RESUMO
We report a case of well leg compartment syndrome (WLCS) in both legs after robot-assisted laparoscopic prostatectomy (RALP). A 65-year-old man underwent surgery for prostate cancer. He was placed in the lithotomy position and both his legs were protected with elastic stockings and intermittent pneumatic com- pression to prevent deep vein thrombosis during sur- gery. After surgery, he complained of pain in both calves. Movement and sensory disorder along with swelling were found in both legs. Computed tomogra- phy of the legs showed damage to the soleus and gas- trocnemius muscles of both legs. The creatinine phos- phokinase level had increased to 10,560 IU · l⻹. The patient was diagnosed with WLCS in both legs and underwent conservative treatment. Symptoms in both legs started to improve from the next day. The right leg swelling receded within 10 days, while the left leg swelling receded 67 days after surgery. WLCS in the legs after RALP is a rare but severe complication requiring early diagnosis and intervention. To prevent WLCS, it is important that we recognize this disease as a potential complication after RALP.
Assuntos
Celulite (Flegmão)/etiologia , Síndromes Compartimentais/etiologia , Eosinofilia/etiologia , Laparoscopia/efeitos adversos , Perna (Membro) , Complicações Pós-Operatórias , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Idoso , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Neoplasias da Próstata/cirurgia , Decúbito DorsalRESUMO
A 73-year-old man (164cm height 51 kg body weight) with a history of Parkinson's disease and dementia was scheduled for a cervical lymph node biopsy under general anesthesia. We induced anesthesia with thiamylal and fentanyl, and maintained with sevoflurane and remifentanil without any incident. The patient did not emerge from anesthesia after the surgery. He developed coma and did not respond to painful stimuli. However, his breathing was spontaneous with stable hemodynamics. Although naloxone was given, he was still comatose. His clinical neurological findings showed no organic abnormalities. Forty minutes after the surgery, he suddenly woke up and followed instructions. We learned that previously he had been diagnosed with dementia with Lewy bodies.
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Anestesia Geral/efeitos adversos , Demência , Corpos de Lewy , Idoso , Conscientização , Demência/complicações , Humanos , MasculinoRESUMO
We encountered three cases of perioperative anaphylaxis identified by using skin-prick tests. [Case 1] A 43-year-old woman was scheduled to undergo elective laparoscopic subtotal gastrectomy under general anesthesia for gastric tumor. However, the procedure was cancelled because of anaphylaxis that was noted at the beginning of the surgery. We performed a skin-prick test and observed a positive reaction with ro- curonium. [Case 2] A 79-year-old man underwent laparoscopic colon resection under general anesthesia for colon cancer. Anaphylaxis was noted at the end of surgery. We performed a skin-prick test and observed a positive reaction with sugammadex. [Case 3] A 44-year-old woman underwent myomectomy under general anesthesia for a uterine fibroid. Anaphylaxis was noted approximately 10 minutes after the beginning of surgery. We performed a skin-prick test and noted a positive reaction with latex. It is difficult to identify the reason for anaphylaxis during surgery under general anesthesia because various agents may be responsible for the anaphylactic reaction. Anaphylaxis during surgery is a rare but life-threatening event and it is important to identify the causative agent for anaphylaxis.
