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1.

001-es BibID:BIBFORM027565
Első szerző:Bak István (vegyész, analitikus, farmakológus)
Cím:Evaluation of systemic and dermal toxicity and dermal photoprotection by sour cherry kernels / Istvan Bak, Attila Czompa, Evelin Csepanyi, Bela Juhasz, Heibatullah Kalantari, Khadija Najm, Nasreen Aghel, Balazs Varga, David D. Haines, Arpad Tosaki
Dátum:2011
ISSN:0160-2446
Megjegyzések:The present report describes outcomes of animal studies conducted to determine the systemic and dermal toxicity of Prunus cerasus (sour cherry) seed kernel contents; and a separate evaluation of the photoprotective capacity of the kernel oil fraction. B6 mice and Hartley guinea-pigs were used for these experiments. Dosage groups of 6-8 animals were administered whole kernel meal in a dose range of 0-3000 mg/kg by gavage for 8 days, following which they were killed. The liver and kidney weights were recorded and histological examination performed on sections of these organs. Kidney function was assessed as blood urea nitrogen and creatinine and liver function by measurement of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase. Dermal toxicity was evaluated in a Hartley guinea-pig model by comparing UVB-irradiated shaved skin to which the kernel oil had been applied with distilled water controls. In conclusion, no evidence of toxicity was observed to result from the consumption or dermal application of sour cherry seed kernel in the dose range at which it is likely to be used in foods or healthcare. Moreover, it was shown to have a powerful capacity to protect skin from UV damage. These results suggest it will prove to be a highly safe and effective addition to a wide range of products for general use. Copyright © 2011 John Wiley & Sons, Ltd.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Phytotherapy Research. - 25 : 11 (2011), p. 1714-1720. -
További szerzők:Czompa Attila (1985-) (gyógyszerész) Csépányi Evelin (1985-) (gyógyszerész) Juhász Béla (1978-) (kísérletes farmakológus) Kalantari, Heybatullah Najm, Khadija Aghel, Nasreen Varga Balázs (1984-) (kísérletes farmakológus) Haines, David Donald (1981-) (gyógyszerész) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM072791
Első szerző:Barta Tünde
Cím:Endothelin-1-induced hypertrophic alterations and heme oxygenase-1 expression in cardiomyoblasts are counteracted by beta estradiol : in vitro and in vivo studies / Tunde Barta, Agnes Tosaki, David Haines, Gyorgy Balla, Istvan Lekli, Arpad Tosaki
Dátum:2018
ISSN:0028-1298
Megjegyzések:Endothelin-1(ET-1),apotentvasoconstrictornormallyactiveinmaintainingvasculartone,maymediatesignificantpathogeniceffects, contributing to several serious diseases when aberrantly expressed or regulated. The present study evaluates the capacity of ET-1 to affect endothelin-1-associated hypertrophic activity and decreased expression of heme oxygenase-1 by H9c2 rat cardiomyoblasts in vitro, corresponding to in vivo processes underlying cardiovascular diseases (CVDs). Beta estradiol (?-E) is tested for its capacity to altertheeffectsofET-1.H9c2cells,cultured48h,werestimulatedwith100?10,000 nM of ET-1andevaluatedfor changes incell size,cellviability,andexpressionofthecytoprotectiveheatshockproteinhemeoxygenase-1(HO-1),with200nMof?-Eincludedin selectedculturestoevaluateitseffectonET-1-mediatedchanges.Theapplicationof100to10,000nMofET-1resultedinasignificant increase in average cell size and decreases in both cell viability and HO-1 protein content (p<0.05). Moreover, 200 nM of ?-E was observedtosignificantlycounteracttheseeffectsbycardiomyoblastsstimulatedwith1000nMofET-1(p<0.05).Sprague-Dawleyrats treated intravenously with 1000 ng/kg of ET-1 demonstrated reduced HO-1 expression in peripheral blood and left ventricular tissue, whichwascounteractedbyinjectionof200ng/kg?-E?demonstratingapossiblecorrespondencebetweeninvitroandinvivoeffects. Anoutcomeofparticularvalueforclinicaluseof ?-E,inthemanagementofcardiachypertrophy,istheobservedcapacityofthedrug to abate ET-1-mediated suppression of HO-1 expression. It has been previously demonstrated that HO-1 inducers exhibit potent cardioprotective properties, thus offering the promise of combining them with ?-E, allowing lower effective dosage of the drug and concomitantly lower adverse side effects associated with its clinical use. Major findings of this investigation are that pretreatment of cardiomyoblasts with ?-E inhibited their hypertrophic response to ET-1 and counteracts the decrease of cell viability. These effects were associated with a restoration of HO-1 protein expression in both under in vitro and in vivo conditions.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
endothelin
H9c2
Beta-estradiol
Megjelenés:Naunyn-Schmiedebergs Archives Of Pharmacology. - 391 : 4 (2018), p. 371-383. -
További szerzők:Tósaki Ágnes (1992-) (bőrgyógyász) Haines, David Donald (1981-) (gyógyszerész) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Lekli István (1981-) (gyógyszerész) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
Pályázati támogatás:OTKA-104017
OTKA
GINOP-2.3.2-15-2016-00043
GINOP
K104017
OTKA
NKFIH-124719
NKFIH
PD-111794
OTKA
TÁMOP-4.2.4. A/2-11-1-2012-0001
TÁMOP
GINOP-2.3.2-15-2016-00043
GINOP
Internet cím:Szerző által megadott URL
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3.

