Purinergic inhibitory regulation of esophageal smooth muscle is mediated by P2Y receptors and ATP-dependent potassium channels in rats.

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10-100 µM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 µM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 µM), and a P2Y receptor antagonist, cibacron blue F3GA (200 µM), inhibited the ATP (100 µM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 µM), did not affect it. A blocker of ATP-dependent potassium channels (KATP channels), glibenclamide (200 µM), inhibited the ATP-induced relaxation and application of an opener of KATP channels, nicorandil (50 µM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of KATP channels.

Repouso eletromiográfico dos músculos mastigatórios de pacientes com disfunção temporomandibular antes e após intervenção fonoaudiológica com e sem bandagem elástica / Electromyographic rest of the masticatory muscles of patients with temporomandibular disorders before and after speech therapy with and without elastic bandage / Resto electromiográfico de los músculos masticatorios de pacientes con trastornos temporomandibulares antes y después de logopedia con y sin venda elástica

Objetivo: A pesquisa tem por objetivo verificar os limiares de repouso eletromiográfico dos músculos masseter e temporal em pacientes com disfunção temporomandibular (DTM) antes e após intervenção fonoaudiológica com e sem a utilização de bandagem elástica terapêutica. Métodos: A coleta contou com 14 participantes do sexo feminino, com idade entre 18 e 40 anos, com diagnóstico de DTM muscular ou mista. As pacientes foram divididas entre dois grupos classificados em: pacientes com bandagem associada à terapia tradicional (CB) e grupo de terapia tradicional (SB). As pacientes inicialmente foram avaliadas pelo exame de eletromiografia de superfície nas situações de contração voluntária máxima e repouso, e após quatro semanas de intervenção, foi realizada nova avaliação com os mesmos instrumentos. A análise dos dados ocorreu de forma quantitativa e qualitativa. Resultados:No grupo SB o músculo masseter direito apresentou aumento dos valores de repouso com significância, foi observado que o mesmo ocorreu para todos os músculos deste grupo, influenciando no equilíbrio da musculatura ipsilateral e contralateral, no entanto sem evidência estatística. O grupo CB não demonstrou valores estatísticos significativos, porém qualitativamente os valores de repouso muscular diminuíram e equilibraram-se de forma contralateral. Conclusão: Não foram observadas mudanças estatisticamente significantes nos limiares eletromiográficos durante repouso dos músculos masseter e temporal em ambos os grupos. Qualitativamente houve aumento dos valores eletromiográficos após terapia manual tradicional em todos os músculos do grupo SB. Com relação ao grupo CB, houve diminuição dos valores do repouso eletromiográfico após terapia, embora sem evidências estatísticas. (AU)

Purpose: Objective: The research aims to verify the electromyographic rest thresholds of the masseter and temporal muscles in patients with temporomandibular disorders (TMD) before and after speech therapy intervention with and without the use of therapeutic elastic bandage. Methods: The collection included 14 female participants, aged between 18 and 40 years, who had a diagnosis of muscular or mixed TMD. The patients were divided into two groups: with traditional therapy (CB) bandage and traditional therapy (SB) only group. The patients underwent initial evaluation, as well as surface electromyography in situations of maximum voluntary contraction and rest and at the end of the four weeks of intervention, a new evaluation was performed with the same instruments. Data analysis occurred quantitatively and qualitatively. Results: In the SB group, the right masseter muscle showed a significant increase in resting values. It was observed that the same occurred for all muscles in this group, influencing the balance of the ipsilateral and contralateral muscles, although without statistical evidence. The CB group did not show statistically significant values, but qualitatively the muscle rest values decreased and balanced in a contralateral way. Conclusion: No statistically significant changes were observed in the resting electromyographic thresholds of the masseter and temporalis muscles in both groups. Qualitatively, there was an increase in electromyographic values after traditional manual therapy in all muscles in the SB group. Regarding the CB group, there was a decrease in electromyographic resting values after therapy, although without statistical evidence. (AU)

