Deterioration of visual quality and acuity as the first sign of ceroid lipofuscinosis type 3 (CLN3), a rare neurometabolic disease.

Ceroid lipofuscinosis type 3 (CLN3) is an autosomal recessive, neurodegenerative metabolic disease. Typical clinical symptoms include progressive visual loss, epilepsy of unknown etiology and dementia. Presence of lipofuscin deposits with typical pattern of 'fingerprints' and vacuolized lymphocytes suggest the diagnosis of CLN3. Cause of CLN3 are mutations in the CLN3 gene, among which the most frequently found is the large deletion 1.02 kb spreading on exons 7 and 8. We present 4 patients from 2 families, in whom the deterioration of visual quality and acuity was observed as first clinical sign, when they were a few years old and it was successively accompanied by symptoms of neurologic deterioration (like generalized convulsions with consciousness impairment). In all patients the 1.02 kb deletion in the CLN3 gene was detected in homo- or heterozygosity with other CLN3 pathogenic variant. Ultrastructural studies revealed abnormal structures corresponding to 'fingerprint' profiles (FPPs) in conjunctival endothelial cells. It should be emphasized that in patients with blindness of unknown cause the diagnosis of ceroid lipofuscinosis should be considered and in older children-especially CLN3. The facility of the analysis for the presence of 1.02 kb deletion and economic costs are a solid argument for intensive use of this test in the diagnostic procedure of CLN3.

Changes in global gene expression indicate disordered autophagy, apoptosis and inflammatory processes and downregulation of cytoskeletal signalling and neuronal development in patients with Niemann-Pick C disease.

Changes in gene expression profiles were investigated in 23 patients with Niemann-Pick C1 disease (NPC). cDNA expression microarrays with subsequent validation by qRT-PCR were used. Comparison of NPC to control samples revealed upregulation of genes involved in inflammation (MMP3, THBS4), cytokine signalling (MMP3), extracellular matrix degradation (MMP3, CTSK), autophagy and apoptosis (CTSK, GPNMB, PTGIS), immune response (AKR1C3, RCAN2, PTGIS) and processes of neuronal development (RCAN2). Downregulated genes were associated with cytoskeletal signalling (ACTG2, CNN1); inflammation and oxidative stress (CNN1); inhibition of cell proliferation, migration and differentiation; ERK-MAPK pathway (COL4A1, COL4A2, CPA4); cell adhesion (IGFBP7); autophagy and apoptosis (CDH2, IGFBP7, COL4A2); neuronal function and development (CSRP1); and extracellular matrix stability (PLOD2). When comparing NPC and Gaucher patients together versus controls, upregulation of SERPINB2 and IL13RA2 and downregulation of CSRP1 and CNN1 were characteristic. Notably, in NPC patients, the expression of PTGIS is upregulated while the expression of PLOD2 is downregulated when compared to Gaucher patients or controls and potentially could serve to differentiate these patients. Interestingly, in NPC patients with (i) jaundice, splenomegaly and cognitive impairment/psychomotor delay-the expression of ACTG2 was especially downregulated; (ii) ataxia-the expression of ACTG2 and IGFBP5 was especially downregulated; and (iii) VSGP, dysarthria, dysphagia and epilepsy-the expression of AKR1C3 was especially upregulated while the expression of ACTG2 was downregulated. These results indicate disordered apoptosis, autophagy and cytoskeleton remodelling as well as upregulation of immune response and inflammation to play an important role in the pathogenesis of NPC in humans.

Influence of dronedarone (a class III antiarrhythmic drug) on the anticonvulsant potency of four classical antiepileptic drugs in the tonic-clonic seizure model in mice.

