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The aim of the present study was to assess the acute toxic potential of cerium oxide nanoparticles (CeO2 NPs) in rats when exposed through the head and nose inhalation route. The rats were exposed to CeO2 NPs and the resultant effects if any, to cause cytotoxicity, oxidative stress and inflammation in the lungs were evaluated on a 24 h, 48 h and 14 day post exposure period. Our results showed a significant decrease in the cell viability, with the increase of lactate dehydogenase, total protein and alkaline phosphatase levels in the bronchoalveolar lavage fluid (BALF) of the exposed rats. Total leukocyte count and the percentage of neutrophils in BALF were elevated within 24 h of post exposure. The concentrations of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) were significantly increased in the BALF and in the blood throughout the observation period. The level of malondialdehyde was elevated with the decreased levels of intracellular reduced glutathione (GSH) in the lung after exposure. The alveolar macrophages (AMs) and neutrophils overloaded with phagocytosed CeO2 NPs were observed along with non-phagocytosed free CeO2 NPs that were deposited over the epithelial surfaces of the bronchi, bronchiole and alveolar regions of lungs within 24 h of post exposure and were consistent throughout the observation period. A well distributed, multifocal pulmonary microgranulomas due to impairment of clearance mechanism leading to biopersistence of CeO2 NPs for an extended period of time were observed at the end of the 14 day post exposure period. These results suggest that acute exposure of CeO2 NPs through inhalation route may induce cytotoxicity via oxidative stress and may lead to a chronic inflammatory response. 相似文献
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We report a case of an elderly lady with a long-term suprapubic catheter who developed purple discoloration of urine around the same time as she developed intussusception. Purple urine bag syndrome is a benign condition known to be associated with intestinal stasis. However, this association with intussusception should be kept in mind before the patient is reassured. 相似文献
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Hameeda Sultana Girish Neelakanta Fred S. Kantor Stephen E. Malawista Durland Fish Ruth R. Montgomery Erol Fikrig 《The Journal of experimental medicine》2010,207(8):1727-1743
Anaplasma phagocytophilum, the agent of human anaplasmosis, persists in ticks and mammals. We show that A. phagocytophilum induces the phosphorylation of actin in an Ixodes ricinus tick cell line and Ixodes scapularis ticks, to alter the ratio of monomeric/filamentous (G/F) actin. A. phagocytophilum–induced actin phosphorylation was dependent on Ixodes p21-activated kinase (IPAK1)–mediated signaling. A. phagocytophilum stimulated IPAK1 activity via the G protein–coupled receptor Gβγ subunits, which mediated phosphoinositide 3-kinase (PI3K) activation. Disruption of Ixodes gβγ, pi3k, and pak1 reduced actin phosphorylation and bacterial acquisition by ticks. A. phagocytophilum–induced actin phosphorylation resulted in increased nuclear G actin and phosphorylated actin. The latter, in association with RNA polymerase II (RNAPII), enhanced binding of TATA box–binding protein to RNAPII and selectively promoted expression of salp16, a gene crucial for A. phagocytophilum survival. These data define a mechanism that A. phagocytophilum uses to selectively alter arthropod gene expression for its benefit and suggest new strategies to interfere with the life cycle of this intracellular pathogen, and perhaps other Rickettsia-related microbes of medical importance.Human Granulocytic Anaplasmosis is an increasingly common tick-borne illness in the United States, Europe, and Asia (Dumler et al., 2005; Bakken and Dumler, 2008). The agent of this disease, Anaplasma phagocytophilum, survives within human neutrophils using several strategies, including delaying apoptosis, inhibiting NADPH oxidase activity, and subverting phagolysosome biogenesis to reside in an inclusion that does not fuse with lysosomes (Carlyon and Fikrig, 2003). Tyrosine phosphorylation of translocated bacterial effector proteins is