Inhibitory activity of quercetin and its metabolite on lipopolysaccharide-induced activation of macrophage U937 cells

The potential of quercetin and its metabolite 3-O-methyl quercetin in inhibiting lipopolysaccharide (LPS)-mediated activation of macrophage U937 cells was investigated. Cells were pre-incubated for different periods with 100 ng/mL phorbol myristate acetate (PMA), and later with LPS and quercetin or 3-O-methyl quercetin (30 μM). Later, the supernatant of each cell culture was assessed for catalase activity, nitric oxide, and the production of tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1 (IL-1). The results showed that when the cells were incubated with LPS, there were elevations in the levels of all the markers over the cells not incubated with LPS (P < 0.05). For the cells that were incubated with LPS, there were significant differences between the various cells when they were pre-incubated with PMA for various periods (P < 0.05). However, greatest production of the markers was attained when the cells were pre-treated with PMA for 48 h. Both quercetin and 3-O-methyl quercetin (at 30 mM) reduced the levels of all the markers with 3-O-methyl quercetin possessing more inhibitory potential (P < 0.05). This suggests that the flavonoids possessed significant immunomodulatory activities which depend on methylation especially at position 3.     

Oral immunization of raccoons and skunks with a canine adenovirus recombinant rabies vaccine

Oral vaccination is an important part of wildlife rabies control programs. Currently, the vaccinia-rabies glycoprotein recombinant virus is the only oral rabies vaccine licensed in the United States, and it is not effective in skunks. In the current study, captive raccoons and skunks were used to evaluate a vaccine developed by incorporating the rabies virus glycoprotein gene into a canine adenovirus serotype 2 vector (CAV2-RVG). Seven of 7 raccoons orally vaccinated with CAV2-RVG developed virus neutralizing antibodies and survived lethal challenge. Five of 5 and 6 of 6 skunks in 2 experimental groups receiving 10-fold different dilutions of CAV2-RVG developed neutralizing antibodies and survived challenge. The results of this preliminary study suggest that CAV2-RVG stimulates protective immunity against rabies in raccoons and skunks.     

How sharp is the short QuickDASH? A refined content and validity analysis of the short form of the disabilities of the shoulder, arm and hand questionnaire in the strata of symptoms and function and specific joint conditions

Purpose  

To assess and compare content, validity, and specificity of the QuickDASH (Disability of the arm, shoulder and hand questionnaire) as compared to the full-length DASH and other instruments to give a recommendation for its use depending on a specific clinical situation.     

Sensitivity to activated protein C during the menstrual cycle in women with and without factor VLeiden

Introduction

Activated protein C (APC) resistance is associated with an increased risk of venous thrombosis. High levels of estradiol and progesterone, e.g. during ovarian stimulation and pregnancy, as well as exogenously administered estrogens and progestagens during oral contraceptive use, induce an acquired form of APC resistance. Several coagulation factors display a cyclic pattern during the menstrual cycle due to the fluctuation of estradiol and progesterone. The aim of the study was to evaluate whether varying levels of estradiol and progesterone during the menstrual cycle are associated with differences in sensitivity to APC.

Materials and methods

Normalized APC sensitivity ratios (nAPCsr) were determined with the thrombin generation-based APC-resistance test at six different time points during the menstrual cycle in thirteen wildtype women and six women with factor V_Leiden.

Results

Mean nAPCsr varied slightly during the menstrual cycle. Women without factor V_Leiden were more likely to have lower nAPCsr at the beginning of the cycle than later on in the cycle (1.34 versus 1.54 and 1.58, Friedman ranking test p = 0.009).

Conclusions

The sensitivity to APC differs between the different phases of the menstrual cycle. This cyclic variability could be useful in improving studies on APC resistance in women.     

The relationship between maintenance dosages of three vitamin K antagonists: acenocoumarol, warfarin and phenprocoumon

Introduction

Vitamin K antagonists of the coumarin type are widely used oral anticoagulants.

Objective

We developed a transition algorithm for the maintenance dosages of three frequently used coumarins: warfarin, phenprocoumon and acenocoumarol.

Methods

The study was conducted at the Leiden Anticoagulation Clinic. Patients were participants in a trial of which the main objective was to compare the quality of an oral anticoagulant therapy with phenprocoumon to warfarin. We included patients who initiated oral anticoagulant therapy and patients who were already using acenocoumarol. Patients were randomized to a treatment with warfarin or phenprocoumon. Patients who were randomized to warfarin switched to phenprocoumon at the end of follow-up. We analysed the switch from acenocoumarol to warfarin or phenprocoumon at the start of follow-up and the switch of warfarin to phenprocoumon at the end of follow-up and calculated the transition factors for stable anticoagulation between these three vitamin K antagonists.

Results

Fifty-eight patients switched from warfarin to phenprocoumon, 39 from acenocoumarol to phenprocoumon and 44 from acenocoumarol to warfarin. The maintenance dose of warfarin was 0.41 (95%CI 0.39-0.43) times the maintenance dose of phenprocoumon. The transition factor between acenocoumarol and phenprocoumon was 0.84 (95%CI 0.79-0.89) and between acenocoumarol and warfarin 1.85 (95%CI 1.78-1.92).

Conclusions

We determined the transition factors between warfarin, phenprocoumon and acenocoumarol. With these transition factors physicians are able to estimate the maintenance dose when it is necessary for a patient to switch from one coumarin to the other.