Le Page A.,Université de Sherbrooke |
Bourgade K.,Université de Sherbrooke |
Lamoureux J.,Université de Sherbrooke |
Frost E.,Université de Sherbrooke |
And 5 more authors.
Journal of Alzheimer's Disease | Year: 2015
Alzheimeŕs disease (AD) is a progressive irreversible neurological brain disorder characterized by accumulation of amyloid-β, amyloid plaques, and neurofibrillary tangles. Inflammation and immune alterations have been linked to AD, suggesting that the peripheral immune system plays a role during the asymptomatic period of AD. NK cells participate in innate immune surveillance against intracellular pathogens and malignancy but their role in AD remains controversial.We have investigated changes in peripheral NK cell phenotypes and functions in amnestic mild cognitive impairment (aMCI, n = 10), patients with mild AD (mAD, n = 11), and healthy elderly controls (n = 10). Patients selected according to NINCDS-ADRDA criteria were classified using neuropsychological assessment tests. Phenotype analysis revealed differences in expression of CD16 (increased in mAD), NKG2A (decreased in aMCI), and TLR2 and TLR9 (both decreased in mAD). Functional assays revealed that NK cell killing activity and degranulation (CD107 expression) were unchanged in the three groups. In contrast, expression of the CD95 receptor was increased in aMCI and mAD. Granzyme B expression and cytokine production (TNFa, IFN.) were increased in aMCI but not in mAD. CCL19- but not CCL21-dependent chemotaxis was decreased in aMCI and mAD, despite the fact that CCR7 expression was increased in aMCI. Our data suggest that the number of alterations observed in peripheral NK cells in aMCI represent an activation state compared to mAD patients and that may reflect an active immune response against a still to be defined aggression. © 2015 - IOS Press and the authors. All rights reserved.
Sawicki W.,Medical University of Gdask |
Mazgalski J.,Medical University of Gdask |
Mazgalski J.,Pharmaceutical Works Polpharma SA |
Jakubowska I.,Medical University of Gdask
Drug Development and Industrial Pharmacy | Year: 2010
Background: Coating, as a processing technique, applied to active pharmaceutical ingredient (API) crystals or particles (carriers) with an appropriate polymer allows to obtain a modified-release pharmaceutical dosage form. Such carriers can be the basic ingredient of a multi-unit dosage form. Additionally, coated API crystals (microcapsules) can provide an alternative to spherical granulate (pellets) as the main and most commonly used component of multi-unit dosage forms. Coating individual API crystals is a complicated process because of the crystals having insufficient size (below 100 μm), irregular shape, low mechanical durability and the fact that API crystals dissolve upon contact with the coating mixture, and other factors. Method: Compaction process was used to eliminate these inconveniences allowing us to obtain tramadol hydrochloride (TH) microcapsule cores in the size range of 212500 μm. The coating of the cores was successfully conducted using a fluidized-bed coating technique with four different polymers that allowed us to attain slow release of TH. Then, the microcapsules were subjected to a hot tabletting process conducted by applying a low compression force of about 1 kN at 56°C. Semi-liquid granules containing melted PEG 3000 combined with TH microcapsules were compressed. A tablet matrix of good physical parameters was created when its temperature decreased to room temperature. In the proposed hot tabletting method, PEG 3000 included in the granulate provided the tableted microcapsules sufficient protection against rupture. Results: The compaction process allowed us to eliminate unwanted physical API properties, which could otherwise have an adverse effect on the fluidized-bed coating process. The microcapsule cores after compaction and coating using a fluidized-bed coating technique showed a THrelease profile similar to that of the compressed microcapsules after applying hot tabletting process. Conclusions: Multi-unit dosage forms can be obtained in a relatively simple way by combining three processes: (i) obtaining TH microcapsule cores by compaction, (ii) coating, and (iii) hot tabletting. © Informa UK, Ltd.
Dzwonkowski M.,Gdask University of Technology |
Dzwonkowski M.,Medical University of Gdask |
Rykaczewski R.,Gdask University of Technology
Journal of Telecommunications and Information Technology | Year: 2015
In this paper Quaternion Feistel Cipher (QFC) with an infinite key space based on quaternion Julia sets is proposed. The basic structure of the algorithm is based on the scheme proposed in 2012 by Sastry and Kumar. The pro-posed algorithm uses special properties of quaternions to per-form rotations of data sequences in 3D space for each of the cipher rounds. It also uses Julia sets to form an infi-nite key space. The plaintext is divided into two square ma-trices of equal size and written using Lipschitz quaternions. A modular arithmetic was implemented for operations with quaternions. A computer-based analysis has been carried out and obtained results are shown at the end of this paper.
