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Nucleophosmin 1 (NPM1) primarily localizes to the nucleus and is passively released into the extracellular milieu by necrotic or damaged cells, or is secreted by monocytes and macrophages. Extracellular NPM1 acts as a potent inflammatory stimulator by promoting cytokine production [e.g., tumor necrosis factor-α (TNF-α)], which suggests that NPM1 acts as a damage-associated molecular pattern. However, the receptor of NPM1 is unknown. Evidence indicates that DAMPs, which include high mobility group box 1 and histones, may bind Toll-like receptors (TLRs). In the present study, it was shown that NPM1 signaling was mediated via the TLR4 pathway, which suggests that TLR4 is an NPM1 receptor. TLR4 binds myeloid differentiation protein-2 (MD-2), which is essential for intracellular signaling. Furthermore, the TLR4 antagonist, LPS-Rhodobacter sphaeroides (an MD-2 antagonist) and TAK-242 (a TLR4 signaling inhibitor) significantly inhibited NPM1-induced TNF-α production by differentiated THP-1 cells as well as reducing ERK1/2 activation. Far-western blot analysis revealed that NPM1 directly bound MD-2. Thus, the results of the present study provide compelling evidence that TLR4 binds NPM1, and it is hypothesized that inhibiting NPM1 activity may serve as a novel strategy for treating TLR4-related diseases.

Background Nuclear histone proteins are released into the extracellular space during sepsis and act as major mediators of death. However, circulating histone levels have not been precisely quantified. Methods We developed a novel enzyme-linked immunosorbent assay (ELISA) for detection of circulating histone H3 levels and evaluated its performance. Using the ELISA, we measured plasma histone H3 levels in C57BL/6 J mice subjected to cecal ligation and puncture (CLP)-induced sepsis. Results The newly developed ELISA enabled reproducible measurement of histone H3 levels with a working range up to 250 ng/mL. Using the ELISA, we found that plasma histone H3 levels were elevated in septic mice compared with sham-operated mice (p

Fifteen males of the Japanese eel (9 as the Japanese eel recombinant LH (rLH) group and 6 as the 0.9% NaCl group), which had received 7 weekly injections of rLH (500 μg/kg BW/wk), were used in the experiment. Two days after the 7th injection, milt was collected until the males were spent just before an injection of rLH (500 μg/kg BW) or 0.9% NaCl solution. After the injection, the amount of expressible milt weight and its quality (percentage motility, the velocity of the sperm movement, and sperm density of the milt) were examined every 6 h until 48 h after injection (h AI). In the 0.9% NaCl group, the amount of expressible milt remained small throughout the experimental period. In the rLH group, however, expressible milt increased after 12 h AI and peaked at 18–24 h AI before decreasing thereafter. The total weight of obtainable milt from each male up to 48 h AI was 13.7 times more in the rLH group compared to that of the 0.9% NaCl group. The percentage motility of sperm increased after 6 h AI of rLH and was maintained at high values (> 60%) until 42 h AI. Thus, a large quantity of high-quality milt was transported at 18–24 h AI from the testes to the sperm duct for storage when treated with rLH. Because female eels that have completed egg yolk formation release eggs within 13 to 14 h after the administration of a maturation-inducing steroid (MIS), the administration of rLH as the final shot for males should be given at 6 h before the MIS injection to females for the effective induction of spontaneous spawning.

Long-term stock decline in the Japanese eel (Anguilla japonica) is a serious issue. To reduce natural resource utilization in Japan, artificial hormonal induction of maturation and fertilization in the Japanese eel has been intensively studied. Recent experiment on feminized (by feeding a commercial diet containing estradiol-17β for first half year) cultured female eels have shown ovulation problems, which is seldom observed in captured wild female eels. Therefore, the aim of this study is to try to investigate causes of ovulation problem frequently seen in cultured female eels by comparative trans-omics analyses. The omics data showed low growth hormone and luteinizing hormone transcription levels in the brain and low sex hormone-binding globulin transcription levels in the liver of the cultured female eels. In addition, it was found that high accumulation of glucose-6-phosphate and, maltose in the liver of the cultured female eel. It was also found that docosahexaenoic (DHA) acid, eicosapentaenoic acid (EPA) and arachidonic acid (ARA) ratios in cultured female eels were quite different from wild female eels. The data suggested that ovulation problem in cultured female eels was possibly resulted from prolonged intake of a high-carbohydrate diet and/or suboptimal DHA/EPA/ARA ratios in a diet.

