Health-related quality of life in the patients on maintenance hemodialysis: the analysis of demographic and clinical factors

Health-related quality of life (HRQoL) among hemodialysis (HD) patients recently became a nephrologist's focus of interest. HRQoL is an important predictor of outcome in HD patients and need to be regularly assessed. The aim of the present study was to compare the HRQoL of chronic HD patients with general population and to analyze influencing sociodemographic and clinical factors. We included 255 prevalent HD patients from four dialysis centers. HRQoL was measured with The Medical Outcomes Study Short Form 36 Health Survey Questionnaire (SF-36). This data were compared with control group (N = 132) from the general Croatian population. Comparisons of SF-36 scale scores of HD patients regarding demographic and clinical factors (age, gender, education level, dialysis vintage and diabetes) were also performed and analyzed with a multivariate regression analysis. HRQoL in prevalent HD patients was relatively low (mean Physical Component Summary, PCS = 33.7, mean Mental Component Summary, MCS = 43.0) and was lower compared to the control group from the general population in all HRQoL domains, PCS and MCS scores. Almost 53% of the HD patients had the critical score PCS < 43 + MCS < 51 as the predictor of death and hospitalization. Better HRQoL was revealed in the patients < 65 years old, males, patients with higher educational level and in the patients on maintenance HD less than one year. Age was the only statistically significant predictor of PCS and MCS. Developments of HD technology, treatment of comorbidities, continuous patients' education, social and psychological support and use of other renal replacement modalities, especially kidney transplantation, may improve the HRQoL in these patients.     

Cross-talk between NKT and regulatory T cells (Tregs) in modulation of immune response in patients with colorectal cancer following different pain management techniques

Natural killer T (NKT) and regulatory T cells (Tregs) play an important role in innate immune response. Natural killer (NK) and NKT cells are indispensable factors in the body's ongoing defense against tumor development, as well as viral infection. NKT cells are a subset of T cells that shares properties of natural killer cells and conventional T cells. They are involved in innate immune responses, tumor rejection, post transplantation immunotherapy, immune surveillance and control of autoimmune diseases. They may also play both protective and harmful roles in the progression of certain autoimmune diseases, such as diabetes, lupus, atherosclerosis, and allergen-induced asthma. Immune surveillance involves the process whereby precancerous and malignant cells are recognized by the host immune system as damaged and are consequently targeted for elimination. The pharmacological management of postoperative pain in patients with malignancies uses very different techniques whose possible cytotoxic functions we still known very poor. The present study compared effects of two different postoperative pain management techniques in patients undergoing colorectal cancer surgery on the innate immunity. Our data indicate that the patients with colorectal cancer have significantly increased the percentage of Tregs and NKT cells. The values were statistically higher during epidural analgesia in comparison with intravenous analgesia, indicating that epidural pain management technique ameliorate the immune suppression after surgery.     

The chronology of third molar eruption in the Croatian population

Dental age estimation is common in orthodontics, paedodontics, paleodontology and forensic dentistry. The aim of this study was to assess chronological course of eruptive developmental phases of third molar and to establish parameters for the Croatian population. Sample of this study consisted of 1249 orthopantomograms of 530 (42.4%) male and 719 (57.6%) female subjects, aged 10 to 25 years. Eruptive phases were classified in 4 stages. No significant sex difference was found. Established chronology of the third molar eruption can be used as a standard for the assessment of dental age in clinical and forensic research on samples of Croatian population.     

