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Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with largely unknown pathogenesis and no effective cure. It is believed that several, not mutually exclusive mechanisms contribute to the pathogenesis and progression of this disease, including, among others, elevated oxidative stress, excitotoxicity, increased neuroinflammation, and protein aggregation. Receptor for advanced glycation end products (RAGE) is a part of immunoglobulin superfamily; it is believed to participate in ALS pathogenesis., Objectives: Our previous studies on ALS demonstrated that RAGE is likely one of the key players in ALS, acting on its own and in tandem with its oxidative stress and pro-inflammatory ligands, such as advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs). In this study, based on our previous results, we aimed to establish blood levels of soluble RAGE, AGE and AOPP in ALS patients., Material and Methods: Forty-six coded and anonymized surplus plasma samples from ALS patients and non-neurological control were used in the study. The plasma levels of RAGE, AGE and AOPP were measured using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Statistical evaluation of data was performed using one-way non-parametric analysis of variance (ANOVA) with Kruskal-Wallis post hoc test., Results: Our results revealed a decline in soluble RAGE level, concurrent with an increase in the levels of AGEs and AOPPs in blood samples from ALS patients, signifying a loss of neuroprotective form of RAGE and a simultaneous increase in AGE and AOPP production and uptake at the early stage of the disease., Conclusions: The results obtained from our study indicate that further longitudinal study of RAGE, AGE and AOPP levels would be beneficial, outlining the dynamics between RAGE and its ligand levels as the disease progresses, and making them valuable diagnostic tools and potential therapeutic targets.

The effects of severe burn injuries on the cardiovascular system, specifically the atria and auricles of the heart, were investigated. The potential benefits of using lyophilized xenodermotransplants as a treatment option were also evaluated. The experiments were conducted on adult guinea pigs divided into three groups: intact animals, animals with burns, and animals with burns who underwent early necrectomy followed by wound closure with lyophilized xenodermotransplants. Third-degree burns caused significant ultrastructural changes in atrial cardiomyocytes, leading to long-term destructive changes in the structural components of the atria. However, the use of lyophilized xenodermotransplants had a positive effect on the atrial ultrastructure over time. This study highlights the complex and varied effects of burn injuries on the body and the potential benefits of lyophilized xenodermotransplants in treating severe burn injuries. By preventing destructive changes in the heart and activating regenerative processes, lyophilized xenodermotransplants can improve the condition of the heart after thermal injury. Further research and development in this area are necessary for understanding the potential of lyophilized xenodermotransplants in tissue repair and regeneration.

Articular cartilage has very low metabolic activity. While minor injuries may be spontaneously repaired within the joint by chondrocytes, there is very little chance of a severely impaired joint regenerating itself when damaged. Therefore, any significant joint injury has little chance of spontaneously healing without some type of therapy. This article is a review that will examine the causes of osteoarthritis, both acute and chronic, and how it may be treated using traditional methods as well as with the latest stem cell technology. The latest regenerative therapy is discussed, including the use and potential risks of mesenchymal stem cells for tissue regeneration and implantation. Applications are then discussed for the treatment of OA in humans after using canine animal models. Since the most successful research models of OA were dogs, the first applications for treatment were veterinary. However, the treatment options have now advanced to the point where patients suffering from osteoarthritis may be treated with this technology. A survey of the literature was performed in order to determine the current state of stem cell technology being used in the treatment of osteoarthritis. Then, the stem cell technology was compared with traditional treatment options.

