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Barrier cream application reduces the formation of DNA adducts in lung tissue of mice dermally exposed to used gasoline engine oil.

Epidemiological evidence suggests that auto mechanics are at higher risk for lung and urinary bladder cancer. Used gasoline engine oils (UGEO), a common exposure for many mechanics, are carcinogenic and increase carcinogen-DNA adduct levels in the skin and lungs of mice treated topically. The ability of a barrier cream to reduce dermal absorption of carcinogens in UGEO was evaluated. Groups of five animals were treated topically for 5 days with 25 microliters/day UGEO. A barrier cream was applied to two groups prior to exposure. Skin of both groups was washed with a commercial hand cleaner, the first group, one hour after UGEO application, the other, eight hours after application. Two other groups did not receive barrier creams before UGEO application, but were washed at one or eight hours after the oil was applied. Another group was treated with UGEO five times but was never washed; other groups consisted of barrier cream and commercial cleaner controls. Skins and lungs were harvested 24 hours after the final exposure and DNA isolated. Carcinogen-DNA adduct levels were determined by 32P-postlabelling followed by thin-layer chromatography to separate the adducts and scintillation counting to quantify the adduct level. Pre-application of barrier cream reduced markedly the carcinogen-DNA adduct levels in both skin and lung tissue of mice treated with UGEO and washed at eight hours. In the lung, this reduction was statistically significant. Adduct levels in both tissues were approximately the same in the groups washed at one hour, indicating that if the skin is washed promptly after exposure, barrier cream application is unnecessary. If, however, washing does not take place until several hours after exposure, the pre-application of barrier cream appears to significantly reduce the DNA adduct levels. These data are of practical importance to mechanics who may be working with oily parts for extended periods.

Administration, Topical↗

Generation of superoxide anion impairs histamine-induced increases in macromolecular efflux.

The first goal of this study was to determine the effect of generation of superoxide anion using pyrogallol on histamine-induced increases in macromolecular efflux. We used intravital microscopy and fluorescein isothiocyanate-dextran (FITC-dextran; MW 70K) to examine macromolecular extravazation from postcapillary venules in the hamster cheek pouch in response to histamine before and following topical application of vehicle or pyrogallol. Extravazation of macromolecules was quantitated by counting venular leaky sites. Histamine elicited reproducible increases in venular leaky sites before and during infusion of vehicle. In contrast, topical application of pyrogallol (0.5 mM) abolished histamine-induced increases in formation of venular leaky sites. Our second goal was to examine whether pyrogallol-induced inhibition of venular leaky site formation could be reversed by superoxide dismutase. Application of superoxide dismutase (300 U/ml) to the cheek pouch in the presence of pyrogallol restored histamine-induced increases in venular leaky sites. Thus, the generation of superoxide anion alters histamine-induced increases in macromolecular efflux. These results support the concept that disease states that produce oxidative stress may impair agonist-induced increases in microvascular permeability via inactivation of nitric oxide.

Animals↗

Acute effects of single doses of recombinant interferon-gamma on blood cell counts and lymphocyte subsets in patients with advanced renal cell cancer.

The object of this study was to investigate the effects of different single doses of recombinant interferon-gamma (rIFN-gamma) on white blood cell counts, differential blood counts, and the relative composition of T-cell subsets in the peripheral blood of cancer patients. Sixteen patients suffering from metastasizing renal cell carcinoma received 10, 100, or 500 micrograms of rIFN-gamma three times at weekly intervals. After a therapy-free interval of 2 weeks, the next dose level was applied. The order of dose levels was assigned randomly to each patient. White blood cells, differential blood counts, and the number of Leu1, Leu3, Leu2a, Leu7, and HLA DR+ cells were measured immediately before and at 4, 24, 48, 72, 96, and 168 h after the administration of single doses of rIFN-gamma. Results indicated that white blood cells were transiently removed from the blood circulation after administration of IFN-gamma. Monocytes, HLA DR+ cells, and Leu7+ cells were reduced to below 50% of pretreatment values 4 h after application of the cytokine. CD8+ cells and granulocyte counts declined to approximately 70% of pretreatment values 24 h after IFN therapy. The preferential reduction of CD8+ lymphocytes resulted in a temporary increase of the T4/T8 ratio in these patients.

Adult↗

Application of unbiased stereology on archival human temporal bone.

