70 research outputs found
Patophysiology of atherosclerosis based on research on apoE-knockout mice and their usefulness in checking new antiatherosclerotic agents
Obecnie wiadomo, że miażdżyca jest chorobą o podłożu zapalnym. Długo brakowało jednoznacznego
dowodu na istotny wpływ zapalenia na rozwój miażdżycy. Uzyskano go dzięki nowemu zwierzęcemu modelowi
miażdżycy - myszy, u której zastosowano technikę celowania genowego (apoE-knockout mice).
Kluczowym etapem rozwoju miażdżycy jest prezentacja limfocytom T antygenu przez komórki dendrytyczne.
Antygenem tym może być fragment "strawionej" przez makrofag, utlenionej lipoproteiny o małej dogęstości
(LDL), białko szoku cieplnego 60 (HSP60), β2 glikoproteina I lub fragmenty antygenów bakteryjnych.
W wyniku oddziaływania tych komórek następuje odpowiedź immunologiczna typu T helper 1
(komórkowa) lub typu T helper 2 (humoralna). Obecnie uważa się, że odpowiedź typu Th1 i jej mediatory:
interferon γ, czynnik martwicy nowotworów α, interleukina 1, interleukina 12 oraz interleukina 18
działają przyspieszająco na rozwój miażdżycy, podczas gdy odpowiedź typu Th2 i jej mediatory: interleukina
4, interleukina 5, interleukina 10 oraz interleukina 13 hamują rozwój miażdżycy.
Koncepcja miażdżycy jako zapalenia ukształtowała się dopiero w ostatnich latach, lecz obecnie jej wartość
jest niekwestionowana, co wiąże się z określonymi konsekwencjami terapeutycznymi. W ostatnich
latach oczywiste stało się więc, że szlak produktów 5-lipooksygenazy może odgrywać istotną rolę patogenezie
miażdżycy. Zaczęto rozważać leki przeciwleukotrienowe jako potencjalną terapię miażdżycy.
W niniejszej pracy omówiono wyniki badań własnych przeprowadzonych na eksperymentalnym modelu
miażdżycy: myszach z podwójnie wyłączonymi genami dla apolipoproteiny E oraz dla receptora LDL.
Wykazano, że inhibitory białka aktywującego 5-lipooksygenazę (FLAP) oraz bloker receptora dla leukotrienów
cysteinylowych zmniejszają miażdżycę u zmienionych genetycznie myszy.Although atherosclerosis was previously thought to be primarily a degenerative disease, it is now well ascertained
that its pathogenesis is inflammatory. This review describes the history of the new atherogenetic concept, including
the pivotal role of apoE-knockout mice in understanding the inflammatory background of atherosclerosis.
The pivotal stage of atherogenesis is antigen presentation by macrophages to T lymphocytes. This antigen
could be a fragment of oxidized LDL"digested" by macrophage, heat shock protein 60, β2 glycoprotein I,
or fragments of bacterial antigens. During interaction between these cells, an immunological response of
type T helper 1 (cellular) or T helper 2 (humoral) arises. Th1 response and its mediators: (IFN-γ, TNF-α,
interleukin 1, interleukin 12, and interleukin 18) increase atherogenesis, whereas Th2 response and its
mediators: (interleukin 4, interleukin 5, and interleukin 10) decrease the development of atherosclerosis.
The concept of atherosclerosis as an inflammatory disease is quite fresh; however, it is already considered
an undisputable achievement of science, bringing particular therapeutic consequences.
Since inflammation plays an important role in atherogenesis, during recent years it has become apparent
that the 5-lipoxygenase (5-LO) pathway may play an important role in modifying the pathogenesis of
atherosclerosis. These data raised the possibility that antileukotriene drugs may be an effective treatment
regimen in atherosclerosis. In fact, we have found that among apoE and LDLR-double knockout mice the
inhibition of FLAP, as well as cysteinyl leukotriene receptor blockade, was able to significantly prevent the
development of atherosclerosis in gene-targeted mice
Exogenous angiotensin i metabolism in aorta isolated from streptozotocin treated diabetic rats
Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR ^{-/-} mice
This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T lymphocytes (rabbit anti-CD3). Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment
Multiple extremely high-risk endovascular interventions in aortic dissection in an infant with interrupted aortic arch
Triple immunofluorescence labeling of atherosclerotic plaque components in apoE/LDLR -/- mice.