Kowalski R.,Medical University of Gdask |
Kreft E.,Medical University of Gdask |
Kasztan M.,Medical University of Gdask |
Jankowski M.,Medical University of Gdask |
And 2 more authors.
Nephrology Dialysis Transplantation | Year: 2012
Background. Kidney noradrenergic innervation regulates tubular function. Adenosine triphosphate (ATP)-a co-transmitter of norepinephrine-acts on purinoceptors, including ion channel receptor, P2X. P2X receptor agonists, α,β-methylene ATP (α,β-meATP) and β,γ-methylene ATP (β,γ-meATP), induce natriuresis. Regarding the functional co-localization of adrenoceptors and P2X receptors, we evaluated rat renal tubular system sensitivity to natriuretic action of P2X receptor agonists in chronically denervated kidney. Methods. Clearance studies with α,β-meATP and β,γ-meATP (intravenous infusion rate, 2 μmol/kg 20 nmol/kg/min) were performed after bilateral surgical kidney denervation (DNx) and sham-operation (Sham). Na/K-ATPase activity was measured in isolated rat renal proximal tubules. Results. In DNx compared with Sham, saline infusion significantly increased renal sodium and urine excretion and P2X receptor agonist infusion was significantly more natriuretic and diuretic. In DNx and Sham, respectively, α,β-meATP increased fractional excretion of sodium (FENa) by 2 ± 0.3 and 0.6 ± 0.1 and urine (FEV) by 1.6 ± 0.3 and 0.9 ± 0.2; β,γ-meATP had similar effects. In both groups of rats, natriuretic and diuretic actions were abolished by P2 receptor blocker (pyridoxal-phosphate-6-azophenyl-2′, 4′-disulphonate, PPADS), mean arterial blood pressure and glomerular filtration rate remained unchanged during infusion of P2X receptor agonists and antagonist and basal Na/K-ATPase activities in isolated proximal tubules were similar. Both α,β-meATP and β,γ-me-ATP decreased the Na/K-ATPase activity, with 20 inhibition (P < 0.05) in denervated and innervated rats; these inhibitory effects were abolished in the presence of PPADS. Conclusions. Decreased renal sympathetic activity enhances the natriuretic effect of P2X receptor stimulation. This effect is probably not related to altered Na/K-ATPase activity in renal proximal tubules. © 2012 The Author.
Hering D.,Medical University of Gdask |
Kucharska W.,Medical University of Gdask |
Kara T.,Mayo Medical School |
Somers V.K.,Mayo Medical School |
And 2 more authors.
Blood Pressure | Year: 2010
Objective. Previous studies have shown that smoking contributes importantly to short-term modulation of sympathetic nerve traffic. However, effect of smoking status on resting muscle sympathetic nerve activity (MSNA) in hypertension is unknown. Therefore, we tested the hypothesis that smoking is associated with chronic sympathetic activation in patients with essential hypertension. Methods. We measured MSNA, heart rate (HR) and blood pressure during undisturbed supine rest and in 30 hypertensive smokers (22 males, age 38±4 years, body mass index, BMI 27±1 kg/m2, mean±SEM). These measurements were compared with those obtained 38 non-smoking hypertensive patients matched for gender, age and BMI. All hypertensives underwent 24-h ambulatory blood pressure monitoring. Patients were newly diagnosed, never treated for hypertension and were free of any other known diseases. Results. In comparison with non-smokers, smokers had smaller officedaytime systolic blood pressure difference (6±2 vs 15±3 mmHg, respectively; p<0.01). Despite similar resting values, HR in smokers was greater than in non-smokers during both daytime (86±3 vs 77±2 beats/min, respectively; p< 0.001) and night-time (73±3 vs 66±2 beats/min, respectively; p<0.01). MSNA was elevated in smokers (36±3 bursts/min) compared with non-smokers (28±3 bursts/min; p<0.01). Similar results were obtained when MSNA was expressed as bursts/100 heart beats. Multiple linear regression analysis revealed that only age and smoking status were linked independently to MSNA (R2=0.42, p< 0.001). Conclusions. In patients with essential hypertension, smoking is independently associated with chronic increase in MSNA. These findings may have implications for our understanding of the mechanisms linking smoking to cardiovascular events. © 2010 Informa UK Ltd.