Objetivo: La investigación tiene como objetivo verificar los umbrales electromiográficos de reposo de los músculos masetero y temporal en pacientes con trastornos temporomandibulares (TMD) antes y después de la terapia del habla con y sin el uso de venda elástica terapéutica. Métodos: La colección incluyó a 14 participantes mujeres, con edades entre 18 y 40 años, diagnosticadas con TTM muscular o mixta. Los pacientes fueron divididos en dos grupos clasificados en: pacientes con vendaje asociado a terapia tradicional (CB) y grupo de terapia tradicional (SB). Los pacientes fueron inicialmente evaluados mediante electromiografía de superficie en situaciones de máxima contracción voluntaria y reposo, luego de cuatro semanas de intervención se realizó una nueva evaluación con los mismos instrumentos. El análisis de datos se llevó a cabo cuantitativa y cualitativamente. Resultados: En el grupo SB, el músculo masetero derecho presentó un aumento significativo en los valores de reposo, se observó que lo mismo ocurrió para todos los músculos de este grupo, influyendo en el equilibrio de los músculos ipsilaterales y contralaterales, sin embargo, sin evidencia estadística. El grupo CB no mostró valores estadísticamente significativos, pero cualitativamente los valores de descanso muscular disminuyeron y se equilibraron contralateralmente. Conclusión: No se observaron cambios estadísticamente significativos en los umbrales electromiográficos en reposo de los músculos masetero y temporal en ambos grupos. Cualitativamente, hubo un aumento de los valores electromiográficos después de la terapia manual tradicional en todos los músculos del grupo SB. En cuanto al grupo CB, hubo una disminución de los valores electromiográficos de reposo después de la terapia, aunque sin evidencia estadística. (AU)

Inhibition of ABCC1 Decreases cAMP Egress and Promotes Human Airway Smooth Muscle Cell Relaxation.

In most living cells, the second-messenger roles for adenosine 3',5'-cyclic monophosphate (cAMP) are short-lived, confined to the intracellular space, and tightly controlled by the binary switch-like actions of Gαs (stimulatory G protein)-activated adenylyl cyclase (cAMP production) and cAMP-specific PDE (cAMP breakdown). Here, by using human airway smooth muscle (HASM) cells in culture as a model, we report that activation of the cell-surface ß2AR (ß2-adrenoceptor), a Gs-coupled GPCR (G protein-coupled receptor), evokes cAMP egress to the extracellular space. Increased extracellular cAMP levels ([cAMP]e) are long-lived in culture and are induced by receptor-dependent and receptor-independent mechanisms in such a way as to define a universal response class of increased intracellular cAMP levels ([cAMP]i). We find that HASM cells express multiple ATP-binding cassette (ABC) membrane transporters, with ABCC1 (ABC subfamily member C 1) being the most highly enriched transcript mapped to MRPs (multidrug resistance-associated proteins). We show that pharmacological inhibition or downregulation of ABCC1 with siRNA markedly reduces ß2AR-evoked cAMP release from HASM cells. Furthermore, inhibition of ABCC1 activity or expression decreases basal tone and increases ß-agonist-induced HASM cellular relaxation. These findings identify a previously unrecognized role for ABCC1 in the homeostatic regulation of [cAMP]i in HASM that may be conserved traits of the Gs-GPCRs (Gs-coupled family of GPCRs). Hence, the general features of this activation mechanism may uncover new disease-modifying targets in the treatment of airflow obstruction in asthma. Surprisingly, we find that serum cAMP levels are elevated in a small cohort of patients with asthma as compared with control subjects, which warrants further investigation.

The role of l-cysteine/Hydrogen sulfide pathway on ß3-Adrenoceptor- induced relaxation in mouse gastric fundus.

