A study on the effects of short-, medium- and long-term professional oral care in elderly persons requiring long-term nursing care at a chronic or maintenance stage of illness

Objective: The purpose of the present study is to clarify the frequency of provision of effective professional oral care by dental health workers in order to improve the oral hygiene state of elderly persons requiring long‐term care. Methods: In 105 patients requiring long‐term nursing care, 55 subjects with positive oral Candida albicans were divided into five groups according to the frequency of oral care intervention at intervals of 1, 2, 3, 4 and 6 weeks. The effects of professional oral care on the improvement of the oral hygiene state were investigated taking the frequency and duration of care into consideration. Results: The results showed that oral hygienic condition could be improved by performing professional oral care at intervals of 1 week for 12 consecutive weeks, and the improved condition could be maintained when professional oral care was continued at intervals of 1 week thereafter. Conclusion: It is necessary to continue professional oral care at intervals of 1 week for 12 consecutive weeks and at intervals of 2 weeks for more than 20 weeks. The oral hygiene state could be improved by professional intervention at intervals of three or four weeks in long‐term oral care, but this was limited to subjects whose Functional Independence Measure (FIM) scores were higher than 3.     

Effect of oral N-acetyl cysteine supplementation in type 2 diabetic patients on intracellular glutathione content and innate immune responses to Burkholderia pseudomallei

Type 2 diabetic patients have increased susceptibility to melioidosis, an infectious disease caused by Burkholderia pseudomallei. We had previously shown that peripheral blood mononuclear cells (PBMCs) from diabetic patients with poor glycemic control had a defective IL-12 and IFNγ response to B. pseudomallei infection, resulting in poor intracellular bacterial control. The impaired IL-12 response was due to glutathione (GSH) deficiency characterized by a low reduced to oxidized glutathione ratio (GSH ratio) and could be restored by the addition of reduced GSH to the infected cells. Our goal is to determine whether N-acetyl cysteine (NAC, a GSH pro-drug) supplementation in diabetic patients could improve their immune control of B. pseudomallei. Type 2 diabetic patients with poor glycemic control were given oral supplementation of NAC for six weeks at 1200 mg daily. Their PBMCs and subsets of immune cells showed a significant increase in free GSH concentration. However, the GSH ratio, IL-12 and IFNγ production, and intracellular bacterial killing upon ex-vivo infection did not improve. Thus, oral NAC supplementation in diabetic patients is sufficient to increase intracellular GSH content in blood cells. However, modulating the free GSH content is not sufficient to improve infection outcome as it is the GSH ratio that regulates the IL-12 response in monocytes.     

Influence of Oral Probiotic <Emphasis Type="Italic">Streptococcus salivarius</Emphasis> K12 on Ear and Oral Cavity Health in Humans: Systematic Review

Traditionally, probiotics are linked to the good health of the intestine and most clinical studies focus on that field. Evidence of oral probiotic use for ear and oral cavity disease prevention with impact on human health is limited. This work reviews existing studies and literature on Streptococcus salivarius K12 as an oral probiotic and effects of S. salivarius K12 on human ear and oral cavity human health. The studies were accessed via database searches: MEDLINE, PubMed, and Elsevier. The search included/focused on/encompassed publications from 2003 to 2016 with keywords related to K12 Streptococcus salivarius, bacteriocin-like inhibitory substances (BLIS) K12, probiotic K12 salivarius, and K12 probiotic health effects. Only a small amount of studies was identified: the total of 68 studies was identified, 35 of which were relevant after screening, and 9 were included in the final analysis. Very little literature is available about the association/correlation between/connection/interrelation of S. salivarius K12 with/and human ear and oral cavity health. S. salivarius K12 may have a role in reducing the occurrence and/or severity of secretory otitis media (SOM) and also in prevention of streptococcal and viral pharyngotonsillitis in children. Research highlights that S. salivarius K12 has shown promising results in treatment of halitosis, but data are still deficient. Further studies need to be initiated to improve understanding of the association of oral probiotic S. salivarius K12 with human ear and oral cavity health.     

