Verletzung des zerebralen Blutflusses in newborn

Verletzung des zerebralen Blutflusses in newborn

Verletzung des zerebralen Blutflusses in newborn UB Heidelberg: 03 Medizinische Fakultät Heidelberg (A - K) Protocols and Video Articles Authored by Richard J. Traystman (Translated to German) Verletzung des zerebralen Blutflusses in newborn


Chirurgische Intensivmedizin - Aloy Springer Verletzung des zerebralen Blutflusses in newborn

Other Publications 65 Journal of Alzheimer's Disease: Detaillierte präoperative, operative und postoperative Schritte beschrieben, um ein konsistentes Modell zu erhalten, Verletzung des zerebralen Blutflusses in newborn.

Recent studies have ins Leben gerufen Varizen Foto apoproteins apo in amyloid plaques and associated with high-density lipoprotein HDL particles in the cerebrospinal fluid CSF. Western blot analysis revealed that serum amyloid A apoSAA protein was Verletzung des zerebralen Blutflusses in newborn in control and AD patients at low levels compared to apoE and apoA-I, however, AD brains showed a significant increase over control values.

Immuno-cytochemical analysis showed that SAA was detected in senile plaques in AD tissue, but was predominantly localized to neuritic plaques. ApoE staining of AD brain confirmed that most plaques contained the apoprotein, similar to Abeta immunoreactivity, whereas apoA-I expressed little staining of senile plaques. One functional difference lies in the antioxidant potential of these alleles; e4 has the poorest potential, Verletzung des zerebralen Blutflusses in newborn.

Interestingly, e4 also correlates with increased oxidative damage in the Alzheimer's disease AD brain, which may explain why the inheritance of the e4 allele is a risk factor for the onset of AD. Beta-amyloid Abeta is also intimately involved in AD and promotes oxidative damage in vitro; therefore, we have examined the role of the different apoE alleles in modulating Abeta -induced oxidation to synaptosomes.

Increases in reactive oxygen species formation and protein and lipid oxidation were always greatest in e4 synaptosomes as compared to e2 and e3 synaptosomes. Our Krampfadern in den Mägen von 1 Grad support the role of apoE as a modulator of Abeta toxicity and, consistent with the antioxidant potentials of the three alleles, suggest that the e4 allele may not be as effective in this role as the e2 or e3 alleles of apoE.

These results are discussed with reference to mechanistic implications for neurodegeneration in the AD brain. Serum amyloid A SAA is an apolipoprotein primarily produced in the liver. Serum protein levels can increase one thousandfold after inflammation. SAA is the precursor to the amyloid A protein found in deposits of systemic amyloid A amyloid AA or reactive amyloid in both mouse and human. To study the factors necessary for cerebral amyloid formation, we have created a transgenic mouse that expresses the amyloidogenic Honig trophischen Geschwüren Behandlung Saa1 protein in the brain.

Using the synapsin promoter to drive expression of the Saa1 gene, the brains of transgenic mice expressed both RNA and protein. Under noninflammatory conditions, transgenic mice do not develop AA amyloid deposits in the brain; however, Verletzung des zerebralen Blutflusses in newborn, induction of a systemic acute-phase response in transgenic mice enhanced amyloid deposition.

This deposition was preceded by an increase in cytokine levels in the brain, suggesting that systemic inflammation may be a contributing factor to the development of cerebral amyloid.

The nonsteroidal anti-inflammatory agent indomethacin reduced inflammation and protected against the deposition of AA amyloid in the brain. These studies indicate that inflammation plays an important role in the process of amyloid deposition, and inhibition of inflammatory cascades may attenuate amyloidogenic processes, such as Alzheimer's disease. Apolipoprotein E and Alzheimer's Disease: Adenoviral vector-mediated SR-BI overexpression in livers of human apoB transgenic mice approximately fold increased expression reduced plasma HDL-cholesterol HDL-C and apolipoprotein apo A-I Verletzung des zerebralen Blutflusses in newborn to nearly undetectable levels 3 days after adenovirus infusion.

However, such uptake was not significantly increased Behandlung von venösen Ulcera der unteren Extremitäten bei der Atherosklerose mice over-expressing SR-BI.

The precise metabolic fate of HDL particles after selective lipid uptake is not known. This remodeling pathway may represent a process that is important in determining the rate of apoA-I catabolism and HDL-mediated reverse cholesterol transport.

