Radiation-induced caries as the late effect of radiation therapy in the head and neck region.

Overall improvement in the nationwide system of medical services has consequently boosted the number of successfully treated patients who suffer from head and neck cancer. It is essential to effectively prevent development of radiation-induced caries as the late effect of radiation therapy. Incidence and severity of radiationinduced changes within the teeth individually vary depending on the patient's age, actual radiation dose, size of radiation exposure field, patient's general condition and additional risk factors. Inadequately managed treatment of caries may lead to loss of teeth, as well as prove instrumental in tangibly diminishing individual quality of life in patients. Furthermore, the need to have the teeth deemed unyielding or unsuitable for the application of conservative methods of treatment duly extracted is fraught for a patient with an extra hazard of developing osteoradionecrosis (ORN), while also increasing all attendant therapeutic expenditures. The present paper aims to offer some practical insights into currently available methods of preventing likely development of radiation-induced caries.

[ApoE-containing HDL and the development of atherosclerosis]. / HDL zawierajace apolipoproteine E a rozwój miazdzycy

The current state of knowledge about the role of high density lipoproteins (HDL) indicates that their anti-atherogenic function is mainly related to the effectiveness of their actions (mostly to the participation in reverse cholesterol transport from tissues to liver) rather than the concentration of HDL itself. HDLs are highly heterogeneous in their structure, lipid and protein composition and metabolic pathways and individual HDL subpopulations differ in their biological activity and effectiveness of anti-atherogenic actions. Apolipoproteins play a key role in HDL metabolism, therefore their presence in lipoproteins is one of the main criterion for HDL classification. According to this criterion HDLs containing apolipoprotein E, called HDL-apoE, are distinguished. Although the anti-atherogenic role of apo E has been demonstrated in many scientific reports, understanding of the mechanisms of formation, transformation and the role of HDL-apoE is still the aim of intense research. The results of epidemiological studies are inconclusive; some of them have demonstrated that high HDL- -apoE concentration has been associated with lower risk of developing coronary heart disease (CHD), while other studies have shown that high levels of HDL-apoE has been an independent risk factor for cardiovascular events and positively correlated with other risk factors for CHD.

Successful treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disease with central nervous system involvement following allogeneic haematopoietic stem cell transplantation - a case study.

Post-transplant lymphoproliferative disease (PTLD) is a rare but severe form of Epstein-Barr virus (EBV)-driven complication that develops in patients after haematopoietic stem cell transplantation. In rare cases it manifests as primary central nervous system (CNS) involvement, which is thought to be the most unfavourable localisation with respect to outcome. Disease confined to the CNS is much more challenging than systemic PTLD, and one of the contributing factors is the limited drug penetration across the blood-brain barrier. We describe the case of a 29-year-old woman who was successfully treated for PTLD with CNS involvement. The patient was diagnosed with T-cell lymphoblastic lymphoma and underwent the procedure of haematopoietic stem cell transplantation from an unrelated donor. Two months after transplantation she manifested severe headache and progressive mental deterioration accompanied by enlargement of the lymph nodes. Magnetic resonance imaging (MRI) scan revealed segmental, asymmetrical thickening of the meninges. Based on the clinical picture and the laboratory findings diagnosis of PTLD was made. The patient was effectively treated with reduction of immunosuppressive therapy and intravenous rituximab. Initially started intrathecal chemotherapy was stopped due to iatrogenic complications. We conclude that in this case the involvement of meninges in the course of the lymphoproliferative process might have compromised the blood-brain barrier. This factor probably improved rituximab's penetration to CNS, contributing to our patient's recovery.

Candidaemia in polish hospitals - a multicentre survey.