In this study, we investigated the possible role of the l-cysteine/hydrogen sulfide pathway in ß3-adrenoceptors-mediated relaxation in isolated mouse gastric fundus tissue. l-cysteine (endogenous H2S; 10-6-10-2 M), sodium hydrogen sulfide (NaHS; exogenous H2S; 10-6-10-3 M), selective ß3-adrenoceptors agonist BRL 37344 (10-9-10-4 M) and non-selective ß-adrenoceptor agonist isoprenaline (10-9-10-4 M) produced concentration-dependent relaxation in mouse gastric fundus. The non-selective ß-adrenoceptors antagonist propranolol (10-6 M) inhibited the relaxant response to isoprenaline but not to BRL 37344. On the other hand, the selective ß3-adrenoceptors antagonist SR 59230A (10-5 M) inhibited the relaxant responses to BRL 37344. In addition, cystathionine-gamma-lyase (CSE) inhibitor D,L-propargylglycine (PAG, 10-2 M), cystathionine-beta-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10-2 M), and the combination of these inhibitors significantly reduced the relaxant responses induced by l-cysteine and BRL 37344. Pre-incubation of gastric fundal strips with propranolol (10-6 M) and SR 59230A (10-5 M) did not affect relaxations to l-cysteine and NaHS. Also, the existence of CSE, CBS, 3-mercaptopurivate sulfur transferase (3-MST) enzymes and ß3-adrenoceptors were detected in gastric fundal tissue. Furthermore, basal H2S release was detected in the measurements. H2S level increased in the presence of l-cysteine, NaHS, and BRL 37344. The increase in H2S level by l-cysteine and BRL 37344 decreased significantly with PAG and AOAA enzyme inhibitors. These results suggest that endogenous H2S is synthesized from l-cysteine at least by CBS and CSE enzymes. Also, ß3-adrenoceptors are found in the mouse stomach fundus and mediate BRL 37344-induced relaxations, and l-cysteine/hydrogen sulfide pathway plays a partial role in ß3-adrenoceptors-mediated relaxation in mouse gastric fundus tissue.

Thermal and behavioral response of horses submitted to functional exercises and acupuncture / Resposta térmica e comportamental de equinos submetidos a exercícios funcionais e acupuntura

The present research evaluated muscle activation degrees and relaxation of patrolling horses submitted to dynamic mobilization exercises, associated or not with acupuncture. Twelve mixed breed gelding, aged 10 ± 2.0 years, were distributed in three treatments. Treatment with a single session of dynamic mobilization exercises (longitudinal cervical flexion of head between hooves, between carpus and to up to chest); treatment with a single acupuncture session during 20 minutes, and treatment with a single session of dynamic mobilization exercises with acupuncture. Thermographic images were analyzed before and after applying treatments to the cervical, thoracic, dorsal, abdominal and pelvic regions. Animal behavior was assessed through five minutes filming, before and ten minutes after the end of each treatment application, in an uninterrupted way. Increase in animals body temperature at the end of the single session of functional exercises (P < 0.0001) at all animal regions were reported, being cervical and thoracic areas with highest final temperature values. There was no temperature variation for other treatments (P > 0.05). All treatments stimulated higher expression frequency (P < 0.05) of relaxation behaviors. A single dynamic mobilization exercises session is enough to promote intense muscular response in entire horse body; and with acupuncture, individually or associated, promoted muscle and mental relaxation, interfering positively in animal welfare.

Objetivou-se avaliar o grau de ativação e relaxamento muscular de equinos de patrulhamento submetidos à exercícios de mobilização dinâmica associados ou não à acupuntura. Doze cavalos castrados, sem raça definida, com idade de 10 ± 2,0 anos, foram distribuídos em três tratamentos: tratamento com uma sessão única de exercícios de mobilização dinâmica (flexão cervical longitudinal da cabeça entre os cascos, entre os carpos e até o peito); tratamento com sessão única de acupuntura (20 minutos); e tratamento com sessão única composta por exercícios de mobilização dinâmica associados a acupuntura. Foram analisadas imagens termográficas antes e após a aplicação dos tratamentos das regiões cervical, torácica, dorsal, abdominal e pélvica. A avaliação comportamental foi obtida por meio de filmagens 5 minutos antes e 10 minutos após o término da aplicação dos tratamentos, de maneira ininterrupta. Houve aumento (P < 0,0001) na temperatura corporal dos animais ao final da sessão única de exercícios funcionais para todas as regiões estudadas, sendo a cervical e torácica aquelas com maior valor de temperatura final. Não houve variação da temperatura nos demais tratamentos (P > 0,05). Todos os tratamentos geraram maior frequência (P < 0,05) na expressão de comportamentos relacionados ao relaxamento. A realização de uma sessão única de exercícios de mobilização dinâmica é suficiente para promover uma intensa resposta muscular em todo o corpo do equino, e tanto os exercícios funcionais quanto a acupuntura, de maneira individual ou associada, foram capazes de promover relaxamento muscular e mental, interferindo de maneira positiva no bem-estar dos animais.

Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter.

The interstitial cells of Cajal (ICCs) play an important role in coordinated gastrointestinal motility. The present study aimed to elucidate whether or how ICCs are involved in the lower esophageal sphincter (LES) relaxation induced by stimulation of the nicotinic acetylcholine receptor. The application of 1,1-dimethyl-4-phenyl-piperazinium (DMPP; a nicotinic acetylcholine receptor agonist) induced a transient relaxation in the circular smooth muscle of the porcine LES. DMPP-induced relaxation was abolished by not only 1 µM tetrodotoxin but also the inhibition of ICC activity by pretreatment with 100 µM carbenoxolone (a gap junction inhibitor), pretreatment with 100 µM CaCCinh-A01 (an anoctamin-1 blocker acting as a calcium-activated chloride channel inhibitor), and pretreatment with Cl--free solution. However, pretreatment with 100 µM Nω-nitro-L-arginine methyl ester had little effect on DMPP-induced relaxation. Furthermore, DMPP-induced relaxation was inhibited by pretreatment with 1 mM suramin, a purinergic P2 receptor antagonist, but not by 1 µM VIP (6-28), a vasoactive intestinal peptide (VIP) receptor antagonist. Stimulation of the purinergic P2 receptor with adenosine triphosphate (ATP) induced relaxation, which was abolished by the inhibition of ICC activity by pretreatment with CaCCinh-A01. In conclusion, membrane hyperpolarization of the ICCs via the activation of anoctamin-1 plays a central role in DMPP-induced relaxation. ATP may be a neurotransmitter for inhibitory enteric neurons, which stimulate the ICCs. The ICCs act as the interface of neurotransmission of nicotinic acetylcholine receptor in order to induce LES relaxation.

Opsin 3-Gαs Promotes Airway Smooth Muscle Relaxation Modulated by G Protein Receptor Kinase 2.

Recently, we characterized blue light-mediated relaxation (photorelaxation) of airway smooth muscle (ASM) and implicated the involvement of opsin 3 (OPN3), an atypical opsin. In the present study, we characterized the cellular signaling mechanisms of photorelaxation. We confirmed the functional role of OPN3 in blue light photorelaxation using trachea from OPN3 null mice (maximal relaxation 52 ± 13% compared with wild-type mice 90 ± 4.3%, P < 0.05). We then demonstrated colocalization of OPN3 and Gαs using co-IP and proximity ligation assays in primary human ASM cells, which was further supported by an increase in cAMP in mouse trachea treated with blue light compared with dark controls (23 ± 3.6 vs. 14 ± 2.6 pmol cAMP/ring, P < 0.05). Downstream PKA (protein kinase A) involvement was shown by inhibiting photorelaxation using Rp-cAMPS (P < 0.0001). Moreover, we observed converging mechanisms of desensitization by chronic ß2-agonist exposure in mouse trachea and correlated this finding with colocalization of OPN3 and GRK2 (G protein receptor kinase) in primary human ASM cells. Finally, an overexpression model of OPN1LW (a red light photoreceptor in the same opsin family) in human ASM cells showed an increase in intracellular cAMP levels following red light exposure compared with nontransfected cells (48 ± 13 vs. 13 ± 2.1 pmol cAMP/mg protein, P < 0.01), suggesting a conserved photorelaxation mechanism for wavelengths of light that are more tissue penetrant. Together, these results demonstrate that blue light photorelaxation in ASM is mediated by the OPN3 receptor interacting with Gαs, which increases cAMP levels, activating PKA and modulated by GRK2.

The mechanisms associated with reflux episodes in ambulant subjects with gastro-esophageal reflux disease.

