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Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes
Get PDFAIMS/HYPOTHESIS:
Better understanding of type 2 diabetes and its prevention is a pressing need. Changes in human plasma N-glycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Variations in glucose metabolism directly affect glycosylation through the hexosamine pathway but studies of plasma glycome in type 2 diabetes are scarce. The aim of this study was to determine whether plasma protein N-glycome is changed in individuals who are at greater risk of developing type 2 diabetes. -----
METHODS:
Using a chromatographic approach, we analysed N-linked glycans from plasma proteins in two populations comprising individuals with registered hyperglycaemia during critical illness (increased risk for development of type 2 diabetes) and individuals who stayed normoglycaemic during the same condition: AcuteInflammation (59 cases vs 49 controls) and AcuteInflammation Replication (52 cases vs 14 controls) populations. N-glycome was also studied in individuals from FinRisk (37 incident cases of type 2 diabetes collected at baseline vs 37 controls), Orkney Complex Disease Study (ORCADES; 94 individuals with HbA1c > 6.5% [47.5 mmol/mol] vs 658 controls) and Southall and Brent Revisited (SABRE) cohort studies (307 individuals with HbA1c > 6.5% [47.5 mmol/mol] vs 307 controls). -----
RESULTS:
Individuals with increased risk for diabetes type 2 development (AcuteInflammation and AcuteInflammation Replication populations), incident cases of type 2 diabetes collected at baseline (FinRisk population) and individuals with elevated HbA1c (ORCADES and SABRE populations) all presented with increased branching, galactosylation and sialylation of plasma protein N-glycans and these changes were of similar magnitude. -----
CONCLUSIONS/INTERPRETATION:
Increased complexity of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes and poorer regulation of blood glucose levels. Although further research is needed, this finding could offer a potential new approach for improvement in prevention of diabetes and its complications
Genetic polymorphism of CYP2C19, CYP2C9 and VKORC1 in Kosovo population [Genetički polimiorfizam CYP2C19, CYP2C9 i VKORC1 u kosovskoj populaciji]
Get PDFBackground: For the first time, we determined and analyzed frequency of the most important variant alleles of CYP2C9, CYP2C19, CYP3A5 and VKORC1 in Kosovo‟s population. Methods: Determination of genetic polymorphism was conducted in 234 nonrelated Kosovars and genotyping was conducted by Real-Time PCR. Results: Allele frequencies of CYP 2C9*2 and 2C9*3 were 17,52% and 10.89% respectively. 16 subjects (6.81%) were anticipated to be poor metabolizers. For CYP2C19, *2 and *17 variant frequencies were 2C19*2=13.03% and 2C19*17=19.01%. CYP2C19 poor metabolizers were predicted to be 2.13%, while 10 subjects (4.27%) were homozygous carriers of *17 allele and were predicted to be UM. For CYP3A5, prevalence of *3 variant allele in Kosovo population was 98.29 % (non-expressors). In relation to VKORC1, 33,3% of subjects of this study were found as homozygous (CC), 51,7% were heterozygous CT and 14.95% were homozygous for T allele. Discussion: For CYP2C9 and CYP2C19, frequency of variant alleles is in accordance with respective data in Caucasians especially with data of Croats, Macedonians, Greeks and French people. For CYP3A5*3, its frequency was in accordance with Croats and Tuscans (Italy) but is different compared to data obtained from other Caucasians. Data on VKORC1 (1173C>T) correspond to the relevant genotypes of the Balkan populations such as Croats, but differ from other European countries such as Italy. Conclusion: Findings of this study showed high accordance of variant alleles, genotypes and predicted phenotypes of Kosovars with that of other Caucasians, specifically with South Eastern European populations
Klinički pristup ginekomastiji [Clinical evaluation of gynecomastia]
Get PDFGynecomastia is characterized by the ennlargement of the male breast caused by glandular proliferation. Gynecomastia occurs when the estrogen-to-androgen ratio is disrupted, in plasma or locally in the breast tissue. The etiology is usually benign. Physiologic gynecomastia is common in newborns, adolescents, and older men. Nonphysiologic gynecomastia may be caused by chronic conditions (e.g. hypogonadism, liver cirrhosis, renal insufficiency), use of certain medications or substances, and, rarely tumors. The diagnostic evaluation starts with careful history taking and physical examination which may be followed by extensive work-up that includes selective imaging and laboratory testing. Discontinuing the use of contributing medications and treating the underlying disease are the mainstay of treatment
