The predictive ability of liver function indexes on 18F-FDG uptake in the liver.

AIM: The liver is an important reference organ for positron emission tomography/ computed tomography (PET-CT) examination using 18F-fluorodeoxyglucose (18F-FDG). However, 18F-FDG uptake by the liver is affected by many factors. We therefore investigated the effect of hepatic function on 18F-FDG uptake in the liver. METHODS: A retrospective analysis of data on the hepatic function and the mean liver standardized up-take value (SUV) of 18F-FDG uptake in the liver during PET-CT examination of 500 (381 males, 119 females, aged 27-71) physical examinees. RESULTS: The mean liver SUV was 1.88 ± 0.20. The correlation coefficient and partial correlation coefficient for age, the levels of conjugated bilirubin, globulin, AST and the mean liver SUV were statistically significant (r' = 0.119, -0.197, -0.089 and 0.151, all p < 0.05). Multiple linear regression analysis showed that age and the levels of conjugated bilirubin, globulin and aspartate amino-transferase (AST) were independent factors that influenced changes in the mean liver SUV (ß = 0.008, -0.025, -0.151 and 0.005, all p < 0.05). The globulin level had the biggest predictive ability (ß' = -0.151, p < 0.05). CONCLUSIONS: The uptake of 18F-FDG in the liver was influenced by some liver function indexes. The levels of conjugated bilirubin, globulin and AST were independent factors for predicting changes in the uptake of 18F-FDG in the liver. Liver function test results should be combined with an evaluation of the metabolic activity of the liver.

Renal function in children treated for central nervous system malignancies.

AIM: The aim of the study was to evaluate renal function and to assess the usefulness of the following nephrotoxicity markers: cystatin C (CYS C), beta-2 microglobulin (B2MG) and neutrophil gelatinase-associated lipocalin (NGAL) in 38 (18 girls, 20 boys) children previously treated for central nervous system malignancy. MATERIAL: Median age at evaluation was 13.7 years (range 2.1-22 years). The mean follow-up time after the completion of chemotherapy was 3.2 years (range 0.16-6.5 years). RESULTS: Subclinical chronic kidney disease (estimated glomerular filtration rate: eGFR 90-60 ml/min/1.73 m(2)) was found in 22 patients (58 %), while renal insufficiency (eGFR 30-60 ml/min/1.73 m(2)) was found in six children (16 %). It has been demonstrated statistically significant negative correlation between the eGFR and cystatin C concentration (p < 0.0001) and eGFR and beta-2 microglobulin concentration (p < 0.02). Conversely, there was no correlation between eGFR and NGAL. Thirteen children (34 %) developed drug-induced tubulopathy: decreased tubular reabsorption of phosphate (TRP) and renal tubular threshold for phosphate (Tmp/GFR). CONCLUSION: Children treated for CNS tumours often develop drug-induced chronic renal disease, involving the glomeruli and/or renal tubules. Cystatin C and beta-2 microglobulin seemed to be good markers for chronic kidney damage in these patients, which is probably not true for NGAL.

The spatio-temporal expression of MHC class I molecules during human hippocampal formation development.

In the immune system, the major histocompatibility complex (MHC) class I molecules mediate both the innate and adaptive immune responses in vertebrates. There has been a dogma that the central nervous system (CNS) is immune privileged and healthy neurons do not express MHC class I molecules. However, recent studies have indicated that the expression and non-immunobiologic roles of MHC class I in mammalian CNS. But data referring to humans are scarce. In this study we report the expression and cellular localization of MHC class I in the human fetal, early postnatal and adult hippocampal formation. The expression of MHC class I was very low in the hippocampus at 20 (gestational weeks) GW and slowly increased at 27-33 GW. The gradually increased expression in the somata of some granular cells in dentate gyrus (DG) was observed at 30-33 GW. Whereas, a rapid increase in MHC class I molecules expression was found in the subiculum and it reached high levels at 31-33 GW and maintained at postnatal 55 days. No expression of MHC class I was found in hippocampal formation in adult. MHC class I heavy chain and ß2 microglobulin (ß2M) showed similar expression in some cells of the hippocampal formation at 30-33 GW. Moreover, MHC class I molecules were mainly expressed in neurons and most MHC class I-expressing neurons were glutamatergic. The temporal and spatial patterns of MHC class I expression appeared to follow gradients of pyramidal neurons maturation in the subiculum at prenatal stages and suggested that MHC class I molecules are likely to regulate neuron maturation. This article is part of a Special Issue entitled Priority to Publish.

