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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Candida albicans (CA) increasingly causes septic shock, acute lung injury, and multiple organ damage during immunosuppression-related neutropenia. However, the effects of neutrophil (PMN) depletion on induction of tumor necrosis factor-alpha (TNF) by CA and its potential mediation of Candida septic shock are unknown. We hypothesized that reduced CA uptake by circulating PMNs during cyclophosphamide (CY)-related neutropenia sensitizes to TNF-mediated shock from enhanced cytokine production after phagocytosis by tissue macrophages. Absolute or relative neutropenia (PMNs < or = 500/microliters or 2,500/microliters) was modeled in rats by intraperitoneal CY 4-8 days before 10(9) yeast-phase CA (acute studies < or = 24 h, n = 81 animals) or 10(6) CA (subacute studies < or = 72 h, n = 25). Compared with neutrophil-sufficient rats, absolute neutropenia accelerated hemodynamic collapse and respiratory distress after 10(9) CA, and pulmonary microvascular permeability was amplified. These changes evolved without increased candidemia or elevations in bioactive or antigenic serum TNF, which remained low even at death (42.3 +/- 14.8 U/ml vs. 12.6 +/- 2.9 U/ml for CY + saline, means +/- SE, P = NS). In contrast, significant TNF in lung tissue and bronchoalveolar lavage fluid (BALF) was evident within 6 h in CY + 10(9) CA rats. Electron microscopy confirmed hyphal proliferation into alveoli from yeast within mononuclear cells in lung capillaries. Subacute disseminated candidiasis after 10(6) CA was not associated with elevated serum, lung, or BALF TNF. We conclude that differential systemic and intrapulmonary TNF production occur in CA septic shock during preexisting neutropenia, with compartmentalized TNF production in the lower respiratory tract accompanying yeast-mycelial transformation. Thus TNF is not an obligate mediator of acute candidemic shock or subacute disseminated candidiasis during CY-induced immunosuppression but may initiate pulmonary injury accompanying high-grade candidemia.
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PMID:Differential systemic and intrapulmonary TNF-alpha production in Candida sepsis during immunosuppression. 144 56

Candida organisms were cultured from 452 of 1,513 hospitalized burned patients during a 6-year study period. Of the 172 patients with colonization of the eschar by this fungus, only 20.7% subsequently developed invasive candidal sepsis. The mortality of untreated Candida burn wound infection was 100%, and with aggressive medical-surgical therapy, 91.6%. Candidemia was present in 52 patients and 76.9% of these died. Candida infection was seen as a preterminal phenomenon, coincident with a generalized collapse of patients' defensive and homeostatic mechanisms. For this reason, mortality was high and the infection rarely responded to treatment. Control of this lethal complication rests with prevention by the judicious use of intravenous broad-spectrum antibiotics and expeditious closure of the burn wound.
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PMID:Candidiasis in the burned patient. 721 86

Candida species are low virulence organisms which inhabit the skin and mucous membranes of most individuals. There has been increasing incidence of disseminated and deep-seated Candida infections owing to the increasing number of immune compromised hosts. However, the Candida species are still rarely suggested as causative pathogens of vertebral osteomyelitis. We present a 51-year-old man with neck pain and cervical radiculopathy. Three months prior to visiting our hospital, he had undergone a urological operation which was complicated by a urinary tract infection. Magnetic resonance imaging and X-rays showed erosion of the body of the 5th cervical spine and collapse of the C5-C6 disc. After open debridement, tissue pathology results revealed Candida infection. Clinical stability was achieved during the 6-month follow-up period with a combination of amphotericin B and posterior fixation method. We reviewed the literature and found a high rate of surgical intervention for patients suggested of having Candida vertebral osteomyelitis. However, the surgical intervention may not be necessary. Early diagnosis using noninvasive percutaneous needle biopsy may help reduce the incidence of delayed treatment.
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PMID:Candida vertebral osteomyelitis: a case report and review of the literature. 1185 98

