Primarily depression manifestation of Wilson's disease-Case report.

Wilson's disease is an inherited autosomal-recessive disorder of biliary copper excretion. It is characterized by hepatic, neurological and ophthalmic manifestations related to the accumulation of copper in the liver, the lenticular nuclei of brain and cornea. The authors present the case of a 29-year-old female with primarily depression manifestation of Wilson's disease. The patient also reported agitation, difficulties with concentration, slowdown of speech, and stuttering. In magnetic resonance imaging, in putamen, the globus pallidus, claustrum, the heads of caudate nucleus and thalamus areas demonstrated the increased signal in T2. A high copper content was obtained in daily urine collection and reduced level in serum. Similarly, ceruloplasmin level was decreased. Despite the antidepressant treatment with venlafaxine, no improvement was observed. Within a week of psychomotor slowdown, symptoms such as Parkinson's syndrome appeared. Due to the rapid progression of the disease symptoms, the patient was referred for further treatment at a specialistic center. After six month, despite the treatment, the progress of disease was so advanced that patient was transferred to the hospice. Two weeks later patient died. Wilson's disease might be consider in differential diagnosis of depression in young patients, especially if they present additional extrapyramidal symptoms and unspecific changes in magnetic resonance imaging.

Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study.

BACKGROUND: According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. METHODS: We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1). RESULTS: Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age. CONCLUSIONS: Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance.

Angiotensin II type 1 receptor blockade by telmisartan prevents stress-induced impairment of memory via HPA axis deactivation and up-regulation of brain-derived neurotrophic factor gene expression.

Physical and psychological aspects of chronic stress continue to be a persistent clinical problem for which new pharmacological treatment strategies are aggressively sought. By the results of our previous work it has been demonstrated that telmisartan (TLM), an angiotensin type 1 receptor (AT1) blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ), alleviates stress-induced cognitive decline. Understanding of mechanistic background of this phenomenon is hampered by both dual binding sites of TLM and limited data on the consequences of central AT1 blockade and PPARγ activation. Therefore, a critical need exists for progress in the characterization of this target for pro-cognitive drug discovery. An unusual ability of novel ARBs to exert various PPARγ binding activities is commonly being viewed as predominant over angiotensin blockade in terms of neuroprotection. Here we aimed to verify this hypothesis using an animal model of chronic psychological stress (Wistar rats restrained 2.5h daily for 21days) with simultaneous oral administration of TLM (1mg/kg), GW9662 - PPARγ receptor antagonist (0.5mg/kg), or both in combination, followed by a battery of behavioral tests (open field, elevated plus maze, inhibitory avoidance - IA, object recognition - OR), quantitative determination of serum corticosterone (CORT) and evaluation of brain-derived neurotrophic factor (BDNF) gene expression in the medial prefrontal cortex (mPFC) and hippocampus (HIP). Stressed animals displayed decreased recall of the IA behavior (p<0.001), decreased OR (p<0.001), substantial CORT increase (p<0.001) and significantly downregulated expression of BDNF in the mPFC (p<0.001), which were attenuated in rats receiving TLM and TLM+GW9662. These data indicate that procognitive effect of ARBs in stressed subjects do not result from PPAR-γ activation, but AT1 blockade and subsequent hypothalamus-pituitary-adrenal axis deactivation associated with changes in primarily cortical gene expression. This study confirms the dual activities of TLM that controls hypertension and cognition through AT1 blockade.

Antioxidant profile of salivary glands in high fat diet-induced insulin resistance rats.

OBJECTIVE: There is no study analyzing the salivary antioxidant profile in the course of the insulin resistance. MATERIALS AND METHODS: Rats were divided into two groups. One group was fed with a normal diet, another one with a high fat diet for 5 weeks. The analysis included: catalase (CAT), superoxide dismutase, peroxidase activities, uric acid, and total antioxidant status concentrations. RESULTS: The activity of peroxidase in both kind of glands of insulin resistance rats was significantly reduced than in the control rats. The protein concentration, total amount of total antioxidant status in the parotid glands of insulin resistance rats were significantly lower than in the control glands The total amount of superoxide dismutase, CAT, and uric acid in the parotid glands of insulin resistance rats were significantly elevated in comparison with the control rats. The median values of the total amount of superoxide dismutase, CAT, peroxidase, total antioxidant status were significantly higher in the parotid than in the submandibular glands of the insulin resistance and control rats. CONCLUSION: Parotid and submandibular glands of rats react differently when exposed to insulin resistance condition; however, the parotid glands seem to be more affected. The main source of antioxidants is parotid glands of rats.

Proton magnetic resonance spectroscopy study of brain metabolite changes after antipsychotic treatment.

INTRODUCTION: Proton magnetic resonance spectroscopy (¹H MRS) enables the observation of brain function in vivo. The aim of our study was to evaluate the effects of antipsychotic medication on metabolite levels in the brain of schizophrenic patients based on a ¹H MRS examination. METHODS: We examined 42 patients previously diagnosed with chronic schizophrenia twice: firstly, after the neuroleptic wash-out (baseline) and secondly, under stable medication (follow-up, after treatment). The study had a naturalistic design and several different neuroleptic medications were used during the treatment phase. The clinical evaluation, MRI and MRS procedures were performed. The group of 26 healthy controls were also examined to compare MRS results. RESULTS: We found a significantly lower NAA/Cr (N-acetylaspartate/creatine) ratio in the frontal lobe and thalamus in patients (after the wash-out) as compared to controls. After treatment a significant decrease of the Glx/Cr ratio in the temporal lobe and a trend for an increase of the NAA/Cr ratio in the thalamus were observed. CONCLUSION: Our results confirm that antipsychotic medication modifies brain metabolism measured by means of ¹H MRS. The pattern of the changes suggests a neuroprotective action of antipsychotic medication in schizophrenia.