Indikacijske smjernice za fetalnu ehokardiografiju i njihov utjecaj na prenatalnu dijagnozu srčane bolesti [Indication guidelines for fetal echocardiography and their influence on prenatal diagnosis of a heart disease]
Get PDFDescriptive study: Fetal echocardiography indications and their role in the development of congenital heart defects in newborns. Hypothesis: Congenital heart defects (CHDs) are the most common birth defects diagnosed with the aid of fetal echocardiography (FE) in pregnant women with certain risk factors for CHD, enabling early treatment. Aim: of this study was to determine the connection between the indications which prompted physicians to refer pregnant women for FE and the CHDs caused by these indications. Results: The study involved 1374 pregnant women with 1380 pregnancies, referred by their primary gynecologist and examined in the Fetal cardiology clinic of theUniversityHospital Centre Zagreb, Croatia, between the 1st January 2012 and the 1st January 2015. Most indications for FE were determined by obstetricians, while some pregnant women were referred for FE by their rheumatologist, genetic medicine specialist or physicians of other subspecialties. A few pregnant women were examined at their own request. The incidence of CHD was 14.2% (196 fetuses were diagnosed out of 1380 examined), the most common being ventricular septal defect (25%), complex CHD (15.3%), arrhythmia (14.79%), cardiomyopathy (10.71%), coarctation of the aorta (7.65%), aortic valve stenosis (6.12%) and bicuspid aortic valve (3.06%). Pathology was more likely to be detected in pregnant women referred for FE with a specific indication, in comparison to those sent for a routine examination. Conclusion: Fetal echocardiography is diagnostically most efficient if we adhere to the prescribed indications which may indicate a primary heart disease (CHD in family, arrhythmias, CMP), fetal syndrome disease, diabetes mellitus or gestational diabetes, and systemic diseases of the mother’s linking tissue (positive specific antibodies)
Usporedba učinkovitosti vježba za stabilizaciju sakroilijakalnih zglobova s nošenjem potpornog pojasa radi smanjenja simptoma sakroilijakalne disfunkcije u trudnoći [Effectiveness of exercise compared to wearing support belt in order to stabilize the sacroiliac joints and reduce the symptoms of sacroiliac dysfunction in pregnancy]
Get PDFTo determine the effectiveness of exercise as a very important therapeutic intervention to stabilize the sacroiliac joints and the supporting belt in pregnant women with sacroiliac dysfunction. Methods: A randomized controlled study involving 240 patients with sacroiliac dysfunction in pregnancy. The subjects were randomly selected into two groups, 120 in each with 40 per each trimester. The study group carried out the exercise to stabilize the sacroiliac joints 3 times a week for 45 minutes while the control group was wearing a support belt during routine daily activities. After two weeks pain intensity by numerical rating scale and the level of disability during daily activities by Quebec scale were assessed. Results: Pain intensity and the degree of disability caused by sacroiliac dysfunction increases from the beginning to the end of pregnancy. There was a statistically significant reduction in pain intensity (P <0.01, P <0.05) and the degree of disability (P <0.01, P <0.05) after both interventions were applied. There was a connection between pain intensity and the degree of disability in the study group (p <0.56). The study group performed significantly better regarding reduction in pain and the degree of disability compared to the control group (P <0.05). Conclusion: Exercise used to stabilize the sacroiliac joints was more effective in stabiliz ation of the sacroiliac joints during pregnancy in women with sacroiliac dysfunction
Metabolic syndrome modulates association between endothelial lipase and lipid/lipoprotein plasma levels in acute heart failure patients
