136 research outputs found
Pilk Richard Viidalepa perekonnaloole
No full textRichard Viidalepp (Widebaum before Estonianising his name, and later Viidebaum; Jan. 23, 1904 - June 3, 1986), the famous Estonian folklorist, was born in the Jalapuu farm in the village of Nurmsi in Central Estonia. The same farm was the home of Urve Buschmann, the author of the article and R. Viidalepp's niece. On the basis of the 1722 list of inhabitants in the Särgavere estate and the registers of the Järva Peetri congregation, the documented genealogy of Viidalepp's family starts with Jüri Jalapuu and his wife Els (?1730-?1761). In more recent registers their son Jüri (?1771-1843) already appears under the name Widebaum. The family was a typical Estonian family, including farmers, handicraftsmen, inventive technicians, later also intellectuals and artists. Some emigrated (the Finnish and American branches of the Viidebaums) and some were deported to Siberia. The fate of family members and descriptions of family history are illustrated by Richard Viidalepp's letters and family photographs. The last Viidalepps born in the Jalapuu farm moved to Tallinn in 1950
A fluorescent host-guest complex of cucurbituril in solution: a molecular Jack O'Lantern
No full textFluorescence enhancement of a probe molecule in solution by the container molecule cucurbituril (CB) is reported for the first time. The fluorescence of the probe 2-anilinonaphthalene-6-sulfonate (2,6-ANS) in aqueous Na2SO4 solution is found to increase by a maximum factor of 5.0 upon addition of cucurbituril. This fluorescence enhancement is the result of the formation of a host-guest inclusion complex, in which the guest 2,6-ANS is incorporated inside the cavity of the host, cucurbituril. Measurement of the enhancement as a function of cucurbituril concentration yielded a value of the equilibrium constant (K) of 52 +/- 10 M-1. It is proposed that the mode of inclusion involves the phenyl group of the 2,6-ANS, because of the relatively small size of the cucurbituril cavity. It is further proposed that the observed enhancement is a result of loss of rotational mobility of the phenyl ring relative to the naphthyl fluorophore of 2,6-ANS upon inclusion of the phenyl ring, Since the name cucurbituril is derived from the Latin word for "pumpkin," this fluorescent host-guest complex is referred to as a "molecular Jack O'Lantern," with the 2,6-ANS serving as the candle.PT: J; CR: BEHREND R, 1905, LIEBIGS ANN CHEM, V339, P1 BORTOLUS P, 1996, ADV PHOTOCHEMISTRY P, P1 BUSCHMANN HJ, 1992, J INCLUS PHENOM MOL, V14, P91 BUSCHMANN HJ, 1997, J INCLUS PHENOM MOL, V29, P167 BUSCHMANN HJ, 1998, THERMOCHIM ACTA, V317, P95 BUSCHMANN HJ, 1999, J PHOTOCH PHOTOBIO A, V121, P99 CINTAS P, 1994, J INCLUS PHENOM MOL, V17, P205 CRAM DJ, 1997, CONTAINER MOL THEIR DANTZ DA, 1998, SUPRAMOL CHEM, V9, P79 DELAPENA AM, 1993, J INCLUS PHENOM MOL, V15, P131 DIAMOND D, 1996, CHEM SOC REV, V25, P15 FREEMAN WA, 1981, J AM CHEM SOC, V103, P7367 HOFFMANN R, 1994, J CHEM SOC FARADAY T, V90, P1507 JEON YM, 1996, J AM CHEM SOC, V118, P9790 KOSOWER EM, 1975, J AM CHEM SOC, V97, P2167 KOSOWER EM, 1978, J AM CHEM SOC, V100, P4179 LI S, 1992, CHEM REV, V92, P1457 MOCK WL, 1983, J ORG CHEM, V48, P3618 MOCK WL, 1995, TOP CURR CHEM, V175, P1 MOCK WL, 1996, COMPREHENSIVE SUPRAM, V2, P477 WAGNER BD, 1998, J PHOTOCH PHOTOBIO A, V114, P151 WAGNER BD, 1999, J PHYS CHEM B, V103, P10114 WAGNER BD, 2000, J INCL PHENOM MACRO, V38, P467 WHANG DM, 1998, J AM CHEM SOC, V120, P4899; NR: 24; TC: 16; J9: CAN J CHEM; PG: 4; GA: 473RESource type: Electronic(1
Arteriogenesis as a new therapeutic intervention strategy in chronic artery disorders. Cellular mechanism and experimental models
No full textInvestigation of the effect of angiotensin receptor neprilysin inhibitors (ARNI) on collateral artery growth in the coronary arteriogenesis model of the rat
No full textHerzinsuffizienzen, ausgelöst durch myokardiale Ischämien, gehören weltweit zu den führenden Todesursachen des Menschen. Präventive Maßnahmen, um die Genese einer Herzinsuffizienz nach einem Myokardinfarkt und schlussendlich das Ereignis eines myokardialen Herztodes zu umgehen, werden laufend erforscht. Studien zeigten, dass Patienten mit hochgradigen Verschlüssen großer koronarer Hauptarterien, die ein ausgeprägtes koronares kollaterales Gefäßnetz besitzen, eine bessere Prognose aufweisen einen Myokardinfarkt zu überleben. Kollateralarterien können hierbei den Blutfluss im Falle eines Myokardinfarktes in dem ischämischen Areal wiederherstellen.
