Role of excitatory amino acids in regulation of rat pial microvasculature

1994 ◽  
Vol 266 (1) ◽  
pp. R158-R163 ◽  
Author(s):  
Q. F. Huang ◽  
A. Gebrewold ◽  
A. Zhang ◽  
B. T. Altura ◽  
B. M. Altura
Keyword(s):  
Amino Acids ◽  
Nmda Receptor ◽  
Excitatory Amino Acids ◽  
Experimental Studies ◽  
In Vivo Studies ◽  
Small Blood Vessel ◽  
Mk 801 ◽  
Pial Arterioles

Recently, attention has been drawn to the possibility that excitatory amino acids (EAAs) may play an important role in the pathogenesis of hypoxic-ischemic neuronal injury. Exaggerated release of EAAs and excessive stimulation of N-methyl-D-aspartate (NMDA) receptors and other EAA receptors have been suggested to contribute to neuronal death in ischemia and anoxia. A number of in vitro and in vivo experimental studies have shown that EAA-receptor antagonists exert a protective effect on the brain after cerebral ischemia. Because neurons are in close apposition to small intracerebral vessels, synaptically released EAAs might also regulate small blood vessel function. With the use of quantitative television microscopic observations, in vivo studies were undertaken on pial arterioles of rats. Perivascular administration of cumulative doses (10(-7)-10(-2) M) of L-glycine, L-glutamate, L-aspartate, and NMDA on the pial microvessels resulted in concentration-dependent constriction of pial arterioles (5-30% decreases in diameter) and cerebrovasospasm; the relative order of potency was aspartate > NMDA > glycine > glutamate. High concentrations of EAAs often resulted in rupture of postcapillary venules. No amine or opiate antagonist or cyclooxygenase inhibitor prevented or attenuated the effects of these putative EAAs. EAA-induced constriction and spasm of pial arterioles as well as rupture of venules could, however, be blocked by the noncompetitive NMDA-receptor antagonist MK-801 and by Mg2+. MK-801 also produced a concentration-dependent relaxation on normal pial arterioles. These results are compatible with the idea that a specific NMDA-receptor complex (RC) exists in rat cortical microvessels, which subserves vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Viscum album (L) extracts in cancer treatment: a systematic review of in vitro and in vivo studies

2021 ◽  
Vol 14 (2) ◽  
pp. 52-52
Author(s):  
Aloisio Cunha de Carvalho ◽  
Leoni Villano Bonamin
Keyword(s):  
Systematic Review ◽  
Experimental Studies ◽  
Pharmaceutical Preparations ◽  
Viscum Album ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Pubmed Database ◽  
Anti Cancer

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database. Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only. Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.

scholarly journals How Harmful Is Particulate Matter Emitted from Biomass Burning? A Thailand Perspective

2019 ◽  
Vol 5 (4) ◽  
pp. 353-377 ◽  
Author(s):  
Helinor J. Johnston ◽  
William Mueller ◽  
Susanne Steinle ◽  
Sotiris Vardoulakis ◽  
Kraichat Tantrakarnapa ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Health Effects ◽  
Biomass Burning ◽  
Large Body ◽  
Experimental Studies ◽  
In Vivo Studies ◽  
Indoor And Outdoor Environments ◽  
Epidemiology Studies

Abstract Purpose of Review A large body of epidemiological evidence demonstrates that exposure to particulate matter (PM) is associated with increased morbidity and mortality. Many epidemiology studies have investigated the health effects of PM in Europe and North America and focussed on traffic derived PM. However, elevated levels of PM are a global problem and the impacts of other sources of PM on health should be assessed. Biomass burning can increase PM levels in urban and rural indoor and outdoor environments in developed and developing countries. We aim to identify whether the health effects of traffic and biomass burning derived PM are similar by performing a narrative literature review. We focus on Thailand as haze episodes from agricultural biomass burning can substantially increase PM levels. Recent Findings Existing epidemiology, in vitro and in vivo studies suggest that biomass burning derived PM elicits toxicity via stimulation of oxidative stress, inflammation and genotoxicity. Thus, it is likely to cause similar adverse health outcomes to traffic PM, which causes toxicity via similar mechanisms. However, there is conflicting evidence regarding whether traffic or biomass burning derived PM is most hazardous. Also, there is evidence that PM released from different biomass sources varies in its toxic potency. Summary We recommend that epidemiology studies are performed in Thailand to better understand the impacts of PM emitted from specific biomass sources (e.g. agricultural burning). Further, experimental studies should assess the toxicity of PM emitted from more diverse biomass sources. This will fill knowledge gaps and inform evidence-based interventions that protect human health.

