Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial.

BACKGROUND: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. METHODS: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. FINDINGS: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. INTERPRETATION: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. FUNDING: AbbVie.

Femur 3D-DXA Assessment in Female Football Players, Swimmers, and Sedentary Controls.

Cortical and trabecular volumetric bone mineral density (vBMD), cortical thickness and surface BMD (sBMD, density-to-thickness ratio) were analyzed in the proximal femur of elite female football players and artistic swimmers using three-dimensional dual-energy X-ray absorptiometry (3D-DXA) software and compared to sedentary controls. Football players had significantly higher (p<0.05) vBMD (mg/cm3) in the trabecular (263±44) and cortical femur (886±69) than artistic swimmers (224±43 and 844±89) and sedentary controls (215±51 and 841±85). Football players had also higher (p<0.05) cortical thickness (2.12±0.19 mm) and sBMD (188±22 mg/cm2) compared to artistic swimmers (1.85±0.15 and 156±21) and sedentary controls (1.87±0.16 and 158±23). Artistic swimmers did not show significant differences in any parameter analyzed for 3D-DXA when compared to sedentary controls. The 3D-DXA modeling revealed statistical differences in cortical thickness and vBMD between female athletes engaged in weight-bearing (football) and non-weight bearing (swimming) sports and did not show differences between the non-weight bearing sport and the sedentary controls. 3D-DXA modeling could provide insight into bone remodeling in the sports field, allowing evaluation of femoral trabecular and cortical strength from standard DXA scans.

Jumping rope and whole-body vibration program effects on bone values in Olympic artistic swimmers.

INTRODUCTION: Artistic swimming seems not to benefit bone development like other out-of-water physical activities. To increase bone acquisition, artistic swimming should combine water training with weight-bearing impact or strength activities. Artistic swimmers can be a population at risk of developing osteopenia and osteoporosis in later life. The aim of the present study was to evaluate the effects of a training program on bone mineral density (BMD), bone mineral content (BMC) and body composition in an Olympic artistic swimming team. METHODS: Sixteen women aged 17-21 years, who train 30 h/week, at the Olympic Training Centre (Barcelona, Spain), were followed up over two seasons. The 1st season involved regular artistic swimming training without specific training to reduce the risk of osteopenia. The exercise intervention, jumping rope and whole-body vibration, was added in the 2nd season. The protocol included 20 min of training 2 days per week, over a 22-week period. Dual energy x-ray absorptiometry measured the bone variables and body composition. The daily diet, medical history and bone turnover markers were evaluated. RESULTS: The intervention program increased BMD on lumbar spine (2.10%, p = 0.002), total hip (2.07%, p = 0.001), and femoral neck (2.39%, p = 0.02). Lower limb's fat mass decreased (10.17%, p = 0.038). No significant differences were found for any of the measured anthropometric characteristics between both time points in the 1st season. In conclusions, combined jump rope and vibration should be considered to reduce the risk of bone damage in artistic swimmers.

Timing of Pulmonary Rehabilitation in Readmitted Patients with Severe Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial.

Early pulmonary rehabilitation (PR), started during hospitalization or within the first month after discharge, has been shown to reduce exacerbations and improve health-related-quality of life (HRQoL) and exercise capacity. However, no randomized clinical trials (RCT) have compared the efficacy of PR started during hospitalization (DHPR) to PR initiated one month post-hospitalization (PHPR). We conducted an RCT to compare DHPR to PHPR in severe patients with COPD readmitted for exacerbations in a tertiary hospital setting. Patients were randomized to receive three months of DHPR or PHPR. Outcomes were assessed at completion of the PR programme and at months 3 and 9. A total of 53 patients (26 DHPR and 27 PHPR) were included. There were no between-group differences in the number of exacerbations (mean, 3.62 vs. 3.04 in the DHPR and PHPR groups, respectively; p = 0.403). Dyspnea in activities of daily living, exercise capacity, and all HRQoL parameters improved in the PHPR group. In the DHPR group, improvement was observed only for some HRQoL parameters. All gains in both groups were lost during follow-up. More adverse events were observed in the DHPR group (20 vs 5, p = 0.023), although none of these were clinically significant. In this sample of patients with severe COPD readmitted to the hospital for exacerbations, both approaches to PR were safe, but PHPR yielded better outcomes overall. These findings suggest that, PR should be initiated in patients with severe COPD only after hospital discharge when the patients' clinical condition has stabilized.