Significant changes in the frequency of candidaemia and the distribution of causative species have been noted worldwide in the last two decades. In this study, we present the results of the first multicentre survey of fungaemia in Polish hospitals. A total of 302 candidaemia episodes in 294 patients were identified in 20 hospitals during a 2-year period. The highest number of infections was found in intensive care (30.8%) and surgical (29.5%) units, followed by haematological (15.9%), 'others' (19.2%) and neonatological (4.6%) units. Candida albicans was isolated from 50.96% of episodes; its prevalence was higher in intensive care unit and neonatology (61.22% and 73.33%, respectively), and significantly lower in haematology (22%; P < 0.001). The frequency of C. krusei and C. tropicalis was significantly higher (24% and 18%) in haematology (P < 0.02); whereas, the distribution of C. glabrata (14.1%) and C. parapsilosis (13.1%) did not possess statistically significant differences between compared departments. Obtained data indicates that species distribution of Candida blood isolates in Polish hospitals reflects worldwide trends, particularly a decrease in the prevalence of infections due to C. albicans.

The standardization of urine particle counting in medical laboratories--a Polish experience with the EQA programme.

BACKGROUND: Given the common problems with the standardization of urine particle counting methods and the great variability in the results obtained by Polish laboratories under international Labquality External Quality Assessment (EQA), we initiated educational recovery activities. METHODS: Detailed instructions on how to perform the standardized examination were sent to EQA participants, as was a questionnaire forms which enabled information to be gathered in respect to the procedures being applied. Laboratory results were grouped according to the method declared on the EQA 'Result' form or according to a manual examination procedure established on the basis of the questionnaire. The between-laboratory CVs for leukocyte and erythrocyte counts were calculated for each group and compared using the Mann-Whitney test. RESULTS: Significantly lower between-laboratory CVs (p = 0.03) were achieved for leukocyte counting among the laboratories that analysed control specimens in accordance with standardized procedures as compared with those which used non-standardized procedures. We also observed a visible lower variability for erythrocyte counting. Unfortunately despite our activities, only a few of the Polish laboratories applied the standardized examination procedures, and only 29% of the results could have been considered to be standardized (16% - manual methods, 13% - automated systems). CONCLUSIONS: The standardization of urine particle counting methods continues to be a significant problem in medical laboratories and requires further recovery activities which can be conducted using the EQA scheme.

Apo A-II participates in HDL-liposome interaction by the formation of new pre-ß mobility particles and the modification of liposomes.

Interaction between high density lipoproteins (HDL) and liposomes results in both a structural modification of HDL and the generation of new pre-ß HDL-like particles. Here, phosphatidylcholine liposomes and human HDL were incubated at liposomal phospholipid/HDL phospholipid (L-PL/HDL-PL) ratios of 1:1, 3:1 and 5:1 with a subsequent assessment of the distribution of apolipoprotein (apo) A-I, apo A-II, free cholesterol (FC) and PL between newly generated pre-ß mobility lipoproteins and non-disrupted liposomes. Both at L-PL/HDL-PL ratios of 3:1 and 5:1 the fraction of liposomal-derived PL associated with pre-ß fraction was significantly higher than those accepted by α-HDL. We found that 78% of apo A-I released from HDL was incorporated into pre-ß mobility fraction. The relative contents of PL and apo A-I in pre-ß fraction were constant irrespective of the initial L-PL/HDL-PL ratio in the incubation mixture and accounted for approximately 83 and 11%, respectively. Apo A-II was detached from HDL to a similar extent as apo A-I and distributed evenly between pre-ß fraction and non-disrupted liposomes. Apo A-II constituted approximately 1%, by weight, in these fractions at all L-PL/HDL-PL ratios investigated. It corresponded approximately to 10% of pre-ß fraction protein mass. Both liposomes and pre-ß fraction accepted comparable amounts of FC released from HDL. This data indicated that during the interaction between human HDL and phosphatidylcholine liposome apo A-II participates both in structural modification of liposomes and in the generation of pre-ß mobility fraction of constant content of PL, apo A-I and apo A-II. Involvement of apo A-II in HDL-liposome interaction may influence the anti-atherogenic properties of liposomes.

Acetyl-CoA and acetylcholine metabolism in nerve terminal compartment of thiamine deficient rat brain.