BACKGROUND: The mechanisms associated with gastro-esophageal reflux (GER) episodes were studied using combined High-resolution Impedance Manometry (HRIM) and pH monitoring in ambulant subjects with different patterns of GERD. METHODS: Sixteen subjects with mild-moderate esophagitis (Los Angeles (LA) grade A&B) (group A) and 11 subjects with severe esophagitis (LA grade C&D) or Barrett's esophagus (BE) were studied before and after a meal, resting, while walking, and during standardized exercise, using a HRIM and a pH probe. KEY RESULTS: Post-prandial acid GER episodes were more common in group B (median 10 range (3-18) vs A (6.5 (0-18), p = 0.048). Postprandial acid clearance time was much longer in group B (median 0.71( 0.07-2.66 min) vs A (0.17 (0.04-2.44 min), p = 0.02). Transient lower esophageal sphincter relaxation (TLESR) was the most frequent mechanism associated with GER episodes in both groups. Post-prandial TLESRs with GER were more common in group B (median 17 (9-24) vs A 13.5 (7-34), p = 0.014), particularly during exercise (B 8 (6-9) vs A 6 (5-6.8), p = 0.007). Post-prandially TLESR with acid reflux increased during exercise in both groups (A rest median 2.4 (0-6.4) per hour vs exercise 4.7 (0-17.3), p = 0.005 and B 4 (0.8-9.6) vs 5.3 (2.7-13.3) per hour, p = 0.045). CONCLUSIONS AND INFERENCES: TLESR was the most common mechanism associated with reflux episodes in all subjects. Acid reflux episodes were more common in subjects with severe esophagitis or BE and esophageal acid clearance was much slower. Post-prandial exercise increased TLESR with acid reflux and GERD patients should be encouraged to avoid exercise immediately after a meal.

Attenuation of relaxing response induced by pituitary adenylate cyclase-activating polypeptide in bronchial smooth muscle of experimental asthma.

Bronchomotor tone is regulated by contraction and relaxation of airway smooth muscle (ASM). A weakened ASM relaxation might be a cause of airway hyperresponsiveness (AHR), a characteristic feature of bronchial asthma. Pituitary adenylyl cyclase-activating polypeptide (PACAP) is known as a mediator that causes ASM relaxation. To date, whether or not the PACAP responsiveness is changed in asthmatic ASM is unknown. The current study examined the hypothesis that relaxation induced by PACAP is reduced in bronchial smooth muscle (BSM) of allergic asthma. The ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. Twenty-four hours after the last antigen challenge, the main bronchial smooth muscle (BSM) tissues were isolated. Tension study showed a BSM hyperresponsiveness to acetylcholine in the OA-challenged mice. Both quantitative RT-PCR and immunoblot analyses revealed a significant decrease in PAC1 receptor expression in BSMs of the diseased mice. Accordingly, in the antigen-challenged group, the PACAP-induced PAC1 receptor-mediated BSM relaxation was significantly attenuated, whereas the relaxation induced by vasoactive intestinal polypeptide was not changed. These findings suggest that the relaxation induced by PACAP is impaired in BSMs of experimental asthma due to a downregulation of its binding partner PAC1 receptor. Impaired BSM responsiveness to PACAP might contribute to the AHR in asthma.

Reproducibility and reliability of performance indicators to evaluate the therapeutic effectiveness of biofeedback therapy after elbow surgery: An observational case series.

Electromyographic biofeedback (EMG-BF) therapy provides information on the state of contraction of the targeted muscles and relaxation of their antagonists, which can facilitate early active range of motion (RoM) after elbow surgery. Our aim in this study was to calculate the minimum detectable change (MDC) during EMG-BF therapy, initiated in the early postoperative period after elbow surgery.This study is an observational case series. EMG-BF of muscle contraction and relaxation was provided during active elbow flexion and extension exercises. Patients completed 3 sets of 10 trials each of flexion and extension over 4 weeks. The total range of flexion-extension motion and scores on the Japanese Society for Surgery of the Hand version of the disability of the arm, shoulder, and hand questionnaire and the Japanese version of the Patient-Rated Elbow Evaluation were obtained at baseline and weekly during the 4-week intervention period. A prediction formula was developed from the time-series data obtained during the intervention period, using the least-squares method. The estimated value was calculated by removing the slope from the prediction formula and adding the initial scores to residuals between the measured scores and predicted scores individually. Systematic error, MDC at the 95th percentile cutoff (MDC95), repeatability of the measures, and the change from the baseline to each time-point of intervention were assessed.The MDC95 was obtained for all 3 outcome measures and the range of values was as follows: RoM, 8.3° to 22.5°; Japanese version of the Patient-Rated Elbow Evaluation score, 17.6 to 30.6 points; and disability of the arm, shoulder, and hand questionnaire subscale: disability and symptoms score, 14.2 to 22.9 points.The efficacy of EMG-BF after elbow surgery was reflected in earlier initiation of elbow RoM after surgery and improvement in patient-reported upper limb function scores. The calculated MDC95 cut-offs could be used as reference values to assess the therapeutic effects of EMG-BF in individuals.