Serum protein profiles in domestic pigeons naturally infected with Mycobacterium avium subsp. avium.

BACKGROUND: Avian tuberculosis is an important disease affecting all species of birds and is most often caused by Mycobacterium avium or Mycobacterium genavense. Blood proteins are important diagnostic constituents in gastrointestinal, hepatic, renal, and infectious diseases. OBJECTIVE: The aim of the study was to compare serum protein profiles of domestic pigeons (Columba livia var. domestica) infected with Mycobacterium avium subsp. avium (MAA), with healthy pigeons. METHODS: Serum samples were collected from 80 pigeons with clinical signs of tuberculosis, all kept in the same loft. All birds were necropsied and cultured for mycobacteriosis; positive cultures were typed for MAA by PCR reactions targeting 16S rRNA, IS901 and IS1245. The concentration of total serum proteins was determined by the biuret method and spectrophotometry. Individual protein fractions were analyzed by cellulose acetate electrophoresis and extrapolated based on total protein concentration. For statistical analysis, the infected birds were compared with healthy pigeons. RESULTS: A total of 37 pigeons with culture results positive for MAA were selected and allocated to 2 groups, a culture-positive group with macroscopic lesions of tuberculosis and another without macroscopic lesions. Six protein fractions were identified: prealbumin, albumin, alpha-1, alpha-2, and beta globulins and gamma globulins. Concentrations of total protein, beta globulins and gamma globulins were statistically significantly higher in the infected pigeons when compared with the control group. There were no significant differences between the groups of birds with or without macroscopic lesions. CONCLUSIONS: Statistically significant differences in total protein, and beta and gamma globulin concentrations in all infected pigeons suggest that serum protein electrophoresis represents a nonspecific but valuable indicator for tuberculosis in pigeons.

Professional exposure to anaesthetic gases in health workers: estimate of some hepatic and renal tests.

OBJECTIVES: The aim of this study is to estimate whether the occupational exposure to low dose of anaesthetic gases could cause alterations of haematochemical hepatic and renal parameters in the health workers of a city hospital. MATERIALS AND METHODS: After excluding the main confounding factors, 154 exposed subjects and 98 not exposed controls were included in the study. The exposed subjects were divided in more exposed (group 1: n.54) and less exposed (group 2: n.100). Each worker included in this study underwent the CBC test (Complete Blood Count test). The differences between means were compared using the Student T test for unpaired data and considered significant when the p value was < 0.05. RESULTS: The mean values of serum albumin, alpha 1, alpha 2, beta and gamma globulins were significantly decreased in health workers of both groups compared to controls. The mean values of serum creatinine and gamma-GT were significantly higher in health workers of group 2 compared to controls. CONCLUSIONS: The obtained results suggest that occupational exposure to low dose of anaesthetic gases could influence haematochemical hepatic and renal parameters in exposed health workers.

[Assessment of the effect of selected mixture of food additives on the protein metabolism--model studies]. / Ocena wplywu mieszaniny wybranych dodatków do zywnosci na wskazniki metabolizmu bialkowego--badania modelowe.