Our objective was to evaluate the effects of hormonal treatments on the milt quality during the induction of spontaneous spawning in male eels. We measured the changes in milt characteristics (sperm motility, milt pH, seminal plasma ionic concentration) during the course of hormonal treatments intended to induce spontaneous spawning, and before and after spawning. Male eels received weekly injections of hCG (1 IU/g BW/wk) to maintain spermiation. To induce spontaneous spawning, males received another priming injection of hCG (1 IU/g BW) two days before spawning, followed 24 h later by an injection of 17α-hydroxyprogesterone (OHP: 1 μg/g BW). Three males, treated as described above, and one female, that had received hormonal injections to induce vitellogenesis and final maturation, were transferred to a tank to spawn. In Experiment 1, we measured the characteristics of milt (1) before administering the priming dose (1–2 days after the weekly injection of hCG), (2) before injection with OHP, (3) after spawning (24 h after the OHP injection), and (4) before weekly injections with hCG (4–5 days after OHP injection). To evaluate the effects of hormonal treatment on the characteristics of milt we administered the same treatments but did not allow spawning (Experiment 2). In both experiments, the percent motility remained high prior to OHP injection, decreased significantly 24 h after OHP injection, then recovered by the beginning of weekly hCG injection. The changes in potassium ion concentration were similar to those in sperm motility (%) but there was no change in pH and sodium ion concentrations. When the results were analyzed by individual in Experiment 1 (n = 34), the relationship between sperm motility (%) and milt pH showed significant correlations without 24 h after the OHP injection. The relationship between sperm motility (%) and potassium ion concentration showed a highly significant correlation 24 h after the OHP injection. Thus, both pH and potassium ion concentration regulate motility in Japanese eel spermatozoa during hormonal treatment. Furthermore, administration of OHP into spermiating males reduced motility by decreasing the potassium ion concentration in the seminal plasma.

The effect of feeding rotifers enriched with taurine on the growth performance and survival of larval amberjack Seriola dumerili was investigated. Rotifers were enriched with a commercial taurine supplement at four levels (0, 200, 400, and 800 mg/l). The larvae were fed the enriched rotifers in triplicate from 3 days post-hatch for 7 days under static conditions. The average taurine contents of the rotifers were 1.5, 2.7, 4.2, and 7.2 mg/g dry matter, respectively. The growth of the fish fed rotifers enriched with the taurine supplement at 800 mg/l was significantly (P

Eggs of spiny dogfish Squalus acanthias are an indispensable and effective component of the compound diets currently used for larvae of the Japanese eel Anguilla japonica. However, this fish species, a natural resource, is becoming more scarce, suggesting that suitable diets should be developed using more sustainable components. In the search for appropriate diets without shark eggs, we have designed test diets in which shark eggs were replaced with general feed materials, such as fish protein hydrolysate (FPH), with the notable improvement that the FPH had been pre-digested with integral enzymes from frozen krill. Feeding trials were conducted to assess the effects of the test diets on survival and growth of Japanese eel larvae at early developmental stages. Larvae fed on the test diets were found to be able to survive up to 65 days after hatching, the maximum total length and body depth were 14.1 and 1.5 mm, respectively. Although larvae fed on the test diets still exhibited a low survival rate and poor growth, the FPH-based diets had a nutritional value that promoted substantial larval growth based on the significant difference between the initial and final body sizes. Our results suggest that the development of FPH-based diets not based on shark eggs but rather on general feed ingredients is promising but that there is much room for improvement.

This study examines how the continuous administration of various hormones using an osmotic pump, a long-term sustained hormone release system, influences the induction of sexual maturation in females of the Japanese eel, Anguilla japonica. Human chorionic gonadotropin (hCG), salmon pituitary extract (SPE), and gonadotropin-releasing hormone analogue (GnRHa) were tested, and the consequent egg quality was evaluated. The implantation of osmotic pumps loaded with SPE induced vitellogenesis and increased the gonadosomatic index (GSI) at 39–110 days. In comparison, pumps loaded with hCG inconsistently induced early vitellogenesis, while those loaded with GnRHa did not exhibit any stimulatory effect. Fewer eels attained full maturity when using the osmotic pump system compared with SPE-injected female eels. However, after the final treatment, the number of eels that ovulated and the time required for ovulation were similar for both the osmotic pump and injection groups. Moreover, more eggs were spawned in the SPE-loaded osmotic pump group than in the SPE-injected group. Egg quality was similar for both experimental groups. Therefore, the implantation of an osmotic pump loaded with SPE represents a reliable method for inducing vitellogenesis and obtaining ovulated eggs from sexually immature Japanese eels.

We conducted a rearing experiment on Pacific bluefin tuna (PBT) larvae, which originated from one female broodstock, and determined the growth history of the larvae to clarify when the growth difference occurs. We investigated the otolith microstructure of the PBT larvae to examine the individual growth history and to predict the age and body size at the onset of individual growth difference. Since total length (TL) of fish can be back-calculated from otolith radius, we back-calculated TLs of 100 fish of 19 days post hatch (dph) divided into three size groups (small, intermediate, large). Growth difference was recognized from 3 dph (mouth opening), and the difference became larger thereafter. Growth of large-size fish was assumed to be promoted by the feeding conditions of PBT larvae.

Background and purpose The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] 10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc. This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. Methods Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. Results A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. Conclusions Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals. Electronic supplementary material The online version of this article (10.1186/s40560-017-0270-8) contains supplementary material, which is available to authorized users.

