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Polymorphisms of inflammatory genes as potential predictors of diabetic nephropathy in patients with type 2 diabetes [Polimorfizam upalnih gena kao mogući predskazatelj diabetičke nefropatije u bolesnika sa šećernom bolesti tipa 2]
Get PDFObjectives One of the more devastating chronic complications of diabetes mellitus (DM) is diabetic nephropathy (DN), with a chronic low-grade inflammation occurring in the background. The aim of this study is to examine the relationship between chosen candidate genes with potential functional importance in inflammation and DN among Caucasians with type 2 (T2DM) as markers to identify patients who are more likely to develop DN. -----
Methods and patients Participants were divided into two groups: patients with DN (276 subjects) and without DN (375 subjects). SNP genotyping for 13 SNPs from four fields of inflammation were performed: Adhesion molecules: ICAM1 gene (rs5498, rs1799969), PECAM1 (rs668); Chemokines: CCL5 (rs2280788, rs2107538), CCR5 (rs1799987) and the CCR2 (rs1799864); Interleukins (ILs): rs3212227, rs187238, rs1800896, rs2243250 of IL12B, IL18, IL10 and IL4 genes, respectively; Nuclear receptors: PPARG (rs1801282) and PPARGC1A (rs8192678). -----
Results No associations were found between the SNPs of chosen adhesion molecules (rs5498, rs1799969, rs668) and chemokines (rs2280788, rs2107538, rs1799987, rs1799864) and DN in T2DM patients. Similarly, no associations were found for SNPs from interleukins (rs3212227, rs187238, rs1800896, and rs2243250) and nuclear receptors (rs1801282, rs8192678) even with DN. Serum levels of sICAM-1, sPECAM-1, IL-18 and IL-10 did not differ between different genotypes of corresponding selected polymorphisms. -----
Conclusions Genetic polymorphisms from our set of genes involved in the inflammatory response were not found to be associated with DN in Caucasians with T2DM and may not be considered as potential markers for DN in this population. Additionally, no differences were found in serum levels of sICAM-1, sPECAM-1, IL-18 and IL-10 according to different genotypes of corresponding genes
The role of mesenchymal stem cells in atherosclerosis: prospects for therapy via the modulation of inflammatory milieu
Get PDFAtherosclerosis is a chronic, inflammatory disease that mainly affects the arterial intima. The disease is more prevalent in middle-age and older individuals with one or more cardiovascular risk factors, including dyslipidemia, hypertension, diabetes, smoking, obesity, and others. The beginning and development of atherosclerosis has been associated with several immune components, including infiltration of inflammatory cells, monocyte/macrophage-derived foam cells, and inflammatory cytokines and chemokines. Mesenchymal stem cells (MSCs) originate from several tissue sources of the body and have self-renewal and multipotent differentiation characteristics. They also have immunomodulatory and anti-inflammatory properties. Recently, it was shown that MSCs have a regulatory role in plasma lipid levels. In addition, MSCs have shown to have promising potential in terms of treatment strategies for several diseases, including those with an inflammatory component. In this regard, transplantation of MSCs to patients with atherosclerosis has been proposed as a novel strategy in the treatment of this disease. In this review, we summarize the current advancements regarding MSCs for the treatment of atherosclerosis
Povezanost operacije senilne katarakte i vrste implantirane leće s kvalitetom spavanja [Association between cataract surgery and type of implanted intraocular lens with sleep quality]
Get PDFA cataract is opacity of lens which causes decrease in vision. Although it is commonly due to
aging, it is a leading cause of blindness worldwide (51%). The only effective treatment of
cataract is surgery, during which the opaque lens is removed and one of two types of artificial
intraocular lens (IOL) is implanted – conventional or blue-light-filtering lens (bf-IOL). The
opacities of the lens decrease transmission of blue light to retina and removal of cataract with
implantation of IOL increases transmission back again. Cataract surgery improves vision but
also improves quality of sleep. Due to more light entering the eye, the concentration of
melatonin increases during the night which plays a key role in circadian rhythm.
