Wyniki wyszukiwania

1

Medycyna translacyjna - czyli z laboratorium do lozka chorego... i z powrotem

100%

Guzik T. J.

Kosmos

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2010

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tom 59

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nr 1-2

257-262

2

Mechanisms of superoxide production in human blood vessels: relationship to endothelial dysfunction, clinical and genetic risk factors

63%

Channon K. M., Guzik T. J.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,1

Common vascular disease states including diabetes, hypertension and atherosclerosis are associated with endothelial dysfunction, characterised by reduced bioactivity of nitric oxide (NO). Loss of the vasculoprotective effects of NO contributes to disease progression, but the mechanisms underlying endothelial dysfunction remain unclear. Increased superoxide production in animal models of vascular disease contributes to reduced NO bioavailability, endothelial dysfunction and oxidative stress. In human blood vessels, the NAD(P)H oxidase system is the principal source of superoxide, and is functionally related to clinical risk factors and systemic endothelial dysfunction. Furthermore, the C242T polymorphism in the NAD(P)H oxidase p22phox subunit is associated with significantly reduced superoxide production in patients carrying the 242T allele, suggesting a role for genetic variation in modulating vascular superoxide production. In vessels from patients with diabetes mellitus, endothelial dysfunction, NAD(P)H oxidase activity and protein subunits are significantly increased compared with matched non-diabetic vessels. Furthermore, the vascular endothelium in diabetic vessels is a net source of superoxide rather than NO production, due to dysfunction of endothelial NO synthase (eNOS). This deficit is dependent on the eNOS cofactor, tetrahydrobiopterin, and is in part mediated by protein kinase C signalling. These studies suggest an important role for both the NAD(P)H oxidases and endothelial NOS in the increased vascular superoxide production and endothelial dysfunction in human vascular disease states.

3

Oxidative stress and inflammatory markers in prediabetes and diabetes

51%

Luc K., Schramm-Luc A., Guzik T. J., Mikolajczyk T. P.

Journal of Physiology and Pharmacology

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2019

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tom 70

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nr 6

4

Cleavage of prothrombin bound in immune complexes results in high thrombin enzymatic activity

51%

Pajdak W., Radwan J., Guzik T. J.

Journal of Physiology and Pharmacology

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2004

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tom 55

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nr 2

Thrombin plays a pivotal role in blood clotting as well as in the regulation of vascular remodeling and oxidative stress. Recent evidence suggests that auto-antibodies directed against prothrombin, may play an important role in the pathogenesis of atherosclerosis. It is however not clear, if prothrombin bound in an immune complex retains its clotting and regulatory properties or acts solely by increasing vascular inflammation. In order to answer this question, we used a newly developed stain for the detection of thrombin activity of such complexes. Plasma and serum samples were subjected to rocket immunoelectrophoresis in an anti-prothrombin antiserum containing agarose gel. Gel plates, covered with a nitrocellulose membrane were soaked with chromogenic thrombin substrate. The product of thrombin activity was diazotized to red azo dye bound to nitrocellulose. Activity stain revealed barely discernible rockets in plasma, but heavily stained ones in serum. Pre-incubation with trypsin enhanced activity of immunoprecipitates deriving from plasma, but not from serum. Densitometric analysis showed, that the trypsin-enhanced activity in plasma derived immune complexes was twice as high as in serum derived immunoprecipitates. Thrombin active centre is not blocked by anti-prothrombin antiserum allowing to retain thrombin activity. Moreover, prothrombin in immunoprecipitate is readily cleaved by proteolytic enzymes. This cleavage could potentially be enhanced by antibody binding, although these results need to be confirmed using different antibodies.

5

Adipocytokines - novel link between inflammation and vascular funktion?

51%

Guzik T. J., Mangalat D., Korbut R.

Journal of Physiology and Pharmacology

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2006

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tom 57

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nr 4

Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-alpha, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.

6

Perivascular adipose tissue as a messenger of the brain-vessel axis: role in vascular inflammation and dysfunction

51%

Guzik T. J., Marvar P. J., Czesnikiewicz-Guzik M., Korbut R.

Journal of Physiology and Pharmacology

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2007

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tom 58

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nr 4

7

Nitric oxide and superoxide in inflammation and immune regulation

51%

Guzik T. J., Korbut R., Adamek-Guzik T.