Amami Station of Fisheries Research Agency, Japan has experienced mass mortalities of Pacific bluefin tuna Thunnus olientalis in the process of seed production since around 2000. The mortalities mostly occurred at larval stages. In some cases of the mortalities, but not all cases, the diseased fish was characterized by vacuolation in the central nervous systems and retina, and a betanodavirus (RGNNV genotype) was detected in the affected fish by PCR and FAT methods and culture isolation. The present results suggest that VNN can be a cause of larval mortality of Pacific bluefin tuna.

We encountered a 2-year-old child with life-threatening hypercapnia, with a PaCO(2) of 238 mm Hg and severe respiratory and metabolic acidosis, due to status asthmaticus that was refractory to steroid and bronchodilator therapy. Suspecting ventilatory failure and excessive ventilation-induced obstructive shock, we started respiratory physiotherapy in synchrony with her respiration, to facilitate exhalation from her over-inflated lungs. Isoflurane inhalation was commenced in preparation for extracorporeal circulation, to reduce the hypercapnia. The combination of respiratory physiotherapy and isoflurane inhalation resulted in a rapid decrease in ventilatory resistance and PaCO(2) levels within a few minutes, with recovery of consciousness within 60 min. Isoflurane inhalation was gradually discontinued and steroid and aminophylline therapy were commenced. The patient recovered completely without any recurrence of her bronchospasm and without any residual neurological deficits. In our patient with a severe asthmatic attack, decreased exhalation secondary to asthma and overventilation during artificial ventilation resulted in overinflation of the lungs, which in turn led to cerebral edema and obstructive cardiac failure. The favorable outcome in this case was due to the short duration of hypercapnia. Hence, we conclude that the duration of hypercapnia is an important determinant of the morbidity and mortality of status asthmaticus-induced severe hypercapnia.

The purpose of this study was to examine the effects of continuous administration of human chorionic gonadotropin (HCG), salmon pituitary extract (SPE), and gonadotropin-releasing hormone analogue (GnRHa) via an osmotic pump with a long-term sustained hormone-release system on the induction of sexual maturation in male Japanese eels ( Anguilla japonica ). Implantation of a single HCG-loaded osmotic pump induced spermatogenesis and increased the gonadosomatic index (GSI) values at 35–42 days postimplantation; GSI values were higher (10.7 ± 1.0) than those of the fish implanted with a cholesterol pellet containing HCG (2.4 ± 0.6). Implantation of an SPE-loaded osmotic pump also stimulated spermatogenesis, although the GSI values were lower than those of the fish implanted with the HCG-loaded osmotic pump. Implantation of a single osmotic pump loaded with various doses of GnRHa (0.94, 1.86, or 3.75 µg/day) did not stimulate spermatogenesis. The GSI values and milt weight of the HCG-administered eels significantly increased at a dosage of 5 IU/day in a dose-dependent manner up to 50 IU/day. Sperm motility was not significantly different among the eels treated with different doses of HCG. Therefore, implantation of a single osmotic pump loaded with HCG (50 IU/day) is a reliable method for inducing spermatogenesis and spermiation in sexually immature Japanese eels.

Nucleophosmin exerts potent biological activities that contribute to systemic inflammation. NPM is a major nucleolar multifunctional protein involved in ribosome biogenesis, centrosome duplication, cell-cycle progression, apoptosis, cell differentiation, and sensing cellular stress. Alarmins are endogenous molecules released from activated cells and/or dying cells, which activate the immune system and cause severe damage to cells and tissue organs. In the present work, stimulation of cells with the alarmin-inducible molecule endotoxin, for 16 h, resulted in NPM release into the culture supernatants of RAW264.7 cells, a murine macrophage cell line. Extracellular NPM was detected in the ascites of the CLP model. NPM was translocated into the cytoplasm from the nucleus in LPS -stimulated RAW264.7 cells; furthermore, NPM was detected in the cytosols of infiltrated macrophages in the CLP model. rNPM induced release of proinflammatory cytokines, TNF-α, IL-6, and MCP-1, from RAW264.7 cells and increased the expression level of ICAM-1 in HUVECs. NPM induced the phosphorylation of MAPKs in RAW264.7 cells. Our data indicate that NPM may have potent biological activities that contribute to systemic inflammation. Further investigations of the role of NPM may lead to new therapies for patients with septic shock or other inflammatory diseases.

Objective— High mobility group box 1 protein (HMGB1) was identified as a mediator of endotoxin lethality. We previously reported that thrombomodulin (TM), an endothelial thrombin-binding protein, bound to HMGB1, thereby protecting mice from lethal endotoxemia. However, the fate of HMGB1 bound to TM remains to be elucidated. Methods and Results— TM enhanced thrombin-mediated cleavage of HMGB1. N-terminal amino acid sequence analysis of the HMGB1 degradation product demonstrated that thrombin cleaved HMGB1 at the Arg10-Gly11 bond. Concomitant with the cleavage of the N-terminal domain of HMGB1, proinflammatory activity of HMGB1 was significantly decreased ( P Conclusions— TM not only binds to HMGB1 but also aids the proteolytic cleavage of HMGB1 by thrombin. These findings highlight the novel antiinflammatory role of TM, in which thrombin-TM complexes degrade HMGB1 to a less proinflammatory form.