BACKGROUND: Contemporarily, food production without food additives is very rare. Increasingly often, however, scientific works report on adverse effects of specified, single food additives on the body. Data is, in turn, lacking on the synergistic effect of a mixture of different food additives on body functions and its main metabolic pathways. OBJECTIVE: The objective of this study, an animal model, was to evaluate if and in what way the compound of chosen and most frequently used and consumed food additives, along with the change of diet composition to processed, purified, influence the selected markers of protein metabolism. MATERIAL AND METHODS: The animals were divided into four groups, which were fed with compound of feed pellets: group I and II with basic compound, group III and IV with modified compound in which part of the full grain was replaced by isocalorie wheat flour type 500 and saccharose. Animals from groups I and III received tap water, which was standing for some time, to drink. Animals from groups II and IV received solution of chosen additives to food and next they were given water to drink. The amount of given food additives was evaluated by taking into consideration their consumption by people recalculated to 1 kg of their body mass. The experiment spanned for 7 weeks. RESULTS: It was ascertained that the applied additives caused significant changes in total protein concentration and its fractions: albumin, alpha1-globulin, alpha2-globulin, beta-globulin and gamma-globulin in the blood serum of the animals under research, which can indicate and contribute to disclosure of creation of undesirable food reaction, especially when recommended levels of consumption of those additives are being exceeded. The organism response to the applied additives and accompanying it change of diet was essentially connected to sex of the animals. Undesirable character of changes taking place under the influence of applied additives, was observed both in animals fed with basic feed and modified feed with various intensity according to the parameter under research. CONCLUSIONS: The analysis of the results achieved enabled concluding that the applied mixture of food additives caused significant changes in the concentration of total protein and its fractions: albumins, alphal-, alpha2-, beta- and gamma-globulins in blood serum of the investigated animals. These changes may indicate but also may contribute to the development or manifestation of undesirable nutritional responses, especially when recommended dietary allowances are exceeded. The body's response to the applied additives and concomitant modification of diet composition was significantly correlated with sex of the animals. The unfavorable character of changes following the administration of additives was observed in both the animals on the basal diet and these fed the modified feed mixture, yet with a different intensity that was found to depend not on the feeding group but on the parameter examined.

[Effects of modified liangge powder contained serum on LPS stimulated TLR4 expression and release of cytokines in mouse platelets].

OBJECTIVE: To observe the effects of Modified Liangge Powder (MLP) on the expressions of platelet toll like receptor 4 (TLR4) and the release of platelet-derived cytokines interleukin 8 (IL-8), beta platelet globulin (beta-TG), soluble CD40 ligand (sCD40L). METHODS: The modulating effects on the release of cytokines from mice platelets by TLR4 ligand through monoclonal antibody blocking TLR4 on platelet were compared. The stimulated platelet by LPS was incubated with low (0.94 g/mL), medium (1.89 g/mL), and high (2.84 g/mL) dose of MLP contained serum. The changes of the platelet TLR4 expression and platelet-derived cytokines were observed. RESULTS: The positive expression rate of platelet TLR4 obviously decreased (P < 0.01) and the release of sCD40L and beta-TG from platelets significantly increased (P < 0.01) after stimulated by LPS. However, the release of sCD40L and beta-TG from platelets obviously decreased by TLR4 monoclonal antibody (P < 0.05, P < 0.01). There was no statistical difference in IL-8 between before and after LPS stimulation (P > 0.05). Platelet TLR4 positive expression rate was significantly higher after incubated by medium and high doses of MLP contained serum (P < 0.01), and the releasing of sCD40L and beta-TG was lower in the serum contained groups. The inhibitory effects were enhanced in a dose-dependent manner. CONCLUSIONS: LPS induced platelet activation by TLR4 and released sCD40L and beta-TG, while the release of platelet IL-8 was not dependent on platelet TLR4-LPS pathway. MLP could inhibit LPS-stimulated sCD40L and beta-TG, inhibit the binding of platelet TLR4 and LPS in a dose-dependent manner, thus reducing the release of platelet cytokines.

Prevalence of monoclonal gammopathy of undetermined significance in Thailand.

Individuals with monoclonal gammopathy of undetermined significance (MGUS) develop multiple myeloma and related malignancies at the rate of 1% per year. Given differences in ethnicity, data on prevalence and risk factors of MGUS in Thai population will be helpful in understanding the pathogenesis of plasma cell disorders and designing an early cancer detection strategy. Subjects of 50 years or older were included. Demographic data and suspected risk factors were collected. Monoclonal proteins were detected using serum protein electrophoresis. Serum was obtained from 3,260 participants; 1,104 males (33.9%) and 2,156 females (66.1%). The median age was 57 years (range 50-93 years). Monoclonal proteins were detectable in 2.3% (95% confidence interval [CI] 1.8-2.8). M spikes were found in gamma- and beta-globulin regions in 50 (1.5%) and 25 (0.8%) subjects, respectively. The prevalence of MGUS in subjects 50-59, 60-69, and 70 years or older was 2.0% (41/1,975), 2.6% (22/851), and 2.8% (12/434), respectively. By multivariate analysis, MGUS was associated with living outside Bangkok (odds ratio 2.25, 95% CI 1.11-4.58). The overall prevalence of MGUS in the Thai population was 2.3%, which was lower than that in Western countries, but comparable to that in Japan.

