[The effectiveness of the complete lateral position method in elderly patients with severe dysphagia].

AIM: This study aimed to clarify the effectiveness of using the complete lateral position method to treat elderly patients with severe dysphagia. METHODS: We enrolled 47 patients >65 years of age who had been diagnosed with severe dysphagia using a video endoscopic examination of swallowing at Hida City Hospital between February 1, 2015, and October 31, 2017. We collected and analyzed data pertaining to patient characteristics, the onset of aspiration pneumonia, and treatment outcomes. RESULTS: Although all patients had severe dysphagia, adopting the complete lateral position method enabled 25 patients (53.2%) to safely perform oral ingestion and be discharged home or to a nursing home. Thirteen (52.0%) of the patients who were discharged were able to safely receive oral intake in the sitting position again. In addition, the serum albumin level and Barthel index were significantly improved. In the patients whose condition worsened due to senility, the fasting period in the complete lateral potion group was significantly shorter than in the control group (7.3 days vs. 17.3 days). CONCLUSIONS: The present study showed that the complete lateral position method enabled safe oral ingestion in elderly patients with severe dysphagia. Safe oral ingestion contributed to improved nutrition and rehabilitation. The complete lateral position method is easy to assume and does not require the use of special appliances or techniques. We believe that the complete lateral position method will prove to be a breakthrough approach in the care of elderly patients with severe dysphagia.

A PRELIMINARY STUDY OF INCREASING SELF-EFFICACY IN JUNIOR HIGH SCHOOL STUDENTS: INDUCED SUCCESS AND A VICARIOUS EXPERIENCE.

Bandura's self-efficacy source hypothesis was examined by testing whether success and a vicarious experience of success would enhance self-efficacy among 159 7th graders (81 boys, 78 girls). Unknown to themselves or their classmates, 20 students (Success condition) were presented with easier anagram tasks, allowing them to outperform their 60 classmates (Control condition). The Success and Control students had been paired with classmates (Cheerers; Vicarious condition) who were to cheer on their partners during the task. The participants rated their self-efficacy for the anagram task before and after the performance. The results showed that successful performance significantly promoted the self-efficacy of Success students. However, the cheerers of Success students did not have increased self-efficacy through the vicarious success experience.

Large blood pressure variability aggravates arteriolosclerosis and cortical sclerotic changes in the kidney in hypertensive rats.

BACKGROUND: It has been shown that increased short-term blood pressure (BP) variability (BPV) aggravates hypertensive cardiac remodeling in spontaneously hypertensive rats (SHRs) through a cardiac angiotensin II (angII) system. However, little was known about the renal damage induced by large BPV. Thus, histological changes in the kidney were investigated and candesartan, an angII type 1 receptor blocker (ARB), was also examined to see whether it would prevent renal damage in SHRs with large BPV. METHODS AND RESULTS: Bilateral sinoaortic denervation (SAD) was performed in SHRs to create a model of a combination of hypertension and large BPV. SAD increased BPV without changing mean BP. Seven weeks later, SAD induced patchy, wedge-shaped, focal sclerotic lesions accompanied by interstitial fibrosis and ischemic changes of glomeruli and tubules in the cortex. The pre-glomerular arterioles adjacent to the sclerotic lesions showed arteriolosclerotic changes associated with vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion. Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also cortical sclerotic lesions in SHRs with SAD without changing BPV. CONCLUSIONS: Large BPV aggravates pre-glomerular arteriolosclerosis, which results in the cortical sclerotic changes in SHRs through a local angII-mediated mechanism. This study raised the possibility that ARB is useful for renal protection in patients who have a combination of hypertension and increased BPV.

Blood pressure variability activates cardiac mineralocorticoid receptor and induces cardiac remodeling in hypertensive rats.