三种不同皮瓣修复口腔颌面组织缺损的临床效果

目的:探讨三种皮瓣在口腔面部组织缺损修复中的临床效果。方法:以2014年1月到2014年12月在我院皮瓣修复口腔面部组织缺损患者64例为研究对象。胸大肌皮瓣26例,前臂皮瓣22例,股前外侧皮瓣16例。术后3~12月对患者临床疗效进行观察评价。结果:患者均采用胸大肌皮瓣、股前外侧皮瓣和前臂皮瓣进行口腔面部组织缺损的修复,不同皮瓣来源数量组间比较差异均无统计学意义(P0.05)。患者术后均治愈,移植成功率100%,组间比较差异无统计学意义(P0.05)。少数患者发生积血、感染不良反应情况,总不良反应发生率为12.5%,不同组间的不良反应发生率比较差异无统计学意义(P0.05)。结论:三种不同的皮瓣修复口腔面部组织缺损临床效果均较好,皮瓣的选择较广泛,显著改善了患者口腔生理功能,提高了患者的生活质量,临床推广使用价值高。     

No mutations found in exon 2 of gene p16CDKN2A during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide

The medium-term tongue carcinogenesis assay is a useful model for studying oral squamous cell carcinomas phase by phase. The present study aimed to investigate mutations in exon 2 of gene p16CDKN2A during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO) using direct DNA-sequencing method. A total of 30 male Wistar rats were treated with 4-nitroquinoline 1-oxide (4NQO) in drinking water for 4, 12, and 20 weeks at 50 ppm dose. Ten animals were used as negative control. No histopathological changes in tongue epithelia were observed among controls or in the group treated for 4 weeks with 4NQO. Following 12-week treatment, hyperplasia and epithelial dysplasia were found in mild and moderate forms. At 20 weeks, the tongue presented moderate and/or severe oral dysplasia and squamous cell carcinoma, with squamous cell carcinoma in the majority of animals. No mutations were found in any experimental period evaluated that corresponded to normal oral mucosa, hyperplasia, dysplasia and squamous cell carcinomas. Taken together, our results suggest that p16CDKN2A mutations in exon 2 are not involved in the multistep tongue carcinogenesis of Wistar rats induced by 4NQO.     

Alkylation-induced genotoxicity as a predictor of DNA repair deficiency following experimental oral carcinogenesis

The aim of this study was to evaluate alkylation induced genotoxicity as a result of DNA repair deficiency during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis by means of single cell gel (comet) assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. Blood samples and oral mucosa cells collected from all animals were divided into two aliquots of 20 μL each to study basal DNA damage and DNA damage due to genotoxin sensitivity. The first aliquot was processed immediately for comet assay to assess basal DNA damage. The second aliquot was treated with a known genotoxin, methylmetanesulfonate. Significantly greater DNA damage was noticed to oral mucosa cells from 4, and 12 weeks post-treatment. Peripheral blood cells did show statistically significant differences (P < 0.05) after 20 weeks-group (squamous cell carcinoma). In conclusion, alkylation induced genotoxicity as a result of DNA repair deficiency is present in oral mucosa cells following oral experimental carcinogenesis.     

Oral and intranasal administration of somatostatin DNA vaccine mediated by attenuated Salmonella enterica serovar Typhimurium to promote growth of piglets

An attenuated strain of Salmonella typhimurium has been used as a carrier for oral and intranasal genetic immunization. Here, we evaluate the efficacy of a vaccine strain of S. typhimurium. CSO22 (pGM-CSF/SS, plasmid granulocyte-macrophage colony-stimulating factor/somatostatin) expressing two copies of SS genes. A total of 115 piglets, aged 2 months old, were either orally or intranasally immunized against the vaccine strain CSO22 (pGM-CSF/SS) with three dosages (5 × 10(10) colony forming units (CFU), 5 × 10(9) CFU and 5 × 10(8) CFU). For oral immunization, the specific anti-SS antibodies were detected in the immunized piglets. The levels of SS antibodies in the high-dose immunized group (5 × 10(10) CFU) were significantly higher than that in the phosphate buffered saline immunized group (P < 0.01) and 40% of animals were positive in SS antibodies in the high-dose immunized group. Moreover, the weight gain of the high-dose group was increased by 20.86%, 10.26% and 15.30% during 4, 8 and 12 weeks, respectively, after immunization in comparison to the control. For intranasal immunization, the growth of the low-dose group was increased by 10.23% in the whole test period (12 weeks). In conclusion, our results suggest that the recombinant strain could elicit anti-SS antibodies and improve the growth performance of immunized piglets, and that the oral immunization program is better than the intranasal program.     

