Prognostic value of electromechanical function of left atrium for appearance of recurent atrial fibrilation treated with radiofrequent therapy

Cilj ove studije je bio da proceni prognostički značaj kašnjenja električnog impulsa unutar leve pretkomore i između dve pretkomore za ponovno javljanje atrijalne fibrilacije nakon lečenja radiofrekventnom izolacijom plućnih vena (RFPVI) I da ispita elektromehaničko remodelovanje leve pretkomore. Metode: Ukupno je 64 bolesnika lečeno prvom radiofrekventnom izolacijom plućnih vena zbog simptomatske, rezistentne na lekove nevalvularne paroksizmalne atrijalne fibrilacije. Svi pacijenti su imali transtoraksni ehokardiografski pregled pre, neposredno nakon, 1,3,6, i 12 meseci nakon RFPVI. Ukupna frakcija leve pretkomore (LA TEF), kašnjenje električnog impulsa unutar leve, desne pretkomore i između dve pretkomore su računati kod svih pacijenata. Rezultati. Tokom praćenja od 12 meseci rekurentna atrijalna fibrilacija se javila kod 17 pacijenata (26%). Na kontroli 12meseci u grupi bez pojave recidiva u odnosu na početne vrednosti LA TEF se značajno popravio (48.21±5.57 vs 48.33±5.56 vs 48.91±6.88 vs 49.29±5.57 vs 51.41±5.92 vs 52.9±6.79, p<0.05). Kašnjenje impulsa unutar leve pretkomore (25.47±6.71 vs 25.91±6.7 vs 22.57±5.61 vs 19.97±7.08 vs 16.45±6.74 vs 14.26±6.62, p=0.017), kao i između dve pretkomore (58.49±9.93 vs 58.61±10.3 vs 51.8±10.31 vs 44.29±11.04 vs 36.36±10.61 vs 30.21±9.49, p=0.001) je značajno smanjeno. Multivarijantna logistička regresija je pokazala da je međupretkomorsko kašnjenje impulsa nezavisni predictor kasnog recidiva atrijane fibrilacije nakon RFPVI (p=0.03, OR 1.15 95% CI OR 1.01-1.3)...The aim of this study was to investigate prognostic value of: inter and intra atrial conduction time to predict atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA), and to assess electromechanical remodelling of left atrium. Methods. A total of 64 patients underwent their first RFCA for symptomatic drug refractory non valvuar paroxysmal AF. All patients had transtoracic echocardiography before, after, 1, 3, 6 and 12 months after RFCA. Left atrial total emptyng fraction (LA TEF), left intra, right intra and interatrial conduction time were calculated in all patients. Results. During follow up of 12 months recurrent atrial arrhythmia was found in 17 (26%) patients. At 12th month visit in non recurrent group compared to baseline LA TEF significantly increased (48.21±5.57 vs 48.33±5.56 vs 48.91±6.88 vs 49.29±5.57 vs 51.41±5.92 vs 52.9±6.79, p<0.05). Both intra left (25.47±6.71 vs 25.91±6.7 vs 22.57±5.61 vs 19.97±7.08 vs 16.45±6.74 vs 14.26±6.62, p=0.017), and interatrial conduction time (58.49±9.93 vs 58.61±10.3 vs 51.8±10.31 vs 44.29±11.04 vs 36.36±10.61 vs 30.21±9.49, p=0.001) significantly decreased. In multivariante logistic regression analysis, only interatrial conduction time was found as independent predictor of late recurrence of atrial fibrillation after RFCA (p=0.03, OR 1.15 95% CI OR 1.01-1.3)..