Assuntos
Anafilaxia/induzido quimicamente , Anafilaxia/diagnóstico , Anestesia Geral/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Testes CutâneosRESUMO
Recent reports have shown interplay between EETs (epoxides) and the heme oxygenase (HO) system in attenuating adipogenesis in cell culture models; prompting an examination of the effectiveness of EET agonist on obesity and associated cardio-metabolic dysfunction. Patho-physiological effects of an EET agonist (NUDSA) were contrasted in the absence and in the presence of stannous mesoporphyrin (an HO inhibitor) in SD rats fed a high fat (58%, HF) for 16 weeks. Animals on HF diet exhibited enhanced oxidative stress, increased levels of inflammatory cytokines and decreased levels of adiponectin along with reduced vascular and adipose tissue levels of EETs, HO-1; as compared to control rats (11% dietary fat). Treatment with NUDSA not only reversed serum adiponectin and vascular and adipose tissue levels of EETs and HO-1, but also, decreased blood pressure, subcutaneous and visceral fat content and serum TNFα and IL-6 levels in rats on HF diet. Aortic endothelial function, peNOS expression and adipose tissue markers of energy homeostasis i.e. pAMPK, Sirt1 and FAS, impaired in rats fed a HF diet, were restored in animals treated with this EET agonist. That NUDSA enhanced HO-1 expression, was accompanied by increase in p-GSK-3ß and pAKT levels along with attenuation of adipose tissue levels of Bach 1--the transcriptional suppresser of HO-1 expression. Prevention of these beneficial effects of NUDSA, in animals on HF diet and concurrently exposed to NUDSA and SnMP, supports the role of EET-HO interaction in mediating such effects. Taken together, our findings suggest that the EETs stimulate HO-1 expression via suppression of Bach 1 and interplay of these two systems affords vascular and metabolic protection in diet induced obesity.
Assuntos
Adiposidade/efeitos dos fármacos , Ácido Aspártico/análogos & derivados , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Dieta Hiperlipídica , Eicosanoides/agonistas , Endotélio Vascular/fisiopatologia , Heme Oxigenase (Desciclizante)/metabolismo , Proteínas Repressoras/metabolismo , Adiponectina/sangue , Animais , Ácido Aspártico/farmacologia , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Eicosanoides/metabolismo , Endotélio Vascular/efeitos dos fármacos , Ferritinas/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Homeostase/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/enzimologia , Metaloporfirinas/farmacologia , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Delirium is a critical challenge in the intensive care unit (ICU) or high care unit (HCU) setting and is associated with poor outcomes. There is not much literature on how many patients in this setting are assessed for delirium and what tools are used. This study investigated the status of delirium assessment tools of patients in the ICU/HCU. We conducted a multicenter prospective observational study among 20 institutions. Data for patients who were admitted to and discharged from the ICU/HCU during a 1-month study period were collected from each institution using a survey sheet. The primary outcome was the usage rate of delirium assessment tools on an institution- and patient-basis. Secondary outcomes were the delirium prevalence assessed by each institution's assessment tool, comparison of delirium prevalence between delirium assessment tools, delirium prevalence at the end of ICH/HCU stay, and the relationship between potential factors related to delirium and the development of delirium. Result showed that 95% of institutions used the Intensive Care Delirium Screening Checklist (ICDSC) or the Confusion Assessment Method for the ICU (CAM-ICU) to assess delirium in their ICU/HCU, and the remaining one used another assessment scale. The usage rate (at least once during the ICU/HCU stay) of the ICDSC and the CAM-ICU among individual patients were 64.5% and 25.1%, and only 8.2% of enrolled patients were not assessed by any delirium assessment tool. The prevalence of delirium during ICU/HCU stay was 17.9%, and the prevalence of delirium at the end of the ICU/HCU stay was 5.9%. In conclusion, all institutions used delirium assessment tools in the ICU/HCU, and most patients received delirium assessment. The prevalence of delirium was 17.9%, and two-thirds of patients had recovered at discharge from ICU/HCU.Trial registration number: UMIN000037834.