The decrease of pyruvate and ketoglutarate dehydrogenase complex activities is the main cause of energy and acetyl-CoA deficits in thiamine deficiency-evoked cholinergic encephalopathies. However, disturbances in pathways of acetyl-CoA metabolism leading to appearance of cholinergic deficits remain unknown. Therefore, the aim of this work was to investigate alterations in concentration and distribution of acetyl-CoA and in acetylcholine metabolism in brain nerve terminals, caused by thiamine deficits. They were induced by the pyrithiamine, a potent inhibitor of thiamine pyrophosphokinase. The thiamine deficit reduced metabolic fluxes through pyruvate and ketoglutarate dehydrogenase steps, yielding deficits of acetyl-CoA in mitochondrial and cytoplasmic compartments of K-depolarized nerve terminals. It also inhibited indirect transport of acetyl-CoA though ATP-citrate lyase pathway being without effect on its direct Ca-dependent transport to synaptoplasm. Resulting suppression of synaptoplasmic acetyl-CoA correlated with inhibition of quantal acetylcholine release (r = 0.91, p = 0.012). On the other hand, thiamine deficiency activated non-quantal acetylcholine release that was independent of shifts in intraterminal distribution of acetyl-CoA. Choline acetyltransferase activity was not changed by these conditions. These data indicate that divergent alterations in the release of non-quantal and quantal acetylcholine pools from thiamine deficient nerve terminals could be caused by the inhibition of acetyl-CoA and citrate synthesis in their mitochondria. They in turn, caused inhibition of acetyl-CoA transport to the synaptoplasmic compartment through ATP-citrate lyase pathway yielding deficits of cholinergic functions.

[Disturbances of lipoprotein metabolism in metabolic syndrome]. / Zaburzenia metabolizmu lipoprotein w zespole metabolicznym.

Dyslipidemia in metabolic syndrome (MS), called the atherogenic triad, includes elevated levels of plasma triglycerides (TGs), low levels of HDL-cholesterol (HDL-CH), and the presence of small dense low-density lipoproteins (sdLDLs) with normal or slightly elevated LDL-CH levels. Insulin resistance drives the increase in the three main sources of TG for VLDL synthesis: fatty-acid flux from adipose tissue, de novo lipogenesis, and uptake of remnant lipoproteins. Overproduction of VLDL, predominantly triglyceride-rich large VLDL1 particles, induces the cascade of events which lead to abnormalities of other plasma lipoproteins. The accumulation of VLDL in plasma and decreased activity of lipoprotein lipase (LPL) impair the catabolism of chylomicrons. Moreover, hyperinsulinemia induces increased intestinal production of chylomicrons. These factors cause augmented postprandial lipemia. Hepatic overproduction of VLDL leads to an increased level of VLDL remnants in plasma. Highly atherogenic sdLDLs are generated from VLDL1 particles by the action of LPL, cholesterol ester transfer protein (CETP), and hepatic lipase (HL). In the presence of hypertriglyceridemia, accelerated CETP-mediated lipid transfer generates TG-enriched HDL particles. This enhances HDL catabolism mediated by HL and endothelial lipase (EL). The assessment of risk of atherosclerotic cardiovascular disease in MS related to low HDL-CH and the presence of sdLDL particles may be improved by the incorporation of measurements of apolipoproteins (apo)-B and apoA-I into clinical practice. In addition, the concentration of non-HDL-CH may be useful in quantifying apo-B-containing atherogenic lipoproteins.

[The role of apolipoproteins A-I and A-II in plasma HDL remodeling]. / Rola apolipoprotein A-I i A-II w przemianach HDL w osoczu.

Apolipoprotein (apo) A-I is a key HDL protein participating in the process of reverse cholesterol transport. A small part of plasma apo A-I exists as free protein which is a substrate for generation of discoid HDL precursors, containing small amounts of phospholipids and free cholesterol. The cycling of apo A-I between precursor and mature forms of HDL is an essential element of HDL remodeling in plasma. The second most abundant protein of human HDL is apo A-II, nevertheless, it is present only in about half of the HDL particles in plasma. The mechanism mediating the formation of HDL containing apo A-I and apo A-II is unknown. The role of apo A-II in reverse cholesterol transport generates controversy. Different observations indicate either proatherogenic or proinflammatory properties of apo A-II. Also the participation of apo A-II in plasma HDL remodeling remains unclear. Apo A-II maybe a factor stabilizing HDL particles. This protein may also take part in regulation of VLDL metabolism. The review presents current knowledge concerning participation of apo A-I and apo A-II in plasma HDL remodeling.

