Biochemical evidence that the atypical antipsychotic drugs clozapine and risperidone block 5-HT(2C) receptors in vivo.
Clozapine and risperidone are two atypical antipsychotic drugs which bind, among other receptors, to 5-HT(2C) receptor subtypes. They inhibit the basal inositol phosphate production in mammalian cells expressing rat or human 5-HT(2C) receptors. This biochemical effect is indicative of inverse agonist activity at these receptors. There is evidence that 5-HT(2C) receptors are involved in the control of the activity of central dopaminergic system. Therefore, the effects of clozapine (5 mg/kg ip), risperidone (0.08 mg/kg ip) and of the typical antipsychotic haloperidol (0.1 mg/kg ip) were studied on the extracellular concentration of dopamine (DA) in the nucleus accumbens of chloral hydrate-ane…
Real-Time Breath Analysis in Type 2 Diabetes Patients During Cognitive Effort
The understanding the functional expression of exhaled volatile organic compounds (VOCs) has gradually expanded from the initial identification of breath pathological markers to direct expression of physiological activity. In the present study we investigated the potential application of breath analysis in real-time monitoring of type 2 diabetes mellitus (T2DM) patients versus control subjects while performing a cognitive task. T2DM is associated with cognitive impairment and neural deficits, because of insulin resistance and high expression of insulin receptors in the hippocampus. We set out to seek the evidence for mutual associations among breath exhale, on the one side, and T2DM and cog…
Volatile organic compounds (VOCs) in exhaled breath as a marker of hypoxia in multiple chemical sensitivity
Abstract In the history of diagnostics, breath analysis was one of the first method used until the breakthrough of biochemical testing technology. Today, breath analysis has made a comeback with the development of gas analyzers and e‐noses, demonstrating its power in its applicability for diagnosing a wide range of diseases. The physical basis of multiple chemical sensitivity (MCS), an emerging environmental disease, is difficult to understand because it is based on the scenario of chronic hypoxia, with a complex of chemical compounds that trigger the syndrome and result in multiple symptoms. The aim of this study was to investigate MCS by analyzing exhaled volatile organic compounds (VOCs)…
Inhibition of Peripheral Dopamine Metabolism and the Ventilatory Response to Hypoxia in the Rat
Dopamine (DA) is a putative neurotransmitter in the carotid body engaged in the generation of the hypoxic ventilatory response (HVR). However, the action of endogenous DA is unsettled. This study seeks to determine the ventilatory effects of increased availability of endogenous DA caused by inhibition of DA enzymatic breakdown. The peripheral inhibitor of MAO – debrisoquine, or COMT – entacapone, or both combined were injected to conscious rats. Ventilation and its responses to acute 8 % O2 in N2 were investigated in a whole body plethysmograph. We found that inhibition of MAO augmented the hyperventilatory response to hypoxia. Inhibition of COMT failed to influence the hypoxic response. Ho…
Selective expression of galanin in neuronal-like cells of the human carotid body
The carotid body is a neural-crest-derived organ devoted to respiratory homeostasis through sensing changes in blood oxygen levels. The sensory units are the glomeruli composed of clusters of neuronal-like (type I) cells surrounded by glial-like (type II) cells. During chronic hypoxia, the carotid body shows growth, with increasing neuronal-like cell numbers. We are interested in the signals involved in the mechanisms that underlie such response, because they are not well understood and described. Considering that, in literature, galanin is involved in neurotrophic or neuroprotective role in cell proliferation and is expressed in animal carotid body, we investigated its expression in human.…
Role of IP3 Receptors in Shaping the Carotid Chemoreceptor Response to Hypoxia But Not to Hypercapnia in the Rat Carotid Body: An Evidence Review
This article addresses the disparity in the transduction pathways for hypoxic and hypercapnic stimuli in carotid body glomus cells. We investigated and reviewed the experimental evidence showing that the response to hypoxia, but not to hypercapnia, is mediated by 1,4,5-inositol triphosphate receptors (IP3R/s) regulating the intracellular calcium content [Ca2+]c in glomus cells. The rationale was based on the past observations that inhibition of oxidative phosphorylation leads to the explicit inhibition of the hypoxic chemoreflex. [Ca2+]c changes were measured using cellular Ca2+-sensitive fluorescent probes, and carotid sinus nerve (CSN) sensory discharge was recorded with bipolar electrode…
Volatile organic compounds fingerprint of Alzheimer’s disease.
Alzheimer's disease (AD) is a profoundly life changing condition and once diagnosis occurs, this is typically at a relatively late stage into the disease process. Therefore, a shift to earlier diagnosis, which means several decades before the onset of the typical manifestation of the disease, will be an important step forward for the patient. A promising diagnostic and screening tool to answer this purpose is represented by breath and exhaled volatile organic compounds (VOCs) analysis. In fact, human exhaled breath contains several thousand of VOCs that vary in abundance and number in correlation with the physiological status. The exhaled VOCs reflect the metabolism, including the neuronal …
Chemoresponsiveness and Breath Physiology in Anosmia
Anosmia is a model to study the interaction among chemoreception systems. In the head injury, the traumatic irreversible anosmia caused by damage to olfactory nerve fibers and brain regions is of enviable research interest. In this study, psychophysiological tests for a comprehensive assessment of olfactory function were utilized to investigate anosmia, together with a new technique based on the breath real-time monitoring of volatile organic compounds (VOCs). We applied the breath and VOCs analysis to investigate chemoresponsiveness in the long-term irreversible post-traumatic anosmia.
Pathologies currently identified by exhaled biomarkers.
Ancient Greek physicians already knew that the smell of human breath could provide a clue to the pathology. Nowadays, volatile breath biomarkers are known to be released in a broad range of diseases. However, their identification, isolation, and quantification as indicative of relevant alterations in clinical status have required the development of new techniques and analytical methods. Breath sample analysis encounters several obstacles. Particularly, there is a need of a system that could work in a continuous manner, with the low concentration and small volume of a sample. Herein we review, in the light of literature and our experience, clinical applications of the metal oxide semiconduct…
Real time analysis of volatile organic compounds (VOCs) in centenarians.
Centenarians are a model to study human longevity and the physiological process of aging. A plethora of studies on this model show the complexity of the system. Laboratory studies fail to find a biomarker of senescence. The real time exhaled breath volatile organic compounds (VOCs) has been suggested as a new biomarker to detect and monitor physiological processes in the respiratory system. VOCs exhaled by centenarians have not been studied in the general population and across-age-groups. In the present study we investigated, in real time, the breath properties and VOC exhaled content in healthy centenarians as compared with non-centenarian seniors and young healthy subjects. We found disti…