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BACKGROUND: Advanced glycation end products (AGEs) accumulate in patients with decreased renal function and exert various toxic effects through the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) is a naturally occurring inhibitor of AGE-RAGE action. The aim of the study is to describe the relationship of sRAGE to renal function and dialysis modalities. METHODS: The studied group consisted of 81 patients: 25 patients with various degrees of decreased renal function, 20 long-term hemodialysis (HD) patients, 15 peritoneal dialysis (PD) patients, and 21 healthy age-matched subjects. sRAGE was assessed immunochemically (enzyme-linked immunosorbent assay), and routine biochemical parameters were measured by means of certified methods. RESULTS: sRAGE level correlates positively with serum creatinine concentration (r = 0.50; P < 0.05), and its relationship to creatinine clearance is hyperbolic. sRAGE levels are elevated significantly, mainly in patients with end-stage renal disease (3,119.0 +/- 968.4 pg/mL in HD patients and 3,652.7 +/- 1,677.7 pg/mL in PD patients versus 1,405.1 +/- 426.1 pg/mL in controls; both P < 0.001 versus controls). In PD patients, sRAGE is detectable in spent dialysate (median, 75.8 pg/mL), correlates with its serum levels (r = 0.67; P < 0.05), and is related to protein losses in dialysate. In HD patients, sRAGE levels increase by 50% (P < 0.001) from 0 to 15 minutes during both HD and hemodiafiltration, and then decrease until the end of the session. CONCLUSION: Serum sRAGE levels increase in patients with decreased renal function, mainly patients with end-stage renal disease. It remains to be elucidated whether the increase is caused just by decreased renal function or whether sRAGE is upregulated to protect against toxic effects of AGEs.
- MeSH
- chronické selhání ledvin krev patofyziologie terapie MeSH
- dialýza ledvin * MeSH
- ledviny patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory imunologické krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory imunologické MeSH
The lung cancer dia-gnosis is still connected with high mortality. Even the new anticancer drugs are not able to preserve long survival in the advanced lung cancer patients. Only a minority of patients is diagnosed with early or locally advanced stages. In the following review, we present interesting data regarding the treatment updates in these potentially curable patients.
- Klíčová slova
- early stage, lung cancer, treatment, type 2 diabetes,
- MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- nádory plic patologie terapie MeSH
- nemalobuněčný karcinom plic patologie terapie MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Chronic renal failure is associated with increased oxidative and carbonyl stresses that contribute to long-term uremic complications. In our study, we determined two markers of these stresses--AGEs (advanced glycation end products) and AOPP (advanced oxidation protein products)--in chronic hemodialysis patients in order to find out their relationship to the dialysis treatment. Plasmas of 20 hemodialyzed patients treated with modified cellulose membranes were examined at 0 and 15 min and at the end (i.e. after 4 h) of the dialysis session. AGEs were estimated using a spectrofluorometric method (excitation 350 nm, emission 440 nm) and are expressed in AU (arbitrary units)/g protein. AOPP were determined spectrophotometrically (absorbance at 340 nm) and are expressed in chloramine units per gram of protein (micromol/g). AOPP decrease slightly from 0 to 15 min of the dialysis procedure (4.0 +/- 1.5 vs. 3.0 +/- 0.9 micromol/g, p < 0.01). However, they are increased at the end of the session (5.0 +/- 2.1 micromol/l vs. 15 min, p < 0.01, not significant vs. beginning). On the other hand, AGEs decrease continuously from the beginning to the end of the session (mainly in the first minutes of the dialysis) (1.52 +/- 0.34 x 10(4) AU/g at 0 min, 1.39 +/- 0.33 x 10(4) AU/g at 15 min, p < 0.001 vs. beginning, 1.30 +/- 0.33 x 10(4) AU/g at the end, p < 0.001 vs. beginning, not significant vs. 15 min). Neither AGEs nor AOPP correlate with the age of hemodialyzed patients and with the number of years of the dialysis treatment. AOPP correlate with AGEs before the dialysis session (r = 0.62, p < 0.05) but not after the session (r = 0.29, not significant). According to our results, AGEs may serve more as a marker of chronic damage while AOPP may better describe acute oxidative stress during the dialysis treatment.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- chloraminy krev MeSH
- chronické selhání ledvin krev terapie MeSH
- dialýza ledvin škodlivé účinky MeSH
- fluorescenční spektrometrie MeSH
- lidé středního věku MeSH
- lidé MeSH
- oxidační stres * MeSH
- produkty pokročilé glykace krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- chloramine MeSH Prohlížeč
- chloraminy MeSH
- produkty pokročilé glykace MeSH