This review focuses on receptor for advanced glycation endproducts/diaphonous related formin 1 (RAGE/Diaph1) interaction as a modulator of actin cytoskeleton dynamics in peripheral nervous system (PNS) in diabetes. Deciphering the complex molecular interactions between RAGE and Diaph1 is crucial in expanding our understanding of diabetic length dependent neuropathy (DLDN). DLDN is a common neurological disorder in patients with diabetes. It is well known that actin cytoskeletal homeostasis is disturbed during DLDN. Thus, we review the current status of knowledge about RAGE/Diaph1 impact on actin cytoskeletal malfunctions in PNS and DLDN progression in diabetes. We also survey studies about small molecules that may block RAGE/Diaph1 axis and thus inhibit the progression of DLDN. Finally, we explore examples of cytoskeletal long-non coding RNAs (lncRNAs) currently unrelated to DLDN, to discuss their potential role in this disease. Most recent studies indicated that lncRNAs have a great potential in many research areas, including RAGE/Diaph1 axis as well as DLDN. Altogether, this review is aimed at giving us an insight into the involvement of cytoskeletal lncRNAs in DLDN., (© 2023 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

One of the most common cyclitols found in eukaryotic cells-Myo-inositol (MI) and its derivatives play a key role in many cellular processes such as ion channel physiology, signal transduction, phosphate storage, cell wall formation, membrane biogenesis and osmoregulation. The aim of this paper is to characterize the possibility of neurodegenerative disorders treatment using MI and the research of other therapeutic methods linked to MI's derivatives. Based on the reviewed literature the researchers focus on the most common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Spinocerebellar ataxias, but there are also works describing other seldom encountered diseases. The use of MI, d-pinitol and other methods altering MI's metabolism, although research on this topic has been conducted for years, still needs much closer examination. The dietary supplementation of MI shows a promising effect on the treatment of neurodegenerative disorders and can be of great help in alleviating the accompanying depressive symptoms.

Epilepsy, with about 70 million affected people worldwide, is one of the biggest challenges of medicine today. It is estimated that about one-third of epileptic patients receive inadequate treatment. Inositols have proved effective in many disorders; hence, in the current study, we tested potential antiepileptic properties of scyllo-inositol (SCI)-one of the most common commercially available inositols-in zebrafish larvae with pentylenetetrazol-induced seizures. First, we studied the general effect of SCI on zebrafish motility, and then we tested SCI antiepileptic properties over short (1 h) and long (120 h) exposure protocols. Our results demonstrated that SCI alone does not reduce zebrafish motility regardless of the dose. We also observed that short-term exposure to SCI groups reduced PTZ-treated larva motility compared to controls ( p < 0.05). In contrast, prolonged exposure did not produce similar results, likely due to the insufficient concentration of SCI given. Our results highlight the potential of SCI use in epilepsy treatment and warrant further clinical studies with inositols as potential seizure-reducing drugs.

Myo -inositol is the most popular inositol in living organisms, where it is present as a sugar alcohol, in a free form, and can also be described as a lipid. The aim of this study was to check the concentration change of a myo-inositol solution from the time of oral administration and over a 48 h period in Wistar-type rats. All rats received 2 g/kg of inositol as a solution in distilled water by oral gavage. Estimated parameters were based on the serum concentration of myo-inositol observed in nine individual rats with regard to time. Observations were described as a one-compartment pharmacokinetic model with first-order absorption and zero-order endogenous input of checked inositol. The highest myo-inositol concentration was observed in the first hour after oral administration in the serum of all tested rats. Then, the concentration began decreasing immediately after the maximal peak. The inositol concentration continued to decrease, but after 24 h its level was still higher than before the administration. The plasma profile of the myo-inositol concentration showed a rapid decline over time, possibly due to the metabolism of this compound.

BACKGROUND Bisphenol A (BPA) and its analogue bisphenol S (BPS), widely utilized in numerous fields of industry, may seep into the environment and into human organisms. Hitherto, BPA was regarded as the bisphenol to which people were exposed to the greatest extent. As endocrine disruptors, bisphenols have negative effects on human health. Therefore, defining the levels of human exposure to these compounds is a key issue in toxicology. Hair analysis has been increasingly used for biomonitoring of bisphenols in humans, but information about the coexistence of BPA and BPS in human hair is extremely scarce. The present study aimed to analyze hair samples from 25 individuals from Olsztyn, northeastern Poland, to evaluate the levels of these 2 industrial pollutants. MATERIAL AND METHODS The method used in the research was liquid chromatography with a mass spectrometry technique. RESULTS BPA was found in 72% of samples analyzed and its concentration levels fluctuated from 3.6 to 52.9 ng/g (median 17.7 ng/g). The BPS concentration levels were higher - from 13.4 to 1054.9 ng/g (median 98.7 ng/g). We also found that gender, age, and the presence of artificial hair color (hair dye) did not affect the BPA and BPS levels in the hair. CONCLUSIONS This study has shown that hair samples may be used to measure the levels of bisphenols, and that exposure to BPS may be greater than that to BPA in this area. The investigation also revealed that hair analysis is a useful approach for the biomonitoring of BPA and BPS levels in human organisms.