[The analysis of usefulness different diagnostic methods in children and adolescents with Helicobacter pylori infection]. / Analiza przydatnosci róznych metod diagnostycznych w ocenie zakazenia Helicobacter pylori u dzieci i mlodziezy.

UNLABELLED: A diagnostics of Helicobacter pylori infection in children and adolescents in practice sometimes is still difficult. Qualification to the tests for detecting infection with invasive and noninvasive methods should start from diligent anamnesis. THE AIM OF THE STUDY: Is to present the clinical course and results of diagnostic tests in children and adolescents with suspicion of Helicobacter pylori infection. MATERIAL AND METHODS: One hundred patients aged between 18 months and 18 years who underwent endoscopy with gastric biopsies, histology, culture and 13carbon urea breath test. There were 36 boys and 64 girls in analysed group, 10% of them were preschool children, 42% school children and 48% teenagers older than 12 years RESULTS: Patients were symptomatic and most frequent were dyspeptic symptoms (91%). A symptom duration time was varied from several days to several years. On the basis of endoscopy and histology gastritis and/or duodenitis were found in 92 patients, esophagitis and gastritis in 5 patients, duodenal ulcer in 2 patients, in 1 case gastric and duodenal mucosa was normal. Helicobacter pylori infection was histopathologically confirmed in 37 patients. In 15 cases Helicobacter pylori strains were isolated with full in vitro sensitivity to amoxicillin, claritromycin and metronidazol. Urea breath test was conducted in 85 analyzed patients and 51 of them had abnormal result. CONCLUSIONS: In clinical picture of Helicobacter infection most frequent were dyspepstic symptoms and by endoscopy chronic gastritis and/or duodenitis were shown. Culture of Helicobacter pylori has a limited usefulness in practice especially in patients who underwent antibiotic/eradication therapy. The statistical significant concordance occurred between culture and noninvasive 13carbon urea breath test.

Interaction between VLDL and phosphatidylcholine liposomes generates new γ-LpE-like particles.

One of the subfractions of HDL involved in reverse cholesterol transport is γ-LpE. It has been assumed that, like preß-LpAI, it can be generated during the interaction between phosphatidylcholine liposomes and lipoproteins and can contribute to more efficient cholesterol efflux after the introduction of liposomes to plasma. However, there has been no evidence concerning what the sources of these particles in plasma might be. Here, we determined whether the interaction of phosphatidylcholine liposomes with VLDL and the subsequent conversions of particles could be a source of new γ-LpE particles. We found that the interaction between liposomes and VLDL affected its lipid and protein composition. The content of phospholipids increased (~96 %) while the content of free cholesterol and apolipoprotein E decreased in VLDL during the reaction with liposomes (~100 and ~24 %, respectively). New particles which did not contain apolipoprotein B were generated. Heterogeneous HDL-sized populations of particles were generated, containing phospholipids and apolipoprotein E as the sole apolipoprotein, with densities from 1.063 to 1.21 g/ml, either with γ-mobility on agarose gel and Stokes diameters from 8.58 to 22.07 nm or with preß-mobility and Stokes diameters from 9.9 to 21.08 nm. The obtained results contribute to the understanding of changes in lipoproteins under the influence of phosphatidylcholine liposomes, showing the formation of new (γ-LpE)-like and (preß-LpE)-like particles, similar in mobility and size to plasma HDL-LpE. These newly generated particles can claim a share of the antiatherogenic effects of liposomes, observed in studies both in vitro and in vivo.

The origin and metabolism of a nascent pre-ß high density lipoprotein involved in cellular cholesterol efflux.

