Regional Inequalities in Oral Frailty and Social Capital.

INTRODUCTION: Oral frailty leads to poor nutritional status, which, in turn, leads to frailty. This cross-sectional study aimed to determine regional differences in the prevalence of oral frailty and to identify factors associated with oral frailty using 3-level multilevel models. METHODS: This study comprised 165,164 participants aged ≥65 y without long-term care requirements in the Japan Gerontological Evaluation Study. The dependent variable was oral frailty, which was calculated based on age, number of teeth, difficulty in eating tough foods, and choking. The individual-level independent variables included sociodemographics, present illness, social participation, frequency of meeting friends, and social capital. The local district-level independent variable was social capital (n = 1,008) derived from exploratory factor analyses. The municipality-level independent variable was population density (n = 62). Three-level multilevel Poisson regression analysis was performed to calculate the prevalence ratios (PRs). RESULTS: The prevalence of oral frailty in municipalities ranged from 39.9% to 77.6%. Regarding district-level factors, higher civic participation was significantly associated with a lower probability of oral frailty. At the municipality level, the PR of the rural-agricultural area was 1.17 (95% confidence interval, 1.11-1.23) (reference: metropolitan). CONCLUSION: These results highlight the usefulness of oral frailty prevention measures in encouraging social participation in rural areas. KNOWLEDGE TRANSFER STATEMENT: The results of the present study showed regional differences in oral frailty. In particular, rural-agricultural areas show higher prevalence rates of oral frailty than those in metropolitan cities. Promoting measures of social participation among older adults may help prevent oral frailty in rural areas.

Contrast Injection from an Intermediate Catheter Placed in an Intradural Artery is Associated with Contrast-Induced Encephalopathy following Neurointervention.

BACKGROUND AND PURPOSE: Contrast-induced encephalopathy can result from neurotoxicity of contrast medium in the affected area. The development of intermediate catheters has allowed guidance of catheters to more distal arteries. This study focused on the association between contrast-induced encephalopathy and contrast injection from an intermediate catheter guided into a distal intradural artery during neurointervention for cerebral aneurysms. MATERIALS AND METHODS: We retrospectively reviewed 420 consecutive aneurysms in 396 patients who underwent neurointervention for extracranial aneurysms and unruptured intracranial aneurysms at our institution from February 2012 to January 2023. Patients were divided into a group with contrast-induced encephalopathy and a group without. To identify risk factors for contrast-induced encephalopathy, we compared clinical, anatomic, and procedural factors between groups by multivariate logistic regression analysis and stepwise selection. RESULTS: Among the 396 patients who underwent neurointervention for cerebral aneurysms, 14 (3.5%) developed contrast-induced encephalopathy. Compared with the group without contrast-induced encephalopathy, the group with contrast-induced encephalopathy showed significantly higher rates of patients on hemodialysis, previously treated aneurysms, intradural placement of a catheter for angiography, nonionic contrast medium, and flow-diversion procedures in univariate analyses. Stepwise multivariate logistic regression analysis revealed intradural placement of a catheter for angiography (OR = 40.4; 95% CI, 8.63-189) and previously treated aneurysms (OR = 8.20; 95% CI, 2.26-29.6) as independent predictors of contrast-induced encephalopathy. CONCLUSIONS: Contrast injection from an intradural artery and retreatment of recurrent aneurysms were major risk factors for contrast-induced encephalopathy. Attention should be paid to the location of the intermediate catheter for angiography to avoid developing contrast-induced encephalopathy.

Gli1+-PDL Cells Contribute to Alveolar Bone Homeostasis and Regeneration.

