Electrical carotid sinus nerve stimulation attenuates experimental colitis induced by acetic acid in rats.

AIMS: The carotid bodies are sensors that detect physiological signals and convey them to the central nervous system, where the stimuli are processed inducing reflexes through efferent pathways. Recent studies have demonstrated that electrical stimulation of the carotid sinus nerve (CSN) triggers the anti-inflammatory reflex under different conditions. However, whether this electrical stimulation attenuates colitis was never examined. This study aimed to evaluate if the electrical CSN stimulation attenuates the experimental colitis induced by intrarectal administration of acetic acid in rats. METHODS: Electrodes were implanted around the CSN to stimulate the CSN, and a catheter was inserted into the left femoral artery to record the arterial pressure. The observation of hypotensive responses confirmed the effectiveness of the electrical CNS stimulation. This maneuver was followed by a 4 % acetic acid or saline administered intrarectally. After 24 h, colons were segmented into distal and proximal parts for macroscopy, histological and biochemical assessment. KEY FINDINGS: As expected, the electrical CSN stimulation was effective in decreasing arterial pressure in saline and colitis rats. Moreover, electrical CSN stimulation effectively reduced colonic tissue lesions, colitis scores, and histopathologic parameters associated with colitis. In addition, the CSN stimulation also reduced the colonic mucosa pro-inflammatory cytokine interleukin-1 beta, and increased the anti-inflammatory interleukin-10, in rats submitted to colitis. SIGNIFICANCE: These findings indicated that electrical CSN stimulation breaks the vicious cycle of local colon inflammation in colitis, which might contribute to its better outcome.

Risk factors and immunological biomarkers in denture stomatitis: An observational cross-sectional study.

OBJECTIVE: Assess risk factors, local and systemic immunological biomarkers in healthy individuals and with Denture Stomatitis (DS). DESIGN: For this observational transversal study, 27 participants without DS (Group 0), 24 with moderate DS (Group 1), and 25 with severe DS (Group 2) were assessed for sociodemographic, behavioral, and clinical parameters, microbial load of Candida spp., Staphylococcus spp., Streptococcus mutans, Pseudomonas spp., and enterobacteria, and cytokine and C-reactive protein levels. ANOVA, Fisher's exact, Kruskal-Wallis, Mann-Whitney, Wilcoxon and Pearson's chi-square tests were used for data analysis (α = 0.05). RESULTS: Group 1 had a significantly higher mean age compared to the other groups (P = 0.018), but no correlation was identified between age and DS (P = 0.830; r = 0.025). No significant differences were found among the groups for other sociodemographic and behavioral characteristics. Group 1 had significantly older upper and lower dentures; however, no correlation was identified between age of upper (P = 0.522; r = 0.075) and lower (P = 0.143; r = 0.195) dentures and DS. The microbial load of Candida albicans on the dentures (P = 0.035) and Candida spp. on the palate (P = 0.008) of the groups 1 and 2 was higher than group 0. Group 1 and 2 had higher Candida spp. counts on denture (P = 0.003) than group 0. There was no difference among groups for bacterial analyzed. Group 1 showed higher and Group 2 intermediate salivary levels of IL-6 compared to Group 0. There was no difference in the C-reactive protein levels among groups. CONCLUSIONS: Microbial load of Candida spp. is the factor with the strongest relationship with DS, with capacity for local signaling through IL-6.

Autonomic Regulation of Inflammation in Conscious Animals.

Bioelectronic medicine is a novel field in modern medicine based on the specific neuronal stimulation to control organ function, cardiovascular, and immune homeostasis. However, most studies addressing neuromodulation of the immune system have been conducted on anesthetized animals, which can affect the nervous system and neuromodulation. Here, we review recent studies involving conscious experimental rodents (rats and mice) to better understand the functional organization of neural control of immune homeostasis. We highlight typical experimental models of cardiovascular regulation, such as electrical activation of the aortic depressor nerve or the carotid sinus nerve, bilateral carotid occlusion, the Bezold-Jarisch reflex, and intravenous administration of the bacterial endotoxin lipopolysaccharide. These models have been used to investigate the relationship between neuromodulation of the cardiovascular and immune systems in conscious rodents (rats and mice). These studies provide critical information about the neuromodulation of the immune system, particularly the role of the autonomic nervous system, i.e., the sympathetic and parasympathetic branches acting both centrally (hypothalamus, nucleus ambiguus, nucleus tractus solitarius, caudal ventrolateral medulla, and rostral ventrolateral medulla), and peripherally (particularly spleen and adrenal medulla). Overall, the studies in conscious experimental models have certainly highlighted to the reader how the methodological approaches used to investigate cardiovascular reflexes in conscious rodents (rats and mice) can also be valuable for investigating the neural mechanisms involved in inflammatory responses. The reviewed studies have clinical implications for future therapeutic approaches of bioelectronic modulation of the nervous system to control organ function and physiological homeostasis in conscious physiology.

