitus, were able to secrete insulin and partially control the status of diabetes mellitus in rats.     

肝包虫病的诊治方法研究进展

肝包虫病是流行于世界畜牧业发达地区的常见人畜共患性寄生虫病。文章介绍了肝包虫病的症状体征、诊断依据,以及各种治疗方法,以期对该病的防治提供参考。     

The effect of short or long sleep duration on quality of life and depression: an internet-based survey in Japan

BackgroundTo date, no previous studies have evaluated the relationship between sleep duration and quality of life (QOL) or depression in the general population after controlling for daytime sleepiness and sleep disturbances.MethodsA web-based cross-sectional survey was conducted with 8698 subjects aged 20–69 years. We examined the relationships between weekday sleep duration and daytime sleepiness, sleep disturbance, QOL and depression, using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (without the item for sleep duration), 8-item Short Form and Center for Epidemiological Studies Depression Scale (CES-D).ResultsDaytime sleepiness tended to increase in proportion to shorter weekday sleep durations. Sleep disturbances, physical and mental QOL, and CES-D scores were worse in both the shorter and longer sleep groups compared with the group with 7–8 h of sleep. Hierarchical logistic regression analyses revealed that short sleep duration but not long sleep duration was significantly associated with reduction of both physical and mental QOL, even after controlling for the presence of daytime sleepiness and sleep disturbance. Both short and long sleep duration were independently and significantly correlated with depression after controlling for daytime sleepiness; however, there was no statistically significant association after adjusting for the effects of sleep disturbance.ConclusionsThe results suggested adverse effects of short sleep but not long sleep on both physical and mental QOL. In addition, the negative impact of specific types of sleep disturbance on depression may be greater than the impact of shortening of sleep duration.     

A peripherally inserted central catheter misplacement into lateral thoracic vein: A case report

IntroductionCentral venous catheter applications and complications are closely related to the tip position. Previous studies have reported some rare cases of catheter misplacement. Here, we report a case of misplacement of a peripherally inserted central catheter into the lateral thoracic vein.Case reportA 56-year-old cancer patient underwent placement of a peripherally inserted central catheter through the left basilic vein under ultrasound-guided puncture. The catheterisation procedure was uneventful, so the catheter was believed to be in the superior vena cava. However, the post-anterior chest X-ray image revealed that after the catheter advanced towards the axilla, it turned downwards and outwards in the direction of the left lateral thoracic region, with the projection of the catheter tip giving the appearance of termination in the subcutaneous tissue of the lateral thoracic wall on the two-dimensional image. The catheter was then repositioned in the distal superior vena cava.DiscussionPeripherally inserted central catheters can be potentially misplaced into the lateral thoracic vein because these catheters can pass through the orifice of the lateral thoracic vein which flows into the axillary vein. Some pathological cases and clinical conditions can cause dilatation of the lateral thoracic vein, which increases the probability of catheter misplacement. Three principles were proposed to avoid this rare complication: a comprehensive review of the patients’ medical history, real-time image-guided catheterisation and routine radiographic identification of the tip position.     

Characterization of Malignant Portal Vein Thrombosis with Contrast-Enhanced Ultrasonography

We prospectively evaluated the effectiveness of contrast-enhanced ultrasonography (CEUS) for differentiation of benign versus malignant portal vein thrombosis (PVT). We studied a total of 43 patients with chronic liver disease, hepatocellular carcinoma-suggestive nodules and confirmed PVT, in whom the nature of the PVT was confirmed by follow-up imaging (US, computed tomography and/or magnetic resonance imaging) performed up to 6 mo after CEUS. PVT was assessed by US, Doppler US and CEUS with respect to vessel wall disruption and/or invasion, color Doppler vascularization, pulsed Doppler vascularization pattern and CEUS enhancement and vascularization pattern, and thrombi were classified as benign or malignant based on these findings. Follow-up studies revealed malignant PVT in 22 of the 43 patients (51%) and benign PVT in 21 patients (49%). CEUS findings were consistent with follow-up studies in 41 of the 43 patients (95%), with κ?=?0.903 (p < 0.0001), sensitivity?=?91% and specificity?=?100%, indicating that CEUS can be confidently used to differentiate benign from malignant portal vein thrombosis in the setting of chronic liver disease.     

Factors Affecting Recurrent Deep Vein Thrombosis after Pharmacomechanical Thrombolysis and Left Iliac Vein Stent Placement in Patients with Iliac Vein Compression Syndrome

PurposeThis study evaluated the factors affecting contralateral and ipsilateral recurrent deep vein thrombosis (DVT) after iliac vein stent placement in patients with iliac vein compression syndrome (IVCS).Materials and MethodsData from 130 patients (95 female patients) who underwent catheter-directed thrombolysis and stent placement for IVCS with left lower leg thrombosis at a single institution were retrospectively analyzed. Mean patient age was 69.0 ± 14.0 years old. Median follow-up was 14 months (range, 3–164 months). Anticoagulation therapy was prescribed for 6 months, followed by lifelong antiplatelet therapy. Multivariate logistic regression analysis was performed to evaluate the factors affecting the development of contralateral and ipsilateral recurrent DVT.ResultsSeven patients (5.4%) developed contralateral DVT (median, 26 months; range, 2–61 months), and 11 patients (8.5%) developed ipsilateral DVT (median, 1 month; range, 0–53 months). Stent location (odds ratio [OR], 11.564; 95% confidence interval [CI], 1.159–115.417) and in-stent thrombosis during follow-up (OR, 15.142; 95% CI, 1.406–163.119) were predictors of recurrent contralateral DVT. Thrombophilia (OR, 47.560; 95% CI, 2.369–954.711), remaining inferior vena cava filter (OR, 30.552; 95% CI, 3.495–267.122), and in-stent thrombosis during follow-up (OR, 82.057; 95% CI, 2.915–2309.848) were predictors of ipsilateral DVT.ConclusionsContralateral DVT occurs late and is associated with extension of the iliac vein stent to the inferior vena cava and in-stent thrombosis. Ipsilateral DVT occurs relatively early and is associated with thrombophilia, remaining inferior vena cava filter, and in-stent thrombosis.