The periodontal ligament (PDL) contains mesenchymal stem cells (MSCs) that can differentiate into osteoblasts, cementoblasts, and fibroblasts. Nevertheless, the distribution and characteristics of these cells remain uncertain. Gli1, an essential hedgehog signaling transcription factor, functions in undifferentiated cells during embryogenesis. Therefore, in the present study, the differentiation ability of Gli1+ cells was examined using Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. In 4-wk-old iGli1/Tomato mice, Gli1/Tomato+ cells were only slightly detected in the PDL, around endomucin-expressing blood vessels. These cells had proliferated over time, localizing in the PDL as well as on the bone and cementum surfaces at day 28. However, in 8-wk-old iGli1/Tomato mice, Gli1/Tomato+ cells were quiescent, as most cells were not immunoreactive for Ki-67. These cells in 8-wk-old mice exhibited high colony-forming unit fibroblast activity and were capable of osteogenic, chondrogenic, and adipogenic differentiation in vitro. In addition, after transplantation of teeth of iGli1/Tomato mice into the hypodermis of wild-type mice, Tomato fluorescence indicating the progeny of Gli1+ cells was detected in the osteoblasts and osteocytes of the regenerated bone. These results demonstrate that Gli1+ cells in the PDL were MSCs and could contribute to the alveolar bone regeneration.

Load distribution and forearm muscle activity during cylinder grip at various grip strength values.

This study aimed to investigate load distribution and forearm muscle activity from strong to weak grip strength, using a cylindrical device (Grip Sensor). We invited 15 students and measured the pressure distribution and forearm muscle activity during grip tasks at 25%, 50%, 75%, and 100% maximum voluntary force (MVF). Pressure data from the Grip Sensor were assigned to seven anatomical regions; the sum of the data from the seven regions (Total force) and proportionate load distribution for each grip task were calculated. Electromyography recorded activity in the extensor carpi radialis longus (ECRL), flexor carpi radialis (FCR), extensor carpi ulnaris (ECU) and flexor carpi ulnaris (FCU) muscles. Forearm muscle activity increased significantly with grip strength (p < 0.05). The load proportion corresponding to the thumb did not significantly change with increasing strength. On the other hand, the fingertip ratio significantly decreased, and the palm ratio significantly increased with increasing strength (p < 0.05). The Grip Sensor showed a shift in the load distribution in the hand from fingertips to palm as grip strength increased. This result indicates that more detailed evaluations of hand function may be possible.

Site-Specific Neutrophil Migration and CXCL2 Expression in Periodontal Tissue.

The oral microbial community is the best-characterized bacterial ecosystem in the human host. It has been shown in the mouse that oral commensal bacteria significantly contribute to clinically healthy periodontal homeostasis by influencing the number of neutrophils that migrate from the vasculature to the junctional epithelium. Furthermore, in clinically healthy tissue, the neutrophil response to oral commensal bacteria is associated with the select expression of the neutrophil chemokine CXCL2 but not CXCL1. This preliminary study examined the contribution of commensal bacteria on neutrophil location across the tooth/gingival interface. Tissue sections from the root associated mesial (anterior) of the second molar to the root associated distal (posterior) of the second molar were examined for neutrophils and the expression of the neutrophil chemokine ligands CXCL1 and CXCL2. It was found that both the number of neutrophils as well as the expression of CXCL2 but not CXCL1 was significantly increased in tissue sections close to the interdental region, consistent with the notion of select tissue expression patterns for neutrophil chemokine expression and subsequent neutrophil location. Furthermore, mice gavaged with either oral Streptococcus or Lactobacillus sp. bacteria induced a location pattern of neutrophils and CXCL2 expression similar to the normal oral flora. These data indicate for the first time select neutrophil location and chemokine expression patterns associated with clinically healthy tissue. The results reveal an increased inflammatory load upon approaching the interproximal region, which is consistent with the observation that the interproximal region often reveals early clinical signs of periodontal disease.

Impact of the Oral Commensal Flora on Alveolar Bone Homeostasis.