Effect of a Hygiene Protocol on Denture-Related Stomatitis Remission, Local Inflammatory Factors, and Hemodynamic Responses by Arterial Pressure.

Denture-related stomatitis (DRS) is frequent oral inflammation in complete denture wearers. This study evaluated the effect of a hygiene protocol on DRS remission, local inflammatory factors, and hemodynamic responses. Thirty-three individuals were enrolled in the study. The outcomes were measured before and after 10 days of a hygiene protocol treatment consisting of brushing the palate with a soft brush and water and denture brushing with a denture-specific brush and mild soap, as well as immersion of the denture for 20 min in a 0.25% sodium hypochlorite solution. Data were analyzed by paired Wilcoxon for biofilm removal and CFU count of microorganisms. The paired T test was used to assess salivary MUC 1, cytokines, and arterial pressure (p < 0.05). A significant difference was found in the DRS degree (p < 0.001), biofilm (p < 0.001), microbial load of Candida spp. (p < 0.001), Gram-negative (p < 0.004), Staphylococcus spp. (p < 0.001), and S. mutans (p < 0.001) of the denture, and S. mutans (p < 0.001) of the palate after use of the protocol. The salivary flow (p = 0.2) and pH (p = 0.97) did not change; there was an increase of MUC 1 (p = 0.049) and a decrease in IL-6 (p = 0.038), IL-2 (p = 0.04), IL-10 (p = 0.041), and IFNγ (p = 0.04). There was also a decrease in systolic (p = 0.012) and mean arterial pressure (p = 0.02). The current hygiene protocol reduced the inflammation degree of DRS and promoted an improvement of local inflammatory factors and a reduction in the systolic arterial pressure of the patients.

Effect of short-term increase in occlusal vertical dimension on masticatory muscle electrical activities and pressure-to-pain threshold: A crossover clinical study.

STATEMENT OF PROBLEM: Increasing the occlusal vertical dimension (OVD) is a common procedure in clinical practice. However, few studies have assessed the short-term influence of an increased OVD on the masticatory muscles. PURPOSE: The purpose of this crossover clinical study was to investigate the effect of increased OVD on the electrical activity of masticatory muscles and the pressure-to-pain threshold (PPT) in asymptomatic participants. MATERIAL AND METHODS: Twenty asymptomatic participants (22.7 ±2.39 years of age; 10 men, 10 women) were submitted to an increase in OVD by using interocclusal devices of different thicknesses (3- and 6-mm) for 24 hours. Masticatory muscle activity was assessed with electromyography (EMG), expressed in microvolts (µV), while the participants masticated 2 pieces of latex of different consistency (latex S and H) with and without the device. The PPT was measured with a digital algometer before and after the mastication. The results were assessed by using analysis of variance (ANOVA) and the Tukey honestly significant difference (HSD) test (α=.05). RESULTS: The change of OVD did not significantly affect the electrical activity of the muscles. The latex of hard consistency (latex H) showed higher electrical activity values than the soft texture (latex S). For the working side anterior temporal muscle, a change in the PPT was detected on the day the 6-mm-device was inserted, but for the other muscles, device thickness and latex mastication did not change the PPT. CONCLUSIONS: For a short time, an increase in occlusal vertical dimension did not affect the electrical activity in the masticatory muscles or pressure-to-pain threshold in asymptomatic participants.

Short-term effect of ligature-induced periodontitis on cardiovascular variability and inflammatory response in spontaneously hypertensive rats.