EFFECT OF MC4R POLYMORPHISM ON PHYSIOLOGICAL STRESS RESPONSE IN PIGS

Melanocortin-4 receptor (MC4R) is a G-protein coupled receptor predominantly expressed in hypothalamic regions which are known for their roles in feeding behavior, energy homeostasis and HPA axis regulation. In this study, we analyzed the effect of a missense mutation (Asp298Asn) in the porcine MC4R gene on physiological stress response and carcass composition in pigs of two crosses: A (♀Duroc x ♂Swedish Landrace) x ♂Pietrain (n=25) and B (♀Swedish Landrace x ♂Large White) x ♂Pietrain (n=21). All pigs included in this study were heterozygous (Nn) for the stress syndrome gen. Blood samples were collected before loading and at exsanguinations to measure cortisol, lactate, glucose, serum enzymes activity and some haematological parameters. Because only one pig with AA genotype was observed, there was no indicated effect of this genotype on investigated parameters. The heterozygous (AG) pigs showed a lower increase (P<0.05) in CK and AST activity after exsanguinations as well as trend towards lower increase (P<0.10) in cortisol and lactate levels and higher increase (P<0.10) in RBC and haemoglobin content. Higher increase (P<0.05) in LDH activity was observed in GG homozygous pigs from group B, but not in pigs from group A. In addition, the heterozygous (AG) pigs had a higher backfat thickness and lower estimated lean (P<0.05) than homozygous (GG) pigs. These results may support a possible role of the MC4R Asp298Asn polymorphism in the genetic basis of stress response and economically important traits in pigs

Somatostatin-14 izaziva različite promene u timusima prepubertalnih i mladih odraslih pacova

Bearing in mind the role of somatostatin in thymus functions, and changes of somatostatin level and expression of its receptors during postnatal life, the aim of this study was to investigate whether centrally applied SRIH-14 induces different changes in the thymic compartments and thymocyte profile in peripubertal and young adult rats. To this end, 4- and 10-week-old male AO rats were cannulated and treated intracerebroventriculary with three doses of SRIH-14, applied every other day. In peripubertal rats, SRIH-14 decreases thymic relative weight and volume, as well as the volume of thymic compartments, especially of deep cortex, as a result of thymocytes loss by apoptosis. Also, SRIH-14 increases the percentage of immature thymocytes preceding the DPTCRαβlow cells (DNTCRαβ-/low, DPTCRαβ-, SPCD8TCRαβ-/low and SPCD4TCRαβ-/low), decreases the percentages of DPTCRαβlow and DPTCRαβhi cells, while the relative proportion of CD4+/CD8+TCRαβhi cells remained unaltered. In young adult rats, SRIH-14 does not lead to changes in relative thymus weight, although decreases the thymic cortex cellularity and volume. In addition, decreases the percentage of DPTCRαβ-/hi cells and increases the percentages of cells within DNTCRαβhi and both SP subpopulations, but much more of the CD8+TCRαβhi subset. These results suggest that the effects of SRIH-14 on the thymus and thymocytes subpopulations are age-dependent.Sa obzirom da literaturni podaci ukazuju da somatostatin ima uticaja na funkciju timusa, kao i da se tokom postnatalnog života menja nivo somatostatina i ekspresija njegovih receptora u timusu, cilj ovog rada je bio da se ispita da li SRIH- 14 davan intracerebroventrikularno u prepubertalnih i mladih odraslih pacova, dovodi do različitih promena u zonama timusa i profilu timocitnih subsetova. Mužjacima pacova AO soja, starim 4 i 10 nedelja, ugrađene su kanile u treću moždanu komoru i oni su tretirani somatostatinom, ukupno tri doze, ubrizgane svakog drugog dana. U prepubertalnih pacova tretman somatostatinom dovodi do smanjenja relativne mase i zapremine timusa, kao i zapremine timusnih zona, naročito dubokog korteksa, što je bila posledica gubitka timocita apoptozom. Takođe, SRIH-14 je doveo do povećanja procenta timocita nezrelog fenotipa (DNTCRαβ-/low, DPTCRαβ-, SPCD8TCRαβ-/low i SPCD4TCRαβ-/low) prekusora DPTCRαβlow subpopulacije, smanjenja procenta DPTCRαβlow i DPTCRαβhi subsetova, dok je relativni odnos najzrelijih CD4TCRαβhi i CD8TCRαβhi timocita ostao neizmenjen. U mladih adulta primena somatostatina, iako dovodi do smanjena zapremine i celularosti korteksa ne dovodi do promena u relativnoj masi timusa. Procenat DPTCRαβ-/hi timocita je bio smanjen, dok je procentualno učešće DNTCRαβhi timocita i obe jednostruko pozitivne subpopulacije (CD4TCRαβhi i CD8TCRαβhi, više CD8TCRαβhi) u ukupnom broju timocita bilo povećano. Navedeni rezultati ukazuju da SRIH-14 različito utiče na morfologiju timusa i na subpopulacije timocita pacova u zavisnosti od uzrasta tretiranih životinja

Effect of feeding olive by-products on certain blood parameters and serum enzyme activities of fattening rabbits