Arteriogenese beschreibt das Wachstum von kleinen kollateralen Gefäßen zu größeren Leitungsgefäßen. Ziel aktueller Forschung ist die therapeutische Stimulation der natürlichen Arteriogenese. Die therapeutische Arteriogenese dient durch das Wachstum von biologischen Bypässen hierbei als wichtiger kompensatorischer Mechanismus zur Prävention von vaskulären Ischämien. Vorherige Studien zeigten, dass die Erhöhung der Bradykininkonzentration und die Reduktion des Abbaus von Kininen die Arteriogenese in der Peripherie und im Gehirn positiv stimulieren. Ziel der vorliegenden Arbeit war zu untersuchen, ob der Angiotensin-Rezeptor-Neprilysin-Inhibitor Entresto®, bestehend aus dem pharmakologischen Kombinationspräparat Sacubitril und Valsartan, in einem Arteriogenesemodell am Rattenherz, durch die Anreicherung von Bradykinin die protektive myokardiale Arteriogenese therapeutisch stimuliert.
Zu Beginn der Studie wurde das repetitiv-okkludierende Programm (ROP) etabliert, um das koronare Kollateralwachstum im Herzen der Sprague-Dawley Ratte zu stimulieren. Dabei wurde in der Initialoperation ein Ballonkatheter auf den Ramus interventricularis paraconalis der Arteria coronaria sinistra implantiert. An den folgenden sieben Tagen löste die Inflation des Katheters mit Luft, nach einem streng kontrollierten Programm, wiederholt eine kurzfristige Okklusion der Arterie aus. Die Steuerung erfolgte mittels eines standardisierten Computerprogramms. Nach sieben Tagen wurde in der Finaloperation durch permanente Inflation des Okkluders ein Herzinfarkt ausgelöst, daraufhin erfolgte die Entnahme des Herzens. Die Studie umfasste vier Versuchsgruppen. Alle Gruppen erhielten die Initialoperation. Eine Gruppe (Rop) wurde danach an das repetitiv-okkludierende Programm angeschlossen. Eine Gruppe diente als Kontrollgruppe und wurde nicht an das ROP angeschlossen. Bei den anderen zwei Versuchsgruppen kam ebenfalls das ROP zur Anwendung, zusätzlich erhielten die Gruppen eine unterschiedliche medikamentöse Therapie. Eine dieser Versuchsgruppen wurde mit dem kombinierten Angiotensin-Rezeptor-Neprilysin Inhibitor Entresto®, die andere Gruppe mit dem Angiotensin-Rezeptor-Blocker Valsartan behandelt. Die primäre Endpunktmessung erfolgte durch die Ermittlung der kollateralen Perfusion mittels Isotop-markierter Mikrosphären, die bei Initialoperation wie auch Finaloperation injiziert wurden.
Nach siebentägiger Anwendung des repetitiv-okkludierenden Programms wurde festgestellt, dass die mittlere kollaterale Perfusion in der Rop-Gruppe signifikant höher war, als in der Kontrollgruppe. In der mit Valsartan behandelten Versuchsgruppe konnte, gegenüber der ausschließlich mit ROP behandelten Gruppe, keine zusätzliche Verbesserung der koronaren Arteriogenese nachwiesen werden. Die zusätzlich mit dem Angiotensin-Rezeptor-Neprilysin-Inhibitor Entresto® therapierte Gruppe zeigte, im Vergleich zu allen anderen Versuchsgruppen, eine signifikant verbesserte kollaterale Perfusion.