BACKGROUND: Cardiovascular disease caused by atherosclerosis remains a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). We evaluated the potential association of cardiovascular risk factors including asymmetric dimethyl L-arginine (ADMA) and the soluble receptor for advanced glycation end products (sRAGE) with preclinical atherosclerosis in patients undergoing kidney transplantation. PATIENTS AND METHODS: In 92 males and 47 females undergoing the first cadaveric renal transplantation, ADMA, sRAGE and common risk factors including lipid parameters were evaluated as potential predictors of preclinical atherosclerosis defined as the Belcaro score (focused on advanced atherosclerotic changes) measured by ultrasound. RESULTS: The prevalence of atherosclerotic changes was approximately 70% in men and women. In logistic regression, age, history of smoking, presence of diabetes mellitus, and plasma triglycerides were the strongest independent predictors for advanced atherosclerosis in the whole group. In unadjusted analyses advanced atherosclerosis was also associated with sRAGE in men and with the atherogenic index of plasma in women. CONCLUSION: Apart from traditional cardiovascular risk factors, plasma triglycerides were found to be strong and independent predictors of advanced atherosclerosis in patients with ESRD. In addition, sRAGE was associated with atherosclerosis in men and the atherogenic index of plasma in women.
- MeSH
- ateroskleróza krev diagnóza epidemiologie MeSH
- chronické selhání ledvin krev diagnóza epidemiologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- pohlavní dimorfismus * MeSH
- průřezové studie MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory imunologické krev MeSH
- rizikové faktory MeSH
- senioři MeSH
- transplantace ledvin trendy MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory imunologické MeSH
Several diseases (atherosclerosis, diabetes mellitus, chronic renal failure) are associated with oxidative and carbonyl stress, microinflammation and eventually autoimmune reaction. Both oxidative and carbonyl stress cause damage to important biological structures-proteins, carbohydrates, lipids and nucleic acids and may enhance inflammatory response. New compounds and modified structures are formed, among them advanced oxidation protein products (AOPP), advanced glycation end products (AGEs-e.g. pentosidine, carboxymethyllysine) and advanced lipoperoxidation end products (ALEs). Accumulation of glycoxidation products, upregulation of protective mechanisms like glyoxalase I as well as enhanced transcription of genes coding for cytokines, growth factors and adhesive molecules via AGE-RAGE (receptor for AGEs) interaction and subsequent increase of classical acute phase reactants (e.g. CRP-C-reactive protein or orosomucoid) can be observed in a variety of chronic diseases. Additionally, several RAGE gene polymorphisms have shown association with some pathological states-diabetic complications, vascular damage, inflammatory response or antioxidant status. Recent advances in understanding the pathogenesis of chronic diseases provide new possibilities for diagnostics and monitoring of severely ill patients, however, further studies are still required to establish efficient therapeutical strategies.
- MeSH
- chronická nemoc * MeSH
- chronické selhání ledvin komplikace metabolismus MeSH
- diabetes mellitus genetika metabolismus MeSH
- klinická chemie metody MeSH
- laktoylglutathionlyasa genetika metabolismus MeSH
- lidé MeSH
- nukleotidy metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres MeSH
- polymorfismus genetický MeSH
- produkty pokročilé glykace analýza metabolismus MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory cytoplazmatické a nukleární metabolismus MeSH
- receptory imunologické genetika metabolismus MeSH
- zánět etiologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- laktoylglutathionlyasa MeSH
- nukleotidy MeSH
- produkty pokročilé glykace MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory cytoplazmatické a nukleární MeSH
- receptory imunologické MeSH
BACKGROUND: Globally, most people with head and neck cancers (HNCs) are diagnosed with advanced-stage disease. HNC diagnostic stage has multifactorial explanations, with the role of health system factors not yet fully investigated. METHODS: HNC centres (n = 18) from the HEADSpAcE Consortium were surveyed via a bespoke health system questionnaire covering a range of factors. Centres were compared using the least square means for the presence/absence of each health system factor to their proportion of advanced-stage HNC. RESULTS: Health system factors associated with lower proportion in advanced-stage diagnosis were formal referral triaging (14%, 95% CI-0.26, -0.03), routine monitoring of time from referral to diagnosis (16%, 95% CI-0.27, -0.05), and fully publicly funded systems (17%, 95% CI-0.29, -0.06). Several health systems factors had no routinely available data. CONCLUSIONS: Through identifying and monitoring health systems factors associated with lower proportions of advanced stage HNC, interventions could be developed, and systems redesigned, to improve early diagnosis.