Wasilewska A.,Medical University of Gdask |
Sczewski F.,Medical University of Gdask |
Gdaniec M.,Adam Mickiewicz University
Acta Crystallographica Section E: Structure Reports Online | Year: 2010
The structure of the title compound, C12H16N 5+·I-, shows that the methyl-ation reaction with CH3I occurred at the imine N atom at position 5 of the 3,6,7,8a-tetra-hydro-2H-diimidazo[1,2-c:1′,2′-e]pyrido[1,2-a][1,3,5] triazine system. In the cation, the sp 3-hybridized C atom belonging to the fused dihydro-pyrine and dihydro-1,3,5-triazine rings deviates by 0.514 (3) Å from the best plane defined by the remaining cationic non-H atoms. The fused dihydropyridine and dihydro-1,3,5-triazine rings are each in a half-chair conformation with the sp 3-hybridized C atom as a flap. The iodide anion is 3.573 (2) Å from the methyl-ated N atom and exhibits five short C - H⋯I- contacts with distances less than 3.16 Å. The structure has been determined from a non-merohedral twin with twin law [-1 0 0 0 - 1 0 0.115 0 1], minor domain = 0.1559 (12).
Szczesio M.,Wroclaw University of Technology |
Olczak A.,Wroclaw University of Technology |
Goka J.,Wroclaw University of Technology |
Gobis K.,Medical University of Gdask |
And 2 more authors.
Acta Crystallographica Section C: Crystal Structure Communications | Year: 2011
Methyl 2-(pyrazin-2-ylcarbon-yl)hydrazinecarbodithio-ate, C 7H8N4OS2, (E1), N′-[bis- (methyl-sulfan-yl)methyl-idene]pyrazine-2-carbohydrazide, C8H 10N4OS2, (F1), N′-[bis(methyl-sulfan-yl) methyl-idene]-6-meth-oxy-pyrazine-2-carbohydrazide, C9H 12N4O2S2, (F2), and methyl 1-methyl-2-(pyrazin-2-ylcarbon-yl)hydrazinecarbodithio-ate, C 8H10N4OS2, (G1), can be con-sid-ered as derivatives of classical (thio)-amide-type tuber-culo-statics, and all are moderately active against Mycobacterium tuberculosis. This study was undertaken in a search for relationships between activity and specific intra-molecular inter-actions, especially conjugations and hydrogen-bond contacts, and the mol-ecular structures were compared with respective amine analogues, also active against the pathogen. Despite the differences between the amine and carbonyl groups with opposite functions in the hydrogen bond, the two types of structure show a surprisingly similar planar geometry, mostly due to the conjugations aided by the bifurcated intra-molecular hydrogen-bond contact between the N-H group of the central hydrazide group as donor and a pyrazine N atom and an S atom of the dithio function as acceptors. Planarity was suggested to be crucial for the tuberculostatic activity of these compounds. The N-methyl-ated derivative (G1) showed a significant twist at the N-N bond [torsion angle =-121.9 (3)°] due to the methyl substitution, which precludes an intra-molecular N-H⋯S contact and the planarity of the whole mol-ecule. Nonetheless, the compound shows moderate tuberculostatic activity. © 2011 International Union of Crystallography.