Assuntos
Cuidados Críticos/métodos , Delírio/diagnóstico , Programas de Rastreamento/métodos , Idoso , Idoso de 80 Anos ou mais , Lista de Checagem , Delírio/epidemiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation that leads to acute lung injury. Carbon monoxide (CO), a by-product of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. The aim of this study was to examine the effects of CO inhalation at low concentration on lung injury induced by HSR in rats. METHODS: Rats were subjected to HSR by bleeding to achieve mean arterial pressure of 30 mm Hg for 60 minutes followed by resuscitation with shed blood and saline as needed to restore blood pressure. HSR animals were either maintained in room air or were exposed to CO at 250 ppm for 1 hour before and 3 hours after HSR. RESULTS: HSR caused an increase in the DNA binding activity of nuclear factor-kappaB and activator protein-1 in the lung followed by the up-regulation of pulmonary gene expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and interleukin (IL)-10. HSR also resulted in an increase in myeloperoxidase activity and wet weight to dry weight ratio in the lung, and more prominent histopathologic changes including congestion, edema, cellular infiltration, and hemorrhage. In contrast, CO inhalation significantly ameliorated these inflammatory events as judged by fewer histologic changes, less up-regulation of inflammatory mediators, and less activation of nuclear factor-kappaB and activator protein-1. Interestingly, the protective effects against lung injury afforded by CO were associated with further increases in mRNA expression of IL-10 in the lung. CONCLUSIONS: These findings suggest that inhaled CO at a low concentration ameliorated HSR-induced lung injury and attenuated inflammatory cascades by up-regulation of anti-inflammatory IL-10.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Monóxido de Carbono/uso terapêutico , Choque Hemorrágico/prevenção & controle , Lesão Pulmonar Aguda/patologia , Administração por Inalação , Animais , Monóxido de Carbono/análise , Carboxihemoglobina/análise , Modelos Animais de Doenças , Pulmão/química , Pulmão/patologia , Masculino , Óxido Nítrico Sintase Tipo II/análise , Peroxidase/análise , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição AP-1/análise , Fator de Necrose Tumoral alfa/análiseRESUMO
We have previously reported that adenoviral-mediated delivery of cytochrome P-450 (CYP) 4A2, which catalyzes the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), results in endothelial dysfunction and hypertension in Sprague-Dawley (SD) rats (Wang JS, Singh H, Zhang F, Ishizuka T, Deng H, Kemp R, Wolin MS, Hintze TH, Abraham NG, Nasjletti A, Laniado-Schwartzman M. Circ Res 98: 962-969, 2006). In this study, we targeted the vascular endothelium by using a lentivirus construct expressing CYP4A2 under the control of the endothelium-specific promoter VE-cadherin (VECAD-4A2) and examined the effect of long-term CYP4A2 overexpression on blood pressure and kidney function in SD rats. A bolus injection of VECAD-4A2 increased blood pressure (P < 0.001) by 26, 36, and 30 mmHg 10, 20, and 30 days postinjection, respectively. Arteries from VECAD-4A2-transduced rats produced increased levels of 20-HETE (P < 0.01), expressed lower levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) (P < 0.05), generated higher levels of superoxide anion, and displayed decreased relaxing responsiveness to acetylcholine (P < 0.05). Proteinuria increased by twofold in VECAD-4A2-transduced rats compared with controls. Treatment of VECAD-4A2-transduced rats with HET0016, an inhibitor of 20-HETE biosynthesis, not only attenuated the increase in blood pressure (P < 0.05) but also improved vascular function (acetylcholine-induced relaxations) and reduced plasma creatinine and proteinuria. HET0016 treatment decreased oxidative stress and increased the phosphorylated state of key proteins that regulate endothelial function, including eNOS, AKT, and AMPK. Collectively, these findings demonstrate that augmentation of vascular endothelial 20-HETE levels results in hypertension, endothelial dysfunction, and renal injury, which is offset by HET0016 through a reduction in vascular 20-HETE coupled with a lessening of oxidative stress and the amplification of pAKT, pAMPK, and p-eNOS levels leading to normalization of endothelial responses.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Endotélio Vascular/metabolismo , Ácidos Hidroxieicosatetraenoicos/biossíntese , Hipertensão/metabolismo , Proteinúria/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Acetilcolina , Animais , Antígenos CD/genética , Pressão Sanguínea , Caderinas/genética , Linhagem Celular , Sistema Enzimático do Citocromo P-450/genética , DNA Complementar , Marcação de Genes , Técnicas de Transferência de Genes , Humanos , Lentivirus , Óxido Nítrico Sintase Tipo III/metabolismo , Oxirredução , Fosforilação , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxidos/metabolismo , VasodilataçãoRESUMO
