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Izraženost i učinci urogvanilina u mozgu miša [Expression and effects of uroguanylin in the mouse brain]
Get PDFUroguanylin (UGN) belongs to the family of guanylin peptides. They regulate electrolyte and water transport in intestine via guanylate cyclase C, the only known receptor for guanylin peptides. In this thesis we are showing expression of UGN in different brain regions which is regulated by feeding, although it was believed that brain is not expressing UGN. Guanylate cyclase C (GC-C) is expressed in midbrain and hypothalamus, while we discovered additional brain regions expressing GC-C in neurons (cerebral cortex, Purkinje cells and deep nuclei of the cerebellum) but not in astrocytes. UGN hyperpolarized Purkinje cells and decreased firing rate while in astrocytes lead to increase in intracellular Ca2+ concentration via GC-C/cGMP independent signalling pathway. Effects of UGN in hypothalamus on diet-induced thermogenesis and brown adipose tissue (BAT) activation after a meal exist in male but not female WT animals and GC-C KO animals of both genders. Similar research was performed on healthy volunteers which showed that activation of BAT after a meal is gender, age, and body mass index dependent. Role of UGN in BAT regulations is of immeasurable importance for development of the new therapeutic approaches in treatment of obesity, metabolic syndrome, and diabetes mellitus
Povezanost ehokardiografskih pokazatelja funkcije desne klijetke srca i vrijednosti širine distribucije volumena eritrocita u bolesnika sa sustavnom sklerozom [Relationship between echocardiographic right ventricular function parameters and red cell distribution width in patients with systemic sclerosis]
Get PDFObjective: The aim of this study was to evaluate echocardiographic parameters of right
ventricular function in patients with systemic sclerosis (SSc) without pulmonary
hypertension and its correlation to red cell distribution width (RDW).
Methods: 21 consecutive SSc patient undervent echocardiography with tissue Doppler
imaging to assess RV function. 19 study patients were investigated at baseline and in
four visits of one year follow up. Echocardiographic measuremets and RDW was
assessed at each visit (0-month visit, 4-month visit, 8-month visit, 12-month visit).
Results: In the highest tertile RDW group (>14,25 for first follow-up visit) RV FAC was
significantly lower 48,00 (45,00-51,00) compared to 50,80 (49,08-53,40); P=0,023.,
and in the highest tertile RDW group (>13,95 for second follow-up visit) PV Acct was
significantly lower (P=0,007) in the follow-up at first and second visit respectively. In
the highest tertile RDW group (>14,25 for first follow-up visit) RV FAC was significantly
lower 48,00 (45,00-51,00) compared to 50,80 (49,08-53,40); P=0,023., and in the
highest tertile RDW group (>13,95 for second follow-up visit) PV Acct was significantly
lower (P=0,007) in the follow-up at first and second visit respectevely. RDW showed a
positive correlation with RIMP (rho=0,537, P=0,012) on the first visit and negative
correlation with PVAcct on the firs (rho=-0,495, P=0,023) and second (rho=-0,497,
P=0,022) visit during the follow-up, respectively.
Conclusion: RDW in SSc may represent an integrative measure of multiple
pathological processes including fibrosis and ongoing inflammation. An increase in
RDW may indicate an impairment of cardiorespiratory function and right ventricular
function but further investigation is needed
Evaluation of cerebrospinal fluid phosphorylated tau231 as a biomarker in the differential diagnosis of Alzheimer's disease and vascular dementia
Get PDFBACKGROUND:
The diagnosis of either Alzheimer's disease (AD) or vascular dementia (VaD) is still largely based on clinical guidelines and exclusion of other diseases that may lead to dementia. ----- AIMS:
In this study, we assessed whether the use of sensitive and specific biomarkers such as phosphorylated tau proteins could contribute to an earlier and more accurate diagnosis of AD and VaD, as well as to their differentiation. ----- MATERIAL AND METHODS:
A total of 198 patients, of which 152 had AD, 28 VaD, and 18 were healthy controls (HC), were included in the analyses. We analyzed cerebrospinal fluid (CSF) levels of total tau protein (t-tau), tau protein phosphorylated at threonine 231 (p-tau231), and factor score (FS) determined by combination of p-tau231 and Mini-Mental State Examination (MMSE) in patients with AD and VaD, as well as in HC. We tested the diagnostic accuracy of these biomarkers in the CSF and FS (p-tau231, MMSE) in differentiating AD from VaD and HC. ----- RESULTS:
Total tau levels were significantly elevated in subjects with AD compared to HC, as well as in VaD subjects compared to HC. ----- DISCUSSION:
p-tau231 levels were significantly higher in patients with ADvsHC as well in patients with VaD vsHC. p-tau231 levels did not distinguish AD from VaD patients. Importantly, FS(p-tau231 and MMSE) showed statistically significant differences in the distribution of subjects with AD and VaD. ----- CONCLUSION:
These results indicate that FS (p-tau231 and MMSE) has a strong potential to provide an early distinction between AD and VaD
Vagal nerve stimulation is beneficial in postural orthostatic tachycardia syndrome and epilepsy
Get PDFHealth literacy of hospital patients using a linguistically validated Croatian version of the Newest Vital Sign screening test (NVS-HR)