Karwacki Z.,Medical University of Gdask |
Niewiadomski S.,Medical University of Gdask |
Rzaska M.,Medical University of Gdask |
Witkowska M.,Medical University of Gdask
Anaesthesiology Intensive Therapy | Year: 2014
Background: Target-controlled infusion (TCI) is used to maintain the desired concentration of a hypnotic drug in th plasma and brain. However, pharmacodynamic variability can cause problems with maintaining the adequate leve of anaesthesia. The bispectral index (BIS) is one of only a few parameters that allow an assessment of the depth o anaesthesia. In the present study, we attempted to determine the optimal dosages of drugs used for total intravenou anaesthesia with TCI based on BIS-guided monitoring of depth of anaesthesia Methods: The study was conducted in 60 ASA I patients undergoing elective surgery due to lumbar discopathy. Th participants were divided into two groups of 30 individuals. The patients were premedicated with 15 mg oral midazolam Group I was the control group; group II received BIS monitoring. Anaesthesia was induced with TCI propofo (4 mg mL-1), fentanyl (2 mg kg-1) and vecuronium (0.12 mg kg-1) and maintained with TCI propofol, continuous infusio of vecuronium (0.03 mg kg-1 h-1) and fractionated doses of fentanyl. ECG, HR, MAP, SaO2, ETCO2, and the degree o neuromuscular blockade were monitored, specifically at the following time points: T-1before induction, T2-Afte induction, T3-After intubation, T4-After positioning of the patient, T5-T13-every 5 min during surgery, T14-o completion of surgery, T15-before extubation, T16-After extubation Results: The study groups were comparable in terms of age, body weight, duration of anaesthesia and recovery time The haemodynamic parameters, such as HR and MAP, did not differ significantly between the groups. In both groups changes in the mean MAP values were observed between T1 and T2, T2 and T3, T3 and T4 as well as T14 and T15. The tota dose of fentanyl and the doses of propofol were lower in the group that received BIS monitoring Conclusion: BIS monitoring reduces the doses of opioids and hypnotics used during total intravenous anaesthesia by TCI.
Mazurkiewicz-Beldziska M.,Medical University of Gdask |
Szmuda M.,Medical University of Gdask |
Zawadzka M.,Medical University of Gdask |
Matheisel A.,Medical University of Gdask
Anaesthesiology Intensive Therapy | Year: 2014
The management of status epilepticus (SE) has changed in recent years. Substantial differences exist regarding th definition and time frame of a seizure, which has been operationally defined as lasting for 5 min. Not only have man new intravenous drugs, such as levetiracetam and lacosamide been introduced but other routes of administration such as intranasal or buccal administration for midazolam, are also being developed. Optimal and successful therap initiated at the appropriate moment, adequately tailored to the clinical state of the patient, determines the first ste in the normalisation of vital functions and leads to the restoration of the physiological homeostatic mechanisms o the organism The aim of this review is to present the current treatment options for the management of convulsive status epilepticu (CSE) that have been widely confirmed as the most effective in clinical trials and approved by the internationa neurology authorities as the actual therapeutic standards. We also intend to indicate distinct and unequivocal differentiatio and therapeutic indications for each phase of CSE, including the precise doses of the related medications to present practical guidelines for clinicians. The treatment of patients with CSE requires emergency physicians neurologists and specialists in intensive care to work together to provide optimal care that should be initiated a soon as possible and conducted as a unified procedure to improve neurocritical care in patients who are transferre from the ambulance service, through the emergency department and finally to the neurology department or ICU Appropriate treatment also involves avoiding mistakes associated with inadequate doses of medications, overdosin a patient or choosing an inappropriate medication.
Hasak L.,Medical University of Gdask |
Wujtewicz M.,Medical University of Gdask |
Owczuk R.,Medical University of Gdask
Anaesthesiology Intensive Therapy | Year: 2014
Background: Tracheal intubation is one of the strongest stimuli during general anaesthesia and may result in an insufficien depth of anaesthesia. The aim of the study was to compare the clinical evaluation of the depth of anaesthesi with an evaluation using entropy during inhalational and intravenous induction of general anaesthesia Methods: This study involved 60 patients undergoing elective surgery under general anaesthesia. Patients wer divided into two groups, group E (etomidate induction) and group S (sevoflurane induction). The systolic arteria pressure (SAP), heart rate (HR), response entropy (RE), and state entropy (SE) were determined at the following seve measurement points: before anaesthesia induction, at the loss of consciousness (LOC) point, before tracheal intubation immediately after intubation, and 2 min, 4 min and 6 min after tracheal intubation. An increase in HR and/or SA of more than 20% and/or the occurrence of lacrimation and/or perspiration in response to tracheal intubation wa considered a marker of inadequate anaesthesia in the clinical evaluation. The depth of anaesthesia was considere insufficient according to entropy monitoring if the RE and SE were above 60 Results: In clinical evaluation, insufficient anaesthesia in response to tracheal intubation was observed in all th patients in group E and in more than half of the patients in group S. At the same time, the majority of patients i both groups had entropy values that did not exceed the recommended value as an appropriate level of anaesthesia Conclusions: We found a discrepancy in the evaluation of the depth of anaesthesia based on clinical criteria compare with evaluations based on entropy values during both intravenous and inhalational induction of general anaesthesia.