Critical Phases of Oral Primordium Development in Tetrahymena pyriformis GL-C: An Analysis Employing Low Temperature Treatment

SYNOPSIS. The effects of temperatures of 12–18 C on cell division and oral primordium development were investigated in cultures of synchronized Tetrahymena pyriformis GL-C. If exposures to 12 or 15 C were initiated prior to a “transition point,” long delays of cell division were generated. After this transition point, cell division could no longer be substantially delayed by exposure to low temperature. The time of the transition point was somewhat earlier with 15 C than with 12 C treatments. At temperatures higher than 15 C long delays of cell division were not generated regardless of time of treatment. The effects of low temperature on oral morphogenesis were strongly dependent on the stage which was affected. (i) The further development of cells initially in the “anarchic field” stage (stage 1) was immediately blocked at both 12 and 15 C. (ii) Cells initially in the stages of incipient membranelle differentiation (stages 2 and 3) continued to develop at both 12 and 15 C, and formed oral primordia in which all 3 membranelles were clearly differentiated (stage 4). The subsequent progress of these stage 4 primordia depended on the temperature: at 12 C virtually all were resorbed (and cell division was blocked); at 15 C only about 1/3 were resorbed, while the remaining 2/3 completed their development (with the concomitant completion of cell division). (iii) Cells initially in intermediate stages of membranelle differentiation (early stage 4) developed to some extent at 12 C, and then underwent resorpton of oral primordia and blockage of cell division; at 15 C such cells completed their development and division normally. (iv) Cells in which the membranelles and undulating membrane were complete or nearly so (stage 5 and very late stage 4) at the time of the beginning of the cold treatment subsequently finished their development and went thru cell division, even at temperatures as low as 5 C. These results indicate that in addition to a “stabilization point” which occurs shortly before the completion of membranelle development, there is an earlier change in the primordium at the time of the onset of membranelle development, which renders development much less sensitive to direct interference by low temperature.     

Design, synthesis, and bioavailability evaluation of coumarin-based prodrug of meptazinol

Based on the known coumarin-based prodrug system, a new meptazinol (Z)-3-[2-(propionyloxy) phenyl]-2-propenoic ester (3) was designed and synthesized as prodrug to minimize the first-pass effect of meptazinol (1) and improve the oral bioavailability. The prodrug (3) showed a 4-fold increase in oral bioavailability over the parent drug meptazinol in rats.     

Effects of oral functional training for nutritional improvement in Japanese older people requiring long-term care

Objectives: The aim of this study was to evaluate the effect of oral functional training and nutrient supplements to improve the nutrition of malnourished elderly people in a nursing home. Background: Malnutrition is a frequent problem in the elderly requiring long‐tem care; however, it is not clear whether oral functional training can be effective to improve nutrition. Subjects and methods: Fourteen subjects of 82 residents (mean age 85.7 ± 6.2 years) in a nursing home, who had a serum albumin level of ≤3.8 g/dl and understood the purpose of this study, were randomly divided into two groups of seven: one group served as the supplement group (mean age 87.0 ± 4.9 years) to which a high‐calorie and high‐protein diet was provided, and the other as the oral training plus supplement group (mean age 84.6 ± 10.1 years) to which oral functional training was given by a dental hygienist once a week as well as the above diet. Nutritional status was evaluated using serum biochemical values as indices at 4 months after the start of the intervention. Results: In the supplement group, serum albumin was 3.44 ± 0.36 g/dl at the start of the study (before intervention) and 3.24 ± 0.45 g/dl at 4 months after intervention. In the oral training plus supplement group, it was 3.56 ± 0.22 g/dl before intervention and significantly increased to 3.70 ± 0.33 g/dl after intervention (p < 0.05: Wilcoxon signed‐rank test). Conclusion: Nutritional supplements alone were not adequate, but with oral functional training to maintain and improve feeding function, nutritional improvement in the elderly could be observed.     

Discovery of 3-aryloxy-lactam analogs as potent androgen receptor full antagonists for treating castration resistant prostate cancer

High throughput cell-based screening led to the identification of 3-aryloxy lactams as potent androgen receptor (AR) antagonists. Refinement of these leads to improve the ADME profile and remove residual agonism led to the discovery of 12, a potent full antagonist with greater oral bioavailability. Improvements in the ADME profile were realized by designing more ligand-efficient molecules with reduced molecular weights and lower lipophilicities.     