OBJECTIVE: The current report presents unbiased stereological sampling and counting strategies for estimating the total number of neurons in the spiral and vestibular ganglia of the archival human temporal bone. STUDY DESIGN: Application of unbiased stereology using archival human temporal specimens. Observational study. METHODS: The practical sampling and counting strategies for estimating the number of neurons are presented. To illustrate the method described, the total number of neurons in spiral and vestibular ganglia from archival human temporal bone was estimated. RESULTS: The study found, on average, 41,643 (coefficient of variation = 0.12) spiral ganglion neurons in the subjects with an average age of 35.6 years (age range, 22-60 y) and, on average, 27,635 (coefficient of variation = 0.10) vestibular ganglion neurons in the subjects with an average age of 28.6 years (age range, 2-58 y). CONCLUSIONS: The total number of primary auditory and vestibular ganglion neurons from the current study differs significantly from the previously published data using assumption-based methods. The unbiased stereological technique presented in the current report thus would be invaluable for future studies on such specimens, including the study of the changes of neurons during aging and various pathological conditions.

Cell Count↗

An intercomparison of whole-body counters at participating region III nuclear power plants.

Seventeen Region III nuclear stations originated and participated in an intercomparison study of their whole body counting procedures using the same calibration standard. The first phase of the study involved transporting a phantom containing four reactor-produced radionuclides and 40K to each plant. The plant staff were asked to follow all procedures applicable for a human subject including routine and investigative counts, if necessary, and to provide a printout of the results to the project investigators. The results from each plant were normalized for intercomparison by calculating the ratio of the reported activity to the actual activity after correcting for the appropriate amount of decay to the time of the count. Five plants reported 60Co values outside 1 standard deviation (SD) of the mean for 60Co and one plant did not detect the presence of 60Co. According to previously established procedures, these six plants were revisited after a period of time in which internal recalibration and corrective actions could be made. Four of the six plants had results which were still outside 1 SD of the mean for the original study. A final report in coded form to protect plant anonymity was provided to those stations to guide them in making further improvements, if they chose to do so.

Cobalt Radioisotopes↗

Chest wall thickness measurements of the LLNL phantom for small area germanium detector counting.

The Lawrence Livermore National Laboratory (LLNL) phantom was developed to calibrate lung counting systems that are used to estimate plutonium and other low energy photon emitting radionuclides deposited in the lung. Originally, low energy photon counting systems consisted of sodium iodide or phoswich detectors, but they have been largely replaced by smaller germanium detector arrays. The average chest wall thicknesses of the LLNL phantom's torso plate and its overlay plates provided by the manufacturer refer to the regions covered by phoswich detectors; however, germanium detectors are of a different size and are placed in different locations on the phantom's torso plate. Previous work has shown that the manufacturer's data were not applicable for large area germanium detectors. The lung counting system at the Korea Atomic Energy Institute (KAERI) is a small area germanium detector array. Although the detectors are placed within the phoswich circles, only about 25% of the area is covered by the detectors. The LLNL phantom at KAERI has been examined to determine if the manufacturer's data are valid or if new chest wall thickness values must be determined. This paper presents chest wall thickness data for the LLNL phantom with and without its B-series overlay plates at 17 keV, 60 keV, 200 keV, and 1,500 keV and shows that these values are different from the manufacturer's values.

Calibration↗

Improved Count Rate and Resolution Performance of a Thermoelectrically Cooled Si(Li) X-ray Detector.

: A new energy-dispersive spectrometer Si(Li) detector for microanalysis applications, cooled by a thermoelectric (Peltier) refrigerator, was significantly improved with regard to the resolution and high count-rate performance. This new detector was mounted on a JEOL 6400 scanning electron microscope, and several application tests were run to analyze its performance. The common resolution test using an Fe55 radioactive source was performed, and it was compared with the conventional liquid nitrogen (LN) detector. The resolution at low and high count-rate was found to be slightly less than the LN detector's performance; however, these differences are minor and most application requirements were easily met. The thermoelectric cooling mechanism was found to be stable and reliable with no degradation in its performance recorded during several years of use. The collected data show improved performance by the new thermoelectrically cooled (TEC) detector compared with the old TEC design and underscore performance very close to the LN product. For most microanalysis applications, the new TEC X-ray detector can easily replace the LN detector and avoid the maintenance associated with LN filling.

Journal Article↗

Endoscopic examination and tissue sampling of the bovine teat and udder cistern.

