A prokalcitonin biológiai szerepének és klinikai jelentőségének vizsgálata bakteriális és gombás fertőzésekben: a prokalcitonin termelődésének bioregulációja = Biological role and clinical importance of procalcitonin in bacterial and fungal infections: bioregulation of procalcitonin production

Prokalcitonin (PCT) vizsgálatok dializált krónikus urémiás betegekben és PCT mRNS expressziója szepszises gyermekek torok és mellűri váladékában Az urémia és hemodialízis (HD) alatti krónikus szisztémás gyulladásos tüneteknek a süllyedés, C-reaktív protein (CRP) nem specifikus markere. 115 hemodializált betegünkből 25-nek volt szepszise. A szérum PCT szinteket vizsgálva a HD elötti enyhén emelkedett értéket a HD szignifikánsan nem befolyásolta. A szisztémás bakteriális infekció urémiásokban azonban szignifikáns (>12x, p12 times, p<0.001) the serum PCT levels of the affected patients and the sensitivity of PCT method was better, the specificity was the same comparing to CRP method. Analysing the PCT mRNA expression in throat lavage, phlegm, bronchial secretion of 8 septic patients with quantitative real time PCR, the mRNA was not expressed in time of analysis, although we could detect the expression of a house-keeping gene used as control. The probable explanation: the transitory type of mononuclear cells PCT mRNA expression, which lasts about 3-4 hours after their adherence to epithelium. However, the inflammatory markers generated by these cells could lead to definitely increased PCT production in the other tissues

Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression

Neonatal rodents chronically treated with the tricyclic antidepressant clomipramine show depression-like behavior, which persists throughout adulthood. Therefore, this animal model is suitable to investigate the pathomechanism of depression, which is still largely unknown at the molecular level beyond monoaminergic dysfunctions. Here, we describe protein level changes in the prefrontal cortex of neonatally clomipramine-treated adult rats correlating with behavioral abnormalities. Clomipramine was administered to rat pups twice daily between postnatal days 8-21, while controls received saline injections. Behavioral tests were performed on 3months old rats. The proteomic study was conducted using two-dimensional differential gel electrophoresis. We have identified 32 proteins by mass spectrometry analysis of the significantly altered protein spots. The changed proteins are related to several biological functions, such as inflammation, transcription, cell metabolism and cytoskeleton organization. Among the altered proteins, the level of macrophage migration inhibitory factor showed the largest alteration, which was confirmed with Western blot. Macrophage migration inhibitory factor showed widespread distribution and was predominantly expressed in astrocytes in the forebrain of rats which were described using immunohistochemistry. We conclude that neonatal clomipramine exposure induces sustained modification in the proteome, which may form the molecular basis of the observed depression-like behavior in adult rats. BIOLOGICAL SIGNIFICANCE: It is known that some of the psychiatric disorders, such as autism, depression or schizophrenia may be at least in part, developmental disorders. We hypothesized that clomipramine treatment in early stage of brain development, which is known to induce depression-like behavior in adult rats, results in pathological distortion in neuronal and glial network development, which can be reflected by the cellular proteome in adulthood. Thus, we performed an unbiased proteomics experiment in adult rats, which were neonatally administered with clomipramine to reveal protein level changes three months after treatment. Many of the identified changed proteins are previously associated with depressive symptoms, e.g., the macrophage migration inhibitory factor (MIF), the level of which showed the largest alteration among the identified proteins. Based on our data, we suggest that neonatal clomipramine treatment is a reliable model to study the developmental effect of psychoactive drugs applied in the sensitive early phase of brain development. Furthermore, our findings support the idea that the alteration of early development of the brain induced by antidepressant treatment could result in sustained pathological changes in the cellular phenotype in the prefrontal cortex leading to depression-like behavioral symptoms

Az immunhisztokémia jelentősége ritka bőrtumorok esetén

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A novel de novo truncating variant in a Hungarian patient with CTNNB1 neurodevelopmental disorder

We aimed to elucidate the underlying disease in a Hungarian family, with only one affected family member, a 16-year-old male Hungarian patient, who developed global developmental delay, cognitive impairment, behavioral problems, short stature, intermittent headaches, recurrent dizziness, strabismus, hypermetropia, complex movement disorder and partial pituitary dysfunction. After years of detailed clinical investigations and careful pediatric care, the exact diagnosis of the patient and the cause of the disease was still unknown.We aimed to perform whole exome sequencing (WES) in order to investigate whether the affected patient is suffering from a rare monogenic disease.Using WES, we identified a novel, de novo frameshift variant (c.1902dupG, p.Ala636SerfsTer12) of the catenin beta-1 (CTNNB1) gene. Assessment of the novel CTNNB1 variant suggested that it is a likely pathogenic one and raised the diagnosis of CTNNB1 neurodevelopmental disorder (OMIM 615,075).Our manuscript may contribute to the better understanding of the genetic background of the recently discovered CTNNB1 neurodevelopmental disorder and raise awareness among clinicians and geneticists. The affected Hungarian family demonstrates that based on the results of the clinical workup is difficult to establish the diagnosis and high-throughput genetic screening may help to solve these complex cases