Prevalence of Sarcopenia and Whole-Body Composition in Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint deformity and disability, as well as muscle involvement. Sarcopenia is characterized by a progressive age-related loss of muscle mass and strength. AIM: The aim of this study was to evaluate the prevalence of sarcopenia and possible contributing factors associated with sarcopenia in RA patients. PATIENTS AND METHODS: Adult RA patients (n = 105) of both sexes and 100 subjects as control group (CG) matched by age, sex, and body mass index were included in this cross-sectional study. Whole-body composition was measured by dual-energy x-ray absorptiometry. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass [ASM] index by dual-energy x-ray absorptiometry). The association between sarcopenia and associated factors was evaluated using logistic regression analyses. RESULTS: Significantly lower percentage of lean mass and ASM were found in the whole RA group compared with controls. However, lower lean parameters (total lean mass, percentage of lean mass, and ASM) were observed only in female subjects. The ASM index was significantly lower in female subjects with RA (RA 31.0% vs CG 11.9%) without differences in male subjects. On the other hand, fat mass and most adipose indices were significantly higher in both female and male subjects with RA. Female RA patients had higher prevalence of sarcopenia and sarcopenic obesity. Through univariate logistic regression analysis, the time of corticosteroids use, cumulative corticosteroid dose, previous fragility fractures, total lean mass, and ASM were associated with sarcopenia. CONCLUSIONS: Higher prevalence of sarcopenia and sarcopenic obesity were found in female RA patients. Sarcopenia was found in younger female subjects with RA compared with healthy control subjects. Sarcopenia was associated with previous fragility fractures in female patients with RA.

DXA-Based 3D Analysis of the Cortical and Trabecular Bone of Hip Fracture Postmenopausal Women: A Case-Control Study.

Methods using statistical shape and appearance models have been proposed to analyze bone mineral density (BMD) in 3D from dual energy X-ray absorptiometry (DXA) scans. This paper presents a retrospective case-control study assessing the association of DXA-derived 3D measurements with osteoporotic hip fracture in postmenopausal women. Patients who experienced a hip fracture between 1 and 6 years from baseline and age-matched controls were included in this study. The 3D-SHAPER software (version 2.7, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from hip DXA scans at baseline. DXA and 3D measurements were compared between groups. Total hip areal BMD of hip fracture group as measured by DXA was 10.7% lower compared to control group. Differences in volumetric BMD (total hip) as measured by 3D-SHAPER were more pronounced in the trabecular compartment (-23.3%) than in the cortex (-8.2%). The area under the receiver operating curve was 0.742 for trabecular volumetric BMD, 0.706 for cortical volumetric BMD, and 0.712 for total hip areal BMD. Differences in the cortex were locally more pronounced at the medial aspect of the shaft, the lateral aspect of the greater trochanter, and the superolateral aspect of the neck. Marked differences in volumetric BMD were observed in the greater trochanter. This case-control study showed the association of DXA-derived 3D measurements with hip fracture. Analysis of large cohorts will be performed in future work to determine if DXA-derived 3D measurements could improve fracture risk prediction in clinical practice.

A Role for RNS in the Communication of Plant Peroxisomes with Other Cell Organelles?