001-es BibID:BIBFORM070163
035-os BibID:(WoS)000404517800086 (Scopus)85019668917
Első szerző:Csépányi Evelin (gyógyszerész)
Cím:Antioxidant Properties and Oxidative Transformation of Different Chromone Derivatives / Csepanyi Evelin, Szabados-Furjesi Peter, Kiss-Szikszai Attila, Frensemeier Lisa M., Karst Uwe, Lekli Istvan, Haines David D., Tosaki Arpad, Bak Istvan
Dátum:2017
ISSN:1420-3049
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Molecules. - 22 : 4 (2017), p. 1-12. -
További szerzők:Szabados-Fürjesi Péter (1988-) (vegyész) Kiss-Szikszai Attila (1975-) (vegyész) Frensemeier, Lisa M. Karst, Uwe Lekli István (1981-) (gyógyszerész) Haines, David Donald (1981-) (gyógyszerész) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész) Bak István (1975-) (vegyész, analitikus, farmakológus)
Pályázati támogatás:K-104017
OTKA
PD-111794
OTKA
GINOP-2.3.2-15-2016-00043
GINOP
TÁMOP-4.2.4. A/2-11-1-2012-0001
TÁMOP
Internet cím:Szerző által megadott URL
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM059782
035-os BibID:(WOS)000363822600014 (Scopus)84940040945
Első szerző:Csépányi Evelin (gyógyszerész)
Cím:Cardiovascular effects of low versus high-dose beta-carotene in a rat model / Evelin Csepanyi, Attila Czompa, David Haines, Istvan Lekli, Edina Bakondi, Gyorgy Balla, Arpad Tosaki, Istvan Bak
Dátum:2015
ISSN:1043-6618
Megjegyzések:?-carotene (BC), a lipid-soluble tetraterpene precursor to vitamin A, widely distributed in plants, including many used in human diet, has well-known health-enhancing properties, including reducing risk of and treatment for certain diseases. Nevertheless, BC may also act to promote disease through the activity of BC derivatives that form in the presence of external toxicants such as cigarette smoke and endogenously-produced reactive oxygen species. The present investigation evaluates the dose-dependent cardioprotective and possibly harmful properties of BC in a rat model. Adult male rats, were gavage-fed BC for 4 weeks, at dosages of either 0, 30 or 150 mg/kg/day. Then hearts excised from the animals were mounted in a "working heart" apparatus and subjected to 30 minutes of global ischemia, followed by 120 minutes of reperfusion. A panel of cardiac functional evaluations was conducted on each heart. Infarct size and total antioxidant capacity of the myocardium were assessed. Heart tissue content of heme oxygenase-1 (HO-1) by Western blot analysis; and potential direct cytotoxic effects of BC by MTT assay were evaluated. Hearts taken from rats receiving 30 mg/kg/day BC exhibited significantly improved heart function at lower reperfusion times, but lost this protection at higher BC dosage and longer reperfusion times. Myocardial HO-1 content was significantly elevated dose-responsively to both BC dosage. Finally, in vitro evaluation of BC on H9c2 cells showed that the agent significantly improved vitality of these cells in a dose range of 2.5-10 ?M.Although data presented here do not allow for a comprehensive mechanistic explanation for reduced cardioprotection at high dose BC, it is speculated that since Fe2+ produced as a metabolite of HO-1 activity, may determine whether BC acts as an antioxidant or prooxidant agent, the strong induction of this enzyme in response to ischemia/reperfusion-induced oxidative stress may account for the high-dose BC loss of cardioprotection.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
beta-carotene
heart
ischemia/reperfusion
heme-oxygenase-1
Megjelenés:Pharmacological Research. - 100 (2015), p. 148-156. -
További szerzők:Czompa Attila (1985-) (gyógyszerész) Haines, David Donald (1981-) (gyógyszerész) Lekli István (1981-) (gyógyszerész) Bakondi Edina (1975-) (biokémikus, vegyész) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész) Bak István (1975-) (vegyész, analitikus, farmakológus)
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5.