We have utilized an animal model for DS, mice with segmental trisomy of chromosome 16 Ts65Dnto study biological events linked to memory loss. Previous studies demonstrated a cognitive decline and loss of cholinergic markers after months of age. In the current study, we found increased levels of amyloid precursor protein APP in the striatum by months of age, and in the hippocampus and parietal cortex by months of age in Ts65Dn but not in normosomic mice.

Additionally, Verletzung des zerebralen Blutflusses in newborn, Ts65Dn mice exhibited alterations in nerve growth factor NGF levels in the basal forebrain and hippocampus. Ts65Dn mice demonstrated a significant decline in NGF levels in the basal forebrain with age, as well as a reduction in hippocampal NGF by months of age.

These findings demonstrate that elevated APP and decreased NGF levels in limbic areas correlate with the progressive memory decline and cholinergic degeneration seen in middle-aged trisomic mice. Neprilysin has recently been implicated as a major extracellular Abeta degrading enzyme in the brain. However, there has been no direct demonstration that neprilysin antagonizes the deposition of amyloid-beta in vivo. To address this issue, a lentiviral vector expressing human neprilysin Lenti-Nep was tested in transgenic mouse models of amyloidosis.

We show that unilateral intracerebral injection of Lenti-Nep reduced amyloid-beta deposits Verletzung des zerebralen Blutflusses in newborn half relative to the untreated side. Furthermore, Lenti-Nep ameliorated neurodegenerative alterations in the frontal cortex and hippocampus of these transgenic mice.

These data further support a role for neprilysin in regulating cerebral amyloid deposition and suggest that gene transfer approaches might have potential for the development of alternative therapies for Alzheimer's disease.

The purpose of the present study was to evaluate whether FGF18 was neuroprotective in a rat model of cerebral ischemia and to compare the results with those obtained with FGF2. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products RAGE -bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier BBB and expression of proinflammatory cytokines and endothelin-1 ET-1the latter mediating Abeta-induced vasoconstriction.

Inhibition of RAGE-ligand interaction Physiotherapie Laser trophischen Geschwüren accumulation of Abeta in brain parenchyma in a mouse transgenic model.

These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis. However, the molecular mechanism by which B[c]PhDE induces tumorigenesis is not fully understood. Cell lines proficient in MMR exhibited several-fold more sensitivity to killing than cell lines defective in either MutS alpha or MutL alpha by B[c]PhDE; the nature of this sensitivity was shown to be due to increased apoptosis.

These findings, combined with previous studies, suggest that the MMR system may serve as a general sensor for chemical-caused DNA damage to prevent damaged cells from mutagenesis and carcinogenesis by promoting apoptosis. Vehicle or FGF18 microg x kg -1 x h -1 was infused at 0. Infusion of FGF18 reduced infarct volumes and improved scores in tests of reference and working memory, motor ability, and exploratory behavior.

Significant reductions in infarct volumes and reductions in deficits of Verletzung des zerebralen Blutflusses in newborn memory and motor activity were also observed with FGF18 infused 24 hours after MCAO. Administration of vehicle or FGF18 had no significant effect on mean arterial blood pressure, heart rate, brain temperature, blood pH, Pco2, or Po2.

Efficacy observed with infusions at later times suggests an expanded time window for Verletzung des zerebralen Blutflusses in newborn neuroprotection. In addition, Verletzung des zerebralen Blutflusses in newborn, we show that infusion of an NEPinhibitor, but not inhibitors of other peptidases, into the brains of an APP transgenic mouse elevates Abeta levels.

Trophischen Geschwüren erhöht have investigated the use of NEP as a potential therapeutic agent to prevent the accumulation of Abeta peptides in the brain.

Lentivirus expressing NEP was initially used to demonstrate the ability of the enzyme to reduce Abeta levels in a model CHO cell line and to make primary hippocampal neurons resistant to Abeta-mediated neurotoxicity. These studies provide the impetus for further investigating of the use of NEP in a gene transfer therapy paradigm to prevent the accumulation of Abeta and prevent or delay the onset of Alzheimer's disease.

Cholesterol and Alzheimer's Disease: Genetic studies have identified mutations in the Abeta precursor protein APP as the key triggers for the pathogenesis of AD.

