Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Development and Validation of a Discriminative Dissolution Test for Betamethasone Sodium Phosphate and Betamethasone Dipropionate Intramuscular Injectable Suspension

The intramuscular administration of the injectable suspension betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BD) has immediate therapeutic activity due to solubilized BSP and prolonged activity resulting from the slow release of BD micro-crystals. The purpose of this study was to develop and validate a dissolution method for BD in intramuscular injectable suspensions with detection by high-performance liquid chromatography (HPLC) method. Five commercial products presented a distribution of particle sizes, ranging between 7.43 and 40.25 μm as measured by laser diffraction. It was also found that particle sizes differed between batches of the same product. The different products were tested using the paddle apparatus, with stirring speeds of 25 and 50 rpm in 300 mL of phosphate buffer; simulated body fluid, muscle fluid, and synovial fluid were used as biorelevant dissolution media at 37 ± 0.5°C. It was verified that not only does average particle size affect the dissolution rate, but also the mode and the polydispersity index of the particles. Discriminatory power was obtained using the in vitro dissolution method with 0.1 M sodium phosphate buffer pH 7.4 containing 0.1% sodium lauryl sulfate and a stirring speed of 50 rpm. The HPLC-method is linear, precise, selective, and accurate for the quantification of BSP and BD in dissolution profile testing. This dissolution method can be utilized as a method to control the quality of these injectable suspensions.Key words: dipropionate betamethasone, dissolution test, intramuscular injectable suspensions, simulated muscular fluid, sodium phosphate betamethasone     

EPR detection of paramagnetic chromium in liver of fish (Anguilla anguilla) treated with dichromate(VI) and associated oxidative stress responses—Contribution to elucidation of toxicity mechanisms

The impact of chromium (Cr) on fish health has been the subject of numerous investigations, establishing a wide spectrum of toxicity, attributed particularly to the hexavalent form [Cr(VI)]. However, reports on the simultaneous assessment of Cr toxicity in fish and its toxico-kinetics, namely involving metal speciation, are scarce. Therefore, keeping in view the understanding of the mechanisms of Cr(VI) toxicity, this work intended to detect the formation of paramagnetic Cr species in liver of Anguilla anguilla following short-term dichromate(VI) intraperitoneal treatment (up to 180 min), assessing simultaneously the pro-oxidant properties. The formation of Cr(V) and Cr(III) was examined by electron paramagnetic resonance (EPR), as an innovative approach in the context of fish toxicology, and related with the levels of total Cr. Cr(V) was successfully detected and quantified by EPR spectrometry, showing a transient occurrence, mostly between 15 and 90 min post-injection, with a peak at 30 min. The limitations of EPR methodology towards the detection and quantification of Cr(III) were confirmed. Although Cr(VI) exposure induced the antioxidant system in the eel's liver, the oxidative deterioration of lipids was not prevented. Overall, the results suggested that Cr(V), as a short-lived species, did not appear to be directly and primarily responsible for the cellular damaging effects observed, since stress responses persisted up to the end of exposure regardless Cr(V) drastic decay. Though further research is needed, ROS mediated pathways (suggested by superoxide dismutase and catalase activity induction) and formation of Cr(III) complexes emerged as the most plausible mechanisms involved in Cr(VI) toxicity.     

Concentration by ultrafiltration and stabilization of phytase produced by solid-state fermentation

Ultrafiltration is an attractive downstream processing technique for concentrating enzymes and could be considered the primary step of purification. However, the efficiency of this process is often limited by protein fouling and shear-induced enzyme inactivation, which decreases permeate flux and results in the loss of enzyme activity. Although the rejection of phytase was higher than 99%, the loss of the enzyme activity was 14% during operation, indicating that the shear forces generated in the filter have significant influences on the enzyme activity. Two preparations using glycerol (25% and 35%, v/v) as a cryo-protecting agent at different temperatures were studied. The preparation containing 35% glycerol retained 70% of the initial enzyme activity at 70 °C after 1 h and had more than 3 and 6 months storage half-life at 29 °C and 4 °C, respectively.     

pH dependence of lipid peroxidation and albumin oxidative modification: possible implications to the pH paradox