001-es BibID:BIBFORM057392
Első szerző:Csiki Zoltán (belgyógyász, allergológus, klinikai immunológus, reumatológus)
Cím:Orally delivered sour cherry seed extract (SCSE) affects cardiovascular and hematological parameters in humans / Zoltan Csiki, Agnes Papp-Bata, Attila Czompa, Aniko Nagy, Istvan Bak, Istvan Lekli, Andras Javor, David D. Haines, Gyorgy Balla, Arpad Tosaki
Dátum:2015
ISSN:0951-418X
Megjegyzések:In the present study, we investigated the effects of sour cherry seed extract (SCSE) on a variety of systemic processes that contribute to general health and viability of human subjects. The experiments were conducted according to a double-blind protocol in which six healthy individuals were administered 250-mg/day SCSE for 14 days, while four were treated with placebo. Peripheral blood was collected before and after the treatment period. Samples were analyzed for levels of selected cells, enzymes, or metabolites. Subjects that received SCSE showed increases in the values of mean cell volume, serum transferrin, mean peroxidase index, and representation of peripheral blood lymphocytes. On the other hand, decreases were observed in circulating neutrophils and ferritin levels. Changes observed in the present study do not fit into a clear pattern that might yield additional in-depth understanding of SCSE-mediated alterations in physiologic responses. The most encouraging result of the present study is the absence of any indication of toxicity by subjects consuming the extract.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
sour cherry seed extract
heme oxygenase-1
human subjects
Megjelenés:Phytotherapy Research. - 29 : 3 (2015), p. 444-449. -
További szerzők:Papp-Bata Ágnes (1986-) Czompa Attila (1985-) (gyógyszerész) Nagy Anikó (1987-) (dietetikus, táplálkozástudományi szakember) Bak István (1975-) (vegyész, analitikus, farmakológus) Lekli István (1981-) (gyógyszerész) Jávor András (1952-) (agrármérnök) Haines, David Donald (1981-) (gyógyszerész) Balla György (1953-) (csecsemő és gyermekgyógyász, neonatológus) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
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6.

001-es BibID:BIBFORM067980
035-os BibID:(WoS)000398743500147 (Scopus)85016285017
Első szerző:Czompa Attila (gyógyszerész)
Cím:Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium / Czompa Attila, Gyöngyösi Alexandra, Szőke Kitti, Bak István, Csépányi Evelin, David D. Haines, Tósaki Árpád, Lekli István
Dátum:2017
ISSN:1420-3049
Megjegyzések:Objective: A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods: Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin?water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM). Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup. Results: Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in blood of ZO and ZO BM-treated, versus Lean rats of total cholesterol (high density lipoprotein HDL-c + low density lipoprotein LDL-c), with an inferred increase in HDL-c/LDL-c ratio?an outcome associated with decreased risk of atherosclerotic disease. Conclusions: BM extract failed to positively affect T2DM- and cardiovascular-related outcomes at a level suggesting use as a standalone treatment. Nevertheless, the encouraging effects of BM in enhancement of cardiac function, suppression of post-ischemic/reperfused infarct size extent and capacity to modulate serum cholesterol, will likely make it useful as an adjuvant therapy for the management of T2DM and related cardiovascular diseases.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Ischemia
diabetes
bitter melon
Megjelenés:Molecules. - 22 : 3 (2017), p. 488. -
További szerzők:Gyöngyösi Alexandra (1990-) (táplálkozástudományi szakember) Szőke Kitti (1989-) (gyógyszerész) Bak István (1975-) (vegyész, analitikus, farmakológus) Csépányi Evelin (1985-) (gyógyszerész) Haines, David Donald (1981-) (gyógyszerész) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész) Lekli István (1981-) (gyógyszerész)
Pályázati támogatás:OTKA-104017
OTKA
TÁMOP-4.2.4. A/2-11-1-2012-0001
TÁMOP
GINOP-2.3.2-15-2016-00043
Egyéb
OTKA-PD-111794
Egyéb
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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7.