Homeostasis of healthy periodontal tissues is affected by innate and adaptive immunosurveillance mechanisms in response to the normal oral flora. Recent comparisons of germ-free (GF) and normal specific-pathogen-free (SPF) mice have revealed the impact of host immunosurveillance mechanisms in response to the normal oral flora on alveolar bone height. Prior reports that alveolar bone height is significantly less in normal SPF mice compared with their age- and strain-matched GF counterparts suggest that naturally occurring alveolar bone loss is a normal component of healthy periodontal tissue homeostasis. In this report, histomorphometric analyses confirmed increased alveolar bone loss and revealed increased numbers of TRAP+ osteoclastic cells lining the alveolar bone surface in SPF compared with GF mice. Increased numbers of RANKL+ cells and IL17+ cells in the periodontium of SPF mice demonstrate possible molecular mechanisms mediating the up-regulated osteoclastogenesis and alveolar bone loss in SPF mice compared with GF mice. Increased numbers of T-lymphocytic cells and T-helper cells in the junctional epithelium of SPF mice compared with GF mice suggest that the adaptive immune response contributes to physiologic alveolar bone loss in the healthy periodontium. This GF animal model study notably begins to elucidate the impact of host immunosurveillance mechanisms in response to the normal oral flora, mediating catabolic alveolar bone homeostasis in the healthy periodontium.

Natural course of dissecting vertebrobasilar artery aneurysms without stroke.

BACKGROUND AND PURPOSE: The natural history and therapeutic management of dissecting vertebrobasilar aneurysms without ischemic or hemorrhagic stroke (nonstroke dissecting vertebrobasilar aneurysms) are not well-established. We conservatively followed patients with nonstroke dissecting vertebrobasilar aneurysms and evaluated the factors related to clinical and morphologic deterioration. MATERIALS AND METHODS: One hundred thirteen patients were enrolled and divided by clinical presentation at diagnosis: asymptomatic (group 1, n = 52), pain only (group 2, n = 56), and mass effect (group 3, n = 5). Patients were conservatively managed without intervention and antithrombotic therapy. Clinical outcomes and morphologic changes were analyzed. RESULTS: A total of 113 patients who were diagnosed with nonstroke dissecting vertebrobasilar aneurysm had a mean follow-up of 2.9 years (range, 27 days to 8 years). Throughout that period, 1 patient in group 1 (1.9%) and 1 patient in group 2 (1.8%) showed clinical deterioration due to mass effect, and 1 patient in group 3 (20%) developed ischemic stroke followed by subarachnoid hemorrhage. Most patients (97.3%) were clinically unchanged. Three patients who had clinical deterioration showed aneurysm enlargement (P < .001). Aneurysms remained morphologically unchanged in 91 patients (80.5%). Aneurysm enlargement was seen in 5 patients (4.4%); risk of enlargement was significantly associated with either maximum diameter (hazard ratio = 1.30; 95% CI, 1.11-11.52; P = .001) or aneurysm ≥10 mm (hazard ratio = 18.0; 95% CI, 1.95-167; P = .011). CONCLUSIONS: The natural course of these lesions suggests that acute intervention is not always required and close follow-up without antithrombotic therapy is reasonable. Patients with symptoms due to mass effect or aneurysms of >10 mm may require treatment.

Effect of ADAMTS-13 on cerebrovascular microthrombosis and neuronal injury after experimental subarachnoid hemorrhage.

BACKGROUND: Microthrombosis and reactive inflammation contribute to neuronal injury after subarachnoid hemorrhage (SAH). ADAMTS-13 cleaves von Willebrand factor multimers, and inhibits thrombus formation and, seemingly, inflammatory reactions. OBJECTIVE: To investigate the effect of ADAMTS-13 in experimental SAH. METHODS: A total of 100 male C57/BL6 mice were randomly assigned to four groups: sham (n = 15), SAH (n = 27), vehicle (n = 25), and ADAMTS-13 (n = 23; 100 µL per 10 g of body weight of 100 µg of ADAMTS-13 per 1 mL of 0.9% NaCl; 20 min after SAH). Neurologic performance was assessed on days 1 and 2 after SAH. Animals were killed on day 2. The amounts of subarachnoid blood, microthrombi, apoptosis and degenerative neurons were compared. The degree of neuronal inflammation and vasospasm was also compared. In five mice each (SAH and ADAMTS-13 groups), bleeding time was assessed 2 h after SAH. RESULTS: Systemic administration of ADAMTS-13 achieved significant amelioration of microthrombosis and improvement in neurologic performance. ADAMTS-13 reduced the amount of apoptotic and degenerative neurons. A tendency for decreased neuronal inflammation was observed. ADAMTS-13 did not show any significant effect on vasospasm. The degree of systemic inflammation was not changed by ADAMTS-13 administration. ADAMTS-13 neither increased the amount of subarachnoid blood nor prolonged the bleeding time. CONCLUSIONS: ADAMTS-13 may reduce neuronal injury after SAH by reducing microthrombosis formation and neuronal inflammation, thereby providing a new option for mitigating the severity of neuronal injury after SAH.