Plant peroxisomes are organelles with a very active participation in the cellular regulation of the metabolism of reactive oxygen species (ROS). However, during the last two decades peroxisomes have been shown to be also a relevant source of nitric oxide (NO) and other related molecules designated as reactive nitrogen species (RNS). ROS and RNS have been mainly associated to nitro-oxidative processes; however, some members of these two families of molecules such as H2O2, NO or S-nitrosoglutathione (GSNO) are also involved in the mechanism of signaling processes mainly through post-translational modifications. Peroxisomes interact metabolically with other cell compartments such as chloroplasts, mitochondria or oil bodies in different pathways including photorespiration, glyoxylate cycle or ß-oxidation, but peroxisomes are also involved in the biosynthesis of phytohormones including auxins and jasmonic acid (JA). This review will provide a comprehensive overview of peroxisomal RNS metabolism with special emphasis in the identified protein targets of RNS inside and outside these organelles. Moreover, the potential interconnectivity between peroxisomes and other plant organelles, such as mitochondria or chloroplasts, which could have a regulatory function will be explored, with special emphasis on photorespiration.

The Proteome of Fruit Peroxisomes: Sweet Pepper (Capsicum annuum L.) as a Model.

Despite of their economical and nutritional interest, the biology of fruits is still little studied in comparison with reports of other plant organs such as leaves and roots. Accordingly, research at subcellular and molecular levels is necessary not only to understand the physiology of fruits, but also to improve crop qualities. Efforts addressed to gain knowledge of the peroxisome proteome and how it interacts with the overall metabolism of fruits will provide tools to be used in breeding strategies of agricultural species with added value. In this work, special attention will be paid to peroxisomal proteins involved in the metabolism of reactive oxygen species (ROS) due to the relevant role of these compounds at fruit ripening. The proteome of peroxisomes purified from sweet pepper (Capsicum annuum L.) fruit is reported, where an iron-superoxide dismutase (Fe-SOD) was localized in these organelles, besides other antioxidant enzymes such as catalase and a Mn-SOD, as well as enzymes involved in the metabolism of carbohydrates, malate, lipids and fatty acids, amino acids, the glyoxylate cycle and in the potential organelles' movements.

Plant peroxisomes at the crossroad of NO and H2 O2 metabolism.

Plant peroxisomes are subcellular compartments involved in many biochemical pathways during the life cycle of a plant but also in the mechanism of response against adverse environmental conditions. These organelles have an active nitro-oxidative metabolism under physiological conditions but this could be exacerbated under stress situations. Furthermore, peroxisomes have the capacity to proliferate and also undergo biochemical adaptations depending on the surrounding cellular status. An important characteristic of peroxisomes is that they have a dynamic metabolism of reactive nitrogen and oxygen species (RNS and ROS) which generates two key molecules, nitric oxide (NO) and hydrogen peroxide (H2 O2 ). These molecules can exert signaling functions by means of post-translational modifications that affect the functionality of target molecules like proteins, peptides or fatty acids. This review provides an overview of the endogenous metabolism of ROS and RNS in peroxisomes with special emphasis on polyamine and uric acid metabolism as well as the possibility that these organelles could be a source of signal molecules involved in the functional interconnection with other subcellular compartments.

Model Study To Assess Softwood Hemicellulose Hydrolysates as the Carbon Source for PHB Production in Paraburkholderia sacchari IPT 101.

