A Case of Non-Operative Management for Sulfuric Acid Burns

It is thought that severe chemical burns usually require a treatment of extended deep skin and subcutaneous tissue debridement and subsequent skin grafting. However, in this report we discuss the successful treatment of a severe dorsal chemical burn caused by sulfuric acid without skin grafting. A 45-year-old man was showered with highly concentrated (80%) sulfuric acid from a pipe burst at a factory. He sustained severe chemical burn injuries to the limbs and back. On arrival at the hospital, total body surface area burned, the burn index, and the prognostic burn index were 61.5%, 57.7, and 102.7, respectively. Considering the patient\u27s functional prognosis, surgical treatment of the limbs involving skin grafting was performed early in the treatment process. Additionally, daily bedside debridement of necrotic tissue of the back resulted in complete epithelialization without skin grafting. It is difficult to accurately assess the depth of dorsal burns due to the thickness of dorsal skin. In cases of chemical burns, skin color changes associated with chemical reaction make the assessment of burn depth even more difficult. The dorsal burn was estimated to be thirddegree on arrival in the present case. However, complete epithelialization without skin grafting suggests that it was a second degree burn. The patient was discharged 218 days after injury. The patient\u27s functional prognosis was satisfactory with soft skin texture and no contractures

ダッシュボード損傷による外傷性気管断裂の1例

鈍的外傷に起因した頸部気管損傷は比較的稀な外傷であり,一般的に緊急で気道を確保しないと致命的である.今回,我々はダッシュボード損傷による頸部気管断裂をきたした重症外傷の1救命例を経験したので報告する.症例は21歳の女性.車の助手席に乗車中,交通事故にて受傷した.心肺停止状態で前医に搬送され蘇生処置に反応したために当院紹介となった.来院時JCS 300,バイタルサインは安定しており,診察上は前頚部に擦過傷を認めたのみであった.その際の画像検査で頸部気管断裂と診断されたが,気道開通は得られており換気可能であったために早急に気管再建術を施行しなかった.その後,待機的に気管切開術と気管断端処理を行い救命できた.本症例を経験し,力学的作用の面から受傷機転を考察するとともに,頸部気管断裂に対する治療戦略について文献的検討を加えて考察したので報告する.Blunt cervical tracheal injury is a rare trauma. However, it is critical and frequently requires emergency airway management with surgical intervention, such as, emergency neck exploration and tracheostomy or reconstruction of the tracheal airway. This is an interesting and rare case of blunt cervical tracheal injury which was successfully managed with only oral tracheal intubation in the initial resuscitation. A 21-year-old female passenger suffered dashboard injury in the neck due to a head-on collision. At the scene of the accident, she was in cardiac arrest on arrival of the rescue team. She was then transported to a near-by emergency hospital with cardio-pulmonary resuscitation. At the hospital she was successfully resuscitated with an uneventful endotracheal intubation. Her vital signs were stabilized but she did not regain consciousness. Therefore she was referred to this hospital for further evaluation of life-threatening injuries and treatment of hypoxic brain damage due to prolonged cardio-pulmonary arrest time. On her arrival to this hospital, her airway was maintained without suspicion of tracheal injury. Although, there was minor abrasion over the anterior neck, there was no noticeable subcutaneous emphysema or suggested tracheal injury. Since she had suffered a high-impact automobile accident, a pan-scan of whole body was performed to rule out fatal life-threatening injuries in the torso. And it turned out that she had a cervical tracheal injury with dislodgment of the tip of an endotrahceal tube through the tracheal rupture into the soft tissue of anterior neck. The airway was maintained by a side hole of the endotracheal tube which enabled air exchange from the tube to distal trachea. This misplacement of the tip was confirmed by a bronchoscopy and the tip position was successfully corrected into distal trachea to the tracheal injury site. After the bronchoscopic procedure, ventilation was successfully maintained without any respiratory problems. Seven days after admission, neurological evaluation revealed that her persistent unconsciousness might have been due to post-resuscitation encephalopathy. Therefore it was feasible to do a permanent tracheostomy rather than reconstruction of the trachea. Finally, the mechanism of the cervical tracheal injury and strategy of staged treatments in this case was discussed with review of past articles