Validation and initial application of a semiautomatic aneurysm measurement software: a tool for assessing volumetric packing attenuation.

BACKGROUND AND PURPOSE: Precise aneurysm measurements and volume embolization ratios are essential for long-term durability of endovascular coil embolization. We evaluated the accuracy of newly developed semiautomatic cerebral aneurysm measurement software, NeuroVision, and explored the value of volume embolization ratio in the prediction of re-treatment. MATERIALS AND METHODS: We compared software-derived volume measurements of 4 silicone aneurysm models with those calculated with an approximation formula and ground truth values (validation study). We used NeuroVision to retrospectively evaluate outcomes of 100 unruptured aneurysms (97 patients) treated with embolization (clinical study). Aneurysm size (height, width, and neck), volume, and volume embolization ratios were calculated for 3 groups (stable, recanalization, and re-treatment) and were compared. RESULTS: This validation study illustrated higher accuracy of NeuroVision in computing aneurysm volume compared with an approximation formula: percentage absolute errors were 4.50% ± 3.18% and 23.07% ± 17.60%, with maximal percentage absolute errors of 8.99% and 45.63%, respectively. Of 100 unruptured aneurysms, 20 recanalized and 12 were re-treated. Average volume embolization ratios of stable and re-treated aneurysms were 24.88% ± 5.91% and 20.50% ± 4.06%, respectively (P ≤ .01). The optimal volume embolization ratio cutoff point for re-treatment was < 19.15%, at which the Youden index was 0.50 (sensitivity, 58.33%; specificity, 87.50%; area under the receiver operating characteristic curve, 0.74). CONCLUSIONS: The NeuroVision software provided accurate aneurysm volume measurements and may be a useful standardized tool to measure aneurysm size and volume, especially for multicenter clinical studies. Volume embolization ratio may be a valuable predictor of aneurysm occlusion changes.

Justification of unruptured intracranial aneurysm repair: a single-center experience.

BACKGROUND AND PURPOSE: Whether to treat UIAs is controversial. The aim of the study was to compare the clinical outcome of patients with UIAs who were either treated conservatively or preventively. MATERIALS AND METHODS: Patients with UIAs referred to our institution were prospectively enrolled in the study. Data collected included baseline characteristics, aneurysmal features, and procedural and follow-up information. Preventive treatment was recommended if the aneurysm was larger than 5 mm and was considered safely treatable. Endovascular surgery was the first-line therapy if the aneurysmal shape was appropriate for coiling. RESULTS: From January 2003 through April 2008, a total of 879 patients with 1110 UIAs were enrolled; 325 patients with 369 UIAs (mean size, 7.8 mm) were treated (treatment group), and 603 patients with 741 UIAs (mean size, 4.4 mm) were managed conservatively (observation group). Mean follow-up was 692.5 days (1405.5 person-years). In the observation group, 26 aneurysms (3.5%) had ruptured (1.8% per year; 1405.5 person-years), 10 patients died, and 7 were disabled (mRS, 3-6: 2.8%). Aneurysmal size was a significant risk factor for rupture (P = .001). The treatment group included aneurysms treated either with coiling (n=315), clipping (n=32), or a combined approach (n=9); 1 patient died, and 3 were disabled (mRS, 3-6: 1.2%). Therapeutic intervention was equal (UIAs of all sizes) or superior (UIAs > 5 mm; P = .025) to conservative management. CONCLUSIONS: Treatment of UIAs was justified in aneurysms larger than 5 mm, and EVS can be safely applied to nearly 90% of UIAs.