Brain monoamine oxidase A in hyperammonemia is regulated by NMDA receptors

2009 ◽  
Vol 4 (3) ◽  
pp. 321-326
Author(s):  
Elena Kosenko ◽  
Yury Kaminsky
Keyword(s):  
Oxidative Stress ◽  
Nmda Receptor ◽  
Monoamine Oxidase ◽  
Nmda Receptors ◽  
Monoamine Oxidase A ◽  
Mk 801 ◽  
Mao A ◽  
Vitro Effect

AbstractMitochondrial enzyme monoamine oxidase A (MAO-A) generates hydrogen peroxide (H2O2) and is up-regulated by Ca2+ and presumably by ammonia. We hypothesized that MAO-A may be under the control of NMDA receptors in hyperammonemia. In this work, the in vivo effects of single dosing with ammonia and NMDA receptor antagonist MK-801 and the in vitro effect of Ca2+ on MAO-A activity in isolated rat brain mitochondria were studied employing enzymatic procedure. Intraperitoneal injection of rats with ammonia led to an increase in MAO-A activity in mitochondria indicating excessive H2O2 generation. Calcium added to isolated mitochondria stimulated MAO-A activity by as much as 84%. MK-801 prevented the in vivo effect of ammonia, implying that MAO-A activation in hyperammonemia is mediated by NMDA receptors. These data support the conclusion that brain mitochondrial MAO-A is regulated by the function of NMDA receptors. The enzyme can contribute to the oxidative stress associated with hyperammonemic conditions such as encephalopathy and Alzheimer’s disease. The attenuation of the oxidative stress highlights MAO-A inactivation and NMDA receptor antagonists as sources of novel avenues in the treatment of mental disorders.

scholarly journals Quercetin as a Novel Therapeutic Approach for Lymphoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Saiedeh Razi Soofiyani ◽  
Kamran Hosseini ◽  
Haleh Forouhandeh ◽  
Tohid Ghasemnejad ◽  
Vahideh Tarhriz ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Hodgkin’S Lymphoma ◽  
Experimental Studies ◽  
Hodgkin's Lymphoma ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Malignant Diseases ◽  
Antitumor Effects

Lymphoma is a name for malignant diseases of the lymphatic system including Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Although several approaches are used for the treatment of these diseases, some of them are not successful and have serious adverse effects. Therefore, other effective treatment methods might be interesting. Studies have indicated that plant ingredients play a key role in treating several diseases. Some plants have already shown a potential therapeutic effect on many malignant diseases. Quercetin is a flavonoid found in different plants and could be useful in the treatment of different malignant diseases. Quercetin has its antimalignant effects through targeting main survival pathways activated in tumor cells. In vitro/in vivo experimental studies have demonstrated that quercetin possesses a cytotoxic effect on lymphoid cancer cells. Regardless of the optimum results that have been obtained from both in vitro/in vivo studies, few clinical studies have analyzed the antitumor effects of quercetin in lymphoid cancers. Thus, it seems that more clinical studies should introduce quercetin as a therapeutic, alone or in combination with other chemotherapy agents. Here, in this study, we reviewed the anticancer effects of quercetin and highlighted the potential therapeutic effects of quercetin in various types of lymphoma.

Ibogaine block of the NMDA receptor: In vitro and in vivo studies

1996 ◽  
Vol 35 (4) ◽  
pp. 423-431 ◽  
Author(s):  
Kang Chen ◽  
Tushar G. Kokate ◽  
Sean D. Donevan ◽  
F.Ivy Carroll ◽  
Michael A. Rogawski
Keyword(s):  
Nmda Receptor ◽  
In Vivo Studies

Excitatory amino acids: new tools for old stories or Pharmacological subtypes of glutamate receptors: electrophysiological studies

1991 ◽  
Vol 69 (7) ◽  
pp. 1123-1128 ◽  
Author(s):  
David Lodge ◽  
Martyn G. Jones ◽  
Andrew J. Palmer
Keyword(s):  
Amino Acids ◽  
Glutamate Receptors ◽  
Binding Sites ◽  
Excitatory Amino Acids ◽  
Channel Blocking ◽  
Electrophysiological Studies ◽  
Spinal Neurones ◽  
Potent Antagonist