Several biochemical and molecular studies using transfected Verletzung des zerebralen Blutflusses in newborn cells and transgenic animals point to mechanisms by which Abeta is generated and aggregated to trigger the neurodegeneration that may cause AD. Three important enzymes collectively known ob Blutegel Thrombophlebitis 'secretases' participate in APP processing leading to the generation of either Abeta or non-amyloid proteins.

However, the mechanisms of neurotoxicity of Abeta and the role of APP function in AD remain important unanswered questions. Although early studies recognized the loss of cholesterol and other lipids in the brain, these findings have been poorly connected with AD pathogenesis, despite the identification of the epsilon4 allele of APOE as a major risk factor in AD.

The recent finding that cholesterol can modulate the yield of potentially toxic Abeta has boosted research on its role in AD. Consequently, several cholesterol-reducing drugs are currently being evaluated for the treatment of AD. The present review summarizes our current understanding of the relationship of AD pathogenesis with cholesterol, lipids and other genetic and environmental risk factors. In addition to the spleen, lymph nodes, and bone marrow, the tissues that exhibit NFkappaB activation now include the newly identified site of the intestinal epithelial cells.

These data indicate that RAGE is a cofactor for Abeta-induced neuronal perturbation in a model of Alzheimer's-type pathology, and suggest its potential as a therapeutic target to ameliorate cellular dysfunction. The PLAU gene within this region encodes urokinase-type plasminogen activator, which converts plasminogen to plasmin.

Abeta aggregates induce PLAU expression thereby increasing plasmin, which degrades both aggregated and non-aggregated forms of Abeta. In knockout mice lacking the PLAU gene, Verletzung des zerebralen Blutflusses in newborn, plasma--but not brain--Abeta42 as well as Abeta40 was significantly elevated, also in an age-dependent manner.

Assessment of the impact of environmental stressors on bottlenose dolphins BND has been difficult because of the protected status die Behandlung von venösen Beingeschwüren Volksmedizin these marine mammals.

The studies presented herein focused on establishing epidermal cell cultures and cell lines as tools for the in vitro evaluation of environmental stressors on BND skin. Epidermal cell cultures were established from skin samples obtained from Atlantic BND and subjected to karyotype analysis. These cultures were further characterized using immunohistochemical methods demonstrating expression of cytokeratins. By two-dimensional polyacrylamide gel electrophoresis 2D-PAGEwe observed that the proteomic profile of BND skin tissue samples shared distinct similarities with that of skin-derived cultures.

Epidermal cell cultures were transfected with a plasmid encoding the SV40 small t- and large T-antigens, as well as the neomycin-resistance gene. Five neomycin-resistant clones were isolated and expanded, and all of them proliferated at a faster rate than nontransfected BND epidermal cultures, which exhibited signs of senescence.

Cell lysates prepared from two transfected clones were shown to express, by Western blot analysis, both SV40 tumor antigens, Verletzung des zerebralen Blutflusses in newborn. These Galle für Krampfadern results are consistent with the concept that transfected clones expressing SV40 tumor antigens represent immortalized BND cell lines.

Epidermal cell lines derived from Tursiops truncatus will provide a unique tool for studying key features of the interaction occurring between dolphins and the environment in which they live at their most Verletzung des zerebralen Blutflusses in newborn interface: Our previous work demonstrates that physiological levels of estradiol protect against cerebral ischemia in the young and aging brain through actions involving estrogen receptors ERs and alterations in gene expression.

The major goal of this study was to establish mechanisms of neuroprotective actions induced by low levels of estradiol. We first examined effects of estradiol on the time-dependent evolution of ischemic brain injury. Because estradiol is known to influence apoptosis, we hypothesized that it acts to decrease the delayed phase of cell death observed after middle cerebral artery occlusion MCAO.

Furthermore, because ERs are pivotal to neuroprotection, we examined the temporal expression profiles of both ER subtypes, ERalpha and ERbeta, after MCAO and delineated potential roles for each receptor in estradiol-mediated neuroprotection. We found that during the first 24 h, Verletzung des zerebralen Blutflusses in newborn, the mechanisms of estradiol-induced neuroprotection after MCAO are limited to attenuation of delayed cell death and do not influence immediate cell death.

Furthermore, we discovered that ERs exhibit distinctly divergent profiles of expression over the evolution of injury, with ERalpha induction occurring early and ERbeta modulation occurring later, Verletzung des zerebralen Blutflusses in newborn. Finally, we provide evidence for a new and functional role for ERalpha in estradiol-mediated protection of the injured brain. These findings indicate that physiological levels of estradiol protect against delayed cell death after stroke-like injury through mechanisms requiring ERalpha.

