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  • Author: Gordana Matić x
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Glucocorticoid Receptor in Health and Disease

Glucocorticoid hormones are essential for life, have a vital place in the treatment of inflammatory and autoimmune diseases and are increasingly implicated in the pathogenesis of a number of common disorders. Their action is mediated by an intracellular receptor protein, the glucocorticoid receptor (GR), functioning as a ligand-inducible transcription factor. Multiple synthetic glucocorticoids are used as potent antiinflammatory and immunosuppressive agents, but their therapeutic usefulness is limited by a wide range and severity of side-effects. One of the most important pharmaceutical goals has been to design steroidal and non-steroidal GR ligands with profound therapeutic efficacy and reduced unwanted effects. The therapeutic benefit of glucocorticoid agonists is frequently compromised by resistance to glucocorticoids, which may depend on: access of the hormones to target cells, steroid metabolism, expression level and isoform composition of the GR protein, mutations and polymorphisms in the GR gene and association of the receptor with chaperone proteins. The major breakthrough into the critical role of glucocorticoid signaling in the maintenance of homeostasis and pathogenesis of diseases, as well as into the molecular mechanisms underlying the therapeutic usefulness of antiinflammatory drugs acting through the GR is expected to result from the current progress in large-scale gene expression profiling technologies and computational biology.

Abstract

Background

Cerebral small vessel disease (CSVD) and metabolic syndrome were separately associated with cognitive impairment and depression. However, whether metabolic syndrome adds to cognitive impairment and depression in patients who already have CSVD remained unanswered.

Objective

The aim of our study was to investigate the association of metabolic syndrome with cognitive impairment and depression in patients with CSVD who have lacunar lesions or white matter hyperintensities.

Methods

This prospective cohort study was conducted at Neurology Clinic, Clinical Center, Kragujevac, Serbia. Main outcomes of the study were cognitive assessment, and assessment of depression among hospitalized patients with or without CSVD.

Results

The study included 74 inpatients, 25 of them having lacunary infarctions, 24 with the white matter hyperintensities, and 25 control patients without CSVD. The CSVD was accompanied by impairment of cognition and depression, the patients with lacunary lesions being more cognitively impaired and more depressive than the patients with the white matter hyperintensities. The patients with CSVD who also had metabolic syndrome were more cognitively impaired and depressed than the patients with CSVD alone.

Conclusions

In conclusion, our study showed that metabolic syndrome is associated with further worsening of already impaired cognition and existing depression in patients with CSVD.

Summary

Real-time RT PCR has been recognized as an accurate, reliable and sensitive method for quantifying gene transcription. However, several steps preceding PCR represent critical points and source of inaccuracies. These steps include cell processing, RNA extraction, RNA storage, assessment of RNA concentration and cDNA synthesis. To compensate for potential variability introduced by the procedure, normalization of target gene expression has been established. Accurate normalization has become an absolute prerequisite for the correct quantification of gene expression. Several strategies are in use for the normalization of data, including normalization to sample size, to total RNA or to an internal reference. Among these, the use of housekeeping genes as an internal (endogenous) control is the most common approach. Given the increased sensitivity, reproducibility and large dynamic range of this methodology, the requirements for a proper reference gene for normalization have become increasingly stringent. The aim of this paper is to discuss the concept of normalization in mRNA quantification, as well as to discuss several statistical algorithms developed to help the validation of potential reference genes. By showing that the use of inappropriate endogenous control might lead to incorrect results and misinterpretation of experimental data, we are joining the creators of Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) in an attempt to convince scientists that proper validation of potential reference genes is an absolute prerequisite for correct normalization and, therefore, for providing accurate and reliable data by quantitative real-time RT PCR gene expression analyses.

Abstract

Stroke is one of leading causes of death worldwide. Different frequency of stroke occurence is observed in days of the week and months in the year, and incidence of stroke has irregular time pattern. We analyzed 516 patients who had acute stroke and were treated in Clinic of Neurology, Clinical Center Kragujevac from January 1, 2013 to January 1, 2014, mean age 72,11±11,52. Statistical analysis is conducted out using the SPSS software version 20.0. We used descriptive statistic, student T-test, chi-square or Fisher exact test.

Friday is day we found the most IS and all stroke types occurences, and Wednesday is day we found the most IS in men. We found the most strokes in women younger than 65 years on Wednesday, but in women older than 65 years on Friday. Monday is day with the most admissions to hospital for patients with IS, and we observed that there is average delay in the refering to the doctor for 1.80±1.44 days. Friday is the day with the most ICH symptom beginings and the most admissions to the hospital, and Saturday is the day with the least symptom beginings and admissions to the hospital in the case of IS and ICH. The most IS occured in winter (in Decembar), and the least in summer (in August). The most ICH occured in May, and the least in July and October.

We confirmed that there is a significant weekly variability in the IS symptom onset day.

ABSTRACT

We reported a case of a 22-year-old male patient with swallowing difficulties and double vision. He was diagnosed on the basis of a positive pharmacological test, damage to the postsynaptic neuromuscular junction and computed tomography of the thorax. Tests for antibodies targeted to acetylcholine receptors and to muscle-specific tyrosine kinase were negative. A partial improvement in neurological findings following treatment with pyridostigmine bromide, cyclosporine and methylprednisolone was notedadministered. Th e patient responded favourably to plasma exchange with a withdrawal of all clinical symptoms, confirming the hypothesis that humoral factors may underlie the pathogenesis of double-negative MG .

Summary

Background: The polycystic ovary syndrome (PCOS) is a frequent endocrine disorder that affects women of reproductive age. As the syndrome is strongly associated with obesity, it is of interest to examine the gene expression diffe rences that accompany its development and the associ a ted metabolic disturbances. Real-time RT PCR is a standard method for studying changes in gene expression. However, to obtain accurate and reliable results, validation of reference genes is obligatory. The aim of this study was to identify a suitable reference for the normalization of gene expression in peripheral blood mononuclear cells (PBMCs) from obese and normal-weight women with PCOS.

Methods: The expression stability of four potential reference genes: hypoxanthine guanine phosphoribosyl trans-ferase 1 (HPRT), β-actin (BA), β2-microglobulin (B2M) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was assessed in PBMCs from healthy women, and from normal-weight and obese women with PCOS. The variability in the expression of potential reference genes was analyzed by the TaqMan real-time RT PCR method, using GeNorm and NormFinder software packages.

Results: Direct comparison of cycle threshold (Ct) values showed inter-individual variations for all validated genes, the Ct values of HPRT being less variable than those of BA, GAPDH and B2M. Both software packages pointed to HPRT as the most steadily expressed gene in the PBMCs of women with PCOS and healthy controls.

Conclusions: Cross-validation of the expression stability of four potential reference genes identified HPRT as the most stable reference, suitable for further investigations of gene expression in PBMCs from women with PCOS.