Reduced glutamine synthetase activity plays a role in control of photosynthetic responses to high light in barley leaves

The chloroplastic glutamine synthetase (GS, EC 6.3.1.2) activity was previously shown to be the limiting step of photorespiratory pathway. In our experiment, we examined the photosynthetic high-light responses of the GS2-mutant of barley (Hordeum vulgare L.) with reduced GS activity, in comparison to wild type (WT). The biophysical methods based on slow and fast chlorophyll fluorescence induction, P700 absorbance, and gas exchange measurements were employed. Despite the GS2 plants had high basal fluorescence (F-0) and low maximum quantum yield (F-v/F-m), the CO2 assimilation rate, the PSII and PSI actual quantum yields were normal. On the other hand, in high light conditions the GS2 had much higher non-photochemical quenching (NPQ), caused both by enhanced capacity of energy-dependent quenching and disconnection of PSII antennae from reaction centers (RC). GS2 leaves also maintained the PSII redox poise (Q((A) over bar)/Q(A) total) at very low level; probably this was reason why the observed photoinhibitory damage was not significantly above WT. The analysis of fast chlorophyll fluorescence induction uncovered in GS2 leaves substantially lower RC to antenna ratio (RC/ABS), low PSII/PSI ratio (confirmed by P700 records) as well as low PSII excitonic connectivity. (C) 2014 Elsevier Masson SAS. All rights reserved.The chloroplastic glutamine synthetase (GS, EC 6.3.1.2) activity was previously shown to be the limiting step of photorespiratory pathway. In our experiment, we examined the photosynthetic high-light responses of the GS2-mutant of barley (Hordeum vulgare L.) with reduced GS activity, in comparison to wild type (WT). The biophysical methods based on slow and fast chlorophyll fluorescence induction, P700 absorbance, and gas exchange measurements were employed. Despite the GS2 plants had high basal fluorescence (F-0) and low maximum quantum yield (F-v/F-m), the CO2 assimilation rate, the PSII and PSI actual quantum yields were normal. On the other hand, in high light conditions the GS2 had much higher non-photochemical quenching (NPQ), caused both by enhanced capacity of energy-dependent quenching and disconnection of PSII antennae from reaction centers (RC). GS2 leaves also maintained the PSII redox poise (Q((A) over bar)/Q(A) total) at very low level; probably this was reason why the observed photoinhibitory damage was not significantly above WT. The analysis of fast chlorophyll fluorescence induction uncovered in GS2 leaves substantially lower RC to antenna ratio (RC/ABS), low PSII/PSI ratio (confirmed by P700 records) as well as low PSII excitonic connectivity. (C) 2014 Elsevier Masson SAS. All rights reserved

Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated <it>Plasmodium falciparum</it> malaria in Uganda

<p>Abstract</p> <p>Background</p> <p>Malaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with <it>Plasmodium falciparum</it> transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated <it>P. falciparum</it> malaria in Uganda.</p> <p>Methods</p> <p>Twenty-one women with uncomplicated <it>P. falciparum</it> malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA) were also performed to enable a comparison with literature values and different modeling strategies.</p> <p>Results</p> <p>The treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug and metabolite. This highlights a potential pitfall when analyzing drug/metabolite data with traditional approaches.</p> <p>Conclusion</p> <p>The population pharmacokinetic properties of artemether and dihydroartemisinin, in pregnant women with uncomplicated <it>P. falciparum</it> malaria in Uganda, were described satisfactorily by a simultaneous drug-metabolite model without covariates. Concentrations of artemether and its metabolite dihydroartemisinin were relatively low in pregnancy compared to literature data. However, this should be interpreted with caution considered the limited literature available. Further studies in larger series are urgently needed for this vulnerable group.</p