Intrapulmonary delivery of ricin at high dosage triggers a systemic inflammatory response and glomerular damage.
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In view of the possibility that ricin may be used as a bioweapon against human populations, we examined the pathological consequences that occur in mice after introduction of ricin into the pulmonary system. Intratracheal instillation of a lethal dose of ricin (20 microg/100 g body weight) resulted in a hemorrhagic inflammatory response in multiple organs, accompanied by activation of mitogen-activated protein kinases, increased synthesis of proinflammatory RNA transcripts, and increased levels of circulating cytokines and chemokines. A sublethal dose of instilled ricin (2 microg/100 g body weight) induced a similar response in lungs but did not cause detectable damage in other organs. Lungs of mice that recovered from a sublethal dose of ricin displayed evidence of fibrosis and residual damage. A lethal dose of ricin caused accumulation of proinflammatory RNA transcripts and substantial damage to 28S rRNA of multiple organs, including lung, kidney, spleen, liver, and blood, demonstrating that instilled ricin gained access to the circulation. The kidneys of mice instilled with a lethal dose of ricin showed accumulation of fibrin/fibrinogen in glomerular capillaries, increased numbers of glomerular leukocytes, and impairment of kidney function. A sublethal dose of ricin failed to induce damage to 28S rRNA in kidney or other extrapulmonary organs. (+info)
Effect of serotonin on small intestinal contractility in healthy volunteers.
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The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase III frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile activity. Platelet-depleted-plasma levels of serotonin increased 2-fold following both intravenous and high doses of intraluminal infusions of serotonin. All subjects reported minor short-lived adverse effects following intravenous serotonin stimulation, while only half of the subjects reported minor short-lived adverse effects following intraluminal serotonin stimulations. We conclude that exogenous serotonin in the lumen of the upper part of the small intestine does not seem to change antro-duodeno-jejunal contractility significantly in healthy adult volunteers. (+info)
Successful treatment of chyluria, glomerular and tubular abnormalities in a young lady with silver nitrate instillation.
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A 21- year-old lady presented with chyluria, severe malnutrition, secondary amenorrhea, profound hypoalbuminemia, heavy proteinuria and renal tubular abnormalities suggestive of Type IV renal tubular acidosis. No particular cause for chyluria could be ascertained. She was successfully treated with an injection of 2% silver nitrate into the left ureter and urinary bladder. She continues to be well after 15 years of follow-up. (+info)
Nasal tolerance with collagen v protein reverts bronchovascular axis remodeling in experimental bronchiolitis obliterans.
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INTRODUCTION: The precise role of the remodeling process and possible therapies for bronchiolitis obliterans remain to be established. OBJECTIVE: [corrected] In the present study, we sought to validate the importance of nasal collagen V tolerance to verify whether bronchovascular axis remodeling could be reverted by this therapeutic approach when compared to steroid treatment. METHODS: Mice were randomly divided into 4 groups: control, bronchiolitis obliterans, collagen V tolerance, and prednisone groups. Morphometry was employed to evaluate bronchovascular axis dimensions, collagen density, and immune cell response. Collagen V nasal tolerance and steroid-treated mice showed significantly lower values of terminal bronchiole wall thickness and reduction in peribronchovascular cells; bronchioalveolar lymphoid tissue; and CD3+, CD4+, CD8+, and CD20+ lymphocytes. A significant decrease in CD68+ macrophage density was found in prednisone-treated mice. In addition, a strong quantitative relationship was found between collagen V tolerance, and reduction in density of immune cells and collagen. RESULTS: Our results indicate that bronchovascular axis remodeling in bronchiolitis obliterans can be reverted by collagen V nasal tolerance, possibly as the result of T-cell suppression. CONCLUSION: We concluded that the tolerance effects in this model were strongly related to the improvement in bronchovascular remodeling, and these may be an appropriate targets for further prospective studies on nasal collagen V tolerance. (+info)
Instillation of povidone iodine to treat lymphocele and leak of lymph after renal transplantation.
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Lymphoceles are common surgical complications of renal transplantation. Recently minimal invasive therapy has been advised. We studied the safety and efficacy of instillation of povidone iodine via transcutaneous catheter for treatment of lymphoceles and leaks of lymph. We studied 10 (four males, six females) kidney transplant recipients who developed lymphoceles after transplantation and four (three males, one female) who developed leaks of lymph. We treated these cases by povidone iodine after placement of transcutaneous catheters with guidance of ultrasound and confirmed the presence of lymph by biochemical analysis. After dilution of povidone iodine to 5% with normal saline, 20cc were instilled and dwelled in the cavity for 30 minute three times daily. The lymph was then allowed to drain by gravity. For the leaks of lymph, which occurred immediately post operation, the catheters were placed during transplantation surgery. All patients were followed up for four months. After one week of instillation, all lymph leaks were completely blocked. Furthermore, nine (90%) cases of lymphocele resolved after 15 days of therapy. We conclude that instillation of diluted povidone iodine for treatment of lymphocele and leak of lymph is safe and effective and it may be considered as first choice for these conditions. (+info)
Local lung responses following endobronchial elastase and lipopolysaccharide instillation in sheep.
