Anti-Allergic Activity of Monoacylated Ascorbic Acid 2-Glucosides

2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2G) is one of the stable ascorbic acid (AA) derivatives known as provitamin C agents. We have previously synthesized two types of monoacylated derivatives of AA-2G, 6-O-acyl-2-O-α-D-glucopyranosyl-L-ascorbic acids having a straight-acyl chain of varying length from C4 to C18 (6-sAcyl-AA-2G) and a branched-acyl chain of varying length from C6 to C16 (6-bAcyl-AA-2G) in order to improve the bioavailability of AA-2G. In this study, 6-sAcyl-AA-2G and 6-bAcyl-AA-2G per se showed the inhibitory effects on hyaluronidase activity and degranulation. 6-sAcyl-AA-2G exhibited strong inhibitory effects on hyaluronidase activity and degranulation in a concentration-dependent manner, and the inhibitory effects tended to become stronger with increasing length of the acyl chain. 2-O-α-D-Glucopyranosyl-6-O-hexadecanoyl-L-ascorbic acid (6-sPalm-AA-2G), which has a straight C16 acyl chain, was the most potent effective for inhibition of hyaluronidase activity and for inhibition of degranulation among the 6-sAcyl-AA-2G derivatives and the two isomers of 6-sPalm-AA-2G. Furthermore, percutaneous administration of 6-sPalm-AA-2G significantly inhibited IgE-mediated passive cutaneous anaphylaxis reaction in mice. These findings suggest that 6-sPalm-AA-2G will be useful for treatment of allergies

Clinico-statistical study of HIV patients in clinical dental departments at Tokushima University Hospital

HIV 感染症診療は，免疫不全の原因治療と免疫不全に伴う日和見感染症の管理が2 本柱とされる．日和見感染症の管理という観点から，口腔衛生管理は重要で歯科医師の果たす役割は大きい．われわれは，徳島大学病院歯科診療科を受診した31 例のHIV 感染者の臨床統計的検討を行い，今後増加すると予想されるHIV感染者に対する歯科医療の留意点について考察した．症例は男性29 例，女性2 例で，平均年齢は31.7 ± 12.4歳であった．感染経路は血液製剤による感染が8 例，性感染による感染が23 例であった．31 例中3 例で抗HIV 療法が導入されていなかった．HIV 感染者の合併症の保有率は高く，血友病群ではHCV 感染症（75.0%），C 型肝硬変（37.5%）が多く，性感染症群では梅毒（30.4%），HBV 感染症（21.7%）が多かった．歯科診断では歯周病，う蝕が多かったが，31 例中7 例に口腔粘膜疾患を認めた．歯科治療内容は抜歯処置15 例，歯周治療12 例，修復治療5 例の順に多かった．血友病群の抜歯の際は血液凝固製剤を術前・術後に補充して抜歯を行った． HIV 感染者の歯科医療は，医科と連携し患者個々のHIV 感染症の病態や合併症を把握し，日和見疾患のリスク因子である口腔感染症を治療し，予防する必要がある．そして，患者にHIV 感染症と口腔症状の関連性と定期的な歯科治療の必要性を説明し，患者にあわせた無理のない口腔衛生指導を行いながら，長期的なメインテナンスが必要であると考えられた．To prevent opportunistic infectious disease in HIV patients with immunodeficiency, oral management is important. In order to identify focal points in dental treatment, we studied the 31 HIV patients（ 29 males and 2 females, mean age 31.7±12.4 years） who visited the clinical dental departments of Tokushima University Hospital from 1981 to 2016. Among the 31 cases, 3 cases did not start antiretroviral therapy （ART）. The HIV patients were classified by infection route, producing a hemophilia group （8 cases） and sexually transmitted disease group（ 23 cases）. Clinical complications were different in these two groups: complications in the hemophilia group included hepatitis C virus （HCV） infection （75.0%） and hepatitis C-related cirrhosis （37.5%）, whereas in the sexually transmitted disease group complications included syphilis （30.4%） and hepatitis B virus （HBV） infection （21.7%）. There were many dental caries and periodontal diseases found in the patients. On the other hand, oral mucosal diseases were observed in seven of 31 cases. Dental treatment consisted of tooth extraction in 15 cases, periodontal treatment in 12 cases, and caries treatment in 5 cases. Blood coagulation formulation was supplied during tooth extraction in the hemophilia group. Careful attention must be given according to the condition of each HIV patient during dental treatment, and the risk of opportunistic infection caused by oral infection must be treated and prevented