The pre-ß HDL fraction constitutes a heterogeneous population of discoid nascent HDL particles. They transport from 1 to 25 % of total human plasma apo A-I. Pre-ß HDL particles are generated de novo by interaction between ABCA1 transporters and monomolecular lipid-free apo A-I. Most probably, the binding of apo A-I to ABCA1 initiates the generation of the phospholipid-apo A-I complex which induces free cholesterol efflux. The lipid-poor nascent pre-ß HDL particle associates with more lipids through exposure to the ABCG1 transporter and apo M. The maturation of pre-ß HDL into the spherical α-HDL containing apo A-I is mediated by LCAT, which esterifies free cholesterol and thereby forms a hydrophobic core of the lipoprotein particle. LCAT is also a key factor in promoting the formation of the HDL particle containing apo A-I and apo A-II by fusion of the spherical α-HDL containing apo A-I and the nascent discoid HDL containing apo A-II. The plasma remodelling of mature HDL particles by lipid transfer proteins and hepatic lipase causes the dissociation of lipid-free/lipid-poor apo A-I, which can either interact with ABCA1 transporters and be incorporated back into pre-existing HDL particles, or eventually be catabolized in the kidney. The formation of pre-ß HDL and the cycling of apo A-I between the pre-ß and α-HDL particles are thought to be crucial mechanisms of reverse cholesterol transport and the expression of ABCA1 in macrophages may play a main role in the protection against atherosclerosis.

Acetyl-CoA deficit in brain mitochondria in experimental thiamine deficiency encephalopathy.

Several pathologic conditions are known to cause thiamine deficiency, which induce energy shortages in all tissues, due to impairment of pyruvate decarboxylation. Brain is particularly susceptible to these conditions due to its high rate of glucose to pyruvate-driven energy metabolism. However, cellular compartmentalization of a key energy metabolite, acetyl-CoA, in this pathology remains unknown. Pyrithiamine-evoked thiamine deficiency caused no significant alteration in pyruvate dehydrogenase and 30% inhibition of α-ketoglutarate dehydrogenase activities in rat whole forebrain mitochondria. It also caused 50% reduction of the metabolic flux of pyruvate through pyruvate dehydrogenase, 78% inhibition of its flux through α-ketoglutarate dehydrogenase steps, and nearly 60% decrease of intramitochondrial acetyl-CoA content, irrespective of the metabolic state. State 3 caused a decrease in citrate and an increase in α-ketoglutarate accumulation. These alterations were more evident in thiamine-deficient mitochondria. Simultaneously thiamine deficiency caused no alteration of relative, state 3-induced increases in metabolic fluxes through pyruvate and α-ketoglutarate dehydrogenase steps. These data indicate that a shortage of acetyl-CoA in the mitochondrial compartment may be a primary signal inducing impairment of neuronal and glial cell functions and viability in the thiamine-deficient brain.

Phospholipids mediated conversion of HDLs generates specific apoA-II pre-beta mobility particles.

Apolipoproteins (apo)A-I and A-II are major proteins of human HDL. The cycling of apoA-I between lipid-poor and lipid-rich forms of HDL plays a key role in the transport of cholesterol by these particles. ApoA-II resides only in part of HDL particles, and little is known about its role in HDL metabolism. Our study investigates the redistribution of apoA-II after HDL remodelling induced by exogenous phospholipids (PL). During incubation with egg yolk lecithin (EYL) liposomes, human HDL became PL-enriched and free cholesterol (FC)-depleted, and lost small amounts of apoA-I and apoA-II. The loss of FC and apolipoproteins correlated with the rise of PL content in HDL. Agarose gel electrophoresis demonstrated the appearance of new pre-beta mobility fractions containing apoA-I and apoA-II in liposomes and HDL mixtures. Two-dimensional nondenaturing 2-27% PAGE has shown that the pre-beta mobility fraction that appeared at initial liposome-PL/HDL-PL ratio 5:1 consisted of two distinct heterogeneous subpopulations of particles containing either apoA-I or apoA-II. Our study provides evidence that during HDL conversion mediated by PL apoA-II dissociated from HDL particles yielding apoA-II-specific pre-beta mobility particles. This observation supports the hypothesis that apoA-II in plasma, like apoA-I, may cycle between lipid-poor and lipid-rich forms of HDL.