Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C
Rashmin C. SavaniRodolfo I. GodinezMarye H. GodinezErica WentzAisha ZamanZheng CuiPatricia M. PoolerSusan H. GuttentagMichael F. BeersLinda W. GonzalesPhilip L. Ballard
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Intratracheal bleomycin in rats is associated with respiratory distress of uncertain etiology. We investigated the expression of surfactant components in this model of lung injury. Maximum respiratory distress, determined by respiratory rate, occurred at 7 days, and surfactant dysfunction was confirmed by increased surface tension of the large-aggregate fraction of bronchoalveolar lavage (BAL). In injured animals, phospholipid content and composition were similar to those of controls, mature surfactant protein (SP) B was decreased 90%, and SP-A and SP-D contents were increased. In lung tissue, SP-B and SP-C mRNAs were decreased by 2 days and maximally at 4--7 days and recovered between 14 and 21 days after injury. Immunostaining of SP-B and proSP-C was decreased in type II epithelial cells but strong in macrophages. By electron microscopy, injured lungs had type II cells lacking lamellar bodies and macrophages with phagocytosed lamellar bodies. Surface activity of BAL phospholipids of injured animals was restored by addition of exogenous SP-B. We conclude that respiratory distress after bleomycin in rats results from surfactant dysfunction in part secondary to selective downregulation of SP-B and SP-C.Summary Introduction It has been proposed that exogenous pulmonary surfactant can be used as a drug delivery system for immunosuppressive agents to the alveolar compartment of the lung while reducing the risk of systemic toxicity. Before using this combination, however, alterations in activity of both substances should be examined. Therefore, this study investigated whether the activity of a natural derived surfactant preparation is changed after it is mixed with cyclosporine A (CsA) or rapamycin (RPM). Methods A surfactant suspension was mixed with CsA or RPM and minimal surface tension of these mixtures was measured in vitro . Surfactant activity was evaluated in vivo by its capacity to restore gas exchange in an established model of surfactant deficiency in rats. CsA–surfactant, RPM–surfactant or surfactant alone was instilled intratracheally and blood gases were measured under standardized ventilatory conditions. Results Minimal surface tension of surfactant–CsA was comparable with that of surfactant alone, whereas minimal surface tension of the surfactant–RPM mixture was increased. In vivo partial arterial oxygen pressure levels increased immediately to prelavage values after instillation of CsA–surfactant, RPM–surfactant and surfactant only and were comparable during the entire study period. Conclusion The activity of a naturally derived surfactant was affected when mixed with RPM but not when mixed with CsA at the used concentrations.
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Bleomycin is an anti-cancer drug used to treat different malignancies, mainly lymphomas, germ cell tumors. Unfortunately, bleomycin has major, pulmonary toxicity that affects 20% of treated individuals with pulmonary fibrosis being the most devastating form. Deglyco-bleomycin is a molecule derived from bleomycin in which the sugar residue D-mannosyl-L-glucose disaccharide has …
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Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures.
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Close spacing bio-surfactant tertiary composite flooding pilot test indicated, compared to tertiary composite surfactant system without adding bio-surfactant, usage of sulphonate surfactant and cost of injected chemical decreased respectively by 1/2 and 30% for bio-surfactant tertiary composite system, which is formed by rhamnoilpid bio-surfactant and sulphonate surfactant. The ultra-low interface tension value between flooding system and crude oil reached 10-3mN/m, and recovery factor for central well site and that for overall area increased by 23. 24% and 16. 34% , respectively.
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人膀胱癌の1つの治療体系の確立を目的として, 温水潅流法による温熱 (Hyperthermia) 療法 (42～43℃) の臨床的検討を行つた. 温熱単独, 温熱と bleomycin の併用療法, 温熱と放射線の併用療法, 温熱と放射線と bleomycin の3者併用療法の4通りの療法を受けた34例の膀胱癌 (移行上皮癌) 患者につき, 治療効果, 副作用, 生体免疫能におよぼす影響につき検討を行つた.温熱単独では6例中2例に, 温熱と bleomycin の併用では4例中1例に, 温熱と放射線の併用では9例中5例に, 温熱と放射線と bleomycin の3者の併用では15例中12例に, 腫瘍の明らかな縮小や消失の治療効果が認められた.副作用は膀胱刺激症状, 尿道痛が主なものであり, 重篤な副作用は認められなかつた.PHAや Con Aによるリンパ球幼若化能等を指標として生体免疫能におよぼす温熱療法の影響を検討した. 温熱と放射線の併用, および温熱と放射線と bleomycin の3者併用療法を受けた患者のこれら指標は, 治療の経過に伴つて抑制されたが, 放射線単独療法を受けた患者のそれとは差が認められなかつた.これらより, 膀胱癌の温熱療法に特に温熱と放射線と bleomycin の3者の併用療法は充分臨床応用が可能と考えられた.
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The key feature of respiratory distress syndrome (RDS) is the insufficient production of surfactant in the lungs of preterm infants. As a result, researchers have looked into the possibility of surfactant replacement therapy as a means of preventing and treating RDS. We sought to identify the role of surfactant in the prevention and management of RDS, comparing the various types, doses, and modes of administration, and the recent development. A PubMed search was carried out up to March 2012 using phrases: surfactant, respiratory distress syndrome, protein-containing surfactant, protein-free surfactant, natural surfactant, animal-derived surfactant, synthetic surfactant, lucinactant, surfaxin, surfactant protein-B, surfactant protein-C.
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We investigated whether artificial surfactant modified pulmonary fibrosis following the intratracheal administration of bleomycin (BLM 3.75 mg/kg) in rats. Twenty-four hours after the administration of bleomycin, the lungs were washed twice with surfactant-TA (S-TA, 1 mg/ml, 6 ml x 2 times), and replaced with 0.5 ml of 10 mg/ml S-TA. Fourteen days later the animals were sacrificed and the lungs were assayed for collagen content and pathologic changes. BLM-treated rats showed both increases in wet lung weights and lung collagen content, and a loss in body weights (due to lung injury and fibrosis), but these changes were significantly inhibited by the intratracheal administration of S-TA. In vitro studies demonstrated that S-TA inhibited lung fibroblast proliferation in a dose dependent manner (0.01-0.5 mg/ml). This inhibition was also seen in native rat lung surfactant and its protein and lipid components. However, S-TA, did not change the number of rat type II pneumocutes in culture, and likely protected type II cells from dedifferentiation. S-TA inhibited BLM-induced pulmonary fibrosis, probably by directly inhibiting lung fibroblast proliferation.
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