franz kerek - Academia.edu (original) (raw)

Papers by franz kerek

Angewandte Chemie International Edition in English, 1971

Physiological Research, 2010

Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic actio... more Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a nonselective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 ºC). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does no...

Atherosclerosis, Jan 15, 2015

Atherosclerosis is associated with chronic inflammatory responses of the arterial blood vessels. ... more Atherosclerosis is associated with chronic inflammatory responses of the arterial blood vessels. The previously observed protective effect of the MCS-18 substance against the initiation of atherosclerosis in a murine model was explained by its pronounced anti-inflammatory activity. Here, we investigated its impact on murine plaque progression in advanced atherosclerosis and on proatherogenic processes. ApoE-deficient mice were fed a high-fat diet for 12 weeks to induce atherosclerosis, followed by normal chow and intraperitoneal injections of either MCS-18 (500 μg, n = 10) or saline (n = 10) twice a week for another 12 weeks. Plaque size was reduced in MCS-18 treated mice compared to controls (p = 0.001), which was associated with a reduced size of the lipid core (p = 0.01). There was a decrease in apoptotic cells (p = 0.02), endothelial ICAM-1 expression (p < 0.001), and macrophage density (p = 0.01) in the MCS-18 group. In addition, human and murine dendritic cells (DCs) and hu...

Chemical Structure–Biological Activity Relationships: Quantitative Approaches, 1980

Romanian Biotechnological Letters

Atherosclerosis, 2014

Inflammation accelerates both plaque progression and instability in the pathogenesis of atheroscl... more Inflammation accelerates both plaque progression and instability in the pathogenesis of atherosclerosis. The inhibition of dendritic cell (DC) maturation is a promising approach to suppress excessive inflammatory immune responses and has been shown to be protective in several autoimmune models. The aim of this study was to investigate the immune modulatory effects of the natural substance MCS-18, an inhibitor of DC maturation, regarding the progression of atherosclerosis in ApoE-deficient mice. ApoE-deficient mice were fed for twelve weeks with a Western-type diet (n = 32) or normal chow (control group; n = 16). Animals receiving high-fat diet were treated with MCS-18 (500 μg/kg body weight, n = 16) or saline (n = 16) twice a week. After 12 weeks, animals were transcardially perfused and sacrificed. The percentage of mature DCs (CD3(-)/CD19(-)/CD14(-)/NK1.1(-)/CD11c(+)/MHCII(+)/CD83(+)/CD86(+)) and T cell subpopulations (CD4(+)/CD25(+)/Foxp3(+), CD3/CD4/CD8) was analyzed in peripher...

Roumanian archives of microbiology and immunology

High-mobility group box protein 1 (HMGB1) is an intracellular protein that may be released active... more High-mobility group box protein 1 (HMGB1) is an intracellular protein that may be released actively from monocytes and macrophages or passively from necrotic or damaged cells. Its inhibition in animal experiments, even in the late phase of septic shock, significantly enhanced the survival rate of rodents. The aim of our study was to investigate the effect of a vegetal fraction isolated and highly purified from Helleborus purpurascens regarding the modulation of HMGB1 release either from tumor cells or human blood mononuclear cells. Our results showed that the vegetal fraction was able to down-regulate the release of HMGB1 from activated human blood mononuclear cells (PBMCs) and tumor cells. By combining the purified fraction with Cyclophosphamide the release of HMGB1 from tumor cells was strongly decreased. This synergism was not noticed when the ve getal product was associated with Doxorubicin. We also studied the effect of the purified fraction in mice with septic shock induced by...

Roumanian archives of microbiology and immunology

Cold atmospheric plasma treatment acts at the cellular level to remove diseased tissue without in... more Cold atmospheric plasma treatment acts at the cellular level to remove diseased tissue without inflammation and damage, to suppress infections and to modulate the viability (apoptosis/necrosis) of tumoral cells. It is also known that, a major cause of anti-tumor chemotherapy failure is the development of multidrug resistance (MDR) of tumors. This study reveals the effect of high voltage pulsed, repetitive cold atmospheric plasma jets which are chemically activated with oxygen, on B16 tumoral cells (murine melanoma cell line) and COLO320DM multidrug resistant cells (human colon cancer cell line). The tests have been performed on human colon cancer cell line COLO320DM and murine melanoma cell line B16-F10. These cell lines have been treated with cold helium or helium-oxygen generated plasma jets and the consequent apoptosis has been analyzed by means of flow cytometric method. A treatment time-dependent apoptosis has been observed only in the case of 816-F10 cells interacting with hel...

Roumanian archives of microbiology and immunology

There are many studies demonstrating by different experimental models that non-steroidal antiinfl... more There are many studies demonstrating by different experimental models that non-steroidal antiinflammatory drugs (NSAIDs), also known as cyclooxygenase-2 (COX-2) inhibitors, can modulate immune response such as lymphoid cells differentiation and proliferation. There are experimental data which show that activated B cells can express mRNA COX-2, release prostaglandins (PGs) and produce immunoglobulins in PGs dependent manner. In this study, using different COX-2 inhibitors and applying personalized immunization scheme, we confirmed that it is possible to modulate in vivo antibody response against T cell dependent antigens, substantiating the importance of PGE2 and E prostanoid receptor (EP-R) in antibody generation. Our results point out the fact that we must be more careful when we apply vaccines containing T-cell dependent antigens, such as tetanus or diphteric anatoxin, to the patients under an intense antiinflammatory treatment.