Increasing evidence indicates that some antiarrhythmic drugs play a pivotal role in seizures, not only in vivo studies on animals, but also in clinical trials. Some of these antiarrhythmic drugs potentiate or alleviate the anticonvulsant action of the classical antiepileptic drugs. The aim of this study was to determine the influence of dronedarone (DRO-a multichannel blocker belonging to the class III of antiarrhythmic drugs) on the anticonvulsant effects of four standard antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the tonic-clonic seizure model in mice. Potential acute adverse effects exerted by the antiepileptic drugs combined with DRO were evaluated in three behavioral tests (chimney, grip-strength and passive avoidance). To confirm the nature of interaction, total brain concentrations of antiepileptic drugs were measured. DRO (50 mg/kg, i.p.) significantly reduces the anticonvulsant potency of phenytoin (P < 0.05), having no impact on that of carbamazepine, phenobarbital and valproate in the tonic-clonic seizure model in mice. DRO (50 mg/kg) neither changed total brain concentrations of phenytoin in mice, nor affected normal behavior in experimental animals subjected to the chimney, grip-strength and passive avoidance tests. In conclusion, DRO should not be combined with phenytoin because it reduced the anticonvulsant effects of the latter drug in experimental animals. The combined administration of DRO with carbamazepine, phenobarbital and valproate resulted in neutral interaction between these drugs in the tonic-clonic seizure model in mice.

A questionnaire-based, multicenter registry of resistant and pseudo-resistant arterial

Introduction: Hypertensive patients with poor blood pressure (BP) control are commonly referred to tertiary centers with a diagnosis of resistant hypertension (RH). The aim of the study was to identify the causes of insufficient BP control and to assess the incidence of true resistant hypertension. Material and Methods: We ran a questionnaire-based, multicenter study (10 high volume tertiary centers in Poland) of patients referred with an initial diagnosis of RH. Only patients with ABPM-confirmed uncontrolled hypertension (systolic ≥140 mmHg and/or diastolic ≥90mmHg despite maximal doses of ≥3 medications, including a diuretic) were included. We assessed the causes of non-optimal BP control, a proportion of patients with excluded secondary hypertension, and the burden of hypertension-related complications. Results: We analyzed 124 patients aged 41-88, with a history of hypertension of 17.5±9 years. 90% of them had developed systemic complications, the most common being LV hypertrophy (73.4%) and LV diastolic dysfunction (63.4%). In only 47% all major causes of secondary hypertension were excluded. In 90.3% of subjects, at least one factor affecting BP control was identified. The most frequent factors were medication noncompliance (52.4%), metabolic syndrome (43.6%) excessive sodium intake (66.1%) and chronic administration of non-steroid anti-inflammatory drugs (40%). The incidence of real resistant hypertension was only 4.8%. Conclusions: Among patients referred with uncontrolled hypertension, the incidence of real resistant hypertension is small. A majority of these patients have multiple factors potentially responsible for poor BP control, the most common being medication non-adherence, use of drugs increasing BP, excessive salt intake and metabolic syndrome.

Influence of Ivabradine on the Anticonvulsant Action of Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice.

Although the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in neuronal excitability and synaptic transmission is still unclear, it is postulated that the HCN channels may be involved in seizure activity. The aim of this study was to assess the effects of ivabradine (an HCN channel inhibitor) on the protective action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) against maximal electroshock-induced seizures in mice. Tonic seizures (maximal electroconvulsions) were evoked in adult male albino Swiss mice by an electric current (sine-wave, 25 mA, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the combinations of ivabradine with classical antiepileptic drugs were measured in mice along with total brain antiepileptic drug concentrations. Results indicate that ivabradine (10 mg/kg, i.p.) significantly enhanced the anticonvulsant activity of valproate and considerably reduced that of phenytoin in the mouse maximal electroshock-induced seizure model. Ivabradine (10 mg/kg) had no impact on the anticonvulsant potency of carbamazepine and phenobarbital in the maximal electroshock-induced seizure test in mice. Ivabradine (10 mg/kg) significantly diminished total brain concentration of phenytoin and had no effect on total brain valproate concentration in mice. In conclusion, the enhanced anticonvulsant action of valproate by ivabradine in the mouse maximal electroshock-induced seizure model was pharmacodynamic in nature. A special attention is required when combining ivabradine with phenytoin due to a pharmacokinetic interaction and reduction of the anticonvulsant action of phenytoin in mice. The combinations of ivabradine with carbamazepine and phenobarbital were neutral from a preclinical viewpoint.

Impact of morbid obesity and bariatric surgery on antioxidant/oxidant balance of the unstimulated and stimulated human saliva.