The aim of this study was to evaluate the application of an endoscopic technique to investigate the teat and udder cisterns of the bovine mammary gland, and to biopsy tissues within the cisterns. An anesthetic protocol for application in standing animals was designed, using a combination of general and local anesthesia. Individual quarter milk production (QMP), quarter somatic cell count (SCC), and occurrence of new intramammary infection were assessed after application of the technique, and possible applications for biopsies collected were investigated. Bovine teat and gland cistern lining could be visualized and small biopsy samples could be collected. The collected biopsy samples were successfully used in histological-histopathological examination and PCR analysis. To study the impact of endoscopy on QMP, milk SCC, and bacteriology, endoscopic examination of 12 low SCC (<200,000 cells/ mL) quarters was performed in 8 different first- and second-lactation cows. Immediately following endoscopy, 8 quarters received antibiotic treatment, whereas 4 quarters remained untreated. During a 15-d follow-up, no new intramammary infection could be observed in the endoscopically treated quarters. For QMP, no significant interaction between time and treatment could be observed throughout the 15-d follow-up period. Quarter SCC did not differ among treatments (control, endoscopy with antibiotics, and endoscopy without antibiotics). In conclusion, the endoscopic technique is suitable for examination and tissue biopsy collection of the bovine mammary gland cisterns without major interference with QMP and quarter SCC.

Animals↗

[The effect of bentazone TP, an herbicide, on hematologic indicators in sheep during acute and subchronic poisoning].

Hematological changes at poisoning with the bentazone herbicide manufactured by the Research Institute of Chemical Technology in Bratislava were investigated in sheep of the Slovak Merino breed. Acute intoxication in seven head of sheep was induced by a single application of bentazone with cannula at a sublethal dose of 1,450 mg/kg live weight. Bentazone was diluted with sunflower oil at a ratio 1:5. Subchronic intoxication was induced by an administration of bentazone in feed to the sheep for 84 days: a dose of 175 mg/kg live weight (1/10 of LD50) for the first experimental group (six head), and a dose of 97.5 mg/kg live weight (1/12 of LD50) for the second experimental group (six head). The control group did not receive any dietary bentazone. Acute intoxication with herbicide did not cause any statistically significant changes in hemoglobin, erythrocyte and leucocyte counts in the sheep within 120 hours after application. In comparison with the physiological standard, a slight increase in the percentage of neutrophils and a decrease in the lymphocyte percentage were observed. The values of eosinophils, basophils and monocytes remained unchanged. Observation of subchronic intoxication did not reveal any significant negative effect of the two doses of the herbicide within 84 days on the hematological parameters. Our experiments demonstrate that bentazone does not negatively influence blood formation.

Animals↗

[Clinical application of data measured by automated blood cell counter].

Rapid progress has been made in automated blood cell counting techniques using several kinds of apparatuses based on different mechanisms of measurement. We report a method of clinical application of the measurements made by an automated blood cell counter in the diagnosis and treatment of diseases, and discuss its usefulness, and its weaknesses that require improvement.

Blood Cell Count↗

Validation and calibration of physical activity monitors in children.

OBJECTIVE: This study was designed to validate accelerometer-based activity monitors against energy expenditure (EE) in children; to compare monitor placement sites; to field-test the monitors; and to establish sedentary, light, moderate, and vigorous threshold counts. RESEARCH METHODS AND PROCEDURES: Computer Science and Applications Actigraph (CSA) and Mini-Mitter Actiwatch (MM) monitors, on the hip or lower leg, were validated and calibrated against 6-hour EE measurements by room respiration calorimetry, activity by microwave detector, and heart rate by telemetry in 26 children, 6 to 16 years old. During the 6 hours, the children performed structured activities, including resting metabolic rate (RMR), Nintendo, arts and crafts, aerobic warm-up, Tae Bo, treadmill walking and running, and games. Activity energy expenditure (AEE) computed as EE - RMR was regressed against counts to derive threshold counts. RESULTS: The mean correlations between EE or AEE and counts were slightly higher for MM-hip (r = 0.78 +/- 0.06) and MM-leg (r = 0.80 +/- 0.05) than CSA-hip (r = 0.66 +/- 0.08) and CSA-leg (r = 0.73 +/- 0.07). CSA and MM performed similarly on the hip (inter-instrument r = 0.88) and on the lower leg (inter-instrument r = 0.89). Threshold counts for the CSA-hip were <800, <3200, <8200, and > or = 8200 for sedentary, light, moderate, and vigorous categories, respectively. For the MM-hip, the threshold counts were <100, <900, <2200, and > or = 2200, respectively. DISCUSSION: The validation of the CSA and MM monitors against AEE and their calibration for sedentary, light, moderate, and vigorous thresholds certify these monitors as valid, useful devices for the assessment of physical activity in children.

Adolescent↗

Changes of coagulation and fat-metabolism following pulmonary microembolism after trauma and hemorrhage.

