Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Response of the photosynthetic apparatus to a flowering-inductive period by water stress in Citrus

The photosynthetic responses to a flowering-inductive water-stress period and recovery were studied and compared in two Citrus species. Under greenhouse conditions, Fino lemon and Owari satsuma trees were subjected to moderate (-2 MPa at predawn) and severe (-3 MPa) water stress levels and were re-watered after 60 days. Vegetative growth was inhibited during the stress assays, and strong defoliation levels were reported, especially in Fino lemon. In both species, bud sprouting was induced after re-watering. Flowers and vegetative shoots developed in Owari satsuma after a drought period, and the development was independent of the stress level. In Fino lemon, vegetative shoots and flowers were primarily formed after moderate and severe stress, respectively. The photosynthetic rate and stomatal conductance were reduced by water stress, and a marked increase in water-use efficiency at the moderate water deficit level was observed. Nevertheless, the photosynthetic apparatus was not damaged, since the maximum quantum yield, photosynthetic pigment concentrations and Rubisco level and activity did not change. Furthermore, the measured malonyldialdehyde (MDA) and peroxidase activity indicated that oxidative stress was not specifically triggered by water stress in our study. Therefore, the gas exchange, fluorescence and biochemical parameters suggested that diffusional limitations to photosynthesis predominated in both of the studied Citrus species, and explained the rapid recovery of the photosynthetic parameters after rehydration. The net CO 2 fixation rate and stomatal conductance were recovered within 24 h in Fino lemon, whereas 3 days were required in Owari satsuma. This suggests the presence of some metabolic limitations in the latter species. Furthermore, the sensibility of the defoliation rates, the accumulation of proline and the stomatal behaviour in response to water stress indicated a higher drought tolerance of Fino lemon, according to its better acclimation to hot climates. © 2011 Springer-Verlag.The authors thank Dr. J. Moreno and co-workers from the Departamento de Bioquimica of the Universidad de Valencia for his help and support in the Rubisco assays, and Dr. F. Fornes, Dr. A. Calatayud and Dr. E. Primo-Millo for the critical review of the manuscript. This work was funded by the Universitat Politecnica de Valencia, Spain (Ayudas para primeros proyectos de investigacion PAID06-06).Ávila Reséndiz, C.; Guardiola Barcena, JL.; González Nebauer, S. (2012). Response of the photosynthetic apparatus to a flowering-inductive period by water stress in Citrus. Trees - Structure and Function. 26(3):833-840. https://doi.org/10.1007/s00468-011-0657-4S833840263Addicott FT (1982) Abscission. University of California Press, BerkeleyBajji M, Kinet JM, Lutts S (1998) Salt stress effects on roots and leaves of Atriplex halimus L. and their corresponding callus. Plant Sci 137:131–142Barbera G, Fatta-del-Bosco G, Lo-Cascio B (1985) Effect of water stress on lemon summer bloom: the Forzatura technique in the Sicilian citrus industry. Acta Hortic 171:391–397Bates LS, Waldren RP, Teare ID (1973) Rapid determination of free proline for water stress studies. Plant Soil 39:205–207Bota J, Medrano H, Flexas J (2004) Is photosynthesis limited by decreased Rubisco activity and RuBP content under progressive water stress? New Phytol 162:671–681Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254Cassin J, Bourdeaut A, Fougue V, Furon V, Gaillard JP, LeBourdelles J, Montagut G, Moreuil C (1969) The influence of climate upon blooming of Citrus in tropical areas. Proc Int Soc Citrus 1:315–323Castel JR, Buj A (1990) Response of Salustiana oranges to high frequency deficit irrigation. Irrig Sci 11:121–127Chaikiatitiyos S, Menzel CM, Rasmussen TS (1994) Floral induction in tropical fruit trees: effects of temperature and water supply. J Hortic Sci 69:397–415Chaves MM, Flexas J, Pinheiro C (2009) Photosynthesis under drought and salt stress: regulation mechanisms from whole plant to cell. Ann Bot 103:551–560Costa JM, Ortuño MF, Chaves M (2007) Deficit irrigation as a strategy to save water: physiology and potential application to horticulture. J Integr Plant Biol 49:1421–1434Davenport TL (1990) Citrus flowering. Hortic Rev 12:249–408Davies FS, Albrigo LG (1994) Citrus. CAB International, Wallingford, pp 126–134Domingo R, Ruiz-Sánchez MC, Sánchez-Blanco MJ, Torrecillas A (1996) Water relations, growth and yield of Fino lemon trees under regulated deficit irrigation. Irrig Sci 16:115–123Erismann ND, Machado EC, Tucci MLS (2008) Photosynthetic limitation by CO2 diffusion in drought stressed orange leaves on three rootstocks. Photosynth Res 96:163–172Flexas J, Bota J, Galmés J, Medrano