Concurrent exposure to thermal stress and oral Ag induces intestinal sensitization in the mouse by a mechanism of regulation of IL-12 expression

The mechanism of food allergy remains unclear. The absorption of intact protein Ag into the intestinal tissue is a prerequisite in the development of intestinal sensitization. Previous studies indicate that thermal stress compromises the intestinal barrier function. Mice were concurrently exposed to thermal stress and oral Ag. Intestinal sensitivity, levels of serum-specific IgE, IL-4 and INF-gamma were assessed. Intestinal dendritic cell, Th1 and Th2 functions were determined. The mice that were treated with thermal stress and oral Ag showed high levels of serum Ag-specific IgE, intestinal mast cell activation in response to oral Ag challenge, suppression of IL-12 expression in the intestinal dendritic cells, inhibition of T-bet expression and Th1 function and marked increases in (GATA)3 expression and Th2 function. Mice exposed to thermal stress alone or oral Ag alone did not show any signs of the intestinal sensitization. Pretreatment with IL-12 inhibited the intestinal sensitization induced by the concurrent exposure to thermal stress and Ag gavage. We conclude that although Ag absorption is essential, Ag absorption alone is insufficient; other accessory factors that can disturb the local immune homeostasis are also required for the induction of intestinal sensitization. The present study illustrates that concurrent exposure to thermal stress and oral Ag can prove to be a factor in the induction of intestinal sensitization by a mechanism of regulating IL-12 expression.     

Effects of oral contraceptives and of the ovarian cycle on auditory performance at 4 and 6 kHz. Demonstration by functional audiometry

Absolute thresholds at 4 and 6 kHz were tested in 3 sessions before and after 20 min exposure to 105 dB (A) pink noise in 12 young normal cycling females 11 young females under oral contraceptives and 8 young men. Women under oral contraceptives show lower resting thresholds, more important TTS2 and higher recovery rate than normal cycling women and men. In normal cycling females, non parametric analysis of the data provides evidence that absolute thresholds at 4 and 6 kHz tend significantly to be higher at menses and lower during the postovulatory phase of the cycle.     

不同方法口服特比萘芬片治疗趾甲甲真菌病的疗效观察

目的评价不同方法口服特比萘芬片治疗趾甲甲真菌病的疗效。方法将入选患者随机分成两组,A组口服特比萘芬片0.25 g/d连续12周,B组前4周0.25 g/d,第5周开始隔天服0.25 g至16周,分别于治疗开始前、16周及26周对观察指标进行记录、分析。结果共入选1 001例,其中A组512例,16周、26周临床有效率分别是83.01%、95.31%,B组489例,16周、26周临床有效率分别是81.12%、93.86%,两组对应观察期有效率经χ2检验,差异无统计学意义,26周时有效率比16周有进一步提高。结论 4周后隔日服药疗法在减少服用14片特比萘芬片的情况下可以达到与常规治疗组近似的疗效,患者依从性较高,特比萘芬片治疗甲真菌病具有明显的后效应。     

Study of effectiveness of long-term per oral and parenteral cincacine administration at parenteral 241Am incorporation into the organism

Effect of long-term (during 4 weeks) cincacine administration following single parenteral 241Am intake has been studied on rats depending on method (per oral or parenteral), dosage and time of treatment initiation. Cincacine administration leads to limitation of radionuclide incorporation in the major organs of deposition for the both methods of introduction. At the parenteral 241Am intake in the organism parenteral cincacine administration was found to be more effective compared to per oral cincacine administration even in case of its dose increase by a factor of 6 and 12. At the parenteral introduction of the preparation, time of treatment beginning is more significant than at per oral administration.     

Oral tolerance: immune mechanisms and the generation of Th3-type TGF-beta-secreting regulatory cells

Oral tolerance is a long recognized method to induce peripheral immune tolerance. Oral tolerance has been used successfully to treat animal models of autoimmune diseases and is being tested in human diseases. Low doses of oral antigen induce active suppression, whereas high doses induce clonal anergy and deletion. Oral antigen preferentially generates a Th2(IL-4/IL-10)- or a Th3(TGF-beta)-type response. Th3-type cells are a unique T-cell subset which primarily secrete TGF-beta, provide help for IgA and have suppressive properties for Th1 and other immune cells. Th3-type cells appear distinct from the Th2 cells as CD4(+) TGF-beta-secreting cells with suppressive properties in the gut have been generated from IL-4-deficient animals. In vitro differentiation of Th3-type cells from Th0 precursors from TCR transgenic mice is enhanced by culture with TGF-beta, IL-4, IL-10 and anti-IL-12. Because regulatory T cells generated by oral antigen are triggered in an antigen-specific fashion but suppress in an antigen-nonspecific fashion, they mediate bystander suppression when they encounter the fed autoantigen at the target organ. Thus, mucosal tolerance can be used to treat inflammatory processes that are not autoimmune in nature. Mucosal antigen has also been used to treat animal models of stroke and of Alzheimer's disease. Induction of low-dose oral tolerance is enhanced by oral administration of IL-4 and IL-10. Coupling antigen to CTB or administration of Flt-3 ligand enhances oral tolerance. Anti-B7.2 but not anti-B7.1 blocks low-dose, but not high-dose oral tolerance. High-dose oral tolerance is blocked by anti-CTLA-4. CD25(+) CD4(+) regulatory T-cell function also appears to be related to TFG-beta.     