Introduction: The response to the COVID-19 pandemic by anesthesiologists has been simply heroic. Unfortunately, there are very few evidence-based studies in the literature that focus on anesthesiologists' burnout during that time. The purpose of our study was to examine the psychological distress, after the COVID-19 pandemic, among anesthesiologists in Poland., Methods: We conducted an anonymous internet survey among a group of anesthesiologists in Poland. It contained a questionnaire, entitled "Oldenburg Burnout Inventory (OLBI)", with demographic questions about sex, age, and family, as well as questions related to working conditions during the COVID-19 pandemic. We received data from 158 people, including 109 women and 49 men., Results: Results from the analysis showed that 73% (115/158) of the participants suffered from burnout. Moreover, 95.6% of the participants thought that the COVID-19 pandemic had had an influence on their level of burnout, and 97.3% found that it had had a negative impact., Conclusions: There is no doubt that healthcare workers, despite the difficulties associated with their daily work, have not faced challenges on such a scale in a very long time. Support for their mental health should be an essential component of the modern public healthcare system.

Current data indicate that heart failure (HF) is associated with inflammation and microvascular dysfunction and remodeling. These mechanisms could be involved in HF development and progression, especially in HF with preserved ejection fraction (HFpEF). We aimed to compare structural changes in retinal arterioles and carotid arteries between HF patients and patients without heart failure. This preliminary, retrospective, case-control study included 28 participants (14 patients with HFpEF and 14 age- and sex-matched healthy controls). Carotid intima-media thickness to lumen ratio (cIMTLR) was assessed using B-mode ultrasonography. Retinal arterioles wall- to-lumen ratio (rWLR) was assessed by adaptive optics camera rtx1. The HF patients had higher IMTLR (Δ median [HFpEF-control group] 0.07, p = 0.01) and eWLR (Δ median 0.03, p = 0.001) in comparison to patients without HF. In the whole study group, rWLR correlated significantly with IMTLR (r = 0.739, p = 0.001). Prevalence of arterial hypertension was similar in both groups, however, patients with HF had a significantly lower office, central and 24-h ambulatory blood pressure (systolic Δ median -21 to -18 mmHg; diastolic Δ median -23 to -10 mmHg). Our data suggests gradual and simultaneous progression of vascular remodeling in both retinal arterioles and carotid arteries in HFpEF patients. This process could be a marker of HF development. Significantly lower blood pressure values in HF group may indicate that vascular remodeling could be independent of BP control. Nevertheless, further and larger prospective studies allowing to reduce the impact of confounding and address temporality are warranted.

Triclosan (TCS) is an organic substance showing antibacterial action, which is commonly used in many branches of industry, including, among others, cosmetics, pharmaceuticals and the food industry. TCS may penetrate into living organisms and negatively affect the health of humans and animals. The majority of previous investigations on TCS biomonitoring in humans have been performed on urine, but currently, studies on hair samples are becoming increasingly important. The aim of this study was to evaluate TCS concentration levels in residents of Olsztyn, a city in northeastern Poland, using a liquid chromatography-mass spectrometry technique. The presence of TCS was observed in 96.7% of samples tested, with concentration levels from 37.9 pg/mg to 3386.5 pg/mg. The mean concentration level of TCS in the present study was 402.6 (±803.6) pg/mg, and the median value was 103.3 pg/mg. Although there were some differences in TCS concentration levels between males and females, humans of various ages and humans with colored and natural hair had no statistically significant differences in TCS concentration levels. The obtained results have clearly indicated that people living in northeastern Poland are exposed to TCS to a large degree, and hair analysis, despite some limitations, is a suitable method for TCS biomonitoring in humans.

