Model to Predict Oral Frailty Based on a Questionnaire: A Cross-Sectional Study.

A statistical model to predict oral frailty based on information obtained from questionnaires might help to estimate its prevalence and clarify its determinants. In this study, we aimed to develop and validate a predictive model to assess oral frailty thorough a secondary data analysis of a previous cross-sectional study on oral frailty conducted on 843 patients aged ≥ 65 years. The data were split into training and testing sets (a 70/30 split) using random sampling. The training set was used to develop a multivariate stepwise logistic regression model. The model was evaluated on the testing set and its performance was assessed using a receiver operating characteristic (ROC) curve. The final model in the training set consisted of age, number of teeth present, difficulty eating tough foods compared with six months ago, and recent history of choking on tea or soup. The model showed good accuracy in the testing set, with an area of 0.860 (95% confidence interval: 0.806-0.915) under the ROC curve. These results suggested that the prediction model was useful in estimating the prevalence of oral frailty and identifying the associated factors.

Is the Association between Green Tea Consumption and the Number of Remaining Teeth Affected by Social Networks?: A Cross-Sectional Study from the Japan Gerontological Evaluation Study Project.

Consumption of green tea without sugar, as well as social networks, are associated with a lower risk of tooth loss. There is a possibility of confounding both factors because tea is often drunk with friends. Therefore, the present study aimed to examine whether green tea consumption is beneficially associated with the number of remaining teeth, while considering social networks. This cross-sectional study was based on the Japan Gerontological Evaluation Study (JAGES) in 2016. Self-administered questionnaires containing questions about green tea consumption were mailed to 34,567 community-dwelling residents aged ≥ 65 years. We used the number of remaining teeth as a dependent variable, and green tea consumption and the number of friends met over the past month (social network size) as independent variables. Linear regression models with multiple imputation were used. A total of 24,147 people responded (response rate = 69.9%), and 22,278 valid data were included into our analysis. Participants' mean age was 74.2 years (standard deviation = 6.3), and 45.9% were men. Among the participants, 52.2% had ≥ 20 teeth, 34.2% drank 2-3 cups of green tea per day, and 32.6% met ≥ 10 people over the past month. After adjusting for all potential confounders, both higher green tea consumption and a larger social network size were associated with more remaining teeth (both p for trend < 0.001). The association of green tea was greater among those with smaller social networks (p for interaction < 0.05). The protective association of green tea was remarkable among people with smaller social networks.

Emergence of a small colony variant of vancomycin-intermediate Staphylococcus aureus in a patient with septic arthritis during long-term treatment with daptomycin.

OBJECTIVES: Small colony variants (SCVs) of Staphylococcus aureus are associated with persistent and drug-resistant infections. We demonstrated for the first time the emergence of SCVs in a patient with vancomycin-intermediate S. aureus (VISA) infection during long-term treatment with daptomycin. METHODS: A 73-year-old man with septic arthritis was infected with VISA. The patient was treated with daptomycin; however, the patient remained infected with VISA, with continuous isolation of VISA from his blood during long-term treatment. Five VISA isolates were characterized by: PFGE; genotyping including staphylococcal cassette chromosome mec (SCCmec), spa and MLST; antimicrobial susceptibility testing; and scanning and transmission electron microscopy. WGS and fatty acid analysis were also performed. RESULTS: The five VISA isolates were from a single clone of ST239/spa3(t037) and, of these, the first three were SCCmecIII positive and daptomycin susceptible, whereas the last two were SCCmecIII negative and daptomycin resistant and exhibited the characteristics of SCVs. The first and last isolates showed 13 remarkable genetic differences in SCCmec and the mprF, cls2, clpX and fabF genes. Of these, mutation of fabF (encoding the fatty acid synthase) seemed to be partially responsible for the slow growth and ultrastructural features, including an abnormal intercellular substance, and for the daptomycin resistance of SCVs. CONCLUSIONS: For the first time, we identified SCVs of VISA in a patient with septic arthritis during long-term treatment with daptomycin. Daptomycin-resistant SCVs of VISA were evolved in a stepwise manner and the mutation of fabF is likely responsible for the physical and ultrastructural characteristics and daptomycin resistance.

