アパタイト セメント ノ ホネ トノ チカン : バイヨウ ハコツ サイボウ オヨビ コツガ サイボウ オ モチイタ ケントウ

アパタイトセメントは、優れた生体親和性と骨伝導性を示す生体活性セメントである。しか し、このアパタイトセメント(従来型)には硬化時間が長い(3O～60分)、硬化前のペー ストが体液と接触すると崩れてしまうなどの問題点があった。そこでわれわれは、約5分で硬 化する迅速硬化型アパタイトセメントを、さらに練和直後に血清に浸漬しても崩れることなく 約5分で硬化する非崩壊型アパタイトセメントを開発し、優れた生体親和性と骨伝導性をもつ ことを明らかとしてきた。 骨欠損部に補填されたアパタイトセメントの骨との置換に関しては、必ずしも一定の見解は 得られていない。そこで本研究では、アパタイトセメントが骨と置換するか否かを検討する目 的で、培養破骨細胞によるセメントの吸収と培養骨芽細胞によるセメント上での骨形成の二面 から検討を行った。 【材料と方法】従来型、迅速硬化型、非崩壊型の3種類のアパタイトセメントを粉液比2.0で練 和し、37℃相対湿度100%の条件下で24時間硬化させたディスク状硬化体を試料とした。対照と して、焼結体アパタイトを用いた。さらに、セメント吸収性の実験には、牛皮質骨より調整し た骨片も対照として用いた。 家兎の長管骨より採取した破骨細胞を含む骨髄細胞を試料上に播種し、48時間培養した後、 酒石酸抵抗性酸ホスファターゼ染色を行い、試料上に付着した破骨細胞数を計測した。また、 走査型電子顕微鏡を用いて、付着破骨細胞の形態を観察するとともに、吸収窩数および、吸収窩 面積について定量的測定を行った。アパタイトセメントが骨芽細胞に及ぼす影響についての実 験では、当教室においてこれまで継代培養されてきたヒト骨芽細胞を各試料上に播種し、初期 接着性、細胞増殖、アルカリホスファターゼ活性、I型コラーゲン合成量、オステオカルシン 産生量について評価を行った。 【結果】破骨細胞を用いたセメント吸収性に関する検討では、付着破骨細胞数はアパタイトセ メント群および、骨片では差がなかったのに対し、焼結体アパタイト上の付着破骨細胞数はアパ タイトセメント群および骨片に比べ、有意に少なかった。また、吸収窩に関して、焼結体アパ タイト表面には破骨細胞による吸収窩が全く認められなかったのに対し、アパタイトセメント 群においては破骨細胞吸収窩が認められた。アパタイトセメント表面に認められた吸収窩数、 吸収窩面積は、骨片のそれと比較してそれぞれ1/12、1/120であった。また、3種のアパタイト セメント間に有意な差は認められなかった。培養骨芽細胞を用いた骨形成に関する検討では、 初期接着性および細胞増殖に関して、アパタイトセメント群と焼結体アパタイトとの間で有意 な差は認められなかった。しかし、骨芽細胞の分化マーカーの発現に関しては、検討したすべ ての時期でアパタイトセメント群は焼結体アパタイトに比較して有意に高い値を示した。な お、アパタイトセメント間に有意差は認められなかった。 【結論】本研究結果から、アパタイトセメントは、焼結体アパタイトに比較して、破骨細胞に より吸収されやすく、また、骨芽細胞の分化を促進させることが明らかとなった。また、迅速 硬化型および非崩壊型アパタイトセメントは、破骨細胞および骨芽細胞に対して従来型アパタ イトセメントと同じ挙動を示すことから、骨と置換される有用な生体材料であることが示唆さ れた。Apatite cement (AC) was invented in 1986 and is used for reconstruction of bony defects but its clinical applications have been limited because it takes 30 min to set and decays immediately upon exposure to liquid before setting. Therefore，we have developed two types of new AC; fast-setting AC and anti-washout type AC. These cements have good biocompatibility and osteoconductivity same as conventional AC in vivo. However，it is a controversial matter whether AC can be replaced with bone in vivo or not. The aim of this study，therefore，is to evaluate the bone replacement of ACs objectively and quantitatively. For that purose，it is necessary to evaluate the resorption of ACs by osteoclasts and bone formation on ACs by osteoblasts，respectively， because bone replacement includes both processes. Sintered hydroxyapatite (sintered HAP) is used as control because sintered HAP is known to be nonresorbable clinically. For the evaluation of the resorption of ACs，osteoclats obtained from rabbit were cultured on sintered HAP，ACs and bone slice. The number of osteoclasts on sintered HAP was significantly less than that on both ACs and bone slice. ACs and bone slice were obviously resorbed by osteoclasts but sintered HAP was not. Intereslingly，the number of lacunae on bone slice was about 12 times as those on ACs and the resorption area on bone slice was about 120 times as those on ACs. There was no significant difference among 3 types of AC. For the evaluation of the bone formation，human osteoblasts were cultured on ACs and sintered HAP. There were no difference in initial cell attachment and proliferation of osteoblasts on between ACs and sintered HAP. The alkaline phosphatase activities of ACs， however，and protein levels for type Ⅰ collagen and osteocalcin of ACs were greater than that of sintered HAP. Thus，the differentiation of osteoblasts was promoted on ACs more than on sintered HAP. There was no difference among ACs. These results suggested that ACs would be resorbed by osteoclasts in vivo. In this study，it is suggested that ACs would be resorbed by osteoclasts and that osteoblasts on ACs would produce larger amount of new bone than those on sintered HAP. In conclusion，ACs are useful biomaterials which can be replaced with bone