CryoEM structure of Drosophila flight muscle thick filaments at 7 Å resolution.

Striated muscle thick filaments are composed of myosin II and several non-myosin proteins. Myosin II's long α-helical coiled-coil tail forms the dense protein backbone of filaments, whereas its N-terminal globular head containing the catalytic and actin-binding activities extends outward from the backbone. Here, we report the structure of thick filaments of the flight muscle of the fruit fly Drosophila melanogaster at 7 Å resolution. Its myosin tails are arranged in curved molecular crystalline layers identical to flight muscles of the giant water bug Lethocerus indicus Four non-myosin densities are observed, three of which correspond to ones found in Lethocerus; one new density, possibly stretchin-mlck, is found on the backbone outer surface. Surprisingly, the myosin heads are disordered rather than ordered along the filament backbone. Our results show striking myosin tail similarity within flight muscle filaments of two insect orders separated by several hundred million years of evolution.

Functional atropine sensitive purinergic responses in the healthy rat bladder.

While acetylcholine is regarded to be the main directly contractile transmitter substance in the urinary bladder, interactions with other transmitters likely occur. Presently, the interplay between purinergic and cholinergic signalling was investigated to unravel the involvement of the urothelium and efferent neurons in the functionally important purinergically evoked release of acetylcholine in vitro. Functional characterization of receptor subtypes involved in this interplay was also performed. In vitro organ bath experiments with electrical field stimulation (EFS) or administration of agonist were performed in the absence and presence of the neurotoxin tetrodotoxin (TTX; 5 × 10-7 M) and/or receptor antagonists, in intact and urothelium-denuded full thickness rat bladder strip preparations. Interestingly, functional contractions to ATP (10-6-10-3 M) remained unaffected by TTX, but were significantly lowered in the presence of the muscarinic antagonist atropine (10-6 M). However, in urothelium-denuded strip preparations, this latter phenomenon was not present and the ATP response remained unaltered. To rule out purinergic interference caused by break-down of ATP, experiments were performed in which the stable ATP-analogue αßMeATP (10-7-10-5 M) gave rise to functional atropine-sensitive contractions. Furthermore, contractions to ATP were not affected by P2Y6 purinoceptor blockade (by MRS2578; 10-7, 10-5 M), nor were relaxatory responses to ATP sensitive to atropine, PPADS (3 × 10-5 M) or αßMeATP. Lastly, relaxations to ADP (10-6-10-3 M) or NECA (10-8-10-5 M) were unaltered by the presence of atropine. To conclude, purinergic functional contractile, but not relaxatory, responses are supported by the cholinergic transmitter system in vitro, through non-neuronal mechanisms in the urothelium. Involved purinoceptors are of the P2X-subtype, most likely P2X1 and/or P2X3.