BACKGROUND: Hypertensive patients with large blood pressure variability (BPV) have aggravated target organ damage. Because the aldosterone/mineralocorticoid receptor (MR) system is a possible mechanism of hypertensive organ damage, we investigated in spontaneously hypertensive rats (SHRs) whether a specific MR blocker, eplerenone, would prevent BPV-induced aggravation of hypertensive cardiac remodeling. METHODS AND RESULTS: A rat model of a combination of hypertension and large BPV was created by performing bilateral sinoaortic denervation (SAD) in SHRs. SAD increased BPV without changing mean BP. SAD induced perivascular macrophage infiltration and aggravated myocardial fibrosis and cardiac hypertrophy, resulting in LV systolic dysfunction. Immunohistostaining revealed SAD-induced translocation of MRs into the nuclei (ie, MR activation) of the intramyocardial arterial medial cells and cardiac myocytes. SAD increased phosphorylation of p21-activated kinase1 (PAK1), a regulator of MR nuclear translocation. Chronic administration of a subdepressor dose of eplerenone prevented MR translocation, macrophage infiltration, myocardial fibrosis, cardiac hypertrophy, and LV dysfunction, while not affecting BPV. Circulating levels of aldosterone and cortisol were not changed by SAD. CONCLUSIONS: Eplerenone inhibited the aggravation of cardiac inflammation and hypertensive cardiac remodeling, and thereby prevented progression of LV dysfunction in SHRs with large BPV. This suggests that the PAK1-MR pathway plays a role in cardiac inflammation and remodeling induced by large BPV superimposed on hypertension, independent of circulating aldosterone.

Temperature Dependence of Metals Accumulation and Removal Kinetics by Arabidopsis halleri ssp. gemmifera.

Cadmium (Cd), which is present in zinc (Zn) ore, is a toxic metal and causes contamination globally. Phytoremediation is a promising technology for the remediation of sites with low and moderate contamination. Temperature is an important factor in phytoremediation because it has an impact on both plant biomass and the accumulation of heavy metals. However, little is known about the influence of temperature on heavy metal accumulation by the Cd and Zn hyperaccumulator Arabidopsis halleri ssp. gemmifera. The effect of temperature on the distribution of Cd and Zn in A. halleri ssp. gemmifera and the mechanism of metal removal from solution were investigated in this study. Our results showed that the temperature dependence of the distribution of Cd and Zn in the plant was different, which may suggest that the mechanisms of xylem loading were different between Cd and Zn. Although Cd and Zn have partially similar transport pathways, the removal kinetics based on the first-order reaction rate constant revealed that the temperature which maximized rate of absorption was different between Cd and Zn. This study suggests a potential for efficient Cd phytoextraction using A. halleri ssp gemmifera in Cd and Zn co-existing environments.

Bayesian network highlights the contributing factors for efficient arsenic phytoextraction by Pteris vittata in a contaminated field.

Phytoextraction is a low-cost and eco-friendly method for removing pollutants, such as arsenic (As), from contaminated soil. One of the most studied As hyperaccumulators for soil remediation include Pteris vittata. Although phytoextraction using plant-assisted microbes has been considered a promising soil remediation method, microbial harnessing has not been achieved due to the complex and difficult to understand interactions between microbes and plants. This problem can possibly be addressed with a multi-omics approach using a Bayesian network. However, limited studies have used Bayesian networks to analyze plant-microbe interactions. Therefore, to understand this complex interaction and to facilitate efficient As phytoextraction using microbial inoculants, we conducted field cultivation experiments at two sites with different total As contents (62 and 8.9 mg/kg). Metabolome and microbiome data were obtained from rhizosphere soil samples using nuclear magnetic resonance and high-throughput sequencing, respectively, and a Bayesian network was applied to the obtained multi-omics data. In a highly As-contaminated site, inoculation with Pseudomonas sp. strain m307, which is an arsenite-oxidizing microbe having multiple copies of the arsenite oxidase gene, increased As concentration in the shoots of P. vittata to 157.5 mg/kg under this treatment; this was 1.5-fold higher than that of the other treatments. Bayesian network demonstrated that strain m307 contributed to As accumulation in P. vittata. Furthermore, the network showed that microbes belonging to the MND1 order positively contributed to As accumulation in P. vittata. Based on the ecological characteristics of MND1, it was suggested that the rhizosphere of P. vittata inoculated with strain m307 was under low-nitrogen conditions. Strain m307 may have induced low-nitrogen conditions via arsenite oxidation accompanied by nitrate reduction, potentially resulting in microbial iron reduction or the prevention of microbial iron oxidation. These conditions may have enhanced the bioavailability of arsenate, leading to increased As accumulation in P. vittata.

The Complete Lateral Position Method Reduced the Mortality Rate among Elderly Patients with Severe Dysphagia.

