Lipemia as a determinant of development of an acute pancreatitis: investigation «case-control»

Objective. To establish the connection between lipemia and course of an acute pancreatitis. Materials and methods. The investigation design: «case - control». There were incorporated 93 patients, suffering an acute pancreatitis. Group «case» - 11 patients with acute pancreatitis and lipemia, Group «control» - 82 patients with acute pancreatitis without lipemia. Interrelationship was investigated in accordance to the relative risk index between lipemia and the factors signs: the acute pancreatitis severity degree, recurrent course of the disease, presence of diabetes mellitus and alcoholic anamnesis. Results. Comparative analysis of rate for the factors signs revealing have established, that possibility of development of severe acute pancreatitis and possibility of the alcohol-induced acute pancreatitis occurrence in groups of patients did not differ statistically meaningful (p > 0.05). While comparing a rate of the acute pancreatitis recurrence and the diabetes mellitus presence in groups of patients there were differences revealed on the significant level: p=0.02 and p=0.04 accordingly. Lipemia constitutes a risk factor for recurrent course of an acute pancreatitis and diabetes mellitus in patients with an acute pancreatitis: relative risk 7.5 (95% CI 1.8 - 26.6, p=0.02), RR 6.1 (95% CI 1.2 - 28.7, p= 0.02) accordingly. Conclusion. Presence of lipemia did not impact the acute pancreatitis severity (p=0.98). Possibility of the acute pancreatitis recurrence in patients with lipemia in 7 times is higher, than in patients with an acute pancreatitis without lipemia (p=0.02). Possibility of diabetes mellitus presence in patients with an acute pancreatitis and lipemia is in 6 times higher, than in patients wihout lipemia (p= 0.02). Timely diagnosis and correction of a dislipoproteinemia constitutes a prophylactic measure, which is capable to lower the rate of an acute pancreatitis recurrence

Інноваційна діяльність та педагогічна комунікація виклaдача загальної хірургії

The authors focused on the aspects of the students’ intellectual abilities improvement of the general surgery department at the medical educational institution. The special feature is the impact of the teacher’s self-management on the working process effectiveness of the future specialists. The authors have provided the knowledge productivity increase in the learning process with the help of a number of modern methods of educational process optimization by students. Knowledge of bases of management and self-management, the practice of self-management improves the teacher’s skills and speeding up the formation of the national intellec tual medical elite.У роботі зосереджено увагу на аспектах покращення інтелектуальних здібностей студентів на кафедрі загальної хірургії ви­щого медичного навчального закладу. Особливістю є вплив самоменеджменту викладача на ефективність робочого процесу майбутніх спеціалістів. Передбачено збільшення продуктивності застосування знань у процесі навчання, що здійснюється шляхом виконання ряду сучасних методів оптимізації навчального процесу студентів. Знання основ менеджменту і само­менеджменту, практика самоменеджменту вдосконалює навички викладача та прискорює темпи формування національної інтелектуальної медичної еліти

Preliminary effects of fertilization on ecochemical soil condition in mature spruce stands experiencing dieback in the Beskid Śla̧ski and Żywiecki Mountains, Poland

In recent years, there has been the phenomena of spruce dieback in Europe. Significant areas of spruce low mortality now cover both sides of the Polish southern border. We evaluated ecochemical parameters influencing the heavy dieback occurring in mature spruce stands in the Polish Carpathian Mountains. Dolomite, magnesite and serpentinite fertilizers were applied to experimental plots located in 100-year-old stands in the autumn of 2008. The experimental plots were located in the mid-elevational forest zone (900-950 m) on two nappes of the flysch Carpathians: Magura (Ujsoły Forest District) and Silesian (Wisła Forest District). The saturation of the studied soils demonstrates moderate resilience of soils in Wisła Forest District in relation to acid load and high flexibility of the Ujsoły soils. After application of the fertilizers, an increase of Mg, Ca and Mb was noted in the soil solution, determined in the overlaying highly acidic organic horizons through the ion-exchange buffering mechanism of highly protonated functional groups with high buffering capacity. Magnesium concentration increased following fertilization, presenting a potential improvement of forest growth capacity without the hazard of adverse side effects of liming. Aluminium stress in old spruce is unlikely, while trees in the control plots in Wisła Forest District may already be sensitive to aluminium stress. Serpentinite fertilization improved the supply of soils in magnesium without causing significant changes in the pH of the soil. Such changes in the pH were found in dolomite and magnesite fertilizer. © The Author(s) 2014

GADD34 keeps the mTOR pathway inactivated in endoplasmic reticulum stress related autophagy

