Analgesic effect of linalool odor on oral ulcerative mucositis-induced pain in rats.

Oral ulcerative mucositis (OUM) induces severe pain, leading to a low quality of life. Linalool odor exposure has recently been reported to suppress inflammatory pain in the hind paws. However, the analgesic effect of linalool odor on orofacial pain remains unclear. In this study, we examined the mechanism underlying the analgesic effect of linalool odor on oral pain caused by OUM using nocifensive behavioral and immunohistochemical analyses in rats. OUM was developed by treating the labial fornix region of the inferior incisors with acetic acid. Linalool at 1% was exposed for 5 min at 30 min before nocifensive behavioral measurements. OUM induced spontaneous pain and mechanical allodynia, which were suppressed by the linalool odor. Mechanical allodynia in the hind paw following the injection of complete Freund's adjuvant was also suppressed by linalool odor. Application of lidocaine to the olfactory bulb attenuated the inhibition of spontaneous pain and hyperactivation of trigeminal spinal nucleus caudalis neurons in OUM model rats. Linalool odor exposure-induced neuronal activation in the locus coeruleus (LC) of OUM model rats was decreased by lidocaine application to the olfactory bulb. The decrease in neuronal activation in the LC was attenuated by the administration of orexin 1 receptor (OX-1) antagonist to the LC. These results suggest that linalool odor stimulation through the olfactory pathway activates LC neurons via OX-1 signaling, leading to the suppression of OUM-induced oral pain.

Changes of the daily and hourly behavioral time of respiratory disease calves in a group rearing system for 7 days prior to the date of clinical diagnosis.

Respiratory disease in calves is one of the most prominent diseases affecting their growth. The early and accurate detection of calf disease on the farm brings proper growth of calves. The objective of this study was to compare the daily and hourly behavioral time of diseased calves with the other calves in same pen (pen-mates) for 7 days prior to the diagnosis day. The calves (from 14 to 20 heads) were reared in a group. Day 0 was defined as the day of diagnosis. The number of diseased calves was 30 in the present experiment. The lying and eating behavior of calves were observed at 10-min intervals. The diseased calves have significantly (P < 0.01) shorter eating times than the pen-mates on the diagnosis day. The longest hourly time of the eating was in the period between 08:00 and 09:00, and shortest lying time was in the period between 09:00 and 10:00. Diseased calves had significantly (P < 0.05) longer daily lying time and shorter daily eating time than the pen-mates almost for the 7 days prior to the diagnosis day. Even though the daily behavioral time was different, the difference of behavioral time in successive hour periods was limited.

Early detection of disease onset through changes in appearance of pre-weaning calves.

The onset of diseases in pre-weaning calves can lead to changes in their appearance, which can aid early disease detection. This study measured the changes in appearance that led to disease onset in 66 pre-weaning Holstein calves. The appearance scores of the calves were recorded for 7 days before the onset of digestive or respiratory diseases. Appearance features (ear position, head position, topline curve, hair coat length, hair coat gloss, eye opening, and sunken eyes) were recorded using video camera images and scored from 0 (healthy) to 2 (poor). Among the calves with respiratory diseases, the proportion of calves with a score of 0 for ear position decreased linearly over time (p = 0.0437). Among the calves with digestive diseases, the proportion of calves with a score of 2 for hair coat length increased linearly over time (p = 0.0197). Among the calves with both respiratory and digestive diseases, the proportion of calves with scores of 1 for the topline curve and 2 for eye opening increased linearly over time (p = 0.0191). Therefore, early signs of disease manifest as different appearance features depending on the type of disease before its onset.

Kinematic Features of Mandibular Movement during Mastication in Geriatric Individuals Who Are Provided with a Dysphagia Diet at Long-Term Care Facilities.