In this study, we show that compared with wild-type mice, C3-deficient mice showed significant improvement in survival, neurological deficit, and infarct size at 24 h after middle cerebral artery occlusion and reperfusion. Furthermore, P-selectin protein expression was undetectable in the cerebral microvasculature of C3-deficient mice following reperfusion, and there was reduced neutrophil influx, reduced microthrombus formation, and increased blood flow postreperfusion in C3-deficient mice.

We further investigated the use of a novel complement inhibitory protein in a therapeutic paradigm. Complement receptor 2 CR2 -Crry inhibits complement activation at the C3 stage and targets to sites of complement activation.

Treatment of normal mice with CR2-Crry at 30 min postreperfusion resulted in a similar level of protection to that seen in C3-deficient mice in all of the above-measured parameters. The data demonstrate an important role for complement in cerebrovascular thrombosis, inflammation, and injury following ischemic stroke. P-selectin expression in the cerebrovasculature, which is also implicated in cerebral ischemia and reperfusion injury, was shown to be distal to and dependent on complement activation.

Data also show that a CR2-targeted approach of complement inhibition provides appropriate bioavailability in cerebral injury to enable complement inhibition at a dose Verletzung des zerebralen Blutflusses in newborn does not significantly affect systemic levels of serum complement activity, a potential benefit for stroke patients where immunosuppression would be undesirable Verletzung des zerebralen Blutflusses in newborn to significantly increased susceptibility to lung infection.

A total of clones were sequenced and contig analysis yielded unigenes archived and annotated at, Verletzung des zerebralen Blutflusses in newborn. In addition, 52 dolphin genes known to be important in innate and adaptive immune function and stress responses of terrestrial mammals were specifically targeted, cloned and added to the unigene collection. The set of dolphin sequences printed on a cDNA microarray comprised the unigenes, Verletzung des zerebralen Blutflusses in newborn, the 52 targeted genes and randomly selected but unsequenced EST clones.

This set was printed in duplicate spots, side by side, and in two replicates per slide, Verletzung des zerebralen Blutflusses in newborn, such that the total number of features per microarray slide was 19, including controls.


Protocols and Video Articles Authored by Mark Kindy (Translated to German) Verletzung des zerebralen Blutflusses in newborn

Verwendung von nitritsalzen zur behandlung von kardiovaskulären erkrankungen Use of nitrite salt for the treatment of cardiovascular diseases translated from German DE T2. Verwendung von nicht-angesäuertem Natriumnitrit Rosskastanie Rezept für Krampfadern Herstellung eines Medikaments zur Behandlung oder Verbesserung eines Leidens ausgewählt aus: Verwendung nach Anspruch 1, worin das Medikament zur Behandlung oder Verbesserung von Leber- oder Herz- oder Hirnischämie-Repertusionsverletzungen vorgesehen ist.

Use according to claim 1, wherein the medicament is for treating or ameliorating hepatic or cardiac or brain ischemia-Repertusionsverletzungen. Verwendung nach Anspruch 2, worin das Medikament zur intravenösen Verabreichung vorgesehen ist. Use according to claim 2, wherein the medicament is provided for intravenous administration. Use according to claim 2 or 3, wherein sodium nitrite is for administration to a circulating concentration of about 0. Verwendung nach Anspruch 1, worin das Medikament zur Behandlung oder Verbesserung pulmonaler Hypertonie vorgesehen ist, Verletzung des zerebralen Blutflusses in newborn.

Use according to claim 1, wherein the medicament is provided for treating or ameliorating pulmonary hypertension. Verwendung nach Anspruch 5, worin die pulmonale Hypertonie eine neonatale pulmonale Hypertonie ist. Use according to claim 5, wherein the pulmonary hypertension is neonatal pulmonary hypertension. Verwendung nach Anspruch 5 oder 6, worin das Medikament zur Verabreichung mittels Inhalation vorgesehen ist.

Use according to claim 5 or 6, wherein the medicament is for administration via inhalation. Verwendung nach Anspruch 7, worin das Natriumnitrit zerstäubt ist.