another key feature that enables pathogens to thwart host cell signaling (Selbach et al., 2009). Several proteins translocated by bacterial type III and IV secretion systems are involved in pedestal formation (Tir of EPEC and Citrobacter), cell scattering (CagA of Helicobacter), invasion (Tarp of Chlamydia), and cell proliferation (BepD-F of Bartonella; Covacci and Rappuoli, 2000). Bacterial protein tyrosine kinases and phosphatases also play a role in pathogenicity and enable the microbe to short circuit host defense mechanisms and thwart signaling (Covacci and Rappuoli, 2000). A. phagocytophilum AnkA protein is tyrosine phosphorylated by Abl-1 kinase to facilitate infection (Lin et al., 2007; IJdo et al., 2007). A. phagocytophilum AnkA also binds to granulocyte DNA and nuclear proteins, leading to speculation about the functional nature of AnkA–host cell DNA interactions (Park et al., 2004). The agent of human granulocytic anaplasmosis also induces the tyrosine phosphorylation of ROCK1 in human neutrophils to aid in intracellular survival (Thomas and Fikrig, 2007). Collectively, these studies demonstrate that this unique obligate intracellular pathogen has evolved diverse mechanisms to persist within mammalian cells and that tyrosine phosphorylation of proteins plays an important role in the manipulation of host cellular events to promote A. phagocytophilum survival.A. phagocytophilum is closely related to other arthropod-borne bacteria in the genera Rickettsia and Ehrlichia that infect the mammalian host (Dumler et al., 2001). Intracellular microorganisms, including Rickettsia, Shigella, Listeria, and vaccinia virus, among others, use actin polymerization to move within and spread between cells (Frischknecht et al., 1999a; Goosney et al., 1999; Gouin et al., 2004; Cossart and Toledo-Arana, 2008). These pathogens recruit host actin and cytoskeletal proteins to their surface and activate the assembly of an actin comet tail (Goldberg, 2001; Gouin et al., 2005; Cossart and Toledo-Arana, 2008). In contrast, Salmonella, Neisseria, and Bartonella intercept actin rearrangements during internalization (Dramsi and Cossart, 1998; Patel and Galán, 2005; Patel et al., 2009). Some microbes manipulate the actin cytoskeleton by directly injecting effectors or virulence factors into cells, thereby specifically targeting crucial intracellular signaling pathways (Sansonetti, 2002; Münter et al., 2006; Bhavsar et al., 2007). Yersinia activates the effector protein YpkA to phosphorylate Gαq and cause the disassembly of actin stress fibers (Navarro et al., 2007). Vaccinia virus achieves actin-based motility by mimicking the tyrosine kinase signaling pathways that control actin nucleation dynamics (Frischknecht et al., 1999b). In mammalian cells, the Rickettsia surface protein RickA activates the Arp2/3 complex to induce actin polymerization and filopodia formation (Martinez and Cossart, 2004). The essential role of actin-based motility and actin dynamics has not been examined in the arthropod vector.Some bacteria use arthropod components and signaling events to survive in the vector or to facilitate transmission to the host. A. phagocytophilum is naturally maintained in a tick-rodent cycle. Humans are merely incidental hosts. Uninfected Ixodes scapularis larvae acquire A. phagocytophilum within 2 d of tick engorgement on A. phagocytophilum–infected mice, and once in the tick, the bacteria migrate through the gut to infect the salivary glands (Hodzic et al., 1998). The larvae molt into nymphs and later into adults, whereas the bacteria persist within the secretory acini of the salivary glands (Hodzic et al., 1998; Katavolos et al., 1998). Upon tick feeding, the bacteria replicate and migrate from the salivary glands to the mammalian host (to invade granulocytes), and the transmission of A. phagocytophilum occurs between 24 and 48 h after tick engorgement (Hodzic et al., 1998; Katavolos et al., 1998). I. scapularis, the black-legged tick, is a vector for viral and bacterial pathogens including A. phagocytophilum and Borrelia burgdorferi, the agent of Lyme disease (Schwan, 1996; Dumler et al., 2005). The extended period of association of these microbes with the vector has resulted in the development of intimate