Parabens (PBs) are a group of substances commonly used in industry. They also pollute the environment, penetrate into living organisms and adversely affect various internal organs. During this study, the degree of exposure of people living in Olsztyn, a city in north eastern Poland, to selected parabens most often used in industry was studied. The chemicals under investigation included: methyl paraben-MePB, ethyl paraben-EtPB, propyl paraben-PrPB, benzyl paraben BePB and butyl paraben -BuPB. To this aim, hair samples collected from the scalps of 30 volunteers were analyzed using a liquid chromatography-mass spectrometry technique. All PBs studied were present in a high percentage of analyzed samples (from 76.7% in the case of BePB to 100% in the case of MePB and PrPB). The mean concentration levels were 4425.3 pg/mg for MeBP, 704.0 pg/mg for EtPB, 825.7 pg/mg for PrPB, 135.2 pg/mg for BePB and 154.5 pg/mg for BuPB. Significant differences in PB concentration levels between particular persons were visible. On the other hand, gender, age and artificial hair coloring did not cause statistically significant differences in PB levels. Obtained results have clearly indicated that people living in north eastern Poland are exposed to various PBs, and therefore these substances may affect their health status. However, the evaluation of PBs influence on human health requires further research., (© 2021. The Author(s).)

Abstract: The use of local antibiogram in guiding clinical decisions is an integral part of the antimicrobial stewardship program. Conventional antibiograms are not disease-specific, ignore the distribution of microorganisms, obscure the in-vitro efficacy interrelationships, and have limited use in polymicrobial infections.We aimed to develop an in-house empiric, disease-specific, antimicrobial prescription auxiliary for the treatment of hospitalized pediatric pneumonia patients and to present the methods which help to choose the first and the second line antimicrobial therapy, while accounting for cost and safety aspects.A retrospective single center observational study was conducted on bronchoscopy obtained sputum culture. Analysis of probabilities, variance minimization, Boolean network modeling, and dominance analysis were applied to analyze antibiogram data. The Kirby-Bauer disk diffusion method was used to test the susceptibility of all isolates. Final optimization analysis included local drug acquisition cost (standardized to price per DDD) and safety profile.Data of 145 pediatric patients hospitalized with pneumonia with 218 isolates over 5 years was collected. A combination of statistical methods such as probabilities of drug efficacy, variance minimization, Boolean network modeling, and dominance analysis can help to choose the optimal first-line and the second-line antimicrobial treatment and optimize patient care. This research reveals that ampicillin is the optimal choice as the first-line drug and piperacillin-tazobactam is the second-line antimicrobial drug if the first one is not effective, while accounting for cost and safety aspects.The paper proposes a new methodology to adapt empiric antimicrobial therapy recommendations based on real world data and accout for costs and risk of adverse events., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Lipopolysaccharides (LPS), also known as lipoglycans or endotoxins, form part of the outer membrane of Gram-negative bacteria. Previous studies have described the various harmful impacts of LPS on humans and animals. Nevertheless, many aspects of these effects are still not fully explained. One of them is the influence of endotoxins on the neurochemical characterization of neurons within the enteric nervous system (ENS), which is found in the intestinal wall and plays important adaptive roles during pathological processes and exposures. In this study, the impact of a low single dose of Salmonella Enteritidis LPS on the duodenal enteric neurons immunoreactive to substance P (SP), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating peptide (PACAP-27), and cocaine- and amphetamine-regulated transcript (CART) was studied using a double immunofluorescence technique. During the study, it was shown that even a low dose of LPS affects the number of enteric neurons containing the neuropeptides studied, and these changes were dependent on the type of the enteric plexus. The most visible changes concerned the SP-like immunoreactive (LI) neurons in the outer submucous plexus (LPS caused an increase in the percentage of these neurons from15.74 ± 0.61 to 21.72 ± 0.79%). Furthermore, the VIP-LI neurons in the inner submucous plexus were seen to decrease from 12.64 ± 0.83 to 5.96 ± 0.58%. The mechanisms behind these noted fluctuations are not clear, but it may be connected with the pro-inflammatory and neurotoxic activity of LPS., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons and grim prognosis. Over the last decade, studies on neurodegenerative diseases pointed on the role of glia in supporting the proper function of neurons. Particularly, oligodendrocytes were shown to be essential through myelin production and supplying axons with energy metabolites via monocarboxylate transporters (MCT). We have used dogs with naturally occurring degenerative myelopathy (DM) which closely resembles features observed in human ALS. We have performed two types of analysis of spinal cord tissue samples: histology and molecular analysis. Histology included samples collected from dogs that succumbed to the DM at different disease stages, which were compared to age-matched controls as well as put in the context of young spinal cords. Molecular analysis was performed on spinal cords with advanced DM and age-matched samples and included real-time PCR analysis of selected gene products related to the function of neurons, oligodendrocytes, myelin, and MCT. Demyelination has been detected in dogs with DM through loss of eriochrome staining and decreased expression of genes related to myelin including MBP, Olig1, and Olig2. The prominent reduction of MCT1 and MCT2 and increased MCT4 expression is indicative of disturbed energy supply to neurons. While Rbfox3 expression was not altered, the ChAT production was negatively affected. DM in dogs reproduces main features of human ALS including loss of motor neurons, dysregulation of energy supply to neurons, and loss of myelin, and as such is an ideal model system for highly translational studies on therapeutic approaches for ALS.