A polyphenol-rich extract from Chaenomeles sinensis (Chinese quince) inhibits influenza A virus infection by preventing primary transcription in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Chaenomeles sinensis Koehne (Chinese quince) are distributed throughout China and Japan. It has traditionally been known to have a therapeutic effect against respiratory symptoms caused by infectious diseases. AIM OF THE STUDY: The polyphenol-rich extract, CSD3, from Chaenomeles sinensis has previously been shown to neutralize influenza virus infectivity. The aim of this study was to clarify which step(s) in the replication cycle in vitro were inhibited. MATERIALS AND METHODS: We examined cell-binding, hemagglutination and hemolytic activities and infectivity of A/Udorn/72(H3N2) virus after pre-treatment with CSD3. We also investigated the time course of synthesis for viral mRNA, cRNA, and vRNA in Madin-Darby canine kidney epithelial cells (MDCK) cells infected with CSD3-treated virus. Finally, we studied the effect of CSD3-treatment on the ultrastructure of the influenza virion. RESULTS: Pre-treatment with CSD3 mildly reduced cell-binding, hemagglutination and hemolytic activities. These activities were reduced by 70% to be equivalent to 30% of the control at 1µg/ml. CSD3 severely reduced infectivity to 1% of the control at 1µg/ml. Primary transcription in MDCK cells infected with CSD3 (1µg/ml)-treated virus was decreased to about 1% of that in cells infected with mock-treated virus. Synthesis of viral cRNA, vRNA and secondary mRNA was also severely decreased. Electron microscopy revealed that the integrity of the virus envelope was damaged by CSD3 and was permeable to uranyl acetate. CONCLUSIONS: The main target step(s) of CSD3 in the replication cycle is after cell-binding but before or at primary transcription. Involvement of the increased permeability of virus envelope as the inhibition mechanism was proposed. CSD3 could be useful in preventing influenza virus infection, and be employed as a lozenge or mouthwash for daily use.

Supplementation of broccoli or Bifidobacterium longum-fermented broccoli suppresses serum lipid peroxidation and osteoclast differentiation on alveolar bone surface in rats fed a high-cholesterol diet.

High-cholesterol diet enhances osteoclastic activity on alveolar bone by increasing serum lipid peroxidation. We hypothesized that supplementation with dietary antioxidants, such as found in broccoli and its fermented products, might suppress increases in serum lipid peroxidation, contributing to the inhibition of osteoclastic activity after high-cholesterol diet intake. The purpose of the present study was to investigate the effects of broccoli and fermented broccoli consumption on serum lipid peroxidation and osteoclast differentiation in alveolar bone of rats fed a high-cholesterol diet. In this 12-week study, rats were divided into 4 groups (n = 6/group): a control group (fed regular diet) and 3 experimental groups (fed a high-cholesterol [1% wt/wt] diet, or a high-cholesterol diet supplemented with either broccoli powder [5% wt/wt] or Bifidobacterium longum-fermented broccoli powder [5% wt/wt]). Serum hexanoyl-lysine (HEL) levels were measured as a parameter of lipid peroxidation. The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in alveolar bone was enumerated to evaluate osteoclast differentiation. When compared with regular diet, the high-cholesterol diet increased serum HEL levels and resulted in a higher number of TRAP-positive osteoclasts at 12 weeks. The high-cholesterol diet supplemented with broccoli or B. longum-fermented broccoli showed lower levels of serum HEL and fewer TRAP-positive osteoclasts than the high-cholesterol diet at 12 weeks. In conclusion, consumption of broccoli, or its fermented product, inhibited the effects of a high-cholesterol diet on osteoclast differentiation in rat alveolar bone by suppressing serum lipid peroxidation.

Supplementation of green tea catechins in dentifrices suppresses gingival oxidative stress and periodontal inflammation.

OBJECTIVE: this study examined the effects of a dentifrice containing green tea catechins on gingival oxidative stress and periodontal inflammation using a rat model. DESIGN: twenty-four male Wister rats were randomly divided into four groups. The first group (Control group) received no treatment for 8 weeks. Periodontal inflammation was induced in the second group for 8 weeks. Periodontal inflammation was induced in the last two groups for 8 weeks and dentifrices with or without green tea catechins were topically applied to the gingival sulcus daily for 4 weeks prior to the end of the experimental period. RESULTS: rats that had experimental periodontal inflammation showed apical migration of the junctional epithelium, alveolar bone loss and inflammatory cell infiltration in the connective tissue subjacent to the junctional epithelium at 8 weeks, whilst the control group showed no pathologic changes. Topical application of a green tea catechin-containing dentifrice reduced inflammatory cell infiltration in the periodontal lesions to a greater degree than the control dentifrice at 8 weeks. The gingiva in which green tea catechin-containing dentifrice was applied also showed a lower level of expression of hexanoyl-lysine (a marker of lipid peroxidation), nitrotyrosine (a marker of oxidative protein damage), and tumour necrosis factor-α (an indicator of pro-inflammatory cytokines) at 8 weeks compared to gingiva in which the control dentifrice was applied. CONCLUSIONS: adding green tea catechins to a dentifrice may contribute to prevention of periodontal inflammation by decreasing gingival oxidative stress and expression of pro-inflammatory cytokines.