Providing a normal diet to a care recipient who is unable to form an adequate bolus may cause suffocation or aspiration pneumonia. We investigated whether differences in kinematic data of mandibular movements during mastication can be used as an indicator of the need for a dysphagia diet in the elderly in long-term care facilities. We included 63 participants who were provided with solid food in two long-term care facilities. The primary outcome variable was the kinematic data on mandibular movement during cracker chewing. The analysis results were compared between the normal and dysphagia diet groups. Logistic regression analysis and receiver operating characteristic curve analyses were performed. Significant differences were observed in the masticatory time, cycle frequency, total change amount, number of linear motions, and circular motion frequency between the normal and modified diet groups. The odds ratio for the circular motion frequency was -0.307, and the calculated cutoff value was 63%, with a sensitivity of 71.4%, a specificity of 73.5%, and an area under the curve of 0.714. Thus, these characteristics may be useful for detecting care recipients who need to be provided with a dysphagia diet. Moreover, the circular motion frequency could be used as a screening test to identify people who need a dysphagia diet.

Use of a commercial indoor positioning system for monitoring resting time and moving distance in group-housed dairy calves.

To assess the usefulness of a commercially available indoor positioning system for monitoring the resting time and moving distance in group-housed dairy calves as indicators of their health status, five dairy calves were housed in a free barn, and their coordinate was recorded. The mean displacement (cm/s) within a minute showed a double-mixture distribution. Actual observations revealed that the minutes in the first distribution with shorter displacement were mostly the time that the calves spent lying. To predict the daily lying time and moving distance, a mixed distribution was divided at a threshold value. The mean sensitivity (the proportion of total minutes predicted correctly as lying, in total minutes observed lying) was more than 92%. The daily fluctuation in lying time correlated well with the actual lying time (r = 0.758, p < 0.01). The range of fluctuations was 740-1308 min/day and 724-1269 m/day for daily lying time and moving distance, respectively. The rectal temperature was correlated with daily lying time (r = 0.441, p < 0.001) and distance moved (r = 0.483, p < 0.001). The indoor positioning system can be a useful tool for early illness detection in calves before the onset of symptoms in group-housing systems.

Simultaneous free fatty acid elevations and accelerated desaturation in plasma and oocytes in early postpartum dairy cows under intensive feeding management.

A severe negative energy balance and high circulating free fatty acids (FFA) in postpartum cows impair fertility. The lipotoxicity of FFA has been shown to decrease the quality of bovine oocytes in vitro. Therefore, excess FFA in cells is converted to triacylglycerol (TAG), a non-toxic form, to avoid lipotoxicity. We recently reported that the TAG content in oocytes was higher in postpartum lactating cows subjected to grazing management than in heifers (Theriogenology 176: 174-182, 2021). The present study investigated the compositions of the energy metabolism-related lipids, FFA and TAG, in the plasma and oocytes of cows at different lactation stages under indoor intensive feeding management in order to obtain insights into lipotoxicity in oocytes, particularly those in early postpartum cows. Blood and oocytes were collected from 20 lactating cows categorized into the following lactation groups: 20-30 days in milk (DIM) (n = 5), 40-50 DIM (n = 5), 60-80 DIM (n = 5), and 130-160 DIM (n = 5). Daily energy balance data were obtained for 3 weeks prior to oocyte collection using the ovum pick up (OPU) method. The contents and compositions of FFA and TAG in plasma and oocytes were analyzed using liquid chromatography-mass spectrometry. As expected, plasma FFA was high at 20-30 DIM, decreased by 50 DIM, and was maintained at a low level for the remainder of the experimental period. Similar changes were observed in oocyte FFA and TAG with DIM as plasma FFA. Oocyte FFA positively correlated with plasma FFA (P < 0.05), but negatively correlated with the mean energy balance 1 and 21 days before OPU (P < 0.05). Relationships were noted between the composition and content of FFA in plasma and oocytes, with the FFA 16:1/16:0 and 18:1/18:0 ratios positively correlating with the total amount of FFA (P < 0.05). Elevated oocyte FFA in cows in the early postpartum period under intensive feeding management suggested that oocytes were at a high risk of FFA lipotoxicity. Furthermore, the present results implied that the severe negative energy balance in the previous few weeks was closely related to increases in oocyte FFA, which supports the importance of long-term cow feeding management for preserving the quality of oocytes in the early postpartum period. The present results provide insights into the effects of high circulating FFA on the fertility of postpartum cows.