Intervertebral disc diseases (IVDDs) form a group of a vertebral column disorders affecting a large number of people worldwide. It is estimated that approximately 30% of individuals at the age of 35 and approximately 90% of individuals at the age of 60 and above will have some form of disc-affecting pathological changes leading to disc herniation, prolapse and degeneration as well as discogenic pain. Here, we aimed to establish the origins and neurochemical characteristics of porcine intervertebral disc sympathetic innervation involved in pain signalling in IVDD patients. Pigs were given an injection of the Ominipaque contrast agent and Fast Blue (FB) retrograde tracer into the L 4 -L 5 intervertebral disc and euthanized at 2, 1, and 3 months post injection. Following euthanasia, bilateral sympathetic chain ganglia (SChG) Th 13 to C 1 were collected. The presence, distribution and neurochemical characteristics of retrogradely labelled SChG neurons were examined. The majority (88.8%) of all FB+ cells were found in the L 3 -L 5 SChG. Most FB+ neurons stained for dopamine beta hydroxylase (DBH); one-third to one-quarter stained for somatostatin (SOM), neuropeptide Y (NPY) or leu-enkephalin (LENK); and only a few stained for galanin (GAL). Compared with the control, the greatest decline in neurochemical immunostaining was observed 2 weeks post injection, and the lowest decline was noticed 1 month post injection. Our study, for the first time, provides insight into the complex patterns of intervertebral disc sympathetic innervation and suggests that the best time for neurochemical balance restoration therapy would be 1 month post-injury, when the neuronal concentration of all studied substances is close to the initial physiological level, thus providing favourable conditions for successful recovery.