OBJECTIVE: There is no study evaluating the influence of morbid obesity and bariatric surgery on antioxidant/oxidant homeostasis of the unstimulated and stimulated human saliva. MATERIALS AND METHODS: Salivary flow rate, total antioxidant status (TAS), total oxidant status (TOS), oxidative status index (OSI), the total amount of uric acid (UA), polyphenols (pPh), catalase (CAT), superoxide dismutase 2 (SOD2), specific activity of peroxidase (Px), as well as malondialdehyde (MDA), and advanced glycation end products (AGE) concentrations were determined in the unstimulated (UWS) and stimulated (SWS) whole saliva of patients with morbid obesity before and after bariatric surgery. RESULTS: In both UWS and SWS, the total amount of TOS, OSI, SOD2, and MDA was statistically higher in patients with morbid obesity as compared to the healthy controls, as well as significantly lower in the patients treated surgically as compared to the obese patients. The median values of the total amount of TAS, CAT, UA, pPh, and specific activity of Px were significantly reduced in UWS and SWS in patients with morbid obesity as compared to the control group and also statistically elevated in patients after bariatric surgery as compared to the patients with morbid obesity. CONCLUSIONS: In morbid obesity, reduced unstimulated and stimulated salivary flow can be observed. Bariatric surgery restored only unstimulated salivary flow to normal values. Disturbances in oxidant/antioxidant homeostasis may be observed in UWS and SWS of obese patients before and after treatment.

Role of emotional control on anxiety and stress among cancer patients.

OBJECTIVE: The article aims to assess the role of stress and anxiety in relation to the level of emotional control among cancer patients. Currently cancer ranks second, after cardiovascular disease, as the most common cause of death. Moreover, it is predicted that in the coming years, cancer will become the leading cause of death worldwide. This is due to the extended lifespan of the population and also to the presence of carcinogenic factors in the surrounding environment. The emergence of cancer is a significant stressor that affects individuals in diverse ways, leading to cognitive, behavioral, and emotional consequences. In line with the adopted aim, emotional issues are the chosen area of exploration in this article. METHODS: The study included 102 patients. The differences between the patients' results according to various scales and the results produced by the validation group data were examined using one-sample t-tests. The relationships between the quantitative variables were determined using Spearman's rho coefficients, and the relationships between the quantitative and qualitative variables were verified using Kruskal-Wallis tests. RESULTS: The participants exhibited higher anxiety suppression levels than individuals in the normalization group. They sought emotional support more frequently than the average person in the population, turned to religion, engaged in other such activities, lived in denial more often, discontinued activities, and displayed a sense of humor less frequently. The more frequently they controlled their anger, the less they sought emotional and instrumental support, catharsis, and attempted to accept the situation and cease being active. Additionally, controlling anxiety, sadness, and depression coexisted with self-blame, denial, and compensatory actions. CONCLUSIONS: Cancer patients face intense anxiety. Emotional and instrumental support, along with the ability to express and manage emotions, are crucial for these patients, especially within the context of facing the challenge of cancer. Finding constructive ways to express strong and difficult emotions prevents their accumulation and reduces the need for emotional suppression. Preventive actions should be oriented toward supporting the emotional competencies of patients.

[Evaluation of selected properties of morphological variants of Acinetobacter baumannii complex]. / Ocena wybranych wlasciwosci morfologicznych wariantów paleczek Acinetobacter baumannii complex.

INTRODUCTION: The ability of growth of Acinetobacter baumannii as morphology colony variants have been observed. However, the importance of this phenomenon for its biology is not known. The aim of this study was to evaluate some properties of light and dark morphology colony variants. METHODS: Fifty two isolates were identified by MALDI TOF MS method (MALDI Biotyper, BRUKER). It was evaluated the adhesion to polystyrene and extracellular mucus production of morphology colony variants and its susceptibility to imipenem and meropenem by agar dilution method. RESULTS: Forty eight (92.3%) out of the 52 morphotypes Acinetobacter sp. were identified as A. baumannii, two (5.8%) as A. genomospecies 3, one as the A. calcoaceticus. Sixteen (61.0%) pairs of isolates showed differences in the similarity of the spectra to the spectra of reference strains in the MALDI-TOF MS method. Adhesion to polystyrene was observed in all dark and 92.3% light morphotypes. Extracellular slime was produced by 15 (57.7%) dark morphotypes, and 7 (26.9%) of clear. The differences in susceptibility to imipenem occurred in two (7.7%), and meropenem in three (11.5%) pairs of morphotypes. CONCLUSIONS: The results show diversity of biological properties of morphology colony variants of A. baumannii complex. Differences in the level of adhesion to polystyrene and slime production may indicate the importance of morphological differentiation in virulence of A. baumannii complex.

