Hand2 Immunohistochemistry in the Diagnosis of Paragangliomas and Other Neuroendocrine Neoplasms.

Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.

Fatty Acid Supplementation Affects Skin Wound Healing in a Rat Model.

Polyunsaturated fatty acids (PUFA) play an important role in reparative processes. The ratio of PUFAs n-3 to n-6 may affect wound healing. The study aimed to evaluate the effect of dietary supplementation with n-3 and n-6 PUFA in two proportions on skin wounds in laboratory rats. Adult male Wistar rats received 20% fat emulsion with a ratio of 1.4:1 (group A) or 4.3:1 (group B) for n-3:n-6 PUFAs at a daily dose of 1 mL/kg. The control group received water under the same conditions. The animals were supplemented a week before and a week after the skin excision performed on the back. The level of wound closure, various parameters of oxidative stress, and plasma fatty acids composition were evaluated. Wound tissue samples were examined by electron microscopy. The administration of fat emulsions led to significant changes in plasma polyunsaturated fatty acid composition. The increased production of reactive nitrogen species, as well as more numerous newly formed blood vessels and a greater amount of highly organized collagen fibrils in both groups A and B may indicate more intensive healing of the skin wound in rats supplemented with polyunsaturated fatty acids in high n-3:n-6 ratio.

Golden Standard or Obsolete Method? Review of ECG Applications in Clinical and Experimental Context.

Cardiovascular system and its functions under both physiological and pathophysiological conditions have been studied for centuries. One of the most important steps in the cardiovascular research was the possibility to record cardiac electrical activity. Since then, numerous modifications and improvements have been introduced; however, an electrocardiogram still represents a golden standard in this field. This paper overviews possibilities of ECG recordings in research and clinical practice, deals with advantages and disadvantages of various approaches, and summarizes possibilities of advanced data analysis. Special emphasis is given to state-of-the-art deep learning techniques intensely expanded in a wide range of clinical applications and offering promising prospects in experimental branches. Since, according to the World Health Organization, cardiovascular diseases are the main cause of death worldwide, studying electrical activity of the heart is still of high importance for both experimental and clinical cardiology.

Three-Dimensional Finger Vein Recognition: A Novel Mirror-Based Imaging Device.

Finger vein recognition has evolved into a major biometric trait in recent years. Despite various improvements in recognition accuracy and usability, finger vein recognition is still far from being perfect as it suffers from low-contrast images and other imaging artefacts. Three-dimensional or multi-perspective finger vein recognition technology provides a way to tackle some of the current problems, especially finger misplacement and rotations. In this work we present a novel multi-perspective finger vein capturing device that is based on mirrors, in contrast to most of the existing devices, which are usually based on multiple cameras. This new device only uses a single camera, a single illumination module and several mirrors to capture the finger at different rotational angles. To derive the need for this new device, we at first summarise the state of the art in multi-perspective finger vein recognition and identify the potential problems and shortcomings of the current devices.

Di-4-ANEPPS Modulates Electrical Activity and Progress of Myocardial Ischemia in Rabbit Isolated Heart.