異なる経過をたどった腎障害を合併したグリホサート中毒の2症例

グリホサート含有除草剤は比較的安全性の高い除草剤として知られているが，大量に内服した場合には死亡例も報告されている．特に腎機能障害を合併した症例は重症とされ血液透析も検討されるが，現在のところその導入基準及び有効性は明らかとなっていない．今回，腎機能障害を呈した重症中毒症例を２例経験したが，大きく異なる経過をとったため，血中グリホサート濃度の推移を踏まえ，透析の有用性について考察した．症例１は40歳代男性．自殺目的でグリホサートイソプロピルアミン塩を250 ml 飲用した後，嘔吐・下痢の症状を認め当院へ搬送された．来院時，意識は清明でバイタルサインは安定していたが，入院後，呼吸不全，腸閉塞，無尿を来したため，人工呼吸管理，イレウス管挿入を施行した．輸液負荷にて再度尿の流出が得られたため血液透析は施行しなかった．その後，腎機能障害は改善し，呼吸状態も安定．第16病日に抜管し第26病日に軽快退院した．症例２は70歳代男性．自殺目的でグリホサートカリウム塩を約250 ml 飲用し，当院へ救急搬送された．意識は清明でバイタルサインは安定していたが，来院時より無尿の状態であった．輸液負荷・利尿剤の持続投与に反応がないため，透析を施行した．透析後より自尿が得られ，第６病日に退院した．これは，同様に腎機能障害を合併した症例１と比較し，入院期間は約1/4と短期間である．血液透析を施行する前後で，グリホサートの血中濃度が低下しており，グリホサートを血液中から除去することで，症状の軽減，及び早期退院に結びついた可能性がある．グリホサート含有除草剤の中毒を２症例経験した．血液透析施行例で非施行例と比べ入院期間が短かったことから，血液透析が有効である可能性が示唆された．有用性の証明には，今後さらなる症例の蓄積が必要であるが，腎機能障害を合併したグリホサート含有除草剤中毒の症例に対し，血液透析を検討する価値があると思われた．Although glyphosate-surfactant herbicides (GlySH) are considered to be relatively safe, the ingestion of large quantities can cause death. Dialysis is often performed when GlySH poisoning is complicated with severe acute kidney injury (AKI). However, the introduction criteria and validity have yet to be determined.Here, we describe two patients with severe AKI that followed different courses after treatment with extracellular fluids and hemodialysis.Case 1: A man in his 40s tried to commit suicide by drinking GlySH containing glyphosate isopropylamine salt, which induced vomiting and diarrhea. His vital signs and consciousness were normal on arrival at hospital. Thereafter, he fell into respiratory failure, and developed intestinal obstruction and anuria. We intubated him and inserted an ileus tube. We intravenously administered extracellular fluid, which improved urine excretion and renal function. He was extubated on hospital day 16 and discharged on hospital day 26.Case 2: A man in his 70s tried to commit suicide by drinking GlySH containing glyphosate potassium salt. His vital signs and consciousness were normal on arrival at hospital, but anuria had already developed. The administration of diuretics and extracellular fluid did not improve his symptoms. Consequently, he was started on hemodialysis. Thereafter, urinary flow normalized and he was discharged on hospital day 6, which was 20 days earlier than Case 1. Although hemodialysis was effective for treating GlySH poisoning in this patient, further evidence is required to confirm this outcome

増山教育学の形成過程と展開

departmental bulletin pape

Cathepsin Release from Lysosomes Promotes Endocytosis of Clostridium perfringens Iota-Toxin

Iota-toxin from Clostridium perfringens type E is a binary toxin composed of two independent proteins: actin-ADP-ribosylating enzyme component, iota-a (Ia), and binding component, iota-b (Ib). Ib binds to target cell receptors and mediates the internalization of Ia into the cytoplasm. Extracellular lysosomal enzyme acid sphingomyelinase (ASMase) was previously shown to facilitate the internalization of iota-toxin. In this study, we investigated how lysosomal cathepsin promotes the internalization of iota-toxin into target cells. Cysteine protease inhibitor E64 prevented the cytotoxicity caused by iota-toxin, but aspartate protease inhibitor pepstatin-A and serine protease inhibitor AEBSF did not. Knockdown of lysosomal cysteine protease cathepsins B and L decreased the toxin-induced cytotoxicity. E64 suppressed the Ib-induced ASMase activity in extracellular fluid, showing that the proteases play a role in ASMase activation. These results indicate that cathepsin B and L facilitate entry of iota-toxin via activation of ASMase