Effects of adenoviral-mediated hepatocyte growth factor on liver regeneration after massive hepatectomy in rats

Resection is the only curative treatment for liver metastasis of colorectal cancers. Despite the supreme regenerative potential of the liver, major hepatectomy sometimes leads to liver failure, and the limitation of resectable liver volumes makes advanced tumors inoperable. This study was attempted to promote liver regeneration using hepatocyte growth factor (HGF) gene transfection by venous-administered adenovirus and to improve the survival of rats after massive hepatectomy. The adenovirus that encodes HGF was administered to rats before 85%-hepatectomy. The administration of HGF gene improved the survival of rats after massive hepatectomy, while the administration of control adenovirus deteriorated their survival. Gene transfection of HGF showed up-regulation of serum HGF, stimulation of hepatocellular proliferation and rapid liver regeneration. Moreover, HGF administration reduced apoptosis of hepatocytes. The administration of HGF gene prevented liver dysfunction after major hepatectomy and may be a new assist for surgery.</p

コウカセイ エシセイ ジュウカクエン オ ハッショウ シタ カガク チシ シュウイエン ノ 1レイ

We present a case of pericoronitis of lower wisdom tooth leading to descending necrotizing mediastinitis. A 52-year-old man visited our hospital because of swelling and pain in buccal region on the right side in spite of chemotherapeutics at a practicing physician, whose diabetic nephropathy had been treated with dialysis treatment by the same physician. Orthopantomography elucidated an impacted wisdom tooth of the right side mandible and osteosclerosis around there. CT revealed inflammatory thickening of subcutaneous fat tissue from buccal to cervical region. In the blood examination, the values of WBCs, RBCs, platelets, CRP, AST, LDH, TG, BUN, creatinine, GLU, K and Ca increased abnormally, while those of hemoglobin, MCV，MCH，MCHC, albumin, Cl, decreased extraordinarily. Immediate medication of antibiotics was worked out under a clinical diagnosis of pericoronitis of lower wisdom tooth, periostitis of the mandible and cervical cellulitis. Nevertheless, rapid inflamation progressed downward; mediastinal abscess was found by CT image taken 6 days later from the beginning of the therapy. Immediately, extraction of pathogenic teeth, cervical drainage, and transcervical and transthoracic mediastinal drainage were performed under a diagnosis of descending necrotizing mediastinitis. Moreover, bacterial examination was performed using a pus specimen derived from abscess; α-Streptococcus and Prevotella intermedia were detected. CT taken 2 weeks later from the beginning of the therapy revealed continuing bilateral pleural and pericardial effusion in spite of intensive care. Unfortunately he was died of multi organ failure caused by septic shock a month later from the beginning of the therapy

Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

Citrus sudachi is a well-known fruit in Tokushima Prefecture, Japan, and its peels are rich in phytochemicals, including phenolic compounds. Although it is expected that the extract of the C. sudachi peel elicits various beneficial physiological activities, the effect on the skin has not been investigated. In this study, we report that the aqueous extract from the peel of C. sudachi suppresses cell proliferation of the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes. The extract of C. sudachi peel suppressed epidermal growth factor (EGF)-induced EGF receptor activation and tumor necrosis factor (TNF)-α-induced extracellular regulated kinase (ERK) 1/2 activation, which suggests that the extract exerts its inhibitory effect through inhibition of both the EGF receptor (EGFR) and its downstream molecules. Additionally, the extract of C. sudachi peel potentiated calcium-induced keratinocyte differentiation. These results suggest that the extract of C. sudachi peel may have beneficial effects against skin diseases that are characterized by hyperproliferation of epidermal keratinocytes, such as those seen in psoriasis and in cutaneous squamous cell carcinoma

Advance Requests of In-patients and Their Families regarding Medical Intervention Practices at the End of Life

Much emphasis is being placed nowadays on Advance Care Planning（ACP）. Under this circumstance, we report on the “advance-request form” prepared by our hospital, along with some relevant considerations. ［Intended Persons and Method］A total of ５３９ newly admitted patients and their families were asked to sign and submit the “advance-request form,” indicating their preferences on the following three kinds of end-of-life interventional practices:（ １）cardiac massage,（２）endotracheal intubation and mechanical ventilation, and（３）use of vasopressors. ［Results］Completed questionnaires were returned by ２１５ male and ３２４ female patients（average age :８２．３ years）. Of the responders, ７２（１４％）indicated their desire for all the three of the aforementioned interventions（［１］,［２］, and［３］）,６５（１２％）indicated their desire for only（１）, ４５（８%）indicated their desire for only（１）and（３）, １４（３%）indicated their desire for only（３）, while the remaining３４１（６３%）requested that none of these to be implemented. Of all the patients, ８７（１６％）patients were able to make their own decisions. ［Conclusion］About ３０％ or more patients and their families indicated their desire for some kind of life-sustaining treatment at the end of life. We believe that ACP only prioritizes a patient’s right to self-determination and that the practice of ACP should not lead to withholding of life-sustaining treatment

イチジルシイ コツキュウシュウ オ トモナッタ シセイ ジョウガクドウエン ノ 1レイ

We present a case of odontogenic maxillary sinusitis with marked perisinuous bone resorption. A 29-year-old man visited to our hospital because of pain in buccal region on left side after extraction of teeth at a dental practitioner. Orthopantomography and CT were performed and revealed inflammatory thickening of maxillary sinus mucosa and marked perisinuous bone resorption. In the blood examination, the values of WBCs and CRP were elevated abnormally. Moreover, bacterial examination was performed using the exudate from maxillary sinus through a fistula after extraction of teeth; α-Streptococcus, Prevotella buccae, Prevotella intermedia, Prevotella melaninogenica and Acinetobacter baumannii were detected. First, medication of antibiotics and irrigation of maxillary sinus was worked out under a clinical diagnosis of odontogenic maxillary sinusitis. These therapies didn't change perisinuous bone resorption for the better. Sequestrum and mucosa of maxillary sinus were biopsied to examine thoroughly; diagnosis of odontogenic maxillary sinusitis was confirmed histopathologically. Moreover, biochemical examination of blood showed normal serum level of specific markers for bone metabolism or Aspergilli. The similar therapies were continued from then and perisinuous bone resorption stopped suddenly for unknown reasons 3 months after these therapies. Time course of perisinuous bone regeneration was found by CT. Finally, operation to close the antrooral fistula with palatal flap was performed. There has been no relapse of inflammation for more than 5 years

バッシゴ シュッケツ オ ケイキ ニ シンダン サレタ コウレイシャ ニオケル センテンセイ ケツユウビョウ A ﾉ 1レイ

Hemophilia A is often diagnosed by gingival change, traumatic injuries, or bleeding after extraction in childhood, but rarely in senior age. We experienced that a 66 year-old man was diagnosed as hemophilia A by bleeding after tooth extraction. He was referred to our hospital for control the bleeding after tooth extraction. Although we tried to stop bleeding by local hemostasis, we repeated to bleed several times. Then we examined the level of hemorrhage factors. As a result, the patient was diagnosed as moderate hemophilia A, and he received recombinant factor VIII intravenously. After that, the bleeding had been stopped completely