厳密な血糖コントロールは重症患者の予後を改善させると言われているが,頻回の血糖測定が必要で,実際の施行には障害が大きい。今回,経静脈的持続血糖測定器を使用する機会を得たので,精度を動脈血血糖値と比較検討し,さらに施行上の問題点について報告する。【対象と方法】当院集中治療室入院中に同意を得た6例のうち,静脈内に20ゲージ専用留置針を留置できた2例に,人工膵臓STG(R)-22(日機装,東京)に接続して血糖値を持続モニターし,動脈血血液ガス分析装置の血糖値と比較検討した。【結果】動脈血と静脈血,血糖値の間にはr=0.964と非常に高い相関関係が得られた。Bland-Altman plotでは,負の相関関係がみられた。【考察および問題点】血糖値が高くなるにつれ,STG(R)-22による静脈血血糖値が動脈血血糖値に比べて低値となったが,これは機械的な性能ではなく,血糖値の増加に従い,動静脈血較差が広がるためと考えられた。また,ICUのベッドサイドにおける使用に際しては機器が大きい,回路が長くできないといった問題があり,今後,さらなる改良の必要性が示唆された。

胸腹部大動脈瘤(thoraco-abdominal aortic aneurysm, TAAA)術後の腸管虚血の診断に血清乳酸値が有用であった症例を経験した。症例は73歳,女性。胸腹部大動脈瘤の診断にてステント挿入術と,腹部分枝に対する人工血管を用いたバイパス術を施行した。術中およびICU入室後,低酸素血症やショックに陥ることがなかったが,腹部分枝バイパス終了6時間後から血清乳酸値の上昇と代謝性アシドーシスが進行した。代謝の亢進や肝不全,循環不全,呼吸不全を示唆する所見がなかったため,腸管虚血を疑った。試験開腹術を行ったところ,上腸間膜動脈にバイパスしたグラフトが屈曲し,血流が遮断されていた。直ちに虚血を解除し,新たにバイパス術を追加した。ICU帰室後,血清乳酸値は4時間で正常化し,患者は合併症を併発せず,第5病日には一般病棟へ退室した。大動脈疾患に伴う腸管虚血の診断は臨床症状以外では困難な場合が多い。血清乳酸値の特性を十分に把握した上での連続モニタリングは,大動脈疾患に伴う腸管虚血の診断に有用な補助手段となることが示唆された。

Guillain-Barre症候群(GBS)は,先行感染に遅れて1-3週間後に四肢の筋力低下,深部腱反射の消失などの症状が出現するが,先行感染による急性炎症反応亢進は軽度であることが多い。一方,critical illness polyneuropathy (CIP)は敗血症,多臓器不全,呼吸不全,SIRSからの回復期に,人工呼吸器からの離脱困難,四肢の筋力低下,腱反射の消失の症状を呈する。重複する感染症の程度によって,両者の鑑別は比較的容易であると考えられる。今回,先行感染があったが,敗血症性ショックからの回復期に四肢の運動障害,意識障害を呈し,CIPとの鑑別に苦慮した軸索型GBSの一例を経験したので報告する。症例は64歳の男性で,2週間前より発熱がみられ,内服薬が処方されていたが,症状の改善がみられず重症肺炎と急性腎不全を合併したため,当院へ緊急搬送された。敗血症性ショックを合併し,抗生物質,人工呼吸管理と持続血液濾過透析などの治療を行った。入院9日目より酸素化能の改善がみられ,ショックから離脱したが,人工呼吸器の圧補助を下げることができなかった。そこでGBSを疑ったが,髄液検査ではタンパク細胞解離はなかった。末梢神経伝導速度では運動神経の軸索型障害がみられた。後日判明した入院4日目のマイコプラズマ抗体価は2560倍であったため,マイコプラズマ肺炎による運動神経障害(acute motor axonal neuropathy; AMAN)型GBSと診断した。CIPは敗血症などの重症急性疾患の治療中に発症し,全身状態の改善とともに症状が改善する。しかし,GBSでは神経障害の回復には血漿交換や大量ガンマグロブリン投与が確立しており,本症例のように敗血症治療後に人工呼吸器からの離脱困難や四肢筋力の低下などのCIPを疑う症状がみられた場合には電気生理学的検査などを行い,GBSを除外する必要があると考えられる。

担癌患者の腹膜炎性敗血症の治療中に血球貪食症候群(hemophagocytic syndrome)を発症した1例を経験した。症例は64歳,男性。既往歴として61歳時に上咽頭癌を発症し肺転移,骨転移が生じたため放射線,手術治療後ステロイド内服中であった。突然の腹痛を生じ当院救命センターへ搬入され上部消化管穿孔を疑い開腹術を施行した。術中の腹水培養でCandida albicansが検出された。術後,急性腎不全の進行,血小板減少,貧血,肝機能障害など多臓器不全が進行したためHPSを疑い第9病日に骨髄生検したところ血球貪食像が確認された。ステロイドパルス療法にて症状は迅速に改善した。その後肺炎を併発したものの第22病日に一般病棟へ退室したが,第29病日に敗血症性ショックのため永眠された。本症例では感染に対する適切な治療の上にステロイドおよび持続血液濾過透析が一時的ではあるがHPSの病勢を抑えることができたと考えられた。敗血症時の血球減少には血球貪食症候群が関与している可能性を念頭に置くことが早期診断・治療に繋がると考えられた。