Heme oxygenase (HO) and cytochrome P450 (P450)-derived epoxyeicosatrienoic acids (EETs) participate in vascular protection, and recent studies suggest these two systems are functionally linked. We examined the consequences of HO deficiency on P450-derived EETs with regard to body weight, adiposity, insulin resistance, blood pressure, and vascular function in HO-2-null mice. The HO-2-null mice were obese, displayed insulin resistance, and had high blood pressure. HO-2 deficiency was associated with decreases in cyp2c expression, EET levels, HO-1 expression, and HO activity and with an increase in superoxide production and an impairment in the relaxing response to acetylcholine. In addition, HO-2-null mice exhibited increases in serum levels of tumor necrosis factor (TNF)-alpha and macrophage chemoattractant protein (MCP)-1 and a decrease in serum adiponectin levels. Treatment of HO-2-null mice with a dual-activity EET agonist/soluble epoxide hydrolase inhibitor increased renal and vascular EET levels and HO-1 expression, lowered blood pressure, prevented body weight gain, increased insulin sensitivity, reduced subcutaneous and visceral fat, and decreased serum TNF-alpha and MCP-1, while increasing adiponectin and restoring the relaxing responses to acetylcholine. The decrease in cyp2c expression and EETs levels in HO-2-null mice underscores the importance of the HO system in the regulation of epoxygenase levels and suggests that protection against obesity-induced cardiovascular complications requires interplay between these two systems. A deficiency in one of these protective systems may contribute to the adverse manifestations associated with the clinical progression of the metabolic syndrome.
Assuntos
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Heme Oxigenase (Desciclizante)/fisiologia , Síndrome Metabólica/enzimologia , Síndrome Metabólica/metabolismo , Ácido 8,11,14-Eicosatrienoico/agonistas , Ácido 8,11,14-Eicosatrienoico/metabolismo , Adiponectina/biossíntese , Adiponectina/sangue , Tecido Adiposo/metabolismo , Animais , Aorta/enzimologia , Aorta/metabolismo , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Western Blotting , Peso Corporal/fisiologia , Quimiocina CCL2/biossíntese , Quimiocina CCL2/sangue , Sistema Enzimático do Citocromo P-450/biossíntese , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase-1/biossíntese , Córtex Renal/enzimologia , Córtex Renal/metabolismo , Proteínas de Membrana/biossíntese , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/prevenção & controle , Camundongos , Camundongos Knockout , Fenótipo , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/sangue , Vasodilatação/fisiologiaRESUMO
Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.
RESUMO
Hemorrhagic shock and resuscitation (HSR) induces a pulmonary inflammatory response and frequently causes acute lung injury. Carbon monoxide-releasing molecule-3 (CORM-3) has been reported to liberate and deliver CO under physiological conditions, which exerts organ-protective effects during systemic insults. The present study aimed to determine whether the administration of CORM-3 following HSR exerts a therapeutic effect against HSR-induced lung injury without any detrimental effects on oxygenation and hemodynamics. To induce hemorrhagic shock, rats were bled to a mean arterial blood pressure of 30 mmHg for 45 min and then resuscitated with the shed blood. CORM-3 or a vehicle was intravenously administered immediately following the completion of resuscitation. The rats were divided into four groups, including sham, HSR, HSR/CORM-3 and HSR/inactive CORM-3 groups. Arterial blood gas parameters and vital signs were recorded during HSR. The histopathological changes to the lungs were evaluated using a lung injury score, while pulmonary edema was evaluated on the basis of the protein concentration in bronchoalveolar lavage fluid and the lung wet/dry ratio. We also investigated the pulmonary expression levels of inflammatory mediators and apoptotic markers such as cleaved caspase-3 and transferase-mediated dUTP-fluorescein isothiocyanate nick-end labeling (TUNEL) staining. Although HSR caused significant lung histopathological damage and pulmonary edema, CORM-3 significantly ameliorated this damage. CORM-3 also attenuated the HSR-induced upregulation of tumor necrosis factor-α, inducible nitric oxide synthase and interleukin-1ß genes, and the expression of interleukin-1ß and macrophage inflammatory protein-2. In addition, the expression of interleukin-10, an anti-inflammatory cytokine, was inversely enhanced by CORM-3, which also reduced the number of TUNEL-positive cells and the expression of cleaved caspase-3 following HSR. Although CORM-3 was administered during the acute phase of HSR, it did not exert any influence on arterial blood gas analysis data and vital signs during HSR. Therefore, treatment with CORM-3 ameliorated HSR-induced lung injury, at least partially, through anti-inflammatory and anti-apoptotic effects, without any detrimental effects on oxygenation and hemodynamics.