Postoperative use of radioiodine (131-I): review of recommendations and guidelines

In the management of large number of patients with differentiated thyroid cancer, the radioactive iodine (131-I) administration plays an important role. The guidelines of numerous international and national medical societies regarding the issue of postoperative 131-I administration have been published and updated in the last few years. The guidelines differ in the shape and content, and contain some specific features. The different methods for evaluation and analysis of clinical evidence level and resulting grades of recommendations have been used in line with the very guidelines. The postoperative 131-I administration refers to the radioiodine ablation as a form of adjuvant treatment and radioiodine therapy in the management of patients with recurrent cancer, persistent disease and regional or distant metastases. According to the indications for the postoperative 131-I administration, the patients could be divided into the three risk groups: the very low risk group in which there is no indication for the postoperative 131-I administration, the low risk group in which the indication could be considered, and the high risk group in which there is a clear indication for the 131-I administration. The different criteria for distribution of patients into these three groups are expressed in a certain guidelines. There are different opinions about the necessary dosage of 131-I for the efficient ablation in the low risk group. Moreover, the opinions are also divided regarding the conduction of postoperative (preablative or pretherapeutic) scintigraphy with 131-I. As regards the instructions on preparation of patients for the radioiodine ablation and therapy, all the guidelines recommend the low iodine diet and endogenous or exogenous stimulation of TSH. The endogenous stimulation is accomplished by the withdrawal of thyroid hormones, whereas the recombinant human TSH (rhTSH) is used for exogenous stimulation. For conducting the therapy with 131-I the level of TSH has to be > 25-30 mU/L.     

Nutritional modulation of CK2 in Saccharomyces cerevisiae: regulating the activity of a constitutive enzyme

CK2 is a highly conserved protein kinase involved in different cellular processes, which shows a higher activity in actively proliferating mammalian cells and in various types of cancer and cancer cell lines. We recently demonstrated that CK2 activity is strongly influenced by growth rate in yeast cells as well. Here, we extend our previous findings and show that, in cells grown in either glucose or ethanol-supplemented media, CK2 presents no alteration in K(m) for both the ATP and the peptide substrate RRRADDSDDDDD, while a significant increase in V (max) is observed. In chemostat-grown cells, no difference of CK2 activity was observed in cells grown at the same dilution rate in media supplemented with either ethanol or glucose, excluding the contribution of carbon metabolism on CK2 activity. By using the eIF2β-derived peptide, which can be phosphorylated by the holoenzyme but not by the free catalytic subunits, we show that the holoenzyme activity requires the concurrent presence of both β and β' encoding genes. Finally, conditions of nitrogen deprivation leading to a G0-like arrest result in a decrease of total CK2 activity, but have no effect on the activity of the holoenzyme. These findings newly indicate a regulatory role of β and β' subunits of CK2 in the nutrient response.     

Voltage-dependent anion channel as a resident protein of lipid rafts: post-transductional regulation by estrogens and involvement in neuronal preservation against Alzheimer's disease

The voltage-dependent anion channel, VDAC, is present at the neuronal membrane, where it appears to participate, among others, in the extrinsic apoptotic pathway and in the modulation of amyloid-beta induced injury, suggesting the involvement of this channel in Alzheimer's disease (AD) neurotoxicity. VDAC is also highly concentrated in neuronal lipid raft microdomains of different mouse and human cognitive areas, where it has been shown associated with estrogen receptor alpha (ERα), as a part of a `signalosome' that may activate some intracellular signal transduction. At the plasma membrane level, estrogens and antiestrogens (tamoxifen) have been demonstrated to exert rapid antagonist effects on the activation of VDAC, through their distinct effects on the channel post-transductional modulation. Therefore, part of the alternative mechanisms of estrogen related to neuroprotection against amyloid-beta may involve VDAC phosphorylation, in order to maintain the channel in an unactivated (closing) state. Interestingly, VDAC-ERα association has been shown to be disrupted in neuronal lipid rafts of AD brains, in correlation with the aberrant lipid composition observed in these microstructures, suggesting that disturbance of protein interactions may be related to variation in the physico-chemical properties of these microdomains.     

