The usefulness of assessing the serum levels of homocysteine in diagnosis of atherosclerosis

Wstęp. Choroby naczyniowe są pierwszą przed chorobami nowotworowymi przyczyną zgonów. Dlatego na całym świecie prowadzi się badania, których celem jest znalezienie łatwo oznaczalnego w płynach ustrojowych czynnika ryzyka miażdżycy. Powinien on być przydatny do badań przesiewowych, mieć znaczenie rokownicze i ułatwiać ocenę stosowanej terapii. Do listy czynników ryzyka chorób układu krążenia niedawno dołączono homocysteinę. Ma ona właściwości cytotoksyczne, a jej podwyższone stężenie we krwi powoduje uszkodzenie komórek śródbłonka, degradację elastyny w błonie wewnętrznej, procesy włóknienia i wapnienia. Celem pracy jest ocena stężenia homocysteiny w surowicy krwi u pacjentów z potwierdzoną klinicznie miażdżycą tętnic. Materiał i metody. Badaniom poddano 68 pacjentów, w tym 26 chorych z miażdżycą tętnic kończyn dolnych, 10 osób po zabiegu pomostowania aortalno-wieńcowego (CABG), 10 chorych z zawałem serca, 15 osób &#8212; z ciężkim udarem niedokrwiennym mózgu, 4 pacjentów &#8212; z tętniakiem aorty brzusznej i 3 osoby &#8212; ze zwężeniem tętnicy nerkowej. Z badań wyłączono pacjentów z niedawno przebytym zawałem serca lub udarem niedokrwiennym mózgu, z niewydolnością nerek, z chorobami autoimmunologicznymi oraz z chorobą nowotworową. Wyniki. U pacjentów we wszystkich badanych grupach schorzeń oprócz grupy z tętniakiem aorty brzusznej (8,71 &#177; 0,77 &#181;mol/l) stwierdzono podwyższone wartości stężenia homocysteiny w porównaniu z grupą kontrolną (stężenie 9,37 &#177; 1,49 &#181;mol/l), przy czym najwyższe wartości odnotowano w grupie chorych po CABG (29,2 &#177; 11,32 &#181;mol/l). Wnioski. Homocysteina jest ważnym, niezależnym czynnikiem ryzyka chorób układu krążenia, a jej oznaczenie powinno być badaniem rutynowym u pacjentów obciążonych genetycznie oraz u osób z innymi czynnikami ryzyka miażdżycy.Background. Cardiovascular diseases are the most common cause of death in Poland. Homocystein has recently been added to the list of atherosclerosis risk factors. Homocystein is an amino acid, which contains sulphur. Homocysteine is toxic for the endothelium. The aim of the study was to assess the plasma levels of the homocysteine in patients with clinical symptoms of atherosclerosis. Material and methods. Sixty-eight patients including 26 with lower extremities atherosclerosis, 10 after CABG, 10 with AMI, 15 with ischemic stroke, 4 with abdominal aortic aneurysm and 3 with renal artery obstruction were enrolled. Patients suffering from acute MI or stroke, kidney failure, autoimmune diseases and neoplasms were excluded from the investigation. Thirty healthy volunteers were the control group. Results. Homocysteine levels in all patient groups were higher than in the control group except patients with abdominal aortic aneurysm. The highest homocysteine concentrations (29.2 &plusmn; 11.32 &micro;mol/l; p < 0.001) were in patients after CABG. Conclusions. homocysteine is an important, independent cardiovascular diseases risk factor and should be routinely examined for in patients with other risk factors

The usefulness of assessing the serum levels of S-100 protein in patients with ischemic stroke

