Deconjugation Kinetics of Glucuronidated Phase II Flavonoid Metabolites by B-glucuronidase from Neutrophils

Flavonoids are inactivated by phase II metabolism and occur in the body as glucuronides. Mammalian ß-glucuronidase released from neutrophils at inflammatory sites may be able to deconjugate and thus activate flavonoid glucuronides. We have studied deconjugation kinetics and pH optimum for four sources of ß-glucuronidase (human neutrophil, human recombinant, myeloid PLB-985 cells, Helix pomatia) with five flavonoid glucuronides (quercetin-3-glucuronide, quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-7-glucuronide, 3'-methylquercetin-3-glucuronide), 4-methylumbelliferyl-ß-D-glucuronide, and para-nitrophenol-glucuronide. All substrate-enzyme combinations tested exhibited first order kinetics. The optimum pH for hydrolysis was between 3.5-5, with appreciable hydrolysis activities up to pH 5.5. At pH 4, the Km ranged 44-fold from 22 µM for quercetin-4'-glucuronide with Helix pomatia ß-glucuronidase, to 981 µM for para-nitrophenol-glucuronide with recombinant ß-glucuronidase. Vmax (range: 0.735-24.012 µmol·min-1·unit-1 [1 unit is defined as the release of 1 µM 4-methylumbelliferyl-ß-D-glucuronide per min]) and the reaction rate constants at low substrate concentrations (k) (range: 0.002-0.062 min-1·(unit/L)-1 were similar for all substrates-enzyme combinations tested. In conclusion, we show that ß-glucuronidase from four different sources, including human neutrophils, is able to deconjugate flavonoid glucuronides and non-flavonoid substrates at fairly similar kinetic rates. At inflammatory sites in vivo the pH, neutrophil and flavonoid glucuronide concentrations seem favorable for deconjugation. However, it remains to be confirmed whether this is actually the case

Effect of dietary fish oil on blood levels of free fatty acids, ketone bodies and triacylglycerol in humans

Although the reduction of serum triacylglycerol concentrations by dietary fish oil is a well-known effect, the exact mechanism of this effect has not been previously studied in human subjects. Therefore, the aim of this study was (i) to examine the effect of short-term fish oil supplementation on blood concentrations of ketone bodies, free fatty acids and triacylglycerol in healthy humans and (ii) to verify whether the observed relationships between these variables would be consistent with reduced lipolysis and/or enhanced hepatic fatty acid oxidation after fish oil supplementation. Twenty subjects (21-23 years, normal liver function tests) were randomly divided into two groups to supplement their usual diet with either 30 g/d of fish oil (n=11) or olive oil (n=9). Venous blood samples were drawn after an overnight fast, before and after 1, 3 and 7 d of fish oil/olive oil supplementation. Blood concentrations of triacylglycerol and free fatty acids decreased consistently after fish oil supplementation; the reduction was already significant after one day of fish oil (P0.10). No significant changes in glucose, insulin or ketone body levels were observed in either group after supplementation. After fish oil, but not after olive oil supplementation, the ratio of blood ketone body levels to free fatty acid levels increased significantly (P<0.05). Furthermore, after fish oil supplementation only, free fatty acid levels were significantly correlated with levels of ketone bodies (day 7 of supplementation: r=0.90, P<0.001) and triacylglycerol (maximum value on day 3: r=0.77, P<0.01). These findings suggest that reduced lipolysis and increased hepatic β-oxidation/ketogenesis may contribute to reduced triacylglycerol levels after ω3 fatty acid supplementation in humans. Turnover studies are needed in order to further quantitate these processes

Multi-tool formaldehyde measurement in simulated and real atmospheres for indoor air survey and concentration change monitoring

International audienceFormaldehyde is of particular health concern since it is carcinogenic for human and ubiquitous in indoor air where people spend most of their time. Therefore, it is important to have suitable methods and techniques to measure its content in indoor air. In the present work, four different techniques have been tested in the INERIS exposure chamber and in indoor environments in comparison to a standard active method: passive sampling method based on the reaction of 2,4-dinitrophenylhydrazine with formaldehyde, two on-line continuous monitoring systems based on fluorescence and UV measurements and a portable commercialised analyser based on electrochemical titration. Two formaldehyde concentrations, about 10 and 25 μg m−3 were generated in an exposure chamber under controlled conditions of temperature, relative humidity, and wind speed to simulate real conditions and assess potential influence on passive sampling and continuous systems response. Influence of sampling periods on passive sampling has also been evaluated. The real atmosphere experiments have been performed in four different indoor environments: an office, a furniture shop, a shopping mall, and residential dwellings in which several potential formaldehyde sources linked to household activities have been tested. The analytical and sampling problems associated with each measurement method have been identified and discussed. An overall agreement between each technique has been observed and continuous analyzers allowed for formaldehyde concentrations change monitoring and secondary formation of that pollutant observation