Prototypic chromatin insulator cHS4 protects retroviral transgene from silencing in Schistosoma mansoni.

Vesicular stomatitis virus glycoprotein (VSVG) pseudotyped murine leukemia virus (MLV) virions can transduce schistosomes, leading to chromosomal integration of reporter transgenes. To develop VSVG-MLV for functional genomics in schistosomes, the influence of the chicken ß-globin cHS4 element, a prototypic chromatin insulator, on transgene expression was examined. Plasmid pLNHX encoding the MLV 5'- and 3'-Long Terminal Repeats flanking the neomycin phosphotransferase gene (neo) was modified to include, within the U3 region of the 3'-LTR, active components of cHS4 insulator, the 250 bp core fused to the 400 bp 3'-region. Cultured larvae of Schistosoma mansoni were transduced with virions from producer cells transfected with control or cHS4-bearing plasmids. Schistosomules transduced with cHS4 virions expressed 2-20 times higher levels of neo than controls, while carrying comparable numbers of integrated proviral transgenes. The findings not only demonstrated that cHS4 was active in schistosomes but also they represent the first report of activity of cHS4 in any Lophotrochozoan species, which has significant implications for evolutionary conservation of heterochromatin regulation. The findings advance prospects for transgenesis in functional genomics of the schistosome genome to discover intervention targets because they provide the means to enhance and extend transgene activity including for vector based RNA interference.

Down-regulation of OPA1 in patients with primary open angle glaucoma.

PURPOSE: Heterozygous optic atrophy type1 (OPA1) mutations are responsible for dominant optic atrophy, and the down regulation of OPA1 expression in patients with Leber hereditary optic neuropathy may imply that Opa1 protein levels in mitochondria play a role in other spontaneous optic neuropathies as well. Mitochondrial and metabolic abnormalities may put the optic nerve at risk in primary open angle glaucoma (POAG), and this preliminary study was designed to investigate whether altered OPA1 expression might be present in the progressive optic neuropathy of POAG. METHODS: Patients were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥ 21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. RNA was extracted from leukocytes and converted to cDNA by reverse transcriptase enzyme, and real time PCR was used to assess expression levels of OPA1 and the ß-globulin (HBB) housekeeping gene. The ratio of OPA1 expression to HBB expression (OPA1/HBB) for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: Forty-three POAG patients and 27 controls were completely phenotyped with a full ophthalmologic examination and static perimetry. Mean age (POAG 67.9 years; controls 61.8 years) and sex (POAG 26 males/17 females; controls 11/16) were similar for the two groups. Mean OPA1/HBB of POAG patients (1.16, SD 0.26) was 18% lower than controls (1.41, SD 0.50), and this difference was statistically significant (p≤0.021). OPA1 expression differed between the groups (p≤0.037), but HBB expression did not differ (p≤0.24). OPA1/HBB was not correlated with any clinical feature of POAG patients. CONCLUSIONS: Transcriptional analysis of peripheral blood leucocytes is a limited model system for studying the consequences of mitochondrial abnormalities in the optic nerve. Nevertheless, OPA1 is known to affect mitochondrial stability and has now been implicated in several spontaneous optic neuropathies. Decreased OPA1 expression in POAG patients is another indication that mitochondrial function, and possibly mitochondrially-induced apoptosis, may play a role in the development of POAG.

Redox potentials of Ti(IV) and Fe(III) complexes provide insights into titanium biodistribution mechanisms.