补阳还五汤口服和药浴对损伤的大鼠坐骨神经传导速度的影响

目的探讨补阳还五汤口服加药浴对坐骨神经传导速度的影响。方法60只SD大鼠暴露左侧坐骨神经。对照组只钳夹;实验组钳夹并加用补阳还五汤口服及药浴治疗。观察钳夹前和钳夹切除后大鼠坐骨神经传导速度（SNCV）。结果于2、4、6周分别测对照组、实验组的坐骨神经传导速度（SNCV）。各时间段实验组坐骨神经传导速度恢复快于对照组,P〈0．01。结论补阳还五汤口服加药浴对坐骨神经传导速度有明显的促进作用。     

Orally active factor Xa inhibitor: synthesis and biological activity of masked amidines as prodrugs of novel 1,4-diazepane derivatives

Factor Xa (fXa) is a serine protease, which plays a pivotal role in the coagulation cascade. To improve the oral anticoagulant activity of fXa inhibitors containing a 1,4-diazepane moiety as the P4 part, a prodrug strategy was examined. Among the compounds evaluated in this study, amidoxime prodrugs bearing an ester moiety, such as compounds 21 and 30, showed effective oral anticoagulant activity in mice.     

Evaluation of the Lon-deficient Salmonella strain as an oral vaccine candidate

We evaluated the efficacy of CS2022 (the Lon protease-deficient mutant strain of Salmonella enterica serovar Typhimurium) as a candidate live oral vaccine strain against subsequent oral challenge with a virulent strain administered to BALB/c and C57BL/6 mice. CS2022 persistently resided in the spleen, mesenteric lymph nodes, Peyer's patches, and cecum of both strains of mice after a single oral inoculation with 1 x 10(8) colony-forming units. Finally, CS2022 almost disappeared from each tissue sample by week 12 in BALB/c mice, whereas CS2022 still resided in each tissue type at week 12 after inoculation of C57BL/6 mice. A significant increase in the serovar Typhimurium lipopolysaccharide-specific secretory immunoglobulin A (s-IgA), as measured for one of the mucosal immune responses, was detected in bile and intestinal samples of both strains of immunized mice at week 4 after immunization. In addition, the expression of gamma interferon mRNA in the spleens of both strains of immunized mice, especially those of C57BL/6 mice, was significantly increased at week 4 after immunization and was boosted during the following 5 days after the challenge was administered to the mice. Furthermore, peritoneal macrophages isolated from immunized mice at week 4 after immunization exhibited an increase in intracellular killing activity against both virulent and avirulent Salmonella. The present results suggested that salmonellae-specific s-IgA on the mucosal surfaces induced by immunization with CS2022 generally prevented mice from succumbing to an oral challenge with a virulent strain. Simultaneously, CS2022 promoted the protective immunity associated with macrophages in both strains of mice.     

Orally tolerant CD4 T cells respond poorly to antigenic stimulation but strongly to direct stimulation of intracellular signaling pathways

The response of splenic CD4 T cells from ovalbumin (OVA)-specific T cell receptor (TCR) transgenic mice after long-term feeding of a diet containing this antigen was examined. These CD4 T cells exhibited a decreased response to OVA peptide stimulation, in terms of proliferation, interleukin-2 secretion, and CD40 ligand expression, compared to those from mice fed a control diet lacking OVA, demonstrating that oral tolerance of T cells had been induced through oral intake of the antigen. We investigated the intracellular signaling pathways, which were Ca/CN cascade and Ras/MAPK cascade, of these tolerant CD4 T cells using phorbol-12-myristate-13-acetate (PMA) and ionomycin, which are known to directly stimulate these pathways. In contrast to the decreased response to TCR stimulation by OVA peptide, it was shown that the response of splenic CD4 T cells to these reagents in the state of oral tolerance was stronger. These results suggest that splenic CD4 T cells in the state of oral tolerance have an impairment in signaling, in which signals are not transmitted from the TCR to downstream signaling pathways, and have impairments in the vicinity of TCR. This revised version was published online in July 2006 with corrections to the Cover Date.