RESUMO
Heme oxygenase (HO) 1 is inducible by a variety of oxidative stress and is thought to play an important role in the protection of tissues from oxidative injuries. Because hemorrhagic shock (HS) is an oxidative stress that results in tissue injury, we examined in this study the role of HO-1 induction in intestinal tissue injuries in a rat model of HS. The levels of HO-1 were significantly increased after HS both at transcriptional and protein levels in mucosal epithelial cells in the duodenum, jejunum, and colon, whereas their expression in the ileum was hardly detectable and not increased at all by the treatment. In contrast, HS-induced mucosal inflammation and apoptotic cell death in the duodenum, jejunum, and colon were far less than those observed in ileum as judged by the levels of expression of TNF-alpha, iNOS, activated caspase 3, and Bcl-2. Of note, inhibition of HO activity by tin-mesoporphyrin resulted in an aggravation of HS-induced tissue inflammation and apoptotic cell death. These findings indicate that HO-1 expression in the intestine is regulated in a highly site-specific manner after HS, and that HO-1 induction plays a fundamental role in protecting mucosal cells of the intestine from oxidative damages induced by HS.
Assuntos
Heme Oxigenase-1/metabolismo , Mucosa Intestinal/metabolismo , Choque Hemorrágico/metabolismo , Animais , Apoptose/efeitos dos fármacos , Northern Blotting , Expressão Gênica , Heme/metabolismo , Heme Oxigenase-1/antagonistas & inibidores , Heme Oxigenase-1/genética , Imuno-Histoquímica , Intestinos/irrigação sanguínea , Intestinos/efeitos dos fármacos , Masculino , Metaloporfirinas/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/fisiopatologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Thin polycrystalline zinc-doped indium oxide (In2O3-ZnO) films were prepared by post-annealing amorphous films with various weight concentrations x of ZnO in the range 0⩽x ⩽0.06. We have studied the dependences of the resistivity ρ and Hall coefficient on temperature T and magnetic field H in the range 0.5⩽T ⩽300 K, H⩽6 Tfor 350 nm films annealed in air. Films with 0⩽x⩽0.03 show the superconducting resistive transition. The transition temperature Tc is below 3.3 K and the carrier density n is about 1025-1026 m-3. The annealed In2O3-ZnO films were examined by transmission electron microscopy and x-ray diffraction analysis revealing that the crystallinity of the films depends on the annealing time. We studied the upper critical magnetic field Hc2 (T) for the film with x = 0.01. From the slope of dHc2 /dT, we obtain the coherence length ξ (0) ≈ 10 nm at T = 0 K and a coefficient of electronic heat capacity that is small compared with those of other oxide materials.
RESUMO
This study was designed to investigate the effect of increased levels of HO-1 on hypertension exacerbated by diabetes. Diabetic spontaneously hypertensive rat (SHR) and WKY (control) animals were treated with streptozotocin (STZ) to induce diabetes and stannous chloride (SnCl(2)) to upregulate HO-1. Treatment with SnCl(2) not only attenuated the increase of blood pressure (p<0.01), but also increased HO-1 protein content, HO activity and plasma adiponectin levels, decreased the levels of superoxide and 3-nitrotyrosine (NT), respectively. Reduction in oxidative stress resulted in the increased expression of Bcl-2 and AKT with a concomitant reduction in circulating endothelial cells (CEC) in the peripheral blood (p<0.005) and an improvement of femoral reactivity (response to acetylcholine). Thus induction of HO-1 accompanied with increased plasma adiponectin levels in diabetic hypertensive rats alters the phenotype through a reduction in oxidative stress, thereby permitting endothelial cells to maintain an anti-apoptotic environment and the restoration of endothelial responses thus preventing hypertension.