Journal of Physiology and Pharmacology

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2003

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tom 54

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nr 4

Nitric oxide (NO) and reactive oxygen species exert multiple modulating effects on inflammation and play a key role in the regulation of immune responses. They affect virtually every step of the development of inflammation. Low concentrations of nitric oxide produced by constitutive and neuronal nitric oxide synthases inhibit adhesion molecule expression, cytokine and chemokine synthesis and leukocyte adhesion and transmigration. Large amounts of NO, generated primarily by iNOS can be toxic and pro-inflammatory. Actions of nitric oxide are however not dependent primarily on the enzymatic source, but rather on the cellular context, NO concentration (dependent on the distance from NO source) and initial priming of immune cells. These observations may explain difficulties in determining the exact role of NO in Th1 and Th2 lymphocyte balance in normal immune responses and in allergic disease. Similarly superoxide anion produced by NAD(P)H oxidases present in all cell types participating in inflammation (leukocytes, endothelial and other vascular cells etc) may lead to toxic effects, when produced at high levels during oxidative burst, but may also modulate inflammation in a far more discrete way, when continuously produced at low levels by NOXs (non-phagocytic oxidases). The effects of both nitric oxide and superoxide in immune regulation are exerted through multiple mechanisms, which include interaction with cell signalling systems like cGMP, cAMP, G-protein, JAK/STAT or MAPK dependent signal transduction pathways. They may also lead to modification of transcription factors activity and in this way modulate the expression of multiple other mediators of inflammation. Moreover genetic polymorphisms exist within genes encoding enzymes producing both NO and superoxide. The potential role of these polymorphisms in inflammation and susceptibility to infection is discussed. Along with studies showing increasing role of NO and free radicals in mediating inflammatory responses drugs which interfere with these systems are being introduced in the treatment of inflammation. These include statins, angiotensin receptor blockers, NAD(P)H oxidase inhibitors, NO-aspirin and others. In conclusion in this mini-review we discuss the mechanisms of nitric oxide and superoxide dependent modulation of inflammatory reactions in experimental animals and humans. We also discuss potential roles of nitric oxide as a mediator of allergic inflammation.

8

Helicobacter pylori in the oral cavity and its implications in gastric infection, periodontal health, immunology and dyspepsia

45%

Czesnikiewicz-Guzik M., Bielanski W., Guzik T. J., Loster B., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 6

77-89

Helicobacter pylori (H. pylori) is an important gastrointestinal pathogen associated with gastritis as well as gastric or duodenal ulcers and gastric cancer. The oral cavity has been considered as a potential reservoir for the gastric infection and reinfection. The objective of our studies was to evaluate the influence of oral H. pylori for the stomach infection and the release of gut hormones affecting food intake such as ghrelin and gastric secretion such as gastrin. Additionally, the contribution of H. pylori in the periodontal disease has been examined. H. pylori infection in stomach was assessed by 13C- Urease Breath Test and presence of the bacteria in oral cavity by culture. The periodontal status was measured by pockets depth with the periodontal probe. We estimated the serum level of IgG anti-H. pylori, anti-VacA, anti-CagA, ghrelin, gastrin, TNF-alpha and IL-8 in blood and the level of IgA anti-H. pylori in saliva. The presence of H. pylori in oral cavity was detected in 54.1% of examined individuals, whereas the H. pylori gastric infection in tested group was found in 51% cases. However, the correlation analysis between those two groups of patients involving together about 100 subjects showed that within the group of patients with positive gastric H. pylori infection only 45.1% did not show the presence of H. pylori in saliva and 43.1% showed no H. pylori in supragingival plaque. In line of these findings patients who did not have gastric H. pylori infection, 53.2 % showed presence of H. pylori in saliva and 42.9% in supragingival plaques. Serum level of ghrelin and gastrin in subjects with oral H. pylori inoculation but without gastric H. pylori infection were not significantly different from those without the presence of this germ in oral cavity. In contrast, gastric H. pylori infection resulted in significant reduction in serum ghrelin levels and significant elevation of gastrin as compared to those who were gastric H. pylori negative. We concluded that oral H. pylori alone does not seem to serve as bacterium sanctuary for gastric H. pylori infection and, unlike gastric infection, it fails to affect serum levels of hormones stimulating appetitive behaviour such as ghrelin and gastric acid secretion such as gastrin.