Effects of electrical stimulation on periodontal tissue remodeling in rats.

BACKGROUND AND OBJECTIVE: Electric current is used to promote wound healing. However, it is unclear whether electrical stimulation contributes to gingival tissue remodeling. This study examined the effects of electrical stimulation on gingival tissue remodeling in a rat periodontitis model. MATERIAL AND METHODS: Male Wistar rats (n = 28, 8 wks of age) were divided into four groups of seven rats each. The control group did not receive any treatment for 6 wks. In the other groups, periodontitis was ligature-induced for 4 wks. After 4 wks, the rats with periodontitis were given daily electrical stimulation of 0, 50 or 100 µA for 2 wks. RESULTS: The periodontitis group stimulated with 0 µA showed a higher density of polymorphonuclear leukocytes and a lower density of collagen in gingival tissue compared with the control group (p < 0.05). The two remaining groups treated with 50 or 100 µA of electrical stimulation exhibited a lower density of polymorphonuclear leukocytes (p < 0.05) and a higher density of collagen than the group stimulated with 0 µA (p < 0.05). They also showed higher expression of fibroblast growth factor-2 than the group treated with 0 µA of electrical stimulation (p < 0.05). CONCLUSION: Electric stimulation may offer a novel approach to promote gingival tissue remodeling in periodontal lesions.

Early accumulation of intracellular fibrillar oligomers and late congophilic amyloid angiopathy in mice expressing the Osaka intra-Aß APP mutation.

Pathogenic amyloid-ß peptide precursor (APP) mutations clustered around position 693 of APP-position 22 of the Aß sequence--are commonly associated with congophilic amyloid angiopathy (CAA) and intracerebral hemorrhages. In contrast, the Osaka (E693Δ) intra-Aß APP mutation shows a recessive pattern of inheritance that leads to AD-like dementia despite low brain amyloid on in vivo positron emission tomography imaging. Here, we investigated the effects of the Osaka APP mutation on Aß accumulation and deposition in vivo using a newly generated APP transgenic mouse model (E22ΔAß) expressing the Osaka mutation together with the Swedish (K670N/M671L) double mutation. E22ΔAß mice exhibited reduced α-processing of APP and early accumulation of intraneuronal fibrillar Aß oligomers associated with cognitive deficits. In line with our in vitro findings that recombinant E22Δ-mutated Aß peptides form amyloid fibrils, aged E22ΔAß mice showed extracellular CAA deposits in leptomeningeal cerebellar and cortical vessels. In vitro results from thioflavin T aggregation assays with recombinant Aß peptides revealed a yet unknown antiamyloidogenic property of the E693Δ mutation in the heterozygous state and an inhibitory effect of E22Δ Aß42 on E22Δ Aß40 fibrillogenesis. Moreover, E22Δ Aß42 showed a unique aggregation kinetics lacking exponential fibril growth and poor seeding effects on wild-type Aß aggregation. These results provide a possible explanation for the recessive trait of inheritance of the Osaka APP mutation and the apparent lack of amyloid deposition in E693Δ mutation carriers.

Effects of topical application of inorganic polyphosphate on tissue remodeling in rat inflamed gingiva.

BACKGROUND AND OBJECTIVE: Inorganic polyphosphate [poly(P)] is a biopolymer found in almost all cells and tissues, and which promotes tissue remodeling. However, there is limited information on how poly(P) affects the connective tissue in inflamed gingiva. This study examined the effects of topical application of poly(P) on gingival connective tissue and its remodeling in a rat periodontitis model. MATERIAL AND METHODS: Male Wistar rats (n = 36, 8 wk of age) were used in this 6-wk study. The rats were divided into six groups of six rats each. The control group received no treatment. In the other groups, periodontitis was ligature-induced for 4 wk. After 4 wk, the rats with periodontitis were further divided into five groups, and were left untreated (periodontitis group) or subjected to topical application of oral rinses containing 0, 0.1, 1 or 5% poly(P) for 2 wk. RESULTS: The periodontitis and 0% poly(P) groups showed a higher density of polymorphonuclear leukocytes and a lower density of collagen in gingival tissue than the control group (p < 0.05). In contrast, groups treated with more than 1% poly(P) exhibited a lower density of polymorphonuclear leukocytes (p < 0.05) and a higher density of collagen than the periodontitis and 0% poly(P) groups (p < 0.05). A higher expression of fibroblast growth factor-2 was observed in the gingiva of rats treated with 1% poly(P) than in those treated with 0% poly(P) (p < 0.05). CONCLUSION: Topical application of poly(P) may induce connective tissue remodeling, contributing to improvement of inflamed gingiva in rats.