AIMS: Although voltage-sensitive dye di-4-ANEPPS is a common tool for mapping cardiac electrical activity, reported effects on electrophysiological parameters are rather. The main goals of the study were to reveal effects of the dye on rabbit isolated heart and to verify, whether rabbit isolated heart stained with di-4-ANEPPS is a suitable tool for myocardial ischemia investigation. METHODS AND RESULTS: Study involved experiments on stained (n = 9) and non-stained (n = 11) Langendorff perfused rabbit isolated hearts. Electrophysiological effects of the dye were evaluated by analysis of various electrogram (EG) parameters using common paired and unpaired statistical tests. It was shown that staining the hearts with di-4-ANEPPS leads to only short-term sporadic prolongation of impulse conduction through atria and atrioventricular node. On the other hand, significant irreversible slowing of heart rate and ventricular conduction were found in stained hearts as compared to controls. In patch clamp experiments, significant inhibition of sodium current density was observed in differentiated NG108-15 cells stained by the dye. Although no significant differences in mean number of ventricular premature beats were found between the stained and the non-stained hearts in ischemia as well as in reperfusion, all abovementioned results indicate increased arrhythmogenicity. In isolated hearts during ischemia, prominent ischemic patterns appeared in the stained hearts with 3-4 min delay as compared to the non-stained ones. Moreover, the ischemic changes did not achieve the same magnitude as in controls even after 10 min of ischemia. It resulted in poor performance of ischemia detection by proposed EG parameters, as was quantified by receiver operating characteristics analysis. CONCLUSION: Our results demonstrate significant direct irreversible effect of di-4-ANEPPS on spontaneous heart rate and ventricular impulse conduction in rabbit isolated heart model. Particularly, this should be considered when di-4-ANEPPS is used in ischemia studies in rabbit. Delayed attenuated response of such hearts to ischemia might lead to misinterpretation of obtained results.

Pathologies affect the performance of ECG signals compression.

The performance of ECG signals compression is influenced by many things. However, there is not a single study primarily focused on the possible effects of ECG pathologies on the performance of compression algorithms. This study evaluates whether the pathologies present in ECG signals affect the efficiency and quality of compression. Single-cycle fractal-based compression algorithm and compression algorithm based on combination of wavelet transform and set partitioning in hierarchical trees are used to compress 125 15-leads ECG signals from CSE database. Rhythm and morphology of these signals are newly annotated as physiological or pathological. The compression performance results are statistically evaluated. Using both compression algorithms, physiological signals are compressed with better quality than pathological signals according to 8 and 9 out of 12 quality metrics, respectively. Moreover, it was statistically proven that pathological signals were compressed with lower efficiency than physiological signals. Signals with physiological rhythm and physiological morphology were compressed with the best quality. The worst results reported the group of signals with pathological rhythm and pathological morphology. This study is the first one which deals with effects of ECG pathologies on the performance of compression algorithms. Signal-by-signal rhythm and morphology annotations (physiological/pathological) for the CSE database are newly published.

Secondary Metabolites of Plants as Modulators of Endothelium Functions.

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time-from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide-cyclic guanosine monophosphate activation, prostacyclin-cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.

Effects of implanting a long-term left ventricle assist device on post-transplant outcomes.

BACKGROUND: An increasing number of patients are receiving left ventricle assist devices as a bridge to heart transplantation. The aim of this study was to determine the difference between patients who received transplants from a left ventricle assist device and those who underwent heart transplantation without a prior left ventricle assist device implantation. MATERIAL AND METHODS: The study included patients who underwent heart transplantation in our institute between January 2010 and November 2018. The following clinical variables were evaluated: donor characteristics, patient's pre-transplant demographical data, post-transplant data, and patient survival. Cardiac allograft vasculopathy progression was prospectively examined (after 1 month and 12 months after heart transplantation) by coronary optical coherence tomography. We were interested in the difference in 1- and 5-year survival between the left ventricle assist device and non-left ventricle assist device groups. RESULTS: A total of 248 patients were identified; out of them, 48 patients received a left ventricle assist device before heart transplantation, whereas 200 had transplants with no prior left ventricle assist device implantation. There were no significant differences in any donor characteristics. The mean duration of cardiopulmonary bypass time in the non-left ventricle assist device group was 156 versus 175 min in the left ventricle assist device group (p = 0.009), blood loss was 650 versus 1045 mL (p < 0.001), the need to implant an extracorporeal membrane oxygenation was 10% versus 23% (p = 0.02). There was no difference in cardiac allograft vasculopathy progression between the groups 1 year after heart transplantation (p = 0.528). The 1- and 5-year survival, according to Kaplan-Meier, was 80% and 70% in the left ventricle assist device group, compared to 80% and 73%, respectively, in the non-left ventricle assist device group (Log-rank test: p = 0.945). CONCLUSION: Our results indicate that patients undergoing heart transplantation from left ventricle assist devices suffer significantly more from intraoperative and post-operative complications; however, only insignificant cardiac allograft vasculopathy progression and survival differences between the two groups were observed.

