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For the past decade protein acetylation has been shown to be a crucial post-transcriptional modification involved in the regulation of protein functions. Histone acetyltransferases (HATs) mediate acetylation of histones which results in the nucleosomal relaxation associated with gene expression. The reverse reaction, histone deacetylation, is mediated by histone deacetylases (HDACs) leading to chromatin condensation followed by transcriptional repression. HDACs are divided into distinct classes: I, IIa, IIb, III, and IV, on the basis of size and sequence homology, as well as formation of distinct repressor complexes. Implications of HDACs in many diseases, such as cancer, heart failure, and neurodegeneration, have identified these molecules as unique and attractive therapeutic targets. The emergence of HDAC4 among the members of class IIa family as a major player in synaptic plasticity raises important questions about its functions in the brain. The characterization of HDAC4 specific substrates and molecular partners in the brain will not only provide a better understanding of HDAC4 biological functions but also might help to develop new therapeutic strategies to target numerous malignancies. In this review we highlight and summarize recent achievements in understanding the biological role of HDAC4 in neurodegenerative processes.

The optic tract section at the optic chiasm is expected to disturb the suprachiasmatic nucleus (SCN) rhythm, circadian rhythm and melatonin secretion rhythms in humans, although detailed studies have never been conducted. The aim of this paper was to describe melatonin and cortisol profiles in patients with a pituitary tumor exerting optic chiasm compression. Six patients with pituitary tumors of different size, four of whom had significant optic chiasm compression, were examined. In each brain, MRI, an ophthalmological examination including the vision field and laboratory tests were performed. Melatonin and cortisol concentrations were measured at 22:00 h, 02:00 h, 06:00 h, and 10:00 h in patients lying in a dark, isolated room. One of the four cases with significant optic chiasm compression presented a flattened melatonin rhythm. The melatonin rhythm was also disturbed in one patient without optic chiasm compression. Larger tumors may play a role in the destruction of neurons connecting the retina with the suprachiasmatic nucleus (SCN) and breaking of basic way for inhibiting effect to the SCN from the retina., (Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by the expansion of a polyglutamine stretch within the huntingtin protein (HTT). The neurological symptoms, that involve motor, cognitive and psychiatric disturbances, are caused by neurodegeneration that is particularly widespread in the basal ganglia and cereberal cortex. HTT is ubiquitously expressed and in recent years it has become apparent that HD patients experience a wide array of peripheral organ dysfunction including severe metabolic phenotype, weight loss, HD-related cardiomyopathy and skeletal muscle wasting. Although skeletal muscles pathology became a hallmark of HD, the mechanisms underlying muscular atrophy in this disorder are unknown. Skeletal muscles account for approximately 40% of body mass and are highly adaptive to physiological and pathological conditions that may result in muscle hypertrophy (due to increased mechanical load) or atrophy (inactivity, chronic disease states). The atrophy is caused by degeneration of myofibers and their replacement by fibrotic tissue is the major pathological feature in many genetic muscle disorders. Under normal physiological conditions the muscle function is orchestrated by a network of intrinsic hypertrophic and atrophic signals linked to the functional properties of the motor units that are likely to be imbalanced in HD. In this article, we highlight the emerging field of research with particular focus on the recent studies of the skeletal muscle pathology and the identification of new disease-modifying treatments.

Introduction: The first part of this paper is related to healthy people and presents concentrations of TGFβ1 and VEGF in blood (with and without dividing data with respect to sex), their single measurement values (at 8 am), Mean Daily Concentrations (MDC), Area Under the Curves (AUC; total daily secretion), and circadian rhythm. The second part of the work is related to Graves' orbitopathy (GO). The aim of the study were: 1) to determine the physiological pattern of TGFβ1 and VEGF secretion; 2) to compare the serum TGFβ1 and VEGF circadian profile in newly diagnosed thyreotoxic patients with active GO and healthy controls (H); and 3) to estimate the influence of high-dose intravenous methylprednisolone pulse therapy (MP) on TGFb1 and VEGF blood levels in GO., Material and Methods: Twenty-two healthy (H) subjects and 16 hyperthyroid GO patients were treated with MP (6 g/14 days) and followed up by ophthalmological assessment. Blood was collected before and after 2 weeks MP-therapy. TGFβ1 and VEGF levels were determined by the ELISA method., Results: No difference was observed in the concentrations of TGFβ1 and VEGF in the blood of healthy women and men - in further analysis, a combined healthy male and female cohort was used (H). While the absence of circadian rhythms in the concentrations of TGFβ1 and VEGF allows the application of a single measurement approach, MDC and AUC measurements were found to be more precise. There were no differences in TGFβ1 MDC/AUC between GO and H. VEGF MDC/AUC in GO were higher than in H. MP-therapy increased TGFb1 MDC/AUC, thus in GO after MP, the TGFβ1 MDC/AUC were higher than in H. There were no differences in VEGF MDC/AUC during MP-therapy. MP-therapy was effective in 15/16 patients., Conclusions: 1. MP-therapy increases MDC and AUC of TGFβ1. The effectiveness of MP-therapy in patients with active GO may be related to its influence on TGFβ1 concentrations in blood. The results suggest the existence of a new mechanism of glucocorticoids action, consisting of an increase in the secretion of TGFβ1.2. The elevated serum VEGF in thyreotoxic patients with active GO may reflect long-standing autoimmune processes in orbital and thyroid tissues and intensified angiogenesis in the thyroid gland.