Exploratory Synthesis for Complex Metal Fluorides Using Solid-State Fluorine Sources.

We attempted to synthesize complex metal fluorides via reaction between metal and solid-state fluorine sources and succeeded in preparing trirutile-type Li2MoF6 using LiF, the metal Mo, and CuF2. We also found a new phase of Li2MoF6 that is isostructural with trigonal Li2ZrF6 via a combination of solid-state fluorine sources and high-pressure synthesis. The reaction occurs exothermically and involves conversion and addition associated with redox reaction, and CuF2 then functions as both an oxidizing agent and fluorine source. Because the overall reaction proceeds stoichiometrically, the required amount of fluorine can be controlled by the amount of solid-state fluorine agents. The synthesis route was also applicable for the preparation of other known fluorides, Li2MF6 (M = Ti, Zr, and Nb) and ß-Li3MF6 (M = Ti and V). The synthetic route using a solid-state fluorine source is suitable for the exploration of novel inorganic complex metal fluorides.

Dietary raffinose ameliorates hepatic lipid accumulation induced by cholic acid via modulation of enterohepatic bile acid circulation in rats.

Enterohepatic circulation of 12α-hydroxylated (12αOH) bile acid (BA) is enhanced depending on the energy intake in high-fat diet-fed rats. Such BA metabolism can be reproduced using a diet supplemented with cholic acid (CA), which also induces simple steatosis, without inflammation and fibrosis, accompanied by some other symptoms that are frequently observed in the condition of non-alcoholic fatty liver in rats. We investigated whether supplementation of the diet with raffinose (Raf) improves hepatic lipid accumulation induced by the CA-fed condition in rats. After acclimation to the AIN-93-based control diet, male Wistar rats were fed diets supplemented with a combination of Raf (30 g/kg diet) and/or CA (0·5 g/kg diet) for 4 weeks. Dietary Raf normalised hepatic TAG levels (two-way ANOVA P < 0·001 for CA, P = 0·02 for Raf and P = 0·004 for interaction) in the CA-supplemented diet-fed rats. Dietary Raf supplementation reduced hepatic 12αOH BA concentration (two-way ANOVA P < 0·001 for CA, P = 0·003 for Raf and P = 0·03 for interaction). The concentration of 12αOH BA was reduced in the aortic and portal plasma. Raf supplementation increased acetic acid concentration in the caecal contents (two-way ANOVA P = 0·001 as a main effect). Multiple regression analysis revealed that concentrations of aortic 12αOH BA and caecal acetic acid could serve as predictors of hepatic TAG concentration (R2 = 0·55, P < 0·001). However, Raf did not decrease the secondary 12αOH BA concentration in the caecal contents as well as the transaminase activity in the CA diet-fed rats. These results imply that dietary Raf normalises hepatic lipid accumulation via suppression of enterohepatic 12αOH BA circulation.

Effect of electromyography-triggered peripheral magnetic stimulation on voluntary swallow in healthy humans.

BACKGROUND: Electrical stimulation therapy is effective for patients with dysphagia. However, because of the pain, strong stimulation cannot be applied. Although magnetic stimulation induces less pain, there are no reports on magnetic stimulation being synchronised with a swallowing reflex. OBJECTIVE: This study aimed to determine whether it is possible to induce magnetic stimulation during a voluntary swallowing using electromyography (EMG)-triggered peripheral magnetic stimulation and to evaluate its effect on healthy individuals. METHODS: A total of 20 healthy adults in seated position were instructed to swallow saliva and 10 ml of barium under videofluoroscopy. For concomitant use of magnetic stimulation, a magnetic stimulus for suprahyoid muscles at 30 Hz frequency was applied for 2 s when the EMG level in the sternohyoid muscle exceeded the threshold. During the voluntary swallowing, the movement of the hyoid bone and opening width of the upper oesophageal sphincter (UES) were measured. Furthermore, pressure topography was evaluated in 6 subjects using high-resolution manometry. RESULTS: The magnetic stimulation significantly extended the movement time of the hyoid bone (p < 0.001). During liquid deglutition, significant increases were observed in the anterior maximum movement distance of the hyoid bone (p < 0.05), opening width of the UES (p < 0.001) and anterior movement distance of the hyoid bone at the maximum UES opening (p < 0.01). In the pressure topography, the maximum pressure immediately after UES closure significantly decreased with magnetic stimulation (p < 0.05). CONCLUSION: EMG-triggered peripheral magnetic stimulation made it possible to apply magnetic stimulation during a voluntary swallowing.