- Klíčová slova
- diagnostic pathway, head and neck cancer, health systems, stage at diagnosis,
- Publikační typ
- časopisecké články MeSH
Uremia and dialysis treatment are associated with uncorrected oxidative and carbonyl stress and microinflammation. Elevation of both oxidative/carbonyl stress end products (advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), and advanced lipoperoxidation end products (ALEs), autoantibodies against modified biological structures, and acute-phase reactants (e.g., C-reactive protein [CRP], fibrinogen) seems to take part in the development of various complications, among them accelerated atherosclerosis. These pathogenic mechanisms are supposed to act synergically; nevertheless, oxidative stress shows a closer relationship to inflammation and acute-phase reaction than advanced glycation. Its end product, AOPP, could, thus, represent a biochemical marker of specific importance.
- MeSH
- autoprotilátky imunologie MeSH
- biologické markery MeSH
- chronické selhání ledvin imunologie metabolismus terapie MeSH
- dialýza ledvin MeSH
- lidé MeSH
- produkty pokročilé glykace imunologie metabolismus MeSH
- proteiny akutní fáze imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- autoprotilátky MeSH
- biologické markery MeSH
- produkty pokročilé glykace MeSH
- proteiny akutní fáze MeSH
BACKGROUND: Advanced glycation end products (AGEs) belong to uremic toxins and some pathological effects of AGEs are linked to RAGE (receptor for AGEs). Their precursors are detoxified by the glyoxalase (GLO) system. The A419C (E111A) polymorphism of the GLO I gene is associated with vascular disease in hemodialysis (HD) patients and some RAGE gene polymorphisms are implicated in various pathological states. AIM: To study the relationship of A419C GLO I and four RAGE polymorphisms (-429T/C, -374T/A, 2184A/G and Gly82Ser) in the prognosis of HD patients. METHODS: The group studied consisted of 214 chronic HD patients prospectively followed up for 43 months. 100 patients died, 48 due to cardiovascular causes. RESULTS: The Kaplan-Meier analysis showed a higher mortality rate in patient-mutated homozygotes for RAGE -429CC, RAGE 2184GG and GLO I 419CC. A higher hazard risk was confirmed by the Cox proportional hazards model when wild-type homozygotes were taken as reference: RAGE -429CC 2.28 (95% CI 1.04-4.99), RAGE 2184GG 3.16 (95% CI 1.44-6.93), and GLO I 419CC 1.75 (95% CI 1.08-2.86). Both RAGE polymorphisms were also associated with cardiovascular mortality: RAGE -429CC 3.54 (95% CI 1.37-9.14) and RAGE 2184GG 5.04 (95% CI 1.93-13.11). CONCLUSION: In summary, our study shows for the first time a link between RAGE and GLO polymorphisms in the prognosis of HD patients.