Background: Non-small cell lung cancer (NSCLC) is a very aggressive and histologically heterogeneous type of lung cancer. The main problem in the treatment of NSCLC is chemoresistance and metastasis. Compared to other malignant tumors, many molecular mechanisms are dysfunctional in NSCLC. Epidermal growth factor receptor (EGFR) is one of the most frequently mutated genes in NSCLC., Materials and Methods: We investigated the effect of afatinib the against A549 NSCLC cell line, because it is active against mutated EGFR. Moreover, we aimed to investigate the mRNA level of HSPA5 (one of the heat shock proteins that can contribute in the down-regulation of the EGF-signaling pathway) before and after afatinib treatment., Results: Afatinib treatment induced apoptosis and decreased levels of HSPA5 mRNA in cancer cells., Conclusion: Advanced analysis, might be helpful in understanding the mechanisms of relations between tyrosine kinase inhibition of EGFR and HSPA5 in lung cancer cells., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Stem cell therapy for neurological disorders reached a pivotal point when the efficacy of several cell types was demonstrated in small animal models. Translation of stem cell therapy is contingent upon overcoming the challenge of effective cell delivery to the human brain, which has a volume ∼1000 times larger than that of the mouse. Intra-arterial injection can achieve a broad, global, but also on-demand spatially targeted biodistribution; however, its utility has been limited by unpredictable cell destination and homing as dictated by the vascular territory, as well as by safety concerns. We show here that high-speed MRI can be used to visualize the intravascular distribution of a superparamagnetic iron oxide contrast agent and can thus be used to accurately predict the distribution of intra-arterial administered stem cells. Moreover, high-speed MRI enables the real-time visualization of cell homing, providing the opportunity for immediate intervention in the case of undesired biodistribution.

Zinc transporter 3 (ZnT3) is one of the zinc transporters family. It is closely connected to the nervous system, where enables the transport of zinc ions from the cytoplasm to synaptic vesicles. This substance has been described within the central and peripheral nervous system, especially in the enteric nervous system (ENS). The aim of the present study was to describe the co-localization of ZnT3 with selected neuromediators and/or neuromodulators participating in sensory stimuli conduction in neurons of the ENS within the porcine esophagus. Co-localization of ZnT3 with substance P (SP), leucine enkephalin (LENK) and calcitonin gene-related peptide (CGRP) was studied using standard double-immunofluorescence technique. The obtained results show that ZnT3, SP and/or LENK may occur in the same enteric neurons, and the degree of co-localization of these substances clearly depends on the fragment of esophagus studied and the type of enteric ganglia. In contrast, the co-localization of ZnT3 with CGRP was not observed during the present investigation. The obtained results suggest that ZnT3 in the ENS may be involved in the conduction of sensory and/or pain stimuli.

Zinc transporter 3 (ZnT3), a member of the SLC 30 zinc transporter family, is involved in the transport of zinc ions from the cytoplasm into synaptic vesicles or intracellular organelles. The aim of the present study was to investigate for the first time the percentage of ZnT3-like immunoreactive (ZnT3-LI) neurons in the enteric nervous system (ENS) of the porcine esophagus and denotation of their neurochemical coding. Routine double- and triple-immunofluorescence labeling of cervical, thoracic, and abdominal fragments of esophagus for ZnT3 with protein gene product (PGP 9.5; used as pan-neuronal marker), nitric oxide synthase (NOS), somatostatin, vasoactive intestinal peptide (VIP), vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), and galanin (GAL) was performed. The percentage of ZnT3-LI neurons in myenteric ganglia amounted to 50.2 ± 4.7, 63.4 ± 8.3, and 77.1 ± 1.1 % of all PGP 9.5-like immunoreactive neuronal cells in cervical, thoracic, and abdominal esophagus, respectively. In submucous ganglia, these values in particular parts of esophagus amounted to 46.3 ± 6.3, 81.0 ± 8.1, and 74.4 ± 4.4 %. Znt3 co-localized mainly with VAChT, NPY, GAL, NOS, and VIP, but the degree of co-localization depended on the "kind" of enteric ganglia and part of esophagus studied. The obtained results suggest that both ZnT3 and zinc ions may play important and various roles in the neuronal regulation of esophageal functions.