RESUMO
Hemorrhagic shock followed by resuscitation (HSR) causes neutrophil sequestration in the lung which leads to acute lung injury (ALI). Neutrophil elastase (NE) is thought to play a pivotal role in the pathogenesis of ALI. This study investigated whether sivelestat, a specific NE inhibitor, can attenuate ALI induced by HSR in rats. Male Sprague-Dawley rats were subjected to hemorrhagic shock by withdrawing blood so as to maintain a mean arterial blood pressure of 30+/-5 mm Hg for 60 min followed by resuscitation with the shed blood. HSR-treated animals received a bolus injection of sivelestat (10 mg/kg) intravenously at the start of resuscitation followed by continuous infusion for 60 min (10 mg/kg/h) during the resuscitation phase, or the vehicle. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, myeloperoxidase (MPO) activity, gene expression of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS), DNA binding activity of nuclear factor (NF)-kappaB, and immunohistochemical analysis of intercellular adhesion molecule (ICAM)-1. HSR treatment induced lung injury, as demonstrated by pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio, MPO activity, gene expression of TNF-alpha and iNOS, and DNA-binding activity of NF-kappaB, and enhanced expression of ICAM-1. In contrast, sivelestat treatment significantly ameliorated the HSR-induced lung injury, as judged by the marked improvement in all these indices. These results indicate that sivelestat attenuated HSR-induced lung injury at least in part through an inhibition of the inflammatory signaling pathway, in addition to the direct inhibitory effect on NE.
Assuntos
Glicina/análogos & derivados , Elastase de Leucócito/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Pulmão/patologia , Choque Hemorrágico/enzimologia , Choque Hemorrágico/patologia , Sulfonamidas/farmacologia , Animais , DNA/metabolismo , Regulação da Expressão Gênica , Glicina/farmacologia , Molécula 1 de Adesão Intercelular/metabolismo , Elastase de Leucócito/metabolismo , Pulmão/enzimologia , Lesão Pulmonar , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Tamanho do Órgão/efeitos dos fármacos , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Ressuscitação , Choque Hemorrágico/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
To determine drug susceptibility of Trichophyton tonsurans endemic in Japan, in vitro MICs of antifungal drugs against a total of 10 clinical isolates of T. tonsurans collected from dermatophytosis patients were measured by the agar dilution method and the broth microdilution method. The agar dilution method was not appropriate as the growth of T. tonsurans on the agar medium was too slow to determine drug activity, while the broth microdilution method was thought to be an appropriate method for this study. The MIC90 values determined by the broth microdilution method for terbinafine, itraconazole, miconazole and ketoconazole were 0.013, 0.1, 0.8 and 0.4 microg/ml, respectively. Meanwhile, the MIC90 values of lanoconazole and luliconazole, known to be antifungal drugs potent against dermatomycosis, were 0.00078 and 0.00039 microg/ ml, respectively. The drug susceptibility of these T. tonsurans isolates to the aforementioned antifungal drugs was found to be on a similar level with that of T. mentagrophytes and T. rubrum, major causative agents of dermatomycosis. The results also demonstrated the strong antifungal activity of lanoconazole and luliconazole against T. tonsurans.
Assuntos
Antifúngicos/farmacologia , Trichophyton/efeitos dos fármacos , Dermatomicoses/microbiologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
A 6-year-old child with Schwartz-Jampel syndrome (SJS) underwent tenotomy of bilateral lower limbs under general anesthesia. Patient with SJS has problems such as difficulty of intubation owing to microstomia and jaw muscle rigidity, and is susceptible to malignant hyperthermia by using volatile inhalation anesthetics. In this case, we used a laryngeal mask for airway management and anesthesia was maintained with inhalation of nitrous oxide and continuous i.v. infusion of propofol with caudal block, and his clinical course was uneventful.