Get PDFWe hypothesised that the established association of endothelial lipase (EL) plasma levels with atherogenic lipid profile is altered in acute heart failure (AHF) and additionally affected by overlapping metabolic syndrome (MetS). We examined the association of EL plasma levels and lipid/lipoprotein plasma levels in AHF patients without and with overlapping MetS. The study was performed as a single-centre, observational study on 152 AHF patients, out of which 85 had overlapping MetS. In the no-MetS group, EL plasma levels were significantly positively correlated with plasma levels of atherogenic lipids/lipoproteins, including total cholesterol, low-density lipoprotein (LDL)-cholesterol, total LDL particles and triglycerides, but also with plasma levels of antiatherogenic high-density lipoprotein (HDL)-cholesterol, total HDL particles and small HDL particles. In the MetS group, EL plasma levels were positively correlated with triglyceride and small LDL-particle levels, and significantly negatively correlated with plasma levels of large HDL particles as well as with LDL- and HDL-particle size, respectively. EL- and lipid/lipoprotein- plasma levels were different in the no-MetS patients, compared to MetS patients. The association of EL with atherogenic lipid profile is altered in AHF and additionally modified by MetS, which strongly modulates EL- and lipid/lipoprotein-plasma levels in AHF
Validation and cross-cultural adaptation of the COMPASS-31 in Croatian and Serbian patients with multiple sclerosis
Get PDFAIM:
To validate and cross-culturally adapt Croatian and Serbian versions of composite autonomic symptom score-31 (COMPASS-31) for the detection of dysautonomia in patients with multiple sclerosis (MS). -----
METHODS:
A total of 179 patients, 67 with clinically isolated syndrome (CIS) and 112 with MS, completed the COMPASS-31 at two MS centers in Zagreb and Belgrade between April 1 and October 31, 2016. Demographic and clinical data including age, gender, MS phenotypes, and the Expanded Disability Status Scale (EDSS) score were collected. -----
RESULTS:
The Cronbach's alpha coefficient of COMPASS-31 total score was 0.844 for the Croatian MS sample and 0.779 for the Serbian MS sample. A joint analysis yielded Cronbach's alpha coefficients ranging from 0.394 to 0.796, with values in four domains higher than 0.700. In Croatian and Serbian samples and the total study sample, the Cronbach's alpha coefficient of COMPASS-31 was 0.785. Reproducibility measured by intra-class correlation coefficient (ICC) was acceptable (ICC=0.795). With regard to the clinical validity, significant correlation was found between EDSS and the COMPASS-31 total score (P0, which implies the existence of at least one of the symptoms investigated in each domain, were detected for secretomotor and bladder domains (P=0.015 and PP<0.001, respectively). -----
CONCLUSION:
COMPASS-31 represents a valid and acceptable self-assessment instrument for the detection of dysautonomia in MS patients
Prognostička vrijednost tkivnog proteomskog profila u stadijima I i II malignoga melanoma kože glave i vrata [Prognostic significance of proteomic profiling applied to stages I and II cutaneous malignant melanoma of the head and neck in stages I and II]
Get PDFMorphohistopathological parameters are the basis for malignant melanoma classification and prognosis. An increasing number of molecular biomarkers offers new potential for refining diagnostic and prognostic disease categories. However, early stage disease prognosis is only partially defined by morphological and histopathological parameters (primary tumor localization, patient age and gender, mitotic rate, lesion thickness and presence of ulceration). This study is based on proteomic profiling of 31 early stage head and neck cutaneus malignant melanoma tissue samples and six pooled benign pigmented nevi tissue, as a control sample. After identifying the global melanoma proteomic profile, expression of individual proteins was correlated with established prognostic factors and patient survival by recursive partitioning. Relations between individual protein expression levels and disease specific survival were analyzed. Analysis revealed, previously unreported proteins, identified as possible prognostic biomarkers. These are: heterogeneous nuclear ribonucleoprotein M, heat shock protein 90 alpha, profilin-1, tubulin - beta chain, annexin-5 and ribosomal protein L7. Heterogeneous nuclear ribonucleoprotein M was identifed as the principal prognostic factor in our data set. It was shown as independent in relation to other prognostic factors, statistically significant and clinically relevant due to an exceedingly high hazard ratio. These findings add a new dimension in relation to novel melanoma biomarkers, especially in for early disease stages
Kardioprotektivni učinak sevoflurana s obzirom na vrijeme primjene pri operacijama aortokoronarnoga premoštavanja [Cardioprotective effect of sevoflurane with regard to time of application in patients undergoing coronary artery bypass grafting]
Get PDFBackground: Sevoflurane is a volatile anaesthetic which belongs to the group of general
anaesthetics. Its cardioprotective effect has been proved in experimental and clinical studies.
