G. G. Krishna Murthy
Harvard University
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Inhalation Toxicology | 1999
Robert W. Clarke; Paul J. Catalano; Petros Koutrakis; G. G. Krishna Murthy; Constantinos Sioutas; Joseph D. Paulauskis; Brent A. Coull; Stephen T. Ferguson; John J. Godleski
Epidemiological studies have reported increased morbidity in human populations following inhalation of elevated levels of urban particulate matter. These responses are especially prevalent in populations with chronic obstructive pulmonary diseases, including chronic bronchitis. Toxicological studies have reported altered pulmonary function and increased pulmonary inflammation following particulate inhalation in the laboratory setting. However, most of these studies have utilized artificial particles that may not accurately mimic outdoor air pollutant conditions. Few studies have utilized actual urban air particle samples in inhalation studies. In the present study, the effects of inhaled concentrated urban air particulates on pulmonary function and pulmonary inflammation are addressed. Normal rats and rats with chronic bronchitis induced by approximately 200 ppm SO(2) for 6 wk were subsequently subjected to filtered air or concentrated air particles (CAPs). Twelve rats per group in 4 groups (48 rats total) were exposed for 5 h/day for 3 consecutive days. The CAPs aerosol levels were 206, 733, and 607 microg/m(3) (MMAD = 0.18 microm, sigma(g) = 2.9) on days 1, 2, and 3, respectively. Following the final day of exposure, pulmonary function parameters, including peak expiratory flow (PEF), tidal volume (TV), respiratory frequency (RF), and minute volume (MV), were measured and compared to preexposure baseline levels. Twenty-four hours following the final day of exposure, bronchoalveolar lavage was performed for total cell counts, differential cell counts, and total lavage protein levels. Pulmonary responses to CAPs in chronic bronchitic animals indicated a significant increase in tidal volume as well as peak expiratory flow. In CAPs-exposed animals without underlying bronchitis, significantly increased tidal volume was observed. Significant pulmonary inflammation was observed in the CAPs-exposed animals, particularly those with chronic bronchitis. Significant increases in neutrophils, lymphocytes, and total lavage protein were observed. These results suggest two distinct mechanistic responses to inhaled particles: a stress-type pulmonary function response marked by increases in flow and volume, that is, deeper breathing; and acute pulmonary inflammation marked by cellular influx, particularly neutrophils. From these data it is concluded that inhaled urban air particles alter pulmonary breathing parameters and increase pulmonary inflammation.
Experimental Lung Research | 1997
James M. Antonini; G. G. Krishna Murthy; Joseph D. Brain
Possible mechanisms were examined whereby welding fumes may elicit injury and inflammation in the lungs. The effects of different welding fumes on lung macrophages and on the in vivo production of two inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), were assessed. Fume was collected during flux-covered manual metal are welding using a stainless steel consumable electrode (MMA-SS) and gas metal are welding using a mild steel electrode (GMA-MS). For the in vitro study, bronchoalveolar lavage was performed on untreated rats to recover lung macrophages, and the effects of the welding fumes on macrophage viability and respiratory burst were examined. In vivo, additional rats were intratracheally instilled with the welding fumes at a dose of 1 mg/100 g body weight. These rats were lavaged 1, 14, and 35 days postinstillation, and indicators of lung damage (cellular differential, albumin. TNF-alpha and IL-1 beta release, and lactate dehydrogenase and beta-n-acetyl glucosaminidase activities) were measured. In vitro, the MMA-SS fume was more cytotoxic to the macrophages and induced a greater release of reactive oxygen species as measured by the respiratory burst compared to the GMA-MS fume. In vivo, evidence of lung damage was observed for both fumes 1 day postinstillation. By 14 days, lung responses to the GMA-MS fume had subsided and were not different from the saline vehicle control group. Significant lung damage was still observed for the MMA-SS group at 14 days, but by 35 days, the responses had returned to control values. One day after the instillations, both welding fumes had detectable levels of TNF-alpha and IL 1 beta within the lavage fluid. However, the MMA-SS particles caused a significantly greater release of both cytokines in the lavage fluid than did the GMA-MS group. The results demonstrate that MMA-SS fume caused more pneumoloxicity than GMA-MS. This increased response may reflect enhanced macrophage activation, the increased production of reactive oxygen species, as well as secretion of TNF-alpha and IL-1 beta.