Pentosan polysulfate treatment preserves renal autoregulation in ANG II-infused hypertensive rats via normalization of P2X1 receptor activation.

Inflammatory factors are elevated in animal and human subjects with hypertension and renal injury. We hypothesized that inflammation contributes to hypertension-induced renal injury by impairing autoregulation and microvascular reactivity to P2X(1) receptor activation. Studies were conducted in vitro using the blood-perfused juxtamedullary nephron preparation. Rats receiving ANG II (60 ng/min) infusion were treated with the anti-inflammatory agent pentosan polysulfate (PPS) for 14 days. The magnitude and progression of hypertension were similar in ANG II and ANG II+PPS-treated rats (169 ± 5 vs. 172 ± 2 mmHg). Afferent arterioles from control rats exhibited normal autoregulatory behavior with diameter decreasing from 18.4 ± 1.6 to 11.4 ± 1.7 µm when perfusion pressure was increased from 70 to 160 mmHg. In contrast, pressure-mediated vasoconstriction was markedly attenuated in ANG II-treated rats, and diameter remained essentially unchanged over the range of perfusion pressures. However, ANG II-treated rats receiving PPS exhibited normal autoregulatory behavior compared with ANG II alone rats. Arteriolar reactivity to ATP and ß,γ-methylene ATP was significantly reduced in ANG II hypertensive rats compared with controls. Interestingly, PPS treatment preserved normal reactivity to P2 and P2X(1) receptor agonists despite the persistent hypertension. The maximal vasoconstriction was 79 ± 3 and 81 ± 2% of the control diameter for ATP and ß,γ-methylene ATP, respectively, similar to responses in control rats. PPS treatment significantly reduced α-smooth muscle actin staining in afferent arterioles and plasma transforming growth factor-ß1 concentration in ANG II-treated rats. In conclusion, PPS normalizes autoregulation without altering ANG II-induced hypertension, suggesting that inflammatory processes reduce P2X(1) receptor reactivity and thereby impair autoregulatory behavior in ANG II hypertensive rats.

Changes of expression of glucose transporters in the fetal lamb brain after MCI-186 administration to the maternal circulation with 10-min persistent umbilical cord occlusion.

OBJECTIVE: To evaluate the effect of MCI-186 (3-methyl-1-phenyl-2-pyrazoline-5-one), a potent hydroxyl radical scavenger, administered to the maternal circulation following umbilical cord occlusion in regard to glucose transporter (GLUT) expression. MATERIALS AND METHODS: Fourteen instrumented lambs were prepared. In three cases, a 10-min persistent umbilical cord occlusion was performed; 30 min after the insult, fetal brains were extirpated (Group A). Four cases had a 10-min occlusion(Group B) and four cases had 10-min occlusion and were administered MCI-186 to the maternal circulation (Group C).Three days following the insult, the fetal brains were extirpated. The remaining three cases had a sham operation (Group D).Brain tissue sections were stained at the locations of GLUT-1, -3 and -5 and were evaluated by two pathologists. RESULTS: The expression of GLUT-1 and -3 significantly increased in the basal ganglia, hippocampi and periventricular region of Group B when compared with that of Group A. The expression of GLUT-1 and -3 in three regions of Group B were significantly higher than that of Group C and D. GLUT-5 was recognised only in Group B. CONCLUSION: On the basis of expression of GLUT, the protective effect of MCI-186 on brain injury resulting from hypoxia/ ischemia-reperfusion is documented.

Vitamin C intake inhibits serum lipid peroxidation and osteoclast differentiation on alveolar bone in rats fed on a high-cholesterol diet.