The study included 188 subjects older than 60 who met the requirements for cataract surgery.
One of two types of lens was assigned to the subjects using randomization with dice.
Conventional IOL was implanted in 94 subjects and bf-IOL in other 94. Respondents
completed the Pittsburgh Sleep Quality Index (PSQI) one month before and three months after
the operation. The questionnaire consists of 19 questions, and the total composite result of all
the questions measures the quality of sleep.
The objectives of the study were to investigate the impact of cataract surgery on sleep quality,
regardless of the type of implanted intraocular lens. Furthermore, the difference in the sleep
quality between subjects with implantation of conventional IOL in compared to those with bf-
IOL.
Results confirm that cataract surgery statistically significantly improves sleep quality,
regardless of the type of implanted lens. Although sleep quality is statistically significantly
better after surgery in both groups, the difference in improvement is not statistically significant
when compared between the groups. In other words, there is no statistically significant
difference in improving sleep quality with regard to the type of implanted lens
Reprogenetics, reproductive risks and cultural awareness: what may we learn from Israeli and Croatian medical students?
Get PDFBackground: Past studies emphasized the possible cultural influence on attitudes regarding reprogenetics and reproductive risks among medical students who are taken to be "future physicians." These studies were crafted in order to enhance the knowledge and expand the boundaries of cultural competence. Yet such studies were focused on MS from relatively marginalized cultures, namely either from non-Western developing countries or minority groups in developed countries. The current study sheds light on possible cultural influences of the dominant culture on medical students in two developed countries, potentially with different dominant cultures regarding reprogenetics and reproductive risks: Israel and Croatia. -----
Methods: Quantitative-statistical analyses were employed, based on anonymous questionnaires completed by 150 first year medical students in Israel and Croatia. The questionnaires pertained to the knowledge and attitudes regarding genetics, reproduction and reproductive risks. These questionnaires were completed before the students were engaged in learning about these topics as part of the curriculum in their medical school. -----
Results: Substantial differences were revealed between the two groups of medical students. Israeli medical students were less tolerant regarding reproductive risks and more knowledgeable about genetics and reproductive risks than Croatian medical students. For example, while nearly all Israeli medical students (96%) disagreed with the idea that "Screening for reproductive risks in prospective parents is wrong," less than 40% of their Croatian counterparts shared a similar stance. Similarly, all (100%) Israeli medical students correctly observed that "A carrier of a recessive genetic disease actually has the disease" was wrong, as opposed to only 82% of Croatian students. -----
Conclusions: By linking applicable theoretical literature to these findings, we suggest that they may reflect the hidden influence of the dominant culture in each country, disguised as part of the "culture of medicine." Acknowledging and learning about such influence of the dominant culture, may be an important addition to the training of medical students in cultural competence, and specifically their cultural awareness. Such an acknowledgement may also pave the road to drawing the attention of existing physicians regarding a less known yet an important aspect of their cultural competence, insofar as the cultural awareness component is concerned
Bendamustine-based conditioning prior to autologous stem cell transplantation is associated with high rate of febrile neutropenia and higher mortality
Get PDFČimbenici rizika za razvoj zloćudnih nemelanomskih tumora kože nakon transplantacije bubrega [Risk factors for development of non-melanoma skin cancer after renal transplantation]
Get PDFPatients on immunosuppressive therapy are more prone to cancer development, with nonmelanoma skin cancers (NMSCs) being the most frequent ones.
The aim of the study was to examine the incidence of NMSCs the group of renal transplant recipients (RTR).
Risk factors for NMSC development were recorded, such as patients’ sex, age at transplantation, geographic background, duration of dialysis, type, intensity and duration of immunosuppression. In order to examine the role of Wnt4, the expression pattern was investigated in NMSCs of RTR and in a control group, a nontransplant group which is not under immunosuppressive therapy (77 paraffin embedded basal cell carcinomas (BCC) and 76 paraffin embedded squamous cell carcinomas (SCC)). Statistical significance was appointed to p<0,05.