Huntington's disease (HD) is a neurodegenerative disorder characterized by a progressive motor and cognitive decline and the development of psychiatric symptoms. The origin of molecular and biochemical disturbances in HD is a mutation in the HTT gene, which is autosomally dominantly inherited. The altered huntingtin protein is ubiquitously expressed in the CNS, as well as in peripheral tissues. In this study we measured the metabolism changes in gene transcription in blood of HD gene carriers (premanifest and manifest combined) versus 28 healthy controls. The comparison revealed statistically significant Global Pattern Recognition Fold Change (FC) for 6 mRNA transcripts, reflecting an increase of: MAOB (FC = 3.07; p = 0.0005) which encodes an outer mitochondrial membrane-bound enzyme called monoamine oxidase type B; TGM2 (FC = 1.8; p = 0.02) encoding a transglutaminase 2 that mediates cellular stress; SLC2A4 (FC = 1.64; p = 0.02) solute carrier family 2 (facilitated glucose transporter) member 4; branched chain ketoacid dehydrogenase kinase (BCKDK) (FC = 1.34; p = 0.02); decrease of LDHA (FC = -1.16; p = 0.03) lactate dehydrogenase A; and brain-derived neurotrophic factor (BDNF) (FC = -2,11; p = 0.03). These distinguished changes coincided with HD progress. The analyses of gene transcription levels in sub-cohorts confirmed these changes and also revealed 28 statistically significant FCs of gene transcripts involved in ATP production and BCAA metabolism.

Introduction: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The aim of this study is to determine whether gender plays a role in the phenotypic expression and progression of HD., Methods: 1267 patients with HD (636 women) from the Registry project of the EHDN were included. A cross-sectional analysis (ANCOVA) controlling for differences in age at onset, disease burden, disease duration, smoking status, alcohol abuse, depression and the number of years of education, was performed to evaluate if there were differences between men and women in UHDRS motor, function and cognitive scores. Additionally, analyses on follow-up data using linear mixed models with the same covariates were performed to test for gender-related differences in progression., Results: Baseline features did not differ between genders, with the exception of a higher frequency of past and current depression among women, and a higher number of years of education as well as more frequent alcohol abuse and smoking among men. In the cross-sectional ANCOVA analyses of patients with a mid-age HD onset, women showed worse scores than men in the functional domain (TFC, P = 0.001; UHDRS functional, P = 0.033), UHDRS motor (P = 0.033). The longitudinal analyses showed a faster rate of progression in women in the functional assessment (P = 0.025), the motor assessment (P = 0.032) and the independence scale (P = 0.008)., Conclusions: These results suggest a complex gender effect on the phenotypical presentation and the rate of disease progression in HD, with slightly more severe phenotype and faster rate of progression in women in especially the motor and functional domains., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Determination of the plasma amino acid (AA) levels in Huntington's disease (HD) can make it possible to find the metabolic markers used in early diagnosis. The aim of the presented study was to determine the AA profile in plasma samples from HD patients and presymptomatic carriers, compared to healthy subjects. The AA profile was analyzed with HPLC. The study concerned 59 participants: 30 subjects with abnormal CAG repeats expansion (>36) in the HTT gene, and 29 healthy subjects. Each participant was analyzed with regard to the parameters characterizing the metabolic state and protein metabolism, such as: urea, creatinine, glucose, total protein, TSH (thyroid-stimulating hormone), cortisol, ESR (erythrocyte sedimentation rate), and CRP (C-reactive protein). Simple statistical comparisons showed 5 AA to be significantly lower in the HD group, compared to the control group, i.e.: Asn, His, Leu, Ser, Thr. Creatinine and creatinine clirens were found to be lower in the HD group, compared to controls, while ESR was noticed to be higher. As a result of Canonical Discriminant Analysis, 5 of all AA assayed (Leu, Gln, Asn, Ser and Lys) were selected as variables that allow distinguishing between HD patients and healthy subjects with 75% of correctness. Concerning AA profile and biochemical markers, Canonical Discriminant Analysis detected a panel of variables (Ser, Asn, Gln, Orn, Pro, Arg, Met, Cit, Val, TSH, glucose, urea, creatinine clirens, total protein, cortisol, CRP) distinguishing HD from the control group, with 90% of correctness. Among all the parameters tested, Asn and Ser were revealed in all statistical analyses and could be considered as potential plasma HD biomarkers.