Acta Crystallographica Section A Foundations of Crystallography, 2010

European Heart Journal, 2013

Roumanian archives of microbiology and immunology

Angiogenesis, the biological process by which new capillaries are formed from pre-existing vessel... more Angiogenesis, the biological process by which new capillaries are formed from pre-existing vessels, is a tightly controlled and complex process involving several factors with both stimulating and inhibiting steps. In solid tumor growth, a specific clinical turning point is the transition to the vascular phase. Once it develops an intrinsic vascular network, a tumor grows indefinitely. Tumor angiogenesis depends mainly on the release by neoplasic cells of growth factors specific for endothelial cells (ECs), able to stimulate growth of the host blood vessels. The aim of this study was to analyze the apoptotic effect of some cytostatics, Vinblastine, Rapamycin and Doxorubicin, and vegetal extracts (called VOB) isolated and purified from Vitis sp., on human EA.hy926 endothelial cell line. In a proliferation assay using Crystal Violet, we demonstrated that Vinblastine and Rapamycin cytostatics have synergistic effect on endothelial cell line EA.hy926 growth inhibition. The inhibitory eff...

Tetrahedron, 1980

... Trotzdem ist die Zahl entsprechender Anwendungen sehr geeing` im Vergleich mit dem elektronis... more ... Trotzdem ist die Zahl entsprechender Anwendungen sehr geeing` im Vergleich mit dem elektronisch doppelt so komplizierten, aber chiroptisch weitaus hfiger untersuchten jC=O-Chromophor.'' Die Schwierigkeiten werden teilweise durch die konurative Labilit der syn-anti ...

Transplantation Proceedings, 1999

Tetrahedron, 1969

ABSTRACT The catalytic (second order) rate constants, obtained in benzene solution at 80°. for si... more ABSTRACT The catalytic (second order) rate constants, obtained in benzene solution at 80°. for six various substituted 1-phenyl-phospholene oxides obeyed a linear ϱσ° relationship excellently (where ϱ = -0·750 and σ° are the “normal” substituent constants). These data indicate a lack of conjugation between aromatic ring and phosphoryl group.

Journal of Membrane Biology, 2005

Angewandte Chemie International Edition in English, 1971

Physiological Research, 2010

Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic actio... more Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a nonselective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 ºC). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does no...

Atherosclerosis, Jan 15, 2015

Atherosclerosis is associated with chronic inflammatory responses of the arterial blood vessels. ... more Atherosclerosis is associated with chronic inflammatory responses of the arterial blood vessels. The previously observed protective effect of the MCS-18 substance against the initiation of atherosclerosis in a murine model was explained by its pronounced anti-inflammatory activity. Here, we investigated its impact on murine plaque progression in advanced atherosclerosis and on proatherogenic processes. ApoE-deficient mice were fed a high-fat diet for 12 weeks to induce atherosclerosis, followed by normal chow and intraperitoneal injections of either MCS-18 (500 μg, n = 10) or saline (n = 10) twice a week for another 12 weeks. Plaque size was reduced in MCS-18 treated mice compared to controls (p = 0.001), which was associated with a reduced size of the lipid core (p = 0.01). There was a decrease in apoptotic cells (p = 0.02), endothelial ICAM-1 expression (p < 0.001), and macrophage density (p = 0.01) in the MCS-18 group. In addition, human and murine dendritic cells (DCs) and hu...

Chemical Structure–Biological Activity Relationships: Quantitative Approaches, 1980

Romanian Biotechnological Letters

Atherosclerosis, 2014

Inflammation accelerates both plaque progression and instability in the pathogenesis of atheroscl... more Inflammation accelerates both plaque progression and instability in the pathogenesis of atherosclerosis. The inhibition of dendritic cell (DC) maturation is a promising approach to suppress excessive inflammatory immune responses and has been shown to be protective in several autoimmune models. The aim of this study was to investigate the immune modulatory effects of the natural substance MCS-18, an inhibitor of DC maturation, regarding the progression of atherosclerosis in ApoE-deficient mice. ApoE-deficient mice were fed for twelve weeks with a Western-type diet (n = 32) or normal chow (control group; n = 16). Animals receiving high-fat diet were treated with MCS-18 (500 μg/kg body weight, n = 16) or saline (n = 16) twice a week. After 12 weeks, animals were transcardially perfused and sacrificed. The percentage of mature DCs (CD3(-)/CD19(-)/CD14(-)/NK1.1(-)/CD11c(+)/MHCII(+)/CD83(+)/CD86(+)) and T cell subpopulations (CD4(+)/CD25(+)/Foxp3(+), CD3/CD4/CD8) was analyzed in peripher...