Transferability and Level of Heterozygosity of Microsatellite Markers in <Emphasis Type="Italic">Citrus</Emphasis> Species

Microsatellite markers are a powerful tool for genetic studies, including germplasm conservation, cultivar identification, and integration of linkage maps. Several works have shown that primer pairs designed for one species can be used in related species to facilitate wider application because it reduces the costs for primer development. The objective of this study was to evaluate the transferability of microsatellite primers which was previously developed from the genomic library of Pêra sweet orange (Citrus sinensis L. Osbeck) and to determine the level of heterozygosity between citrus accessions and related genera. Twenty-four microsatellite loci were evaluated on 12 genotypes of Citrus, Poncirus, and an intergeneric hybrid. All analyzed markers were transferable across all genotypes. Seventeen loci were polymorphic, and the number of alleles per loci ranged from one to six. The lowest level of heterozygosity was observed for Poncirus trifoliata (L.) Raf. cultivars while the highest level was for Swingle citrumelo. In general, microsatellite markers showed wide genetic variation and demonstrated that they can be useful in citrus breeding programs.     

IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion

Interferon-induced transmembrane proteins (IFITMs) inhibit infection of diverse enveloped viruses, including the influenza A virus (IAV) which is thought to enter from late endosomes. Recent evidence suggests that IFITMs block virus hemifusion (lipid mixing in the absence of viral content release) by altering the properties of cell membranes. Consistent with this mechanism, excess cholesterol in late endosomes of IFITM-expressing cells has been reported to inhibit IAV entry. Here, we examined IAV restriction by IFITM3 protein using direct virus-cell fusion assay and single virus imaging in live cells. IFITM3 over-expression did not inhibit lipid mixing, but abrogated the release of viral content into the cytoplasm. Although late endosomes of IFITM3-expressing cells accumulated cholesterol, other interventions leading to aberrantly high levels of this lipid did not inhibit virus fusion. These results imply that excess cholesterol in late endosomes is not the mechanism by which IFITM3 inhibits the transition from hemifusion to full fusion. The IFITM3''s ability to block fusion pore formation at a post-hemifusion stage shows that this protein stabilizes the cytoplasmic leaflet of endosomal membranes without adversely affecting the lumenal leaflet. We propose that IFITM3 interferes with pore formation either directly, through partitioning into the cytoplasmic leaflet of a hemifusion intermediate, or indirectly, by modulating the lipid/protein composition of this leaflet. Alternatively, IFITM3 may redirect IAV fusion to a non-productive pathway, perhaps by promoting fusion with intralumenal vesicles within multivesicular bodies/late endosomes.     

Diarylheptanoids from Green Alder Bark and Their Potential for DNA Protection

Nine diarylheptanoids, 1 – 9 , catechin ( 11 ), and a phenolic glucoside, 10 , were isolated from the bark of green alder (Alnus viridis). Four of the isolated compounds, i.e., 2, 5, 8, 10 , are new. The structures of 1 – 11 were determined on the basis of spectroscopic data. All isolated compounds were evaluated for their in vitro protective effects on chromosome aberrations in peripheral human lymphocytes using cytokinesis‐block micronucleus (CBMN) assay. Almost all of them exerted a pronounced effect of decreasing DNA damage of human lymphocytes, acting stronger than the known synthetic protector amifostine.     

Leaf n‐Alkanes as Characters Differentiating Coastal and Continental Juniperus deltoides Populations from the Balkan Peninsula

The composition of the cuticular n‐alkanes isolated from the leaves of nine populations of Juniperus deltoides R.P.Adams from continental and coastal areas of the Balkan Peninsula was characterized by GC‐FID and GC/MS analyses. In the leaf waxes, 14 n‐alkane homologues with chain‐lengths ranging from C₂₂ to C₃₅ were identified. n‐Tritriacontane (C₃₃) was dominant in the waxes of all populations, but variations between the populations in the contents of all n‐alkanes were observed. Several statistical methods (ANOVA, principal component, discriminant, and cluster analyses) were used to investigate the diversity and variability of the cuticular‐leaf‐n‐alkane patterns of the nine J. deltoides populations. This is the first report on the n‐alkane composition for this species. The multivariate statistical analyses evidenced a high correlation of the leaf‐n‐alkane pattern with the geographical distribution of the investigated samples, differentiating the coastal from the continental populations of this taxon.