Softwood hemicellulose hydrolysates are a cheap source of sugars that can be used as a feedstock to produce polyhydroxybutyrates (PHB), which are biobased and compostable bacterial polyesters. To assess the potential of the hemicellulosic sugars as a carbon source for PHB production, synthetic media containing softwood hemicellulose sugars (glucose, mannose, galactose, xylose, arabinose) and the potentially inhibitory lignocellulose degradation products (acetic acid, 5-hydroxymethylfurfural (HMF), furfural, and vanillin) were fermented with the model strain Paraburkholderia sacchari IPT 101. Relative to pure glucose, individual fermentation for 24 h with 20 g/L mannose or galactose exhibited maximum specific growth rates of 97% and 60%, respectively. On the other hand, with sugar mixtures of glucose, mannose, galactose, xylose, and arabinose, the strain converted all sugars simultaneously to reach a maximum PHB concentration of 5.72 g/L and 80.5% PHB after 51 h. The addition of the inhibitor mixture at the following concentration, sodium acetate (2.11 g/L), HMF (0.67 g/L), furfural (0.66 g/L), and vanillin (0.93 g/L), to the sugar mixture stopped the growth entirely within 24 h. Individually, the inhibitors either had no effect or only reduced growth. Moreover, it was found that a bacterial inoculum with high initial cell density (optical density, OD ≥ 5.6) could overcome the growth inhibition to yield an OD of 13 within 24 h. Therefore, softwood hemicellulose sugars are viable carbon sources for PHB production. Nevertheless, real softwood hemicellulose hydrolysates need detoxification or a high inoculum to overcome inhibitory effects and allow bacterial growth.

Nail dryer devices: a measured spectral irradiance and labelling review.

The popularity of nail beauty has increased during the last few years in Spain, as well as in other countries. Nowadays there are a large number of nail dryer devices in the market with ultraviolet (UV) fluorescent lamps, light emitting diodes (LED) or a combination of both. The different spectral emissions of each individual nail dryer device require particular nail polishes, which are polymerized by specific wavelengths and a controlled exposure time to achieve the desired results. We have measured and analyzed the emission of 28 nail dryer devices currently in use in Spanish beauty centers. The emission of each individual nail dryer device showed a particular spectral distribution and maximum intensity, especially those with fluorescent lamps or LED/UV combinations. About 30% of the devices emitted more UV-A radiation than that received in Barcelona at solar noon in summer. Nevertheless, in all cases the erythemal irradiance was low, similarly to ambient values at solar noon in winter or when the solar altitude is low. The erythemal doses corresponding to a typical session were, therefore, lower than those received from sunlight at summer midday at equivalent exposure times. The biological irradiances for photoaging (skin sagging and elastosis) showed high variability depending on the device, especially for fluorescent lamps. Since the emission of LED-based devices is centered in the visible region, erythemal and photoaging irradiances were low. An analysis of the labelling showed that 85% of the devices had a visible label, although 23% contained some errors, according to the EN 60335-1 guideline.

ROS Generation in Peroxisomes and its Role in Cell Signaling.

In plant cells, as in most eukaryotic organisms, peroxisomes are probably the major sites of intracellular H2O2 production, as a result of their essentially oxidative type of metabolism. In recent years, it has become increasingly clear that peroxisomes carry out essential functions in eukaryotic cells. The generation of the important messenger molecule hydrogen peroxide (H2O2) by animal and plant peroxisomes and the presence of catalase in these organelles has been known for many years, but the generation of superoxide radicals (O2·- ) and the occurrence of the metalloenzyme superoxide dismutase was reported for the first time in peroxisomes from plant origin. Further research showed the presence in plant peroxisomes of a complex battery of antioxidant systems apart from catalase. The evidence available of reactive oxygen species (ROS) production in peroxisomes is presented, and the different antioxidant systems characterized in these organelles and their possible functions are described. Peroxisomes appear to have a ROS-mediated role in abiotic stress situations induced by the heavy metal cadmium (Cd) and the xenobiotic 2,4-D, and also in the oxidative reactions of leaf senescence. The toxicity of Cd and 2,4-D has an effect on the ROS metabolism and speed of movement (dynamics) of peroxisomes. The regulation of ROS production in peroxisomes can take place by post-translational modifications of those proteins involved in their production and/or scavenging. In recent years, different studies have been carried out on the proteome of ROS metabolism in peroxisomes. Diverse evidence obtained indicates that peroxisomes are an important cellular source of different signaling molecules, including ROS, involved in distinct processes of high physiological importance, and might play an important role in the maintenance of cellular redox homeostasis.

ROS and RNS in plant physiology: an overview.