Get PDFThe Newest Vital Sign (NVS) is a simple, quick and accurate screening test for health literacy (HL). It has been validated for different languages but, to date, not for the Croatian language. The aim of this study was to develop a linguistically validated Croatian version of the NVS and to use it at a later stage in a pilot study of health literacy assessment of hospital patients in Croatia. A full linguistic validation procedure was applied, including forward and backward translation, expert panel review, cognitive interview with 10 respondents from general population, and full involvement in the procedure of one of the screening test developers, the lead author of the NVS-UK version. HL testing on 100 hospital patients (55% women, median age 63.5 years) revealed 58% of patients had less than adequate HL level (scores less than 4), and mean NVS total score was 3.34. A positive significant association was observed between HL and educational level (p = 0.002). A high percentage of patients (92%) did not object to being tested for HL by their primary care physician or in hospital, and 99% of patients would recommend HL testing among patients in general. The respondents' positive views on HL testing and mean completion time of 4 minutes indicate that the Croatian version of the NVS (NVS-HR) could be recommended for use in both clinical and research settings in Croatia
Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
Get PDFProstate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling
Impact of pre-pregnancy BMI on blood glucose levels in pregnancy and on the anthropometry of newborns – preliminary insights from the Croatian Islands' Birth Cohort Study (CRIBS)
Get PDFThe aim of this study was to investigate the relationship between pre-pregnancy body mass index (BMI) and fasting blood
glucose level in pregnancy on the anthropometry of newborns. The sample consisted of 171 healthy pregnant women and
their newborns from the Croatian Islands’ Birth Cohort Study. Peripheral blood of pregnant women was taken in the second
trimester and fasting glucose values >5.1 mmol/l were considered elevated. Anthropometric variables (body weight, height
and waist circumference) were measured according to the International Biological Program. Pre-pregnancy BMI and fasting
glucose levels during pregnancy were significantly positively correlated (p<0,01), as were pre-pregnancy BMI and birth
weight (p<0,05), length (p<0,01), and head circumference (p<0,05) of the newborns. Hyperglycaemic women gave birth to
significantly heavier newborn girls then normal glycaemic women (p<0.05). In conclusion, there was a positive correlation
between pre-pregnancy BMI, fasting glucose during pregnancy and the anthropometry of newborns in this study
Digital dermatoscopy as a useful tool for evaluating therapeutic efficacy in a patient with eruptive keratoacanthomas
Get PDFAntidepressant drug-specific prediction of depression treatment outcomes from genetic and clinical variables
Get PDFIndividuals with depression differ substantially in their response to treatment with antidepressants. Specific predictors explain only a small proportion of these differences. To meaningfully predict who will respond to which antidepressant, it may be necessary to combine multiple biomarkers and clinical variables. Using statistical learning on common genetic variants and clinical information in a training sample of 280 individuals randomly allocated to 12-week treatment with antidepressants escitalopram or nortriptyline, we derived models to predict remission with each antidepressant drug. We tested the reproducibility of each prediction in a validation set of 150 participants not used in model derivation. An elastic net logistic model based on eleven genetic and six clinical variables predicted remission with escitalopram in the validation dataset with area under the curve 0.77 (95%CI; 0.66-0.88; p = 0.004), explaining approximately 30% of variance in who achieves remission. A model derived from 20 genetic variables predicted remission with nortriptyline in the validation dataset with an area under the curve 0.77 (95%CI; 0.65-0.90; p < 0.001), explaining approximately 36% of variance in who achieves remission. The predictive models were antidepressant drug-specific. Validated drug-specific predictions suggest that a relatively small number of genetic and clinical variables can help select treatment between escitalopram and nortriptyline
Diagnostic significance of immunoglobulin G avidity in symptomatic and asymptomatic West Nile virus infection
Get PDFINTRODUCTION:
West Nile virus (WNV) immunoglobulin M (IgM) antibodies have been shown to persist for up to 500 days in certain patients. To evaluate the usefulness of immunoglobulin G (IgG) avidity assessment in the diagnosis of WNV infection, we analyzed 54 WNV IgM- and/or IgG-positive serum samples from 39 patients with neuroinvasive disease and 15 asymptomatic cases tested during a seroprevalence investigation. -----
METHODS:
Serological tests (WNV IgM/IgG antibody detection, IgG avidity) were performed using commercially available enzyme-linked immunosorbent assays. -----
RESULTS:
WNV IgM antibodies were detected in 47 (87%) samples. Acute/recent WNV infection was confirmed based on low/borderline avidity index (AI) in 44 IgM-positive samples (93.6%). In three IgM-positive samples (6.4%), high IgG AIs were detected, thus indicating persisting IgM antibodies from previous infections. All IgM-negative samples showed high AIs. Patients with WNV neuroinvasive disease tested within 30 days showed low AIs. In six patients tested 34-50 days after disease onset, AI was borderline (42%-60%), suggesting earlier WNV IgG maturation. Samples with the highest IgM values were associated with the lowest AIs (Spearman's rho coefficient -0.767, p < 0.001). -----
CONCLUSIONS:
Our results indicate that IgG avidity differentiates current/recent WNV infection from persistent IgM seropositivity from the previous WNV transmission season both in patients with WNV neuroinvasive disease and in asymptomatic persons. A strong negative correlation between IgM antibody levels and AI indicates that in cases with very high IgM levels, determination of IgG avidity may not be necessary. As many patients showed rapid avidity maturation, low IgG avidity is indicative of WNV infection within the previous month