[Adhesion and slime production by wild and clinical strains of Acinetobacter baumannii]. / Adhezja oraz wytwarzanie sluzu zewnatrzkomórkowego przez dzikie i kliniczne szczepy paleczek Acinetobacter baumannii.

INTRODUCTION: Adhesion of bacteria to the surface plays a key role in the development of infection, and is the first stage of biofilm formation. The ability of A. baumannii strains to adhesion and forming biofilms on abiotic surfaces, as well as eucaryotic cells was described.A. baumannii is also capable of secretion of the exopolysaccharide (EPS) - a substance that allows the binding of bacterial cells to the surface, and with each other. The aim of this study was to evaluate the ability of biofilm formation and slime production by wild-type and clinical strains of A. baumannii. METHODS: We examinated 51 strains ofA. baumannii, including 14 isolated from lower respiratory tract, 17 from wound swabs and 20 from the soil. Adhesion to polystyrene was evaluated by modified Christensen methods and slime production by Ishiguro method. RESULTS: Adhesion to polystyrene was observed in 51,0% of strains, including 70,0% of wild-type and 38,7% of clinical strains (64,7% strains from wound swabs and one strain from lower respiratory tract). Slime production was found in 31,4% of strains, of which the largest (42.9%) group strains were isolated from lower respiratory tract. There was no correlation between production of extracellular slime, and the adhesion of strains to polystyrene. CONCLUSIONS: Different levels of expression of virulence factors in A. baumannii strains isolated from different origin indicates their importance in the colonisation ecological niches and the development of infections at various sites.

The Occurrence of Stress, Illness Acceptance and the Quality of Life of Patients after Pacemaker Implantation.

Pacemaker implantation improves the quality of life of most patients, especially in the initial period after implantation. It is necessary to measure the long-term quality of life and factors that can affect it-stress and illness acceptance. The aim of the study was to assess the impact of stress and illness acceptance on the quality of life of patients after pacemaker implantation. To obtain final conclusions, we performed a survey on a group of 100 patients with implanted pacemakers. Our survey consists of standardized research tools to check the quality of life (WHOQOL-BREF), perceived stress and ways to cope with it (PSS-10, mini-COPE) and acceptance of illness (AIS). The results of the study were summarized in a statistical analysis. At least a good quality of life was declared by more than half of the respondents [Me = 4; 95% PU (4, 4)]. The average result obtained by the respondents when converted to the STEN scale was six. The respondents were characterized by a moderate level of stress compared to the PSS-10 norms and it was related to the quality of life. Similar, statistically significant correlations were presented as mini-COPE and AIS results. Respondents were most likely to use acceptance strategies, active coping methods, when dealing with something else and planning. The rarest strategies were doing nothing and taking pharmaceuticals. The average score on the acceptance of illness scale was (M = 22.14; SD = 6.05), which is more than the result obtained by patients from the AIS normalization group. It shows that assessed patients after pacemaker implantation declare the general quality of life as good or higher. Additionally, this quality of life is closely related to stress levels, coping strategies and acceptance of illness, which shows us the importance of research in this area.

Spatial properties affecting the sensitivity of soil water dissolved organic carbon long-term median concentrations and trends.

It is increasingly clear that increases in dissolved organic carbon in upland waters in recent decades have often been dominated by acid deposition, but reasons for substantial variation in rates of change remain unclear. This paper focuses on the extent to which spatial properties, such as variation in soil properties, atmospheric deposition and climate, affect the sensitivity of DOC concentrations in soil water. The purpose is to i) examine evidence for differences in site average concentrations and trends in soil water DOC between sites with contrasting ecosystem properties, i.e. vegetation cover and soil type, and ii) identify the wider combination of site characteristics that best explain variation in these DOC metrics between sites. We collated soil water and deposition chemistry, soil chemistry and meteorological data from 15 long-term UK monitoring sites (1992-2010) covering a range of soils, vegetation, climate and acid deposition levels. Mineral soils under forests showed the greatest range of long-term mean DOC concentrations and trends. Regression analysis indicated that acid and sea-salt deposition, and soil sensitivity to acidification were the factors most strongly associated with spatial variation in mean DOC concentrations. Spatial variation in DOC trends were best explained by Al saturation and water flux. Overall, the sensitivity of DOC release from soil to changes in pollutant deposition could be related to the type of vegetation cover and soils chemistry properties, such as Al saturation, divalent base cation content and hydrological regime. The identification of the ecosystem properties that appear most influential in modifying DOC production and responses to long-term drivers, helps elucidate potential mechanistic explanations for differences in DOC dynamics across seemingly similar ecosystems, and points to the importance of DOC mobility in regulating its dynamics.

[Thermography in cardiology]. / Termowizja jako metoda diagnostyczna stosowana w kardiologii.

Thermography is a diagnostic method which is totally non-invasive, painless and safe for both a patient and a diagnostician. It enables to define the physiological condition of the examined tissues or organs basing on the emission of the infrared radiation. Thermography examination has its application in almost every branch of medicine. For a few years in cardiology, there has been an intensive research on introducing the new methods of identifying the high risk atherosclerotic plaques which is largely based on evaluating the degree of escalation of the inflammation process within the atherosclerotic changes. Thanks to applying thermography within the vessels, it is possible to measure the temperature of the wall of the vessel in order to detect the high risk atherosclerotic plaques and evaluate the potential risk of occurrence of the acute coronary syndrome.

[Carbapenem-resistant Acinetobacter baumannii strains]. / Szczepy acinetobacter baumannii oporne na karbapenemy.

A. baumannii rods are opportunistic pathogens responsible generally for nosocomial infections. Resistance to carbapenems, observed among them, is a serious threat due to ability to be transmitted between bacterial species. The aim of our study was to evaluate the frequency of isolation and susceptibility to antibiotics of resistant to imipenem and/or meropenem A. baumannii strains isolated between 2007 and 2009 from patients of University Hospital of dr A. Jurasz Collegium Medicum of L. Rydygier in Bydgoszcz Nicolaus Copernicus University in Torun. Study shows increasing frequency of isolation that type of strains from 4 in 2007 to 95 in 2008 and 67 in 2009. Percentage of imipenem-resistant isolates raised to 27.6% in 2008 and 31.0% in 2009. Meropenem-resistant A. baumannii isolates frequency changed from 2.1% in 2007 to 31.2% and 34.6%, in 2008 and 2009, respectively. The majority of strains were obtained from patients of the Intensive Care Units and surgery clinics. Examined A. baumannii strains were generally isolated from bronchoalveolar lavage (25.3%) and wound (18.1%) or throat (12.0%) swabs samples. The isolates demonstrated full resistance to norfloxacin, ciprofloxacin, and chloramphenicol. Ampicillin/sulbactam (24.8%), tobramycin (8.1%) and colistin (1.5%) presented the highest in vitro activity against isolated strains.

[Antibiotic sensitivity of beta-hemolytic streptococci isolated from throat swabs and purulent material]. / Lekowrazliwosc paciorkowców beta-hemolizujacych izolowanych z wymazów z gardla i materialu ropnego.

The aim of this study was to evaluate the prevalence and susceptibility of beta-hemolytic streptococci isolated from throat swabs (142--29.9%) and purulent material (333--70.1%) taken from patients treated at University Hospital dr. A. Jurasz in Bydgoszcz Collegium Medicum. L. Rydygier in Bydgoszcz, Nicolaus Copernicus University in Torun in 2005-2009. Of the 475 tested strains, 156 (32.8%) were identified as S. pyogenes. This species accounted for 38.8% of strains isolated from purulent material and 19.0% of swabs from the throat. Among the strains isolated from throat swabs of 62 (43.7%) were identified as Streptococcus group C. Only 5.1% strains were identified as Streptococcus group F. All strains of beta-hemolytic streptococci were susceptible to ampicillin or penicillin, fluoroquinolones, vancomycin and linezolid. Erythromycin-susceptible strains was 83.8%, and 89.1% for clindamycin. A total of 51.3% of erythromycin resistance strains had the cMLS(B) phenotype (63.3% for strains from throat swabs and 46.3% of the purulent materials). Sensitivity to tetracycline was characterized by 51.2% of strains of beta-hemolytic streptococci. The percentage of strains susceptible to this antibiotic among isolates from throat swabs was 63.1%, and purulent material--48.0%. The lowest percentage of strains susceptible to tetracycline (14.1%) were found among S. agalactiae and Streptococcus group G (33.6%) strains. During the study time, saw an increase in the percentage of strains susceptible to tetracycline and erythromycin.

[Thermography in medical diagnostics]. / Termowizja jako metoda diagnostyczna stosowana w medycynie.

Measuring the body temperature belongs to the oldest and the most frequently performed diagnostic examination. Current technical progress enables for measurment of body temperature on its surface not only in one particular place, but in lots of different places at the same time and it can also be done from some distance. Invisible for the eye temperature dispersion, which is presented in the form of thermographic photographs, is becoming more popular in medical diagnostics. Thermography is a totally non-invasive, painless and safe for both the patient and the diagnostician examining. The method allows for defining the physiological condition of the tissues or organs on the basis of emitted ultrared radiation.

[Evaluation of occurrence of Alcaligenes faecalis in clinical samples of patients of the university hospital in Bydgoszcz]. / Udzial paleczek Alcaligenes faecalis w zakazeniach pacjentów szpitala uniwersyteckiego w Bydgoszczy.

Alcaligenes faecalis is an aerobic Gram-negative, non-fermentative rod. It's saprophyte of water and soil. It may be recovered from wet places of hospital environment. It is considered as an opportunistic pathogen. The aim of this review was evaluation of occurrence in clinical samples and susceptibility to antibiotics of 72 A. faecalis strains isolated in years 2003-2008. Over 30% of strains were isolated from patients in surgical ward, 19.6% from patients in outpatient clinic and almost 14% from patients in Department of Dermatology. 70.8% of strains were isolated from purulent material samples, whereas from urine--16.7% of strains. Nearly 88% out of examined strains were grown in mixed culture together with one (26.4%), two (32.0%), three (23.6%) or four (5.6%) microorganisms. All out of strains were sensitive to piperacyline, piperacyline/tazobactam and carbapenems. Sensitivity to aztreonam was observed at 22.2% of strains and to co-trimoxazole at 57.1% of strains.

Dronedarone (a multichannel blocker) enhances the anticonvulsant potency of lamotrigine, but not that of lacosamide, pregabalin and topiramate in the tonic-clonic seizure model in mice.

Accumulating experimental evidence indicates that some recently licensed antiarrhythmic drugs, including dronedarone (a multichannel blocker) play a crucial role in initiation of seizures in both, in vivo and in vitro studies. Some of these antiarrhythmic drugs elevate the threshold for maximal electroconvulsions and enhance the anticonvulsant potency of classical antiepileptic drugs in preclinical studies. This study was aimed at determining the influence of dronedarone (an antiarrhythmic drug) on the anticonvulsant potency of four novel antiepileptic drugs (lacosamide, lamotrigine, pregabalin and topiramate) in the maximal electroshock-induced seizure model in mice. To exclude any potential pharmacokinetic contribution of dronedarone to the observed interactions, total brain concentrations of antiepileptic drugs were measured. Dronedarone (50 mg/kg, i.p.) significantly enhanced the anticonvulsant potency of lamotrigine, by reducing its ED50 value from 7.67 mg/kg to 4.19 mg/kg (P < 0.05), in the maximal electroshock-induced seizure test in mice. On the contrary, dronedarone (50 mg/kg, i.p.) did not affect the anticonvulsant properties of lacosamide, pregabalin or topiramate in the maximal electroshock-induced seizure test in mice. Measurement of total brain concentrations of lamotrigine revealed that dronedarone did not significantly alter total brain concentrations of lamotrigine in experimental animals. Additionally, the combination of dronedarone with pregabalin significantly impaired motor coordination in animals subjected to the chimney test. In contrast, the combinations of other studied antiepileptic drugs with dronedarone had no negative influence on motor coordination in mice. It is advisable to combine dronedarone with lamotrigine to enhance the anticonvulsant potency of the latter drug. The combinations of dronedarone with lacosamide, pregabalin and topiramate resulted in neutral interactions in the maximal electroshock-induced seizure test in mice. However, a special caution is advised to patients receiving both, pregabalin and dronedarone due to some possible adverse effects that might occur with respect to motor coordination.

Gene expression profile in patients with Gaucher disease indicates activation of inflammatory processes.

Gaucher disease (GD) is a rare inherited metabolic disease caused by pathogenic variants in the GBA1 gene. So far, the pathomechanism of GD was investigated mainly in animal models. In order to delineate the molecular changes in GD cells we analysed gene expression profile in cultured skin fibroblasts from GD patients, control individuals and, additionally, patients with Niemann-Pick type C disease (NPC). We used expression microarrays with subsequent validation by qRT-PCR method. In the comparison GD patients vs. controls, the most pronounced relative fold change (rFC) in expression was observed for genes IL13RA2 and IFI6 (up-regulated) and ATOH8 and CRISPLD2 (down-regulated). Products of up-regulated and down-regulated genes were both enriched in genes associated with immune response. In addition, products of down-regulated genes were associated with cell-to-cell and cell-to-matrix interactions, matrix remodelling, PI3K-Akt signalling pathway and a neuronal survival pathway. Up-regulation of PLAU, IFIT1, TMEM158 and down-regulation of ATOH8 and ISLR distinguished GD patients from both NPC patients and healthy controls. Our results emphasize the inflammatory character of changes occurring in human GD cells indicating that further studies on novel therapeutics for GD should consider anti-inflammatory agents.

ArF excimer laser debrides burns without destruction of viable tissue: A pilot study.

INTRODUCTION: Recent evidence indicates that early removal of eschar by tangential debridement can promote healing. Laser debridement can be used for debridement of areas that prove challenging for debridement using tangential excision. In particular, irradiation with an ArF excimer laser ablates desiccated eschar and is self-terminating, preserving hydrated or viable tissue. METHODS: Thermal burns were created on the flanks of two outbred, female Yorkshire pigs using aluminum bars heated to 70°C and applied for different lengths of time. Three days after injury, burns were debrided using an ArF excimer laser (193nm). Tissue was harvested immediately after debridement and 7days after debridement (10days after burn). RESULTS: Data from a pilot study demonstrates that ArF excimer laser irradiation removes burn eschar and promotes healing at 10days after burn. ArF excimer laser debridement is self-terminating and preserves underlying and adjacent perfused tissue. Potentially, this modality would be ideal for the complex curvilinear structures of the body.

Chronically administered fluoxetine enhances the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock model.

Interactions between chronically administered fluoxetine and valproate, carbamazepine, phenytoin, or phenobarbital were studied in the maximal electroshock test in mice. Fluoxetine administered for 14 days at doses up to 20 mg/kg failed to affect the electroconvulsive threshold. Nevertheless the drug (at 15 and 20 mg) enhanced the anticonvulsant activity of valproate, carbamazepine, and phenytoin. When applied at 20 mg/kg, it potentiated the protective action of phenobarbital. Fluoxetine, antiepileptic drugs, and their combinations did not produce significant adverse effects evaluated in the chimney test (motor coordination) and passive-avoidance task (long-term memory). Chronically applied fluoxetine significantly increased the brain concentrations of valproate, carbamazepine, phenobarbital and phenytoin, indicating a pharmacokinetic contribution to the observed pharmacodynamic interactions. In conclusion, long-term treatment with fluoxetine exhibited some favorable effects on the anticonvulsant properties of conventional antiepileptic drugs, resulting, however, from pharmacokinetic interactions.