In Vivo Interaction Proteomics Reveal a Novel p38 Mitogen-Activated Protein Kinase/Rack1 Pathway Regulating Proteostasis in Drosophila Muscle

Several recent studies suggest that systemic aging in metazoans is differentially affected by functional decline in specific tissues, such as skeletal muscle. In Drosophila, longevity appears to be tightly linked to myoproteostasis, and the formation of misfolded protein aggregates is a hallmark of senescence in aging muscle. Similarly, defective myoproteostasis is described as an important contributor to the pathology of several age-related degenerative muscle diseases in humans, e.g., inclusion body myositis. p38 mitogen-activated protein kinase (MAPK) plays a central role in a conserved signaling pathway activated by a variety of stressful stimuli. Aging p38 MAPK mutant flies display accelerated motor function decline, concomitant with an enhanced accumulation of detergent-insoluble protein aggregates in thoracic muscles. Chemical genetic experiments suggest that p38-mediated regulation of myoproteostasis is not limited to the control of reactive oxygen species production or the protein degradation pathways but also involves upstream turnover pathways, e.g., translation. Using affinity purification and mass spectrometry, we identified Rack1 as a novel substrate of p38 MAPK in aging muscle and showed that the genetic interaction between p38b and Rack1 controls muscle aggregate formation, locomotor function, and longevity. Biochemical analyses of Rack1 in aging and stressed muscle suggest a model whereby p38 MAPK signaling causes a redistribution of Rack1 between a ribosome-bound pool and a putative translational repressor complex.     

Treatment of post-traumatic trabecular mashwork thrombosis and secondary glaucoma with intracameral tissue plasminogen activator in previously unrecognized sickle cell anemia

Intracameral tissue plasminogen activator (t-PA) application in a child with previously unrecognized sickle cell anemia, post-traumatic hyphema, thrombosis in trabecular mashwork and consecutive acute glaucoma showed positive results. Thirteen year-old boy, son of African father and Caucasian mother, was admitted to hospital, with symptoms of acute glaucoma and partial hyphema after right eye trauma. Visual acuity of affected eye was 0.5 and intraocular pressure (IOP) 46 mm Hg. Despite a common therapy three days later clinical condition of patient's right eye was getting worst. Visual acuity was only hand motion (HM) and IOP 53 mmHg. At this point rose suspicion of sickle cell disease (SCD) and decision about injecting t-PA (20 microg) into anterior chamber was made. Cytological examination of aqueous humor revealed 10% sickled erythrocytes. Hemoglobin electrophoresis discovered hemoglobin S so that diagnosis of SCD was confirmed. Intraocular application of t-PA showed excellent results in post-traumatic hyphema with trabecular mashwork thrombosis in the patient with sickle cell anemia. Two-years follow up confirmed permanent normalisation of IOP and visual acuity. Successful outcome with anterior chamber paracentesis and intracameral injection of t-PA is promising novel approach, which we recommend in treatment of post-traumatic hyphema in SCD.     

Self-Medication Practices and Risk Factors for Self-Medication among Medical Students in Belgrade,Serbia

Introduction

Self-medication among future health care professionals can represent a serious threat to professionalism in medicine and it has potential to put at risk public trust into this profession. The aim of this research was to investigate prevalence and risk factors for self-medication among population of medical students, because it was previously shown that their attitudes towards pharmacotherapy could affect the way they could prescribe medication in the future.

Material and Methods

Research was performed as a cross-sectional study and it included 1296 (84.1%) 1st, 3rd and 6th year students of School of Medicine, University of Belgrade. Students filled out a demographic and self-medication questionnaire created for the purpose of this research and the Physical Health Questionnaire – 9 (PHQ-9). Questions about self-medication were related to the period of the previous year.

Results

Self-medication was reported by 79.9% students. The most frequently self-prescribed medications were analgesics (55.4%). Independent risk factors for self-medication were possession of home-pharmacies (OR = 5.3, CI 95% 3.89–7.23), lower level of father''s education (OR = 1.6, CI 95% 1.18–2.25), consumption of alcoholic beverages (OR = 1.5, CI 95% 1.13–2.08), less than 1 hour spent in physical activity per week (OR = 1.4, CI 95% 1.00–2.02), female gender (OR = 1.4, CI 95% 1.02–1.89), older age (OR = 1.1, CI 95% 1.07–1.21) and higher PHQ-9 score (OR = 1.09, CI 95% 1.05–1.12).

Conclusions

Self-medication is an important issue among population of medical students. Prevalence of self-medication could be controlled through regulatory authorities and further education.     

Dielectric and conductivity studies of the hydration mechanisms in plant seeds.

The hydration mechanism of various plant seeds has been investigated by a) sorption-desorption isotherms, b) ac-dielectric spectroscopy in the 10 Hz to 1 GHz frequency range and the -80 to + 40 degrees C temperature range, and c) thermally stimulated depolarization current techniques in the -170 to + 23 degrees C temperature range. Seeds of different chemical composition were studied at water contents varying between 0 and 40% w/w (dry weight basis). Our experimental results permitted us to determine i) the diffusion constant of water in the samples, found to be between 1.4 x 10(-11) and 3.7 x 10(-11) m2/s; ii) a critical water content corresponding to the completion of the primary hydration layer, which is in the range 0.11-0.17 w/w, depending on the seed nature; and iii) the activation energy of the main relaxation mechanism, found to be equal to 0.54 +/- 0.05 eV. Moreover, they make it possible to investigate the dependence of various parameters (conductivity, molecular mobility, plasticizing effect of water) on the water content of the sample, to follow the crystallization of water in the seeds as a function of temperature and confirm that it is not a reversible process, to study the dehydration process as a function of temperature and time, and to propose an alternative technique for the determination of the moisture content in seeds.