経皮二酸化炭素分圧(PtcCO2)測定とパルスオキシメータの小型センサーを同時に搭載した耳朶センサーを用いた測定装置TOSCA(R)(Linde社,スイス)の集中治療室での使用経験を報告した。対象はICUに入室した12症例の重症患者とし,左右いずれかの耳朶にセンサーを装着し,PtcCO2およびSpO2を測定した。適宜動脈血ガス分析を行い,PaCO2とPtcCO2とを比較検討したところ,相関係数0.95と良好な相関関係が得られたが,PaCO2が50mmHg以上ではPtcCO2がPaCO2よりも高くなり解離していく傾向があった。測定に伴う重篤な合併症はなく,体位変換に伴う体動でも測定が可能であった。ノルエピネフリン投与後PtCO2とPaCO2とが解離する症例があった。TOSCA(R)を用いたPtcCO2は,実測値と比べ若干高値に表示されるものの追従性も良く有用と考えられるが,重症患者における低灌流状態でのSpO2を含めた検討がさらに必要である。

Neuronal cell injury after global cerebral ischemic insult is not well understood in humans. We performed serial examination of diffusion-weighted imaging and magnetic resonance spectroscopy in three patients after cardiopulmonary resuscitation. The presence of the signal for lactate in magnetic resonance spectroscopy in the acute stage after cardiopulmonary resuscitation was closely correlated to irreversible damage. In addition, high intensity in diffusion-weighted magnetic resonance image in the acute stage also predicted a poor outcome. Lesions that were positive for these factors in the acute stage led to serious brain damage in the subacute and chronic stages. The results indicated that after cardiopulmonary resuscitation, diffusion-weighted magnetic resonance imaging and magnetic resonance spectroscopy is an extremely useful modality to estimate the prognosis of patients, which is not always easy using conventional methods.

消化管穿孔による後腹膜膿瘍が,大腿輪を経て左側腹部から下腿に波及したために生じた壊死性筋膜炎のまれな1例を経験した。症例は65歳の女性。左側腹部から大腿部にかけての疼痛と皮膚壊死を認めたため壊死性筋膜炎を疑い,当院高度救命救急センターに搬入された。搬入時,呼吸,循環動態は安定していたが,左躯幹から大腿部,外陰部の浮腫,紫斑,硬結,皮膚壊死を認めた。搬入後直ちに,躯幹から下肢にかけての皮膚の壊死部分を筋膜上までdebridementし人工真皮にて被覆した。術中,左鼠径靭帯下部に便の付着と後腹膜方向の交通部があった。開腹したところ結腸脾湾曲部の後腹膜腔への穿孔があり,後腹膜腔には膿瘍が充満した状態であったため,結腸左半切除を行った。穿孔部結腸の病理組織検査では憩室や悪性所見はなかった。術中,術後にわたりショック状態や臓器不全に陥ることなく順調に経過し,第5, 10病日に人工真皮による被覆を行い,さらに第20病日と32病日には,autograftによる植皮術を施行し欠損部を被覆した。下肢壊死性筋膜炎の原因として後腹膜腔への腸管穿孔は非常にまれであるが,原因の一つとして常に可能性を念頭に置く必要がある。本症例では早期かつ広範に壊死した皮膚や皮下組織,筋膜を徹底的にdebridementし,その原因となった腸管に対して処置し得たことが,その後の敗血症の発症や,臓器障害への進展を防止できたと考えられた。

急性膵炎と急性肝不全に陥った急性バルプロ酸(valproate sodium; VPA)中毒の1例を経験した。症例は53歳の男性で妻とともに倒れているところを発見され,当院に搬入された。搬入時意識レベルはJCS 300で嘔吐,尿失禁がみられた。血液検査では,高ナトリウム血症と高乳酸血症,高アンモニア血症があった。搬入8時間後に妻がVPAを処方されていたことが判明し,搬入6時間後のVPA血中濃度1,555(治療域100μg/ml以下)μg/ml,アセチルサリチル酸(acetylsalicylate; ASA)濃度114μg/ml(治療域150-300μg/ml)だった。臨床症状と併せて急性VPA中毒と診断し,搬入15時間後に直接血液灌流を施行した。第2病日には膵酵素と肝逸脱酵素の上昇,DICを認めた。腹部造影CT上,肝部分壊死と重症急性膵炎であることが判明した。患者は多臓器不全が進行し,第3病日死亡した。他院に搬入された妻も搬入6時間後のVPA血中濃度は1,534μg/mlだった。搬入8時間後に直接血液灌流を施行し,意識レベルの改善がみられた。経過中,膵酵素の上昇,DICがみられたものの肝障害や急性膵炎の所見は認めず,順調に回復し第18病日ICUを退室した。本症例のようにVPAの大量服用にASAを同時に服用した場合には,VPAの中毒症状が増強される可能性が示唆された。また,重症急性VPA中毒では早期の血液浄化が救命に繋がるのではないかと考えられた。

Rhabdomyolysis in four children was evaluated by bone scintigraphy using 99mTecnetium-methyldiphosphate (99mTc-MDP). The ages of the patients ranged from 7 to 14 years old. The causes of rhabdomyolysis were toxic shock syndrome in one patient, excessive exercise in one patient and cardiopulmonary arrest after cardiac surgery and after drowning in two patients. Peak serum creatine kinase (CK) and myoglobin (Mb) levels ranged from 5, 093 to 91, 150IU/l and 7, 486 to 111, 900ng/ml, respectively. Peak serum CK and Mb levels reached during the period from the first to third ICU day. Renal impairment occurred in the patient with toxic shock syndrome. After treatment with continuous hemodiafiltration, the renal impairment improved. Bone scintigraphy using 99mTc-MDP was performed during the period from the third to fifth ICU day. Abnormal accumulation of radioactivity was found in the two patients in whom rhabdomyolysis had been caused by excessive exercise and cardiopulmonary arrest after drowning. Despite the fact that peak CK raised to 12, 500IU/l in the patient of toxic shock syndrome, abnormal accumulation of radioactivity was not found. It was shown that bone scintigraphy using 99mTc-MDP is available for evaluation of rhabdomyolysis in children as it is in adults. However, in children with rhabdomyolysis, greater elevation of CK may be required to detect abnormal accumulation of radioactivity by bone scintigraphy using 99mTc-MDP compared with that in adults.

Background/Aims: This study evaluated the mechanism of hemodynamic improvement in polymyxin B-immobilized fiber (PMX) treatment. Methods: Fifteen septic patients with endotoxemia and/or gram negative infection were treated with PMX. Plasma concentrations of calcitonin gene-related peptide (CGRP) and nitric oxide metabolites were measured. Results: CGRP and nitric oxide metabolites before treatment were significantly higher than in healthy controls. CGRP had a significantly inverse correlation with diastolic blood pressure and a positive correlation with the Septic Severity Score and the number of failed organs. Systolic and diastolic blood pressure and systemic vascular resistance index increased significantly both immediately after and 24 h after PMX treatment. CGRP decreased significantly 24 h after the treatment. In contrast, there were no significant changes in nitric oxide metabolites. Conclusion: PMX treatment improved hemodynamic parameters in septic patients, and CGRP increased with increasing severity of sepsis. We conclude that a decrease in CGRP levels may be related to hemodynamic improvement resulting from PMX treatments.

We report a case of an abdominal aortic aneurysm which ruptured into the inferior vena cava indicated by CT and angiography in a patient that had been transferred to our hospital with a diagnosis of acute cardiac failure. The patient was a 73-year-old male who had been examined at another hospital for chest pain, hypotension, vomiting and vertigo and had been admitted to our hospital for examination of acute cardiac failure of unknown cause. A pulsating giant mass was palpable in the abdomen, and a continuous murmur was also audible in the abdomen. The patient showed no anemia or abdominal pain, but CT indicated the possibility of the rupture of an abdominal aortic aneurysm into the inferior vena cava. Emergency surgery was successfully performed following confirmation of the rupture by angiography. The results of this case indicate the need to consider a ruptured abdominal aortic aneurysm as a possible cause of symptoms resembling acute cardiac failure.

Summary This is a guideline for the management of sepsis, developed by the Sepsis Registry Committee of The Japanese Society of Intensive Care Medicine (JSICM) launched in March 2007. This guideline was developed on the basis of evidence-based medicine and focuses on unique treatments in Japan that have not been included in the Surviving Sepsis Campaign guidelines (SSCG), as well as treatments that are viewed differently in Japan and in Western countries. Although the methods in this guideline conform to the 2008 SSCG, the Japanese literature and the results of the Sepsis Registry Survey, which was performed twice by the Sepsis Registry Committee in intensive care units (ICUs) registered with JSICM, are also referred. This is the first and original guideline for sepsis in Japan and is expected to be properly used in daily clinical practice. This article is translated from Japanese, originally published as “The Japanese Guidelines for the Management of Sepsis” in the Journal of the Japanese Society of Intensive Care Medicine (J Jpn Soc Intensive Care Med), 2013; 20:124–73. The original work is at http://dx.doi.org/10.3918/jsicm.20.124. Electronic supplementary material The online version of this article (doi:10.1186/s40560-014-0055-2) contains supplementary material, which is available to authorized users.

This study was carried out to investigate whether readily available paprika can replace astaxanthin as a source of carotenoids in soft-dry pellets for broodstock yellowtail Seriola quinqueradiata (Temminck & Schlegel). Five months prior to spawning, 120 fish of average body weight (BW) 6.2 ± 1.5 kg were divided into three groups and fed basal soft-dry pellets (SDP), SDP supplemented with 30 mg/kg astaxanthin (a-SDP), or SDP supplemented with 2% paprika (p-SDP). Feeding was carried out in floating net cages and two spawning trials were performed. Fish were selected (five male and five female per group per trial), injected with human chorionic gonadotropin (600 IU kg−1 fish) and transferred to 100 m3 indoor concrete tanks for spawning. In trial 1, egg production during the first day of spawning was highest for the p-SDP group, followed by the a-SDP and SDP groups. For the p-SDP, a-SDP and SDP groups, fertilization rates were 76.0%, 69.7% and 61.9% and hatching rates were 75.2%, 63.9% and 59.4%, respectively. In trial 2, fertilization rates were 80.9%, 78.0% and 86.8% and hatching rates followed the same trend as in trial 1, at 61.8%, 52.9% and 37.2%, respectively. Moreover, larvae of the p-SDP groups showed better survival at day 3 after hatching. Apart from the darker yellow colour of fertilized eggs of the astaxanthin or paprika supplemented diet groups, analysis showed that carotenoids from paprika were successfully incorporated into the eggs, mainly as zeaxanthin and lutein. Paprika supplementation did not affect the fatty acid and lipid class profiles of eggs and unfed larvae. These results indicate that paprika supplementation in soft-dry pellets is effective for good quality egg production in yellowtail.

This study was conducted to investigate the effect of squid meal and astaxanthin in dry pellets on the spawning performance of striped jack. Two groups of 8-year-old fish with an average bodyweight of 3.5 ± 0.4 kg were used. The control group was fed a raw fish mix (RF) and the exper- imental group was fed steam dry pellets (as-DP) containing 10 p.p.m. astaxanthin and squid meal, the latter replacing half the fish meal. Each group was fed once a day, three times a week in float- ing net cages for a period of 5 months. Seven females and seven males were selected from each group and transferred to 65 m 3 indoor concrete tanks for spawning, where they were kept at optimum spawning conditions (22∞C) for 1 month. The average bodyweights of selected fish were 3.8 ± 0.5 kg and 3.8 ± 0.6 kg for the RF and as-DP groups, respectively. Both groups spawned a total of 18 times and the mean total egg production and egg quality, measured in terms of buoyancy, fertilization and hatching rates, showed no significant differences (P > 0.05) between groups. Total larval production was 679.9 ¥ 10 3 and 678.1 ¥ 10 3 larvae/kg-female for the RF and as-DP groups, respectively. These results show that the combination of astaxanthin and squid meal in dry pellets for striped jack brood- stock improved the overall spawning performance to a level similar to that of fish fed on RF.

Anandamide (ANA) and 2-arachidonoylglycerol (2-AG), two endogenous cannabinoids, can be generated by activated macrophages and platelets, respectively, in the context of endotoxic shock, and are proposed to play a crucial role in the induction of the shock-related hypotension. Taking advantage of our recently discovered function of polymyxin B (PMB) binding to ANA and 2-AG, we developed a new method for measuring ANA and 2-AG by applying PMB-immobilized beads to selectively adsorb them in biological fluids, instead of organic solvent extraction. The eluate from beads can be directly fractionated by reverse-phase high-performance liquid chromatography (HPLC), and the fractionations corresponding to authentic ANA and 2-AG are collected and derivatized with fluorogenic reagent and subsequently quantified by HPLC with fluorometric detection. The calibration graphs of ANA and 2-AG were linear over a range of 1 to 500 pmol/ml. The limits of detection for ANA and 2-AG were 20 and 50 fmol, respectively. Intraassay precision was 2.24-4.25 and 3.47-5.44%, and interassay was 4.05-6.14 and 4.92-7.28% for ANA and 2-AG, respectively. Using this method, we first determined a 4-fold and 3-fold higher level of ANA and 2-AG, respectively, in the sera of patients with endotoxic shock than in normal serum. This finding should help in elucidating the role of the endogenous cannabinoids in the hypotension of human endotoxic shock. This method is rapid, sensitive, and reliable for simultaneously quantifying ANA and 2-AG in biological fluids, and has potential for clinical usage.

But: Evaluer le rapport entre les parametres cliniques et plasmatiques et les modifications d'activite d'endotoxines plasmatiques, d'une part, et l'utilisation de polymyxin B (PMX, Toray Medical Co., Ltd., Tokyo, Japon), un absorbant d'endotoxine, pendant 2 heures, d'autre part. Patients et methodes: Au total, 88 patients consecutifs, admis pour traitement d'un sepsis severe ou une defaillance viscerale par PMX. Pendant le traitement, la reanimation etait sans particularite. On a mesure, avant, immediatement et 24 h apres l'administration de PMX, les facteurs endotoxine et tumor necrosis factor (TNF)-alpha, l'interleukine (IL)-6, IL-10, les activites du plasminogen activator inhibitor-1 (PAI-1), et certains autres parametres cliniques. Resultats: Les scores moyens APACHE II et III ont ete, respectivement, de 24,2 ± 1,0 et de 85,8 ± 3,0. La survie a deux semaines a ete de 51,1%. Les activites du TNF-alpha, d'IL-6, d'IL-10 et de PAI-1 ont ete significativement reduites chez les survivants pendant le traitement par PMX et/ou le jour apres. Chez les non survivants, aucune modification significative n'a ete notee pour ces parametres sauf en ce qui concerne le TNF-alpha. Dans le sous-groupe de patients ou l'endotoxine plasmatique a diminue de plus de 30%, on a remarque une diminution significative de l'IL-6, du TNF-alpha et du PAI-1 apres 2 h et/ou le jour d'apres, mais aucun de ces quatre parametres n'a change chez les non-survivants. Conclusion: Le PMX, pendant les deux heures du traitement, contribue a absorber des endotoxines du plasma et reduit le taux de cytokines inflammatoires, ameliorant les parametres cliniques.

SUMMARY: This study was carried out to investigate the effects of dietary squid meal or a combination of squid meal and krill meal as part of the protein source in dry pellets on the spawning of striped jack Pseudocaranx dentex. Five months prior to spawning, 7-year-old fish were divided into three groups of 10 fish each (male : female ratio, 5 : 5). The control group was fed a raw fish mix (RF) and the other two groups were fed either steam-dry pellets with squid meal replacing 50% of their fish meal (fs-DP) or steam-dry pellets containing equal proportions of fish, squid and krill meals (fsk-DP). Feeding was carried out once every other day in 5 × 5 × 5 m floating net cages and the fish were transferred to 65 m3 indoor tanks for spawning. Eggs and yolksac larvae produced were evaluated for their quality and those obtained during the first 2 weeks of spawning were sampled for chemical analysis. The fish had an average bodyweight of 3.5 ± 0.4 kg at spawning. Although egg production of the RF group was significantly higher (P < 0.05) than that of the dry pellet groups, the fs-DP group produced the best quality eggs with higher fertilization and hatching rates. The fsk-DP group had the lowest egg production and quality. Lipid classes and fatty acid compositions of eggs and yolksac larvae were dependent on the broodstock diets. These results show that the combination of fish meal and squid meal in dry pellets for striped jack improved egg quality but not production whereas the combination of fish meal, squid meal and krill meal was not effective.

SUMMARY: This experiment was conducted to investigate the effect of astaxanthin supplemented steam-dry pellets on the spawning of striped jack Pseudocaranx dentex. Five months before spawning, 7-year-old fish were divided into three groups, each consisting of five females and five males. The control group was fed a raw fish mix (RF) and the test diets consisted of steam-dry pellets (DP) and steam-dry pellets supplemented with 10 p.p.m. astaxanthin (a-DP). Feeding was carried out once per day, three times a week in floating net cages. The RF and the a-DP groups produced more than three times the amount of eggs produced by the DP group. The buoyancy, fertilization, and hatching rates were higher and similar for the RF and the DP groups. Total lipid contents of the diets, eggs, and larvae were similar among the groups. Highly unsaturated fatty acids (n-3 HUFA) and polar and non-polar lipids in eggs and larvae were also related to their dietary availability. These results indicate that astaxanthin, due to its various physiological functions, improved the condition of the broodstock and enhanced total egg production but not egg quality as striped jack do not incorporate carotenoids into their eggs. Therefore we confirm that the nutritional quality of diets given to striped jack prior to spawning plays a fundamental role in egg production, quality and egg composition.

A case of transfusion-related acute lung injury (TRALI) that was successfully treated with extracorporeal membranous oxygenation (ECMO) is reported. A 58-year-old male patient underwent hepatectomy, and pulmonary edema occurred after the administration of fresh-frozen plasma and packed red cells. In the postoperative period, the impaired oxygenation progressively worsened, resulting in life-threatening hypoxemia, despite vigorous treatments. ECMO was therefore applied to the patient as a method of safe emergency support. Aggressive treatments under ECMO led to the successful improvement of the impaired oxygenation. TRALI is recognized as part of acute respiratory distress syndrome (ARDS). As a treatment for ARDS, ECMO does not cure the underlying disease of the lungs, however, with ECMO, TRALI, usually improves within 96 h with respiratory support. ECMO for TRALI-induced lethal hypoxemia is useful for providing time to allow the injured lung to recover. It is suggested that ECMO might be a useful option for the treatment of TRALI-induced, potentially lethal hypoxemia.

急性腎不全は多臓器不全の一分症として高率に生じる臓器不全の一つであり,死亡率は依然として高い.原因疾患として敗血症が多く,病態には種々のmediatorと組織酸素代謝の失調が関与する.対策としては,十分な輸液を行い,腎毒性のある薬剤を避けるとともに,循環への影響が少なく,体液の正常化と溶質除去の他に,多臓器不全共通の発症因子であるmediator除去を目的に持続的血液濾過透析を用いることが推奨される.