The effect of feeding different levels (10 and 20%) of dehydrated olive cake pulp on certain blood parameters and on the catalytic activity of serum enzymes was studied in fattening rabbits. A total of 60 rabbits were divided into a control group (C) and two experimental groups (E1, E2), each comprising 10 males and 10 females. Rabbits of Group C received no dehydrated olive cake pulp in their diet, while rabbits of Group E1and Group E2were fed 10% and 20% dehydrated olive cake pulp, respectively. After Day 56 of the experiment, blood samples were obtained by cardiac puncture and certain blood parameters as well as the catalytic activity of serum enzymes were determined. Following the experimental feeding period no significant differences were found between Group C and Groups E1and E2in red blood cell (RBC) and white blood cell (WBC) count, haemoglobin concentration and haematocrit value. Similarly, after 56 days of experimental fattening no significant differences were found between the control group and the experimental groups in the catalytic activity of the serum enzymes alkaline phosphatase (AP), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and lactate dehydrogenase (LDH). However, Group E2 rabbits manifested a significantly higher alanine aminotransferase (ALT) activity in the serum than did rabbits of Group E1. The results indicate that the inclusion of dehydrated olive cake pulp in the diet at the rate of 10% or 20% caused no changes in the investigated blood parameters and serum enzyme activities of fattening rabbits

Toksikokinetika prometrina u mozgu miševa

Prometryne is a methylthio-s-triazine herbicide. Signifi cant trace amounts are found in the environment, mainly in water, soil, and food plants. The aim of this study was to establish brain and blood prometryne levels after single oral dose (1 g kg-1) in adult male and female mice. Prometryne was measured using the GC/MS assay at 1, 2, 4, 8, and 24 h after prometryne administration. Peak brain and blood prometryne values were observed 1 h after administration and they decreased in a time-dependent manner. Male mice had consistently higher brain and blood prometryne levels than female mice. The observed prometryne kinetics was similar to that reported for the structurally related herbicide atrazine.Prometrin je metiltio-s-triazinski herbicid. Značajne količine prometrina zaostaju u tragovima u okolišu, poglavito u vodi, tlu i biljkama koje rabimo za prehranu. Cilj je rada izmjeriti količinu prometrina koja se apsorbira u mozgu i krvi nakon primijenjene akutne oralne doze (1 g kg-1 tjelesne mase) u odraslih miševa obaju spolova. Razine prometrina u mozgu i krvi izmjerene su GC/MS-om tijekom 1., 2., 4., 8. i 24. sata nakon izlaganja. Utvrđeno je da je udio prometrina koji se zadržava u živčanom tkivu relativno nizak ali detektabilan u odnosu na koncentraciju u krvi i koncentraciju primijenjene doze. Najviše koncentracije u krvi i maseni udjeli u mozgu zabilježeni su tijekom 1. sata nakon izlaganja, a s vremenom izmjerene vrijednosti značajno opadaju. Uočena je značajna razlika između mužjaka i ženki pri čemu mužjaci imaju značajno više razine prometrina u mozgu i krvi nego ženke. Opisana toksikokinetika prometrina pokazuje sličnosti s otprije opisanom i poznatom toksikokinetikom strukturalno sličnog herbicida atrazina

Development of ADPribosyl ubiquitin analogues to study enzymes involved in Legionella infection

Legionnaires’ disease is caused by infection with the intracellularly replicating Gram‐negative bacterium Legionella pneumophila. This pathogen uses an unconventional way of ubiquitinating host proteins by generating a phosphoribosyl linkage between substrate proteins and ubiquitin by making use of an ADPribosylated ubiquitin (UbADPr) intermediate. The family of SidE effector enzymes that catalyze this reaction is counteracted by Legionella hydrolases, which are called Dups. This unusual ubiquitination process is important for Legionella proliferation and understanding these processes on a molecular level might prove invaluable in finding new treatments. Herein, a modular approach is used for the synthesis of triazole‐linked UbADPr, and analogues thereof, and their affinity towards the hydrolase DupA is determined and hydrolysis rates are compared to natively linked UbADPr. The inhibitory effects of modified Ub on the canonical eukaryotic E1‐enzyme Uba1 are investigated and rationalized in the context of a high‐resolution crystal structure reported herein. Finally, it is shown that synthetic UbADPr analogues can be used to effectively pull‐down overexpressed DupA from cell lysate.Macromolecular Biochemistr

Prognostic value of electromechanical function of left atrium for appearance of recurent atrial fibrilation treated with radiofrequent therapy