Assuntos
Anestesia Geral , Osteocondrodisplasias/cirurgia , Anestesia Geral/métodos , Anestésicos Inalatórios , Criança , Contraindicações , Humanos , Máscaras Laríngeas , Extremidade Inferior , Masculino , Hipertermia Maligna/etiologia , Hipertermia Maligna/prevenção & controle , Óxido Nitroso , Propofol , Tendões/cirurgiaRESUMO
To study spontaneous intraocular hemorrhage in rats during postnatal ocular development and to elucidate the underlying mechanism, postnatal ocular development in the albino Wistar Hannover (WH) and Sprague-Dawley (SpD) and pigmented Long-Evans (LE) strains was analyzed. Pups (n = 2 to 5) from each strain were euthanized daily on postnatal days (PND) 0 through 21 and their eyes examined macroscopically and histologically; similar analyses were performed in 26 to 39 additional WH pups daily from PND 7 to 14. At necropsy, ring-shaped red regions and red spots were present in the eyes of WH and SpD rats. These lesions were attributed histologically to hemorrhage of the tunica vasculosa lentis or of the retina, choroid, and hyaloid artery, respectively. Similar intraocular hemorrhages occurred in LE rats, although the macroscopic alterations found in WH and SpD rats were not present in this strain. Among the 3 strains evaluated, the incidence of the intraocular hemorrhage was highest in WH rats. We here showed that intraocular hemorrhage occurs spontaneously during normal ocular development in rats regardless of the strain; however, the region, degree, and incidence of intraocular hemorrhage differ among strains. Hemorrhage in the tunica vasculosa lentis and hyaloid artery may result from the leakage of erythrocytes from the temporary vasculature of these tissues during regression. The mechanisms underlying hemorrhage in the retina and choroid remain unclear. To our knowledge, this report is the first to describe the spontaneous intraocular hemorrhage that occurs during postnatal ocular development in rats.
Assuntos
Hemorragia da Coroide/veterinária , Olho/crescimento & desenvolvimento , Olho/patologia , Hemorragia Retiniana/veterinária , Doenças dos Roedores/patologia , Fatores Etários , Animais , Animais Recém-Nascidos , Hemorragia da Coroide/etiologia , Hemorragia da Coroide/patologia , Olho/irrigação sanguínea , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Ratos Wistar , Hemorragia Retiniana/etiologia , Hemorragia Retiniana/patologia , Doenças dos Roedores/etiologia , Índice de Gravidade de Doença , Especificidade da EspécieRESUMO
Androgen receptor (AR) is an essential component to activate AR dependent gene transcriptions. Despite wide acceptance of pharmacological controls on transcriptional pathway depending on competitive inhibitions of ligand binding, only a few examples, AR antagonism via ligand-independent mechanisms, have been recognized. Pyrifluquinazon(PFQ), a newly developed pesticide, induced representative AR antagonism against rats in in vivo and in vitro. Intriguingly, this AR antagonism was not based on inhibition of ligand binding. Instead, the evidence suggested that the AR antagonism was induced as a consequence of decline of cellular AR protein level. This study demonstrated that AR N-terminal region could be an essential element for a ligand-independent mechanism underling the AR antagonism by PFQ. Our findings should provide a novel insight into the regulation of AR-mediated transcription.