Human T-cell leukemia virus type 1 (HTLV-I) is associated with adult T-cell leukemia (ATL), an aggressive lymphoproliferative disease with a dismal prognosis. We have previously described the presence of Notch1 activating mutations and constitutive Notch1 signaling in patients with acute ATL. In this study, we report a high frequency of F-box and WD repeat domain containing 7 (FBXW7)/hCDC4 mutations within the WD40 substrate-binding domain in 8 of 32 acute ATL patients (25%). Functionally, ATL FBXW7 mutants lost their ability to interact with intracellular Notch (NICD), resulting in increased protein stability and constitutive Notch1 signaling. Consistent with the loss-of-function found in ATL patients, expression of WT FBXW7 in several patient-derived ATL lines demonstrated strong tumor-suppressor activity characterized by reduced proliferation of ATL cells. Remarkably, two FBXW7 mutants, D510E and D527G, demonstrated oncogenic activity when expressed in the presence of HTLV-I Tax, mutated p53 R276H, or c-Myc F138C found in human cancers. Transforming activity was further demonstrated by the ability of the FBXW7 D510E mutant to provide IL-2-independent growth of Tax-immortalized human T cells and increase the tumor formation in a xenograft mouse model of ATL. This study suggests that FBXW7, normally a tumor suppressor, can act as an oncogene when mutated and may play an important role in the pathogenesis of ATL.

The superior cervical ganglion (SCG) is a center of sympathetic innervation of all head and neck organs. SCG sympathetic preganglionic neurons (SPN) were found in the nucleus intermediolateralis pars principalis (IMLpp), the nucleus intermediolateralis pars funicularis (IMLpf), the nucleus intercalatus spinalis (IC), and the nucleus intercalatus spinalis pars paraependymalis (ICpe). Despite its importance, little is known of SCG innervation and chemical coding in the laboratory pig, a model that is physiologically and anatomically representative of humans. Here in our study, we established the distribution and chemical coding of Fast Blue (FB) retrogradely labelled SPN innervating porcine SCG. After unilateral injection of FB retrograde tracer into the left SCG, labeled neurons were found solely on the ipsilateral side with approximately 98% located in Th1-Th3 segments and predominantly distributed in the IMLpp and IMLpf. Neurochemical analysis revealed that approximately 80% of SPN were positive both to choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) and were surrounded by a plethora of opioidergic and peptiergic nerve terminals. The results of our study provide a detailed description of the porcine preganglionic neuroarchitecture of neurons controlling the SCG, setting the stage for further studies concerning SPN plasticity under experimental/pathological conditions.

The aim of the present study was to establish the origin of the motor, autonomic and sensory innervation of the L1-L2 segment of the porcine longissimus dorsi muscle (LDM), in order to provide morphological basis for further studies focusing on this neural pathway under experimental conditions, e.g. phototerapy and/or lateral electrical surface stimulation. To reach the goal of the study, multiple injections of the fluorescent neuronal tracer Fast Blue (FB) were made into the LDM region between the spinal processes of the vertebrae L1 and L2. The spinal cord (Th13-S1 segments) as well as the sensory and autonomic ganglia of interest, i.e., dorsal root (DRG) and sympathetic chain ganglia from corresponding spinal cord levels were collected three weeks later. FB-positive (FB+) motoneurons were observed exclusively within the nucleus ventromedialis at L1 and L2 spinal cord level, forming the most ventro-medially arranged cell column within this nucleus. Primary sensory and sympathetic chain neurons were found in appropriate ipsilateral ganglia at Th15-L3 levels. The vast majority of retrogradely traced neurons (virtually all motoneurons, approximately 76% of sensory and 99.4% of sympathetic chain ganglia neurons) was found at the L1 and L2 levels. The morphometric evaluation of FB-labeled DRG neurons showed that the majority of them (approximately 66%) belonged to the class of small-diameter perikarya (10-30 microm in diameter), whereas those of medium size (30-80 microm in diameter) and of large diameter (more than 80 microm) constituted 22.6% and 11.5% of all DRG neurons, respectively. The results of the present study demonstrated that the nerve terminals supplying porcine LDM originated from different levels of the spinal cord, dorsal root and sympathetic chain ganglia. Thus, the study has revealed sources and morphological characteristic of somatic, autonomic and spinal afferent neurons supplying porcine LDM, simultaneously pointing out the characteristic features of their distribution pattern.