Occlusal disharmony increases amyloid-ß in the rat hippocampus.

Amyloid-ß plays a causative role in Alzheimer's disease. Occlusal disharmony causes chronic psychological stress, and psychological stress increases amyloid-ß accumulation. The purpose of the present study was to investigate whether occlusal disharmony-induced psychological stress affects the accumulation of amyloid-ß and its related gene expressions in the rat hippocampus. Eight-week-old male Wistar rats (n = 18) were divided into three groups of six rats each: (1) a control group that received no treatment for 8 weeks; (2) an occlusal disharmony group that underwent cutoff maxillary molar cusps for 8 weeks; and (3) a recovered group that underwent cutoff maxillary molar cusps for 4 weeks followed by recovery for 4 weeks. Occlusal disharmony increased plasma corticosterone levels in a time-dependent manner. Levels of amyloid-ß 40 and 42, glucocorticoid receptor (Gr) protein, and cleaved caspase 3 (Casp3) as well as gene expressions of amyloid precursor protein, beta-secretase, Casp3, and Gr in the hippocampus in the occlusal disharmony group were significantly higher than those in the control group (P < 0.016). These findings were significantly improved by recovery of occlusion (P < 0.016). These results indicate that psychological stress induced by occlusal disharmony reversibly induces amyloid-ß 40 and 42 in the rat hippocampus through the glucocorticoid signal.

Relationship between periodontal condition and arterial properties in an adult population in Japan.

UNLABELLED: Oral Diseases (2010) 16, 781-787 OBJECTIVE: This study addressed the relationship between periodontal condition and second derivative of the finger photoplethysmogram (SDPTG) in Japanese adults. SUBJECT AND METHODS: The Community Periodontal Index (CPI) and SDPTG were recorded in 415 subjects (mean age: 44.0 years). For assessing SDPTG, we mainly focused on the ratio of the absolute value of the height of the early negative 'b' wave and ratio of the late re-decreasing 'd' wave to the height of the initial positive 'a' wave, namely the b/a and d/a ratios. RESULTS: The CPI score was positively correlated with the b/a ratio (P < 0.001), and negatively correlated with the d/a ratio (P < 0.001). Logistic regression analysis showed that subjects with CPI scores ≥ 3 were more likely to have a higher level (male > -0.69, female > -0.64) of b/a ratio (Odds ratio = 1.7, P = 0.026) and lower level (male ≤ -0.29, female ≤ -0.32) of d/a ratio (Odds ratio = 2.2, P =0.001) than those with CPI scores 0-2, after adjusting for age, gender, smoking status, pulse rate and presence of hypertension. CONCLUSION: There was a statistical association between the CPI scores and SDPTG indices in Japanese adults.

Periodontitis-induced lipid peroxidation in rat descending aorta is involved in the initiation of atherosclerosis.