La rigidez cadavérica, el espasmo cadavérico y tipos de fibras musculares / The cadaveric rigidity, the cadaveric spasm and types of muscle fibers

La rigidez cadavérica (rigor mortis) es un proceso no muy bien comprendido por la mayoría de los médicos. El conocimiento de la intimidad del proceso de la rigidez cadavérica es de vital importancia ya que es una de las variables que junto con las livideces (livor mortis) y la temperatura (algor mortis) del cadáver ayudan a determinar el cronotanatodiagnóstico, tanatocronodiagnóstico o intervalo postmortal del período inmediato de la muerte. Para entender el mecanismo de la rigidez y el espasmo cadavérico es preciso hacer un repaso de la contracción muscular fisiológica en el vivo. Hay que tener presente que el tipo de fibra muscular predominante modificará las características de la contracción muscular fisiológica en el vivo, y también la rigidez y el espasmo cadavérico. (AU)

The cadaveric rigidity (rigor mortis) is a process which is not very well understood by the majority of the doctors. The knowledge of the intimacy of the cadaveric stiffness process is of vital importance since it is one of the variables that, as well as the postmortem lividity (livor mortis) and the body temperature post mortem (algor mortis) help determine the chronotanatodiagnostic, tanatochronodiagnostic or postmortal interval of the immediate period of death. In order to understand the mechanism of stiffness and cadaveric spasm, it is necessary to review the physiological muscle contraction in vivo. We should keep in mind that the predominant type of muscle fiber will modify the characteristics of physiological muscle contraction in vivo, as well as stiffness and cadaveric spasm. (AU)

Effect of EP1 Receptor Antagonist on Transient Lower Esophageal Sphincter Relaxations in Humans.

BACKGROUND/AIMS: Transient lower esophageal sphincter relaxations (TLESRs) are the major cause of gastroesophageal reflux. Recently, an EP1 receptor antagonist, ONO-8539, showed the reduction of TLESRs in monkeys. However, its effect on TLESRs in humans remains unclear. This study investigated the effect of ONO-8539 on postprandial TLESRs in healthy male subjects. METHODS: Twenty-seven subjects participated in this placebo-controlled, cross-over study. The subjects received either placebo or ONO-8539 (450 mg) after a standardized breakfast. A 30-min basal recording was performed 4 h after drug administration. Subsequently, TLESR recordings were performed after a high-fat test meal for 3 h. The examination was repeated at least 7 days from the first evaluation for washout. RESULTS: Thirteen patients were ultimately analyzed. The basal lower esophageal sphincter pressure was not different between the 2 groups (16.3 and 18.0 mm Hg for placebo and ONO-8539, respectively; p = 0.88). ONO-8539 significantly reduced the number of TLESRs from 15.0 to 12.0 for 3 h (p < 0.05). The proportion of terminating events of TLESRs was significantly different between the 2 groups (p < 0.05). No events and swallowing terminated more TLESRs with ONO-8539 than with placebo. CONCLUSIONS: ONO-8539 suppressed TLESRs mildly. EP1 receptor may be involved with the mechanism of human TLESRs.

Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum

ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.

Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum.

Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.

Duodenal nutrient exposure contributes to enhancing gastric accommodation.

BACKGROUND: The gastric accommodation reflex consists of a relaxation which creates a reservoir for the ingested food before emptying to the duodenum occurs. The mechanisms that control gastric accommodation are not fully understood. This study aims to use intragastric pressure (IGP) measurement and pyloric balloon obstruction to determine the contribution of duodenal nutrient exposure to gastric accommodation and meal-induced satiation. METHODS: Two conditions were tested in 11 healthy subjects (28.3 ± 3.2 years; 23.6 ± 0.7 kg/m2 ; four females). IGP was measured during an intragastric nutrient drink (ND) infusion at a constant rate (60 mL/min) in the presence of a deflated (control) or inflated (pyloric obstruction) balloon placed into the pylorus. During the study, subjects filled out Likert scales for satiation scores and visual analogue scale for 9 epigastric symptoms (hunger, expected amount to eat, satiation, bloating, fullness, nausea, belching, gastric cramps, and pain) before and during ND infusion until maximal satiation. KEY RESULTS: During pyloric obstruction, the IGP drop and the area above the IGP curve (AAC) were significantly smaller compared with the control condition (6.7 ± 1.0 mm Hg vs3.6 ± 0.8 mm Hg, P = .03 and 69.7 ± 13.5 mm Hg × min vs 20.1 ± 9.0 mm Hg × min, P = .001, respectively). Pyloric obstruction decreased nutrient tolerance compared with the control condition (787.9 ± 73.1 mL vs 970.9 ± 79.2 mL, respectively, P < .05). Pyloric obstruction increased symptoms of bloating (1.3 ± 0.4 vs 2.6 ± 0.6; P = .04), fullness (2.3 ± 0.5 vs 3.6 ± 0.3; P = .03), and nausea (0.4 ± 0.2 vs 1.3 ± 0.4; P = .04) compared to control. CONCLUSION & INFERENCES: Duodenal nutrient exposure contributes to enhancing gastric accommodation. Preventing the passage of nutrients from the stomach to the duodenum inhibits gastric accommodation and increases meal-induced satiation, bloating, nausea, and fullness.