Use according to claim 7, wherein said sodium nitrite is nebulized. Verwendung nach Anspruch 1, worin das Medikament zur Behandlung oder Verbesserung von Vasospasmus der Arteria cerebri vorgesehen ist. Use according to claim 1, wherein the medicament is for treating or ameliorating cerebral artery vasospasm is provided.

Verwendung nach Anspruch 10, Verletzung des zerebralen Blutflusses in newborn, worin das Medikament zur intravenösen Verabreichung vorgesehen ist. Use according to claim 10, wherein the medicament is provided for intravenous administration.

Verwendung nach einem der Ansprücheworin das Natriumnitrit zur Verabreichung in Kombination mit zumindest einem weiteren Mittel vorgesehen ist. Use according to any of claimswherein said sodium nitrite is for administration in combination with at least one other agent. Verwendung nach einem der Ansprücheworin das Subjekt ein Säugetier ist.

Use according to any of claimswherein the subject is a mammal. Verwendung nach Anspruch 14, worin das Subjekt ein Mensch ist. Use according to claim 14, wherein the subject is a human. The last decade has witnessed an increase in the understanding of the critical role of nitric oxide as a blood vessel dilator, which contributes to the regulation of blood flow and cardiovascular homeostasis.

Stickstoffoxid kann in Blut zu Nitrit NO 2 - oxidiert werden, ein Anion, das als inertes Stoffwechselendprodukt einer solchen Stickstoffoxidoxidation angesehen wird. Nitric oxide can in blood to nitrite NO 2 - can be oxidized, an anion which is considered to be inert metabolic end product of such a Stickstoffoxidoxidation.

Es ist berichtet worden, dass In-vivo-Plasmaspiegel von Nitrit von bis Verletzung des zerebralen Blutflusses in newborn reichen und die Nitritkonzentration im Aortenringgewebe über It has been reported that in vivo plasma levels of nitrite ranging from to nM and the nitrite concentration in Aortenringgewebe over 10, nM [Rodriguez et al.

USAVerletzung des zerebralen Blutflusses in newborn,Gladwin et al. USA; Gladwin et al. USA 97,und Rassaf et al. USA 97,and Rassaf et al.

This potential storage pool for NO is greater than plasma S-nitrosothiols, one of which has been reported to be less than 10 nM in human plasma [Rassaf et al. Acta, und Samouilov et al. There are mechanisms for the in vivo conversion of nitrite to NO has been proposed, eg. Actaand Samouilov et al. Es sind arterielle-zu-venöse-Gradienten von Nitrit über dem menschlichen Unterarm in Ruhe und während regionaler NO-Synthaseinhibition beobachtet worden, mit erhöhtem Verletzung des zerebralen Blutflusses in newborn von Nitrit, der bei Sport auftritt [Gladwin et al.

There were arterial-to-venous gradients of nitrite observed over the Verletzung des zerebralen Blutflusses in newborn forearm at rest and during regional NO Synthaseinhibition with increased consumption of nitrite, which occurs in Sport [Gladwin et al. USA 97,Verletzung des zerebralen Blutflusses in newborn, Gladwin et al. USA 97,und Cicinelli et al, Verletzung des zerebralen Blutflusses in newborn.

USA 97,and Cicinelli et al. Kelm and colleagues have reported that large artery-to-vein gradients of nitrite during NO Synthaseinhibition about the human forearm form [Lauer et al.

USA 98, ]. Anders als der einfachere Fall von Sauerstoffextraktion über ein vaskuläres Bett kann Nitrit sowohl konsumiert werden, wie durch Arterie-zu-Vene-Gradienten während NO-Synthaseinhibition und Sport belegt wird, Verletzung des zerebralen Blutflusses in newborn, als auch im vaskulären Bett durch endotheliale von Stickstoffoxidsynthase abstammende NO-Reaktionen mit Sauerstoff produziert werden.

Unlike the more simple case of oxygen extraction across a vascular bed nitrite may be both consumed, as evidenced by artery-to-vein gradients during NO Synthaseinhibition and sports as well as in the vascular bed by endothelial-derived nitric oxide NO reactions with oxygen are produced.

Es ist berichtet worden, dass Nitrit in hohen Konzentrationen ein In-vitro-Vasodilatator ist Ignarro et al. Acta, Ignarro et al. Pharmacol, 11,Gruetter et al. It has been reported that nitrite is a vasodilator in vitro is in high concentrations Ignarro et al.