Objective This study aimed to validate the efficacy of the complete lateral position method among elderly patients with severe dysphagia. Methods We enrolled 103 patients >65 years old who were diagnosed with severe dysphagia via the fiberoptic endoscopic examination of swallowing and were treated with the complete lateral position method at Hida Municipal Hospital between February 1, 2015, and October 31, 2020. Patients treated with the complete lateral position method were included in the lateral position group, and patients treated with conventional methods were included in the control group. The mortality rates were then compared between the lateral position and control groups. Results All patients had severe dysphagia. However, the complete lateral position method significantly decreased the mortality rate in the lateral position group compared with the control group (64.7% vs. 38.8%; p<0.01). In the lateral position group, approximately 55.6% of patients who were discharged from the hospital were able to safely take food orally again in the sitting position. Furthermore, the complete lateral position method significantly shortened the fasting period and improved the prognosis in patients whose condition had progressed due to senility in the lateral position group compared with the control group (17.3 vs. 8.8 days, p<0.05; 28.4 vs. 67.5 days, p<0.05) Conclusion The complete lateral position method facilitated safe oral ingestion among elderly patients with severe dysphagia. Furthermore, safe oral ingestion decreased the mortality rate and shortened the fasting period at the end of life. The method is easy to implement and does not require the use of special devices or techniques. It can therefore be a useful approach in the care of elderly patients with severe dysphagia.

Determination of hydrogen concentration in solids by transmission ERDA under nuclear-elastically enhanced recoiling of H by 8 and 9 MeV He.

Hydrogen concentrations in thin self-supporting samples of polyphenylene sulfide (PPS) and muscovite have been determined by nuclear-elastic recoil detection analysis (ERDA) of transmission layout. The analysis procedure is based only on the database of stopping power and recoil cross section for material analysis, without using any reference sample of known H content. For the PPS sample, the determined value of(2.87±0.26)×1022H cm-3is in good agreement with the calculated value of3.01×1022H cm-3. For the muscovite sample, the H concentration originating each from bound water and absorbed water is uniform over the entire thickness of the sample. The determined concentration(9.43±0.75)×1021H cm-3of the muscovite agrees excellently with the value of9.36×1021H cm-3obtained from other quantitative analyses typically applied for minerals. The present results demonstrate the capability of accurate determination of H contents in materials and minerals by transmission ERDA.

Effects of Growth Stage and Cd Chemical Form on Cd and Zn Accumulation in Arabidopsis halleri ssp. gemmifera.

Cadmium is a hazardous heavy metal and causes contamination globally. Phytoremediation can potentially become a low-cost and eco-friendly technique for mitigating Cd contamination. Arabidopsis halleri ssp. gemmifera hyper-accumulates Cd and Zn, and may be used to remediate Cd-contaminated sites. However, few studies have focused on Cd accumulation by A. halleri ssp. gemmifera. Herein, we demonstrate the accumulation of Cd by A. halleri ssp. gemmifera. The biomass, Cd, and Zn concentration of the plant increased in the 103 days of experimentation. Cd concentration of soil significantly decreased compared to its initial concentration (≈10%). The material balance of Cd uptake by plant and Cd decrement from soil ranged from 63.3% to 83.7% in each growth stage. Analysis indicated that the water-eluted and exchangeable forms of Cd were stable during the experiment. However, Cd concentration extracted with 0.1 M HCl decreased (25% of initial), and this fraction was not bioavailable. The study exhibits the mass balance of Cd between plant uptake and decrement from the soil and the changes in the chemical form of Cd during stages of A. halleri ssp. gemmifera cultivation.

Depth resolution of transmission ERDA for H in Al under nuclear-elastically enhanced recoiling of H by 8 MeV He.

Using stacked samples of Al foil and H-containing resin film, we have carried out elastic recoil detection analysis with transmission layout (T-ERDA) to investigate the depth resolution in the measurements of H distribution in Al. For narrow and wide acceptance conditions of the detector, the depth resolutions of 1.5-4.9µm at several depths in Al of 50 and 80µm thicknesses have been determined for incidence of 8 MeV4He. While the main factor to degrade the depth resolution is the energy straggling of recoil H for narrow acceptance conditions, it is the extended low-energy side of the H spectrum for wide acceptance conditions. The knowledge obtained in this work is useful for analysis of 3D images of H distribution measured by T-ERDA, for example, future analysis of minerals or natural glass samples to determine abundances and distributions of water or OH in the samples.

Increased medial laxity of the elbow in preadolescent baseball players with or without medial elbow apophysitis.