The hydrogen ion concentration may have an important influence in biological free radical reactions. We studied the effect of an acidic pH on two models of free radical-mediated damage: copper-induced lipid peroxidation in plasma and copper/hydrogen peroxide-induced oxidative modification of albumin. A reduction of pH from 7·4 to 6·6 decreased diene conjugation by 32%, thiobarbituric acid-reactive substances formation by 25% and fluorescence generation by 53% in plasma exposed to cupric chloride. At pH values lower than 6·6 an even greater inhibition of lipid peroxidation in plasma was obtained. Visible fluorescence development in albumin by exposure to site-specific generation of free radicals was also increasingly reduced by decreasing pH values. From pH 7·4 to 6·6 there was a 50% fluorescence generation inhibition. The observed partial protection of lipids and proteins against oxidative damage by an acidic pH alerts to the need for rigorously controlling the pH values when assaying compounds for antioxidant properties in vitro. It may also contribute to the explanation for the protective effect of an acidic pH against anoxic cell injury and for cell death that is precipitated by a rapid return to a normal pH following reperfusion (the ‘pH paradox’).     

Detection of DNA strand breakage in a marine amphipod by agarose gel electrophoresis: exposure to X-rays and copper

This article describes the leading steps to develop an assay of DNA damage for the marine amphipod Gammarus locusta, using agarose gel electrophoresis (AGE). To test the sensitivity and feasibility of the AGE technique, X-ray assays were performed with naked DNA and with live amphipods. These positive controls demonstrated the effectiveness of the AGE technique to not only discriminate distinct levels of DNA strand breakage in a dose-dependent manner, but also to identify and quantify the type of strand breakage induced. It was also shown that it is possible to detect DNA damage using whole-body DNA extracts from amphipods. To explore the potential of this technique for use in ecotoxicological studies with amphipods, a 96-h waterborne-copper toxicity test was performed. Copper-induced DNA strand breakage was first observed after 24 h of exposure, and was recorded again at 96 h, at a copper concentration of 20 μg l -1 . The absence of strand breakage after 48 h of exposure is discussed in the light of the underlying mechanisms of copper toxicity and DNA repair. These studies demonstrated the feasibility of including DNA damage as a biomarker in ecotoxicological studies with amphipods. Information gained from the use of this biomarker would help with the interpretation of chronic toxicity tests and would contribute to our understanding of the impact of genotoxic insult in marine invertebrates, particularly crustaceans.     

Differentially expressed proteins during an incompatible interaction between common bean and the fungus Pseudocercospora griseola

The common bean (Phaseolus vulgaris L.) is the main source of protein and an important source of minerals in several countries around the world. Angular leaf spot, caused by the fungus Pseudocercospora griseola, is one of the major diseases of the common bean. In this work, we used two-dimensional gel electrophoresis and mass spectrometry to analyze alterations in the proteome of common bean leaves challenged with an incompatible race of P. griseola. Twenty-three differentially expressed proteins were detected in leaves of cultivar AND 277 collected at 12, 24 and 48 h after inoculation. The proteins were digested with trypsin and submitted to MALDI-TOF/TOF and MicrOTOF-Q electrospray mass spectrometry. Nineteen of them were identified upon MS/MS fragmentation. Most of these proteins are involved with amino acid metabolism, terpenoid metabolism, phenylpropanoid biosynthesis, antioxidant systems, vitamin and cofactor metabolism, plant–pathogen interaction, carbohydrate metabolism, photosynthesis, or genetic information processing, showing that the interaction in this pathosystem affects different genes from various metabolic pathways and processes.     

Effects of surrounding landscape on parasitism of alfalfa aphids in an IPM crop system in northern Catalonia

The parasitism (Hymenoptera, Braconidae, Aphidiinae) of alfalfa aphids (Hemiptera, Aphididae) was determined during three crop growing seasons. The highest rates of parasitism of Acyrthosiphon pisum Harris and of Therioaphis trifolii Monell occurred during the first-second and the fourth alfalfa intercuts, respectively. The landscape surrounding the fields affected only parasitism rates of A. pisum. During the second intercut the forest area had a negative influence on parasitism rates, whereas the bordering surfaces of alfalfa and winter cereals had a positive influence. Positive correlations were found between the rates of parasitism of A. pisum and the rate of aphid population increase in the first intercut. By contrast, negative correlations were found in the second intercut, when the aphid population peaked, suggesting that parasitoids contribute to the regulation of the aphid. This study stresses that regulation of alfalfa aphids cannot be explained solely on the basis of one functional group of natural enemies.     

Nucleolar organizer regions in Sittasomus griseicapillus and Lepidocolaptes angustirostris (Aves,Dendrocolaptidae): Evidence of a chromosome inversion

Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae) are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs). Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group.