In 16 of 24 anesthetized mongrel dogs a standardized bone trauma was performed to both hind legs by open osteootmy. During the following 6 hours the most important hemodynamic parameters, total platelet count (GTZ) and its separate fractions (NKF, KF) were continously monitored. Five hours after the trauma 50% of the total blood volume (taken to be 80 ml/kg body weight) was withdrawn from two of the four groups of animals. The trauma caused no direct effect on the pulmonary hemodynamics. In the following hours there was a slight decrease of cardiac output (HZV) in the traumatised animals. Besides a moderate increase in mean pulmonary pressure (MPP), pulmonary vascular resistance (PVR) increased by 72% of the pretraumatic values. The application of intravascular catheters diminished the total platelet count markedly in the injured, as in the uninjured animals. The increase in PVR was caused less by a mechanical obstruction of the pulmonary capillary bed than by vasoactive substances released by the platelets. The following hemorrhage led to a more marked hemodynamic reaction in the injured animals. All these animals died before the end of the calculated hemorrhage. All animals without trauma survived. Irreversible aggregation of platelets developed in the pulmonary capillary bed caused by the marked pulmonary hypocirculation. Histological examination showed a marked disseminated pulmonary microthrombosis in all animals with trauma and hemorrhage. The initial phase of experimental pulmonary microembolism caused by trauma was characterized by pulmonary hypocirculation and an activated coagulation with simultaneously diminished total platelet count.

Animals↗

Rat intercostal nerves as experimental nerve grafts.

In this study, we dissected and measured both sets of intercostal nerves including lengths, diameters, and axon counts in 12 adult rats to provide data applicable to experimental nerve graft research. Dissections showed that total lengths of intercostal nerves from the spinal bifurcation to their last arborizations near the midline ranged from 10 to 89 mm, and diameters ranged from less than 0.1 to 0.5 mm from the thinnest to the thickest part. The segment of easiest dissection was the part between the spinal bifurcation and the lateral cutaneous branch. This part was 4-27 mm (mean, 13.3 mm) long and had an almost constant diameter of 0.18-0.5 mm (mean, 0.32 mm). Counts ranged from 201 to 566 axons/ nerve. The segment proximal to the lateral cutaneous branch was the most convenient part to be harvested as a nerve graft, especially in the 8th to 12th intercostal nerves. These nerves could serve as sources for experimental grafts.

Abdominal Muscles↗

Effects of aerially applied fenthion on survival and reproduction of the panacea sand fiddler, Uca panacea, in laboratory habitats.

Sand fiddler crabs, Uca panacea, were exposed in laboratory habitats to measured concentrations of ULV-grade fenthion via simulated aerial spray at 5% and 50% of field rate application of 6-12 mg fenthion/m(2) (0.05-0.10 lbs fenthion/acre). Two habitats served as controls, and two habitats served as replicates for each of the test exposures. The aerial application was repeated 12 times between July 7, 1997, and August 15, 1997, during the period of the most active larval production of the crabs. The resulting measured concentrations of fenthion at the surface and in the water were consistently lower than what the application rate would have suggested. Statistical analysis of total, daily larval counts showed a periodicity of approximately 14 days that did not appear to be affected by fenthion, at least at the 5% application rate, where a 15% reduction in larval production was noted by the end of the second hatching cycle and a 25% reduction by the end of the third. Larval production in the habitats exposed to the 50% application rate was reduced by 18% at the end of the first hatching cycle, 77% at the end of the second, and 100% at the end of the third hatching cycle. At the end of the third hatching cycle, adult crab mortality observed at the surface was 0%, 3%, and 20% for the control, 5%-, and 50%-exposure habitats, respectively. Three weeks after the final fenthion application, survival of adult crabs was 100% in the control habitats, 75% in the 5%-exposure habitats, and 3% in the 50%-exposure habitats. Survival of unfed first-stage zoeae released during the night following the sprays averaged 4.6 +/- 0.9, 3.7 +/- 0.9 and 1.7 +/- 0.6 days for control, 5%-, and 50%-exposure habitats, respectively. Forty-eight-hour LC-50s (nominal) for fenthion exposure of adult crabs submerged in water and for first-stage zoeae were 215 microg fenthion/L and 0.8 microg fenthion/L, respectively.

Animals↗

The assessment of hemispheric lateralization in functional MRI--robustness and reproducibility.