BACKGROUND: Medial elbow apophysitis is a traction apophysitis observed in the medial epicondyle of the elbow in preadolescent baseball players. The purpose of this study was to determine the relationship between medial elbow apophysitis and elbow valgus instability in preadolescent baseball players. METHODS: The participants were classified into a control group and an injury group; the injury group included participants diagnosed with a medial elbow injury (inclusion criteria were only symptoms of the elbow joint or positive findings on physical examinations, or both). Elbow valgus instability was assessed by measuring the differences in ulnohumeral joint gapping width, with and without gravity stress induced by weight loading of the forearm using ultrasonography. RESULTS: The control and injury groups consisted of 81 and 23 preadolescent baseball players, respectively. In the throwing elbow, valgus instability in the injury group was significantly greater than that in the control group (1.07 vs. 0.57 mm, P = .001). In the non-throwing elbow, valgus instability in the injury group was significantly greater than that in the control group (0.57 vs. 0.37 mm, P = .011). The area under the curve for valgus instability of the throwing elbow was 0.89 mm (95% confidence interval, 0.64-0.77), and the cut-off value for elbow pain appearance was 0.80 mm. CONCLUSION: The increased elbow valgus instability in the injury group was associated with a medial elbow injury. For the elbow valgus instability of the non-throwing side in the injury group, we considered that players with medial elbow apophysitis inherently have elbow laxity.

Tumor necrosis factor-alpha accelerates apoptosis of steatotic hepatocytes from a murine model of non-alcoholic fatty liver disease.

Non-alcoholic steatohepatitis (NASH) develops in a subset of patients with non-alcoholic fatty liver disease (NAFLD), but the exact mechanisms involved in the progression of NAFLD to NASH remain poorly understood. We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in the apoptosis of hepatocytes that is related to the severity of NASH. We separated primary hepatocytes from the NAFLD liver caused by a high-fat diet. The production of intracellular reactive oxygen species was increased in steatotic hepatocytes, which were also sensitive to TNF-alpha. This factor induced significant apoptosis through the signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) pathway. We describe here a novel culture model of steatotic hepatocytes separated from the NAFLD liver, and demonstrate that TNF-alpha induces their apoptosis in vitro.

Supratentorial glioblastoma treated with radiotherapy: use of the Radiation Therapy Oncology Group recursive partitioning analysis grouping for predicting survival.

OBJECTIVE: This study aimed to evaluate the usefulness of recursive partitioning analysis model established by the Radiation Therapy Oncology Group for predicting the survival of patients with supratentorial glioblastoma treated with radiotherapy and to determine prognostic factors for the subgroups of this prognostic model. METHODS: A total of 108 glioblastoma patients treated with radiotherapy between January 1987 and December 2005 were retrospectively reviewed. Recursive partitioning analysis classes III, IV, V and VI included 8, 29, 32 and 39 patients, respectively. These classes were divided into two subgroups: a good prognostic group containing classes III-IV and a poor prognostic group containing classes V-VI. The median radiation dose was 60 Gy. Seventy-five patients received chemotherapy and/or immunotherapy. RESULTS: The overall survival differed significantly among classes III, IV, V and VI, with median survival times of 34, 15, 11 and 7 months, respectively. Among the good prognostic group, patients with basal ganglia invasion showed poorer survival outcomes than patients without basal ganglia invasion. Among the poor prognostic group, patients with tumor sizes of <5 cm and patients treated with nimustine hydrochloride showed better survival outcomes than those with tumor sizes of > or =5 cm and those without treatment with nimustine hydrochloride, respectively. CONCLUSIONS: This study confirms the prognostic value of the recursive partitioning analysis grouping. Basal ganglia invasion could be a useful predictive factor for survival in the good prognostic group, whereas tumor size and treatment with nimustine hydrochloride could be useful predictive factors in the poor prognostic group.

Lipopolysaccharide triggered TNF-alpha-induced hepatocyte apoptosis in a murine non-alcoholic steatohepatitis model.