Wstęp. W ostatnim okresie opublikowano wiele prac podkreślających konieczność poszukiwania nowych biochemicznych czynników, które obok badania klinicznego oraz badań neuroobrazujących mogłyby pomóc w określeniu stopnia ciężkości udaru niedokrwiennego mózgu, a w konsekwencji w prowadzonym leczeniu i określaniu rokowania. Od kilku lat w związku z nowymi możliwościami terapeutycznymi przy zastosowaniu leczenia neuroprotekcyjnego oraz fibrynolitycznego podkreśla się znaczenie oceny stopnia uszkodzenia mózgu już w pierwszych godzinach wystąpienia choroby. Celem pracy jest ocena stężenia białka S-100 w surowicy krwi u chorych z udarem niedokrwiennym mózgu w zależności od stopnia ciężkości udaru oraz ustalenie wartości diagnostycznej takiej oceny. Materiał i metody. Badaniem objęto 47 chorych z udarem niedokrwiennym mózgu. Rozpoznanie ustalono na podstawie badania klinicznego i tomografii komputerowej wykonywanej po 2. dobie od wystąpienia udaru. Stężenie białka S-100 w surowicy oznaczano w 1. dobie od zachorowania. Stan chorych przy przyjęciu do szpitala oraz po 30 dniach oceniano, stosując Skandynawską Neurologiczną Skalę Udarową, a oceny powrotu funkcji neurologicznych dokonywano, używając wskaźnika Barthel w 14. i 30. dobie po zachorowaniu. Grupę kontrolną stanowiło 10 zdrowych ochotników dobranych pod względem płci i wieku. Oznaczenia wykonano za pomocą metod enzymoimmunologicznych, stosując zestawy komercyjne. Wyniki. W grupie badanej stwierdzono znamiennie statystycznie wyższe stężenia białka S-100 niż w grupie kontrolnej. Wniosek. Białko S-100 jest parametrem o istotnej wartości diagnostycznej.Background. It is important to identify new biochemical markers of strokes to monitor and predict the neurological outcome, as well as to elucidate the multiple molecular mechanisms after ischemic brain infarction. Recently, an elevation of S-100 protein in serum were reported in strokes, but still, different biochemical techniques must be developed as soon as possible in order to help us to improve effective treatment. Modern neuroradiological techniques help to predict the outcome; however, repeating neuroradiological imaging is impractical. The aim of the study was to evaluate the serum levels of S-100 protein after brain infarction in correlation with clinical data and prognosis. Material and methods. S-100 protein serum levels were determined in 47 patients with an acute ischemic brain infarction in the first day (within 12 hours after the onset of symptoms) and sex and age matched control subjects. The clinical status was documented using the Scandinavian Stroke Scale. The functional deficit 4 weeks after stroke onset was scored with the Barthel Index. A cranial computed tomography (CCT) was performed after 2 days. Results. Elevated concentrations of S-100 protein were observed in patients with strokes. The S-100 concentrations in serum were significantly higher in patients with severe neurological deficits at the time of admission and correlated with the functional prognosis. Conclusions. The measurement of S-100 protein in serum is useful to diagnose and predict the outcome in patients after brain infarction

CD40L and IL-4 stimulation of acute lymphoblastic leukemia cells results in upregulation of mRNA level of FLICE--an important component of apoptosis.

The use of cancer vaccines based on dendritic cells (DC) presenting tumor antigens can be a promising tool in the treatment of leukemia. The functional characteristics of leukemia derived DC is still to be elucidated. CD40 promotes survival, proliferation and differentiation of normal B cells. CD40 triggering was used to enhance the poor antigen-presenting capacity of leukemic B-cells. Since it is still unclear whether CD40 ligation drives neoplastic B-cells to apoptosis or not, we assessed the mRNA expression of FLICE, FAS, FADD and TRADD - important components of apoptosis machinery, using real-time PCR in acute lymphoblastic leukemia cells before and after CD40 and IL-4 stimulation. ALL cells stimulated with CD40L/IL-4 expressed dendritic cell phenotype at mRNA and protein levels (upregulation of main costimulatory and adhesion molecules noted in real-time RT PCR and flow cytometry); they also expressed higher amounts of mRNA for FLICE, TRADD and FADD after CD40L/IL-4 stimulation. However differences statistically significant comparing cells cultured with CD40L/IL-4 and medium alone regarded only FLICE. Concluding, we showed upregulation of important elements of apoptosis at mRNA level in ALL cells after CD40 ligation

Plastic scintillators for positron emission tomography obtained by the bulk polymerization method

This paper describes three methods regarding the production of plastic scintillators. One method appears to be suitable for the manufacturing of plastic scintillator, revealing properties which fulfill the requirements of novel positron emission tomography scanners based on plastic scintillators. The key parameters of the manufacturing process are determined and discussed.Comment: 7 pages, 4 figure

Application of the compress sensing theory for improvement of the TOF resolution in a novel J-PET instrument

Nowadays, in positron emission tomography (PET) systems, a time of fl ight (TOF) information is used to improve the image reconstruction process. In TOF-PET, fast detectors are able to measure the difference in the arrival time of the two gamma rays, with the precision enabling to shorten signifi cantly a range along the line-of-response (LOR) where the annihilation occurred. In the new concept, called J-PET scanner, gamma rays are detected in plastic scintillators. In a single strip of J-PET system, time values are obtained by probing signals in the amplitude domain. Owing to compressive sensing (CS) theory, information about the shape and amplitude of the signals is recovered. In this paper, we demonstrate that based on the acquired signals parameters, a better signal normalization may be provided in order to improve the TOF resolution. The procedure was tested using large sample of data registered by a dedicated detection setup enabling sampling of signals with 50-ps intervals. Experimental setup provided irradiation of a chosen position in the plastic scintillator strip with annihilation gamma quanta