However, it still hasn't been studied whether this effect on the myocardium differs depending
on the time of the administration. The aim of this study was to determine whether the
cardioprotective effect of sevoflurane was more expressed when administered before the onset
of myocardial ischaemia (during preconditioning phase of coronary bypass grafting
operations) compared to its administration after the period of ischaemia (during
postconditioning).
Methods: Seventy-two patients scheduled for elective coronary artery bypass graft surgery
were randomly assigned to one of three groups: a group of patients who were anaesthetised by
sevoflurane administered before the onset of ischaemia (SEVO pre; n=24), a group of patients
who were anaesthetised by sevoflurane administered after the ischaemic period (SEVO post;
n=24) and a control group who were anaesthetised only by midazolam and fentanyl (Control;
n=24). The effect on myocardium was assessed by successive measurements of cardiac
biomarkers in the perioperative period: troponin I (cTnI), creatine kinase (CK), CK-MB
isoenzyme and lactate dehydrogenase (LD). The degree of myocardial injury was estimated
quantitatively on the basis of the summary values of the cardiac biomarkers and categorically
on the basis of the distribution of peak troponin I concentrations in the perioperative period.
The following summary variables were: peak value, time to reach the peak value, difference
between the peak and the first measured value, percent difference between the peak and the
first measured value, difference between the last and the first measured values, percent
difference between the last and the first measured values, the area under the curve of the
measured values through the period. The categorical assessment of periprocedural myocardial
injury was done on the basis of peak troponin I at 2, 4, 8 and 12 μg/L. Results: Quantitatively the estimated degree of perioperative myocardial injury did not differ
significantly between the groups for any of the monitored parameters. The only difference
found was a significantly lower value of CK-MB difference between the peak and the first
measured value in the group SEVO pre in comparison to the SEVO post group (p = 0.010).
This may speak in favour of smaller periprocedural myocardial injury in the SEVO pre group.
Based on peak troponin I concentrations, the number of patients who had perioperative
myocardial injury did not differ significantly between the groups, although there was a trend
of the smallest number of such patients in the SEVO pre group for all monitored peak
concentrations of troponin I. In a univariate analysis of predictor variables for the
development of periprocedural myocardial injury (peak troponin I > 2 μg/L), lower body
surface area (p = 0.010) was found the only significant variable. In a multivariate analysis
model for the same outcome, in which the body surface area and administration mode of
anaesthetic were included, the body surface area (OR = 0.020; 95% CI = 0.001 − 0.401, p =
0.011), and SEVO pre group compared to SEVO post group (OR = 0.277; 95% CI = 0.078 −
0.977, p = 0.046) were found as significant favourable predictors. Within patients that were
operated in CABG method and also within those operated in OPCAB method, the
quantitatively and categoricaly estimated degree of perioperative myocardial injury, did not
differ significantly between the groups for any of the monitored parameters.
Conclusion: This research did not unequivocally establish the cardioprotective effect of
sevoflurane when administered before the onset of ischaemia compared to midazolam and
fentanyl, nor did it establish the cardioprotective effect when compared to sevoflurane
administered after the ischaemic period. Some of our results may suggest possible
cardioprotective effect of sevoflurane when administered before ischaemia compared to
sevoflurane administered after ischaemia in terms of a minor periprocedural myocardial
injury. However, further randomized controlled trials are necessary to confirm this result