The incidence of NMSC among RTRs was 6,81%., with basal cell carcinoma being the most prevalent one (BCC:SCC ratio 1,76:1). Males were more affected than females (P=0,007), with shorter mean interval between the time of transplantation and first cancer development (P=0,0001). Mean dialysis time before transplantation was 3 years (2–6 years), and mean time to first NMSC development was 5 years respectively. There was difference between age at transplantation; mean age at transplantation for patients transplanted before the year 2010 was 44 (32–53) and mean age at transplantation after 2010 was 53 (43–61) (P<0,0001). Time to first NMSC development is decreasing in later group. NMSC was observed in 5,3% of RTR who live along the Adriatic coast and in 7,3% of RTR who live in the continental part of Croatia; the difference is not statistically significant (P =0,241), nor is the time to first NMSC development between those two groups of patients (P=0,564). Patients receiving more intense therapy (which includes 3 immunosuppressive agents) did not develop more NMSC then patients receiving only 2 immunosuppressive agents (6,64% compared to 8,42 %) (P=0,556). There was significant difference in the incidence of NMSC between the groups of patients treated with different immunosuppressive agents; 3,1% of patients receiving tacrolimus developed NMSC which is significantly lower than 14,3% of NMSC among patients receiving cyclosporinA (P<0,0001). In addition, 5,9% of patients receiving mycophenolat mofetil and 15,8% of patients receiving azathioprine developed NMSC (P=0,001).
Immunohistochemical staining to Wnt4 antibody revealed cytoplasmic staining in NMSC cells and in the healthy tissue. Wnt4 staining was weaker in BCC and SCC when compared to the healthy skin (p<0,0001), pointing to influence of Wnt signaling in initial NMSC carcinogenesis. The difference between Wnt4 staining in RTR compared to control group indicates possible activation of different Wnt signaling pathways in carcinogenesis or coactivation of another Wnt ligands in the NMSC progression. However, the role of immunosuppression in Wnt4 expression and activation was not completely made clear.
Our results indicate RTRs as a high-risk group for NMSC development. Therefore, patients should undergo a dermatological skin examination prior to transplantation as well as regular dermatological follow up after transplantation considering the guidelines and risk factors for each individual patient
Calretinin neurons in the primate prefrontal cortex [Kalretininski neuroni u prefrontalnom korteksu primata]
Get PDFNeuronal circuitries of the cerebral cortex are the main biological substrates for mental
abilities found in mammals. Diversity of primate synaptic architecture enable appearance of
complex cognition and their disorganization leads to many neurological and behavioral
disturbances. Substantial reorganization of cortical network occurring during primate
evolution is necessary to achieve complex information processing. We performed systematic
quantitative analysis in prefrontal cortical areas 9, 32 and 24 of monkey and human to
determine the proportion, distribution and neurotransmitter phenotype of calretinin neurons,
whose proportion dramatically increases when primates are compared to rodents.