- MeSH
- chronické selhání ledvin genetika mortalita terapie MeSH
- dialýza ledvin * MeSH
- genetická predispozice k nemoci epidemiologie MeSH
- Kaplanův-Meierův odhad MeSH
- laktoylglutathionlyasa genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- polymorfismus genetický MeSH
- produkty pokročilé glykace genetika metabolismus MeSH
- prognóza MeSH
- prospektivní studie MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory imunologické genetika metabolismus MeSH
- senioři MeSH
- uremie genetika metabolismus terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- laktoylglutathionlyasa MeSH
- produkty pokročilé glykace MeSH
- receptor pro konečné produkty pokročilé glykace MeSH
- receptory imunologické MeSH
UNLABELLED: Oxidative and carbonyl stress may, on one hand, contribute to the progression of cancer, on the other hand, they may have some antiproliferative effects. We examined serum levels of AGEs (advanced glycation end-products), CML (carboxymethyllysine) and AOPP (advanced oxidation protein products) in 86 patients with breast cancer subdivided based on the clinical stage (TNM classification), histologic grading, expression of hormonal and C-erb B2 receptors and in 14 healthy age-matched women as controls. Breast cancer patients had higher serum concentrations of AGEs (325,581 +/- 66,037 vs. 271,322 +/- 34,826 AU, p < 0.01) even in the early stage of the disease; patients with advanced breast cancer (stage III and IV) had significantly higher both AGEs and AOPP (113.0 +/- 44.9 vs. 78.1 +/- 28.4 micromol/l, p < 0.05) levels, not only compared to controls, but also compared to stages I and II. Serum levels of AOPP were higher in patients having only weakly positive expression of C-erb 2/Her-neu compared to controls and the patients having the highest C-erb2/Her-neu expression. Serum concentrations of AGEs in patients with breast cancer correlated with the age and also with the serum concentration of AOPP. IN CONCLUSION: breast cancer patients had an early increase of AGEs (marker of the carbonyl stress) followed by further increase of AGEs and elevation of AOPP (marker of oxidative stress) in patients with progressive disease. As the clinical significance of these observations is currently uncertain further studies are clearly warranted, especially with respect to their potential therapeutic implications.
- MeSH
- estrogeny metabolismus MeSH
- karbonylace proteinů * MeSH
- krevní proteiny analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- lysin analogy a deriváty krev MeSH
- nádory prsu krev diagnóza terapie MeSH
- oxidace-redukce MeSH
- oxidační stres * MeSH
- produkty pokročilé glykace krev MeSH
- prognóza MeSH
- receptor erbB-2 metabolismus MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- estrogeny MeSH
- krevní proteiny MeSH
- lysin MeSH
- N(6)-carboxymethyllysine MeSH Prohlížeč
- produkty pokročilé glykace MeSH
- receptor erbB-2 MeSH
The aim of the study was to point out the contribution of new invasive therapeutic procedures in the treatment of advanced stages of Parkinson's disease (PD) in comparison with classical oral pharmacotherapy. Data originated from a group of 43 patients with PD, 39% (17) with classic treatment, 23% (10) with intestinal gel of methyl ester levodopa (Duodopa), 19% (8) of patients were using subcutaneous delivery of apomorphine (APO) and the same quantity of patients had undergone deep brain stimulation (DBS). Majority of patients had advanced stages of PD, stage 4, by standards of Hoehn and Yahr scale (Hoehn and Yahr, 1967). Research observed improvement in majority of patients with novel treatments. A positive effect was also noted in the reduced need for oral therapy, where there was a significant decrease in all new therapies. Benefits were observed in the amount of antiparkinsonic drugs taken per os, where we observed reduction in all new therapies. A positive effect of the new therapeutic approaches in reducing "off" periods in patients has also been noted. In the case of Duodopa and DBS, the "off" period was shortened up to 50% and in the apomorphine pump up to 40%. Patients also reported reduction of some symptoms like rigidity, tremor and bradykinesis while dyskinesis still remains suba challenge. On the basis of the obtained results, it can be concluded that new therapeutic procedures for PCh will make it possible to manage symptoms typical of advanced stages of the disease, which without these procedures would lead to disability, which is the main reason for their indication. However, in early stages, well responding patients or in slow progressing disease oral antiparkinsonics are remaining as golden standard of treatment. This is not just due to good response but also because these classic drug formulations are significantly less expensive. In Slovakia, novel treatments are accessible through healthcare insurance only after secondary revision by insurance company doctors.
- Klíčová slova
- Duodopa, Parkinson’s disease, apomorphine pump, deep brain stimulation, pharmacotherapy,
- MeSH
- aplikace orální MeSH
- apomorfin MeSH
- estery MeSH
- lidé MeSH
- Parkinsonova nemoc * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
- Názvy látek
- apomorfin MeSH
- estery MeSH