The production of reactive oxygen species (ROS) is the unavoidable consequence of aerobic life. ROS is a collective term that includes both oxygen radicals, like superoxide (O 2. -) and hydroxyl (·OH) radicals, and other non-radicals such as hydrogen peroxide (H2O2), singlet oxygen ((1)O2 or (1)Δg), etc. In plants, ROS are produced in different cell compartments and are oxidizing species, particularly hydroxyl radicals and singlet oxygen, that can produce serious damage in biological systems (oxidative stress). However, plant cells also have an array of antioxidants which, normally, can scavenge the excess oxidants produced and so avoid deleterious effects on the plant cell bio-molecules. The concept of 'oxidative stress' was re-evaluated in recent years and the term 'oxidative signalling' was created. This means that ROS production, apart from being a potentially harmful process, is also an important component of the signalling network that plants use for their development and for responding to environmental challenges. It is known that ROS play an important role regulating numerous biological processes such as growth, development, response to biotic and environmental stresses, and programmed cell death. The term reactive nitrogen species (RNS) includes radicals like nitric oxide (NO· ) and nitric dioxide (NO2.), as well as non-radicals such as nitrous acid (HNO2) and dinitrogen tetroxide (N2O4), among others. RNS are also produced in plants although the generating systems have still not been fully characterized. Nitric oxide (NO·) has an important function as a key signalling molecule in plant growth, development, and senescence, and RNS, like ROS, also play an important role as signalling molecules in the response to environmental (abiotic) stress. Similarly, NO· is a key mediator, in co-operation with ROS, in the defence response to pathogen attacks in plants. ROS and RNS have been demonstrated to have an increasingly important role in biology and medicine.

Physiology of pepper fruit and the metabolism of antioxidants: chloroplasts, mitochondria and peroxisomes.

BACKGROUND AND AIMS: Pepper (Capsicum annuum) contains high levels of antioxidants, such as vitamins A and C and flavonoids. However, information on the role of these beneficial compounds in the physiology of pepper fruit remains scarce. Recent studies have shown that antioxidants in ripe pepper fruit play a key role in responses to temperature changes, and the redox state at the time of harvest affects the nutritional value for human consumption. In this paper, the role of antioxidant metabolism of pepper fruit during ripening and in the response to low temperature is addressed, paying particular attention to ascorbate, NADPH and the superoxide dismutase enzymatic system. The participation of chloroplasts, mitochondria and peroxisomes in the ripening process is also investigated. SCOPE AND RESULTS: Important changes occur at a subcellular level during ripening of pepper fruit. Chloroplasts turn into chromoplasts, with drastic conversion of their metabolism, and the role of the ascorbate-glutathione cycle is essential. In mitochondria from red fruits, higher ascorbate peroxidase (APX) and Mn-SOD activities are involved in avoiding the accumulation of reactive oxygen species in these organelles during ripening. Peroxisomes, whose antioxidant capacity at fruit ripening is substantially affected, display an atypical metabolic pattern during this physiological stage. In spite of these differences observed in the antioxidative metabolism of mitochondria and peroxisomes, proteomic analysis of these organelles, carried out by 2-D electrophoresis and MALDI-TOF/TOF and provided here for the first time, reveals no changes between the antioxidant metabolism from immature (green) and ripe (red) fruits. CONCLUSIONS: Taken together, the results show that investigation of molecular and enzymatic antioxidants from cell compartments, especially chloroplasts, mitochondria and peroxisomes, is a useful tool to study the physiology of pepper fruit, particularly in the context of expanding their shelf-life after harvest and in maintaining their nutritional value.

Spatial and temporal regulation of the metabolism of reactive oxygen and nitrogen species during the early development of pepper (Capsicum annuum) seedlings.