Effects of grazing adaptation on herbage intake, milk production, and body weight change in lactating dairy cows after turning out to pasture in early spring.

The present study investigated the effects of adaptation to grazing in early spring on the herbage intake, milk production, and body weight changes in lactating dairy cows. The experiment included 12 Holstein lactating cows during early spring. Six cows were allowed to gradually adapt to grazing (ADP) over 10 days. They were allowed to graze on a pasture for 4 h during the first week and for 19 h during the remaining 3 days (adaptation period). During the 10-day period, the remaining six cows were housed in a barn (CON). Cows in both groups received adequate silage, hay, and concentrate during the adaptation period. Subsequently, cows in both groups were allowed to graze together for 19 h for 4 weeks (experimental period). No cow received supplements during the experimental period. In the first week of the experimental period, the ADP cows showed a higher herbage intake than the CON cows. During the subsequent weeks, there were no differences in herbage intake between the two groups. At the start of the experimental period, milk production and body weight of the ADP cows were higher than those of the CON cows, and this difference lasted until the end of the experiment.

Effects of soybean meal supplementation on ruminal kinetics of feed particle size reduction and passage in dairy cows fed rice straw.

Six ruminal-cannulated nonlactating Holstein Friesian cows (mean body weight:660 ± 42.9 kg) were used to investigate the effect of soybean meal (SBM) supplementation on voluntary rice straw (RS) intake, feed particle size reduction, and passage kinetics in the rumen. They were allocated to two dietary treatments: RS alone or RS supplemented with SBM. Voluntary dry matter intake of RS and total tract fiber digestibility was increased by SBM supplementation (p < 0.05). Supplementation with SBM decreased rumination time per dietary dry matter (DM) and neutral detergent fiber (NDFom) intake (p < 0.01). Particle size distribution in the rumen and total ruminal NDFom digesta weights were not affected by SBM supplementation. However, the disappearance rates of total digesta and large and small particles from the rumen were increased by SBM supplementation (p < 0.01). Moreover, SBM supplementation increased the rate of size reduction in ruminal particles (p < 0.05). In situ disappearance of DM and NDFom of RS in the rumen was greater in SBM-supplemented cows than in nonsupplemented cows (p < 0.05). This study clearly showed that increased ruminal RS particle size reduction, passage, and fermentation due to SBM supplementation accelerated the RS particle clearance from the rumen and resulted in increased voluntary RS intake of dairy cows.

Regional differences in the fatty acid composition, and vitamin and carotenoid concentrations in farm bulk milk in Hokkaido, Japan.

In this study, we investigated the regional differences in the composition of farm bulk milk produced at three different dairy areas in Hokkaido, Japan. A field survey was conducted at Central, Tokachi, and North areas of Hokkaido, three or four times a year. At each farm, an interview questionnaire for farm basal data was conducted, and 500 ml of bulk tank milk sample was obtained. Fatty acid composition, and vitamin and carotenoid concentrations in the milk samples were determined. In Central and Tokachi areas, corn silage was used as the main forage. In North area, fresh herbage was the dominant feed in the summer season, and grass hay was the main feed in the winter season. Discriminant analysis revealed that the composition of milk samples differed among the areas and seasons. Milk from Central and Tokachi areas contained a higher ratio of linoleic acid compared with that from North area, but there were only slight differences in the composition of milk between Central and Tokachi areas. The concentrations of carotenoids and α-tocopherol were higher in samples from North area and the ratios of trans-vaccenic acid and conjugated linoleic acid were higher in the summer season than in the indoor season.