Complex study on compression of ECG signals using novel single-cycle fractal-based algorithm and SPIHT.

Compression of ECG signal is essential especially in the area of signal transmission in telemedicine. There exist many compression algorithms which are described in various details, tested on various datasets and their performance is expressed by different ways. There is a lack of standardization in this area. This study points out these drawbacks and presents new compression algorithm which is properly described, tested and objectively compared with other authors. This study serves as an example how the standardization should look like. Single-cycle fractal-based (SCyF) compression algorithm is introduced and tested on 4 different databases-CSE database, MIT-BIH arrhythmia database, High-frequency signal and Brno University of Technology ECG quality database (BUT QDB). SCyF algorithm is always compared with well-known algorithm based on wavelet transform and set partitioning in hierarchical trees in terms of efficiency (2 methods) and quality/distortion of the signal after compression (12 methods). Detail analysis of the results is provided. The results of SCyF compression algorithm reach up to avL = 0.4460 bps and PRDN = 2.8236%.

Calcium signaling affects migration and proliferation differently in individual cancer cells due to nifedipine treatment.

Several papers have reported that calcium channel blocking drugs were associated with increased breast cancer risk and worsened prognosis. One of the most common signs of breast tumors is the presence of small deposits of calcium, known as microcalcifications. Therefore, we studied the effect of dihydropyridine nifedipine on selected calcium transport systems in MDA-MB-231 cells, originating from triple negative breast tumor and JIMT1 cells that represent a model of HER2-positive breast cancer, which possesses amplification of HER2 receptor, but cells do not response to HER2 inhibition treatment with trastuzumab. Also, we compared the effect of nifedipine on colorectal DLD1 and ovarian A2780 cancer cells. Both, inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) and type 1 sodium calcium exchanger (NCX1) were upregulated due to nifedipine in DLD1 and A2780 cells, but not in breast cancer MDA-MB-231 and JIMT1 cells. On contrary to MDA-MB-231 and JIMT1 cells, in DLD1 and A2780 cells nifedipine induced apoptosis in a concentration-dependent manner. After NCX1 silencing and subsequent treatment with nifedipine, proliferation was decreased in MDA-MB-231, increased in DLD1 cells, and not changed in JIMT1 cells. Silencing of IP3R1 revealed increase in proliferation in DLD1 and JIMT1 cells, but caused decrease in proliferation in MDA-MB-231 cell line after nifedipine treatment. Interestingly, after nifedipine treatment migration was not significantly affected in any of tested cell lines after NCX1 silencing. Due to IP3R1 silencing, significant decrease in migration occurred in MDA-MB-231 cells after nifedipine treatment, but not in other tested cells. These results support different function of the NCX1 and IP3R1 in the invasiveness of various cancer cells due to nifedipine treatment.

Home-based training using neuromuscular electrical stimulation in patients on continuous ambulatory peritoneal dialysis: A pilot study.

There is ample evidence that maintenance of basic physical fitness through exercise training is crucial for patients with chronic renal insufficiency. Rehabilitation based on neuromuscular electrical stimulation (NMES) of thigh muscles has been shown to have many beneficial effects in patients with chronic diseases. It is likely that NMES could have beneficial effects also in patients on chronic ambulatory peritoneal dialysis (CAPD). NMES was applied for 20 weeks to 14 patients on CAPD, mean age 61.9 (8.7) years, using battery-powered stimulators (CEFAR-REHAB X2; Sweden) and self-adhesive electrodes 80 × 130 mm (PALS Platinum; Denmark). Stimulation characteristics: biphasic current, pulse width 400 µs, 8 seconds contraction-12 seconds relaxation, frequency modulation 40-60 Hz, and maximal intensity 60 mA. NMES was home-based and applied simultaneously to quadriceps muscles of both legs (2 × 30 min/day). Functional performance, muscle power (Fmax ), arterial stiffness (assessed by cardio-ankle vascular index-CAVI), and quality of life by KDQOL-SF evaluation was done at baseline and at the end of program. Home NMES improved significantly the main functional parameters: VO2peak /kg increased by +2.2 (1.6) mL O2 /kg/min (P < 0.002), peak workload by +0.1 (0.1) W/kg (P < 0.005), and distance walked in 6 MWT by +44.7 (58.4) m (P < 0.008). Only insignificant changes were observed in CAVI and Fmax . KDQOL-SF analysis showed significant improvement in seven parameters of QoL (P < 0.012-0.049). This pilot study is the first clinical report dealing with the use of NMES in patients on CAPD. The results demonstrate that an improvement of exercise capacity and QoL can be achieved by home-based NMES in CAPD patients.