Roumanian archives of microbiology and immunology

High-mobility group box protein 1 (HMGB1) is an intracellular protein that may be released active... more High-mobility group box protein 1 (HMGB1) is an intracellular protein that may be released actively from monocytes and macrophages or passively from necrotic or damaged cells. Its inhibition in animal experiments, even in the late phase of septic shock, significantly enhanced the survival rate of rodents. The aim of our study was to investigate the effect of a vegetal fraction isolated and highly purified from Helleborus purpurascens regarding the modulation of HMGB1 release either from tumor cells or human blood mononuclear cells. Our results showed that the vegetal fraction was able to down-regulate the release of HMGB1 from activated human blood mononuclear cells (PBMCs) and tumor cells. By combining the purified fraction with Cyclophosphamide the release of HMGB1 from tumor cells was strongly decreased. This synergism was not noticed when the ve getal product was associated with Doxorubicin. We also studied the effect of the purified fraction in mice with septic shock induced by...

Roumanian archives of microbiology and immunology

Cold atmospheric plasma treatment acts at the cellular level to remove diseased tissue without in... more Cold atmospheric plasma treatment acts at the cellular level to remove diseased tissue without inflammation and damage, to suppress infections and to modulate the viability (apoptosis/necrosis) of tumoral cells. It is also known that, a major cause of anti-tumor chemotherapy failure is the development of multidrug resistance (MDR) of tumors. This study reveals the effect of high voltage pulsed, repetitive cold atmospheric plasma jets which are chemically activated with oxygen, on B16 tumoral cells (murine melanoma cell line) and COLO320DM multidrug resistant cells (human colon cancer cell line). The tests have been performed on human colon cancer cell line COLO320DM and murine melanoma cell line B16-F10. These cell lines have been treated with cold helium or helium-oxygen generated plasma jets and the consequent apoptosis has been analyzed by means of flow cytometric method. A treatment time-dependent apoptosis has been observed only in the case of 816-F10 cells interacting with hel...

Roumanian archives of microbiology and immunology

There are many studies demonstrating by different experimental models that non-steroidal antiinfl... more There are many studies demonstrating by different experimental models that non-steroidal antiinflammatory drugs (NSAIDs), also known as cyclooxygenase-2 (COX-2) inhibitors, can modulate immune response such as lymphoid cells differentiation and proliferation. There are experimental data which show that activated B cells can express mRNA COX-2, release prostaglandins (PGs) and produce immunoglobulins in PGs dependent manner. In this study, using different COX-2 inhibitors and applying personalized immunization scheme, we confirmed that it is possible to modulate in vivo antibody response against T cell dependent antigens, substantiating the importance of PGE2 and E prostanoid receptor (EP-R) in antibody generation. Our results point out the fact that we must be more careful when we apply vaccines containing T-cell dependent antigens, such as tetanus or diphteric anatoxin, to the patients under an intense antiinflammatory treatment.

Acta Crystallographica Section A Foundations of Crystallography, 2010

European Heart Journal, 2013

Roumanian archives of microbiology and immunology

Angiogenesis, the biological process by which new capillaries are formed from pre-existing vessel... more Angiogenesis, the biological process by which new capillaries are formed from pre-existing vessels, is a tightly controlled and complex process involving several factors with both stimulating and inhibiting steps. In solid tumor growth, a specific clinical turning point is the transition to the vascular phase. Once it develops an intrinsic vascular network, a tumor grows indefinitely. Tumor angiogenesis depends mainly on the release by neoplasic cells of growth factors specific for endothelial cells (ECs), able to stimulate growth of the host blood vessels. The aim of this study was to analyze the apoptotic effect of some cytostatics, Vinblastine, Rapamycin and Doxorubicin, and vegetal extracts (called VOB) isolated and purified from Vitis sp., on human EA.hy926 endothelial cell line. In a proliferation assay using Crystal Violet, we demonstrated that Vinblastine and Rapamycin cytostatics have synergistic effect on endothelial cell line EA.hy926 growth inhibition. The inhibitory eff...

Tetrahedron, 1980

... Trotzdem ist die Zahl entsprechender Anwendungen sehr geeing` im Vergleich mit dem elektronis... more ... Trotzdem ist die Zahl entsprechender Anwendungen sehr geeing` im Vergleich mit dem elektronisch doppelt so komplizierten, aber chiroptisch weitaus hfiger untersuchten jC=O-Chromophor.'' Die Schwierigkeiten werden teilweise durch die konurative Labilit der syn-anti ...

Transplantation Proceedings, 1999

Tetrahedron, 1969

ABSTRACT The catalytic (second order) rate constants, obtained in benzene solution at 80°. for si... more ABSTRACT The catalytic (second order) rate constants, obtained in benzene solution at 80°. for six various substituted 1-phenyl-phospholene oxides obeyed a linear ϱσ° relationship excellently (where ϱ = -0·750 and σ° are the “normal” substituent constants). These data indicate a lack of conjugation between aromatic ring and phosphoryl group.

Journal of Membrane Biology, 2005