BACKGROUND: We previously reported that periodontal disease (PD) induces high arterial pressure variability (APV) consistent with sympathetic overactivity and elicits myocardial inflammation in Balb/c mice. However, it is unknown whether PD can change APV and heart rate variability (HRV) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. This study aimed to evaluate the hemodynamic level, HRV, and APV associating with myocardial inflammation and plasma concentrations of oxide nitric (NO) in SHR and WKY rats with PD. METHODS: Three weeks after bilateral ligation of the first mandibular molar, or Sham operation, the rats received catheters into the femoral artery and had their arterial pressure (AP) recorded the following day. Subsequently, plasma, heart, and jaw were collected. The NO was quantified by the chemiluminescence method in plasma, and the myocardial IL-1ß concentrations were evaluated by ELISA. In the jaw was evaluated linear alveolar bone loss induced by PD. RESULTS: The linear alveolar bone loss in jaws of SHR with PD was higher than in all other groups. AP and heart rate were higher in SHR than in their WKY counterparts. SHR with PD showed lower AP than control SHR. HRV and APV were different between SHR and WKY rats; however, no differences in these parameters were found between the animals with PD and their control counterparts. Plasma NO and myocardial IL-1ß concentrations were higher in SHR with PD as compared to control WKY. A significant correlation was found between linear alveolar bone loss and plasma NO and myocardial IL-1ß concentrations. CONCLUSION: Our results demonstrated that short-term PD lowered the AP in SHR, which might be due to the higher levels of plasma NO. Even though PD did not affect either HRV or APV, it did induce myocardial inflammation, which can determine cardiovascular dysfunction in long-term PD.

The Bezold-Jarisch Reflex and The Inflammatory Response Modulation in Unanesthetized Endotoxemic Rats.

Evidence indicates that the activation of the parasympathetic branch of the autonomic nervous system may be effective in treating inflammatory diseases. Previously, we have described that baroreflex activation displays anti-inflammatory properties. Analogous to the baroreflex, the Bezold-Jarisch reflex also promotes parasympathetic activation with simultaneous inhibition of the sympathetic system. Thus, the present study aimed to evaluate whether the activation of the Bezold-Jarisch reflex would also have the ability to reduce inflammation in unanesthetized rats. We used lipopolysaccharide (LPS) injection (5mg/kg, i.p.) to induce systemic inflammation in male Wistar Hannover rats and phenylbiguanide (PBG) administration (5µg/kg, i.v.) to activate the Bezold-Jarisch reflex. Spleen, heart, hypothalamus, and blood samples were collected to determine the levels of cytokines. Compared to baseline, PBG reduced the arterial pressure (115±2 vs. 88±5mmHg) and heart rate (380±7 vs. 114±26bpm), immediately after its administration, confirming the activation of the parasympathetic system and inhibition of the sympathetic system. From the immunological point of view, the activation of the Bezold-Jarisch reflex decreased the plasma levels of TNF (LPS: 775±209 vs. PBG + LPS: 248±30pg/ml) and IL-6 levels in the spleen (LPS: 39±6 vs. PBG + LPS: 24±4pg/mg of tissue). However, it did not change the other cytokines in the plasma or the other tissues evaluated. These findings confirm that the activation of the Bezold-Jarisch reflex can modulate inflammation and support the understanding that the cardiovascular reflexes regulate the immune system.

Carotid sinus nerve stimulation attenuates alveolar bone loss and inflammation in experimental periodontitis.

Baroreceptor and chemoreceptor reflexes modulate inflammatory responses. However, whether these reflexes attenuate periodontal diseases has been poorly examined. Thus, the present study determined the effects of electrical activation of the carotid sinus nerve (CSN) in rats with periodontitis. We hypothesized that activation of the baro and chemoreflexes attenuates alveolar bone loss and the associated inflammatory processes. Electrodes were implanted around the CSN, and bilateral ligation of the first mandibular molar was performed to, respectively, stimulate the CNS and induce periodontitis. The CSN was stimulated daily for 10 min, during nine days, in unanesthetized animals. On the eighth day, a catheter was inserted into the left femoral artery and, in the next day, the arterial pressure was recorded. Effectiveness of the CNS electrical stimulation was confirmed by hypotensive responses, which was followed by the collection of a blood sample, gingival tissue, and jaw. Long-term (9 days) electrical stimulation of the CSN attenuated bone loss and the histological damage around the first molar. In addition, the CSN stimulation also reduced the gingival and plasma pro-inflammatory cytokines induced by periodontitis. Thus, CSN stimulation has a protective effect on the development of periodontal disease mitigating alveolar bone loss and inflammatory processes.