Die vorliegende Studie beweist somit erstmalig, dass die Behandlung mit dem Angiotensin-Rezeptor-Neprilysin-Inhibitor Entresto® durch eine beschleunigte Stimulation des kollateralen Gefäßwachstums zu einer deutlichen Verbesserung der kollateralen Perfusion führt. Ausschlaggebend für die Wirkung von Entresto® könnte die Erhöhung bzw. Stabilisierung des Bradykininspiegels sein. Diese geschieht aufgrund der Inhibition von Neprilysin, dem Enzym, das für den Bradykininabbau verantwortlich ist. Gleichzeitig dient Valsartan als Modulator der Blutdruckregulation, um möglichen überschießenden Effekten eines Neprilysin-Inhibitors entgegenzuwirken. Es wird deutlich, dass der aufgezeigte pharmakologische Mechanismus, welcher durch die Behandlung mit Entresto® ausgelöst wird, als präventiv-medikamentöse Behandlungsoption einen hohen klinischen Nutzen bei Herzinsuffizienz und Myokardinfarkt haben kann.Heart failure triggered by myocardial ischemia is one of the leading causes of human death worldwide. Research into preventive measures to avoid the development of heart failure after myocardial infarction and ultimately the event of sudden cardiac death has been ongoing for many years. Studies have shown that patients with high-grade occlusions of large coronary arteries with a distinct coronary collateral vascular network have a better prognosis to survive myocardial infarction, since collateral arteries can restore blood flow in the ischemic area in the case of myocardial infarction.
Arteriogenesis describes the growth of small collateral blood vessels into larger conducting blood vessels. Current research aims to stimulate natural arteriogenesis by various therapeutic measures. Therapeutic arteriogenesis serves as an important compensatory mechanism for the prevention of vascular ischemia through the growth of biological bypasses. Previous studies showed that increasing bradykinin concentration and reducing kinin degradation positively stimulate arteriogenesis in the periphery and brain. The aim of the dissertation at hand was to investigate whether the angiotensin receptor/ neprilysin inhibitor Entresto®, consisting of the pharmacological combination preparation sacubitril and valsartan, therapeutically stimulates protective myocardial arteriogenesis in a rat heart arteriogenesis model by enhancing bradykinin.
At the start of the study, the repetitive-occluding program (ROP) was established to stimulate coronary collateral growth in the heart of the Sprague-Dawley rat. To achieve this, a balloon catheter was surgically implanted on the ramus interventricularis paraconalis of the coronary sinistra artery. Over the next seven days, the catheter was repeatedly inflated with air following a tightly controlled schedule, each time triggering the short-term occlusion of the artery. This procedure was monitored by a standardized computer program. After seven days, myocardial infarction was triggered by the permanent inflation of the occluder during the final surgery, which was followed by the removal of the heart. The study included four experimental groups. All groups received the initial operation. One group (Rop) was then connected to the repetitiveoccluding program. One group served as a control group and was not connected to the ROP. The other two experimental groups also used the ROP, and in addition, the groups received different drug therapies. One of these experimental groups was treated with the combined angiotensin receptor-neprilysin inhibitor Entresto®, whereas the other group was treated with the angiotensin receptor blocker valsartan. The primary end-point measurement was performed by determining the collateral perfusion using isotope-labeled microspheres injected during both the initial and final surgery.
After using the repetitive-occluding program for seven days, the mean collateral perfusion was found to be significantly higher in the ROP group than in the control group. In the experimental group treated with valsartan, no additional improvement in coronary arteriogenesis could be detected compared with the group treated with ROP alone. The group additionally treated with the angiotensin receptor/neprilysin inhibitor Entresto® showed a significantly improved collateral perfusion compared with the other experimental groups.