BACKGROUND AND AIMS: The development of seedlings involves many morphological, physiological and biochemical processes, which are controlled by many factors. Some reactive oxygen and nitrogen species (ROS and RNS, respectively) are implicated as signal molecules in physiological and phytopathological processes. Pepper (Capsicum annuum) is a very important crop and the goal of this work was to provide a framework of the behaviour of the key elements in the metabolism of ROS and RNS in the main organs of pepper during its development. METHODS: The main seedling organs (roots, hypocotyls and green cotyledons) of pepper seedlings were analysed 7, 10 and 14 d after germination. Activity and gene expression of the main enzymatic antioxidants (catalase, ascorbate-glutathione cycle enzymes), NADP-generating dehydrogenases and S-nitrosoglutathione reductase were determined. Cellular distribution of nitric oxide ((·)NO), superoxide radical (O2 (·-)) and peroxynitrite (ONOO(-)) was investigated using confocal laser scanning microscopy. KEY RESULTS: The metabolism of ROS and RNS during pepper seedling development was highly regulated and showed significant plasticity, which was co-ordinated among the main seedling organs, resulting in correct development. Catalase showed higher activity in the aerial parts of the seedling (hypocotyls and green cotyledons) whereas roots of 7-d-old seedlings contained higher activity of the enzymatic components of the ascorbate glutathione cycle, NADP-isocitrate dehydrogenase and NADP-malic enzyme. CONCLUSIONS: There is differential regulation of the metabolism of ROS, nitric oxide and NADP dehydrogenases in the different plant organs during seedling development in pepper in the absence of stress. The metabolism of ROS and RNS seems to contribute significantly to plant development since their components are involved directly or indirectly in many metabolic pathways. Thus, specific molecules such as H2O2 and NO have implications for signalling, and their temporal and spatial regulation contributes to the success of seedling establishment.

Role of peroxisomes as a source of reactive oxygen species (ROS) signaling molecules.

Peroxisomes are very dynamic and metabolically active organelles and are a very important source of reactive oxygen species (ROS), H2O2, O2 (.-) and · OH, which are mainly produced in different metabolic pathways, including fatty acid ß-oxidation, photorespiration, nucleic acid and polyamine catabolism, ureide metabolism, etc. ROS were originally associated to oxygen toxicity; however, these reactive species also play a central role in the signaling network regulating essential processes in the cell. Peroxisomes have the capacity to rapidly produce and scavenge H2O2 and O2 (.-) which allows to regulate dynamic changes in ROS levels. This fact and the plasticity of these organelles, which allows adjusting their metabolism depending on different developmental and environmental cues, makes these organelles play a central role in cellular signal transduction. The use of catalase and glycolate oxidase loss-of-function mutants has allowed to study the consequences of changes in the levels of endogenous H2O2 in peroxisomes and has improved our knowledge of the transcriptomic profile of genes regulated by peroxisomal ROS. It is now known that peroxisomal ROS participate in more complex signaling networks involving calcium, hormones, and redox homeostasis which finally determine the response of plants to their environment.

Peroxisomes as cell generators of reactive nitrogen species (RNS) signal molecules.

Nitric oxide is a gaseous free radical with a wide range of direct and indirect actions in plant cells. However, the enzymatic sources of NO and its subcellular localization in plants are still under debate. Among the different subcellular compartments where NO has been found to be produced, peroxisomes are the best characterized since in these organelles it has been demonstrated the presence of NO and it has been biochemically characterized a L-arginine-dependent nitric oxide synthase activity. This chapter summarizes the present knowledge of the NO metabolism and its derived reactive nitrogen species (RNS) in plant peroxisomes and how this gaseous free radical is involved in natural senescence, and is released to the cytosol under salinity stress conditions acting as a signal molecule.

Distribution of serum ßCTX in a population-based study of postmenopausal women taking into account different anti-osteoporotic therapies (the FRODOS Cohort).