H, Ribas-Carbó M (2006) Keeping a positive carbon balance under adverse conditions: responses of photosynthesis and respiration to water stress. Physiol Plant 127:343–352Gallé A, Florez-Sarasa I, Tomas M, Pou A, Medrano H, Ribas-Carbó M, Flexas J (2009) The role of mesophyll conductance during water stress and recovery in tobacco (Nicotiana sylvestris): acclimation or limitation? J Exp Bot 60:2379–2390Galmés J, Medrano H, Flexas J (2007) Photosynthetic limitations in response to water stress and recovery in Mediterrenean plants with different growth forms. New Phytol 175:81–93García-Luis A, Kanduser M, Santamarina P, Guardiola JL (1992) Low temperature influence on flowering in Citrus. The separation of inductive and bud dormancy releasing effects. Physiol Plant 86:648–652García-Sánchez F, Syvertsen JP, Gimeno V, Botía P, Pérez-Pérez JG (2007) Responses to flooding and drought stress by two citrus rootstock seedlings with different water-use efficiency. Physiol Plant 130:532–542Genty B, Briantais JM, Baker NR (1989) The relationship between quantum yield of photosynthetic electron transport and quenching of chlorophyll fluorescence. Biochim Biophys Acta 990:87–92Gómez-Cadenas A, Tadeo FR, Talon M, Primo-Millo E (1996) Leaf abscission induced by ethylene in water-stressed intact seedlings of Cleopatra mandarin requires previous abscisic acid accumulation in roots. Plant Physiol 112:401–408Gordo O, Sanz JJ (2010) Impact of climate change on plant phenology in Mediterranean ecosystems. Glob Chang Biol 16:1082–1106Heath RL, Packer L (1968) Photoperoxidation in isolated chloroplasts. I. Kinetics and stoichiometry of fatty acid peroxidation. Arch Biochem Biophys 125:189–190Hoagland DR, Arnon DI (1950) The water culture method for growing plants without soil. California Agricultural Experiment Station Circular no. 347, p 32IPCC (2001) Climate change 2001. In: Houghton JT (ed) The scientific basis. Cambridge University Press, CambridgeLawlor DW (1995) The effects of water deficit on photosynthesis. In: Smirnoff N (ed) Environment and plant metabolism. Bios Scientific Publishers, Oxford, pp 129–160Lichtenthaler HK, Buschmann C (2001) Current protocols in food analytical chemistry, F4.2.1 and F4.3.1. John Wiley and Sons, Inc, NJLorimer GH, Badger MR, Andrews TJ (1977) D-Ribulose-1, 5-bisphosphate carboxilase-oxigenase. Improved methods for activation and assay of catalytic activities. Anal Biochem 78:66–75Miyashita K, Tanakamaru S, Maitani T, Kimura K (2005) Recovery responses of photosynthesis, transpiration, and stomatal conductance in kidney bean following drought stress. Environ Exp Bot 53:205–214Nir I, Leshem B, Goren R (1972) Effects of water stress, gibberellic acid and 2-chloroethylammoniumchloride (CCC) ob flower differentiation in Eureka lemon trees. J Am Soc Hortic Sci 97:774–778Peñarrubia L, Moreno J (1988) Ribulose 1, 5-bisphosphate carboxylase oxygenase from citrus leaves. Phytochemistry 27:1999–2004Pérez-Pérez JG, Syvertsen JP, Botía P, García-Sánchez F (2007) Leaf water relations and net gas exchange responses of salinized carrizo citrange seedlings during drought stress and recovery. Ann Bot 100:335–345Pérez-Pérez JG, Robles JM, Tovar JC, Botía P (2009) Response to drought and salt stress of lemon ‘Fino 49’ under field conditions: water relations, osmotic adjustment and gas Exchange. Sci Hortic 122:83–90Reynolds M, Tuberosa R (2008) Translational research impacting on crop productivity in drought-prone environments. Curr Opin Plant Biol 11:171–179Ruiz-Sánchez MC, Domingo R, Savé R, Biel C, Torrecillas A (1997) Effects of water stress and rewatering on leaf water relations of lemon plants. Biol Plant 39:623–631Sarris D, Christodoulakis D, Körner C (2007) Recent decline in precipitation and tree growth in the eastern Mediterranean. Glob Chang Biol 13:1187–1200Sharkey TD (1990) Water-stress effects on photosynthesis. Photosynthetica 24:651Southwick SM, Davenport TL (1986) Characterization of water stress and low temperature effects on flower induction in Citrus. Plant Physiol 81:26–29Spiegel-Roy P, Goldschmidt EE (1996) Biology of Citrus. Cambridge University Press, Cambridge, pp 131–136Syvertsen JP, Lloyd J (1994) Citrus. In: Schaffer BA, Andersen PC (eds) Handbook of environmental physiology of fruit crops. Vol II Subtropical and tropical crops. CRC Press, Boca Raton, pp 65–99Syvertsen JP (1996) Water stress and carbon budgets. Proc Int Soc Citrus 1:46–50Valladares F, Arrieta S, Aranda I, Lorenzo D, Sánchez-Gómez D, Tena D, Suarez F, Pardos JA (2005) Shade tolerance, photoinhibition sensitivity and phenotypic plasticity of Illex aquifolium in continental Mediterranean sites. Tree Physiol 25:1041–1052Vu JCV, Yelenosky G (1988) Solar irradiance and drought stress effects on the activity and concentration of ribulose bisphosphate carboxylase in ‘Valencia’ orange leaves. Isr J Bot 37:245–25