Relationship between the muscle relaxation effect and body muscle mass measured using bioelectrical impedance analysis: A nonrandomized controlled trial.

OBJECTIVE: The dose of neuromuscular blocking drugs is commonly based on body weight, but using muscle mass might be more effective. This study investigated the relationship between the effect of neuromuscular blocking drugs and muscle mass measured using bioelectrical impedance analysis. METHODS: Patients who were scheduled for elective surgery using a muscle relaxant were screened for inclusion in this study. Under intravenous anaesthesia, 12 mg or 9 mg of rocuronium was administered to males and females, respectively; and the maximal relaxation effect of T1 was measured using a TOF-Watch-SX® acceleromyograph. RESULTS: This study enrolled 40 patients; 20 males and 20 females. For both sexes, the maximal relaxation effect of T1 did not correlate with the body weight-based dose of neuromuscular blocking drugs (males, r2 = 0.12; females, r2 = 0.26). Instead, it correlated with the dose based on bioelectrical impedance analysis-measured muscle mass when injected with the same dose of rocuronium (males, r2 = 0.78, female, r2 = 0.82). CONCLUSIONS: This study showed that the muscle relaxation effect of rocuronium was correlated with muscle mass and did not correlate with body weight when using the same dose. Therefore, a muscle mass-based dose of neuromuscular blocking drugs is recommended.

Peroral Endoscopic Myotomy Is Effective for Patients With Achalasia and Normal Lower-Esophageal Sphincter Relaxation Pressures.

Increased lower esophageal sphincter integrated relaxation pressure (LES-IRP) is a cardinal feature of achalasia. However, some patients with characteristic features of achalasia have normal LES-IRP.1,2 The efficacy of peroral endoscopic myotomy (POEM) in achalasia patients with normal LES-IRP is not well known. Hence, we aimed to compare POEM outcomes in achalasia patients with normal (<15 mm Hg) and increased (≥15 mm Hg) LES-IRP.

Branched Short-Chain Fatty Acid Isovaleric Acid Causes Colonic Smooth Muscle Relaxation via cAMP/PKA Pathway.

BACKGROUND: Isovaleric acid (IVA) is a 5-carbon branched-chain fatty acid present in fermented foods and produced in the colon by bacterial fermentation of leucine. We previously reported that the shorter, straight-chain fatty acids acetate, propionate and butyrate differentially affect colonic motility; however, the effect of branched-chain fatty acids on gut smooth muscle and motility is unknown. AIMS: To determine the effect of IVA on contractility of colonic smooth muscle. METHODS: Murine colonic segments were placed in a longitudinal orientation in organ baths in Krebs buffer and fastened to force transducers. Segments were contracted with acetylcholine (ACh), and the effects of IVA on ACh-induced contraction were measured in the absence and presence of tetrodotoxin (TTx) or inhibitors of nitric oxide synthase [L-N-nitroarginine (L-NNA)] or adenylate cyclase (SQ22536). The effect of IVA on ACh-induced contraction was also measured in isolated muscle cells in the presence or absence of SQ22536 or protein kinase A (PKA) inhibitor (H-89). Direct activation of PKA was measured in isolated muscle cells. RESULTS: In colonic segments, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion; the IVA response was not affected by TTx or L-NNA but inhibited by SQ22536. Similarly, in isolated colonic muscle cells, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion and the effect blocked by SQ22536 and H-89. IVA also increased PKA activity in isolated smooth muscle cells. CONCLUSIONS: The branched-chain fatty acid IVA acts directly on colonic smooth muscle and causes muscle relaxation via the PKA pathway.