Cardiorespiratory effects of intertrigeminal area stimulation in vagotomized rats

A igualdade relaciona-se ao processo civil, nas mais diversas formas. O trabalho tem por objetivo contribuir para uma renovada compreensão da normatividade da isonomia em suas relações com o processo civil, a partir da análise dos seus perfis conceitual, funcional e estrutural. No seu plano conceitual, essa revigorada compreensão apresentase a partir de duas perspectivas. De uma perspectiva macro, busca-se demonstrar a passagem da igualdade perante a lei – formal - (que pressupõe a segurança jurídica pela completude e univocidade da legislação) à igualdade na lei – material – (que pressupõe a vedação às discriminações arbitrárias na formulação dos textos normativos) e à isonomia na interpretação e aplicação do direito (que pressupõe a segurança jurídica pelo respeito ao precedente). De uma perspectiva micro, busca-se demonstrar como a passagem da igualdade perante a lei à igualdade na lei influiu no processo civil. Assim, pretende-se apresentar a passagem da garantia da paridade de armas (entendida como simetria de posições das partes, de caráter estático) ao Direito Fundamental à Isonomia no Processo (entendido como equilíbrio dos sujeitos do processo, de caráter dinâmico). A isonomia, no plano funcional, ostenta duas finalidades distintas quando das suas relações com o processo civil: de um lado, a partir de uma perspectiva geral e objetiva, serve para todo o sistema, como um norte a ser seguido, agregando coerência institucional, com vistas a uma ordem jurídica isonômica; de outro lado, a partir de uma perspectiva particular e subjetiva, serve, em cada caso, como instrumento para que os sujeitos do processo possam desempenhar as suas capacidades de modo equilibrado, permitindo-se o exercício efetivo do contraditório entendido como potencialidade de influência, com vistas a uma decisão justa. Por fim, em seu perfil estrutural, a igualdade pode ser sistematizada a partir de três óticas: igualdade ao processo (imposição de que o direito preveja – e o judiciário atue para tanto - os meios necessários para que as partes possam chegar ao processo em posição equilibrada), igualdade no processo (imposição de que o processo seja dotado – e o judiciário as utilize - de técnicas processuais que permitam que os sujeitos do processo possam atuar em posição equilibrada) e igualdade pelo processo (imposição de que o processo seja dotado – e o judiciário as promova e respeite - de técnicas processuais voltadas a conferir congruência, aceitação e unidade ao direito).L‘uguaglianza può essere pensata in relazione al processo civile in diversi modi. Proponiamo di contribuire ad una rinnovata portata della normatività dell‘uguaglizana nelle sue relazioni con il processo civile, sulla base dell'analisi dei suoi profili concettuale, funzionale e strutturale. Nel piano concettuale, si presentano due prospettive. Dal punto di vista macro, cerchiamo di dimostrare il passaggio dall‘uguaglianza davanti alla legge - formale - (che richiede la certezza del diritto per la completezza e la univocità delle norme) all'uguaglianza nel diritto - sostanziale - (che richiede il divieto di discriminazioni arbitrarie nella formulazione di testi normativi) e all'uguaglianza nell'interpretazione e applicazione del diritto (che assume certezza giuridica rispetto al precedente). Da un punto di vista micro, cerchiamo di dimostrare come il passaggio dall‘uguaglianza davanti alla legge all'uguaglianza nel diritto sostanziale ha influenzato il processo. Quindi, intendiamo presentare il passaggio della garanzia della parità delle armi (intesa come posizioni simmetriche delle parti, con carattere statico) al diritto fondamentale all‘uguaglianza processuale (inteso come equilibrio tra i soggetti del processo, con carattere dinamico). L'uguaglianza in termini funzionali ha due scopi distinti nel suo rapporto con il processo: da un lato, da un punto di vista generale e oggettivo, è versata sull'intero sistema, cercando di aggiungere coerenza istituzionale e un diritto isonomico e, d'altra parte, dal punto di vista personale e soggettivo, serve come strumento perché i soggetti del processo possano eseguire le proprie competenze in modo equilibrato, consentendo l'esercizio effettivo del contraddittorio inteso come dirritto di influenza, verso una decisione giusta. Infine, nel suo profilo strutturale, l‘uguaglianza può essere sistematizzata da tre punti di vista: l‘uguaglianza al processo (che impone che la legge preveda - e la magistratura agisca – i mezzi necessarie per consentire alle parti di arrivare al processo in posizioni bilanciate), l'uguaglianza nel processo (che impone che il processo sia dotato – e la magistratura ne faccia uso – di tecniche processuali che consentino i soggetti processuali ad agire in una posizione di equilibrio) e l'uguaglianza come risultato del processo (imposizione di che il processo preveda - e la magistratura le promuova - tecniche processuali mirate a dare congruenza, accettazione e l'unità al diritto)