001-es BibID:BIBFORM054296
Első szerző:Czompa Attila (gyógyszerész)
Cím:Cardioprotection afforded by sour cherry seed kernel : the role of heme oxygenase-1 / Attila Czompa, Alexandra Gyongyosi, Andras Czegledi, Evelin Csepanyi, Istvan Bak, David D. Haines, Arpad Tosaki, Istvan Lekli
Dátum:2014
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Molekulatudomány
Doktori iskola
Megjelenés:Journal of Cardiovascular Pharmacology. - 64 : 5 (2014), p. 412-419. -
További szerzők:Gyöngyösi Alexandra (1990-) (táplálkozástudományi szakember) Czeglédi András Csépányi Evelin (1985-) (gyógyszerész) Bak István (1975-) (vegyész, analitikus, farmakológus) Haines, David Donald (1981-) (gyógyszerész) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész) Lekli István (1981-) (gyógyszerész)
Pályázati támogatás:K-104017
OTKA
PD-83808
OTKA
TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
Kardiovaszkuláris megbetegedések génterápiás befolyásolása
TÁMOP-4.2.2/B-10/1-2010-0024
TÁMOP
Gyógyszerészeti Tudományok Doktori Iskola
TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Gyógyszerhatástan Kutatócsoport
TÁMOP 4.2.4. A/2-11-1-2012-0001
TÁMOP
Internet cím:Szerző által megadott URL
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

8.

