Extract and the quassinoid ailanthone from Ailanthus altissima inhibit nematode reproduction by damaging germ cells and rachis in the model organism Caenorhabditis elegans.

Bark and leaves of Ailanthus altissima (Mill.) Swingle are widely used in European folk medicine to treat intestinal worm infections. The study aimed to rationalize a potential anthelmintic effect of A. altissima extract against the model organism Caenorhabditis elegans. A methanol-water (7:3, v/v) extract of the primary stem bark was tested on L4 larvae of C. elegans for induction of mortality and influence on reproduction. Bioactivity-guided fractionation was performed by chromatography on MCI-gel, preparative HPLC on RP18 stationary phase and fast-centrifugal-partition-chromatography. Structural elucidation of isolated quassinoids was performed by NMR and HR-ESI-MS. The sterilizing effect on C. elegans was investigated by light microscopy and atomic force microscopy of ultra-sections. Different GFP-tagged reporter strains were used to identify involved signaling pathways. A. altissima extract (1 mg/mL) irreversibly inhibited the reproduction of C. elegans L4 larvae. This effect was dependent on the larval stage since L3 larvae and adults were less affected. Bioactivity-guided fractionation revealed the quassinoid ailanthone 1 as the major active compound (IC50 2.47 µM). The extract caused severe damages to germ cells and rachis, which led to none or only poorly developed oocytes. These damages led to activation of the transcription factor DAF-16, which plays a major role in the nematode's response to stress. A regulation via the respective DAF-2/insulin-like signaling pathway was not observed. The current findings support the traditional use of A. altissma in phytotherapy to treat helminth infections and provide a base for standardization of the herbal material.

Parp mutations protect against mitochondrial dysfunction and neurodegeneration in a PARKIN model of Parkinson's disease.

The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is an essential co-factor for cellular energy generation in mitochondria as well as for DNA repair mechanisms in the cell nucleus involving NAD(+)-consuming poly (ADP-ribose) polymerases (PARPs). Mitochondrial function is compromised in animal models of Parkinson's disease (PD) associated with PARKIN mutations. Here, we uncovered alterations in NAD(+) salvage metabolism in Drosophila parkin mutants. We show that a dietary supplementation with the NAD(+) precursor nicotinamide rescues mitochondrial function and is neuroprotective. Further, by mutating Parp in parkin mutants, we show that this increases levels of NAD(+) and its salvage metabolites. This also rescues mitochondrial function and suppresses dopaminergic neurodegeneration. We conclude that strategies to enhance NAD(+) levels by administration of dietary precursors or the inhibition of NAD(+)-dependent enzymes, such as PARP, that compete with mitochondria for NAD(+) could be used to delay neuronal death associated with mitochondrial dysfunction.

A novel time-resolved laser fluorescence spectroscopy system for research on complexation of uranium(IV).

To date only a small number of studies have investigated the chemical speciation of complexes and the fluorescence properties of metal ions whose emitted fluorescence lifetime is in the range of only few nanoseconds. This is due to a lack of advanced methods which allow the conduction of these measurements. In the current study we set up a new time-resolved laser fluorescence spectroscopy system with which the fluorescence properties of metal ions with very short fluorescence lifetimes such as uranium(IV) and its compounds can be investigated. By studying the fluorescence properties of uranium(IV) in perchloric acid, we showed uranium(IV) to have a detection limit of 5 x 10(-7)M and a fluorescence decay time of 2.74+/-0.36 ns. We further investigated the fluorescence properties of uranium(IV) during the reaction with fluoride and applied our novel laser system to study the complexation of uranium(IV) with fluoride. Our data revealed the formation of a 1:1 complex of uranium(IV) and fluoride. The corresponding complex formation constant of uranium(IV) fluoride UF(3+) was found to be log beta(0)=9.43+/-1.94. Our results demonstrate that our novel time-resolved laser fluorescence spectroscopy system can successfully conduct speciation measurements of metal ions and their compounds with very short-lived fluorescence lifetimes. Using this laser system, it is possible to analytically investigate such elements and compounds in environmentally relevant concentration ranges.

Predictors for response to rehabilitation in patients with hip or knee osteoarthritis: a comparison of logistic regression models with three different definitions of responder.

OBJECTIVE: To identify pre-treatment predictors of who will benefit from a 3-4-week comprehensive rehabilitation intervention in patients with osteoarthritis (OA) of the knee or hip. METHODS: A prospective cohort study with assessments at admission to the clinic and after 6 months was conducted. Two hundred and fifty patients from the rehabilitation clinic Rehaclinic Zurzach, Switzerland, were included. Three different measures of response to a 3-4-week comprehensive rehabilitation intervention were used: one indirect measure (minimal clinically important difference (MCID) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score=18% improvement), one direct measure (transition question) and a combination of both criteria. Responders were predicted by a sequential logistic regression analysis with nine personal variables, five lifestyle risk factors, seven psychological status variables and the WOMAC global baseline score. RESULTS: The set of statistically significant predictors was dependent on the definition of response. The comparison of predictors that were statistically significant in any of the prediction models showed similar odds ratios (ORs) for the majority of predictors across three regression models with the different response definitions as dependent variable. Female gender, absence of depressive symptoms (dep), history of complementary medicine (cm) and low comorbidity (com) were the most stable predictors and had ORs above 2.0 (female) and above 1.5 (dep, cm, com) across the three regression models with different response definitions. CONCLUSION: A set of predictors for the outcome of rehabilitation in patients with OA was identified. If these predictors could be confirmed in future research, this knowledge might help to adopt and individualize the treatment of patients who are, at present, less likely to respond.

Improvement in immune function in ICU patients by enteral nutrition supplemented with arginine, RNA, and menhaden oil is independent of nitrogen balance.

Hypermetabolism and multiple organ failure syndrome (MOFS) after trauma, surgery, or sepsis is associated with accelerated catabolism, the rapid onset of malnutrition, and immune system failure. Current nutritional support, enteral or parenteral, can achieve an acceptable nutritional response but appears unable to improve immune function. Nutrients such as arginine, refined menhaden oil, and RNA have been found to have immune-stimulating properties. This randomized blind prospective trial compared two nutritionally complete enteral formulas, one supplemented with arginine, menhaden oil, and RNA, on the disease-specific effects of anergy and suppression of in vitro tests of immune function in intensive-care patients and the nutritional outcome of nitrogen balance. After 7-10 days of enteral nutrition in patients with persistent sepsis syndrome, both formulas were associated with the achievement of net nitrogen retention and improved visceral protein status but with nonresolution of anergy. However, the supplemented formula was associated with marked stimulation of in vitro lymphocyte proliferative responses and a significant reduction in 3-methylhistidine excretion. Six and 12-mo follow-up data demonstrated no long-term effects. Nutrients targeted to effect the disease-induced in vitro suppression of immune function in MOFS appear to achieve that end independent of the nutritional outcome of nitrogen balance and without adverse clinical outcome.