Proof of concept trial of dronabinol in obstructive sleep apnea

Study Objective: Animal data suggest that Δ(9)-TetraHydroCannabinol (Δ(9)THC) stabilizes autonomic output during sleep, reduces spontaneous sleep-disordered breathing, and blocks serotonin-induced exacerbation of sleep apnea. On this basis, we examined the safety, tolerability, and efficacy of dronabinol (Δ(9)THC), an exogenous Cannabinoid type 1 and type 2 (CB1 and CB2) receptor agonist in patients with Obstructive Sleep Apnea (OSA). Design and Setting: Proof of concept; single-center dose-escalation study of dronabinol. Participants: Seventeen adults with a baseline Apnea Hypopnea Index (AHI) ≥15/h. Baseline polysomnography (PSG) was performed after a 7-day washout of Continuous Positive Airway Pressure treatment. Intervention: Dronabinol was administered after baseline PSG, starting at 2.5 mg once daily. The dose was increased weekly, as tolerated, to 5 mg and finally to 10 mg once daily. Measurements and Results: Repeat PSG assessments were performed on nights 7, 14, and 21 of dronabinol treatment. Change in AHI (ΔAHI, mean ± SD) was significant from baseline to night 21 (-14.1 ± 17.5; p = 0.007). No degradation of sleep architecture or serious adverse events was noted. Conclusion: Dronabinol treatment is safe and well-tolerated in OSA patients at doses of 2.5-10 mg daily and significantly reduces AHI in the short-term. These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy

Monotone Signal Segments Analysis as a novel method of breath detection and breath-to-breath interval analysis in rat

We applied a novel approach to respiratory waveform analysis-Monotone Signal Segments Analysis (MSSA) on 6-h recordings of respiratory signals in rats. To validate MSSA as a respiratory signal analysis tool we tested it by detecting: breaths and breath-to-breath intervals; respiratory timing and volume modes; and changes in respiratory pattern caused by lesions of monoaminergic systems in rats. MSSA differentiated three respiratory timing (tachypneic, eupneic, bradypneic-apneic), and three volume (artifacts, normovolemic, hypervolemic-sighs) modes. Lesion-induced respiratory pattern modulation was visible as shifts in the distributions of monotone signal segment amplitudes, and of breath-to-breath intervals. Specifically, noradrenergic lesion induced an increase in mean volume (p = 0.06). MSSA of timing modes detected noradrenergic lesion-induced interdependent changes in the balance of eupneic (decrease; p <= 0.02), and tachypneic (an increase; p <= 0.02) breath intervals with respect to control. In terms of breath durations within each timing mode, there was a tendency toward prolongation of the eupneic (p <= 0.08) and bradypneic-apneic (p <= 0.06) intervals. These results demonstrate that MSSA is sensitive to subtle shifts in respiratory rhythmogenesis not detectable by simple respiratory pattern descriptive statistics. MSSA represents a potentially valuable new tool for investigations of respiratory pattern control. (C) 2008 Elsevier B.V. All rights reserved.nul

Intranodose ganglion injections of dronabinol attenuate serotonin-induced apnea in Sprague-Dawley rat**not yet published**

Obstructive sleep apnea represents a significant public health concern. Afferent vagal activation is implicated in increased apnea susceptibility by reducing upper airway muscle tone via activation of serotonin receptors in the nodose ganglia. Previous investigations demonstrated that systemically administered cannabinoids can be used therapeutically to decrease the apnea/hypopnea index in rats and in humans. However, cannabinoids have effects on both the central and peripheral nervous systems, and the exact mechanism of decreased apnea/hypopnea index with cannabinoids is unknown. Here, we hypothesized that intranodose ganglion injections of a cannabinoid will attenuate 5-HT-induced reflex apnea and increase upper airway muscle tone. We show that dronabinol injected locally into the nodose ganglia suppresses 5-HT-induced reflex apnea, and increases phasic, but not tonic, activation of the genioglossus. These data support the view that dronabinol stabilizes respiratory pattern and augments upper airway muscles by acting at the nodose ganglia. These findings underscore a therapeutic potential of dronabinol for the treatment of obstructive sleep apnea

Coupling changes in cortical and pontine sigma and theta frequency oscillations following monoaminergic lesions in rat