Acupuncture and rehabilitation of the painful shoulder: study protocol of an ongoing multicentre randomised controlled clinical trial [ISRCTN28687220]

BACKGROUND: Although the painful shoulder is one of the most common dysfunctions of the locomotor apparatus, and is frequently treated both at primary healthcare centres and by specialists, little evidence has been reported to support or refute the effectiveness of the treatments most commonly applied. According to the bibliography reviewed, physiotherapy, which is the most common action taken to alleviate this problem, has not yet been proven to be effective, because of the small size of sample groups and the lack of methodological rigor in the papers published on the subject. No reviews have been made to assess the effectiveness of acupuncture in treating this complaint, but in recent years controlled randomised studies have been made and these demonstrate an increasing use of acupuncture to treat pathologies of the soft tissues of the shoulder. In this study, we seek to evaluate the effectiveness of physiotherapy applied jointly with acupuncture, compared with physiotherapy applied with a TENS-placebo, in the treatment of painful shoulder caused by subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). METHODS/DESIGN: Randomised controlled multicentre study with blind evaluation by an independent observer and blind, independent analysis. A study will be made of 465 patients referred to the rehabilitation services at participating healthcare centres, belonging to the regional public health systems of Andalusia and Murcia, these patients presenting symptoms of painful shoulder and a diagnosis of subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). The patients will be randomised into two groups: 1) experimental (acupuncture + physiotherapy); 2) control (TENS-placebo + physiotherapy); the administration of rescue medication will also be allowed. The treatment period will have a duration of three weeks. The main result variable will be the change produced on Constant's Shoulder Function Assessment (SFA) Scale; as secondary variables, we will record the changes in diurnal pain intensity on a visual analogue scale (VAS), nocturnal pain intensity on the VAS, doses of non-steroid anti-inflammatory drugs (NSAIDs) taken during the study period, credibility scale for the treatment, degree of improvement perceived by the patient and degree of improvement perceived by the evaluator. A follow up examination will be made at 3, 6 and 12 months after the study period has ended. Two types of population will be considered for analysis: per protocol and per intention to treat. DISCUSSION: The discussion will take into account the limitations of the study, together with considerations such as the choice of a simple, safe method to treat this shoulder complaint, the choice of the control group, and the blinding of the patients, evaluators and those responsible for carrying out the final analysis

