[Pharmacodynamics of Huanglian Jiedu decoction in Alzheimer's disease (AD) model rats and effect on improvement of inflammation microenvironment in brain].

To study the pharmacokinetics of active ingredients (alkaloids, iridoids and flavonoids) in Huanglian Jiedu decoction (HLJDD) in Alzheimer's disease (AD) model rats, and investigate its mechanism in treatment of AD. All of rats were divided into normal control group (n=6), shame operation group (n=6) and model group (n=12). Rats in shame operation group received daily subcutaneous injection of D-galactose (D-gal 50 mg·kg⁻¹) for a total of 45 d to induce subacute aging model. Based on the operation of shame operation group, the rats in model group were given with an injection of Aß25₋35 (4.0 g·L⁻¹)-ibotenic acid (2.0 g·L⁻¹) into the nucleus basalis magnocellularis. Then rats in model group were divided into HLJDD one day administration group (n=6) and HLJDD one week group (n=6). The plasma concentration of alkaloids, iridoid and flavonoids was determined by liquid chromatography tandem mass spectrometry (LC-QQQ-MS) at different time points. The levels of seven inflammatory factors (MIP-2, IL-1ß, IL-2, IL-8, IL-10, IL-13, TNF-α) in cerebrospinalfluid (CSF) were measured by Bio-Plex multi-factor detection technology. Iridoids in AD model rats, with high bioavailability, were easily absorbed and eliminated. The plasma concentration of alkaloid was lower, and the AUC (area under the curve) was higher in HLJDD one week group than that in HLJDD one day group. The plasma concentration-time curves of flavonoids showed obvious bimodal phenomena. After the gastric administration of HLJDD, the inflammatory factors in CSF of AD rats demonstrated a callback trend, including IL-1ß/IL-10 (P<0.05) with significant difference. The pharmacokinetic behaviors of iridoids, alkaloids and flavonoids (41 compounds) in AD model rats were fundamentally elucidated, and HLJDD can improve the central inflammatory status of AD rats by regulating the levels of inflammatory factors.

The role and mechanism of action of activin A in neurite outgrowth of chicken embryonic dorsal root ganglia.

Activin A, a member of the transforming growth factor ß (TGFß) superfamily, plays an essential role in neuron survival as a neurotrophic and neuroprotective factor in the central nervous system. However, the effects and mechanisms of action of activin A on the neurite outgrowth of dorsal root ganglia (DRG) remain unclear. In the present study, we found that activin A is expressed in DRG collected from chicken embryos on embryonic day 8 (E8). Moreover, activin A induced neurite outgrowth of the primary cultured DRG and maintained the survival of monolayer-cultured DRG neurons throughout the observation period of ten days. Follistatin (FS), an activin-binding protein, significantly inhibited activin A-induced neurite outgrowth of DRG, but failed to influence the effect of nerve growth factor (NGF) on DRG neurite outgrowth. Furthermore, the results showed that activin A significantly upregulated mRNA expression of activin receptor type IIA (ActRIIA) and calcitonin gene-related peptide (CGRP) in DRG, and stimulated serotonin (5-HT) production from DRG, indicating that activin A might induce DRG neurite outgrowth by promoting CGRP expression and stimulating 5-HT release. These data suggest that activin A plays an important role in the development of DRG in an autocrine or paracrine manner.

Optimal threshold for the diagnosis of anemia severity on unenhanced thoracic CT: A preliminary study.

OBJECTIVE: To investigate and evaluate the value as accuracy of diagnosis different degrees of anemia through the unenhanced thoracic computed tomography (CT) scan. MATERIALS AND METHODS: The CT attenuation of right ventricle (RV) cavity, left ventricular (LV) cavity, interventricular septum and difference between the interventricular septum and left ventricle cavity (IVS-LV) were retrospectively analyzed and measured in 317 patients with different degrees of anemia and the normal patients. The hemoglobin (Hb) level was estimated within 24 h. Statistical analysis was made to obtain the best diagnostic threshold of anemia levels by CT scan, measurement repeatability was assessed using the intra-class correlation coefficient (ICC) values. RESULTS: An obvious parallel correlation of hemoglobin concentration and CT attenuation of IVS-LV existed (the determination coefficient was 0.818; P < .001). Based on receiver operating characteristic (ROC) curves, the conclusion was that when the threshold of CT attenuation of IVS-LV at (5.5-9.5) HU in male and (4.5-8.5) HU in female, the specificity for diagnosing mild anemia was low, while the sensitivity was very high (87.1%, 100%, respectively), if the CT value was among (9.5-13.5) HU in male or (8.5-13.5) HU in female, the sensitivity and specificity for diagnosing moderate anemia were fine (92.9% and 74.8% in male; 93.9% and 60.0% in female), and once the CT value was more than 13.5 HU the sensitivity and specificity for diagnosing severe anemia in all gender were greatly good (94.7% and 83.6% in male; 82.4% and 84.6% in female). The intra-and inter-observer reliability and reproducibility were good (ICC were all more than 0.99). CONCLUSION: The CT attenuation of IVS-LV could predict the severity of anemia with good sensitivity and specificity, which could add value to clinical practice and more importantly facilitating patient care as hematologic laboratory investigations are lacking.

Correlation between polymorphisms of the NR3C1 gene and glucocorticoid effectiveness in patients with pemphigus vulgaris.

Glucocorticoid (GC) resistance is the major obscule in the treatment of pemphigus vulgaris (PV) for both patients and clinicans with unclear mechanism. A hypotheis for this resistance is the mutations or polymorphisms present in the nuclear receptor subfamily 3, group C, member 1 (NR3C1) gene that encodes receptors for steroid hormones. This study aimed to investigate the association between NR3C1 gene polymorphisms and GC effectiveness in PV patients. 94 PV patients (64 GC-sensitive and 30 GC-resistant) and 100 healthy volunteers were enrolled in this case-control study. The genotyping of single nucleotide polymorphisms (SNPs) in BCL1, Arg23Lys, Asn363Ser 1548 t-insert, and le747Met, together with tag-SNP sites of the NR3C1 gene were evaluated. No significant differences were observed in genotypic and allelic frequencies of the 16 SNPs between PV patients and healthy volunteers. However, SNPs rs 11745958 C/T (OR: 8.95) and rs17209237 A/G (OR: 4.07) may be associated with an increased risk of GC resistance, while rs 33388 A/T (OR: 0.45) and rs7701443 A/G (OR: 0.51) may indicate a decreased risk of GC resistance in PV patients. NR3C1 gene variation may be associated with GC resistance in PV patients. More extensive genetic analyses and mechanistic analysis are required for further exploration.