Structural and Functional Magnetic Resonance Imaging of Dementia With Lewy Bodies.

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). Although diagnosis may be challenging, there is increasing evidence that the use of biomarkers according to 2017 revised criteria for diagnosis and management of dementia with Lewy bodies can increase diagnostic accuracy. Apart from nuclear medicine techniques, various magnetic resonance imaging (MRI) techniques have been utilized in attempt to enhance diagnostic accuracy. This chapter reviews structural, functional and diffusion MRI studies in DLB cohorts being compared to healthy controls, AD or dementia in Parkinson's disease (PDD). We also included relatively new MRI methods that may have potential to identify early DLB subjects and aim at examining brain iron and neuromelanin.

Haloperidol affects coupling between QT and RR intervals in guinea pig isolated heart.

Prolonged QT interval is an independent risk factor for development of ventricular arrhythmias. Haloperidol is one of the drugs inducing QT prolongation. Previous studies showed that haloperidol affects not only QT duration but also heart rate (RR interval). The present work focused on relationship between QT and RR and its changes under acute and chronic haloperidol administration. The study included 14 male guinea pigs divided into control and haloperidol-treated group. After 21-days administration of haloperidol or vehiculum, electrograms in isolated hearts were recorded. QT/RR and dQT/dRR coupling were calculated. Chronic haloperidol administration significantly decreases the coupling between QT and RR. Acute haloperidol exposure significantly decreases the dQT/dRR coupling in both treated and untreated guinea pig hearts. Flatter QT/RR relationship reveals a lack of QT adaptation to increased heart rate. It should be emphasized that in such situation ECG recording will not show significant QT prolongation evaluated according to clinical rules. However, if QT interval does not adapt to increased heart rate sufficiently, the risk of ventricular arrhythmias may be increased despite practically normal QT interval length. The results are supported by findings in biochemical analyses, which proved eligibility of the used model.

Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study.

BACKGROUND: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing. MATERIALS AND METHODS: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores. RESULTS: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053). CONCLUSION: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.

Haloperidol Affects Plasticity of Differentiated NG-108 Cells Through σ1R/IP3R1 Complex.

Haloperidol is an antipsychotic agent that primarily acts as an antagonist of D2 dopamine receptors. Besides other receptor systems, it targets sigma 1 receptors (σ1Rs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). Aim of this work was to investigate possible changes in IP3Rs and σ1Rs resulting from haloperidol treatment and to propose physiological consequences in differentiated NG-108 cells, i.e., effect on cellular plasticity. Haloperidol treatment resulted in up-regulation of both type 1 IP3Rs (IP3R1s) and σ1Rs at mRNA and protein levels. Haloperidol treatment did not alter expression of other types of IP3Rs. Calcium release from endoplasmic reticulum (ER) mediated by increased amount of IP3R1s elevated cytosolic calcium and generated ER stress. IP3R1s were bound to σ1Rs, and translocation of this complex from ER to nucleus occurred in the group of cells treated with haloperidol, which was followed by increased nuclear calcium levels. Haloperidol-induced changes in cytosolic, reticular, and nuclear calcium levels were similar when specific σ1 blocker -BD 1047- was used. Changes in calcium levels in nucleus, ER, and cytoplasm might be responsible for alterations in cellular plasticity, because length of neurites increased and number of neurites decreased in haloperidol-treated differentiated NG-108 cells.