Qualidade de vida dos cuidadores familiares de crianças e adolescentes com transtorno do espectro autista / Quality of life of family caregivers of children and adolescents with autist spectrum disorder

O presente estudo teve como objetivo avaliar a qualidade de vida dos cuidadores familiares de crianças e adolescentes com transtorno do espectro autista por meio de questionários, um elaborado pelos pesquisadores com variáveis sociodemográficas, comportamentais do cuidador e condições de saúde da criança e adolescente com TEA e o World Health Organization of Life (WHOQOL-bref) usado para avaliar a qualidade de vida dos cuidadores. Trata-se de um estudo descritivo exploratório do tipo transversal, realizado na Fundação Casa da Esperança, no município de Fortaleza, Ceará, nos meses de outubro e novembro de 2018. Foram convidados a participar do estudo, cuidadores familiares de crianças e adolescentes com autismo na faixa etária de 4 a 19 anos incompletos em acompanhamento na Fundação Casa da Esperança. Todos os dados foram analisados por meio do programa estatístico SPSS na versão 20.0. Colaboraram com a pesquisa 102 participantes, a maioria do sexo feminino (97,1%), com idade variando de 35 a 45 anos (39,2%), casadas (47,1%), com ensino médio completo (36,3%), 52% sem atividade remunerada e com renda mensal de 1 salário mínimo (60,8%). 85,3% passam 24 horas cuidando do filho, 73,5% sentem-se sobrecarregadas e estressadas (72,5%), não realizam nenhuma atividade física 73,5%, não costumam ter lazer 37,3% e se sentem sozinhas no cuidar 66,7%. As variáveis associadas ao domínio meio ambiente, foram em sua maioria ruim 54,9%, os demais domínios físicos 65,7%, psicológicos 55,9% e relações sociais 41,2% tiveram suas variáveis descritas como nem ruim nem boa. Os resultados confirmaram haver uma diminuição na qualidade de vida dos cuidadores familiares, reforçando a necessidade de uma atenção maior dessa população.

The present study aimed to assess the quality of life of family caregivers and adolescents with autism spectrum disorder through questionnaires, one prepared by researchers with sociodemographic and behavioral variables of the caregiver and healthconditions of children and adolescents with ASD and o World Health Life Organization (WHOQOL-bref) used to assess caregivers' quality of life. This is a descriptive exploratory cross-sectional study, carried out at the Casa da Esperança Foundation in the city of Fortaleza, Ceará, in the months of October and November 2018. Family assistants of children and adolescents with autism aged between 4 and 19 years of age who were incompletein the monitoring of the Casa da Esperança Foundation were invited to participate in a study. All data were analyzed using the SPSS statistical program in version 20.0. A total of 102 participants collaborated with a research, most of them female (97.1%), aged 35 to 45 years (39.2%), married (47.1%), with complete secondary education (36.3%), 52% without paid activity and with a monthly income of 1 minimum wage (60.8%). 85.3% spend 24 hours taking care of the child, 73.5% feel overwhelmed and stressed (72.5%), do not perform any physical activity 73.5%, do not usually have leisure 37.3% and feel alone not caring 66.7%. As variables selected in the environment domain, the worst ones were 54.9%, the other domains 65.7%, psychological 55.9% and social relations 41.2% had the variations described as neither bad nor good. The results confirmed a reduction in the quality of life of family caregivers, reinforcing the need for greater attention from this population.

Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis.