FoxP3+ T regulatory cells in cancer : prognostic biomarkers and therapeutic targets

T Regulatory cells (Tregs) can have both protective and pathological roles. They maintain immune homeostasis and inhibit immune responses in various diseases, including cancer. Proportions of Tregs in the peripheral blood of some cancer patients increase by five-to ten-folds, compared to those in healthy individuals. Tregs contribute to cancer development and progression by suppressing T effector cell functions, thereby compromising tumor killing and promoting tumor growth. Highly immunosuppressive Tregs express upregulated levels of the transcription factor, Forkhead box protein P3 (FoxP3). Elevated levels of FoxP3+ Tregs within the tumor microenvironment (TME) showed a positive correlation with poor prognosis in various cancer patients. Despite the success of immunotherapy, including the use of immune checkpoint inhibitors, a significant proportion of patients show low response rates as a result of primary or acquired resistance against therapy. Some of the mechanisms which underlie the development of therapy resistance are associated with Treg suppressive function. In this review, we describe Treg contribution to cancer development/progression, and the mechanisms of Treg-mediated immunosuppression. We discuss the prognostic significance of FoxP3+ Tregs in different cancers and their potential use as prognostic biomarkers. We also describe potential therapeutic strategies to target Tregs in combination with other types of immunotherapies aiming to overcome tumor resistance and improve clinical outcomes in cancer patients. Overall, understanding the prognostic significance of FoxP3+ Tregs in various cancers and their contribution to therapeutic resistance could help in the development of more effective targeted therapeutic strategies to enhance the clinical outcomes in cancer patients

Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review

Background Biomarkers that can predict the prognosis of colorectal cancer (CRC) patients and that can stratify high-risk early stage patients from low-risk early stage patients are urgently needed for better management of CRC. During the last decades, a large variety of prognostic DNA methylation markers has been published in the literature. However, to date, none of these markers are used in clinical practice. Methods To obtain an overview of the number of published prognostic methylation markers for CRC, the number of markers that was validated independently, and the current level of evidence (LoE), we conducted a systematic review of PubMed, EMBASE, and MEDLINE. In addition, we scored studies based on the REMARK guidelines that were established in order to attain more transparency and complete reporting of prognostic biomarker studies. Eighty-three studies reporting on 123 methylation markers fulfilled the study entry criteria and were scored according to REMARK. Results Sixty-three studies investigated single methylation markers, whereas 20 studies reported combinations of methylation markers. We observed substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology. The median (range) REMARK score for the studies was 10.7 points (4.5 to 17.5) out of a maximum of 20 possible points. The median REMARK score was lower in studies, which reported a p value below 0.05 versus those, which did not (p = 0.005). A borderline statistically significant association was observed between the reported p value of the survival analysis and the size of the study population (p = 0.051). Only 23 out of 123 markers (17%) were investigated in two or more study series. For 12 markers, and two multimarker panels, consistent results were reported in two or more study series. For four markers, the current LoE is level II, for all other markers, the LoE is lower. Conclusion This systematic review reflects that adequate reporting according to REMARK and validation of prognostic methylation markers is absent in the majority of CRC methylation marker studies. However, this systematic review provides a comprehensive overview of published prognostic methylation markers for CRC and highlights the most promising markers that have been published in the last two decades

Mie and Bragg plasmons in subwavelength silver semi‐shells

2D arrays of silver semi-shells of 100 and 200 nm diameter display complex reflection and transmission spectra in the visible and near-IR. Here these spectral features are deconstructed and it is demonstrated that they result from the coupling of incident light into a delocalized Bragg plasmon, and the latter\u27s induction of localized Mie plasmons in the arrays. These phenomena permit the excitation of transverse dipolar plasmon resonances in the semi-shells despite an ostensibly unfavorable orientation with respect to normally incident light. The resulting spectral feature in the mid-visible is strong and tunable

Fabrication of hollow metal “nanocaps” and their red‐shifted optical absorption spectra

The optical and infrared radiation (IR) absorption spectra of randomly oriented suspensions of discrete cap-shaped metal nanoparticles were discussed. Nanocaps of gold, silver, aluminum, copper, and chromium were produced and the effect of variations in deposition angle and thickness were analyzed. The nanocaps were fabricated with the application of 200 nm diameter PSPs onto a glass substrates by spin-coating. The results show that the absorption peaks of these nanocaps are strongly red shifted relative to those of solid nanospheres