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At least 1,459 records · Page 81Linked to original sources
PubMed1992

Fate of isopropyl-iodoamphetamine (IMP) in rat liver microsomes.

Para-iodoamphetamines are currently used in nuclear medicine to detect brain perfusion abnormalities with tomoscintigraphy. Little is known about their metabolism pathways in rat and humans. N-isopropyl-125I-iodoamphetamine (IMP) interactions were studied with rat liver microsomes. The first dealkylated metabolite (IAMP) at low concentration gave a type I binding complex then, with a high concentration, a very stable type II complex with oxidized cytochrome P-450 FeIII. In contrast, IMP only gave a type I binding complex in the absence of NADPH. In the presence of NADPH, IAMP and IMP produced 455 nm absorbing complexes, which were enhanced when phenobarbital-treated rat liver microsomes were used. During in vitro metabolic activation, covalent binding of IMP and IAMP on rat liver microsomal proteins was observed. This process was mixed function oxidase (MFO) dependent. The covalent binding level was higher with IAMP and was not affected by flavine oxidase inhibitors. These results confirm the interaction of IMP and IAMP with microsome proteins and cytochrome P-450 and suggest that an N-oxidation of IMP occurs after N-dealkylation. As cytochrome P-450 and dealkylated IMP (IAMP) were found in brain, cerebral metabolism in brain and evolution of activity biodistribution with the course of time can be suggested.

Amphetamines↗
PubMed2003

Update on pharmacological strategies for stroke: prevention, acute intervention and regeneration.

Given the few options that are currently available for patients following ischemic stroke, the search for novel therapeutic approaches becomes more critical. Pharmaceutical intervention strategies for the treatment of stroke include preventative (prophylactic or stroke pretreatment), neuroprotective (early acute post-stroke treatment) and regenerative (delayed post-stroke treatment for long-term benefit) therapeutic approaches. Experimental evidence has suggested that the majority of stroke patients have a slow evolution of brain injury that occurs over several hours. This 'evolving stroke' may ultimately be a realistic target for therapeutic intervention, with the goal of inhibiting the progression of detrimental changes that normally follow the acute ischemic event. Preventing or reducing this delayed cellular injury may improve neurological outcome and also facilitate brain recovery from injury. Significant impact on stroke can be expected as additional research is conducted on biological targets or processes important in facilitating the brain's regenerative capacity following cellular/tissue loss. This review provides updates on stroke prevention therapies (anticoagulant and antiplatelet), the advances in the development of pharmacological agents that target the acute phase of stroke (thrombolytics and neuroprotective drugs), and newly evolving approaches that may facilitate brain regeneration (i.e., neurobehavioral recovery) following brain damage.

Animals↗
PubMedDate not supplied

[Ontogeny-specific interaction of psychophysiological mechanisms of emotional perception and educational achievement in students].

In order to explore the process of adaptation of children to school environment psychophysiological characteristics of perception of emotional speech information and school progress were experimentally studied. Forty-six schoolchildren of three age groups (7-10, 11-13, and 14-17 years old) participated in the study. In experimental session, a test sentence was presented to a subject through headphones with two emotional intonations (joy and anger) and without emotional expression. A subject had to recognize the type of emotion. His/her answers were recorded. School progress was determined by year grades in Russian, foreign language, and mathematics. Analysis of variance and linear regression analysis showed that ontogenetic features of a correlation between psychophysiological mechanisms of emotion recognition and school progress were gender- and subject-dependent. This correlation was stronger in 7-13-year-old children than in senior children. This age boundary was passed by the girls earlier than by the boys.

Adolescent↗
PubMed1995

The evolution of the concept of brain death.

The definition of death has taken many forms throughout history. Because of advances in critical care and developments in transplantation, a new definition of death has evolved over the past 30 years. The first accounts of brain death were published in 1959, in relative obscurity. They were only considered to be of academic interest. In the mid-1960s, advances in transplantation and the need for viable organs started debate about the use of "brain-dead" patients as organ donors. Conceptual advances by the ad hoc committee of the Harvard medical school and the use of angiography and the electroencephalogram both advanced and confused the issue. Acceptance by the medical community remained divided. During the 1970s, brain-stem death was proposed as the true definition of death by pioneers in the United States and Britain. In the 1980s, the clinical diagnosis of brain-stem death was officially accepted and many of the controversies subsided.