OBJECTIVE: A high-cholesterol diet stimulates osteoclast differentiation, which may be induced by increased serum lipid peroxidation. The inhibition of serum lipid peroxidation by vitamin C may offer beneficial effects on osteoclast differentiation including increased expression of receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) and NF-kappaB. This study investigated the effects of vitamin C intake on RANKL and NF-kappaB expression in periodontal tissue of rats fed a high-cholesterol diet. DESIGN: Twenty-four rats (8 weeks old) were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1 and 2 g/l vitamin C/day) in this 12-week study. Vitamin C was provided by its addition to drinking water. As an index of serum lipid peroxidation, hexanoyl-lysine (HEL) level was determined by a competitive enzyme-linked immunosorbent assay method. Immunohistological analysis was performed to evaluate RANKL and NF-kappaB expression on the alveolar bone surface. The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was also counted. RESULTS: Feeding a high-cholesterol diet increased not only the serum HEL level but also the number of TRAP-positive osteoclasts on the alveolar bone surface, with an increase in RANKL and NF-kappaB expression on alveolar bone surface. Intake of vitamin C reduced the serum HEL level and osteoclast differentiation, with decreasing RANKL and NF-kappaB expression. CONCLUSIONS: Vitamin C intake could suppress osteoclast differentiation, including RANKL and NF-kappaB expression on the alveolar bone surface, by decreasing serum lipid peroxidation in rats fed a high-cholesterol diet.

Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats.

Hypertension and Type 2 diabetes are co-morbid diseases that lead to the development of nephropathy. sEH (soluble epoxide hydrolase) inhibitors are reported to provide protection from renal injury. We hypothesized that the sEH inhibitor AUDA [12-(3-adamantan-1-yl-ureido)-dodecanoic acid] protects the kidney from the development of nephropathy associated with hypertension and Type 2 diabetes. Hypertension was induced in spontaneously diabetic GK (Goto-Kakizaki) rats using AngII (angiotensin II) and a high-salt diet. Hypertensive GK rats were treated for 2 weeks with either AUDA or its vehicle added to drinking water. MAP (mean arterial pressure) increased from 118+/-2 mmHg to 182+/-20 and 187+/-6 mmHg for vehicle and AUDA-treated hypertensive GK rats respectively. AUDA treatment did not alter blood glucose. Hypertension in GK rats resulted in a 17-fold increase in urinary albumin excretion, which was decreased with AUDA treatment. Renal histological evaluation determined that AUDA treatment decreased glomerular and tubular damage. In addition, AUDA treatment attenuated macrophage infiltration and inhibited urinary excretion of MCP-1 (monocyte chemoattractant protein-1) and kidney cortex MCP-1 gene expression. Taken together, these results provide evidence that sEH inhibition with AUDA attenuates the progression of renal damage associated with hypertension and Type 2 diabetes.

Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats.

BACKGROUND: A high-cholesterol diet stimulates alveolar bone resorption, which may be induced via tissue oxidative damage. Vitamin C reduces tissue oxidative damage by neutralizing free radicals and scavenging hydroxyl radicals, and its antioxidant effect may offer the clinical benefit of preventing alveolar bone resorption in cases of hyperlipidemia. We examined whether vitamin C could suppress alveolar bone resorption in rats fed a high-cholesterol diet. METHODS: In this 12-week study, rats were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1, or 2 g/l vitamin C). Vitamin C was provided by adding it to the drinking water. The bone mineral density of the alveolar bone was analyzed by microcomputerized tomography. As an index of tissue oxidative damage, the 8-hydroxydeoxyguanosine level in the periodontal tissue was determined using a competitive enzyme-linked immunosorbent assay. RESULTS: Hyperlipidemia, induced by a high-cholesterol diet, decreased rat alveolar bone density and increased the number of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of 8-hydroxydeoxyguanosine was upregulated in the periodontal tissues. Intake of vitamin C reduced the effect of a high-cholesterol diet on alveolar bone density and osteoclast differentiation and decreased periodontal 8-hydroxydeoxyguanosine expression. CONCLUSION: In the rat model, vitamin C suppressed alveolar bone resorption, induced by high dietary cholesterol, by decreasing the oxidative damage of periodontal tissue.

Inhibitory effect of antimicrobial agents and anisodamine on the staphylococcal superantigenic toxin-induced overproduction of proinflammatory cytokines by human peripheral blood mononuclear cells.

Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), produces superantigenictoxins, such as toxic shock syndrome toxin-1 (TSST-1). TSST-1 abnormally activates T cells to overproduce inflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) leading to shock. In this study, we investigated the inhibitory effect of antimicrobial agents and anisodamine (a Chinese herbal extract) on TSST-1-induced cytokine production. Among the macrolides and related agents examined, azithromycin and rokitamycin showed the greatest inhibitory activity against the TSST-1-induced cytokine production. This inhibitory effect was similar to that of anisodamine, which, however, had no inhibitory activity against bacterial growth. Vancomycin, teicoplanin, arbekacin, and linezolid (anti-MRSA and related agents) had no significant inhibitory effect on cytokine production. The inhibitory effect of the drugs on cell proliferation was not significant. These data indicate that some antimicrobial agents, e.g., azithromycin and rokitamycin, manifest anti-superantigenic toxin activity through the inhibition of cytokine production, just like anisodamine.