Cilj ove studije je bio da proceni prognostički značaj kašnjenja električnog impulsa unutar leve pretkomore i između dve pretkomore za ponovno javljanje atrijalne fibrilacije nakon lečenja radiofrekventnom izolacijom plućnih vena (RFPVI) I da ispita elektromehaničko remodelovanje leve pretkomore. Metode: Ukupno je 64 bolesnika lečeno prvom radiofrekventnom izolacijom plućnih vena zbog simptomatske, rezistentne na lekove nevalvularne paroksizmalne atrijalne fibrilacije. Svi pacijenti su imali transtoraksni ehokardiografski pregled pre, neposredno nakon, 1,3,6, i 12 meseci nakon RFPVI. Ukupna frakcija leve pretkomore (LA TEF), kašnjenje električnog impulsa unutar leve, desne pretkomore i između dve pretkomore su računati kod svih pacijenata. Rezultati. Tokom praćenja od 12 meseci rekurentna atrijalna fibrilacija se javila kod 17 pacijenata (26%). Na kontroli 12meseci u grupi bez pojave recidiva u odnosu na početne vrednosti LA TEF se značajno popravio (48.21±5.57 vs 48.33±5.56 vs 48.91±6.88 vs 49.29±5.57 vs 51.41±5.92 vs 52.9±6.79, p<0.05). Kašnjenje impulsa unutar leve pretkomore (25.47±6.71 vs 25.91±6.7 vs 22.57±5.61 vs 19.97±7.08 vs 16.45±6.74 vs 14.26±6.62, p=0.017), kao i između dve pretkomore (58.49±9.93 vs 58.61±10.3 vs 51.8±10.31 vs 44.29±11.04 vs 36.36±10.61 vs 30.21±9.49, p=0.001) je značajno smanjeno. Multivarijantna logistička regresija je pokazala da je međupretkomorsko kašnjenje impulsa nezavisni predictor kasnog recidiva atrijane fibrilacije nakon RFPVI (p=0.03, OR 1.15 95% CI OR 1.01-1.3)...The aim of this study was to investigate prognostic value of: inter and intra atrial conduction time to predict atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA), and to assess electromechanical remodelling of left atrium. Methods. A total of 64 patients underwent their first RFCA for symptomatic drug refractory non valvuar paroxysmal AF. All patients had transtoracic echocardiography before, after, 1, 3, 6 and 12 months after RFCA. Left atrial total emptyng fraction (LA TEF), left intra, right intra and interatrial conduction time were calculated in all patients. Results. During follow up of 12 months recurrent atrial arrhythmia was found in 17 (26%) patients. At 12th month visit in non recurrent group compared to baseline LA TEF significantly increased (48.21±5.57 vs 48.33±5.56 vs 48.91±6.88 vs 49.29±5.57 vs 51.41±5.92 vs 52.9±6.79, p<0.05). Both intra left (25.47±6.71 vs 25.91±6.7 vs 22.57±5.61 vs 19.97±7.08 vs 16.45±6.74 vs 14.26±6.62, p=0.017), and interatrial conduction time (58.49±9.93 vs 58.61±10.3 vs 51.8±10.31 vs 44.29±11.04 vs 36.36±10.61 vs 30.21±9.49, p=0.001) significantly decreased. In multivariante logistic regression analysis, only interatrial conduction time was found as independent predictor of late recurrence of atrial fibrillation after RFCA (p=0.03, OR 1.15 95% CI OR 1.01-1.3)..

Triage procedure in early hospital management of patients in emergency centres

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FAM134B-RHD protein clustering drives spontaneous budding of asymmetric membranes

Living cells constantly remodel the shape of their lipid membranes. In the endoplasmic reticulum (ER), the reticulon homology domain (RHD) of the reticulophagy regulator 1 (RETR1/FAM134B) forms dense autophagic puncta that are associated with membrane removal by ER-phagy. In molecular dynamics (MD) simulations, we find that FAM134B-RHD spontaneously forms clusters, driven in part by curvature-mediated attractions. At a critical size, as in a nucleation process, the FAM134B-RHD clusters induce the formation of membrane buds. The kinetics of budding depends sensitively on protein concentration and bilayer asymmetry. Our MD simulations shed light on the role of FAM134B-RHD in ER-phagy and show that membrane asymmetry can be used to modulate the kinetic barrier for membrane remodeling