9

Prolactin - not only lactotrophin a 'new' view of the 'old' hormone

39%

Ignacak A., Kasztelnik M., Sliwa T., Korbut R. A., Rajda K., Guzik T. J.

Journal of Physiology and Pharmacology

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2012

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tom 63

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nr 5

10

Chemokine RANTES is increased at early stages of coronary artery disease

33%

Podolec J., Kopec G., Niewiara L., Komar M., Guzik B., Bartus K., Tomkiewicz-Pajak L., Guzik T. J., Plazak W., Zmudka K.

Journal of Physiology and Pharmacology

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2016

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tom 67

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nr 2

11

Association of the presence the Helicobacter pylori in the oral cavity and in the stomach

33%

Czesnikiewicz-Guzik M., Karczewska E., Bielanski W., Guzik T. J., Kapera P., Targosz A., Konturek S. J., Loster B.

Journal of Physiology and Pharmacology. Supplement

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2004

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tom 55

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nr 2

105-115

Helicobacter pylori is a gram-negative, microaerophilic rod-shaped bacteria that lives beneath the gastric mucous layer, on the surface of epithelial cells. Stomach infection with this organism causes inflammation of the gastric mucosa, which can lead to gastritis, duodenal or gastric ulcer and even in rare cases to gastric carcinoma or MALT lymphoma. Approximately 50% of the world's population is believed to be infected with H. pylori. Most infections is probably acquired in childhood, but the exact route of transmission is unknown. It has been speculated that dental plaque might harbour Helicobacter pylori and, therefore, might be a source of gastric infection. In order to address this issue we studied the relationships between oral and gastric infections with H. pylori in 100 subjects. Methods: Gastric H. pylori infection was determined by 13C-urea breath test (UBT) and the presence of the bacteria in oral cavity was monitored by the culture from the saliva and from dental plaque. Results: H. pylori was found in the stomach in 51% of studied individuals, while oral H. pylori was found in 54% (in saliva) and in 48.3% (in gingival pockets), the difference was not statistical significant (p=NS). Interestingly, anti-Hp IgA was found in 84% of studied individuals. No relationship was found between the presence of the bacteria in the oral cavity and the H. pylori gastric infection. 54.9% of subjects with stomach infection showed concomitant presence of H. pylori in saliva. 53.2% of examined subjects with negative UBT-test revealed the presence of H. pylori in culture from the saliva. The X2 value of relationship between UBT and culture H pylori in saliva was 0.029 (p=0.9). Similarly, no relationship was found between the presence of H. pylori in the stomach and in the dental plaque (X2=0.6; p=0.4). As expected, the presence of H. pylori in the dental plaque was significantly correlated with the presence of bacteria in the saliva (X2=18.4; p=0.0002). We also compared the presence of H. pylori in the saliva of patients with and without teeth. The cultured H. pylori was found in 63.7% of patients without teeth and in 52.9% of patients with teeth. This indicates that the presence of teeth does not seem to affect the occurrence of H. pylori in saliva. We conclude that oral cavity contamination with of H. pylori occurs at similar degree to that in the stomach. However, there was no significant correlation between the occurrence of H. pylori in the stomach and in the oral cavity indicating that other factors, like susceptibility to infection due to acid environment in the stomach may be the major factor in gastric infection with that bacteria, while oral cavity may serve only as transient food-related contamination without clear relation to gastric infection.

12

Prevalence and characterization of Helicobacter pylori [H. pylori] infection and colonization in dentists

33%

Loster B. W., Czesnikiewicz-Guzik M., Bielanski W., Karczewska E., Loster J. E., Kalukin J., Guzik T. J., Majewski S., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2009

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tom 60

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nr 8

13-18

13

Effects of novel plant antioxidants on platelet superoxide production and aggregation in atherosclerosis

33%

Ryszawa N., Kawczynska-Drozdz A., Pryjma J., Czesnikiewicz-Guzik M., Adamek-Guzik T., Naruszewicz M., Korbut R., Guzik T. J.