In primate brain up to 15% of neurons express calretinin and they are mostly positioned in
upper cortical layers (up to 40% in layer II, and up to 70% in layer I). VGAT mRNA was found
in all calretinin neurons, which directly confirmed their GABAergic phenotype. Double
labeling showed that calretinin neurons are more numerous than other subpopulation of
interneurons. This data suggest that GABAergic neurons in layer I and II of the primate
associative areas outnumber the principal glutamatergic neurons. There were no areal
differences in laminar distribution of calretinin neurons in the primate brain, but we found
spatial reorganization inside the cortical lamina favoring the upper cortico-cortical layers and
affecting higher order neocortical areas in monkey and all of human prefrontal cortical areas
HDL subclasses and mortality in acute heart failure patients
Get PDFThe link between HDL subclasses and the prognosis of cardiovascular diseases remains controversial. We thus evaluated the prognostic value of the HDL subclasses 3 and 2 cholesterol (HDL3-C, HDL2-C) as well as of total HDL-C for 3-month mortality in acute heart failure (AHF) patients. The serum levels of HDL3-C and total HDL-C were determined by detergent-based homogeneous assay. HDL2-C was computed by the difference between total HDL-C and HDL3-C. Out of the 132 analyzed patients, 35 (26.5%) died within three months after onset of AHF. Univariate logistic regression analyses revealed a significant inverse association of HDL3-C (odds ratio (OR) 0.46 per 1-SD increase, 95% confidence interval (CI) 0.27-0.72, p = 0.001) with 3-month mortality, whereas concentrations of total HDL-C and HDL2-C showed no significant association. After adjustment for various laboratory and clinical parameters known to be associated with mortality in heart failure patients, HDL3-C concentrations remained significantly associated with 3-month mortality (OR 0.34 per 1-SD increase, 95% CI 0.15-0.74, p =0.010). We conclude that low admission serum levels of HDL3-C are associated with an increased 3-month mortality in AHF patients, whereas total HDL-C and HDL2-C showed no association. HDL3-C might thus be useful as a prognostic parameter in AHF
HPV-driven oropharyngeal squamous cell cancer in Croatia — demography and survival
Get PDFObjectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Main HNSCC risk factors are tobacco, alcohol, and high-risk human papillomavirus (HPV). HPV+ oropharyngeal squamous cell cancer (OPSCC) usually have different etiology, increasing incidence and often show an improved survival when compared to HPV-negative cases. The objective of the current study was to retrospectively examine the influence of HPV on the survival of OPSCC patients in a non-Western population setting. ----- Materials and methods: We determined the presence of HPV DNA and/or RNA in 99 formalin-fixed paraffin embedded (FFPE) tissue samples of OPSCC patients treated between 2002 and 2015. Patients were compared based on laboratory, demographic, clinical, life style characteristics and survival. ----- Results: HPV RNA was found in 29.3% cases. However, groups based on HPV data (either RNA, DNA or retrospectively collected p16 staining) did not show significant differences. Overall, 5-year survival was 30% with minimal influence of the HPV positivity. ----- Conclusions: The HPV influence on survival of OPSCC patients is not identical between populations probably due to other factors overshadowing the HPV effect. This should be taken into account when treatment or policy decisions are made in each particular setting
Epidemiological and clinical features of primary biliary cholangitis in two Croatian regions: a retrospective study
Get PDFAim: To assess the measures of disease frequency and determine the clinical features of primary biliary cholangitis (PBC) in two Croatian regions.
Methods Databases of two tertiary hospitals, one located in the continental and one in the coastal region of Croatia, were retrospectively searched for PBC patients diagnosed from 2007 to 2018. Epidemiologic data analysis was restricted to patients from each hospital’s catchment area. We analyzed factors related to response to therapy and event-free survival (EFS), defined as absence of ascites, variceal bleeding, encephalopathy, hepatocellular carcinoma, liver transplantation (LT), or death. In addition, we determined clinical and demographic data of transplanted PBC patients.
----- Results: Out of 83 PBC patients, 86.7% were female, with a median age at diagnosis of 55 years. Average PBC incidence for the 11-year period was 0.79 and 0.89 per 100 000 population, whereas the point prevalence on December 31, 2017 was 11.5 and 12.5 in the continental and coastal region, respectively. Of 76 patients with complete medical records, 21% had an advanced disease stage, 31.6% had an associated autoimmune condition, and all received ursodeoxycholic acid. EFS rate at 5 years was 95.8%. In an age and sex-adjusted multivariate Cox regression model, the only factor significantly associated with inferior EFS was no response to therapy (HR = 18.4; P = 0.018). Of all Croatian patients who underwent LT, 3.8% had PBC, with the survival rate at 5 years after LT of 93.4%.
----- Conclusion: This study gives pioneer insights into the epidemiological and clinical data on PBC in Croatia, thus complementing the PBC map of Southeast Europe