Thus, the study at hand proves for the first time that treatment with the angiotensin receptor/neprilysin inhibitor Entresto® leads to a marked improvement in collateral perfusion by accelerating the stimulation of collateral vessel growth. Crucial to the effect of Entresto® may be the increase or stabilization of bradykinin levels. This occurs due to the inhibition of neprilysin, the enzyme responsible for bradykinin degradation. At the same time, valsartan serves as a modulator of blood pressure regulation to counteract possible exaggerated effects of a neprilysin inhibitor. The demonstrated pharmacological mechanism triggered by Entresto® treatment may have a high clinical benefit as a preventive drug treatment option in heart failure and myocardial infarction
Arteriogenesis: egy új terápiás intervenciós stratégia krónikus artériabetegségekben. Sejtes mechanizmus és kísérletes modellek = Arteriogenesis as a new therapeutic intervention strategy in chronic artery disorders. Cellular mechanism and experimental models
No full textAz arteriogenesis fogalmát csak néhány évvel ezelőtt definiálták. Ez az endogén folyamat, egy természetes kompenzációs mechanizmus a stenosis vagy artériás okklúzió indukálta szöveti hipoperfúzió ellen, ami a vér már meglévő kollaterális arteriákba történő jobb megoszlását és az erek újjászerveződését jelenti. A főbb krónikus artériabetegségeket, mint amilyen a coronariabetegség, a perifériás artériabetegség és a cerebrovascularis betegség, széles körben tanulmányozták az angiogenesis és az arteriogenesis szempontjából az elmúlt évtizedben. Az in vivo állatkísérletek és a kollaterális artériák fejlődése mögött álló sejtes és molekuláris mechanizmusok ex vivo analízise feltárta a keringő monociták, endothel- és simaizom-sejtek alapvető szerepét a kollaterális erek újrastrukturálódásában. Az adaptív arteriogenesis a szívben, az agyban és a periférián különböző kemokinekkel és növekedési faktorokkal stimulálható. Ezen anyagok terápiás alkalmazása ígéretes eredményeket hozott preklinikai állatmodellekben, úgymint javuló kollaterális konduktanciát, kiterjedt neovascularisatiót a kollaterális-függő szöveti régióban, csökkent infarktusterületet hemodinamikus stroke-ban és jobb funkcionális paramétereket miocardialis ischaemiában. A humán vizsgálatok tervezése során föl kell tennünk a következő kérdéseket: mi az optimális alkalmazási megközelítés, a megfelelő dózis, az időzítés és a követés időtartama? Ez az összefoglaló közlemény áttekintést szeretne adni az arteriogenesis mechanizmusának főbb elemeiről és a spontán és stimulált kollaterális artérianövekedésre vonatkozó legfontosabb kísérletes adatokról.
The term arteriogenesis became clarified only some years ago. This endogenous process is a natural compensation mechanism against stenosis or arterial occlusion-induced tissue hypoperfusion via improvement of blood distribution in the pre-existent collateral arteries. The main chronic artery disorders like coronary heart disease, peripheral artery disease and cerebrovascular disease were extensively studied for angiogenesis and arteriogenesis during the last decade. The in vivo animal experiments and the ex vivo
analysis of the cellular and molecular mechanisms behind collateral artery development revealed the crucial role of circulating monocytes, endothelial and smooth muscle cells in the remodelling of collateral blood vessels. The adaptive arteriogenesis in the heart, brain and periphery can be stimulated by different chemokines and growth factors. The therapeutic application of these substances resulted in promising data in pre-clinical animal models, i.e. improved collateral conductance, extended neo-vascularization in the collateral dependent tissue regions, decreased infarct area after hemodynamic stroke and better functional parameters in myocardial ischemia. The questions that have to be addressed during the design of human investigations are the optimal delivery approach, the appropriate dosage, timing and the durability of the follow up. The present review tries to give an overview about the main points of the mechanism and the most important experimental data concerning spontaneous and stimulated collateral artery growth, this new and promising therapeutic approach for chronic artery diseases