001-es BibID:BIBFORM110555
035-os BibID:(Scopus)85055661719 (WOS)000447758100012
Első szerző:Haines, David Donald (gyógyszerész)
Cím:Role of Heme Oxygenases in Cardiovascular Syndromes and Co-morbidities / David D. Haines, Arpad Tosaki
Dátum:2018
ISSN:1381-6128
Megjegyzések:Cardiovascular Diseases (CVD), are the leading cause of human mortality worldwide and the focus of the intensive investigation is to characterize their pathogenesis. This review examines contribution to CVD of heme oxygenases (HOs), heat shock protein enzymes, comprising 3 isoforms: HO-1 (inducible), HO-2 (constitutively expressed) and HO-3 (function presently undefined), which constitute a primary endogenous countermeasure to oxidative tissue damage. Their role as CVD countermeasures is considered in the context of atherosclerosis, consequences of which are the leading cause of CVD deaths and from which 5 major syndromes may develop, namely: coronary artery disease and stroke, peripheral artery disease, kidney disease, cardiopulmonary disease and cerebrovascular disease. Over 75% of CVD deaths result from Coronary artery disease and stroke, with the severity of these conditions correlating with a systemic increase of the endogenous antioxidant bilirubin, produced by HO degradation of heme. Peripheral artery disease, (PAD) resulting from constricted arteries of the extremities is a painful and disabling condition, the severity of which correlates with elevated serum HO. Whether this represents an adaptive response or the enzyme is a contributor to PAD, remains to be determined. CVD symptoms, particularly hypertension, damage the vasculature and filtering structures of the kidneys and may be ameliorated by HO inducers. Interestingly, constitutive renal expression of HO-2 indicates that the enzyme is vital for healthy kidney function. Right ventricular hypertrophy and increased vascular resistance in blood vessels of the lungs exhibit mutually reinforcing positive feedback to result in cardiopulmonary heart disease, with morbidity and mortality resulting from associated inflammation and may be decreased with HO-1 inducers. Cerebrovascular disease, a major CVD complication affecting brain vasculature, with resulting susceptibility to stroke, maybe potently ameliorated by HO-1 inducers. Conclusion: Each of the six major categories of CVD exhibit features of pathogenesis that hold potential as future therapeutic targets, for modulated heme oxygenase activity.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Heme oxygenase
cardiovascular disease
atherosclerosis
stroke
endothelium
kidney
Megjelenés:Current Pharmaceutical Design. - 24 : 20 (2018), p. 2322-2325. -
További szerzők:Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
Pályázati támogatás:GINOP-2.3.2-15-2016-00043
GINOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM091400
035-os BibID:(cikkazonosító)9698 (scopus)85098074818 (wos)000602785000001
Első szerző:Haines, David Donald (gyógyszerész)
Cím:Heme Degradation in Pathophysiology of and Countermeasures to Inflammation-Associated Disease / Donald David Haines, Arpad Tosaki
Dátum:2020
ISSN:1661-6596 1422-0067
Megjegyzések:The class of tetrapyrrol "coordination complexes" called hemes are prosthetic group components of metalloproteins including hemoglobin, which provide functionality to these physiologically essential macromolecules by reversibly binding diatomic gasses, notably O2, which complexes to ferrous (reduced/Fe(II)) iron within the heme porphyrin ring of hemoglobin in a pH- and PCO2-dependent manner?thus allowing their transport and delivery to anatomic sites of their function. Here, pathologies associated with aberrant heme degradation are explored in the context of their underlying mechanisms and emerging medical countermeasures developed using heme oxygenase (HO), its major degradative enzyme and bioactive metabolites produced by HO activity. Tissue deposits of heme accumulate as a result of the removal of senescent or damaged erythrocytes from circulation by splenic macrophages, which destroy the cells and internal proteins, including hemoglobin, leaving free heme to accumulate, posing a significant toxicogenic challenge. In humans, HO uses NADPH as a reducing agent, along with molecular oxygen, to degrade heme into carbon monoxide (CO), free ferrous iron (FeII), which is sequestered by ferritin protein, and biliverdin, subsequently metabolized to bilirubin, a potent inhibitor of oxidative stress-mediated tissue damage. CO acts as a cellular messenger and augments vasodilation. Nevertheless, disease- or trauma-associated oxidative stressors sufficiently intense to overwhelm HO may trigger or exacerbate a wide range of diseases, including cardiovascular and neurologic syndromes. Here, strategies are described for counteracting the effects of aberrant heme degradation, with a particular focus on "bioflavonoids" as HO inducers, shown to cause amelioration of severe inflammatory diseases.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
therapies
diseases
heme oxygenase
heme degradation
Megjelenés:International Journal Of Molecular Sciences. - 21 : 24 (2020), p. 1-25. -
További szerzők:Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

10.

001-es BibID:BIBFORM078800
Első szerző:Haines, David Donald (gyógyszerész)
Cím:Emerging Clinical Applications of Heme Oxygenase / David Haines, Arpad Tosaki
Dátum:2018
ISSN:1381-6128
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok beszámoló
Megjelenés:Current Pharmaceutical Design. - 24 : 20 (2018), p. 2227-2228. -
További szerzők:Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
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Intézményi repozitóriumban (DEA) tárolt változat
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11.