An update on retinal prostheses

Retinal prostheses are designed to restore a basic sense of sight to people with profound vision loss. They require a relatively intact posterior visual pathway (optic nerve, lateral geniculate nucleus and visual cortex). Retinal implants are options for people with severe stages of retinal degenerative disease such as retinitis pigmentosa and age-related macular degeneration. There have now been three regulatory-approved retinal prostheses. Over five hundred patients have been implanted globally over the past 15 years. Devices generally provide an improved ability to localize high-contrast objects, navigate, and perform basic orientation tasks. Adverse events have included conjunctival erosion, retinal detachment, loss of light perception, and the need for revision surgery, but are rare. There are also specific device risks, including overstimulation (which could cause damage to the retina) or delamination of implanted components, but these are very unlikely. Current challenges include how to improve visual acuity, enlarge the field-of-view, and reduce a complex visual scene to its most salient components through image processing. This review encompasses the work of over 40 individual research groups who have built devices, developed stimulation strategies, or investigated the basic physiology underpinning retinal prostheses. Current technologies are summarized, along with future challenges that face the field

Intravenous ATP infusions can be safely administered in the home setting: a study in pre-terminal cancer patients

The aim of the study was to investigate the safety of adenosine 5′-triphosphate (ATP) administration at home in pre-terminal cancer patients. Included were patients with cancer for whom medical treatment options were restricted to supportive care, who had a life expectancy of less than 6 months, a World Health Organization performance status 1 or 2, and suffered from at least one of the following complaints: fatigue, anorexia or weight loss >5% over the previous 6 months. Side effects were registered systematically on a standard form according to the National Cancer Institute (NCI) Common Toxicity Criteria. Fifty-one patients received a total of 266 intravenous ATP infusions. Of these, 11 infusions (4%) were given at the lowest dose of 20 μg kg−1 min−1, 85 infusions (32%) at 25–40 μg kg−1 min−1, and 170 (64%) at the highest dose of 45–50 μg kg−1 min−1 ATP. The majority of ATP infusions (63%) were without side effects. Dyspnea was the most common side effect (14% of infusions), followed by chest discomfort (12%) and the urge to take a deep breath (11%). No symptoms of cardiac ischemia occurred in any of the infusions. All side effects were transient and resolved within minutes after lowering the ATP infusion rate. Side effects were most frequent in the presence of cardiac disorders. We conclude that ATP at a maximum dose of 50 μg kg−1 min−1 can be safely administered in the home setting in patients with pre-terminal cancer

Insecticide resistance enhances male reproductive success in a beetle

peer reviewe

Breast-feeding duration and infant atopic manifestations, by maternal allergic status, in the first 2 years of life (KOALA study).

Objective To investigate the potential effect of modification by maternal allergic status on the relationship between breast-feeding duration and infant atopic manifestations in the first 2 years of life. Study design Data from 2705 infants of the KOALA Birth Cohort Study (The Netherlands) were analyzed. The data were collected by repeated questionnaires at 34 weeks of gestation and 3, 7, 12, and 24 months postpartum. Total and specific immunoglobulin E measurements were performed on venous blood samples collected during ionic visits at age 2 years. Relationships were analyzed using logistic regression analyses. Results Longer duration of breast-feeding was associated with a lower risk for eczema in infants of mothers without allergy or asthma (P-trend = .01) and slightly lower risk in those of mothers with allergy but noasthma(P-trend =.14). There was no such association for asthmatic mothers (P-trend =.87). Longer breast-feeding duration decreased the risk of recurrent wheeze independent of maternal allergy (P-trend =.02) or asthma status See editorial, p 331 and (P-trend =.06). related articles, p 352 Conclusions Our findings show that the relationship between breast-feeding and and p 359 infant eczema in the first 2 years of life is modified by maternal allergic status. The protective effect of breast-feeding on recurrent wheeze may be associated with protection against respiratory infection