Transferrin, the human iron transport protein, binds Ti(IV) even more tightly than it binds Fe(III). However, the fate of titanium bound to transferrin is not well understood. Here we present results which address the fate of titanium once bound to transferrin. We have determined the redox potentials for a series of Ti(IV) complexes and have used these data to develop a linear free energy relationship (LFER) correlating Ti(IV) <==> Ti(III) redox processes with Fe(III) <==> Fe(II) redox processes. This LFER enables us to compare the redox potentials of Fe(III) complexes and Ti(IV) complexes that mimic the active site of transferrin and allows us to predict the redox potential of titanium-transferrin. Using cyclic voltammetry and discontinuous metalloprotein spectroelectrochemistry (dSEC) in conjunction with the LFER, we report that the redox potential of titanium-transferrin is lower than -600 mV (lower than that of iron-transferrin) and is predicted to be ca. -900 mV vs. NHE (normal hydrogen electrode). We conclude that Ti(IV)/Ti(III) reduction in titanium-transferrin is not accessible by biological reducing agents. This observation is discussed in the context of current hypotheses concerning the role of reduction in transferrin mediated iron transport.

Effects of Iscador preparations on the reactivity of mouse immune system.

OBJECTIVES: Anticancer preparations made from plants have been an object of scientific interest for many years. It is worth noting that as many as 25% of cytostatics used in the anticancer chemotherapy are obtained from plants. One of the medical preparations which significantly influences cell metabolism is Iscador. Iscador preparations are used as complementary therapy in the conventional anticancer treatment. These are aqueous extracts of mistletoe (Viscum album L.). One repeatedly finds that mistletoe (Viscum album L.) extracts show immune-modulating effects. THE AIM at the present work was to study the influence of iscador Qu, M, P at a dose 5 mg/kg b.w., on the total protein concentration in blood serum and proportions of blood protein fractions determined by electrophoresis. Additionally leukocyte activity was estimated, which, served as indicators of the immune system reactivity in mice treated with anticancer preparations of vegetable origin. RESULTS: The experiment indicated statistically significant increase in albumin fraction level and lymphocyte count. Moreover, decrease of the total protein content, protein fractions globulins alpha2, beta, gamma and neutrophil, monocyte count in mouse serum was observed.

Electrophoretic profile of serum proteins in opium and heroin dependents.

OBJECTIVES: In this cross-sectional case-control study, albumin and globulin profile in the serum of opium and heroine addicts have been compared with correspondent values in a matched control group. METHODS: Opioid consumption was confirmed by laboratory diagnostic tests on urine samples and protein electrophoresis of serum was performed to determine the concentration and profile of serum proteins. RESULTS: There was no significant difference in albumin, alpha(1)-globulin, alpha(2)-globulin, and beta-globulin concentration among groups. Gamma-globulin concentration in opium and heroin addicts showed no significant difference, but it was significantly lower in comparison to the control group. CONCLUSION: This finding may be attributed to the higher probability of infectious diseases in opioids addicts.

[Biochemical criteria of occupationally related diseases formation in firemen].

Results of medical examination among working firemen and firemen with diagnosed occupational disease prove changes in protein and lipid metabolism. Decreased alpha-globulin fractions and increased beta-globulins could result from toxic chemical load and stress. Thus early changes in cholesterol metabolism without hepatic involvement are seen.

[Blood plasma proteins following long-duration space flight].

Protein composition of blood plasma was an object of investigation in 29 Russian cosmonauts flown on the MIR station from 125 to 366 days. Protein fractions were analyzed using acetate cellulose electrophoresis. Concentration of total protein was determined with the help of the biuret reaction on an automated analyzer. On the second day post flight, mean concentration of total protein and percentage of the protein fractions were equal to baseline values. In the interval between days 7 and 14 post flight, total protein was statistically reduced, alphal- N alpha2-globulins increased and y-globulin reduced, whereas albumin and beta-globulins were unchanged in the average. These results may point to development of an acute reaction in the early period of readaptation to the return from long-duration space flight.

The effect of high-flux hemodialysis on dialysis-associated amyloidosis.