Die Nitritspiegel, die gezeigt haben, dass sie in vitro vasodilatieren, sind immer über The nitrite levels, which have shown that they are vasodilatieren in vitro, has always been more thannM uM and are usually in Milimolkonzentrationen. In conformity with the high concentrations of nitrite required to vasodilatieren in vitro, as Lauer and colleagues infused nitrite into the circulation of the forearm of human subjects, have been reported no vasodilatory effects, even at concentrations of uM in the lower arm [Lauer et al.

Weiters konnten Rassaf et al. Furthermore, could Rassaf et al. Therefore, in vivo studies have come to the conclusion that physiological levels of nitrites do not serve as a source of NO, and that physiological nitrite levels play a role in the regulation of blood pressure. Historisch gesehen ist Nitrit als Behandlung von Cyanidvergiftung verwendet worden.

Historically, nitrite has been used as a treatment for cyanide poisoning. Hohe Konzentrationen werden in ein Subjekt infundiert, das unter Cyanidvergiftung leidet, um Hämoglobin zu Methämoglobin zu oxidieren, das Cyanid binden soll. High concentrations are infused into a subject suffering cyanide poisoning in order to oxidize hemoglobin to methemoglobin, which will bind cyanide.

Diese hohen Konzentrationen von Nitrit produzierten klinisch signifikante Methämoglobinämie, was möglicherweise Sauerstofflieferung verringerte. These high concentrations of nitrite produced clinically significant methemoglobinemia, potentially reduced oxygen Verletzung des zerebralen Blutflusses in newborn. While it has been shown that these high concentrations reduces blood pressure in people of nitrite, the Methämoglobinmenge formed preclude the use of nitrite in the treatment of other medical conditions.

Therefore, Behandlung von Venengeschwüren Salbe stellanin prior art was that nitrite was not a significant vasodilator at concentrations below microns in vitro, and even when it was infused into humans at concentrations of uM in the forearm.

Es war auch Stand der Technik, dass Nitrit nicht in Stickstoffoxid im menschlichen Blutstrom überführt wurde. It was also prior art that nitrite was not converted to nitric oxide in the human blood stream. Zusammenfassung Verletzung des zerebralen Blutflusses in newborn Offenbarung Abstract of the Disclosure. Es ist überraschenderweise herausgefunden worden, dass die Verabreichung von pharmazeutisch annehmbaren Salzen von Nitrit für die Regulation des kardiovaskulären Systems nützlich ist.

It has been surprisingly discovered that administration of pharmaceutically acceptable salts of nitrite is useful for regulation of the cardiovascular system.

Es ist auch überraschenderweise herausgefunden worden, Verletzung des zerebralen Blutflusses in newborn Nitrit in vivo zu Stickstoffoxid reduziert wird und dadurch produziertes Stickstoffoxid ein wirkungsvoller Vasodilatator ist, Diese Wirkungen treten überraschenderweise in Dosen auf, die keine klinisch signifikante Methämoglobinämie produzieren.

It has also been surprisingly found that nitrite is reduced in vivo nitric oxide and nitric oxide produced thereby is an effective vasodilator These effects are surprisingly at doses that do not produce clinically significant methemoglobinemia. Diese Entdeckungen ermöglichen nun Verfahren, Leiden zu vermeiden und zu behandeln, die mit dem kardiovaskulären System assoziiert sind, zB hohen Blutdruck, pulmonale Hypertonie, zerebralen Vasospasmus und Gewebsischämie-Reperfusionsverletzung.

Verletzung des zerebralen Blutflusses in newborn discoveries now enable methods to prevent and treat ailments associated with the cardiovascular system, such as high blood pressure, pulmonary hypertension, cerebral vasospasm and tissue ischemia-reperfusion injury. These discoveries also provide methods to increase blood flow in tissue prepared as tissue in regions of low oxygen pressure.

Es ist insbesondere überraschend, dass das Nitrit nicht in einem angesäuerten Zustand angewendet werden muss, damit es in der Regulation des kardiovaskulären Systems nützlich ist, und noch spezieller, um in vivo als Vasodilatator zu wirken. It is particularly surprising that the nitrite does not need to be applied in an acidified condition, so that it is useful in the regulation of the cardiovascular system, and more particularly to act as a vasodilator in vivo.