BACKGROUND/AIMS: Endogenous gut-derived bacterial endotoxins have been implicated as an important cofactor in the pathogenesis of liver injury, although their contribution to the progression of non-alcoholic steatohepatitis (NASH) remains unclear. METHODS: Male C57BL/6 mice were fed a methionine-choline-deficient (MCD) diet or a standard diet for 17 days, following which they were injected with lipopolysaccharide (LPS) intraperitoneally and sacrificed after 6h. In an in vitro experiment, RAW264.7 cells, a mouse macrophage cell line, and primary mouse hepatocytes were co-treated with hydrogen peroxide (H(2)O(2)) and LPS or tumour necrosis factor (TNF)-alpha. RESULTS: Compared to the control mice, LPS treatment significantly increased hepatic TNF-alpha production in MCD mice. LPS also significantly increased TUNEL-positive cells, which were especially observed in the perivenular area. The apoptotic change was inhibited by co-treatment with a neutralizing anti-mouse TNF receptor antibody or pentoxifylline. In an in vitro experiment, treatment with H(2)O(2) synergistically enhanced LPS-induced TNF-alpha production in RAW264.7 cells, accompanied by an up-regulation of CD14 mRNA. Moreover, co-treatment with TNF-alpha- and H(2)O(2)-induced apoptosis in primary hepatocytes, although neither TNF-alpha nor H(2)O(2) could do so independently. CONCLUSIONS: LPS up-regulated TNF-alpha production, which induced hepatocyte apoptosis in a murine NASH model. LPS may play a key role in the pathogenesis of NASH.

Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are the hepatic manifestation of metabolic syndrome. However, its therapeutic strategy has not been established. Recently, an angiotensin II type 1 receptor blocker, telmisartan (Tel), has received a great deal of attention as a therapeutic tool for metabolic syndrome. The aim of this study was to investigate the efficacy and mechanisms of Tel on a murine NASH model. METHODS: C57BL/6 mice were fed a methionine- and choline-deficient high-fat diet (MCDHF) or a standard diet with/without the administration of Tel (10 mg/kg/day) for 8 weeks. RESULTS: MCDHF feeding induced marked steatohepatitis with macrophage infiltration. Tel attenuated liver steatosis with decreased hepatic triglycerides (P<0.05) and fibrogenesis with decreased type I collagen and transforming growth factor-beta1 mRNA expressions (P<0.05). Tel also suppressed the infiltration of macrophages into the liver and decreased hepatic monocyte chemoattractant protein-1 and its receptor (CC-chemokine receptor 2; CCR2) mRNA expressions, especially CCR2. In vitro, Tel suppressed CCR2 expression, which was induced by low-density lipoprotein. The size of adipocyte in visceral fat tissue was reduced with an increased serum adiponectin concentration in the Tel group. CONCLUSIONS: In this study, we revealed that Tel attenuated steatohepatitis progression by suppressing the macrophage infiltration into the liver. Tel also affected the reduction of adipocyte size and elevation of serum adiponectin. Tel might serve as a new therapeutic strategy for NASH.

Large blood pressure variability and hypertensive cardiac remodeling--role of cardiac inflammation.

An increase in short-term blood pressure (BP) variability is a characteristic feature of hypertensive patients, especially in elderly patients. There is increasing evidence that large BP variability aggravates hypertensive target organ damage and is an independent risk factor for the cardiovascular events in elderly hypertensive patients. However, little is known about the underlying mechanism. We have created a rat model of a combination of hypertension and large BP variability by performing sinoaortic denervation (SAD) in spontaneously hypertensive rats (SHRs). SAD aggravates left ventricular (LV)/myocyte hypertrophy and myocardial fibrosis to a greater extent and impairs LV systolic function without changing mean BP in SHR. SAD upregulates cardiac monocyte chemoattractant protein-1 and transforming growth factor-beta, and induces macrophage infiltration. Cardiac angiotensinogen expression is increased and the angiotensin II type 1 receptor is activated by SAD. A subdepressor dose of angiotensin receptor blocker abolishes SAD-induced inflammatory changes and cardiac remodeling and subsequently prevents systolic dysfunction in SHR+SAD. Accordingly, it is suggested that cardiac inflammation via activation of the cardiac angiotensin II system would play a role in the aggravation of cardiac remodeling and dysfunction in hypertensives with large BP variability.

[A case of CNS metastasis from gastric MALT lymphoma].

Recently, the incidence of primary CNS lymphoma (PCNSL) is increasing. Metastatic CNS lymphoma occurs much less than PCNSL. We report the case of a 53-year-old man who presented with CNS metastasis from gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The symptoms at the time of diagnosis were dizziness and aphasia. MRI revealed a left parietal lobe tumor with a large peritumoral edema. About 4 years ago, he had suffered from gastric MALT lymphoma with a high grade component. Eradication of Helicobacter pylori led to remission of the disease 18 months after the treatment. From his past history, the brain tumor was suspected of being a metastatic lymphoma. Stereotactic biopsy revealed diffuse large B-cell lymhoma. Histopathological findings including lymphocytic subsets were almost identical between the primary gastric MALT lymphoma and metastatic brain lymphoma. Complete remission was obtained by repeated high-dose methotrexate chemotherapy. There has been no recurrence for 5 years without additional therapy. This case is probably the first report of CNS metastasis from gastric MALT lymphoma.