Aerosol Science and Technology | 2004
Lupita D. Montoya; Joy Lawrence; G. G. Krishna Murthy; Jeremy A. Sarnat; John J. Godleski; Petros Koutrakis
The total deposition fraction (TDF) of fine and ultrafine aerosols was measured in a group of six healthy adults exposed to polydisperse ambient aerosols in Boston. Fifteen repeated inhalation-exhalation cycles were conducted during a given exposure session. Deposition efficiency for particles with aerodynamic diameter ranging from 63.5 to 2045 nm was determined using the average concentration of inhaled and exhaled particles measured during these cycles. Deposition efficiencies ranged from 7.3±18.7%(240-275 nm) to 98.6±28.1%(1545-2045 nm). Subjects exhibited similar deposition patterns with minimum efficiencies between 200-400 nm. Results from ANOVA and mixed-model regression analyses showed significant differences (p < 0.05) in particle deposition efficiency by particle size as well as among the subjects. Deposition efficiencies varied most among the subjects for particles between 100 and 1000 nm in size. A comparison with the ICRP model showed good agreement, with best agreement for male subjects and particle sizes <400 nm.
Metallurgical transactions. A, Physical metallurgy and materials science | 1993
Marcelo Breda Mourão; G. G. Krishna Murthy; John F. Elliott
Interactions of carbonaceous materials in liquid Fe-C melts have been investigated experimentally by determining the rates of dissolution at temperatures ranging from 1623 to 1935 K. The rates of dissolution of spectroscopic graphite and an industrial coke obeyed the correlation for natural convection under turbulent conditions. The experimental data for the graphite suggested that the rate of dissolution was controlled by mass transfer in liquid boundary layer adjacent to the solid sample. The value of the empirical parameter correlating the dissolution coefficient and the operating variables was found to be 0.19, which was close to that reported in the literature. The comparison of the results obtained for coke and low-volatile coal char samples with those for the graphite revealed that impurities and porosity of the samples can effect the dissolution rates. The values ofk1, for coke decreased with increasing the dissolution time. The examination of some of the partially dissolved coke samples by electron micro-scopy revealed that a thin, viscous ash layer was forming on the sample surface, which must be the main reason for the behavior. The dissolution rates were controlled by both mass transfer and phase boundary reactions when sulfur was present in the bath. The extent of devolatilization and dissolution of coal particles when they were injected into an Fe-C melt depended on the particle size and location.
Inhalation Toxicology | 2000
Robert W. Clarke; Paul J. Catalano; Brent A. Coull; Petros Koutrakis; G. G. Krishna Murthy; Timothy M. Rice; John J. Godleski
Epidemiological studies have reported that elderly individuals have a higher risk of detrimental responses following exposure to elevated levels of ambient particulate matter. To investigate this finding in a toxicological model, aged Fisher rats were exposed for 3 days to concentrated urban air particles (CAPs) from Boston. The hypothesis tested was that older animals would exhibit more severe pulmonary inflammation and hematological changes following the CAPs exposure when compared to young, normal animals. Aged Fisher rats (> 17 mo) and juvenile Fisher rats (4–6 wk) were maintained in a virus-antigen free facility for 3 mo prior to exposure. Following this period, aged and young rats were exposed to CAPs or sham-exposed to filtered air for 5 h/day (or 3 consecutive days (10 rats/group X 4 groups total = 40 rats). Daily integrated CAPs concentrations were 80, 170, and 50 μ/m3 on day 1, 2, and 3, respectively. None of the animals died throughout the duration of exposure. Twenty-four hours following the last day of exposure, blood was collected by cardiac puncture, and bronchoalveolar lavage (BAL) was performed. Young rats had significantly higher total BAL cell counts compared to old rats, as well as a significant increase in BAL polymorphonuclear leukocytes (PMN) following CAPs exposure compared to sham. Old rats also exhibited a small, but significant, increase in BAL PMN following exposure to CAPs compared to sham. There were no CAPs-related significant changes in aged animals in total BAL cell counts, BAL lactate dehydrogenase, total white blood cell (WBC) counts, or the percent of WBC PMN, lymphocytes, and monocytes. When comparing aged versus young (CAPs-or filtered air-exposed) animals, advanced age was associated with significant decrements in the total BAL cell counts, total WBC counts, percent of blood lymphocytes, and blood hemoglobin; a significant increase in the percent of blood PMN was also observed. The above results suggest: 1I) Young Fisher rats may represent a sensitive model for the examination of pulmonary inflammatory responses following CAPs exposure, and (2) the lack of a pulmonary inflammatory response in the aged rats, despite the presence of a higher percentage of circulating neutrophils, may reflect decreased sensitivity to inhaled particles.