This cross-sectional study evaluated the distribution of serum cross-linked C-telopeptides of collagen type I (ßCTXs) in postmenopausal women, the characteristics of bone remodeling, and the factors influencing this bone marker, especially the use of anti-osteoporotic drugs. Women (n = 4,175) aged 59-70 years randomly selected from the community were invited to participate, measuring ßCTXs and lumbar and femoral bone mineral density at recruitment. Risk factors for osteoporosis and the use of anti-osteoporotic treatment were collected with a structured questionnaire. We evaluated the percentage of women with increased (ßCTXs >0.620 ng/mL) and decreased bone turnover (ßCTXs <0.100 ng/mL) and those reaching the so-called treatment target (values of ßCTXs within the lower half of the reference range for healthy young premenopausal women). Two thousand nine hundred sixty-eight women (70 %) participated (2,405 non-treated and 563 treated). Increased and decreased bone turnover was observed in 16.4 and 1.8 %, respectively, of non-treated women with significant differences compared with treated women (9.7 and 14.2 %, respectively, p < 0.001); 28 % of non-treated osteoporotic individuals had increased bone turnover versus 14 % of osteopenic participants and 8.8 % of women with normal bone density (p < 0.001). Women receiving bisphosphonates presented the highest percentages of decreased bone turnover (27 %) and ßCTXs (43 %) within the treatment target. Increased bone turnover is observed in 16.4 % of non-treated postmenopausal women and is more frequent in individuals with osteoporosis, whereas decreased bone turnover is unusual. Most participants taking bisphosphonates had values within the treatment target, but nearly one quarter had decreased bone turnover.

Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome.

OBJECTIVE: We evaluated the safety of testosterone treatment and its efficacy on body composition in males with testosterone deficiency syndrome (TDS) over 24 months. METHODS: 50 males aged 50-65 years with TDS (Aging Males Symptoms Scale [AMS] > 26 and calculated free testosterone [cFT] 250 pmol/l) were administered 50 mg testosterone gel daily for one year. During the second year, patients received 1000 mg of testosterone undecanoate every 2-3 months. Outcome measures were clinical chemistry values and total testosterone; sex hormone-binding globulin and cFT, changes in AMS and International Prostate Symptom Score; and changes in body composition measured by dual-energy-x-ray absorptiometry. RESULTS: There were no clinically significant changes in clinical chemistry safety parameters. There were significant improvements in both total and cFT and in AMS scores after three months (p < 0.001). Lean mass increased 2.35% at 12 months and 4.5% at 24 months, but proportionally more muscle mass was gained in arms and legs than in the trunk. Fat mass decreased 4.2% at 12 months and 9.1% at 24 months. CONCLUSIONS: Testosterone treatment in males with TDS leads to body changes affecting lean and fat mass with significant improvement in AMS scores, and has an excellent safety profile.

Fat tissue measurements by dual-energy x-ray absorptiometry: cross-calibration of 3 different fan-beam instruments.

Analysis of total tissue composition and, particularly, body fat measurements has become progressively important in the diagnosis and follow-up of patients with different clinical conditions. Dual-energy X-ray absorptiometry (DXA) fan-beam scanners are widely used to measure body composition, but the development of translational equations to be able to compare data of different scanning systems is necessary. The aim of this study was to assess the extent of agreement for regional measurements of body composition among the following 3 fan-beam DXA scanners: (1) Hologic Discovery (Hologic, Inc., Waltham, MA), (2) Lunar iDXA (GE Healthcare, Madison, WI), and (3) Lunar Prodigy Advance (GE Healthcare, Madison, WI). The study population consisted of 91 adult healthy volunteers (40 males and 51 females; mean age 48.5±14.4yr) who underwent DXA evaluation of the lumbar spine, hip, and whole body in each machine on the same day. Agreement among the 3 scanners was evaluated according to the Bland-Altman method and Lin's concordance correlation coefficient. Results showed a better agreement and concordance for the Lunar iDXA scanner than for any of them with the Hologic scanner. Differences were higher for any tissue or region than for the whole tissue mass. Translational equations were developed to ensure comparability of body composition measurements obtained with each of these 3 scanners.