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Chronic lipopolysaccharide (LPS) exposure may contribute to the pathogenesis of a number of lung diseases including COPD and emphysema. We sought to develop a large-animal model of emphysema using repeated LPS administration into sheep lung segments. An experimental protocol was designed to facilitate comparisons with elastase-treated and control segments within the same lung of individual sheep. Histopathologic evaluation of segments treated with LPS demonstrated low-grade inflammation characterized by an increase in the number of intra-alveolar macrophages and lymphocytes. Treated segments demonstrated a significant reduction in airspace surface area (ASA), an increase in percent disrupted alveolar attachments and the distance between normal alveolar attachments, and a reduction in the number of normal alveolar attachments surrounding nonrespiratory bronchioles. Coefficient of variation of individual ASA measurements in elastase-treated segments was indicative of a heterogeneous parenchymal response, in contrast to that associated with chronic LPS treatment. Our results demonstrate that chronic LPS treatment of individual lung segments in sheep induces microscopic emphysema qualitatively and quantitatively consistent with both accepted pathologic definitions of this condition and with that produced by airway instillation of elastolytic enzymes. Development of this phenotype is associated with evidence of downregulated activation of transforming growth factor beta. (+info)
Particularities of vascular reactivity of the conjunctiva and iris in rats.
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Considering that the conjunctiva and iris are developed from different embryological origins, an analysis of any possible differences in the density and type of adrenoceptors between these two areas was tried. An experimental study on male adult Wistar rats was performed. Six groups (six rats per group) were used by recording the iris and conjunctival vessels after eye instillations with solutions of adrenaline 0.1%, isoprenaline chlorhydrate 0.00002% and distilled water. The image analyze were carried out using VirtualDub 1.5.1 and Adobe PhotoShop 6.0., measuring the variations of the vessels diameters before and after the solutions instillations at fixed time intervals. The means of each eye values were compared with the control value using a statistical significance T test. The analysis of the two groups treated with adrenaline 0.1% showed a different reactivity of the vessels from the conjunctiva and iris, respectively. The iris vessels performed a gradual vasoconstriction. On the contrary, the conjunctival vessels showed initially mild, but significant vasodilatation, while vasoconstriction started later and was not as intense as for the iris vessels. The iris vessels treated with isoprenaline 0.00002% showed no significant changes in the vascular diameters. On the contrary, the conjunctival vessels showed a significant vasodilatation. The differences in the vascular reactivity of the two ocular areas (conjunctiva and iris) to vasoactive amines (epinephrine, isoprenaline) support the idea that beta 2 adrenergic receptors are present only in conjunctiva vessels but not in iris vessels, while alpha adrenoceptors are present in both vascular territories. (+info)
Effects of pentoxifylline on TNF-alpha and lung histopathology in HCL-induced lung injury.
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OBJECTIVE: To evaluate the effects of pentoxifylline on hydrochloric acid-induced lung lesions in rats subjected to mechanical ventilation. METHODS: Twenty male, adult Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: control-MV (mechanical ventilation, MV group); bilateral instillation of HCl (HCl group); bilateral instillation of HCl followed by pentoxifylline (50 mg/kg bw) infusion (HCl+PTX group) and pentoxifylline infusion followed by bilateral instillation of HCl (PTX+HCl group). At 20, 30, 90 and 180 min after treatments, the blood partial pressures of CO2 and O2 were measured. The animals were euthanized, and bronchoalveolar lavages were taken to determine the contents of total proteins, corticosterone [corrected] and TNF-alpha. Samples of lung tissue were used for histomorphometric studies and determining the wet-to-dry (W/D) lung weight ratio. RESULTS: In the MV group, rats had alveolar septal congestion, and, in the HCl group, a remarkable recruitment of neutrophils and macrophages into the alveoli was noticed; these events were reduced in the animals with PTX+HCl. The partial pressure of oxygen increased in PTX+HCl animals (121+/-5 mmHg) as compared with the HCl (62+/-6 mmHg) and HCl+PTX (67+/-3 mmHg) groups within 30 minutes. TNF-alpha levels in bronchoalveolar lavage were significantly higher in the HCl group (458+/-50 pg/mL), reduced in the HCl+PTX group (329+/-45 pg/mL) and lowest in the PTX+HCl group (229+/-41 pg/mL). The levels of corticosterone [corrected] in bronchoalveolar lavage were significantly lower in the HCl (8+/-1.3 ng/mL) and HCl+PTX group (16+/-2 ng/mL) and were highest in the PTX+HCl (27+/-1.9 ng/mL). CONCLUSION: Pretreatment with PTX improves oxygenation, reduces TNF-alpha concentration and increases the concentration of corticosterone [corrected] in bronchoalveolar lavage upon lung lesion induced by HCl. (+info)