Amyloidosis is an important cause of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). In this study, depending on the idea that the clearance of middle and high molecular weight toxins could be improved, we aimed to investigate the effect of high-flux dialyzer on clearance of beta-2 microglobulin (beta2-MG) and calcium (Ca) phosphorus (P) metabolism in patients under HD treatment. Forty-eight patients with ESRD under chronic HD treatment were included in the study. All patients were randomized into two groups, and HD was performed with low-flux or high-flux dialyzer for 6 months. In the high-flux group, the reduction of beta2-MG and P levels during dialysis was significantly higher when compared with the low-flux group (p<0.001). During the follow-up period, while beta2-MG levels decreased significantly in the high-flux group (p<0.05), there was an increase in the low-flux group (p<0.05). As a result, our findings suggest that use of high-flux dialyzer can be an efficient alternative in terms of controlling the clearance of beta2-MG and impaired Ca and P metabolism. These beneficial effects of high-flux dialyzers are probably mediated by the improved clearance of middle and high molecular weight toxins.

[Features of biochemical parameters in firemen].

The authors present results of examinations covering firemen with varying length of service and intensity of chemical load. Those results prove lower amount of alpha1-globulines and increased beta1-globulines content. Lipid metabolism disorders in idividuals with lower frequency of fires attended are caused by discrepancy between hormonal demands in stress expectation and actual utilization of energy substrates by various body tissues.

[The influence of hepatitis G virus infection on the course of chronic virus hepatitis B or C in children]. / Wplyw zakazenia wirusem zapalenia watroby typu G na przebieg przewleklego wirusowego zapalenia watroby typu B lub C u dzieci.

Hepatitis G virus (HGV) infection is often observed in patients with hepatitis B or C virus (HBV or HCV) infections. The aim of this study was an evaluation of the influence of HGV infection on the course of virus hepatitis B and C in children. 113 children aged 2-15 years old, with hepatitis B or C were enrolled to the study. In the study group children were examined for the presence of virus genetic material, e.g. HGV-RNA. The analysis of children records with respect to results of physical examination and additional tests (laboratory tests, abdomen ultrasonography) was carried out. On the basis of the analysis it was showed that HGV infection did not significantly change the course of basic liver disease.

The analogue of thymidine triphosphate containing a methylene group in place of the 5' oxygen can serve as a substrate for reverse transcriptase.

The thymidine 5'-triphosphate analogue containing a methylene group in place of the 5' oxygen atom can be prepared using modifications of published procedures and can substitute for the natural thymidine triphosphate in chain extension reactions catalyzed by Moloney-MLV reverse transcriptase. Using rabbit beta-globin mRNA as the template together with an appropriate primer, the enzyme readily makes full-length DNA transcripts in which all thymidine 5' oxygen atoms have been replaced with methylene groups. In sequence analyses using the partial depurination procedure, the analogue DNA transcript produces electrophoretic gel patterns identical with those of the corresponding natural DNA transcript. Experiments on second strand synthesis using the four regular triphosphates show that the analogue DNA transcript, like the natural transcript, can serve as a template. The two DNA duplexes (natural/natural and analogue/natural) formed by these reactions produce similar electrophoretic cleavage patterns when treated with either of the endonucleases HaeIII and EcoRI. However, further studies on template properties indicate that, while the enzyme makes a full-length product when using the analogue substrate with a natural DNA strand as template, it appears unable to use the analogue transcript as template with the analogue triphosphate as substrate during second strand synthesis. Preliminary experiments have also been carried out with a DNA polymerase. No products are detected reactions using Taq polymerase with PCR protocols containing the analogue triphosphate as the only source of thymidine.

Y14 and hUpf3b form an NMD-activating complex.

Messenger RNAs with premature translation termination codons (PTCs) are degraded by nonsense-mediated mRNA decay (NMD). In mammals, PTCs are discriminated from physiological stop codons by a process thought to involve the splicing-dependent deposition of an exon junction complex (EJC), EJC-mediated recruitment of Upf3, and Upf2 binding to the N terminus of Upf3. Here, we identify a conserved domain of hUpf3b that mediates an interaction with the EJC protein Y14. Tethered function analysis shows that the Y14/hUpf3b interaction is essential for NMD, while surprisingly the interaction between hUpf3b and hUpf2 is not. Nonetheless, hUpf2 is necessary for NMD mediated by tethered Y14. RNAi-induced knockdown and Y14 repletion of siRNA-treated cells implicates Y14 in the degradation of beta-globin NS39 mRNA and demonstrates that Y14 is required for NMD induced by tethered hUpf3b. These results uncover a direct role of Y14 in NMD and suggest an unexpected hierarchy in the assembly of NMD complexes.