Various methods have been proposed to calculate a lateralization index (LI) on the basis of functional magnetic resonance imaging (fMRI) data. Most of them are either based on the extent of the activated brain region (i.e., the number of "active" voxels) or the magnitude of the fMRI signal change. The purpose of the present study was to investigate the characteristics of various variants of these approaches and to identify the one that yields the most robust and reproducible results. Robustness was assessed by evaluating the dependence on arbitrary external parameters, reproducibility was assessed by Pearson's correlation coefficient. LIs based on active voxels counts at one single fixed statistical threshold as well as LIs based on unthresholded signal intensity changes (i.e., based on all voxels in a region of interest) yielded neither robust nor reproducible laterality results. Instead, the lateralization of a cognitive function was best described by "thresholded" signal intensity changes where the activity measure was based on signal intensity changes in those voxels in a region of interest that exceeded a predefined activation level. However, not all other approaches should be discarded completely since they have their own specific application fields. First, LIs based on active voxel counts in the form of p-value-dependent lateralization plots (LI=LI(p)) can be used as a straightforward measure to describe hemispheric dominance. Second, LIs based on active voxel counts at variable thresholds (standardized by the total number of active voxels) are a good alternative for big regions of interest since LIs based on signal intensity changes are restricted to small ROIs.

Adult↗

Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy.

Fifteen healthy adult volunteers received in their drinking water a lower Escherichia coli phage T4 dose (10(3) PFU/ml), a higher phage dose (10(5) PFU/ml), and placebo. Fecal coliphage was detected in a dose-dependent way in volunteers orally exposed to phage. All volunteers receiving the higher phage dose showed fecal phage 1 day after exposure; this prevalence was only 50% in subjects receiving the lower phage dose. No fecal phage was detectable a week after a 2-day course of oral phage application. Oral phage application did not cause a decrease in total fecal E. coli counts. In addition, no substantial phage T4 replication on the commensal E. coli population was observed. No adverse events related to phage application were reported. Serum transaminase levels remained in the normal range, and neither T4 phage nor T4-specific antibodies were observed in the serum of the subjects at the end of the study. This is, to our knowledge, the first safety test in the recent English literature which has measured the bioavailability of oral phage in humans and is thus a first step to the rational evaluation of phage therapy for diarrheal diseases.

Administration, Oral↗

Application-dependent immunomodulating and antimetastatic efficacy of thymic peptides in BALB/c-mice.

The immunomodulating and antimetastatic activity of clinically approved, low molecular weight, standardized thymic peptide (TP) preparations was evaluated in BALB/c-mice. Daily applications (subcutaneously, s.c.; intraperitoneally, i.p.; intramusculary, i.m.) of two commercially available TP preparations (7 consecutive days, 10, 50 and 100 micrograms per mouse and injection) up-regulated the thymus weight and thymocyte counts as well as peripheral blood leukocyte and lymphocyte counts in liver metastases-bearing mice. The immunomodulating activity of TP application was most pronounced and statistically significant for thymus weight and counts of thymocytes, leukocytes and lymphocytes after s.c. administration of both TP preparations and concentrations. I.p. and i.m. TP-injections were less effective at reaching statistical significance, however, for defined dosages and parameters, only. To evaluate the influence of TP on experimental liver metastases, RAW 117 lymphosarcoma cells were intravenously inoculated into BALB/c-mice. TP (10, 50, 100 micrograms/mouse) were s.c., i.p. and i.m. administered daily for 7 consecutive days starting 24 hours after tumor cell challenge. Liver colonization was investigated on day 14 after tumor cell inoculation and demonstrated a statistically significant (p < 0.05) reduction of experimental liver metastases for s.c. (both preparations and concentrations) as well as i.p. and i.m. (dose-dependent) TP-treated mice.

Adjuvants, Immunologic↗

Physiology and clinical applications of platelet growth factors.

Recombinant human thrombopoietin, or pegylated recombinant human megakaryocyte growth and development factor, produces log-linear increases in megakaryocytopiesis and platelet production. Recent clinical studies investigating the efficacy, safety, and cost benefit of administering platelet growth factors indicate that appropriate dosing of pegylated recombinant human megakaryocyte growth and development factor, or recombinant human thrombopoietin, during chemotherapeutic marrow suppression produces these increases in four ways. First, these factors improve ensuant thrombocytopenia without producing platelet-dependent thrombo-occlusive complications. Second, recombinant human thrombopoietin or pegylated recombinant human megakaryocyte growth and development factor mobilize hematopoietic progenitor cells into the peripheral blood. Third, chronic dosing of HIV-infected thrombocytopenic patients with pegylated recombinant human megakaryocyte growth and development factor normalizes peripheral platelet counts without antibody formation. Fourth, the administration of pegylated recombinant human megakaryocyte growth and development factor to normal human volunteer platelet donors increases platelet yields nearly fourfold, with corresponding increases in peripheral platelet counts when transfused into thrombocytopenic recipients. The clinical application of platelet growth factors is continuing to be defined.

Controlled Clinical Trials as Topic↗