The fungicidal activity of Cassia spectabilis leaf extracts was investigated using the disk diffusion technique and the broth dilution method. The extract showed a favorable antimicrobial activity against Candida albicans with a minimum inhibition concentration(MIC) value of 6.25 mg / ml. Apart from the fungicidal effects, imaging using scanning electron microscopy (SEM) was done to determine the major alterations in the microstructure of the C. albicans. The main abnormalities noted in the SEM studies were the alterations in morphology and complete collapse of the yeast cells after 36 h of exposure to the extract. The in vitro time-kill study performed using the leaf extract at 1/2, 1 or 2 times of the MIC significantly inhibited the yeast growth with a noticeable drop in optical density (OD) of yeast culture, thus confirming the fungicidal effect of the extract on C. albicans. In addition, in vivo antifungal activity studies on candidiasis in mice showed a 5-fold decrease in Candida in kidneys and blood samples in the groups of animals treated with the extract (2.5 g / kg body weight). In an acute toxicity study using mice, the acute minimum fatal dose of the extract was greater than 2000 mg / kg, and we found no histopathological changes in macroscopic examination by necropsy of mice treated with extract. We conclude that the extract may be safely used as an anticandidal agent.
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PMID:Fungicidal effect and oral acute toxicity of Cassia spectabilis leaf extract. 1900 57

Cassia fistula seeds have many therapeutic uses in traditional medicine practice. The present investigation was undertaken to demonstrate the anticandidal activity of the C. fistula seed extract at ultra-structural level through transmission electron microscope (TEM) and scanning electron microscope (SEM) observations. The effect of seed extract on the growth profile of the Candida albicans was examined via time-kill assays and in vivo efficacy of the extract was tested in an animal model. In addition, the anticandidal effect of seed extract was further evaluated by microscopic observations using SEM and TEM to determine any major alterations in the ultrastructure of C. albicans. The complete inhibition of C. albicans growth was shown by C. fistula seed extract at 6.25 mg/mL concentration. The time-kill assay suggested that C. fistula seed extract had completely inhibited the growth of C. albicans and also exhibited prolonged anti-yeast activity. The SEM and TEM observations carried out to distinguish the metamorphosis in the morphology of control and C. fistula seed extract-treated C. albicans cells revealed the notable effect on the outer cell wall and cytoplasmic content of the C. albicans and complete collapse of yeast cell exposed to seed extract at concentration 6.25 mg/mL at 36 h. The in vitro time-kill study performed using the leaf extract at 1/2, 1 or 2 times of the MIC significantly inhibited the yeast growth with a noticeable drop in optical density (OD) of yeast culture, thus confirming the fungicidal effect of the extract on C. albicans. In addition, in vivo antifungal activity studies on candidiasis in mice showed a 6-fold decrease in C. albicans in kidneys and blood samples in the groups of animals treated with the extract (2.5 g/kg body weight). The results suggested that the C. fistula seed extract possessed good anticandidal activity and is a potential candidate for the development of anticandidal agents.
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PMID:In vitro, in situ and in vivo studies on the anticandidal activity of Cassia fistula seed extract. 2267 14

Candida albicans, the most prevalent human fungal pathogen, is generally diploid. However, 50% of isolates that are resistant to fluconazole (FLC), the most widely used antifungal, are aneuploid and some aneuploidies can confer FLC resistance. To ask if FLC exposure causes or only selects for aneuploidy, we analyzed diploid strains during exposure to FLC using flow cytometry and epifluorescence microscopy. FLC exposure caused a consistent deviation from normal cell cycle regulation: nuclear and spindle cycles initiated prior to bud emergence, leading to "trimeras," three connected cells composed of a mother, daughter, and granddaughter bud. Initially binucleate, trimeras underwent coordinated nuclear division yielding four daughter nuclei, two of which underwent mitotic collapse to form a tetraploid cell with extra spindle components. In subsequent cell cycles, the abnormal number of spindles resulted in unequal DNA segregation and viable aneuploid progeny. The process of aneuploid formation in C. albicans is highly reminiscent of early stages in human tumorigenesis in that aneuploidy arises through a tetraploid intermediate and subsequent unequal DNA segregation driven by multiple spindles coupled with a subsequent selective advantage conferred by at least some aneuploidies during growth under stress. Finally, trimera formation was detected in response to other azole antifungals, in related Candida species, and in an in vivo model for Candida infection, suggesting that aneuploids arise due to azole treatment of several pathogenic yeasts and that this can occur during the infection process.
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PMID:A tetraploid intermediate precedes aneuploid formation in yeasts exposed to fluconazole. 2464 52