Влияние лечения тиотриазолином на состояние перекисного окисления липидов и уровни иммуновоспалительных и вазоактивных эндотелиальных факторов у больных с хронической сердечной недостаточностью и helicobacter pylori-негативными гастропатиями

Показано, что включение в схему патогенетического лечения больных с ХСН, hp-негативной гастропатией и умеренным или высоким риском сердечно-сосудистых осложнений (ССО) антиоксиданта тиотриазолина сопровождается достоверно более выраженными позитивными эффектами на процессы перекисного окисления липидов и содержание в крови иммуновоспалительных и вазоактивных эндотелиальных факторов по сравнению с динамикой при лечении без использования тиотриазолина, причем степень положительной динамики у больных с высоким риском ССО достоверно больше.Показано, що включення у схему патогенетичного лікування хворих із ХСН, hр-негативною гастропатією і з помірним або високим ризиком серцево-судинних ускладнень (ССУ) антиоксиданта тіотриазоліна супроводжується достовірно більш вираженими позитивними ефектами на процеси перекисного окислення ліпідів та вміст у крові імунозапальних і вазоактивних ендотеліальних факторів порівняно з динамікою при лікуванні без використання тіотриазоліну, причому ступінь позитивної динаміки у хворих із високим ризиком ССУ достовірно більший.It is shown that the use of tiotriazolin in the scheme of pathogenetic treatment of patients with chronic heart failure, Hp-negative gastropathy, and moderate or high risk of cardiovascular complications (CVC) is accompanied by significantly higher positive effect on the processes of lipid peroxidation and the amount of immune inflammation and vasoactive endothelial factors in the blood when compared with the dynamics at treatment without the use of tiotriazolin, the degree of positive dynamics in patients with a high risk of CVC being significantly higher

Comparative ecology of the European eel, Anguilla anguilla (L.1758), in a large Iberian river

A total of 1,816 eels were sampled in 1988, from seven sampling areas. Four areas were located in brackish water and the remaining three were located in freshwater reaches of the Tagus river basin. Eels were more abundant in the middle estuary and decreased both in the upstream and in the downstream directions, with a predominance of males in higher density areas. Smaller individuals preferred more peripheral areas, such as margins and upper reaches in the brackish water zone, and the tributaries of the freshwater habitats. It was assumed that this distribution pattern resulted from three main factors: (i) the dominance of larger specimens; (ii) the need to avoid predators and; (iii) the search for better trophic conditions. The condition of the individuals generally decreased toward the upper reaches, apparently due to a corresponding decrease in feeding intensity. The presence of the Belver dam in the main river, 158 km upstream from the sea, seemed to impose major alterations to the described patterns. The concentration of specimens below this impassable obstacle yielded a reduction in the proportion of females and a decrease in the condition and survival of the eels, contributing to a reduction in the spawning success of this population. Suggestions to diminish the effects of the dam, and to preserve the fishery are also presente

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac