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Introduction: We sought to identify patients with amyotrophic lateral sclerosis (ALS) who displayed suspected peripheral nervous system (PNS) inflammation to compare them to those with suspected PNS degeneration.Methods: We measured sonographic median and ulnar nerve cross-sectional area (CSA) and cerebrospinal fluid albumin/serum albumin ratio (Qalb ) in patients with ALS to classify them as having suspected PNS degeneration (small CSA/low Qalb ) or inflammation (larger CSA/high Qalb ).Results: Fifty-seven percent of patients had suspected PNS degeneration, 21% had suspected PNS inflammation, and 21% displayed suspected "normal PNS state." Suspected PNS degeneration was related to classic ALS, shorter disease duration, and a smaller hypoechoic nerve area. Suspected PNS inflammation was associated with men, longer disease duration, and a larger hypoechoic nerve area and was the dominant finding in superoxide dismutase 1 mutation carriers.Discussion: Our simple approach might aid in the in vivo differentiation of supposed ALS subtypes, those with suspected PNS degeneration vs. inflammation, for stratification in clinical trials. Muscle Nerve 59:567-567, 2019. [ABSTRACT FROM AUTHOR]

Cardiac ischaemia‐reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re‐perfused post‐ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post‐anoxic heart mitochondria. However, post‐ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up‐regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro‐fibrotic and pro‐apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label‐free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC‐derived signals during cardiac adaptive remodelling and identified ROS as a possible effector. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to investigate whether sonographic peripheral cross-sectional nerve area (CSA) and progranulin (PGRN), a neuritic growth factor, are related to each other and whether they interact to predict clinical and paraclinical measures in amyotrophic lateral sclerosis (ALS).Methods: We included 55 ALS patients who had forearm median and ulnar nerve CSA, cerebrospinal fluid (CSF) PGRN, and serum PGRN measures available. CSF PGRN was normalized against the CSF / serum albumin ratio (Qalb ). Using age, sex, height, and weight adjusted general linear models, we examined CSA × CSF PGRN interaction effects on various measures.Results: There was a medium-effect size inverse relationship between CSA and CSF PGRN, but not between CSA and serum PGRN. Lower CSA values together with higher CSF PGRN levels were linked to smaller motor amplitudes.Discussion: In ALS, the constellation of peripheral nerve atrophy together with higher CSF PGRN levels indicates pronounced axonal damage. Muscle Nerve 57: 273-278, 2018. [ABSTRACT FROM AUTHOR]

Introduction: In this study we investigated whether peripheral nerve sonography could be used as a biomarker to monitor disease progression in amyotrophic lateral sclerosis (ALS).Methods: In 37 patients, ulnar and median nerve cross-sectional area (CSA) was determined in at least 2 ultrasound sessions; mean follow-up was 14.5 months. Linear mixed-effects models were conducted to analyze time effects on CSA.Results: Ulnar nerve CSA declined significantly at a monthly rate of -0.04 mm(2) (forearm) and -0.05 mm(2) (wrist); the decrease was more pronounced when baseline CSA was greater. To detect a 50% treatment effect on ulnar nerve CSA, 332 patients would need to be entered in a hypothetical randomized, controlled clinical trial. Time had no significant impact on median nerve CSA.Conclusions: Distal ulnar nerve ultrasound may be a useful biomarker to monitor disease progression in ALS, especially as hypothetical treatment effects on CSA seem to be detectable in manageable cohort sizes. Muscle Nerve 54: 391-397, 2016. [ABSTRACT FROM AUTHOR]

Introduction In various countries, standard doses of anti-D IgG used for postpartum immunoprophylaxis of hemolytic disease of fetus and newborn ( HDFN) vary from 100 μg to 300 μg. There are also different regulations concerning FMH assessment, and opinions about applicable tests are inconclusive. Methods Three flow cytometry tests ( FCTs) with anti-D, anti-HbF, anti-HbF+ CA antibodies, and two modifications of microscopic Kleihauer-Betke test ( KBT) were used. Results In all artificial mixtures with known concentrations, FCTs and KBT with counting 10 000 RBCs had similar satisfying sensitivity and specificity. KBT with counting 2000 RBCs had to be disqualified because of significant discrepancies between expected and measured values of FMH. The test procedure with anti-D was easier and shorter than the remaining tests, but it can be only used for FMH assessment in RhD-negative mothers with RhD-positive newborns. In one clinical sample, it was impossible to distinguish fetal RBCs from maternal F cells in KBT and FC with anti-HbF but other tests were useful. Conclusion In the four tests, correlation between expected and obtained results was appropriate ( CCC ̴1). Each test had some advantage and limitation in any clinical situation. Therefore, it is best to have opportunity to perform two or three assays in the laboratory. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: In this study we sought to determine the cross-sectional area (CSA) of peripheral nerves in patients with distinct subtypes of amyotrophic lateral sclerosis (ALS). Methods: Ulnar and median nerve ultrasound was performed in 78 ALS patients [classic, n = 21; upper motor neuron dominant (UMND), n = 14; lower motor neuron dominant (LMND), n = 20; bulbar, n = 15; primary lateral sclerosis (PLS), n = 8] and 18 matched healthy controls. Results: Compared with controls, ALS patients had significant, distally pronounced reductions of ulnar CSA (forearm/wrist level) across all disease groups, except for PLS. Median nerve CSA (forearm/wrist level) did not differ between controls and ALS. Conclusion: Ulnar nerve ultrasound in ALS subgroups revealed significant differences in distal CSA values, which suggests it has value as a marker of LMN involvement. Its potential was particularly evident in the UMND and PLS groups, which can be hard to separate clinically, yet their accurate separation has major prognostic implications. Muscle Nerve 51:669-675, 2015 [ABSTRACT FROM AUTHOR]

Abstract: Three types of potassium channels cooperate with the permeability transition pore (PTP) in the inner mitochondrial membranes of various tissues, mtK(ATP), mtBK, and mtKv1.3. While the latter two share similarities with their plasma membrane counterparts, mtK(ATP) exhibits considerable differences with the plasma membrane K(ATP)-channel. One important function seems to be suppression of release of proapototic substances from mitochondria through the PTP. Open potassium channels tend to keep the PTP closed thus acting as antiapoptotic. Nevertheless, in their mode of action there are considerable differences among them. This review introduces three K+-channels and the PTP, and discusses known facts about their interaction. [Copyright &y& Elsevier]

Objectives To describe the prevalence, management and outcome of spontaneous twin anemia polycythemia sequence (TAPS) diagnosed in the prenatal period. Method Retrospective analysis of 142 consecutive monochorionic twin pregnancies not diagnosed with twin to twin transfusion syndrome. TAPS cases were identified based on the presence of discordant middle cerebral artery peak systolic velocity (MCA-PSV) measurements and signs suggestive of a chronic intertwin transfusion imbalance: either an elevated reticulocyte count in the anemic twin or the presence of few small unidirectional anastomoses during fetoscopy or at postnatal placental examination. Results Three cases were identified, giving an estimated prevalence of 2%. Prenatal interventions were tailored to the characteristics of each case and consisted of intrauterine transfusion and interruption of the shared circulation by cord coagulation or laser separation. Conclusion In monochorionic twin pregnancies, TAPS is an uncommon prenatal finding. Nonetheless, its incidence seems high enough to recommend screening for this disease by MCA-PSV measurements. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Patients with chronic renal failure (CRF) receive recombinant human erythropoietin (rhEPO) for the correction of anemia. However, rhEPO also has an immunomodulatory effect. Detailed changes of phenotype and function of CD4+ T lymphocytes in CRF patients receiving rhEPO have not been reported yet; their study may bring insight into understanding of this immunomodulatory action of rhEPO. Two groups of CRF patients were included into the study: those treated; and those not receiving rhEPO. The expression of activation markers on CD4+ lymphocytes was measured with flow cytometry, both ex vivo and in vitro. The kinetics of CD4+ T lymphocytes proliferation was calculated using a dividing cells tracing method and numerical approach. Significantly higher percentages of CD4+CD95+, CD4+HLA-DR+ cells, and lower percentages of CD4+CD69+ and CD4+CD28+ cells were observed in both rhEPO-treated and untreated patients when compared with healthy controls. Changes in the proportions of CD4+CD28+ and CD4+HLA-DR+ subpopulations were dependent on the type of rhEPO, being more pronounced for rhEPOβ. CD4+ lymphocytes from untreated patients exhibited decreased expression of CD28 and CD69 after stimulation in vitro, whereas the expression of these antigens on lymphocytes of rhEPO-treated patients was similar to that observed in healthy controls. Fewer CD4+CD28+ T lymphocytes of untreated patients proliferated in vitro; these cells had longer G0→G1 time, which negatively correlated with surface expression of CD28. Our study confirms that rhEPO treatment normalizes activation parameters of CD4+ T lymphocytes and their proliferative capacity, which could explain earlier described immunomodulatory effects of rhEPO in patients suffering from CRF. [ABSTRACT FROM AUTHOR]

In patients with mesial temporal lobe epilepsy (MTLE) it remains an unresolved issue whether the interictal decrease in N-acetyl aspartate (NAA) detected by proton magnetic resonance spectroscopy (1H-MRS) reflects the epilepsy-associated loss of hippocampal pyramidal neurons or metabolic dysfunction. To address this problem, we applied high-resolution 1H-MRS at 14.1 Tesla to measure metabolite concentrations in ex vivo tissue slices from three hippocampal subfields (CA1, CA3, dentate gyrus) as well as from the parahippocampal region of 12 patients with MTLE. In contrast to four patients with lesion-caused MTLE, we found a large variance of NAA concentrations in the individual hippocampal regions of patients with Ammon's horn sclerosis (AHS). Specifically, in subfield CA3 of AHS patients despite of a moderate preservation of neuronal cell densities the concentration of NAA was significantly lowered, while the concentrations of lactate, glucose, and succinate were elevated. We suggest that these subfield-specific alterations of metabolite concentrations in AHS are very likely caused by impairment of mitochondrial function and not related to neuronal cell loss. A subfield-specific impairment of energy metabolism is the probable cause for lowered NAA concentrations in sclerotic hippocampi of MTLE patients. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. Visualizing corresponding metabolic changes in the brain of patients with ALS with proton magnetic resonance spectroscopy (1H-MRS) may provide surrogate markers for an early disease detection, for monitoring the progression and for evaluating a treatment response. The primary objective of our study was to evaluate whether modifications in MR metabolite levels occur before clinical disease onset, and whether these changes are directly linked to a distinct spatial progression pattern in the CNS. Therefore, age-dependent alterations in the cerebral and spinal metabolic profile in the mouse model of ALS overexpressing the mutated human G93A-superoxide dismutase 1 (G93A-SOD1) were determined by high-resolution MRS of tissue extracts at 14.1 Tesla. Both non-transgenic mice (control mice) and transgenic mice overexpressing the non-mutated human SOD1 (tg-SOD1) served as controls. In the spinal cord of G93A-SOD1 mice significantly decreased levels of N-acetyl aspartate were already detected 34 days postpartum, i.e. about 60 days before the average disease onset caused by motor neuron decline. In addition, glutamine and γ-aminobutyric acid concentrations were significantly diminished at Day 75, which is still in the presymptomatic phase of the disease. These metabolic changes were further progressive in the course of the disease and started to involve the brainstem at Day 75. Overall, high-resolution 1H-MRS allows a sensitive spatial and temporal metabolite profiling in the presymptomatic phase of ALS even before significant neuronal cell loss occurs. [ABSTRACT FROM AUTHOR]

Abstract: Poly(l-lysine)s, PLLs, are commonly used for DNA compaction and cell transfection. We report that, although PLLs of low (2.9kDa), L-PLL, and high (27.4kDa), H-PLL, Mw in free form and DNA-complexed cannot only cause rapid plasma membrane damage in human cell lines, phosphatidylserine “scrambling” and loss of membrane integrity, but later (24h) initiate stress-induced cell death via mitochondrial permeabilization without the involvement of processed caspase-2. Mitochondrially mediated apoptosis was confirmed by detection of cytochrome c (Cyt c) release, activation of caspases-9 and -3, and subsequent changes in mitochondrial membrane potential. Plasma membrane damage and apoptosis were most prominent with H-PLL. Cytoplasmic level of Cyt c was more elevated following H-PLL treatment, but unlike L-PLL case, inhibition of Bax channel-forming activity reduced the extent of Cyt c release from mitochondria by half. Inhibition of Bax channel-forming activity had no modulatory effect on L-PLL-mediated Cyt c release. Further, functional studies of isolated mitochondria indicate that H-PLL, but not L-PLL, can directly induce Cyt c release, membrane depolarization, and a progressive decline in the rate of uncoupled respiration. Combined, our data suggest that H-PLL and L-PLL are capable of initiating mitochondrially mediated apoptosis differently. The observed PLL-mediated late-phase apoptosis may provide an explanation for previously reported transient gene expression associated with PLL-based transfection vectors. The importance of our data in relation to design of novel and safer cationic non-viral vectors for human gene therapy is discussed. [Copyright &y& Elsevier]

Antidiabetic sulphonylureas can bind to various intracellular organelles including mitochondria. The aim of this study was to monitor the influence of antidiabetic sulphonylureas on membrane permeability in mitochondria isolated from rat skeletal muscle.The effects of glibenclamide (and other sulphonylurea derivatives) on mitochondrial function were studied by measuring mitochondrial swelling, mitochondrial membrane potential, respiration rate and Ca2+ transport into mitochondria.We observed that glibenclamide induced mitochondrial swelling (EC50=8.2±2.5 μM), decreased the mitochondrial membrane potential and evoked Ca2+ efflux from the mitochondrial matrix. These effects were blocked by 2 μM cyclosporin A, an inhibitor of the mitochondrial permeability transition.Moreover, 30 μM glibenclamide accelerated the respiratory rate in the presence of glutamate/malate, substrates of complex I of the mitochondrial respiratory chain.In conclusion, we postulate that the antidiabetic sulphonylureas activate the mitochondrial permeability transition in skeletal muscle by increasing its sensitivity to Ca2+.British Journal of Pharmacology (2005) 145, 785–791. doi:10.1038/sj.bjp.0706214; published online 16 May 2005 [ABSTRACT FROM AUTHOR]

Summary: Purpose: For the antiepileptic drug (AED) topiramate (TPM), neuroprotective effects have been reported in models of focal cerebral ischemia and experimental status epilepticus, but the putative mechanism of action has remained elusive. Methods: We studied the effects of TPM on mitochondrial function in the pilocarpine rat model of chronic epilepsy and in isolated mitochondria from rat brain. Results: TPM treatment in status epilepticus at doses ranging from 20 to 100 mg/kg considerably improved the survival of rats and improved CAl and CA3 pyramidal cell survival in a dose-dependent manner. This treatment increased the activity of mitochondrial respiratory chain complex I in the CAl and CA3 pyramidal sublields and resulted in lower seizure frequencies in chronic epileptic rats. In vitro investigations of the action of TPM on isolated rat brain mitochondria ruled out any direct effects of the drug on mitochondrial oxidative phosphorylation but revealed a protective effect on hippocampal mitochondria against an external calcium challenge. This can explain its observed neuroprotective action in the concentration range tested. The in vitro effects of TPM on the calcium handling of isolated brain mitochondria was found to be comparable to the action of cyclosporin A. Conclusions: The neuroprotective action of TPM seems to be directly related to its inhibitory effect on the mitochondrial permeability transition pore. [ABSTRACT FROM AUTHOR]

B ackground : Ozone as a strong oxidant may induce an inflammatory response. Aim : The hypothesis was verified as to whether ozonated autohemotherapy using an ozone dose in therapeutic range changes the plasma concentration of C-reactive protein and interleukin-6, markers of inflammation. Methods : In a controlled, single-blind, cross-over study, 12 chronically hemodialyzed patients with peripheral arterial disease were exposed to nine sessions of autohemotherapy with blood exposure to oxygen as a control followed by nine sessions of ozonated autohemotherapy with an ozone concentration of 50 μg/ml. Results : There was no statistical difference between C-reactive protein levels at baseline (1.53±1.01 mg/l), after nine sessions of control autohemotherapy (1.48±0.96 mg/l), and after nine sessions of ozonated autohemotherapy (1.55±0.84 mg/l). There was also no statistical difference between the interleukin-6 serum concentration at baseline (438±118 pg/ml), after nine sessions of control autohemotherapy (444±120 pg/ml), and after nine sessions of ozonated autohemotherapy (466±152 pg/ml). Conclusion : The results of this study suggest that ozonated autohemotherapy using an ozone concentration of 50 μg/ml does not induce an inflammatory response. [ABSTRACT FROM AUTHOR]