Visualization of therapeutic arteriogenesis by MR angiography: Functional measurements are superior to surrogate parameters
No full textFluorescence enhancement of curcumin upon inclusion into cucurbituril
No full textThe effect of the macrocyclic host compounds cucurbit[n]urils (Qn), with n = 5 - 7, on the fluorescence of the biologically active compound curcumin has been studied. Curcumin, the main constituent of the Indian spice turmeric, is of growing interest because of its wide-ranging pharmaceutical properties. This compound forms strong 2:1 host-guest inclusion complexes with Q6 (the original cucurbituril), with an overall equilibrium constant of (1.9 +/- 0.8) X 10(4) M-2. It is postulated that a Q6 host partially encapsulates each of the two phenyl groups at the ends of the curcumin molecule. The difference in magnitude of the equilibrium constants K-1 (72 +/- 2 M-1) and K-1 (260 +/- 120 M-1) for stepwise encapsulation of the two ends of the curcumin molecule indicates that encapsulation by the first Q6 significantly alters its entire electronic structure, resulting in a more favorable second encapsulation. A very large enhancement of the fluorescence of curcumin results from this complex formation, on the order of 5.0; this is a significant fraction of the polarity sensitivity factor (PSF) of 39 measured for curcumin, that is the ratio of fluorescence intensity in ethanol vs. water. Surprisingly, no such enhancement could be observed in the case of Q7, indicating that the interactions between the guest and the host cavity are not favorable in this case, contrary to expectations. Similarly, no enhancement was observed in the case of Q5, which is not unexpected, because of the extremely small size of the host cavity and portal in this case.PT: J; CR: BARIK A, 2003, PHOTOCHEM PHOTOBIOL, V77, P597 BONG PH, 2000, B KOR CHEM SOC, V21, P81 BUSCHMANN HJ, 1997, J INCLUS PHENOM MOL, V29, P167 BUSCHMANN HJ, 1998, J SOLUTION CHEM, V27, P135 BUSCHMANN HJ, 1998, THERMOCHIM ACTA, V317, P95 BUSCHMANN HJ, 2000, J INCL PHENOM MACRO, V37, P231 BUSCHMANN HJ, 2000, SUPRAMOL CHEM, V11, P225 CHIGNELL CF, 1994, PHOTOCHEM PHOTOBIOL, V59, P295 CHOI S, 2002, MACROMOLECULES, V35, P3526 CINTAS P, 1994, J INCLUS PHENOM MOL, V17, P205 DAHL TA, 1994, PHOTOCHEM PHOTOBIOL, V59, P290 DALTON L, 2003, CHEM ENG NEWS SEP, P8 DAY A, 2001, J ORG CHEM, V66, P8094 DELAPENA AM, 1993, J INCLUS PHENOM MOL, V15, P131 ELHAOUAJ M, 2001, J CHEM SOC PERK NOV, P2104 ELHAOUAJ M, 2001, J CHEM SOC PERK T 2, P804 FREEMAN WA, 1981, J AM CHEM SOC, V103, P7367 FREEMAN WA, 1984, ACTA CRYSTALLOGR B, V40, P382 HAMAI S, 1996, B CHEM SOC JPN, V69, P2469 HOFFMANN R, 1994, J CHEM SOC FARADAY T, V90, P1507 JANSEN K, 2000, VOM WASSER, V95, P229 JEON YM, 1996, J AM CHEM SOC, V118, P9790 JOVANOVIC SV, 2001, J AM CHEM SOC, V123, P3064 KHOPDE SM, 2000, PHOTOCHEM PHOTOBIOL, V72, P625 KIM J, 2000, J AM CHEM SOC, V122, P540 LAGONA J, 2003, ORG LETT, V5, P3745 LEE JW, 2003, ACCOUNTS CHEM RES, V36, P621 LIU Y, 2000, J ORG CHEM, V65, P6227 MARQUEZ C, 2001, ANGEW CHEM INT EDIT, V40, P3155 MARQUEZ C, 2001, ANGEW CHEM INT EDIT, V40, P4387 MESCHKE C, 1997, THERMOCHIM ACTA, V297, P43 MOCK WL, 1983, J ORG CHEM, V48, P3618 MOCK WL, 1986, J ORG CHEM, V51, P4440 MOCK WL, 1989, J AM CHEM SOC, V111, P2697 MOCK WL, 