Sigma and theta frequency electroencephalogram (EEG) oscillations exhibit substantial and well-recognized shifts with transitions across sleep and wake states. We aimed in this study to test the changes in coupling between these characteristic oscillations of non-rapid-eye-movement (NREM)/rapid-eye-movement (REM) sleep within and between cortical and pontine EEGs following monoaminergic lesion, by using the Pearson's product-moment correlation coefficients. Experiments were performed in 14 adult, male Sprague Dawley rats chronically instrumented for sleep recording. We lesioned the dorsal raphe nucleus axon terminals in four rats using PCA neurotoxin (p-chloroamphetamine; Sigma-Aldrich, MO) administered as two intraperitoneal (IP) injections (6 mg/kg) 24 h apart. Lesioning of locus coeruleus axon terminals was performed in five rats using DSP-4 neurotoxin (N-2-chloroethyl-N-ethyl-2-bromobenzilamine; Sigma-Aldrich, MO) in a single IP dose of 50 mg/kg. Our previous study [Saponjic et al., Physiol Behav 90:1-10, 2007] demonstrated that these systemically induced monoaminergic lesions failed to produce significant changes in sleep/wake distribution from control conditions. The present study, by using spectral analysis and by examining the Pearson's correlation coefficients and their approximate probability density (APD) distribution profiles in control and lesion condition, demonstrates significant augmentation of the sigma/theta coupling strength, an inversion of cortical sigma/theta coupling direction and emergence of an additional sigma/theta coupling "mode" specific to the post-lesion state only within the cortex. By using the Pearson's correlation coefficients and their APD profiles, instead of classical sleep/wake distribution analysis, as a measure of direction and strength of sigma/theta coupling within and between cortex and pons, we were able to uncover the impact of a tonically decreased level of brain monoamines as altered strength and mode of coupling between sigma and theta oscillations. Specifically, a new mode of sigma/theta coupling emerged following lesion, which was specific to NREM sleep, suggests that loss of monoaminergic signaling interferes with NREM sleep consolidation. Our results also indicate an importance of monoamines in control of the sleep spindle and theta rhythm generators.Serbian Ministry of Science and Technological Development [143005, 143027]; NIH [AG01630

Coupling changes in cortical and pontine sigma and theta frequency oscillations following monoaminergic lesions in rat

Sigma and theta frequency electroencephalogram (EEG) oscillations exhibit substantial and well-recognized shifts with transitions across sleep and wake states. We aimed in this study to test the changes in coupling between these characteristic oscillations of non-rapid-eye-movement (NREM)/rapid-eye-movement (REM) sleep within and between cortical and pontine EEGs following monoaminergic lesion, by using the Pearson's product-moment correlation coefficients. Experiments were performed in 14 adult, male Sprague Dawley rats chronically instrumented for sleep recording. We lesioned the dorsal raphe nucleus axon terminals in four rats using PCA neurotoxin (p-chloroamphetamine; Sigma-Aldrich, MO) administered as two intraperitoneal (IP) injections (6 mg/kg) 24 h apart. Lesioning of locus coeruleus axon terminals was performed in five rats using DSP-4 neurotoxin (N-2-chloroethyl-N-ethyl-2-bromobenzilamine; Sigma-Aldrich, MO) in a single IP dose of 50 mg/kg. Our previous study [Saponjic et al., Physiol Behav 90:1-10, 2007] demonstrated that these systemically induced monoaminergic lesions failed to produce significant changes in sleep/wake distribution from control conditions. The present study, by using spectral analysis and by examining the Pearson's correlation coefficients and their approximate probability density (APD) distribution profiles in control and lesion condition, demonstrates significant augmentation of the sigma/theta coupling strength, an inversion of cortical sigma/theta coupling direction and emergence of an additional sigma/theta coupling "mode" specific to the post-lesion state only within the cortex. By using the Pearson's correlation coefficients and their APD profiles, instead of classical sleep/wake distribution analysis, as a measure of direction and strength of sigma/theta coupling within and between cortex and pons, we were able to uncover the impact of a tonically decreased level of brain monoamines as altered strength and mode of coupling between sigma and theta oscillations. Specifically, a new mode of sigma/theta coupling emerged following lesion, which was specific to NREM sleep, suggests that loss of monoaminergic signaling interferes with NREM sleep consolidation. Our results also indicate an importance of monoamines in control of the sleep spindle and theta rhythm generators.Serbian Ministry of Science and Technological Development [143005, 143027]; NIH [AG01630

Monotone Signal Segments Analysis as a novel method of breath detection and breath-to-breath interval analysis in rat

We applied a novel approach to respiratory waveform analysis-Monotone Signal Segments Analysis (MSSA) on 6-h recordings of respiratory signals in rats. To validate MSSA as a respiratory signal analysis tool we tested it by detecting: breaths and breath-to-breath intervals; respiratory timing and volume modes; and changes in respiratory pattern caused by lesions of monoaminergic systems in rats. MSSA differentiated three respiratory timing (tachypneic, eupneic, bradypneic-apneic), and three volume (artifacts, normovolemic, hypervolemic-sighs) modes. Lesion-induced respiratory pattern modulation was visible as shifts in the distributions of monotone signal segment amplitudes, and of breath-to-breath intervals. Specifically, noradrenergic lesion induced an increase in mean volume (p = 0.06). MSSA of timing modes detected noradrenergic lesion-induced interdependent changes in the balance of eupneic (decrease; p <= 0.02), and tachypneic (an increase; p <= 0.02) breath intervals with respect to control. In terms of breath durations within each timing mode, there was a tendency toward prolongation of the eupneic (p <= 0.08) and bradypneic-apneic (p <= 0.06) intervals. These results demonstrate that MSSA is sensitive to subtle shifts in respiratory rhythmogenesis not detectable by simple respiratory pattern descriptive statistics. MSSA represents a potentially valuable new tool for investigations of respiratory pattern control. (C) 2008 Elsevier B.V. All rights reserved.nul