[A case of hepatocellular carcinoma rapidly progressing after percutaneous radiofrequency ablation successfully treated with low-dose 5-FU and CDDP].

A 65-year-old Japanese man was admitted to our hospital for treatment of hepatocellular carcinoma (HCC) with alcoholic liver cirrhosis. He had been treated by transarterial chemoembolization (TACE) in another hospital before this admission. In our hospital, percutaneous radiofrequency ablation (PRFA) to HCC (2.5 cm diameter) in hepatic S8 was done, and the tumor was ablated completely with the treated margin. After 8 months of the PRFA procedure, abdominal CT revealed diffused-type HCC located in contact with the post RFA area and was diagnosed as a local recurrence of HCC. He was then treated with hepatic arterial infused chemotherapy, low-dose 5-FU and CDDP (FP); one course consisted of (5-FU 250 mg/day + CDDP 10 mg/day) x 5 days/w x 4 wks using a port-infusion system. He was treated with 3 courses of low-dose FP, and the diffuse-type HCC was completely diminished. No recurrence was seen 22 months after chemotherapy. Although rapidly progressing recurrent HCC after PRFA is potentially fatal and useful treatments have only rarely been reported, hepatic arterial infusion chemotherapy including low-dose FP should be considered a possible treatment.

Expression of silent information regulator 2 homolog 1 (SIRT1) in periapical granulomas.

Silent information regulator 2 homolog 1 (SIRT1) inhibits oxidative injury and has anti-inflammatory effects. SIRT1 may be involved in healing of periapical periodontitis; however, SIRT1 expression in periapical periodontitis lesions has not been investigated. This study evaluated SIRT1 expression and a marker of oxidative stress-8-hydroxy-2'-deoxyguanosine (8-OHdG)-in periapical granulomas. First, we used real-time polymerase chain reaction to determine whether U-937 monocytes express SIRT1. U-937 cells treated with the SIRT1 activator resveratrol exhibited the highest SIRT1 mRNA level after 6-h incubation. By contrast, treating cells with the SIRT1 inhibitor sirtinol returned SIRT1 expression level to that of the control. In addition, immunocytochemical analysis using cytospin specimens showed that U-937 cells co-expressed SIRT1 and Ki-67. Dual-color immunofluorescence imaging showed that round cells in periapical granulomas co-expressed SIRT1 and 8-OHdG; however, neither was expressed in healthy gingival tissues. The number of 8-OHdG-expressing cells was significantly greater than the number of SIRT1-expressing cells. Our findings suggest that macrophages express SIRT1 and that wound healing in periapical granulomas is enhanced by a SIRT1-mediated reduction in the level of oxidative stress.

Connexin 43 expression in satellite glial cells contributes to ectopic tooth-pulp pain.

Pulpitis often causes referred pain in opposing teeth. However, the precise mechanism underlying ectopic pain associated with tooth-pulp inflammation remains unclear. We performed the present study to test the hypothesis that functional interactions between satellite glial cells (SGCs) and trigeminal ganglion (TG) neurons are involved in ectopic orofacial pain associated with tooth-pulp inflammation. Digastric muscle electromyograph (D-EMG) activity elicited by administration of capsaicin into the upper second molar pulp (U2) was analyzed to evaluate noxious reflex responses. D-EMG activity was significantly increased in rats with lower first molar (L1) inflammation relative to saline-treated rats. Significantly increased expression of glial fibrillary acid protein (GFAP), a marker of activated glial cells, and connexin 43 (Cx43), a gap-junction protein, was observed in activated SGCs surrounding U2-innervating TG-neurons after L1-pulp inflammation. Daily administration of Gap26, a Cx43-inhibiting mimetic peptide, into the TG significantly suppressed capsaicin-induced D-EMG activity enhancement and reduced the percentage of fluorogold-labeled (U2-innervated) cells that were surrounded by GFAP-immunoreactive (IR) and Cx43-IR cells after L1-pulp inflammation. These findings indicate that tooth-pulp inflammation induces SGC activation and subsequent spread of SGC activation in the TG via Cx43-containing gap junctions. Thus, remote neuron excitability becomes enhanced in the TG following tooth-pulp inflammation, resulting in ectopic tooth-pulp pain in the contralateral tooth.