Verletzung des zerebralen Blutflusses in newborn has now been surprisingly discovered by the inventors that nitrite can serve as a vasodilator in humans at much lower concentrations as low as 0. Der Mechanismus soll eine Reaktion von Nitrit mit desoxidiertem Hämoglobin und roten Blutzellen umfassen, um vasodilatierendes Stickstoffoxid-Gas zu produzieren.

The mechanism is intended to encompass a reaction of nitrite with deoxygenated hemoglobin and red blood cells in order Verletzung des zerebralen Blutflusses in newborn produce vasodilating gas nitric oxide. Es ist herausgefunden worden, dass Nitrit in vivo in Stickstoffoxid überführt wird und dass das dadurch produzierte Stickstoffoxid ein wirkungsvoller Vasodilatator ist.

It has been found that nitrite in vivo is converted into nitric oxide and that the nitric oxide produced thereby is an effective vasodilator. Verletzung des zerebralen Blutflusses in newborn ist überraschenderweise festgestellt worden, dass die Verabreichung von Nitrit, beispielsweise eines pharmazeutisch annehmbaren Salzes von Nitrit, an ein Subjekt eine Reduktion des Blutdrucks und einen Anstieg des Blutflusses zu Geweben verursacht, zB zu Geweben in Regionen mit niedrigem Sauerstoffdruck.

Furthermore, it has surprisingly been found that administration of nitrite, for example, Verletzung des zerebralen Blutflusses in newborn, a pharmaceutically acceptable salt of nitrite, to a subject causes a reduction in blood pressure and an increase in blood flow to tissues, for example, to tissues in regions of low oxygen pressure.

Diese Entdeckungen ermöglichen nun nützliche Verfahren, das kardiovaskuläre System zu regulieren, Verletzung des zerebralen Blutflusses in newborn, zB um Leiden, die mit dem kardiovaskulären System verbunden sind, zB hohen Blutdruck, oder Organe, Gewebe oder Systeme, die an einem Fehlen des inadäquaten Blutflusses leiden, zu vermeiden und zu behandeln. Non-limiting examples of the diseases mentioned include stroke, heart disease, Verletzung des zerebralen Blutflusses in newborn, kidney disease and failure, eye damage, including retinopathy hypertensive, diabetes and migraines.

Die vorliegende Erfindung stellt in den Ansprüchen definierte Verwendungen bereit. The present invention provides in claims willing defined uses. Die vorangegangenen und andere Eigenschaften und Vorteile werden aus der folgenden detaillierten Beschreibung mehrerer Ausführungsformen offensichtlicher, die unter Verweis auf die Zeichnungen im Anhang folgen.

The foregoing and other features and advantages will be apparent that follow from the following detailed description of several embodiments with reference to the appended drawings. Kurzbeschreibung der Zeichnungen Brief Description of Drawings. Legende wie für Legend as for 1 1plus: Show on hemodynamic and metabolic measurements. Daten für Eisennitrosylhämoglobin, gemessen durch Flächen der Austrittspeaks nach Triiodid-basierter reduktiver Chemilumineszenz Data for Eisennitrosylhämoglobin measured by the exit surfaces peaks after tri-iodide based reductive chemiluminescence 12B 12B und durch Tiefe des Peaks bei Gauss in paramagnetischer Elektronenresonanz EPR And depth of the peak at Gauss in electron paramagnetic resonance EPR 12C 12Crote Linie: Hypoxmeasured for 20 minutes after nitrite inhalation was begun.

Shows hemodynamic and metabolic measurements during Hypox induced pulmonary hypertension. Behandlung mit Nitritaerosol resultierte in einer raschen nachhaltigen Reduktion in Hypoxie-induzierter Lungenvasokonstriktion und einem abgestuften Anstieg der ausgeatmeten NO-Gaskonzentration mit keiner Veränderung des mittleren arteriellen Blutdrucks.

Treatment with nitrite aerosol resulted in a rapid sustained reduction in hypoxia-induced Lungenvasokonstriktion and a graded increase in exhaled NO gas concentration with no change in mean arterial blood pressure. Diese Ergebnisse stehen im Gegensatz zu der raschen Rückkehr des Lungenarteriendrucks auf hypoxe Grundlinie nach Beendigung des eingeatmeten NO-Gases These results are in contrast to the rapid return in pulmonary artery pressure to hypoxic baseline after termination of inhaled NO gas 13A 13A.


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