Interaction of Clostridium perfringens Iota Toxin and Lipolysis-Stimulated Lipoprotein Receptor (LSR)

Iota toxin produced by Clostridium perfringens is a binary, actin ADP-ribosylating toxin that is organized into the enzymatically active component Ia and the binding component Ib. Lipolysis-stimulated lipoprotein receptor (LSR) has been identified as a cellular receptor of Ib. Here, we investigated the functional interaction between Ib and LSR, where siRNA for LSR blocked the toxin-mediated cytotoxicity and the binding of Ib. The addition of Ib to LSR-green fluorescence protein (GFP)-transfected cells at 4 °C resulted in colocalization with LSR and Ib on the cell surface. Upon transfer of the cells from 4 °C to 37 °C, LSR and Ib were internalized and observed in cytoplasmic vesicles. When the cells were incubated with Ib at 37 °C and fractionated using the Triton-insoluble membrane, Ib oligomer was localized in insoluble factions that fulfilled the criteria of lipid rafts, and LSR was clustered in lipid rafts. To examine the interaction between N-terminal extracellular region of LSR and Ib, we constructed a series of LSR N-terminal deletions. Ten amino acids residues can be deleted from this end without any reduction of Ib binding. However, deletion of 15 N-terminal residues drastically reduces its ability to bind Ib. These results demonstrate that Ib binds to the LSR N-terminal 10 to 15 residues and endocytoses into trafficking endosomes together with LSR

Clostridium perfringens Delta-Toxin Damages the Mouse Small Intestine

Clostridium perfringens strains B and C cause fatal intestinal diseases in animals. The secreted pore-forming toxin delta-toxin is one of the virulence factors of the strains, but the mechanism of intestinal pathogenesis is unclear. Here, we investigated the effects of delta-toxin on the mouse ileal loop. Delta-toxin caused fluid accumulation and intestinal permeability to fluorescein isothiocyanate (FITC)-dextran in the mouse ileal loop in a dose- and time-dependent manner. Treatment with delta-toxin induced significant histological damage and shortening of villi. Delta-toxin activates a disintegrin and metalloprotease (ADAM) 10, leading to the cleavage of E-cadherin, the epithelial adherens junction protein, in human intestinal epithelial Caco-2 cells. In this study, E-cadherin immunostaining in mouse intestinal epithelial cells was almost undetectable 1 h after toxin treatment. ADAM10 inhibitor (GI254023X) blocked the toxin-induced fluid accumulation and E-cadherin loss in the mouse ileal loop. Delta-toxin stimulated the shedding of intestinal epithelial cells. The shedding cells showed the accumulation of E-cadherin in intracellular vesicles and the increased expression of active caspase-3. Our findings demonstrate that delta-toxin causes intestinal epithelial cell damage through the loss of E-cadherin cleaved by ADAM10

Internalization of Clostridium botulinum C2 Toxin Is Regulated by Cathepsin B Released from Lysosomes

Clostridium botulinum C2 toxin is a clostridial binary toxin consisting of actin ADP-ribosyltransferase (C2I) and C2II binding components. Activated C2II (C2IIa) binds to cellular receptors and forms oligomer in membrane rafts. C2IIa oligomer assembles with C2I and contributes to the transport of C2I into the cytoplasm of host cells. C2IIa induces Ca2+-induced lysosomal exocytosis, extracellular release of the acid sphingomyelinase (ASMase), and membrane invagination and endocytosis through generating ceramides in the membrane by ASMase. Here, we reveal that C2 toxin requires the lysosomal enzyme cathepsin B (CTSB) during endocytosis. Lysosomes are a rich source of proteases, containing cysteine protease CTSB and cathepsin L (CTSL), and aspartyl protease cathepsin D (CTSD). Cysteine protease inhibitor E64 blocked C2 toxin-induced cell rounding, but aspartyl protease inhibitor pepstatin-A did not. E64 inhibited the C2IIa-promoted extracellular ASMase activity, indicating that the protease contributes to the activation of ASMase. C2IIa induced the extracellular release of CTSB and CTSL, but not CTSD. CTSB knockdown by siRNA suppressed C2 toxin-caused cytotoxicity, but not siCTSL. These findings demonstrate that CTSB is important for effective cellular entry of C2 toxin into cells through increasing ASMase activity