Specific inhibitory action of anisodamine against a staphylococcal superantigenic toxin, toxic shock syndrome toxin 1 (TSST-1), leading to down-regulation of cytokine production and blocking of TSST-1 toxicity in mice.

Toxic shock syndrome toxin 1 (TSST-1), produced by Staphylococcus aureus (including methicillin-resistant S. aureus), is a superantigenic toxin responsible for toxic shock syndrome as well as neonatal TSS-like exanthematous disease. TSST-1 exhibits its deleterious effects by leading to the abnormal proliferation of, e.g., Vbeta2+ T cells and overproduction of proinflammatory cytokines. In the present study we examined the inhibitory effect of a Chinese herbal extract, anisodamine, on TSST-1 using human peripheral blood mononuclear cells (PBMCs). Anisodamine inhibited the production of proinflammatory cytokines better than interleukin-10 (an anti-inflammatory cytokine). The inhibitory effect of anisodamine was greater than that of any tropane alkaloid examined. Anisodamine acted directly on both monocytes and T cells in human PBMCs, and the effect was confirmed at the transcriptional level. Inhibition of NF-kappaB activation was also demonstrated. In contrast, no significant inhibition of Vbeta2+ T-cell proliferation was observed. In mice injected with TSST-1, anisodamine treatment significantly decreased serum proinflammatory cytokine levels and prevented TSST-1-induced death. These results suggest that anisodamine specifically acts against the production of cytokines (inflammatory cytokines in particular) and not against Vbeta2+ T-cell proliferation and that anisodamine may have a beneficial effect on TSST-1-associated disease.

The plasma glucose lowering action of tetrandrine in streptozotocin-induced diabetic rats.

The effect of tetrandrine, an active principle of Stephaniae tetrandrae, on the plasma glucose level in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. A single intravenous injection of tetrandrine decreased the plasma glucose in a dose-dependent manner in STZ-diabetic rats. Moreover, tetrandrine (1.0 mg x kg(-1)) significantly attenuated the rise in plasma glucose induced by the intravenous glucose challenge test in normal rats. A stimulatory effect of tetrandrine on glucose uptake was obtained in soleus muscles isolated from STZ-diabetic rats with a concentration-dependent manner from 0.01 to 10.0 micromol L(-1). The increase in glucose utilization by tetrandrine was further characterized using the enhancement of glycogen synthesis in the hepatocytes of STZ-diabetic rats. These results suggest that tetrandrine has the ability to enhance glucose utilization in peripheral tissue, resulting in the lowering of plasma glucose in diabetic rats lacking insulin.

Mediation of beta-endorphin by the isoflavone puerarin to lower plasma glucose in streptozotocin-induced diabetic rats.

We investigate the mechanism(s) of plasma glucose lowering action of puerarin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Puerarin at the effective dosage to lower higher plasma glucose increased plasma beta-endorphin-like immunoreactivity (BER) in STZ-diabetic rats. Both effects of puerarin were abolished by the pretreatment with prazosin. Also, puerarin enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that can be abolished by prazosin. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of puerarin including the plasma glucose lowering effect and plasma BER elevating effect. In addition, naloxone and naloxonazine inhibited the plasma glucose lowering action of puerarin. Unlike in wild-type diabetic mice, puerarin failed to lower the plasma glucose in opioid micro-receptor knockout diabetic mice. In conclusion, our results suggest that puerarin may activate alpha (1)-adrenoceptors on the adrenal gland to enhance the secretion of beta-endorphin to result in a decrease of plasma glucose in STZ-diabetic rats.

Graves' disease associated with anticardiolipin antibody positivity and acquired protein S deficiency.

A 33-year-old woman had experienced recurrent pregnancy loss. She had positive anticardiolipin antibody and protein S deficiency. Her pregnancy was managed with anticoagulant therapy and she delivered a healthy infant. Three years after delivery, she reported progressive sweating, tremor, tachycardia, and a 4-kg weight loss. She was diagnosed with Graves' disease. This is a rare case of combined anticardiolipin antibody positivity, acquired protein S deficiency, and Graves' disease.