Serum procalcitonin as an index of inhalation injury in burns.

The molecular heterogeneity of serum immunoreactive calcitonin (iCT) was analyzed from a prospective study of 41 burn patients. Using different region-specific anticalcitonin antisera, the ratio of mid-region-recognizing to carboxyl terminal-region-recognizing iCT was found to increase acutely in those who subsequently died. The highest ratios occurred in those who died early of respiratory complications. Sephadex chromatography and reversed-phase HPLC demonstrated that the serum iCT circulated predominantly in the large molecular mass prohormone form (16 kDa). In comparison, iCT of normal human lung and of normal thyroid was shown to consist primarily of smaller monomeric mass forms. Furthermore, in 12 normal volunteers who were evaluated with a calcium-pentagastrin infusion, the ratio of iCT levels did not differ from the baseline ratio despite a 50% increase in serum iCT. These results suggest that in burns, the inhalational injury-associated hypercalcitonemia is characterized by a preferential release of procalcitonin; a form of constitutive secretion. The measurement of serum procalcitonin levels would appear to be a useful prognostic indicator of the severity of inhalational injury occurring in burn patients.     

Plasminogen activator activity in lung and alveolar macrophages of rats exposed to graded single doses of gamma rays to the right hemithorax

Male rats were sacrificed 2 or 6 months after a single dose of 0-30 Gy of 60Co gamma rays to the right hemithorax. At autopsy, macrophages were lavaged from the right lung, counted, and frozen. The right (irradiated) and the left (shielded) lungs were frozen, then assayed for plasminogen activator (PLA) activity by the fibrin plate lysis method. Freeze-thawed macrophages were assayed for both PLA activity (125I-fibrin clot lysis method) and fibrinolytic inhibitor activity (inhibition of urokinase-induced fibrin lysis). There was a linear, dose-dependent decrease in right lung PLA activity over the dose range of 10-30 Gy at 2 and 6 months postirradiation, reductions of 3.1 and 2.6% per Gy, respectively. PLA activity at all radiation doses was 10-15% higher at 6 months than at 2 months (P less than 0.05), indicative of a partial recovery of this endothelial function in the irradiated lung. There were no significant changes in PLA activity in the shielded left lung at any dose or time. There also was a linear, dose-dependent increase in the number of macrophages lavaged from the right lung at both 2 and 6 months postirradiation, with larger numbers recovered after all doses at 2 months. PLA activity per 10(6) macrophages decreased with increasing radiation dose at both autopsy times, closely paralleling lung PLA activity. This radiation-induced decrease in macrophage PLA activity was not due to increased fibrinolytic inhibitor activity in the irradiated macrophages. These data quantitate the dose response and time course of radiation-induced fibrinolytic defects in rat lung and suggest that information obtained from a minimally invasive procedure such as bronchoalveolar lavage may serve as an index of the degree of pulmonary fibrinolytic dysfunction after irradiation.     

Serum SP-D is a marker of lung injury in rats

Pulmonary surfactant protein D (SP-D) is expressed in alveolar type II and bronchiolar epithelial cells and is secreted into alveoli and conducting airways. However, SP-D has also been measured in serum and is increased in patients with acute respiratory distress syndrome, pulmonary fibrosis, and alveolar proteinosis. To demonstrate that SP-D can be measured in rat serum, we instilled rats with keratinocyte growth factor, which produces type II cell hyperplasia and an increase in SP-D in bronchoalveolar lavage fluid (BALF). To evaluate serum SP-D as a biomarker of lung injury, we examined several injury models. In rats treated with 1 unit of bleomycin, serum SP-D was elevated on days 3, 7, 14, and 28 after instillation, and SP-D mRNA was increased in focal areas as detected by in situ hybridization. However, there was no increase in whole lung SP-D mRNA when the expression was normalized to whole lung 18S rRNA. After instillation of 2 units of bleomycin, the serum levels of SP-D were higher, and SP-D was also increased in BALF and lung homogenates. In another model of subacute injury, serum SP-D was increased in rats treated with paraquat plus oxygen. Finally to evaluate acute lung injury, we instilled rats with HCl; SP-D was increased at 4 h after instillation. Our data indicate that serum SP-D may be a useful indicator of lung injury and type II cell hyperplasia in rats.     

Renal copper as an index of copper status in marginal deficiency

Marginal copper (Cu) deficiency is difficult to study, in part because its effects may be small, but also because feeding of a deficient diet may not cause a discernable change in Cu status. The key to resolution of effects may be in the choice of Cu status index. In this study, liver Cu concentration, a commonly used index of Cu status, was compared with activity of ceruloplasmin (CP), a circulating Cu-dependent enzyme, and kidney Cu concentration for their utility in resolving effects of marginal Cu deficiency. Seventy male, weanling rats were fed diets containing, nominally, 0, 1.5, 3, 4.5, or 6 mg Cu/kg diet for 5 wk. All three indices showed strong depression with severe deficiency (dietary Cu=0), but were relatively weak in their ability to distinguish between animals fed marginally deficient diets when compared by group statistics (ANOVA). Further, group statistics revealed no effect of marginal deficiency on six other variables known to change with severe Cu deficiency: heart weight/body weight, hematocrit, red cell distribution width, neutrophil count, glycated hemoglobin, and platelet count. To take into account interanimal variation, the three putative indices were plotted against these six variables and linear regression was performed on points representing marginally deficient rats. None of the variables showed significant regression with liver Cu or serum ceruloplasmin, but three showed significant regression with kidney Cu. These findings indicate that kidney Cu is preferable to liver Cu or ceruloplasmin as an index of Cu status in marginal deficiency and that linear regression is a possible way of testing for effects of marginal Cu deficiency, especially when effects are subtle.     

Acetylcholine in the brain of rats exposed to acute irradiation

A two-fold increase in acetylcholine, that can randomly be released by brain synaptosomes, is registered 60 min following whole-body X-irradiation of rats with a dose of 0.21 C/kg; depolarization of the synaptosome membranes by potassium chloride increases the release of acetylcholine the augmentation of the release in this case being lower than that in the control. The initial rate of spontaneous neuromediator release from synaptosomes grows by 80 per cent whereas after depolarization of synaptosome membranes by potassium chloride, by 15 per cent. There is a 2.5-fold increase in the maximum rate of a highly specific uptake of choline with Km value being constant. Acetylcholine content of gray substance of irradiated rat brain is invariable.     

Modification of hepatic proteins in rats exposed to high oxygen concentration

The effect of high concentrations of oxygen on cellular proteins was examined in hepatocytes isolated from rats exposed to 100% oxygen for 0, 24, 48, or 54 h. Previous studies have demonstrated that protein oxidation mediated by mixed-function oxidase systems is accompanied by the formation of protein carbonyl derivatives that can be detected by the formation of protein hydrazone derivatives on treatment with 2,4-dinitrophenylhydrazine (DNPH). In these studies the levels of DNPH-reactive proteins increased steadily during 48 h of continuous oxygen treatment and then decreased to control levels by 54 h. Although the specific activity of two hepatic enzymes, glutamine synthetase and glucose-6-phosphate dehydrogenase, decreased during oxygen treatment, antibody titration of each enzyme indicated that the levels of immunological cross-reactive protein either remained constant or increased slightly during 48 h of oxygen treatment. After 54 h of oxygen exposure the levels of immunologically cross-reactive material were significantly reduced. These results suggest that exposure of rats to high concentrations of oxygen leads to the oxidative inactivation of enzymes and the accumulation of oxidized proteins that are subsequently degraded.     

Serum progesterone levels as an index of pregnancy in buffaloes

Higher levels of serum progesterone on the 20th or 23rd day following impregnation were indicative of establishment of pregnancy in buffaloes. Buffaloes with serum progesterone levels of 1 ng/ml or more on these days were taken as pregnant. The accuracy of this test for diagnosing pregnancy was 75% on the 20th and 83.3% on the 23rd day after artificial insemination. The non-pregnancy diagnosis by this test was 100% accurate on both days of the test. Subclinical endometritis and/or early embryonic deaths seem to interfere with the exact diagnosis of pregnancy.     

Structure-functional states of liver mitochondrial membranes of rats exposed to irradiation

The effect of the low dose gamma-irradiation (270 cGy--one-fold; 90 cGy per day during 3 days) on oxidative phosphorylation, lipid peroxidation, microviscosity of the annular and free lipids membrane, and membrane protein structural state was studied. The post-radiation influence on membrane functional activity and structural state in accordance with the irradiation regimes was established.     

Serum vibriolytic activity as an index of antibacterial immunity in cholera

As a result of study of the vibriolytic activity of the serum during the immunity formation in the vaccinated animals in comparison with the specific antibodies titres and nonspecific immunity factors (complement and lysozyme) there was revealed a dependence of the reaction on the vaccine dose and the immunization method; there was also found a relationship between the vibriolytic activity and the serological indices in the sera of volunteers. On the basis of study a conclusion was drawn that the vibriolytic activity of the serum could serve as an index of antibacterial immunity in cholera.     

The susceptibility to stress-induced gastric injury of rats exposed to cadmium

In this experimental study, the effect of cadmium on cold and restraint stress-induced gastric lesions has been studied. Rats received 15 μg/mL cadmium-containing water for 30 d, and at the end of this period, they were subjected to cold and restraint stress. Cadmium accumulation in gastric mucosa was associated with increased mucosal lesions, as well as decreased mucin and PGE₂ levels in rats exposed to cadmium. Stress-induced mucosal injury was more pronounced, and the hemoglobin leakage into gastric lumen owing to breakdown in the barrier was 17.30±3.45 μg/mL in control and 35.71±6.18 μg/mL in treated rats. Our data suggest that high cadmium intake facilitates the occurence of stress-induced mucosal lesions by diminishing the mucin content and PGE₂ generation in gastric mucosa.     

Measurement of total lung aerosol deposition as an index of lung abnormality

Total aerosol deposition in the lung was measured in 100 subjects with various lung conditions. The subjects consisted of 40 normals (N), 15 asymptomatic smokers (S), 10 smokers with small airway disease (SAD), 20 with chronic simple bronchitis (SB), and 15 with chronic obstructive bronchitis (COPD), and a relationship of total aerosol deposition to degree of lung abnormality was investigated. The subjects were categorized by medical history and a battery of pulmonary function tests, including spirometry, body plethysmography, and single and multiple N2 washout measurements. Subjects repeatedly breathed a monodisperse test aerosol (1.0 micron diam) from a collapsible rebreathing bag (0.5 liter volume) at a rate of 30 breaths/min, while inhaled and exhaled aerosol concentrations were continuously monitored by a laser aerosol photometer in situ and recorded on a strip-chart recorder. The number of rebreathing breaths resulting in 90% aerosol loss from the bag (N90) was determined, and percent predicted N90 values were then determined from the results of computer simulation and used as a deposition index. The percent predicted N90 values were 99.7 +/- 14, 86.5 +/- 15, 66.9 +/- 17, 51 +/- 12, and 30.9 +/- 9, respectively, for N, S, SAD, SB, and COPD. All of these values were significantly different from each other (P less than 0.05). There was no difference between male and female but percent predicted N90 values were slightly higher in young than in old normals. Percent predicted N90 values showed a strong linear correlation with spirometric measurements of forced expiratory volume in 1 s and maximum midexpiratory flow rate. However, many of the SAD and SB with normal spirometry showed abnormal N90. These results suggest that total lung aerosol deposition is a sensitive index of lung abnormality and may be of potential use for nonspecific general patient screening.     

NF-kB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves

Blast lung injury(BLI)is the major cause of death in explosion-derived shock waves;however,the mechanisms of BLI are not well understood.To identify the time-de...     

Disorders of vaginal development in the progeny of white rats exposed to x-ray irradiation

One hundred and twenty white rat embryos 13-22-day-old have been irradiated with x-rays (the dose 250 R) on the 12th-14th day of embryogenesis. The embryos have been divided into series of sagittal, frontal, transversal sections and stained by means of general histological methods. The irradiation performed on the days mentioned does not affect formation of the paramesonephric ducts. In all the experimental animals the caudal end of the paramesonephric duct is separated from the mesonephric duct as a solid cellular cord in which the lumen appears later. In the experimental females the disturbances developed after irradiation are manifested first of all in retardation of the main stages of the organ's formation; the retardation is observed: in fusion of the paramesonephric ducts, in resorption of the medial septum between the fused ducts, in separating the sinuous part of the vagina from the urogenital sinus, in recanalization of the vaginal epithelial cord. More severe lesions are presented as agenesia of the vaginal sinuous part and as its atresia represented by a transversal septum of the organ. The disorders in the vagina development are depended on massive primary necrobiotic radial lesions of the mesenchymal cells around the epithelial anlages of the small pelvis.     

Alteration of lung lipids in ozone exposed rats.

Exposure of adult male rats to 1.1 ± 0.3 ppm of ozone gave a 10-fold elevation of arachidonic acid in the lipid of the endobronchial washings. Arachidonate and linoleate increased in the cholesteryl esters from 6.5% to 55.5% and 4.7% to 20.4%, respectively. Similar changes also occurred in the composition of phosphatidyl choline. Serum lecithin:cholesterol acyl transferase (LCAT) activity was increased by exposure to ozone and returned to normal levels upon reexposure to an atmosphere of uncontaminated air. The results suggest that the lipid enzyme systems are strongly influenced by ozone exposure.     

Aerosolized bovine lactoferrin reduces lung injury and fibrosis in mice exposed to hyperoxia

This study investigated the ability of aerosolized bovine lactoferrin (bLF) to protect the lungs from injury induced by chronic hyperoxia. Female CD-1 mice were exposed to hyperoxia (FiO₂ = 80 %) for 7 days to induce lung injury and fibrosis. The therapeutic effects of bLF, administered via an aerosol delivery system, on the chronic lung injury induced by this period of hyperoxia were measured by bronchoalveolar lavage, lung histology, cell apoptosis, and inflammatory cytokines in the lung tissues. After exposure to hyperoxia for 7 days, the survival of the mice was significantly decreased to 20 %. The protective effects of bLF against hyperoxia were further confirmed by significant reductions in lung edema, total cell numbers in bronchoalveolar lavage fluid, inflammatory cytokines (IL-1β and IL-6), pulmonary fibrosis, and apoptotic DNA fragmentation. The aerosolized bLF protected the mice from oxygen toxicity and increased the survival fraction to 66.7 % in the hyperoxic model. The results support the use of an aerosol therapy with bLF in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure or chronic obstructive pulmonary disease.     

Isoproterenol improves ability of lung to clear edema in rats exposed to hyperoxia.

Exposure of adult rats to 100% O(2) results in lung injury and decreases active sodium transport and lung edema clearance. It has been reported that beta-adrenergic agonists increase lung edema clearance in normal rat lungs by upregulating alveolar epithelial Na(+)-K(+)-ATPase function. This study was designed to examine whether isoproterenol (Iso) affects lung edema clearance in rats exposed to 100% O(2) for 64 h. Active Na(+) transport and lung edema clearance decreased by approximately 44% in rats exposed to acute hyperoxia. Iso (10(-6) M) increased the ability of the lung to clear edema in room-air-breathing rats (from 0.50 +/- 0.02 to 0.99 +/- 0. 05 ml/h) and in rats exposed to 100% O(2) (from 0.28 +/- 0.03 to 0. 86 +/- 0.09 ml/h; P < 0.001). Disruption of intracellular microtubular transport of ion-transporting proteins by colchicine (0. 25 mg/100 g body wt) inhibited the stimulatory effects of Iso in hyperoxia-injured rat lungs, whereas the isomer beta-lumicolchicine, which does not affect microtubular transport, did not inhibit active Na(+) transport stimulated by Iso. Accordingly, Iso restored the lung's ability to clear edema after hyperoxic lung injury, probably by stimulation of the recruitment of ion-transporting proteins (Na(+)-K(+)-ATPase) from intracellular pools to the plasma membrane in rat alveolar epithelium.