The balance of protein synthesis and proteolysis (i.e. proteostasis) is maintained by a complex regulatory network in which mTOR (mechanistic target of rapamycin serine/threonine kinase) pathway and unfolded protein response are prominent positive and negative actors. The interplay between the two systems has been revealed; however the mechanistic details of this crosstalk are largely unknown. The aim of the present study was to investigate the elements of crosstalk during endoplasmic reticulum stress and to verify the key role of GADD34 in the connection with the mTOR pathway. Here, we demonstrate that a transient activation of autophagy is present in endoplasmic reticulum stress provoked by thapsigargin or tunicamycin, which is turned into apoptotic cell death. The transient phase can be characterized by the elevation of the autophagic marker LC3II/I, by mTOR inactivation, AMP-activated protein kinase activation and increased GADD34 level. The switch from autophagy to apoptosis is accompanied with the appearance of apoptotic markers, mTOR reactivation, AMP-activated protein kinase inactivation and a decrease in GADD34. Inhibition of autophagy by 3-methyladenine shortens the transient phase, while inhibition of mTOR by rapamycin or resveratrol prolongs it. Inhibition of GADD34 by guanabenz or transfection of the cells with siGADD34 results in down-regulation of autophagy-dependent survival and a quick activation of mTOR, followed by apoptotic cell death. The negative effect of GADD34 inhibition is diminished when guanabenz or siGADD34 treatment is combined with rapamycin or resveratrol addition. These data confirm that GADD34 constitutes a mechanistic link between endoplasmic reticulum stress and mTOR inactivation, therefore promotes cell survival during endoplasmic reticulum stress. © 2016 Holczer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Hyperthermia Induces the ER Stress Pathway

The ER chaperone GRP78/BiP is a homolog of the Hsp70 family of heat shock proteins, yet GRP78/BiP is not induced by heat shock but instead by ER stress. However, previous studies had not considered more physiologically relevant temperature elevation associated with febrile hyperthermia. In this report we examine the response of GRP78/BiP and other components of the ER stress pathway in cells exposed to 40°C.AD293 cells were exposed to 43°C heat shock to confirm inhibition of the ER stress response genes. Five mammalian cell types, including AD293 cells, were then exposed to 40°C hyperthermia for various time periods and induction of the ER stress pathway was assessed.The inhibition of the ER stress pathway by heat shock (43°C) was confirmed. In contrast cells subjected to more mild temperature elevation (40°C) showed either a partial or full ER stress pathway induction as determined by downstream targets of the three arms of the ER stress pathway as well as a heat shock response. Cells deficient for Perk or Gcn2 exhibit great sensitivity to ER stress induction by hyperthermia.The ER stress pathway is induced partially or fully as a consequence of hyperthermia in parallel with induction of Hsp70. These findings suggest that the ER and cytoplasm of cells contain parallel pathways to coordinately regulate adaptation to febrile hyperthermia associated with disease or infection

Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds

BACKGROUND: Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. METHODS: Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients. RESULTS: Overexpression of hypoxia marker CAIX was associated with low PCFT expression and decreased MPM cell growth inhibition by pemetrexed. Through integration of PCR arrays in hypoxic cells and spheroids and following PCFT silencing, we identified the upregulation of LDH-A, which correlated with shorter survival of MPM and DMPM patients. Novel LDH-A inhibitors enhanced spheroid disintegration and displayed synergistic effects with pemetrexed in MPM and gemcitabine in DMPM cells. Studies with bioluminescent hypoxic orthotopic and subcutaneous DMPM athymic-mice models revealed the marked antitumour activity of the LDH-A inhibitor NHI-Glc-2, alone or combined with gemcitabine. CONCLUSIONS: This study provides novel insights into hypoxia/PCFT-dependent chemoresistance, unravelling the potential prognostic value of LDH-A, and demonstrating the preclinical activity of LDH-A inhibitors

A novel hybrid promoter responsive to pathophysiological and pharmacological regulation

The aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic conditions or through pharmacological induction, and also show pharmacological repression. In vivo studies utilised electroporation of plasmid to mouse paws, a delivery method shown to be effective by bioluminescence imaging. For gene therapy, the promoter was used to drive expression of IL-1Ra in a paw inflammation model with therapeutic effect observed which was further enhanced when the promoter was additionally induced with a pharmacological activator. One of the most important observations from this study was that promoter induction by hypoxia or inflammation could be prevented by the pharmacological repressor in the absence of doxycycline. These studies demonstrate that hybrid promoters enable pharmacological adjustment to the pathophysiological level of gene expression and, importantly, that they allow termination of gene expression even in the presence of pathophysiological stimuli

From endoplasmic-reticulum stress to the inflammatory response

The endoplasmic reticulum is responsible for much of a cell's protein synthesis and folding, but it also has an important role in sensing cellular stress. Recently, it has been shown that the endoplasmic reticulum mediates a specific set of intracellular signalling pathways in response to the accumulation of unfolded or misfolded proteins, and these pathways are collectively known as the unfolded-protein response. New observations suggest that the unfolded-protein response can initiate inflammation, and the coupling of these responses in specialized cells and tissues is now thought to be fundamental in the pathogenesis of inflammatory diseases. The knowledge gained from this emerging field will aid in the development of therapies for modulating cellular stress and inflammation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62741/1/nature07203.pd