PREVENTION OF ROS GENERATION VIA STABILIZATION OF Nrf2 ACTIVATION

Chemotherapy‑induced oral mucositis is a common adverse event in patients with oral squamous cell carcinoma, and is initiated through a variety of mechanisms, including the generation of reactive oxygen species (ROS). In this study, we examined the preventive effect of γ‑tocotrienol on the 5‑FU‑induced ROS production in human oral keratinocytes (RT7). We treated RT 7 cells with 5‑FU and γ‑tocotrienol at concentrations of 10 μg/ml and 10 nM, respectively. When cells were treated with 5‑FU alone, significant growth inhibition was observed as compared to untreated cells. This inhibition was, in part, due to the RO S generated by 5‑FU treatment, because N‑acetyl cysteine (NAC), a RO S scavenger, significantly ameliorated the growth of RT7 cells. γ‑tocotrienol showed no cytotoxic effect on the growth of RT 7 cells. Simultaneous treatment of cells with these agents resulted in the significant recovery of cell growth, owing to the suppression of RO S generation by γ‑tocotrienol. Whereas 5‑FU stimulated the expression of NF‑E2‑related factor 2 (Nrf2) protein in the nucleus up to 12 h after treatment of RT 7 cells, γ‑tocotrienol had no obvious effect on the expression of nuclear Nrf2 protein. Of note, the combined treatment with both agents stabilized the 5‑FU‑induced nuclear Nrf2 protein expression until 24 h after treatment. In addition, expression of Nrf2‑dependent antioxidant genes, such as heme oxygenase‑1 (HO‑1) and NAD(P)H:quinone oxidoreductase‑1 (NQO‑1), was significantly augmented by treatment of cells with both agents. These findings suggest that γ‑tocotrienol could prevent 5‑FU ‑induced ROS generation by stabilizing Nrf2 activation, thereby leading to ROS detoxification and cell survival in human oral keratinocytes

PREVENTION OF ROS GENERATION VIA STABILIZATION OF Nrf2 ACTIVATION

Chemotherapy‑induced oral mucositis is a common adverse event in patients with oral squamous cell carcinoma, and is initiated through a variety of mechanisms, including the generation of reactive oxygen species (ROS). In this study, we examined the preventive effect of γ‑tocotrienol on the 5‑FU‑induced ROS production in human oral keratinocytes (RT7). We treated RT 7 cells with 5‑FU and γ‑tocotrienol at concentrations of 10 μg/ml and 10 nM, respectively. When cells were treated with 5‑FU alone, significant growth inhibition was observed as compared to untreated cells. This inhibition was, in part, due to the RO S generated by 5‑FU treatment, because N‑acetyl cysteine (NAC), a RO S scavenger, significantly ameliorated the growth of RT7 cells. γ‑tocotrienol showed no cytotoxic effect on the growth of RT 7 cells. Simultaneous treatment of cells with these agents resulted in the significant recovery of cell growth, owing to the suppression of RO S generation by γ‑tocotrienol. Whereas 5‑FU stimulated the expression of NF‑E2‑related factor 2 (Nrf2) protein in the nucleus up to 12 h after treatment of RT 7 cells, γ‑tocotrienol had no obvious effect on the expression of nuclear Nrf2 protein. Of note, the combined treatment with both agents stabilized the 5‑FU‑induced nuclear Nrf2 protein expression until 24 h after treatment. In addition, expression of Nrf2‑dependent antioxidant genes, such as heme oxygenase‑1 (HO‑1) and NAD(P)H:quinone oxidoreductase‑1 (NQO‑1), was significantly augmented by treatment of cells with both agents. These findings suggest that γ‑tocotrienol could prevent 5‑FU ‑induced ROS generation by stabilizing Nrf2 activation, thereby leading to ROS detoxification and cell survival in human oral keratinocytes

トクシマ ダイガク ビョウイン セイシンカ シンケイカ ニュウイン カンジャ ニ タイスル コウクウ ケア ノ イギ

For patients with mental diseases, safe food-intake and the maintenance of good oral hygiene become difficult due to a decline in the ability of daily livings. In addition, a majority of patients suffer from the lack of reflection of both deglutition and cough as well as clinical silent aspiration, resulting from the extrapyramidal symptom (EPS) caused by antipsychotics. In this clinical study, we evaluated the oral environment in 10 inpatients with psychiatry neurology, and examined the usefulness of professional oral care. They were divided into 2 groups: the physical restriction group (restriction group) and the non-physical restriction group (control group), followed by the estimation of the conditions of oral hygiene and the days accompanied by fever, one of the symptoms of aspiration-related pneumonia, before and after professional oral care intervention. As a result, restriction group had poor oral hygiene condition as compared to the control group. After professional oral care intervention, oral hygiene condition was significantly improved in the restriction group, and reached to the same levels as in the control group. The days with fever were 7.3 and 5.0 days per month in the restriction group before and after the intervention, respectively. In the control group, those were 0.6 and 0 day per month before and after intervention, respectively. The cause of the difference in days with fever between 2 groups was considered to be the effect of clinical silent aspiration by EPS induced by antipsychotics. The professional oral care contributed to the improvement of the oral hygiene in inpatients with psychiatry neurology, resulting in the reduction of aspiration-related pneumonia. Therefore, the role of dentistry in the field of psychiatry neurology would be inevitable in the future