Health-related quality-of-life instruments are critical for assessing disease burdens. Generic tools allow comparison between diseases but do not discriminate between disease severities. Specific tools also tend to be more sensitive. No specific tool is available to assess quality of life in patients with Huntington's disease (HD). In the context of the European study on HD burden, a specific tool was created: the Huntington Quality of Life Instrument (H-QoL-I). The aim of this study was to optimize the content and validate the H-QoL-I. After a semistructured interview with patients, caregivers and HD specialists, we conducted a patient focus group. A self-reported questionnaire was then developed in French and Italian. A total of 252 patients were recruited to answer the questionnaire. Face, internal and external validities were examined using a variety of methods. The shortened H-QoL-I that resulted from the successive analyses comprises 11 items, which are divided into three dimensions: motor functioning (four items), psychology (four items) and socializing (three items). These three domains were identified as being essential to cover the full domain of the quality of life for patients affected by HD. The H-QoL-I showed an acceptable reliability (Cronbach's α>0.84). Factor analyses demonstrated satisfactory construct validity. Moreover, the item internal consistency and item discriminant validity criteria were fulfilled. No differential item functioning was detected. External validity supported the scale's robustness. These data support the validity of the H-QoL-I in patients with HD.

Becker myotonia is a recessive muscle disease with prevalence of > 1:50,000. It is caused by markedly reduced function of the chloride channel encoded by CLCN1. We describe a Polish patient with severe myotonia, transient weakness, and muscle cramps who only responds to lidocaine. In addition, the patient has Prinzmetal angina pectoris and multiple lipomatosis. He is compound heterozygeous for a novel p.W303X and a frequent p.R894X CLCN1 mutation. CLCN1 exon number variation was excluded by MLPA. His son with latent myotonia was heterozygeous for p.R894X. We discuss the potential relations of the three rare diseases and the inheritance of p.R894X., (Copyright © 2011 Elsevier B.V. All rights reserved.)

However rare, dissection of extracranial cerebral arteries is one of the most often causes of ischemic stroke in young people. Early diagnosis and treatment promote artery recanalization that results in total symptom regression. The proper diagnosis is in many cases is difficult. The reason is the variety of causative factors, clinical symptoms and difficulty of direct dissected vertebral arteries visualisation in common Duplex-Doppler examination. In our article we present 3 causes of vertebral arteries dissection. We would like to call your attention to consider this causative factor in differentiation diagnostics of central nervous system ischemia. This complication may occur not only due to a communication accident, but also during playing tennis and bowling.

The aim of this study was to investigate the environmental factors influencing the tangible changes in the incidence of multiple sclerosis (MS) over a period of the past 30 years in the town Gniezno, Poland. We analysed many environmental factors to which the whole population was exposed in the respective period. The following factors were considered: viral infections (influenza, measles, varicella, rubella, mumps), atmospheric air pollution and climate conditions. A positive correlation has been found between the incidence of influenza and the incidence of MS in the same year (r = 0.37; p = 0.04) as well as with the MS incidence assessed after 5 years (r = 0.64; p = 0.0005). No significant correlation has been found between the incidence of MS and other investigated environmental factors. These results support the hypothesis that influenza infection could precipitate MS onset.

Huntington's disease (HD) is a neurological condition of progressive course that results from abnormally increased number of CAG repeats within IT-15 gene, coding for huntington. The main symptoms consist of choraetic movements, dementia, and characteropathy. The aim of the present study was to search for possible correlation between the age of the onset of HD, time from the onset, clinical status of the patients, and CAG repeats number. Ten patients were studied altogether. Modified UHDRS (MUHDRS) was applied for the estimation of patients' clinical status. The number of CAG repeats in examination of the IT-15 gene was determined by polymerase chain reaction (PCR) and separation of radioisotope labelled PCR product against DNA size marker in polyacrylamide gel. A negative significant correlation was found between the CAG repeats number and the disease onset age (r = -0.67; p < 0.05) and MUHDRS score (r = 0.75; p < 0.05), as well. Negative significant correlation between time from the onset and MUHDRS score (r = -0.95; p < 0.05) and negative correlation between summarised: time from the onset and CAG number on the one site and MUHDRS on the other (p = -0.91) were found, as well. Our findings indicate an interdependence between CAG repeats number within the IT-15 gene, the course of the disease and the clinical status of HD patients.