In the work, the design of experiments (DOE) method was used to obtain a modified epoxy resin of reduced fragility. As modifiers of commercial epoxy resin, urethane prepolymers with isocyanate terminal groups were used. Experimental points (samples of specified composition of resin prepolymer and a curing agent) were generated by the STATISTICA program module Design of Experiments using a central composition design. A study of the mechanical properties of modified resin samples was carried out for five intermediate values of input variables x1 (resin/hardener ratio) and x2 (modifier, wt %), designated for the normalized values 0, ± 1, and ±1.414. The STATISTICA algorithms analyzing the results of the practical implementation of the planned experiments allowed us to develop a model describing the dependence of the mechanical properties of composite resins on the composition and then to select the optimal compositions of epoxy resin for their practical applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46761. [ABSTRACT FROM AUTHOR]

An abstract of the article "Astrocytoma diagnosed in a fetus: a case report," by M. Debska and colleagues is presented.

An abstract of the article "Technical aspects of fetal cardiac interventions," by M. Debska and colleagues is presented.

An abstract of the article "Successful in utero treatment of primary fetal hypothyroidism with goiter and heart insufficiency," by M. Debska and colleagues is presented.

An abstract of the article "Management of fetal megacystis with a balloon catheter: a report of two cases," by M. Debska and colleagues is presented.

An abstract of the research paper "Prenatal diagnosis and treatment of alpha-thalassemia major" by M. Debska, P. Kretowicz, P. Turowski and others, presented at the 24th World Congress on Ultrasound in Obstetrics and Gynecology held in Barcelona, Spain from September 14-17, 2014, is presented.

An abstract of the article "Fetal balloon atrioseptostomy and interatrial stent: a single center experience" by M. Debska and others, is presented.

An abstract of the article "Prenatal ultrasound diagnosis of lissencephaly associated with Miller-Dieker syndrome: a case report," by M. Debska, P. Kretowicz, K. Muzyka, J. H. Dangel and R. Debski is presented.

An abstract of the article "Enlarged fetal thymus mimicking right-sided congenital diaphragmatic hernia," by S. Mista, M. Debska, P. Kretowicz, J. H. Dangel, A. Kolesnik, C. Niszczota, and R. Debski is presented.

An abstract of the article "Flow cytometry as a diagnostic tool in assessing fetal anemia caused by feto-maternal hemorrhage," by M. Debska, P. Kretowicz, A. Tarasiuk, R. Debski, J. Fabijanska-Mitek and A. Gielezynska is presented.

An abstract of the article "First trimester diagnosis of a 48,XXYY syndrome," by M. Debska, P. Kretowicz, R. Debski, and J. H. Dangel is presented.

An abstract of the article "Intrauterine platelet transfusion following fetal blood sampling in alloimmune thrombocytopenia: analysis of the safety of the procedure," by M. Debska, P. Kretowicz, R. Debski, J. Antoniewicz-Papis, K. Guz, K. Maslanka, M. Uhrynowska, and E. Brojer is presented.

An abstract of the article "Prenatal diagnosis of hemimegalencephaly and hydrops in a fetus with suspected tuberous sclerosis," by M. Debska, P. Kretowicz, K. Muzyka, R. Debski, and J. Witwicki is presented.

An abstract of the article "Cervical teratoma-differentiation from thyroid goiter," by M. Debska and colleagues is presented.

An abstract of the article "Early treatment in posterior urethral valve-does it change the prognosis?," by M. Debska and colleagues is presented.

An abstract of the article "Treatment of severe fetal and neonatal alloimmune thrombocytopenia caused by anti-HPA-3b antibodies in monochorionic diamniotic twin pregnancy: a case report," by M. Debska and colleagues is presented.

An abstract of the article "Pleuro-amniotic shunting in bronchopulmonary sequestration with fetal hydrops-outcome in three cases depending on gestational age on birth and size of the lesion," by M. Debska and colleagues is presented.

An abstract of the article "Successfully treated fetus and mother - a case of mirror syndrome as the complication of fetal PVB19 infection," by M. Debska and colleagues is presented.

An abstract of the conference paper "The twin anemia polycythemia sequence from a prenatal perspective" by L. Gucciardo and colleagues is presented.