ECG features and methods for automatic classification of ventricular premature and ischemic heartbeats: A comprehensive experimental study.

Accurate detection of cardiac pathological events is an important part of electrocardiogram (ECG) evaluation and subsequent correct treatment of the patient. The paper introduces the results of a complex study, where various aspects of automatic classification of various heartbeat types have been addressed. Particularly, non-ischemic, ischemic (of two different grades) and subsequent ventricular premature beats were classified in this combination for the first time. ECGs recorded in rabbit isolated hearts under non-ischemic and ischemic conditions were used for analysis. Various morphological and spectral features (both commonly used and newly proposed) as well as classification models were tested on the same data set. It was found that: a) morphological features are generally more suitable than spectral ones; b) successful results (accuracy up to 98.3% and 96.2% for morphological and spectral features, respectively) can be achieved using features calculated without time-consuming delineation of QRS-T segment; c) use of reduced number of features (3 to 14 features) for model training allows achieving similar or even better performance as compared to the whole feature sets (10 to 29 features); d) k-nearest neighbours and support vector machine seem to be the most appropriate models (accuracy up to 98.6% and 93.5%, respectively).

Effect of increased left ventricle mass on ischemia assessment in electrocardiographic signals: rabbit isolated heart study.

BACKGROUND: Detailed quantitative analysis of the effect of left ventricle (LV) hypertrophy on myocardial ischemia manifestation in ECG is still missing. The associations between both phenomena can be studied in animal models. In this study, rabbit isolated hearts with spontaneously increased LV mass were used to evaluate the effect of such LV alteration on ischemia detection criteria and performance. METHODS: Electrophysiological effects of increased LV mass were evaluated on sixteen New Zealand rabbit isolated hearts under non-ischemic and ischemic conditions by analysis of various electrogram (EG) parameters. To reveal hearts with increased LV mass, LV weight/heart weight ratio was proposed. Standard paired and unpaired statistical tests and receiver operating characteristics analysis were used to compare data derived from different groups of animals, monitor EG parameters during global ischemia and evaluate their ability to discriminate between unchanged and increased LV as well as non-ischemic and ischemic state. RESULTS: Successful evaluation of both increased LV mass and ischemia is lead-dependent. Particularly, maximal deviation of QRS and area under QRS associated with anterolateral heart wall respond significantly to even early phase (the 1st-3rd min) of ischemia. Besides ischemia, these parameters reflect increased LV mass as well (with sensitivity reaching approx. 80%). However, the sensitivity of the parameters to both phenomena may lead to misinterpretations, when inappropriate criteria for ischemia detection are selected. Particularly, use of cut-off-based criteria defined from control group for ischemia detection in hearts with increased LV mass may result in dramatic reduction (approx. 15%) of detection specificity due to increased number of false positives. Nevertheless, criteria adjusted to particular experimental group allow achieving ischemia detection sensitivity of 89-100% and specificity of 94-100%, respectively. CONCLUSIONS: It was shown that response of the heart to myocardial ischemia can be successfully evaluated only when taking into account heart-related factors (such as LV mass) and other methodological aspects (such as recording electrodes position, selected EG parameters, cut-off criteria, etc.). Results of this study might be helpful for developing new clinical diagnostic strategies in order to improve myocardial ischemia detection in patients with LV hypertrophy.

Impaired Baroreflex Function during Orthostatic Challenge in Patients after Spinal Cord Injury.