Although the N-methyl-D-aspartate (NMDA) subtype of L-glutamate receptor is well characterized, the significance of non-NMDA glutamate-sensitive binding sites is not well documented. In this study, a new tricyclic quinoxalinedione (NBQX) and an arthropod toxin (philanthotoxin) were shown to block responses of spinal neurones in vivo to kainate, quisqualate, and AMPA in parallel but had little effect on responses to NMDA. Philanthotoxin appeared to be a use-dependent antagonist consistent with a channel-blocking mode of action. On cortical wedges in vitro, however, NBQX proved to be a more potent antagonist of AMPA and quisqualate than of kainate (pA2 values of 7.1, 7.0, and 5.6, respectively) with no effect at 10 μM on responses to NMDA. These studies provide evidence that on cortical neurones, but not on spinal neurones, AMPA and kainate depolarize by pharmacologically different mechanisms.Key words: glutamate receptors, quinoxalinediones, philanthotoxin, AMPA, kainate.

scholarly journals Identification of Two Mutations (F758W and F758Y) in the N -methyl-D-aspartate Receptor Glycine-binding Site that Selectively Prevent Competitive Inhibition by Xenon without Affecting Glycine Binding

2012 ◽  
Vol 117 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Scott P. Armstrong ◽  
Paul J. Banks ◽  
Thomas J. W. McKitrick ◽  
Catharine H. Geldart ◽  
Christopher J. Edge ◽  
...  
Keyword(s):  
Amino Acids ◽  
Nmda Receptor ◽  
Binding Site ◽  
Competitive Inhibition ◽  
Site Directed Mutagenesis ◽  
Glycine Site ◽  
General Anesthetic ◽  
Hek 293

Background Xenon is a general anesthetic with neuroprotective properties. Xenon inhibition at the glycine-binding site of the N-Methyl-D-aspartate (NMDA) receptor mediates xenon neuroprotection against ischemic injury in vitro. Here we identify specific amino acids important for xenon binding to the NMDA receptor, with the aim of finding silent mutations that eliminate xenon binding but leave normal receptor function intact. Methods Site-directed mutagenesis was used to mutate specific amino-acids in the GluN1 subunit of rat NMDA receptors. Mutant GluN1/GluN2A receptors were expressed in HEK 293 cells and were assessed functionally using patch-clamp electrophysiology. The responses of the mutant receptors to glycine and anesthetics were determined. Results Mutation of phenylalanine 758 to an aromatic tryptophan or tyrosine left glycine affinity unchanged, but eliminated xenon binding without affecting the binding of sevoflurane or isoflurane. Conclusions These findings confirm xenon binds to the glycine site of the GluN1 subunit of the NMDA receptor and indicate that interactions between xenon and the aromatic ring of the phenylalanine 758 residue are important for xenon binding. Our most important finding is that we have identified two mutations, F758W and F758Y, that eliminate xenon binding to the NMDA receptor glycine site without changing the glycine affinity of the receptor or the binding of volatile anesthetics. The identification of these selective mutations will allow knock-in animals to be used to dissect the mechanism(s) of xenon's neuroprotective and anesthetic properties in vivo.

scholarly journals The Coming Age of Flavonoids in the Treatment of Diabetic Complications

2020 ◽  
Vol 9 (2) ◽  
pp. 346 ◽  
Author(s):  
Teresa Caro-Ordieres ◽  
Gema Marín-Royo ◽  
Lucas Opazo-Ríos ◽  
Luna Jiménez-Castilla ◽  
Juan Antonio Moreno ◽  
...  
Keyword(s):  
Diabetic Complications ◽  
Low Cost ◽  
Scientific Evidence ◽  
Experimental Studies ◽  
Unmet Need ◽  
In Vivo Studies ◽  
Antioxidant Compounds ◽  
Randomized Controlled Studies

Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding therapies to prevent or retard the progression of diabetic complications remains an unmet need due to the complexity of mechanisms involved, which include inflammation, oxidative stress and angiogenesis, among others. Flavonoids are natural antioxidant compounds that have been shown to possess anti-diabetic properties. Moreover, increasing scientific evidence has demonstrated their potential anti-inflammatory and anti-oxidant effects. Consequently, the use of these compounds as anti-diabetic drugs has generated growing interest, as is reflected in the numerous in vitro and in vivo studies related to this field. Therefore, the aim of this review is to assess the recent pre-clinical and clinical research about the potential effect of flavonoids in the amelioration of diabetic complications. In brief, we provide updated information concerning the discrepancy between the numerous experimental studies supporting the efficacy of flavonoids on diabetic complications and the lack of appropriate and well-designed clinical trials. Due to the well-described beneficial effects on different mechanisms involved in diabetic complications, the excellent tolerability and low cost, future randomized controlled studies with compounds that have adequate bioavailability should be evaluated as add-on therapy on well-established anti-diabetic drugs.

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