BACKGROUND AND OBJECTIVE: Periodontitis is a risk factor for the development of atherosclerosis. Recent studies indicate that oxidative mechanisms, including lipid peroxidation, are involved not only in periodontitis but also in atherosclerosis. Lipid peroxidation may play an important role in the pathogenesis of atherosclerosis, particularly during its earliest stages. The purpose of this study was to investigate the relationship between lipid peroxidation induced by periodontitis and the initiation of atherosclerosis. MATERIAL AND METHODS: Sixteen rats were randomly divided into two groups of eight rats each. Periodontitis was ligature-induced for 4 wk in the experimental group, whereas the control group was left untreated. After the experimental period, the mandibular first molar regions were resected and then subjected to histological analysis and measurement of hexanoyl-lysine expression as an indicator of lipid peroxidation. Descending aorta was used for measuring the levels of hexanoyl-lysine, reactive oxygen species and lipid deposits, and for real-time polymerase chain reaction microarray analysis. The level of hexanoyl-lysine was also measured in serum. RESULTS: In the experimental group, the levels of hexanoyl-lysine in periodontal tissue and serum increased. Only aorta samples in the experimental group showed lipid accumulation, with increased expression of hexanoyl-lysine, reactive oxygen species and oxidative stress-related genes (including nitric oxide synthases 2 and 3), whereas the superoxide dismutase 1 gene level was down-regulated. CONCLUSION: In a ligature-induced periodontitis rat model, increased lipid peroxidation was found in serum and aorta as well as in periodontal tissue. Atherosclerosis-related gene expression and histological changes were also stimulated. Periodontitis-induced lipid peroxidation in the aorta may be involved in the early stage of atherosclerosis.

Effects of ethanol consumption on periodontal inflammation in rats.

Studies suggest a correlation between ethanol consumption and periodontal disease. We hypothesized that elevated levels of blood reactive oxygen species following ethanol consumption may increase inflammation in periodontal tissue. Rats were divided into 4 groups (6-7 rats/group). Two groups were fed an ethanol-containing liquid diet, and 2 groups were fed a pair-fed control diet. In one of each dietary group, periodontitis was ligature-induced, while the other group was left unligated. Chronic ethanol feeding alone decreased the ratio of reduced/oxidized glutathione and increased 8-hydroxydeoxy-guanosine and tumor necrosis factor (TNF)-alpha levels in the gingiva. Blood hydroperoxides were also increased. In ligature-induced periodontitis lesions, ethanol feeding enhanced polymorpho-nuclear leukocyte infiltration and TNF-alpha expression. The results suggest that chronic alcohol consumption increased periodontal inflammation, oxidative damage, and TNF-alpha production and had an additive effect on polymorphonuclear leukocyte infiltration and gingival oxidative damage, increasing the severity of periodontal inflammation in the ligature model.

Delta 9-tetrahydrocannabinol-induced catalepsy-like immobilization is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons.

Delta(9)-tetrahydrocannabinol (THC) has been reported to induce catalepsy-like immobilization, but the mechanism underlying this effect remains unclear. In the present study, in order to fully understand the neural circuits involved, we determined the brain sites involved in the immobilization effect in rats. THC dose-dependently induced catalepsy-like immobilization. THC-induced catalepsy-like immobilization is mechanistically different from that induced by haloperidol (HPD), because unlike HPD-induced catalepsy, animals with THC-induced catalepsy became normal again following sound and air-puff stimuli. THC-induced catalepsy was reversed by SR141716, a selective cannabinoid CB(1) receptor antagonist. Moreover, THC-induced catalepsy was abolished by lesions in the nucleus accumbens (NAc) and central amygdala (ACE) regions. On the other hand, HPD-induced catalepsy was suppressed by lesions in the caudate putamen (CP), substantia nigra (SN), globus pallidus (GP), ACE and lateral hypothalamus (LH) regions. Bilateral microinjection of THC into the NAc region induced catalepsy-like immobilization. This THC-induced catalepsy was inhibited by serotonergic drugs such as 5-hydroxy-L-tryptophan (5-HTP), a 5-HT precursor, and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a 5-HT receptor agonist, as well as by anti-glutamatergic drugs such as MK-801 and amantadine, an N-methyl-d-aspartate (NMDA) receptor antagonist. THC significantly decreased 5-HT and glutamate release in the NAc, as shown by in vivo microdialysis. SR141716 reversed and MK-801 inhibited this decrease in 5-HT and glutamate release. These findings suggest that the THC-induced catalepsy is mechanistically different from HPD-induced catalepsy and that the catalepsy-like immobilization induced by THC is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons.