RESUMO
A moment magnitude (Mw) 7.5 earthquake (the Global IDentifire (GLIDE) number: # Q-2024-000001-JPN) struck the Noto Peninsula of Ishikawa Prefecture on 1 January 2024 at 16:10 (Japan Standard Time). The reversed fault, 150 km in length and subducting beneath the peninsula, resulted in maximum seismic intensity 7 shaking, triggered the tsunami, destroyed over 43 thousand buildings, and disrupted roads and lifelines. The disaster claimed 236 deaths, including 15 indirect disaster deaths as of Jan. 28, 2024. There were Disaster Base Hospitals (DBHs) in the region, which survived structurally but suffered from impaired functions and the surge of medical needs of affected people. The disaster medical system of Japan immediately responded and coordinated the hundreds of emergency medical teams (EMTs), i.e., the Japan Disaster Medical Assistance Team (DMAT), from all over the country. Tohoku University Hospital, which had the experience of the 2011 Great East Japan Earthquake (GEJE), joined the coordinated response, dispatching a chain of DMATs, which helped the medical and public health coordination in Wajima City. The medical and public health needs included injuries, non-communicable diseases, infectious diseases, mental health issues, and maternal and child health issues, which were similar in the affected communities in GEJE. Although the actual damage far exceeded expectations, the structural retrofitting and business continuity plans of DBHs and the coordinated response of the national disaster medical system enhanced the effectiveness of medical and public health response.
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Planejamento em Desastres , Desastres , Terremotos , Criança , Humanos , Hospitais Universitários , Tsunamis , JapãoRESUMO
In plants, F1 hybrids showing hybrid weakness exhibit weaker growth than their parents. The phenotypes of hybrid weakness are often suppressed at certain temperatures. However, it is unclear whether hybrid weakness in Capsicum annuum × C. chinense is temperature-dependent or not. Our study showed that Capsicum hybrid weakness was suppressed at 30 and 35 °C and was induced at 15, 20, and 25 °C. Moreover, we investigated the time course of hybrid weakness in cell death, metabolite content, and gene expression in leaves of plants transferred to 20 °C after growing at 30 °C for 21 days. The expression of pathogen defense-related genes was upregulated at 1 day after transfer to 20 °C (DAT). Cell death was detected at 7 DAT, plant growth had almost stopped since 14 DAT, and sugars were accumulated at 42 DAT in hybrid plants. The study revealed that some sugar transporter genes, which had been upregulated since 7 DAT, were involved in sugar accumulation in Capsicum hybrid weakness. Thus, our results demonstrated that gene expression changes occur first, followed by physiological and morphological changes after induction of hybrid weakness. These responses observed in this study in Capsicum hybrid weakness are likely to be owed to plant defense responses-like reactions.
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Capsicum , Capsicum/genética , Capsicum/metabolismo , Regulação da Expressão Gênica de Plantas , Fenótipo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Açúcares , TemperaturaRESUMO
BACKGROUND AND PURPOSE: Inflammation has emerged as a key component of the pathophysiology of intracranial aneurysms. Mast cells have been detected in human intracranial aneurysm tissues, and their presence was associated with intramural microhemorrhage and wall degeneration. We hypothesized that mast cells play a critical role in the development of aneurysmal rupture, and that mast cells can be used as a therapeutic target for the prevention of aneurysm rupture. METHODS: Intracranial aneurysms were induced in adult mice using a combination of induced systemic hypertension and a single injection of elastase into the cerebrospinal fluid. Aneurysm formation and rupture were assessed over 3 weeks. Roles of mast cells were assessed using a mast cell stabilizer (cromolyn), a mast cell activator (C48/80), and mice that are genetically lacking mature mast cells (KitW-sh/W-sh mice). RESULTS: Pharmacological stabilization of mast cells with cromolyn markedly decreased the rupture rate of aneurysms (80% versus 19%, n=10 versus n =16) without affecting the aneurysm formation. The activation of mast cells with C48/80 significantly increased the rupture rate of aneurysms (25% versus 100%, n=4 versus n=5) without affecting the overall rate of aneurysm formation. Furthermore, the genetic deficiency of mast cells significantly prevented aneurysm rupture (80% versus 25%, n=10 versus n=8, wild-type versus KitW-sh/W-sh mice). CONCLUSIONS: These results suggest that mast cells play a key role in promoting aneurysm rupture but not formation. Stabilizers of mast cells may have a potential therapeutic value in preventing intracranial aneurysm rupture in patients.
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Aneurisma Roto/imunologia , Aneurisma Intracraniano/imunologia , Mastócitos/imunologia , Aneurisma Roto/patologia , Aneurisma Roto/prevenção & controle , Animais , Catepsina G/genética , Quimases/genética , Cromolina Sódica/farmacologia , Modelos Animais de Doenças , Interleucina-6/genética , Aneurisma Intracraniano/patologia , Masculino , Estabilizadores de Mastócitos/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Transgênicos , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Angiotensina/genética , Hemorragia Subaracnóidea/imunologia , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/prevenção & controle , Triptases/genética , Fator de Necrose Tumoral alfa/genética , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
During a disaster, all hospitals are expected to function as "social critical institutions" that protect the lives and health of people. In recent disasters, numerous hospitals were damaged, and this hampered the recovery of the affected communities. Had these hospitals business continuity plans (BCPs) to recover quickly after the disaster, most of the damage could have been avoided. This study conducted a scoping review of the historical trend and regional differences in hospital BCPs to validate the improvement of the BCP concept based on our own experience at Tohoku University Hospital, which was affected by the 2011 Great East Japan Earthquake and Tsunami (GEJET). We searched PubMed by using keywords related to BCP and adapted 97 articles for our analysis. The number of articles on hospital BCPs has increased in the 2000s, especially after Hurricane Katrina in 2005. While there are regional specificity of hazards, there were many common topics and visions for BCP implementation, education, and drills. From our 2011 GEJET experience, we found that BCPs assuming region-specific disasters are applicable in various types of disasters. Thus, we suggest the following integral and universal components for hospital BCPs: (1) alternative methods and resources, (2) priority of operation, and (3) resource management. Even if the type and extent of disasters vary, the development of BCPs and business continuity management strategies that utilize the abovementioned integral components can help a hospital survive disasters in the future.
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Planejamento em Desastres/tendências , Terremotos , Administração Hospitalar/tendências , Tsunamis , Medicina de Desastres/tendências , Hospitais Universitários , Humanos , Japão , Melhoria de QualidadeRESUMO
Background and Purpose- Tobacco cigarette smoking is considered to be a strong risk factor for intracranial aneurysmal rupture. Nicotine is a major biologically active constituent of tobacco products. Nicotine's interactions with vascular cell nicotinic acetylcholine receptors containing α7 subunits (α7*-nAChR) are thought to promote local inflammation and sustained angiogenesis. In this study, using a mouse intracranial aneurysm model, we assessed potential contributions of nicotine exposure and activation of α7*-nAChR to the development of aneurysmal rupture. Methods- Intracranial aneurysms were induced by a combination of deoxycorticosterone-salt induced hypertension and a single-dose elastase injection into cerebrospinal fluid in mice. Results- Exposure to nicotine or an α7*-nAChR-selective agonist significantly increased aneurysm rupture rate. Coexposure to an α7*-nAChR antagonist abolished nicotine's deleterious effect. In addition, nicotine's promotion of aneurysm rupture was absent in smooth muscle cell-specific α7*-nAChR subunit knockout mice but not in mice lacking α7*-nAChR on endothelial cells or macrophages. Nicotine treatment increased the mRNA levels of vascular endothelial growth factor, platelet-derived growth factor-B, and inflammatory cytokines. α7*-nAChR antagonist reversed nicotine-induced upregulation of these growth factors and cytokines. Conclusions- Our findings indicate that nicotine exposure promotes aneurysmal rupture through actions on vascular smooth muscle cell α7*-nAChR.
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Aneurisma Roto/tratamento farmacológico , Aneurisma Intracraniano/tratamento farmacológico , Nicotina/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/efeitos dos fármacos , Animais , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Camundongos Transgênicos , Agonistas Nicotínicos/farmacologia , Receptores Nicotínicos/efeitos dos fármacos , Receptores Nicotínicos/genética , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: Inflammatory cells play a significant role in secondary injury after ischemic stroke. Recent studies have suggested that a lack of autophagy in myeloid cells causes augmented proinflammatory cytokine release and prolonged inflammation after tissue injury. In this study, we investigated the roles of myeloid cell autophagy in ischemic brain injury. METHODS: Focal cerebral ischemia was induced via transient middle cerebral artery occlusion in mice with autophagy-deficient myeloid lineage cells (Atg5flox/flox LysMCre+) and in their littermate controls (Atg5flox/flox). Infarct volume, neurological function, inflammatory cell infiltration, and proinflammatory cytokine expression levels were evaluated. RESULTS: Mice lacking autophagy in myeloid lineage cells had a lower survival rate for 14 days than control mice (20% versus 70%; P<0.05). Although there was no difference in infarct volume at 12 hours between the 2 groups, mice lacking autophagy in myeloid lineage cells had larger infarct volumes at later time points (3 and 7 days after reperfusion) with worse neurological deficit scores and lower grip test scores. There were a higher number of ionized calcium binding adaptor molecule 1-positive cells and cells expressing M1 marker CD16/32 in mice lacking autophagy in myeloid cells at the later time points. Moreover, these mice had higher expression levels of proinflammatory cytokines at later time points; however, there was no difference in ionized calcium binding adaptor molecule 1-positive cells or mRNA levels of proinflammatory cytokines at the earlier time point (12 hours after reperfusion). CONCLUSIONS: These data suggest that the lack of myeloid cell autophagy aggravates secondary injury by augmenting and prolonging inflammation after ischemic stroke without affecting the initial injury.
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Autofagia/fisiologia , Lesões Encefálicas/metabolismo , Linhagem da Célula/fisiologia , Células Mieloides/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Inflamação/metabolismo , Camundongos TransgênicosRESUMO
BACKGROUND AND PURPOSE: Inflammation is emerging as a key component of the pathophysiology of intracranial aneurysms. Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear hormone receptor of which activation modulates various aspects of inflammation. METHODS: Using a mouse model of intracranial aneurysm, we examined the potential roles of PPARγ in the development of rupture of intracranial aneurysm. RESULTS: A PPARγ agonist, pioglitazone, significantly reduced the incidence of ruptured aneurysms and the rupture rate without affecting the total incidence aneurysm (unruptured aneurysms and ruptured aneurysms). PPARγ antagonist (GW9662) abolished the protective effect of pioglitazone. The protective effect of pioglitazone was absent in mice lacking macrophage PPARγ. Pioglitazone treatment reduced the mRNA levels of inflammatory cytokines (monocyte chemoattractant factor-1, interleukin-1, and interleukin-6) that are primarily produced by macrophages in the cerebral arteries. Pioglitazone treatment reduced the infiltration of M1 macrophage into the cerebral arteries and the macrophage M1/M2 ratio. Depletion of macrophages significantly reduced the rupture rate. CONCLUSIONS: Our data showed that the activation of macrophage PPARγ protects against the development of aneurysmal rupture. PPARγ in inflammatory cells may be a potential therapeutic target for the prevention of aneurysmal rupture.
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Aneurisma Roto/prevenção & controle , Anilidas/farmacologia , Hipoglicemiantes/farmacologia , Aneurisma Intracraniano/prevenção & controle , PPAR gama/antagonistas & inibidores , Tiazolidinedionas/farmacologia , Aneurisma Roto/genética , Aneurisma Roto/metabolismo , Aneurisma Roto/patologia , Animais , Artérias Cerebrais/metabolismo , Artérias Cerebrais/patologia , Citocinas/genética , Citocinas/metabolismo , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/metabolismo , Aneurisma Intracraniano/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout , PPAR gama/genética , PPAR gama/metabolismo , PioglitazonaRESUMO
INTRODUCTION: The aim of this study was to shed light on damage to water supply facilities and the state of water resource operation at disaster base hospitals in Miyagi Prefecture (Japan) in the wake of the Great East Japan Earthquake (2011), in order to identify issues concerning the operational continuity of hospitals in the event of a disaster. METHODS: In addition to interview and written questionnaire surveys to 14 disaster base hospitals in Miyagi Prefecture, a number of key elements relating to the damage done to water supply facilities and the operation of water resources were identified from the chronological record of events following the Great East Japan Earthquake. RESULTS: Nine of the 14 hospitals experienced cuts to their water supplies, with a median value of three days (range=one to 20 days) for service recovery time. The hospitals that could utilize well water during the time that water supply was interrupted were able to obtain water in quantities similar to their normal volumes. Hospitals that could not use well water during the period of interruption, and hospitals whose water supply facilities were damaged, experienced significant disruption to dialysis, sterilization equipment, meal services, sanitation, and outpatient care services, though the extent of disruption varied considerably among hospitals. None of the hospitals had determined the amount of water used for different purposes during normal service or formulated a plan for allocation of limited water in the event of a disaster. CONCLUSION: The present survey showed that it is possible to minimize the disruption and reduction of hospital functions in the event of a disaster by proper maintenance of water supply facilities and by ensuring alternative water resources, such as well water. It is also clear that it is desirable to conclude water supply agreements and formulate strategic water allocation plans in preparation for the eventuality of a long-term interruption to water services.
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Terremotos , Hospitais , Abastecimento de Água , Planejamento em Desastres , Humanos , Japão , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: When disasters that affect a wide area occur, external medical relief teams play a critical role in the affected areas by helping to alleviate the burden caused by surging numbers of individuals requiring health care. Despite this, no system has been established for managing deployed medical relief teams during the subacute phase following a disaster. After the Great East Japan Earthquake and tsunami, the Ishinomaki Medical Zone was the most severely-affected area. Approximately 6,000 people died or were missing, and the immediate evacuation of approximately 120,000 people to roughly 320 shelters was required. As many as 59 medical teams came to participate in relief activities. Daily coordination of activities and deployment locations became a significant burden to headquarters. The Area-based/Line-linking Support System (Area-Line System) was thus devised to resolve these issues for medical relief and coordinating activities. METHODS: A retrospective analysis was performed to examine the effectiveness of the medical relief provided to evacuees using the Area-Line System with regards to the activities of the medical relief teams and the coordinating headquarters. The following were compared before and after establishment of the Area-Line System: (1) time required at the coordinating headquarters to collect and tabulate medical records from shelters visited; (2) time required at headquarters to determine deployment locations and activities of all medical relief teams; and (3) inter-area variation in number of patients per team. RESULTS: The time required to collect and tabulate medical records was reduced from approximately 300 to 70 minutes/day. The number of teams at headquarters required to sort through data was reduced from 60 to 14. The time required to determine deployment locations and activities of the medical relief teams was reduced from approximately 150 hours/month to approximately 40 hours/month. Immediately prior to establishment of the Area-Line System, the variation of the number of patients per team was highest. Variation among regions did not increase after establishment of the system. CONCLUSION: This descriptive analysis indicated that implementation of the Area-Line System, a systematic approach for long-term disaster medical relief across a wide area, can increase the efficiency of relief provision to disaster-stricken areas.
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Planejamento em Desastres , Terremotos , Incidentes com Feridos em Massa , Equipe de Assistência ao Paciente/organização & administração , Socorro em Desastres , Eficiência , Humanos , Japão , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Fatores de TempoRESUMO
INTRODUCTION: Telecommunication systems are important for sharing information among health institutions to successfully provide medical response following disasters. HYPOTHESIS/PROBLEM: The aim of this study was to clarify the problems associated with telecommunication systems in the acute phase of the Great East Japan Earthquake (March 11, 2011). METHODS: All 72 of the secondary and tertiary emergency hospitals in Miyagi Prefecture were surveyed to evaluate the telecommunication systems in use during the 2011 Great Japan Earthquake, including satellite mobile phones, multi-channel access (MCA) wireless systems, mobile phones, Personal Handy-phone Systems (PHS), fixed-line phones, and the Internet. Hospitals were asked whether the telecommunication systems functioned correctly during the first four days after the earthquake, and, if not, to identify the cause of the malfunction. Each telecommunication system was considered to function correctly if the hospital staff could communicate at least once in every three calls. RESULTS: Valid responses were received from 53 hospitals (73.6%). Satellite mobile phones functioned correctly at the highest proportion of the equipped hospitals, 71.4%, even on Day 0. The MCA wireless system functioned correctly at the second highest proportion of the equipped hospitals. The systems functioned correctly at 72.0% on Day 0 and at 64.0% during Day 1 through Day 3. The main cause of malfunction of the MCA wireless systems was damage to the base station or communication lines (66.7%). Ordinary (personal or general communication systems) mobile phones did not function correctly at any hospital until Day 2, and PHS, fixed-line phones, and the Internet did not function correctly at any area hospitals that were severely damaged by the tsunami. Even in mildly damaged areas, these systems functioned correctly at <40% of the hospitals during the first three days. The main causes of malfunction were a lack of electricity (mobile phones, 25.6%; the Internet, 54.8%) and damage to the base stations or communication lines (the Internet, 38.1%; mobile phones, 56.4%). CONCLUSION: Results suggest that satellite mobile phones and MCA wireless systems are relatively reliable and ordinary systems are less reliable in the acute period of a major disaster. It is important to distribute reliable disaster communication equipment to hospitals and plan for situations in which hospital telecommunications systems do not function.
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Terremotos , Sistemas de Comunicação entre Serviços de Emergência , Telefone Celular , Planejamento em Desastres , Hospitais , Humanos , Internet , JapãoRESUMO
BACKGROUND: Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress. METHODS: Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture. RESULTS: Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture. CONCLUSIONS: Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage.
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Aneurisma Roto , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Camundongos , Animais , Aneurisma Intracraniano/prevenção & controle , Aneurisma Intracraniano/genética , Hemorragia Subaracnóidea/prevenção & controle , Aneurisma Roto/metabolismo , Receptores ErbB , RNA Mensageiro , Estresse do Retículo Endoplasmático , InflamaçãoRESUMO
BACKGROUND: In coil embolization of neurovascular aneurysms, we have noted that few wide-necked unruptured aneurysms are successfully embolized. This prompted us to search for useful factors to assist the choice of methods of coil embolization. METHOD: We first measured aneurysm size and volume using auto measurement (NVvol) and VER (NVver). Second, we calculated the volume (NVapp) and VER (NVapp) using approximation expressions. Third, we measured the end-on view neck angle using a 3 dimensional digital subtraction angiography (3D-DSA) image. RESULTS: NVvol and NVapp were correlated (y=0.87x). NVvol VER and NVapp VER approached 24% in 41 clinical cases. The dome/neck ratio averaged 1.15. Length of neck and the end-on view neck angle were significantly different between the stent-assisted group and the balloon-assisted group. NVvol and NVapp showed a good correlation with basic examination results in 41 clinical cases. CONCLUSION: The end-on view neck angle is significantly different. This boundary neck angle was 100° for the two groups. The end on-view neck angle is thus a useful factor for deciding medical treatment strategy.
Assuntos
Embolização Terapêutica/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Angiografia Digital , Humanos , Aneurisma Intracraniano/patologia , Imagens de FantasmasRESUMO
Background: Hepatic compartment syndrome (HCS) is a complication of nonoperative management in patients with blunt hepatic injury. Although decompression of elevated intrahepatic pressure through surgical exploration or drainage and hemorrhage control are required to manage this condition, evidence for such a management for this complication is insufficient. Herein, we report a pediatric patient treated with a planned combination strategy of surgical decompression with perihepatic packing to reduce intrahepatic pressure and subcapsular hemorrhage control as well as angioembolization to control intraparenchymal hemorrhage. Case presentation: A 12-year-old boy was referred to our emergency department 5 h after sustaining severe bruising in the upper abdomen in a traffic accident. Computed tomography (CT) showed an intraparenchymal hematoma in the right lobe of the liver; nonoperative management was selected based on stable hemodynamic status. Two days after the injury, he complained of severe abdominal pain and shock. CT showed an intraparenchymal and large subcapsular hematoma with right branch compression of the portal vein and extravasation of contrast material. Laboratory data showed progression of hepatocellular damage. We successfully managed this patient with a planned combination strategy of surgical decompression with perihepatic packing for reduction of intrahepatic pressure and subcapsular hemorrhage control, followed by angioembolization for control of intraparenchymal hemorrhage. Conclusion: Our study suggests that for the management of HCS, a planned combination strategy of damage control surgery and angioembolization is a therapeutic option.
RESUMO
BACKGROUND: The distribution of body mass in populations of Western countries differs from that of populations of East Asian countries. In East Asian countries, fewer people have a high body mass index than those in Western countries. In Japan, the country with the highest number of older adults worldwide, many people have a low body mass index. Therefore, this study aimed to determine the association between a low body mass index and mortality in patients with sepsis in Japan. METHODS: We conducted this retrospective analysis of 548 patients with severe sepsis from a multicenter prospective observational study. Multivariate logistic regression analyses determined the association between body mass index and 28-day mortality adjusted for age, sex, pre-existing conditions, the occurrence of septic shock, Acute Physiology and Chronic Health Evaluation II scores, and Sequential Organ Failure Assessment scores. Furthermore, the association between a low body mass index and 28-day mortality was analyzed. RESULTS: The low body mass index group represented 18.8% of the study population (103/548); the normal body mass index group, 57.3% (314/548); and the high body mass index group, 23.9% (131/548), with the 28-day mortality rates being 21.4% (22/103), 11.2% (35/314), and 14.5% (19/131), respectively. In the low body mass index group, the crude and adjusted odds ratios (95% confidence intervals) for 28-day mortality relative to the non-low body mass index (normal and high body mass index groups combined) group were 2.0 (1.1-3.4) and 2.3 (1.2-4.2), respectively. CONCLUSION: A low body mass index was found to be associated with a higher 28-day mortality than the non-low body mass index in patients with sepsis in Japan. Given that older adults often have a low body mass index, these patients should be monitored closely to reduce the occurrence of negative outcomes.
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Índice de Massa Corporal , Mortalidade Hospitalar/tendências , Escores de Disfunção Orgânica , Sepse/mortalidade , Magreza/mortalidade , Redução de Peso , Idoso , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sepse/epidemiologia , Taxa de SobrevidaRESUMO
[Figure: see text].
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Aneurisma Roto/metabolismo , Encéfalo/metabolismo , Armadilhas Extracelulares/metabolismo , Aneurisma Intracraniano/metabolismo , Animais , Humanos , CamundongosRESUMO
Inflammation is emerging as a critical factor in the pathophysiology of intracranial aneurysm. TLR4 (toll-like receptor 4) contributes not only to the innate immune responses but also to the inflammatory processes associated with vascular disease. Therefore, we examined the contribution of the TLR4 pathway to the development of the rupture of intracranial aneurysm. We used a mouse model of intracranial aneurysm. TLR4 inhibition significantly reduced the development of aneurysmal rupture. In addition, the rupture rate and levels of proinflammatory cytokines were lower in TLR4 knockout mice than the control littermates. Macrophage/monocyte-specific TLR4 knockout mice had a lower rupture rate than the control littermate mice. Moreover, the deficiency of MyD88 (myeloid differentiation primary-response protein 88), a key mediator of TLR4, reduced the rupture rate. These findings suggest that the TLR4 pathway promotes the development of intracranial aneurysmal rupture by accelerating inflammation in aneurysmal walls. Inhibition of the TLR4 pathway in inflammatory cells may be a promising approach for the prevention of aneurysmal rupture and subsequent subarachnoid hemorrhage.
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Aneurisma Roto/genética , Regulação da Expressão Gênica , Aneurisma Intracraniano/genética , RNA/genética , Receptor 4 Toll-Like/genética , Aneurisma Roto/metabolismo , Animais , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Aneurisma Intracraniano/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/biossínteseRESUMO
Gut microbiota modulates metabolic and immunoregulatory axes and contributes to the pathophysiology of diseases with inflammatory components, such as atherosclerosis, diabetes mellitus, and ischemic stroke. Inflammation is emerging as a critical player in the pathophysiology of an intracranial aneurysm. Therefore, we hypothesized that the gut microbiota affects aneurysm formation by modulating inflammation. We induced intracranial aneurysms in mice by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid. Depletion of the gut microbiota was achieved via an oral antibiotic cocktail of vancomycin, metronidazole, ampicillin, and neomycin. Antibiotics were given 3 weeks before aneurysm induction and either continued until the end of the experiment or stopped 1 day before aneurysm induction. We also assessed the effects of the gut microbiota depletion on macrophage infiltration and mRNA levels of inflammatory cytokines. Gut microbiota depletion by antibiotics reduced the incidence when antibiotics were started 3 weeks before aneurysm induction and continued until the end of the experiment (83% versus 6%, P<0.001). Even when antibiotics were stopped 1 day before aneurysm induction, the gut microbiota depletion significantly reduced the incidence of aneurysms (86% versus 28%, P<0.05). Both macrophage infiltration and mRNA levels of inflammatory cytokines were reduced with gut microbiota depletion. These findings suggest that the gut microbiota contributes to the pathophysiology of aneurysms by modulating inflammation. Human studies are needed to determine the exact contribution of the gut microbiota to the pathophysiology of aneurysm formation and disease course in humans.
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Microbioma Gastrointestinal/fisiologia , Aneurisma Intracraniano/etiologia , Animais , Anticorpos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Aneurisma Intracraniano/microbiologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: Disseminated intravascular coagulations (DIC), acute respiratory distress syndrome (ARDS), and acute kidney injury (AKI) are major organ dysfunctions that occur in patients with sepsis. This study aimed to elucidate the impact of these organ dysfunctions on mortality in patients with severe sepsis. MATERIAL AND METHODS: A prospective observational study was performed in 10 ICUs to obtain data from patients with severe sepsis. Multivariate analyses to examine in-hospital mortality were performed. RESULTS: Data of 573 patients were analyzed. In-hospital mortality rate was 19.4% (111/573). The incidences of DIC, ARDS, and AKI were 58.4%, 18.7%, and 41.7%, while the associated mortality rates were 28.9%, 36.4%, and 31.8%, respectively. In multiple regression model, DIC (odds ratio 2.71, 95% confidence interval [CI] 1.45-5.27) and AKI stage 3 (odds ratio 1.98, 95% CI 1.07-3.63) were significantly associated with higher in-hospital all-cause mortality. DIC (hazard ratio 2.58, 95% CI 1.53-4.55) and AKI stage 3 (hazard ratio 1.73, 95% CI 1.07-2.80) were also significantly associated with longer survival durations. However, severe ARDS was not associated with these outcomes. CONCLUSIONS: DIC and AKI are frequent complications in patients with severe sepsis. In this study, DIC, and AKI stage 3 were independent risk factors of in-hospital mortality.
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Insuficiência de Múltiplos Órgãos/mortalidade , Sepse/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Unidades de Terapia Intensiva , Japão , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Razão de Chances , Estudos Prospectivos , Fatores de RiscoRESUMO
Angiotensin-(1-7) (Ang-(1-7)) can regulate vascular inflammation and remodeling, which are processes that have important roles in the pathophysiology of intracranial aneurysms. In this study, we assessed the effects of Ang-(1-7) in the development of intracranial aneurysm rupture using a mouse model of intracranial aneurysms in which aneurysmal rupture (i.e., aneurysmal subarachnoid hemorrhage) occurs spontaneously and causes neurologic symptoms. Treatment with Ang-(1-7) (0.5 mg/kg/day), Mas receptor antagonist (A779 0.5 mg/kg/day or 2.5 mg/kg/day), or angiotensin II type 2 receptor (AT2R) antagonist (PD 123319, 10 mg/kg/day) was started 6 days after aneurysm induction and continued for 2 weeks. Angiotensin-(1-7) significantly reduced the rupture rate of intracranial aneurysms without affecting the overall incidence of aneurysms. The protective effect of Ang-(1-7) was blocked by the AT2R antagonist, but not by the Mas receptor antagonist. In AT2R knockout mice, the protective effect of Ang-(1-7) was absent. While AT2R mRNA was abundantly expressed in the cerebral arteries and aneurysms, Mas receptor mRNA expression was very scarce in these tissues. Angiotensin-(1-7) reduced the expression of tumor necrosis factor-α and interleukin-1ß in cerebral arteries. These findings indicate that Ang-(1-7) can protect against the development of aneurysmal rupture in an AT2R-dependent manner.
Assuntos
Aneurisma Roto/prevenção & controle , Angiotensina I/uso terapêutico , Encéfalo/irrigação sanguínea , Fragmentos de Peptídeos/uso terapêutico , Hemorragia Subaracnóidea/prevenção & controle , Aneurisma Roto/complicações , Aneurisma Roto/genética , Aneurisma Roto/patologia , Angiotensina II/análogos & derivados , Angiotensina II/uso terapêutico , Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Animais , Artérias Cerebrais/efeitos dos fármacos , Artérias Cerebrais/metabolismo , Artérias Cerebrais/patologia , Citocinas/análise , Imidazóis/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Piridinas/uso terapêutico , RNA Mensageiro/genética , Receptor Tipo 2 de Angiotensina/genética , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/genética , Hemorragia Subaracnóidea/patologiaRESUMO
Licorice, Glycyrrhiza glabra Linn., is one of herbal medicines widely used for various purposes, including as a sweetener and for gastric ulcer treatment. However, environmental destruction due to the harvesting of wild licorice is becoming a serious problem. We cultured licorice in a hydroponic system to examine the relation between the concentration of nutritional solution applied and glycyrrhizin content to determine the optimal nutrient solution concentration for commercial licorice production. Licorice growth and glycyrrhizin content in the root reached the highest values when the plants received nutrient solution approximately equivalent to a quarter unit of Hoagland solution. The results also indicated that the glycyrrhizin content does not correlate with the concentration of nutrient solution applied and/or inorganic contents absorbed, i.e., licorice may absorb large amounts of nutrient solution but the glycyrrhizin content may not increase.