Assuntos
Antagonistas de Receptores de Andrógenos/toxicidade , Praguicidas/toxicidade , Quinazolinonas/toxicidade , Receptores Androgênicos/metabolismo , Animais , Linhagem Celular Tumoral , Células HEK293 , Humanos , Ligantes , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Próstata/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/genética , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacosRESUMO
High-dietary fat intake is a major risk factor for development of metabolic and cardiovascular-renal dysfunction including obesity, coronary artery disease, hypertension, and chronic renal failure. We examined the effect of a high-fat diet on renal function and morphology in spontaneously hypertensive rats (SHR), a phenotype designed to mimic metabolic syndrome. High-fat diet induced increase (P < 0.05) in blood pressure, body weight, and renal lipid deposition in these rats. This increase in body weight was accompanied by elevations (P < 0.05) of blood glucose and low-density lipoprotein (LDL) levels, a decrease (P < 0.05) in adiponectin and increases (P < 0.05) in plasma monocyte chemotactic protein-1 (MCP-1) along with renal macrophage infiltration. These pathophysiological perturbations were attenuated (P < 0.05) by heme oxygenase-1 (HO-1) induction by treatment with cobalt protoporphyrin (CoPP). Further effects of CoPP included increased (P < 0.05) renal expression of adiponectin along with enhancement (P < 0.05) of pAKT, pAMPK, and p-eNOS in SHRs fed a high-fat diet. Prevention of such beneficial effects of CoPP by the concurrent administration of the heme-HO inhibitor stannous mesoporphyrin (SnMP) corroborates the role of HO system in mediating such effects. Taken together, our results demonstrate that high-fat diet induces a metabolic syndrome-like phenotype in hypertensive rats, which is amenable to rescue by increases in HO-1- and adiponectin-dependent pathways.
Assuntos
Adiponectina/sangue , Dieta Hiperlipídica/efeitos adversos , Heme Oxigenase-1/farmacologia , Rim/metabolismo , Síndrome Metabólica/sangue , Obesidade/sangue , Animais , Glicemia/metabolismo , Pressão Sanguínea , Quimiocina CCL2/sangue , Heme Oxigenase-1/sangue , Rim/patologia , Lipoproteínas LDL/sangue , Masculino , Fenótipo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de SinaisRESUMO
We examined the hypothesis that vascular and renal dysfunction caused by angiotensin II (Ang II) through increased levels of blood pressure, inflammatory cytokines, and oxidative stress in Sprague-Dawley rats can be prevented by lentiviral-mediated delivery of endothelial heme oxygenase (HO)-1. We targeted the vascular endothelium using a lentiviral construct expressing human HO-1 under the control of the endothelium-specific promoter VE-cadherin (VECAD-HO-1) and examined the effect of long-term human HO-1 expression on blood pressure in Ang II-mediated increases in blood pressure and oxidant stress. A bolus injection of VECAD-HO-1 into the renal artery resulted in expression of human HO-1 for up to 6-9 weeks. Sprague-Dawley rats were implanted with Ang II minipumps and treated with lentivirus carrying either the HO-1 or green fluorescent protein. Renal tissue from VECAD-HO-1-transduced rats expresses human HO-1 mRNA and proteins without an effect on endogenous HO-1. Infusion of Ang II increased blood pressure (p < 0.001) but decreased vascular relaxation in response to acetylcholine, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS) levels, and renal and plasma levels of adiponectin (p < 0.05); in contrast, plasma tumor necrosis factor-α and monocyte chemoattractant protein-1 levels increased. Ang II-treated animals had higher levels of superoxide anion and inducible nitric oxide synthase and increased urinary protein and plasma creatinine levels. Lentiviral transduction with the VECAD-HO-1 construct attenuated the increase in blood pressure (p < 0.05), improved vascular relaxation, increased plasma adiponectin, and prevented the elevation in urinary protein and plasma creatinine in Ang II-treated rats. Endothelial-specific expression of HO-1 also reduced oxidative stress and levels of inflammatory cytokines resulting in increased expression of the anti-apoptotic proteins phosphorylated AKT, phosphorylated AMP-activated protein kinase, peNOS, and eNOS. Collectively, these findings demonstrate that endothelial-specific increases in HO-1 expression attenuate Ang II hypertension and the associated vascular dysfunction that is associated with increases in adiponectin and peNOS and reductions in oxidative stress and levels of inflammatory cytokines.