Journal of Physiology and Pharmacology

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2006

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tom 57

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nr 4

Superoxide anion is produced in human platelets predominantly by Nox2-dependent NADPH oxidases. In vitro experiments have shown that it might play a role in modulating platelet functions. The relationship between platelet superoxide production and aggregation remains poorly defined. Accordingly, we aimed to study superoxide production and aggregation in platelets from subjects with significant cardiovascular risk factors (hypertension, hypercholesterolemia, smoking and diabetes mellitus) and from control individuals. Moreover, we studied the effects of novel polyphenol-rich extracts of Aronia melanocarpa (chokeberry) berries on platelet function in vitro. Superoxide production was significantly increased in patients with cardiovascular risk profile when compared to controls, while platelet aggregation in response to either collagen or thrombin were borderline higher, and did not reach statistical significance. Interestingly, no relationship was observed between platelet aggregation ex vivo and platelet superoxide production in either of studied groups. No correlation was found between endothelial function (measured by FMD) and platelet aggregation ex vivo either. Polyphenol-rich extracts of A. melanocarpa berries caused a significant concentration dependent decrease in superoxide production only in patients with cardiovascular risk factors, while no effect was observed in the control group. A. melanocarpa extracts abolished the difference in superoxide production between risk factor patients and controls. A. melanocarpa extracts exerted significant concentration dependent anti-aggregatory effects in both studied groups, which indicated that these effects may be independent of it’s ability to modulate superoxide production. The anti-aggregatory effects of chokeberry extracts were similar irrespective of aggregation inducing agent (collagen or thrombin). Moreover, they appear to be independent of platelet NO release as NOS inhibition by L-NAME did not lead to their abrogation. Platelet superoxide production is increased in subjects with cardiovascular risk factor profile, which may precede changes in platelet aggregation itself. Novel polyphenol rich extracts of A. melanocarpa berries exert significant anti-platelet effects ex vivo.

14

NADPH oxidase and uncoupled nitric oxide synthase are major sources of reactive oxygen species in oral squamous cell carcinoma. Potential implications for immune regulation under high oxidative stress conditions.

33%

Czesnikiewicz-Guzik M., Lorkowska B., Zapala J., Czajka M., Szuta M., Loster B., Guzik T. J., Korbut R.

Journal of Physiology and Pharmacology

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2008

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tom 59

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nr 1

The development of cancer is associated with high oxidative stress and at the same time with immune system activation. Tumors develop efficient mechanisms of protection against the immune response, which allow them to escape the immune surveillance. Simultaneously, key events in the process of carcinogenesis are related to oxidative stress. The relationship between the two remains unknown. Novel understanding of oxidative stress shows that discrete changes of activities of certain enzyme systems such as NADPH oxidases or nitric oxide synthases may be more important than the overall balance of production and removal of reactive oxygen species. Such imbalance of nitric oxide and superoxide production could modify inflammation and immune regulation. We studied superoxide anion production (by lucigenin enhanced chemiluminescence - 5 µM), NADPH oxidase activity and nitric oxide synthase (NOS) dysfunction. In parallel mRNA expression of immunomodulatory markers such as FoxP3 (T regulatory cell marker), CCR6 (mucosal homing effector T cell marker) and CD85j (NK cell/CD8 T cell Ig-like MHC class I inhibitory receptor) was determined. Basal superoxide production and NADPH oxidase activity are increased in oral squamous cell carcinoma. Tumor superoxide production was inhibited by NADPH oxidase inhibitor apocynin and by NOS inhibitor L-NAME. This indicates, for the first time, that oral squamous cell carcinoma is characterized by dysregulated nitric oxide synthase, which apart from increased NADPH oxidase activity contributes to oxidative stress and may be related to the immuno-pathology of these tumors. Studied tumors were infiltrated by CCR6+, but showed lower expression of both CD85j and FoxP3 mRNA. Finally, the CD85j mRNA expression was inversely correlated to oxidative stress parameters. These preliminary studies indicate that tumor oxidative stress, related to NADPH oxidase activity and NOS activity could be related to immune responses to cancer, thus therapeutic modification of oxidative stress, which could include the correction of NOS dysfunction, could facilitate immune surveillance.