Inhalation Toxicology | 1997
K. Okabe; G. G. Krishna Murthy; J. A. Vallarino; W. A. Skornik; V. C. Hatch; M. R. Katler; Akira Tsuda; John J. Godleski
Deposition efficiency, a necessary parameter in models of pulmonary deposition and clearance, has not been extensively studied with inhaled fibers. Accurate assessment of pulmonary deposition requires brief exposures with sufficiently high numbers of particles for quantification, and concomitant measurements of pulmonary ventilation. We produced aerosols of fiberglass fibers with mean diameter of 0.98 0.40 (SD) m, length of 17.2 3 14.2 m, airborne mass concentration determined gravimetrically of 5.6 0.9 mg/m, and 6 3 fiber number of 7.3 1.1 x 10 fibers/m. Preliminary studies showed that 10-min exposures were ideal in that they provided adequate numbers of particles without significant clearance. Five hamsters were exposed to the aerosol for 10 min by nose-only exposure, and pulmonary function was measured using plethysmography. Following exposure, the lung and conducting airways were digested by bleach, and deposited fibers were quantified on membrane filters. Deposition efficiency, calculated as the depo...
Inhalation Toxicology | 1996
Kazunori Okabe; J. A. Vallarino; G. G. Krishna Murthy; Akira Tsuda; John J. Godleski
AbstractSlagwool can be used in studies of fiber deposition as a surrogate for more toxic fibers. However, we found that slagwool fibers are quickly dissolved in the process of mounting filters onto slides for counting. The mixture of 35% dimethylformamide, 15% acetic acid, and 50% water (DMF) is used widely to clear filters made of mixed cellulose ester in the determination of particle number by the membrane filter method. Although the DMF/Euparal technique has been thought to be the best method compared to other clearing and mounting techniques for membrane filters, we found fiber dissolution to be a serious limitation. We examined the dissolution of three man-made vitreous fibers (slagwool, rockwool, and fiberglass) by the DMF mixture. Each fiber was soaked in the DMF mixture and monitored for 1 h using phase-contrast microscopy at 400x. Only slagwool fibers were dissolved rapidly and severely. Possible explanations for the dissolution of slagwool fibers include low pH (2.5) of the DMF mixture, a high ...
Environmental Health Perspectives | 2002
Sonia A Gurgueira; Joy Lawrence; Brent A. Coull; G. G. Krishna Murthy; Beatriz González-Flecha
American Journal of Respiratory and Critical Care Medicine | 2002
Paulo Hilário Nascimento Saldiva; Robert W. Clarke; Brent A. Coull; Rebecca C. Stearns; Joy Lawrence; G. G. Krishna Murthy; Edgar A. Diaz; Petros Koutrakis; Helen Suh; Akira Tsuda; John J. Godleski
Environmental Health Perspectives | 2002
Joao R. F. Batalha; Paulo Hilário Nascimento Saldiva; Robert W. Clarke; Brent A. Coull; Rebecca C. Stearns; Joy Lawrence; G. G. Krishna Murthy; Petros Koutrakis; John J. Godleski