1990, J CHEM SOC CHEM COMM, P1509 MOCK WL, 1995, TOP CURR CHEM, V175, P1 MOCK WL, 1996, COMPREHENSIVE SUPRAM, V2, P477 NEUGEBAUER R, 1998, J CHEM SOC PERK MAR, P529 NIGAM S, 1996, J PHYS CHEM-US, V100, P7135 ROBINSON TP, 2003, BIOORG MED CHEM LETT, V13, P115 SHIM JS, 2003, CHEM BIOL, V10, P695 SUN YM, 2002, ORG LETT, V4, P2909 SZELTLI J, 1998, CHEM REV, V98, P1743 TANG B, 2002, J AGR FOOD CHEM, V50, P1355 TONNESEN HH, 2002, INT J PHARM, V244, P127 WAGNER BD, 2000, J INCL PHENOM MACRO, V38, P467 WAGNER BD, 2001, CAN J CHEM, V79, P1101 WAGNER BD, 2003, J PHYS CHEM B, V107, P10741 WHANG D, 1996, J AM CHEM SOC, V118, P11333 WHANG D, 1998, ANGEW CHEM INT EDIT, V37, P78 WRIGHT JS, 2002, J MOL STRUC-THEOCHEM, V591, P207; NR: 51; TC: 8; J9: SUPRAMOL CHEM; PG: 7; GA: 876JJSource type: Electronic(1
Effects of the pharmacological influence of bradykinin receptors on arteriogenesis in animal models
No full textHintergrund – In dieser Studie wurde der Einfluss der Bradykininrezeptoren auf
die Arteriogenese untersucht, um neue Therapiestrategien in Patienten mit
Gefäßverschlusskrankeiten entwickeln zu können. Methoden – Im ersten Teil
dieser Studie wurden C57/Bl6-Mäuse für sieben Tage nach
Femoralarterienokklusion (FAO) und Sprague Dawley (SD)-Ratten für 21 Tage nach
bilateralem Verschluss der Arteriae certebrales und anschließender Ligatur der
Arteria carotis communis (3-VO) mit Antagonisten der Bradykinin-Rezeptoren
(BR) 1 (Bachem H1960) und 2 (Icatibant) behandelt. Im zweiten Teil erfolgte
dagegen in Ratten für sieben Tage nach 3- VO die Behandlung mit einem
BR1-Agonisten (Tocris R916). Die Validierung der Bradykinin-Effekte erfolgte
anhand funktioneller Parameter wie der Bestimmung der zerebrovaskulären
Reservekapazität (CVRC) nach 3-VO und des kollateralen Perfusinsindexes (CPI)
nach FAO sowie anhand morphologischer Parameter wie der angiographischen
Darstellung und Bestimmung der Gefäßdurchmesser der Arteria cerebri posterior
(PCA) nach 3-VO. Die Wirkung von Bradykinin auf die Monozytenfunktion wurde
mittels Migration humaner THP-1-Zellen bestimmt. Ergebnisse – Der Kollaterale
Perfusionsindex (CPI) ist nach sieben Tagen nach FAO bei Antagonisierung von
BR1 (41 ± 10%) und BR2 (46 ± 15%) gegenüber Kontrollen signifikant geringer.
Die CVRC (BR1i: -4 ± 8%; BR2i: 0 ± 12%) und die PCA-Durchmesser (BR1i: ipsi:
194 ±12 μm, kontra: 203 ± 24 μm; BR2i: ipsi: 209 ±25 μm, PCA kontra: 215 ±30
μm) 21 Tage nach 3-VO bestätigen diese Daten. Dagegen zeigt die
BR1-Stimulation signifikante proarteriogene Effekte (CVRC: 13 ± 14%, PCA ipsi:
253 ± 33%, PCA kontra: 225 ± 18%). In vivo zeigen Monozyten eine gehemmte bzw.
gesteigerte Migration auf Bradykininantagonisten sowie -agonisten.
Schlussfolgerung – Die vorliegende Studie konnte zeigen, dass Bradykinin
während des Kollateralwachstums eine entscheidende Rolle spielt. Therapeutisch
scheint der Vorteil bei der BR1-Stimulation zu liegen, da diese zum einen den
biologischen Bypass stimuliert und zum anderen keinen Einfluss auf die
Ausbreitung des vasogenen Hirnödems hat.Background – With this study, effects of pharmacologic influences of
bradykinin receptors on arteriogenesis were investigated in order to be able
to develop new therapies for patients with arterial occlusive diseases.
Methods – In the first part of the study, femoral artery occlusion (FAO) was
performed in C57Bl/6 mice. In addition, Sprague Dawley (SD) rats underwent a
bilateral occlusion of the Arteriae cerebrales and a ligation of the Arteria
carotis communis (3-VO). The mice were treated with a bradykinin receptor (BR)
1 (Bachem H1960) or BR2 antagonist (Icatibant) for seven days, whereas rats
were treated likewise for 21 days. The second part of the study involved a
treatment with a BR1 agonist (Tocris R916) for seven days after 3-VO in rats.