Brain Death↗
PubMedDate not supplied

[FOXP2: from the specific disorder to the molecular biology of language. II. Implications for the ontogenesis and phylogenesis of language].

INTRODUCTION: Cloning FOXP2, the first gene linked to a hereditary variant of specific language impairment (SLI), has allowed researchers to conduct more precise studies into the nature and developmental path of the molecular bases governing the organisation and functioning of the neuron centres responsible for language processing. DEVELOPMENT: The FOXP2 gene codes for a transcriptional repressor that regulates the proliferation and/or migration of certain neuronal populations in the basal ganglia, cortex, cerebellum and thalamus, and presumably plays a part in the organisation and/or functioning of the fronto-thalamic-striatal system. Moreover, the analysis of the developmental history of the gene suggests that the transcriptional factor FOXP2, although it is quite old, has undergone certain modifications in its secondary structure and has acquired a potential site for phosphorylation for protein kinase C during the recent developmental history of the human species. CONCLUSIONS: The evidence discussed in this article allows us to suggest FOXP2 plays a significant role in the ontogenetic and phylogenetic development of language. On the one hand, it seems to validate certain general models of linguistic processing that call for a more important role of the subcortical structures (above all for the basal ganglia) in that processing. On the other hand, it seems to suggest that the modifications undergone by FOXP2 would have also allowed certain regions (such as Broca's area) to be recruited for language, either by facilitating the appearance of syntax and/or verbal working memory or by transferring control of articulation to those regions, thereby laying down the foundations for the appearance of spoken language.

Brain↗
PubMed2005

Third nature: the co-evolution of human behavior, culture, and technology.

Within a dynamical-systems framework, human behavior is seen as emergent from broad evolutionary processes associated with three basic forms of nature. First nature, matter, emerged from the big bang some 12-15 billion years ago; second nature, life, from the first bacteria up to 4 billion years ago; third nature, ideology and cultural artifacts (e.g., institutions and technology), with a shift to self-reflective, symbolic thought and agrarianism in humans some 8-40 thousand years ago. The co-evolution of these three natures has dramatically altered human behavior and its relationship to the whole planet. Third nature has infused human minds with several powerful ideas, or memes, including the idea of progress. These ideas have fueled the evolution of a complex institutional order (e.g., political systems and technology) and myriad attendant global problems (e.g., wars and environmental degradation). The human brain/mind is seen as the primary medium by which third nature governs human behavior and, therefore, self perpetuates.

Behavior↗
PubMed2006

Treatment of embolic stroke in rats with bortezomib and recombinant human tissue plasminogen activator.

Stroke elicits a progressive vascular dysfunction, which contributes to the evolution of brain injury. Thrombolysis with tissue plasminogen activator (tPA) promotes adverse vascular events that limit the therapeutic window of stroke to three hours. Proteasome inhibitors reduce vascular thrombotic and inflammatory events, and consequently protect vascular function. The present study evaluated the neuroprotective effect of bortezomib, a potent and selective inhibitor of the proteasome, alone and in combination with delayed thrombolytic therapy on a rat model of embolic focal cerebral ischemia. Treatment with bortezomib reduces adverse cerebrovascular events including secondary thrombosis, inflammatory responses, and blood brain barrier (BBB) disruption, and hence reduces infarct volume and neurological functional deficit when administrated within 4 h after stroke onset. Combination of bortezomib and tPA extends the thrombolytic window for stroke to 6 h, which is associated with the improvement of vascular patency and integrity. Real time RT-PCR of endothelial cells isolated by laser-capture microdissection from brain tissue and Western blot analysis showed that bortezomib upregulates endothelial nitric oxide synthase (eNOS) expression and blocks NF-kappaB activation. These results demonstrate that bortezomib promotes eNOS dependent vascular protection, and reduces NF-kappaB dependent vascular disruption, all of which may contribute to neuroprotection after stroke.

Animals↗