This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T lymphocytes (rabbit anti-CD3). Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment
Exonic deletions of mismatch repair genes MLH1 and MSH2 correlate with prognosis and protein expression levels in malignant melanomas
The mutations of MLH1 and MSH2 have been reported to be responsible for malignant transformation and tumour progression in several sporadic tumours. Eighty-six primary malignant melanomas with known follow-up were investigated. Point mutations of DNA mismatch repair MLH1 and MSH2 in malignant melanomas were not found. Exon 12 (MSH2) was not present in 26 out of the 86 melanomas and exon 13 (MSH2) was lost in 25 of the tumours. The loss of exon 15 (MLH1) was observed in 22 out of the 86 tumours and the loss of exon 16 (MLH1) in 24 melanomas. The loss of exons correlated strongly with the loss of MLH1 and MSH2 protein expression. In multivariate analysis, including all 4 exons and expressions of MLH1 and MSH2, prognostic significance was found only for loss of exon 12 (MSH2) and loss of exon 15 (MLH1)
Polymorphism rs7023923 and monocyte count in blood donors and coronary artery disease patients
Inactivation of heparin by cationically modified chitosan
This study was performed to evaluate the ability of N-(2-hydroxypropyl)-3- tri methylammonium chitosan chloride (HTCC), the cationically modified chitosan, to form biologically inactive complexes with unfractionated heparin and thereby blocking its anticoagulant activity. Experiments were carried out in rats in vivo and in vitro using the activated partial thromboplastin time (APTT) and prothrombin time (PT) tests for evaluation of heparin anticoagulant activity. For the first time we have found that HTCC effectively neutralizes anticoagulant action of heparin in rat blood in vitro as well as in rats in vivo. The effect of HTCC on suppression of heparin activity is dose-dependent and its efficacy can be comparable to that of protamine-the only agent used in clinic for heparin neutralization. HTCC administered i.v. alone had no direct effect on any of the coagulation tests used. The potential adverse effects of HTCC were further explored using rat experimental model of acute toxicity. When administered i.p. at high doses (250 and 500 mg/kg body weight), HTCC induced some significant dose-dependent structural abnormalities in the liver. However, when HTCC was administered at low doses, comparable to those used for neutralization of anticoagulant effect of heparin, no histopathological abnormalities in liver were observed
The current state of knowledge on the prevention of venous thromboembolism in orthopaedic and trauma surgery — selected topics
Profilaktyka żylnej choroby zakrzepowo-zatorowej w ortopedii i traumatologii narządu ruchu należy do
zagadnień najlepiej zbadanych i opracowanych w formie szczegółowych zaleceń i protokołów postępowania
oraz do najszybciej rozwijających się w całym zakresie problematyki zakrzepowej. Najnowsze doniesienia
naukowe dotyczące tego zagadnienia zmuszają do nieustannej modyfikacji podglądów oraz aktualizacji
zasad jej stosowania.
Zmiany te mogą być publikowane jako opracowania indywidualne lub prace zespołów badawczych powoływanych
w tym celu przez stowarzyszenia naukowe. Takim przedsięwzięciem było wyodrębnienie interdyscyplinarnej
grupy specjalistów, której celem było określenie aktualnego stanu wiedzy i opracowanie propozycji zaleceń
dotyczących wybranych zagadnień z zakresu profilaktyki żylnej choroby zakrzepowo-zatorowej. Grupa ta
działała pod auspicjami Prezesa Polskiego Towarzystwa Ortopedycznego i Traumatologicznego oraz Prezesa
Polskiej Fundacji do Walki z Zakrzepicą THROMBOSIS. Wyniki prac zespołu zawarto w poniższym opracowaniu.
Acta Angiol 2011; 17, 1: 1–36Prevention of venous thromboembolism in orthopaedic and trauma surgery is one of the best-studied topics,
with respect to which the most detailed recommendations and management protocols have been drawn up.
It is also the fastest-developing area of the study of thrombotic conditions. The most recent reports make us
continually modify our views and update the principles of its use.
These changes may be published by individual authors or by research teams appointed for this particular
purpose by scientific societies. An example of such efforts was the appointment of a multidisciplinary group
of specialists whose aim was to determine the current state of knowledge on the prevention of VTE and to propose recommendations on selected aspects of this topic. The group carried out its activities under the
auspices of the Chair of the Polish Society of Orthopaedic and Trauma Surgeons and the Chair of the Polish
Foundation Against Thrombosis. This paper presents the results of this team’s efforts.
Acta Angiol 2011; 17, 1: 1–3
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