The validation of bradykinin’s effects were ensued with the help of functional
parameters like cerebrovascular reserve capacity (CVRC) after 3-VO and the
collateral perfusion index (CPI) after FAO. Angiography and the measurement of
diameters of the Arteria cerebri posterior (PCA) after 3-VO were used as
morphological parameter. The induced effects of bradykinin on the function of
monocytes was assessed through migration of human THP-1 cells. Results – 7
days after FAO the collateral perfusion index (CPI) showed significant
restrictions with BR1 (41 ± 10%) and BR2 (46 ± 15%) antagonization in contrast
to control groups. The measurement of the CVRC (BR1i: -4 ± 8%; BR2i: 0 ± 12%)
and PCA diameters (BR1i: ipsi: 194 ±12 μm, kontra: 203 ± 24 μm; BR2i: ipsi:
209 ±25 μm, PCA kontra: 215 ±30 μm) 21 days post-3-VO confirms this data. On
the other hand the BR1-stimulation showed significant proarteriogenic effects
(CVRC: 13 ± 14%, PCA ipsi: 253 ± 33 μm, PCA kontra: 225 ± 18 μm). The analysis
of monocyte migration confirms the anti- and pro-arteriogenic in vivo data.
Conclusion – The presented study revealed that bradykinin plays a crucial role
in collateral growth. Therapeutically, stimulation of BR1 has an obvious
benefit. On the one hand, it induces the biological bypass. On the other hand,
it does not influence vasogenic cerebral edema
Role of short-acting nitroglycerin in the management of ischemic heart disease
No full textWilliam E Boden,1–3 Santosh K Padala,1–3 Katherine P Cabral,4 Ivo R Buschmann,5 Mandeep S Sidhu1–31Department of Medicine, Division of Cardiology, Albany Medical College, 2Department of Medicine, Division of Cardiology, Albany Stratton Veterans Affairs Medical Center, 3Department of Medicine, Division of Cardiology, Albany Medical Center, 4Department of Pharmacy, Albany College Pharmacy and Health Sciences, Albany, NY, USA; 5Department of Angiology, Medical University of Brandenburg & Charité, Berlin, GermanyAbstract: Nitroglycerin is the oldest and most commonly prescribed short-acting anti-anginal agent; however, despite its long history of therapeutic usage, patient and health care provider education regarding the clinical benefits of the short-acting formulations in patients with angina remains under-appreciated. Nitrates predominantly induce vasodilation in large capacitance blood vessels, increase epicardial coronary arterial diameter and coronary collateral blood flow, and impair platelet aggregation. The potential for the prophylactic effect of short-acting nitrates remains an under-appreciated part of optimal medical therapy to reduce angina and decrease myocardial ischemia, thereby enhancing the quality of life. Short-acting nitroglycerin, administered either as a sublingual tablet or spray, can complement anti-anginal therapy as part of optimal medical therapy in patients with refractory and recurrent angina either with or without myocardial revascularization, and is most commonly used to provide rapid therapeutic relief of acute recurrent angina attacks. When administered prophylactically, both formulations increase angina-free walking time on treadmill testing, abolish or delay ST segment depression, and increase exercise tolerance. The sublingual spray formulation provides several clinical advantages compared to tablet formulations, including a lower incidence of headache and superiority to the sublingual tablet in terms of therapeutic action and time to onset, while the magnitude and duration of vasodilatory action appears to be comparable. Furthermore, the sublingual spray formulation may be advantageous to tablet preparations in patients with dry mouth. This review discusses the efficacy and utility of short-acting nitroglycerin (sublingual spray and tablet) therapy for both preventing and aborting an acute angina attack, thereby leading to an improved quality of life.Keywords: angina, coronary artery disease, nitroglycerin spray, nitroglycerin sublingual tablets, optimal medical therap
Effects of acetylsalicyl acid and clopidogrel on collateral growth in the hypoperfused rat brain model
No full textHintergrund: Zerebrovaskuläre Erkrankungen sind weltweit die zweithäufigsten
Todesursachen. Acetylsalicylsäure (ASS) und Clopidogrel finden als Mono- oder
Kombinationstherapien routinemäßigen Einsatz im Rahmen der Sekundärprävention.