The level of spinal cord injury (SCI) affects baroreflex regulation of blood pressure. While a parasympathetic cardiac chronotropic effect is preserved, baroreflex response could be impaired by sympathetic dysfunction under the SCI level. This study was aimed to evaluate the baroreflex function in SCI patients by the analysis of causal interaction between systolic blood pressure (SBP) and inter-beat intervals (IBI). Blood pressure was continuously recorded in 13 cervical SCI patients (CSCI), nine thoracic SCI (ThSCI) and 13 able-bodied controls (Con) during two phases: sitting (PS) and orthostatic challenge (PO). Beat-to-beat SBP and IBI sequences were obtained from continuous blood pressure recording. Closed loop of SBP-IBI interaction was mathematically opened by bivariate autoregressive model; causal coherence and baroreflex sensitivity (BRS) were calculated in baroreflex direction. Coherence quantifies causal synchronicity between SBP and IBI. The gain of transfer function from SBP to IBI represents BRS. PS (medians of CSCI/ThSCI/Con) coherence was 0.28/0.33/0.25 (no significant difference) and PS BRS was 6.98/7.54/6.66 (no difference). PO coherence was 0.18/0.58/0.45 (CSCI < ThCSI and Con; p < 0.01) and PO BRS was 2.38/5.87/6.22 (CSCI < ThCSI and Con; p < 0.01). For position change effect, there was no change in CSCI coherence; for ThSCI and Con, PS < PO (p < 0.05). For BRS in the CSCI group, PS < PO (p < 0.01); for ThSCI and Con, there was no change. BRS and coherence correlated negatively with SCI level (p < 0.01). In conclusion, baroreflex dysfunction in SCI patients was detected using causal analysis methods during orthostatic challenge only. Baroreflex dysfunction is probably an important mechanism of the more expressed blood pressure decrease associated with CSCI. The severity of autonomic dysfunction was related to SCI level.

Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression.

BACKGROUND: Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed. METHODS: Amino acid profiles were examined using an ion-exchange liquid chromatography. Intracellular zinc content was measured by atomic absorption spectrometry. Metallothionein was quantified using differential pulse voltammetry. The content of reduced glutathione was determined using high performance liquid chromatography coupled with an electrochemical detector. Cellular antioxidant capacity was determined by the ABTS test and gene expression analysis was performed by qRT-PCR. RESULTS AND CONCLUSIONS: Long-term zinc treatment was shown to reroute cell metabolism from benign to more malignant type. Long-term application of high concentration of zinc(II) significantly enhanced cisplatin resistance, invasiveness, cellular antioxidant capacity, synthesis of glutathione, and expression of treatment resistance- and stemness-associated genes (SOX2, POU5F1, BIRC5). Tumorous cell lines universally displayed high accumulation of aspartate and sarcosine and depletion of essential amino acids. Increased aspartate/threonine, aspartate/methionine, and sarcosine/serine ratios were associated with cancer phenotype with high levels of sensitivity and specificity. Prostate 77: 604-616, 2017. © 2017 Wiley Periodicals, Inc.

Reduction of Doxorubicin-Induced Cardiotoxicity Using Nanocarriers: A Review.

BACKGROUND: Anthracycline antibiotic doxorubicin (DOX) is a very potent and extensively prescribed chemotherapeutic drug. It is widely utilized in the therapy of variety of haematological and solid tumours, although its administration is commonly accompanied with several severe side effects. The most serious one is a development of dose-dependent and cumulative cardiotoxicity. In the course of time, many strategies have been investigated in order to avoid or at least to diminish DOX-induced cardiac dysfunction; these include reduction of toxic effect by coadministration with iron chelators (dexrazoxane), trastuzumab, taxanes, statins, and ACE-inhibitors. However, the attenuation of cardiotoxic effect is still not satisfactory yet. OBJECTIVE: This review represents an overall appraisal of studies concerning with the utilization of various doxorubicinloaded nanoparticles in the cancer treatment with specific emphasis on those studies evaluating their influence on the reduction of heart tissue damage. CONCLUSION: Introduction of nanoscale drug delivery systems undoubtedly represents nowadays one of the most promising tools for lowering systemic toxicity. Nanoparticles enable to target the therapeutic payload directly towards the tumor tissue, thus leading to the increased accumulation of the drug in the desired tissue and simultaneously protecting surrounding healthy tissues.