Prediction of oral intake recovery for inpatients with aspiration pneumonia by videoendoscopic evaluation using the Hyodo-Komagane score in Japan.

OBJECTIVE: To verify the validity of the prediction of oral intake recovery for inpatients with aspiration pneumonia using the Hyodo-Komagane score. BACKGROUND: Patients admitted for treatment of aspiration pneumonia sometimes have difficulty in resuming oral intake due to decreased swallowing function. Predicting whether the swallowing function will recover enough to achieve oral ingestion at discharge is an important factor in developing a treatment strategy. No studies have investigated the prediction of oral intake recovery using videoendoscopic examination. METHODS: Subjects were 65 patients who were admitted to an acute care hospital for the treatment of aspiration pneumonia. The patients were divided into two groups, the oral feeding group and the tube feeding group, according to their oral intake status at discharge or transfer. Logistic regression analysis was performed using the condition that tube feeding was not required as an objective variable and the items with significant differences between the two groups as explanatory variables. Additionally, the receiver operating characteristic curve was used to identify patients who could take food orally at discharge. RESULTS: The odds ratios for the Hyodo-Komagane score and the pharyngeal clearance score were 1.485 and 3.379, respectively. When the cut-off values of the Hyodo-Komagane score and the pharyngeal clearance score were 6 and 1, the sensitivity was 0.88 and 0.91, and the specificity was 0.64 and 0.70, respectively. CONCLUSION: The Hyodo-Komagane score and especially the pharyngeal clearance score are useful indices to predict oral intake recovery for inpatients with aspiration pneumonia.

Relationship between oral intake level and oral health assessment tool scores in the convalescent ward.

PURPOSE: To examine the relationship between oral intake function and oral health status in convalescent inpatients. METHODS: Subjects were 222 patients admitted to a convalescent hospital between 1 January and 30 June 2018. Investigation items were age, sex, causative disease, body mass index, functional oral intake scale (FOIS), functional independence measure, occlusal contact, assistance with oral cleaning, and oral health assessment tool (OHAT) scores. Multiple regression analysis was performed with FOIS as the dependent variable, and investigation items were related to FOIS as independent variables. RESULTS: Results of multiple regression analysis for all patients suggested that saliva and denture scores were significantly associated with FOIS. However, analysis excluding non-oral feeding patients did not show a significant association between FOIS and OHAT scores. CONCLUSION: The results of this study suggest that oral health status is associated with oral intake function. In addition, the oral health status of inpatients may be strongly related to whether or not they are eating orally. Therefore, it is necessary to take good care of oral health in non-oral feeding patients in the convalescent ward.

Effects of grazing adaptation on intake, ruminal fermentation, blood metabolites, and body weight change in dairy cows after turning out to pasture in early spring.

This study investigated the effect of adaptation to grazing in early spring on herbage intake, ruminal fermentation parameters, blood metabolite concentrations, and body weight change in dairy cows. The experiment was conducted on eight rumen-cannulated non-lactating cows in the early spring period. Four cows were adapted to grazing by stocking for 4 hr for 1 week (ADP group). The other cows were kept in a barn during the period (CON group). Then, both groups of cows were stocked together throughout a day on a 1 ha pasture for 3 weeks (experimental period). In the first week of the experimental period, compared to the CON group, the ADP group had a higher herbage intake, ruminal NH3 -N and total VFA concentration, and blood urea concentration, but the NEFA concentration was lower in the ADP group (p < .01). During the subsequent weeks, there were little differences in ruminal fermentation parameters and blood metabolites. Cows in the ADP group maintained their body weight, but cows in the CON group lost 60 kg of body weight in the first week of the experimental period.

Glucose transporter 4 mediates LPS-induced IL-6 production in osteoblasts under high glucose conditions.