ノウソッチュウ カンジャ ノ コウクウナイ ショケン ト シカ カイニュウ ノ ユウヨウセイ ニツイテ

We analyzed the need for dental intervention in patients with acute cerebral vascular disorders. In this study, we enrolled 43 individuals in SCU (male: 28, female: 15) in need of oral health management. The mean age of the patients was 68.0 ± 14.9. They had been diagnosed as cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, or transient ischemic attack. Thirteen subjects were affected with pneumonia and could not handle self-care management. Furthermore, 10 subjects had poor oral hygiene. There were clearly more pneumonia patients in the intubation group compared to the non-intubation group. In addition, 18 cases (41.9%) needed dental treatment, and 5 cases received dental treatment. Patients with acute stroke had poor oral hygiene with disturbance of consciousness and paralysis, suggesting a possible cause of pneumonia in these patients. Half of patients required dental intervention, indicating that oral management may be necessary for stroke patients to prevent the occurrence of pneumonia

トクシマ ダイガク ビョウイン ニオケル シュウジュツキ コウクウ キノウ カンリ ノ ゲンジョウ ト カダイ

It has been shown that oral hygiene affects the onset of perioperative complications. The usefulness of perioperative oral function management aiming at the outbreak decrease in treatment complications and an early discharge was recognized. As a result, perioperative oral function management fee was founded at revision of medical service fees in Fiscal year 2012. 　In this clinical study, we evaluated the implementation of perioperative oral function management in Tokushima University Hospital. We examined 781 patients, including 563 patients for surgery and 218 patients for chemotherapy and radiotherapy. The mean age of patients was 58.8 ± 12.4 years old. 　The implementation rate of perioperative oral function management was 9.7% in the patients of surgery, and 17.4% in those of chemotherapy and radiotherapy. The highly required medical department was neurosurgery in the patients of surgery, and hematology in those of chemotherapy and radiotherapy. The mean number of tooth present was 21.3 ± 7.1 in the patients of surgery, and 19.8 ± 7.2 in those chemotherapy and radiotherapy. The rate of dental treatment was required in 40.5% of total patients who received surgery, and in 51.4% of patients who received chemotherapy and radiotherapy. The rate of patients who received denture treatment attained to 11.9% of the whole patients receiving surgery, and 13.3% of patients receiving chemotherapy and radiotherapy. 　It was revealed that there were many patients required potential demands in perioperative oral function management, and that there were many patients who need dental or denture treatment. We would like to develop perioperative oral function management by the interprofessional collaboration in health and social care

Anti-Allergic Activity of Monoacylated Ascorbic Acid 2-Glucosides

2-O-α-d-Glucopyranosyl-l-ascorbic acid (AA-2G) is one of the stable ascorbic acid (AA) derivatives known as provitamin C agents. We have previously synthesized two types of monoacylated derivatives of AA-2G, 6-O-acyl-2-O-α-d-glucopyranosyl-l-ascorbic acids having a straight-acyl chain of varying length from C4 to C18 (6-sAcyl-AA-2G) and a branched-acyl chain of varying length from C6 to C16 (6-bAcyl-AA-2G) in order to improve the bioavailability of AA-2G. In this study, 6-sAcyl-AA-2G and 6-bAcyl-AA-2G per se showed the inhibitory effects on hyaluronidase activity and degranulation. 6-sAcyl-AA-2G exhibited strong inhibitory effects on hyaluronidase activity and degranulation in a concentration-dependent manner, and the inhibitory effects tended to become stronger with increasing length of the acyl chain. 2-O-α-d-Glucopyranosyl-6-O-hexadecanoyl-l-ascorbic acid (6-sPalm-AA-2G), which has a straight C16 acyl chain, was the most potent effective for inhibition of hyaluronidase activity and for inhibition of degranulation among the 6-sAcyl-AA-2G derivatives and the two isomers of 6-sPalm-AA-2G. Furthermore, percutaneous administration of 6-sPalm-AA-2G significantly inhibited IgE-mediated passive cutaneous anaphylaxis reaction in mice. These findings suggest that 6-sPalm-AA-2G will be useful for treatment of allergies