Immune cells exploit reactive oxygen species (ROS) and cationic fluxes to kill microbial pathogens, such as the fungus Candida albicans. Yet, C. albicans is resistant to these stresses in vitro. Therefore, what accounts for the potent antifungal activity of neutrophils? We show that simultaneous exposure to oxidative and cationic stresses is much more potent than the individual stresses themselves and that this combinatorial stress kills C. albicans synergistically in vitro. We also show that the high fungicidal activity of human neutrophils is dependent on the combinatorial effects of the oxidative burst and cationic fluxes, as their pharmacological attenuation with apocynin or glibenclamide reduced phagocytic potency to a similar extent. The mechanistic basis for the extreme potency of combinatorial cationic plus oxidative stress--a phenomenon we term stress pathway interference--lies with the inhibition of hydrogen peroxide detoxification by the cations. In C. albicans this causes the intracellular accumulation of ROS, the inhibition of Cap1 (a transcriptional activator that normally drives the transcriptional response to oxidative stress), and altered readouts of the stress-activated protein kinase Hog1. This leads to a loss of oxidative and cationic stress transcriptional outputs, a precipitous collapse in stress adaptation, and cell death. This stress pathway interference can be suppressed by ectopic catalase (Cat1) expression, which inhibits the intracellular accumulation of ROS and the synergistic killing of C. albicans cells by combinatorial cationic plus oxidative stress. Stress pathway interference represents a powerful fungicidal mechanism employed by the host that suggests novel approaches to potentiate antifungal therapy. Importance: The immune system combats infection via phagocytic cells that recognize and kill pathogenic microbes. Human neutrophils combat Candida infections by killing this fungus with a potent mix of chemicals that includes reactive oxygen species (ROS) and cations. Yet, Candida albicans is relatively resistant to these stresses in vitro. We show that it is the combination of oxidative plus cationic stresses that kills yeasts so effectively, and we define the molecular mechanisms that underlie this potency. Cations inhibit catalase. This leads to the accumulation of intracellular ROS and inhibits the transcription factor Cap1, which is critical for the oxidative stress response in C. albicans. This triggers a dramatic collapse in fungal stress adaptation and cell death. Blocking either the oxidative burst or cationic fluxes in human neutrophils significantly reduces their ability to kill this fungal pathogen, indicating that combinatorial stress is pivotal to immune surveillance.
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PMID:Mechanisms underlying the exquisite sensitivity of Candida albicans to combinatorial cationic and oxidative stress that enhances the potent fungicidal activity of phagocytes. 2590 Jun 57

BACKGROUND Invasive candidiasis is a potential problem for patients receiving long-term immunosuppressive treatment. Psoriatic arthritis is one of many chronic diseases that can be successfully treated with immunosuppressive drugs, in spite of a documented and accepted risk for infectious complications. Critical awareness of possible infection must be part of the surveillance of such patients. CASE REPORT This is the case of a 68-year-old Norwegian male, treated with long-term immunosuppression for psoriatic arthritis, hospitalized with acute subcutaneous and mediastinal emphysema of unknown cause. He died of acute respiratory failure with circulatory collapse shortly after admission. The autopsy revealed mediastinal and subcutaneous emphysema and a mediastinal abscess containing Candida with probable entrance from the esophagus. CONCLUSIONS We consider invasive candidiasis of the esophagus to be the cause of both the chronic abscess and the acute mediastinal emphysema. This case illustrates the importance of awareness of invasive candidiasis as a possible complication in a patient with long-term immunosuppression.
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PMID:Invasive Esophageal Candidiasis with Chronic Mediastinal Abscess and Fatal Pneumomediastinum. 2738 22