15

Effects of controlled physical activity on immune cell phenotype in peripheral blood in prehypertension - studies in preclinical model and randomised crossover study

27%

Mazur M., Glodzik J., Szczepaniak P., Nosalski R., Siedlinski M., Skiba D., Rewiuk K., Salakowski A., Czesnikiewicz-Guzik M., Grodzicki T., Guzik T. J., Mikolajczyk T. P.

Journal of Physiology and Pharmacology

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2018

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tom 69

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nr 6

16

Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice

27%

Jawien J., Toton-Zuranska J., Gajda M., Niepsuj A., Gebska A., Kus K., Suski M., Pyka-Fosciak G., Nowak B., Guzik T. J., Marcinkiewicz J., Olszanecki R., Korbut R.

Journal of Physiology and Pharmacology

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2012

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tom 63

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nr 1

17

Superoxide dismutase activity and expression in human venous and arterial bypass graft vessels

27%

Guzik T. J., Olszanecki R., Sadowski J., Kapelak B., Rudzinski P., Jopek A., Kawczynska A., Ryszawa N., Loster J., Jawien J., Czesnikiewicz-Guzik M., Channon K. M., Korbut R.

Journal of Physiology and Pharmacology

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2005

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tom 56

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nr 2

Venous bypass grafts are more prone to accelerated atherosclerosis than arterial grafts, which is partly related to increased oxidative stress and diminished nitric oxide bioavailability. In veins superoxide production is dependent primarily on nox2 NAD(P)H oxidase expression, while in arteries nox4 appears to play an important role. This may in part explain differences in susceptibility to graft failure. Net levels of oxidative stress are however determined in parallel by the production as well as by degradation of free radicals (eg. by superoxide dimutases, catalases, thioredoxins etc). The differences in superoxide dismutase (SOD) expression and activity in human bypass conduit vessels remain unclear. Accordingly, we aimed to compare SOD activity and protein levels as well as its functional effects on superoxide production in segments of human internal mammary arteries (IMA) and saphenous veins (HSV) from patients undergoing bypass graft surgery (n=24). SOD activity was assessed by inhibition of pyrogallol autoxidation, Cu-Zn SOD and Mn SOD protein levels were studied by immunoblotting. Basal superoxide release was detected by lucigenin (5µM) enhanced chemiluminescence. Total SOD activity did not differ significantly between HSV and IMA. Similarly, no difference was observed in SOD activity in the presence of KCN (Mn-SOD). Human bypass conduit vessels show amounts of Cu-Zn SOD or Mn-SOD protein levels. In both HSV and IMA segments superoxide production was more than doubled in the presence of SOD inhibitor - DETC. Conclusions: These studies suggest that the differences in oxidative stress between human arteries and veins are unlikely to be caused by SOD activity. However SOD plays and important role in amelioration of oxidative stress in both types of vessels.

Ograniczanie wyników

Medycyna translacyjna - czyli z laboratorium do lozka chorego... i z powrotem

Mechanisms of superoxide production in human blood vessels: relationship to endothelial dysfunction, clinical and genetic risk factors

Oxidative stress and inflammatory markers in prediabetes and diabetes

Cleavage of prothrombin bound in immune complexes results in high thrombin enzymatic activity

Adipocytokines - novel link between inflammation and vascular funktion?

Perivascular adipose tissue as a messenger of the brain-vessel axis: role in vascular inflammation and dysfunction

Nitric oxide and superoxide in inflammation and immune regulation

Helicobacter pylori in the oral cavity and its implications in gastric infection, periodontal health, immunology and dyspepsia

Prolactin - not only lactotrophin a 'new' view of the 'old' hormone

Chemokine RANTES is increased at early stages of coronary artery disease

Association of the presence the Helicobacter pylori in the oral cavity and in the stomach

Prevalence and characterization of Helicobacter pylori [H. pylori] infection and colonization in dentists

Effects of novel plant antioxidants on platelet superoxide production and aggregation in atherosclerosis

NADPH oxidase and uncoupled nitric oxide synthase are major sources of reactive oxygen species in oral squamous cell carcinoma. Potential implications for immune regulation under high oxidative stress conditions.

Effects of controlled physical activity on immune cell phenotype in peripheral blood in prehypertension - studies in preclinical model and randomised crossover study

Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice

Superoxide dismutase activity and expression in human venous and arterial bypass graft vessels