PURPOSE: Diabetes causes hyperglycemic disorders due to insufficient activity of insulin, and it also increases blood glucose level. Recent studies have reported the relationship between diabetes and periodontal disease. Periodontitis is advanced by inflammatory cytokines stimulated with LPS. The purpose of this study was to investigate the effects of hyperglycemia on the expression of inflammatory cytokines induced by LPS in osteoblasts. METHODS: Cells were cultured for 7 and 14 days in the presence or absence of LPS and glucose. The expression mRNA level of IL-6, RANKL and OCN was determined using real-time PCR. The protein expression of IL-6 and RANKL was also measured using ELISA. RESULTS: LPS and glucose increased the mRNA expression of IL-6, coupled with a decrease in the mRNA expression of OCN, which is associated with IL-6 and glucose. It also increased the protein expression of IL-6 compared to LPS. However, LPS+Glucose did not affect the mRNA and protein expression of RANKL. Furthermore, GLUT4 inhibitor, WZB117, blocked the stimulatory effect of glucose on LPS-induced IL-6 mRNA expression. WZB117 did not affect LPS-reduced OCN mRNA expression. CONCLUSION: These results suggest that high glucose levels increase LPS-induced IL-6 expression mediated by GLUT4.

Synthesis of the perovskite-type oxyfluoride AgTiO2F: an approach adopting the HSAB principle.

A synthetic approach for oxyfluorides involving the hard and soft acids and bases (HSAB) principle was examined. Using AgF composed of the Ag+ ion as a soft acid and F- as a hard base, we attempted to synthesize an oxyfluoride, AgTiO2F, that included the O2- ion as a softer base than the F- ion and the Ti4+ ion as a harder acid than the Ag+ ion. Consequently, a perovskite (Pv)-type oxyfluoride AgTiO2F was synthesized by a solid-state reaction under ambient pressure and under high pressure, and a heat treatment at 1000 °C for 30 min under a pressure of 4 GPa produced the Pv-type phase with minimal impurity phases. The lack of an optical second harmonic generation (SHG) response and the result of Rietveld refinement indicated that the compound is centro-symmetric and shows the anti-phase tilt of Ti(O, F)6 octahedra along the c-axis on the basis of the space group I4/mcm. O/F ordering on the anion site was not clarified. The phase stability of a Pv-type AgTiO2F is discussed in terms of the HSAB principle and the thermodynamics in the formation of the Pv-type phase by comparing KTiO2F and NaTiO2F. AgTiO2F has a light yellow color and a band gap energy of 2.8 eV in the visible region, which originates from the covalent bonding between the soft cation Ag+ and O2- as a softer anion than F-. We propose that the HSAB principle is useful for selecting a cation for the synthesis of oxyfluorides.

Relationship between the timing of the first postpartum ovulation and antral follicle counts in Holstein cows.

BACKGROUND: The timing of the first postpartum ovulation is an important factor affecting the timing of estrous resumption in dairy cows. The first postpartum ovulation is delayed in cows producing large amounts of milk with an intensive negative energy balance. The antral follicle count (AFC) and serum anti-Müllerian hormone concentrations are known to be indicators of the ovarian reserve, which is the number and quality of follicles left in a pair of ovaries and known as an indicator of female fertility. Cows with higher AFC have been proven to show higher pregnancy rate and shorter calving to conception intervals; however, the relationship between the timing of the first postpartum ovulation and ovarian reserve remains unclear. Therefore, this study examined the relationships between postpartum follicular dynamics, the ovarian cycle, nutritional status, and ovarian reserve. METHODS: Transrectal ultrasonography was conducted from calving to 70-120 days in milk (DIM) in 26 cows to monitor AFC, follicular dynamics and the ovarian cycle. Body weight (BW) and milk yield were used as indicators of nutritional status. RESULTS: The first postpartum ovulation was significantly later in cows with low AFC (< 25) than in those with high AFC (≥25), while changes in BW from calving to the nadir and milk production were similar in both groups. The present results also suggested that cows with low AFC and a delayed first postpartum ovulation had a shorter first ovarian cycle after the first postpartum ovulation. The mean DIM of the first postpartum artificial insemination (AI) and days open (days from calving to AI with which pregnancy was achieved) were similar in high and low AFC groups. CONCLUSIONS: The first postpartum ovulation was significantly earlier in cows with high AFC than in those with low AFC. The assumed reason for this result was higher sensitivity to luteinizing hormone and larger androstenedione and estradiol production in follicles in high AFC cows. Therefore, cows with high AFC may be more fertile than those with low AFC while their milk production increase and BW decrease; it means they are in negative energy balance. (340/350 words).