relationships between pathogen and arthropod. For example, B. burgdorferi uses Salp15, a tick salivary gland protein, to facilitate infection of the mammalian host (Ramamoorthi et al., 2005). Salp15 is selectively increased in B. burgdorferi–infected tick salivary glands during engorgement, and silencing of the salp15 gene in I. scapularis reduced the capacity of tick-borne spirochaetes to infect mice (Ramamoorthi et al., 2005). In addition, Salp15 binds B. burgdorferi, thereby protecting the spirochete from antibody-mediated killing (Ramamoorthi et al., 2005). A. phagocytophilum up-regulates Salp16, a tick salivary gland protein, to survive in its arthropod vector (Sukumaran et al., 2006). Acquisition of A. phagocytophilum from the infected mammalian host was severely inhibited and the bacterial loads were substantially lower in the salivary glands of salp16-silenced ticks, thereby suggesting that A. phagocytophilum specifically requires salp16 to infect salivary glands (Sukumaran et al., 2006). When Salp16 is not present in I. scapularis, as demonstrated in RNAi studies, A. phagocytophilum can no longer effectively persist within tick salivary glands (Sukumaran et al., 2006). The mechanisms used by A. phagocytophilum to influence its arthropod vector, including the expression of I. scapularis genes, are not known. We now explore whether A. phagocytophilum selectively modulates arthropod signaling by altering protein phosphorylation and whether these processes influence I. scapularis gene expression and survival of A. phagocytophilum within ticks. 相似文献
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STUDY OBJECTIVE: Preoperative risk factors for pulmonary aspiration of gastric contents during anesthesia are well studied. There is lack of information as to factors or circumstances leading to aspiration. DESIGN: A retrospective review of cases of pulmonary aspiration reported to the Departmental Quality Assurance (QA) Committee was undertaken. SETTING: This study took place at a large tertiary care university hospital based in a metropolitan city. PATIENTS: The study identified all patients reported to the QA Committee as having pulmonary aspiration during January 1991 to December 1994 and July 1996 to December 2000. INTERVENTIONS: No interventions were done. MEASUREMENTS: The medical records of all patients thus identified were reviewed to see if they had pulmonary aspiration according to strict criteria. Presence of preoperative known risk factors, prophylactic measures used against pulmonary aspiration, and perioperative events were noted. MAIN RESULTS: A total of 47 patients were reported to the QA Committee as having pulmonary aspiration during this period. Upon review, 23 patients had pulmonary aspiration (definite aspiration, n = 12; probable aspiration, n = 11) and 24 patients did not meet the criteria for pulmonary aspiration of gastric contents. The incidence of pulmonary aspiration overall was 1 per 8671 anesthetics and 1 per 4385 anesthetics in patients younger than 16 years. If all 47 cases reported to QA Committee are presumed to have had pulmonary aspiration, then the overall incidence of aspiration is 1 in 4243 anesthetics. Eighteen of 23 patients had a preoperative risk factor, but preventive measures against aspiration had been used in only 4 patients. Five patients did not have any apparent preoperative risk factor. CONCLUSIONS: This study confirms that pulmonary aspiration of gastric contents is a rare complication during modern anesthesia. Preoperative risk factor was present in most patients who had pulmonary aspiration. A clear understanding of risk factor/s is needed to prevent further cases of pulmonary aspiration. 相似文献
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A patient with familial amyloid polyneuropathy underwent a living, nonrelated orthotopic liver transplant and developed hypotension after induction of anesthesia. Causes of hypotension in patients with familial amyloid polyneuropathy are discussed. Transesophageal echocardiographic monitoring was invaluable in differentiating various causes of hypotension and in diagnosing peripheral vasodilation as the predominant cause of hypotension. 相似文献
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