The present study examined the hemodynamics [arterial pressure (AP), AP variability (APV), heart rate (HR), and heart rate variability (HRV)], cardiac function (echocardiographycally), and myocardial inflammation in Balb/c mice submitted to Periodontitis, through the ligation of the left first molar, or Sham surgical procedure. The first protocol indicated that the AP was similar (136 ± 2 vs. 132 ± 3 mmHg in Sham), while the HR was higher in mice with Periodontitis (475 ± 20 vs. 412 ± 18 bpm in Sham), compared to their Sham counterparts. The APV was higher in mice with Periodontitis when evaluated in the time domain (4.5 ± 0.3 vs. 3.4 ± 0.2 mmHg in Sham), frequency domain (power of the LF band of systolic AP), or through symbolic analysis (patterns 0V + 1V), indicating a sympathetic overactivity. The HRV was similar in the mice with Periodontitis, as compared to their Sham counterparts. In the second protocol, the mice with Periodontitis showed decreased cardiac output (10 ± 0.8 vs. 15 ± 1.4 mL/min in Sham) and ejection fraction (37 ± 3 vs. 47 ± 2% in Sham) associated with increased myocardial cytokines (Interleukin-17, Interleukin-6, and Interleukin-4). This study shows that experimental Periodontitis caused cardiac dysfunction, increased heart cytokines, and sympathetic overactivity, in line with epidemiological studies indicating an increased risk of cardiovascular events in clinical Periodontitis.

Cholecystokinin Modulates the Mucosal Inflammatory Response and Prevents the Lipopolysaccharide-Induced Intestinal Epithelial Barrier Dysfunction.

The intestinal mucosa plays a critical role in the organism, acting as an interface between the lamina propria and the harmful antigens in the lumen. Sepsis is associated with primary injury to the intestinal mucosa, which in turn induces bacterial translocation and hyperpermeability. Cholecystokinin (CCK) is a peptide synthesized by several cell types, whose immunomodulatory activity has been reported in experimental models of inflammation. We hypothesized that the CCK treatment could modulate the inflammatory response and protect the integrity of the intestinal barrier in endotoxemic rats. Ten minutes before the endotoxemia induction by lipopolysaccharide (LPS) administration, rats were pretreated with CCK at two doses (0.4 µg/kg or 40 µg/kg). Mucosal permeability, bacterial translocation, cytokines production, histology injury, and expression of tight junction (TJ) proteins were the parameters assessed. In the early phase of endotoxemia, rats exhibited impaired intestinal barrier function, increased mucosal permeability, bacterial translocation, and also hyperactivation of the inflammatory response. On the other hand, the pretreatment with CCK modulated the mucosal production of pro-inflammatory cytokines and increased the expression of seal-forming TJ proteins (occludin, claudin-1 and junctional adhesion molecule (JAM-A)) only in the colon and also, reduced the bacterial counts in the mesenteric lymph nodes. However, CCK has a site-specific mechanism of action in the colon via CCK-1R, which is upregulated by the CCK treatment. In synergy with previous findings from our research group, the present results demonstrated that CCK preserves the integrity of the intestinal mucosa and might be a promising hormonal adjuvant therapy for the treatment of sepsis.

Dexamethasone Prevents Lipopolysaccharide-Induced Epithelial Barrier Dysfunction in Rat Ileum.

Inflammatory mediators have been postulated as elementary inducing factors to the disruption of the intestinal tight junctions (TJ) and consequently, gut permeability and bacterial translocation. Corticosteroids are considered the mainstay in the treatment of septic shock; however, the impact of this therapy on the intestinal epithelial barrier dysfunction during septic shock remains unknown. Our aims were to demonstrate the role of low dexamethasone (DEX) doses in modulation of the inflammatory response, as well as the expression and the arrangement of TJ proteins in endotoxemic rats. One hour before the endotoxemia induction by lipopolysaccharide (LPS) administration, rats were pretreated with DEX at two low-doses (0.1 and 1.0 mg/kg). The parameters assessed included intestinal permeability, bacterial translocation, cytokines production, histology injury, localization, and expression of TJ proteins. Endotoxemic rats displayed intestinal epithelial barrier dysfunction, characterized by increased permeability and bacterial translocation, TJ disruption (opening and changes to its constituent proteins expression) and hyperactivation of the inflammatory response. On the other hand, the pretreatment with DEX attenuated the systemic and mucosal production of inflammatory mediators and also reverted the LPS-induced ileal injuries, increasing the expression of occludin and claudin-1, but also reducing claudin-2. Moreover, the histological damages and the morphology of the TJ were preserved by the DEX administration, therefore reducing their LPS-induced opening. The present study sheds light on the fact that early DEX treatment breaks the vicious cycle of local gut inflammation and barrier dysfunction in endotoxemia, especially preserving an essential structure of this monolayer epithelium, the TJ.