In dieser Studie wurden die Auswirkungen der anti-inflammatorischen Wirkungen
von ASS gegenüber Clopidogrel auf die zerebrale Arteriogenese untersucht.
Methoden: Im ersten Teil der Studie, der Untersuchung der Effekte auf das
natürliche Kollateralwachstum, wurde bei Sprague Dawley-Ratten die 3-VO-
Methode durchgeführt, bei der beide Vertebralarterien und die linke Arteria
carotis communis verschlossen werden. Die Tiere wurden dann für 7 oder 21 Tage
entweder mit Trinkwasser als Kontrolllösung, ASS oder Clopidogrel behandelt.
Im zweiten Teil wurde das Kollateralwachstum durch Gabe des Granulocyte
Colony-Stimulating Factors (G-CSF) über eine Woche therapeutisch induziert.
Gleichzeitig erfolgte die Behandlung mit Trinkwasser, ASS und Clopidogrel.
Nach ein oder drei Wochen wurden jeweils entweder eine zerebrovaskuläre
Reaktion oder eine postmortem Latexangiographie zur Bestimmung der
Gefäßdurchmesser durchgeführt. Ergebnisse: Während die PCA-Diameter sowohl
nach einer als auch nach drei Wochen nach 3-VO unter ASS- oder Clopidogrel-
Behandlung keinen Unterschied gegenüber der Kontrollgruppe zeigten, war die
hämodynamische Reserve unter ASS zu beiden Zeitpunkten aufgehoben. Der
kombinierte Einsatz von ASS und G-CSF verbesserte die Reserve zwar, dennoch
blieb sie signifikant schlechter gegenüber der Kombination aus Clopidogrel und
G-CSF sowie der Monotherapie mit G-CSF. Die Diameter zeigten nach der
Kombination aus ASS und G-CSF keinen Unterschied gegenüber der ASS-
Monotherapie und blieben damit bedeutend kleiner gegenüber der G-CSF-
Monotherapie. Schlussfolgerung: Die vorliegende Studie konnte zeigen, dass ASS
das zerebrale Kollateralwachstum und die hämodynamische Reserve nach
therapeutischer Induktion durch G-CSF hemmte, während Clopidogrel dies nicht
beeinflusste. Diese Daten haben eine herausragende klinische Bedeutung für
deren Einsatz in der Sekundärprävention zerebrovaskulärer Erkrankungen.Background and Purpose: Ischemic heart diseases and cerebrovascular diseases
are the leading causes of death worldwide (WHO). Acetylsalicyl acid (ASA) and
clopidogrel are well-used in the secondary prevention in their combination or
alone. Because of their anti-inflammatory effects ASA inhibits peripheral
arteriogenesis, whereas clopidogrel had neutral effects. In this study we
investigated the effects of ASA and clopidogrel on adaptive and
therapeutically induced cerebral arteriogenesis. Methods: For the first part
of the study, the evaluation of the effects on adaptive cerebral
arteriogenesis, male Sprague Dawley rats underwent 3-VO surgery, the occlusion
of both vertebral arteries and the left common carotid artery, and were
treated with either drinking water, ASA or clopidogrel for 7 or 21 days. For
evaluation of the effects on therapeutically induced arteriogenesis rats
received Granulocyte colony-stimulating factor (G-CSF) every other day for one
week in addition to drinking water, ASA or clopidogrel. After one or three
weeks rats underwent cerebrovascular reactivity or post-mortem
latexangiography. Results: One as well as three weeks after 3-VO PCA diameters
were significantly increased compared to untreated rats, but no differences
were found in ASA or clopidogrel treated animals compared to 3-VO controls.
Hemodynamic reserve capacity was completely abolished at one and three weeks
after 3-VO by ASA. The reserve capacity was improved after treatment combined
with ASA and G-CSF, but was still significantly decreased compared to the
combination of clopidogrel and G-CSF and the single treatment with G-CSF. The
diameters were not different after combined treatment with ASA and G-CSF
compared to ASA alone and still smaller compared to the G-CSF single
treatment. Conclusions: In this study it was shown, that ASA, but not
Clopidogrel inhibited collateral growth and hemodynamic reserve capacity after
therapeutically induction with G-CSF. These results of the pro-arteriogenic
G-CSF as well as the anti-arteriogenic ASA are eminent for their clinical
application in the secondary prevention of cerebrovascular events
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