We studied both morphology and steroidogenic activity of ovaries in gilts after bilateral surgical denervation performed on day 3 of the estrous cycle. Blood samples were collected from day 4 of the first estrous cycle to day 11 of the subsequent cycle. Denervation resulted in a dramatic reduction in the number or in the disappearance of tyrosine hydroxylase/dopamine-beta-hydroxylase- and/or neuropeptide Y-immunoreactive nerve fibres. On day 11 of the second cycle, the number of follicles (3-6 mm in diameter) was lower (p<0.001) in the denervated ovaries, while corpora lutea were not present. Neurectomy also led to a decrease in the concentrations of progesterone, androstendione and 17beta-estradiol in the follicular fluid originated from small (1-3 mm in diameter) as well as medium-sized follicles (3-6 mm in diameter). Similar to follicular fluid, concentration of androstendione in the follicular wall of medium-sized follicles decreased in experimental gilts in comparison to that of control animals. In addition, plasma concentrations of LH and steroid hormones were lower in the control than in the experimental group. Our results show that denervation of ovaries during the early luteal phase of the estrous cycle in gilts resulted in the changes in both morphology and steroidogenic activity. These results confirm the important role of the peripheral nerves in the function of ovaries.

Lateral electrical surface stimulation is one of methods used in the therapy of the progressive form of idiopathic scoliosis (IS) in children and youth. However, there are data suggesting that this method may lead to serious adverse side effects, when used for a too long period of time per day. To clarify this issue, the present study was aimed at disclosing possible changes in the ultrastructural appearance of rabbit supraspinal muscles undergoing long-term stimulation (9 h per day, 3 months), an animal model successfully used to mimic the situation in humans. In comparison to the control animals, muscles of "overstimulated" rabbits exhibited clear signs of microscopical lesions, including depletion and disintegration of myofilaments, proliferation, dilatation and, sometimes, swelling of sarcoplasmic reticulum and/or mitochondria, as well as signs of destruction of the Z line. The above-mentioned abnormalities, especially the signs of degenerative processes associated with the Z line and the observed microlesions strongly suggest that the failure of the long-term LESS therapy of the IS may be attributable to these ultrastructural lesions.

The sympathetic nerve fibers originating from the superior cervical ganglia and supplying the pineal gland play the most important role in the control of the pineal activity in mammals. NPY and CPON are also present in the majority of the pinealopetal sympathetic neurons. In this study, immunohistochemical techniques were used to demonstrate the existence and coexistence of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH) as well as NPY and CPON in the nerve fibers supplying the chinchilla pineal gland. Ten two-year-old female chinchillas housed in natural light conditions were used in the study. The pineals were fixed by perfusion. ABC immunohistochemical technique and immunofluorescence labelling method were employed. TH-immunoreactive (TH-IR) varicose nerve fibers were observed in the pineal gland as well as in the posterior commissural area. Within the chinchilla pineal gland, TH-IR nerve fibers were located in the capsule and connective tissue septa. Numerous varicose TH-IR branches penetrated into the parenchyma and formed a network showing the highest density in the proximal region of the gland. In the central and distal parts of the pineal parenchyma, a subtle network, composed of thin varicose nerve branches, was observed. Double immunostaining revealed that the majority of TH-IR nerve fibers was positive for DbetaH or NPY. TH- and DbetaH-positive neuron-like cells were observed in the proximal region of the gland. The pattern of pineal innervation immunoreactive to CPON was similar to the innervation containing NPY, TH and DbetaH. The chinchilla intrapineal innervation containing TH, DbetaH, NPY and CPON is characterized by the higher density in the proximal part of the gland than in the middle and distal ones. The specific feature of the chinchilla pineal is also the presence of single TH/DbetaH-immunoreactive neuron-like cells in the proximal part of the gland.