001-es BibID:BIBFORM047699
035-os BibID:PMID:23789967
Első szerző:Haines, David Donald (gyógyszerész)
Cím:Management of multicellular senescence and oxidative stress / David D. Haines, Béla Juhasz, Arpad Tosaki
Dátum:2013
ISSN:1582-1838
Megjegyzések:Progressively sophisticated understanding of cellular and molecular processes that contribute to age-related physical deterioration is being gained from ongoing research into cancer, chronic inflammatory syndromes and other serious disorders that increase with age. Particularly valuable insight has resulted from characterization of how senescent cells affect the tissues in which they form in ways that decrease an organism's overall viability. Increasingly, the underlying pathophysiology of ageing is recognized as a consequence of oxidative damage. This leads to hyperactivity of cell growth pathways, prominently including mTOR (mammalian target of rapamycin), that contribute to a build-up in cells of toxic aggregates such as progerin (a mutant nuclear cytoskeletal protein), lipofuscin and other cellular debris, triggering formation of senescent cellular phenotypes, which interact destructively with surrounding tissue. Indeed, senescent cell ablation dramatically inhibits physical deterioration in progeroid (age-accelerated) mice. This review explores ways in which oxidative stress creates ageing-associated cellular damage and triggers induction of the cell death/survival programs' apoptosis, necrosis, autophagy and 'necroapoptophagy'. The concept of 'necroapoptophagy' is presented here as a strategy for varying tissue oxidative stress intensity in ways that induce differential activation of death versus survival programs, resulting in enhanced and sustained representation of healthy functional cells. These strategies are discussed in the context of specialized mesenchymal stromal cells with the potential to synergize with telocytes in stabilizing engrafted progenitor cells, thereby extending periods of healthy life. Information and concepts are summarized in a hypothetical approach to suppressing whole-organism senescence, with methods drawn from emerging understandings of ageing, gained from Cnidarians (jellyfish, corals and anemones) that undergo a unique form of cellular regeneration, potentially conferring open-ended lifespans.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
apoptosis
autophagy
necroptosis
necrosis
oxidative stress
senescence
Megjelenés:Journal of Cellular and Molecular Medicine. - 17 : 8 (2013), p. 936-957. -
További szerzők:Juhász Béla (1978-) (kísérletes farmakológus) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
Pályázati támogatás:OTKA 78223
OTKA
OTKA 104017
OTKA
TÁMOP-4.2.2/B-10/1-2010-0024
TÁMOP
TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
TÁMOP-4.2.4.A/2-11-1-2012-0001
TÁMOP
Internet cím:Szerző által megadott URL
DOI
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12.

001-es BibID:BIBFORM037298
Első szerző:Haines, David Donald (gyógyszerész)
Cím:Role of haeme oxygenase-1 in resolution of oxidative stress-related pathologies : focus on cardiovascular, lung, neurological and kidney disorders / D. D. Haines, I. Lekli, P. Teissier, I. Bak, A. Tosaki
Dátum:2012
ISSN:1748-1708
Megjegyzések:The present review examines the role of the cytoprotective enzyme haeme oxygenase-1 (HO-1) in adaptive responses to inflammatory disease and explores strategies for its clinical use, with particular emphasis on use of therapeutic use of the enzyme using phytochemical inducers of HO-1 such as extracts of Ginkgo biloba, curcumin, and flavonoids extracted from seeds of the sour cherry (Prunus cerasus). This laboratory has identified strategies by which combinations of dietary phytochemicals may be configured to synergistically strengthen immunoregulatory mechanisms that normally prevent inflammation from leading to disease. A major focus of this research initiative has been HO-1, which is capable of substantially reducing oxidative stress by several mechanisms. HO-1 metabolizes haeme that accumulates in tissues because of red blood cell turnover. Two products of this degradation - carbon monoxide (CO) and bilirubin - have potent capacity for reducing oxidative stress and for counteracting its effects. A description will be provided of how HO-1 products maintain healthy tissue function and remediate oxidative tissue damage. This will be explored in four major organ systems, including the cardiovascular system, the lungs, the central nervous system and the kidneys. Particular focus will be given to the physiological coordination of cardiovascular functions mediated by CO produced by HO-1 and to nitric oxide (NO), a gaseous second messenger expressed by nitric oxide synthetase. A major unifying theme of the present review is an exploration of the potential use of dietary phytochemical formulations as tools for the clinical application of HO-1 in therapeutic reduction of oxidative stressors, with resultant improved treatment of inflammatory pathologies.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Molekulatudomány
flavonoids
oxidative stress
haeme oxygenase-1
Megjelenés:Acta Physiologica. - 204 : 4 (2012), p. 487-501. -
További szerzők:Lekli István (1981-) (gyógyszerész) Teissier, P. Bak István (1975-) (vegyész, analitikus, farmakológus) Tósaki Árpád (1958-) (kísérletes farmakológus, gyógyszerész)
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
Kardiovaszkuláris megbetegedések génterápiás befolyásolása
TÁMOP-4.2.2/ B-10/1-2010-0024
TÁMOP
TÁMOP-4.2.2-08/1-2008-0007
TÁMOP
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
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