Effects of bolus consistency and reclining position on kinematic swallowing events in analysis using 320-row area detector computed tomography.

This study used 320-row area detector computed tomography (320-ADCT) to determine whether kinematic swallowing events and bolus movement through the oropharynx are affected by bolus consistency and angle of recline. Fourteen healthy adults (4 men, 10 women; age, 22-90 years) underwent 320-ADCT assessment during three 10-mL barium swallow tests, with honey-thick liquid at 60° recline (60°thick), thin liquid at 60° recline (60°thin), and thin liquid at 45° recline (45°thin). The times of swallowing events were measured and compared among the different tests. Bolus propulsion, onset time of true vocal cord (TVC) closure, and upper esophageal sphincter opening were significantly earlier for 60°thin than for 60°thick. Onset time did not significantly differ between 60°thin and 45°thin; however, greater variability was noted for onset of TVC closure with 45°thin, as the TVC started to close before onset of swallowing in 30% of participants. Modulation of TVC closure depends on bolus transport in different reclining positions. The 45° reclining position elicited pre-swallow TVC closure in some participants, which suggests that excessive recline can increase perceived risk of airway invasion during swallowing.

The Periodontopathic Bacterium Fusobacterium nucleatum Induced Proinflammatory Cytokine Production by Human Respiratory Epithelial Cell Lines and in the Lower Respiratory Organs in Mice.

BACKGROUND/AIMS: The most prevalent infectious disease, chronic periodontitis which leads to alveolar bone destruction and subsequent tooth loss, develops due to proinflammatory cytokine production induced by periodontopathic bacteria. Chronic obstructive pulmonary disease (COPD), a non-infectious disease, is the third leading cause of death globally. This condition exacerbates frequently, and which is attributable to proinflammatory cytokine production induced by infection by respiratory microorganisms such as Streptococcus pneumoniae. Although a positive association has recently been revealed between chronic periodontitis and COPD, how periodontitis contributes to the pathogenesis of COPD remains unclear. Therefore, we hypothesized that some periodontopathic bacteria are involved in the exacerbation of COPD through the induction of proinflammatory cytokine production by respiratory epithelial cells. In this connection, COPD develops in the airways; however, because most periodontopathic bacteria are anaerobic, they are unlikely to exhibit stable virulence in the lower respiratory organs in humans. Hence, we aimed to elucidate whether exposure to heat-inactivated periodontopathic bacteria induces proinflammatory cytokine production by several human respiratory epithelial cell lines and in the lower respiratory organs and serum in mice. METHODS: Real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) were used to investigate in vitro induction by heat-inactivated periodontopathic bacteria and S. pneumoniae for mRNA expression and protein production of interleukin (IL)-8 and IL-6 by human respiratory epithelial cell lines. ELISA was also used to determine in vivo induction of cytokine production in the lower respiratory organs and serum of intratracheally heat-inactivated Fusobacterium nucleatum-inoculated mice. RESULTS: Some, but not all, periodontopathic bacteria, especially F. nucleatum, strongly induced IL-8 and IL-6 production by BEAS-2B bronchial epithelial cells. In addition, F. nucleatum induced IL-8 production by A549 alveolar epithelial cells as well as IL-8 and IL-6 production by Detroit 562 pharyngeal epithelial cells. Furthermore, F. nucleatum induced considerably higher cytokine production than S. pneumoniae. This was also observed in the entire lower respiratory organs and serum in mice. CONCLUSION: Exposure to increased number of F. nucleatum potentially induces proinflammatory cytokine production by human bronchial and pharyngeal epithelial cells, which may trigger exacerbation of COPD.