Biomedical subjects

Judy H Richards

Publications and source records attributed to Judy H Richards.

13 recordsLinked to original sources

PubMed2006

The spontaneously hypertensive rat: an experimental model of sulfur dioxide-induced airways disease.

Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation, and mucus hypersecretion, features that are common in bronchitis, emphysema, and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisposed spontaneously hypertensive (SH) rats display phenotypes such as systemic inflammation, hypercoagulation, oxidative stress, and suppressed immune function that are also apparent in COPD patients, we hypothesized that SH rat may offer a better model of experimental bronchitis. We, therefore, exposed SH and commonly used Sprague Dawley (SD) rats (male, 13- to 15-weeks old) to 0, 250, or 350 ppm sulfur dioxide (SO(2)), 5 h/day for 4 consecutive days to induce airway injury. SO(2) caused dose-dependent changes in breathing parameters in both strains with SH rats being slightly more affected than SD rats. Increases in bronchoalveolar lavage fluid (BALF) total cells and neutrophilic inflammation were dose dependent and significantly greater in SH than in SD rats. The recovery was incomplete at 4 days following SO(2) exposure in SH rats. Pulmonary protein leakage was modest in either strain, but lactate dehydrogenase and N-acetyl glucosaminidase activity were increased in BALF of SH rats. Airway pathology and morphometric evaluation of mucin demonstrated significantly greater impact of SO(2) in SH than in SD rats. Baseline differences in lung gene expression pattern suggested marked immune dysregulation, oxidative stress, impairment of cell signaling, and fatty acid metabolism in SH rats. SO(2) effects on these genes were more pronounced in SH than in SD rats. Thus, SO(2) exposure in SH rats may yield a relevant experimental model of bronchitis.

Acetylglucosaminidase↗

PubMed2005

Disruption of iron homeostasis in the lungs of transplant patients.

BACKGROUND: Oxidative stress has been proposed as a mechanism of injury underlying obliterative bronchiolitis. Catalytically reactive iron is a potential source of reactive oxygen species in transplanted tissue. Using samples acquired from surveillance bronchoalveolar lavage (BAL), we tested the postulate that there is a disruption of iron equilibrium in transplanted lung, which can worsen with time. METHODS: A control group of 5 healthy, non-smoking volunteers underwent BAL. Five bilateral lung transplant patients underwent surveillance BAL with transbronchial lung biopsies. The BAL fluid concentrations of protein, albumin, total iron, lactoferrin, ferritin, transferrin receptor and total iron binding capacity were measured. RESULTS: The mean ages in the control and transplant groups were 25.0 +/- 2.4 and 34.6 +/- 5.0 years, respectively. Patients were transplanted for cystic fibrosis (n = 3), primary ciliary dyskinesia (n = 1) and bronchiolitis obliterans (n = 1). Surveillance bronchoscopies were performed at 100.6 +/- 63.3, 175.0 +/- 87.7 and 259.2 +/- 82 days post-transplant. No significant differences were noted in BAL protein, albumin and total iron binding capacity (TIBC) levels between the 2 groups. The BAL iron, transferrin, transferrin receptor, lactoferrin and ferritin levels were significantly elevated in transplant patients relative to controls. With time after transplantation, there were increases in lavage iron, transferrin receptor, lactoferrin and ferritin concentrations. CONCLUSIONS: Abnormally high levels of iron and its homeostatic proteins were found in the lung allografts, and levels appeared to increase with time. This supports a disruption in the normal homeostasis of this metal after transplantation and a potential role for a catalyzed oxidative stress in bronchiolitis obliterans. The use of iron-depleting therapy is a possible means for preventing injury in the lung allograft.

Adolescent↗

PubMed2005

Cardiovascular and blood coagulative effects of pulmonary zinc exposure.

Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Male Wistar Kyoto rats were instilled intratracheally with saline or zinc sulfate, 131 microg/kg (2 micromol/kg); the alterations were determined at 1, 4, 24, and 48 h postexposure. High-dose zinc enabled us to show changes in circulating levels of zinc above normal and induce significant pulmonary inflammation/injury such that cardiac impairments were likely. At 1-24 h postexposure, plasma levels of zinc increased to nearly 20% above the base line. Significant pulmonary inflammation and injury were determined by analysis of bronchoalveolar lavage fluid and histopathology in zinc-exposed rats at all time points. Starting at 4 h postexposure, pulmonary damage was accompanied by persistently increased gene expressions of tissue factor (TF) and plasminogen activator-inhibitor-1 (PAI-1), but not thrombomodulin (TM). Cardiac tissues demonstrated similar temporal increases in expressions of TF, PAI-1, and TM mRNA following pulmonary instillation of zinc. In contrast to extensive pulmonary edema and inflammation, only mild, and focal acute, myocardial lesions developed in a few zinc-exposed rats; no histological evidence showed increased deposition of fibrin or disappearance of troponin. At 24 and 48 h postexposure to zinc, increases occurred in levels of systemic fibrinogen and the activated partial thromboplastin time. These data suggest that cardiovascular blood coagulation impairments are likely following pulmonary zinc exposure and associated pulmonary injury and inflammation.

Air Pollutants↗

PubMed2005

Consistent pulmonary and systemic responses from inhalation of fine concentrated ambient particles: roles of rat strains used and physicochemical properties.

Several studies have reported health effects of concentrated ambient particles (CAP) in rodents and humans; however, toxicity end points in rodents have provided inconsistent results. In 2000 we conducted six 1-day exposure studies where spontaneously hypertensive (SH) rats were exposed to filtered air or CAPs (< or = 2.5 microm, 1,138-1,765 microg/m3) for 4 hr (analyzed 1-3 hr afterward). In seven 2-day exposure studies in 2001, SH and Wistar Kyoto (WKY) rats were exposed to filtered air or CAP (< or = 2.5 microm, 144-2,758 microg/m3) for 4 hr/day times 2 days (analyzed 1 day afterward). Despite consistent and high CAP concentrations in the 1-day exposure studies, no biologic effects were noted. The exposure concentrations varied among the seven 2-day exposure studies. Except in the first study when CAP concentration was highest, lavageable total cells and macrophages decreased and neutrophils increased in WKY rats. SH rats demonstrated a consistent increase of lavage fluid gamma-glutamyltransferase activity and plasma fibrinogen. Inspiratory and expiratory times increased in SH but not in WKY rats. Significant correlations were found between CAP mass (microgram per cubic meter) and sulfate, organic carbon, or zinc. No biologic effects correlated with CAP mass. Despite low chamber mass in the last six of seven 2-day exposure studies, the levels of zinc, copper, and aluminum were enriched severalfold, and organic carbon was increased to some extent when expressed per milligram of CAP. Biologic effects were evident in those six studies. These studies demonstrate a pattern of rat strain-specific pulmonary and systemic effects that are not linked to high mass but appear to be dependent on CAP chemical composition.

Air Pollutants↗

PubMed2004

Hypertensive rats are susceptible to TLR4-mediated signaling following exposure to combustion source particulate matter.

Toll-like receptor 4 (TLR4) has been shown to play a role in cell signaling that results in neutrophilic inflammation in response to lipopolysaccharide and respiratory syncytial virus infection. TLR4 also interacts with CD14, which upon complex formation triggers TLR4-associated signaling pathways to produce a proinflammatory response. This mechanism results in the activation of NF-kappa B and subsequent inflammatory gene induction. In order to determine the effect of combustion source particle matter (PM), rich in zinc and nickel but with negligible endotoxin, on a possible activation of TLR4-mediated cell signaling and inflammation, we intratracheally (IT) instilled 3.3 mg/kg of PM into 12-w-old healthy male Wistar Kyoto (WKY) and susceptible spontaneously hypertensive (SH) rats. Inflammation, inflammatory-mediator gene expression, bronchoalveolar lavage fluid (BALF) protein and LDH, TLR4 and CD14 protein, and NF-kappa B activation in the lung were determined after 24 h. Dose-response data (0.0, 0.83, 3.33, and 8.3 mg/kg PM) for BALF LDH were obtained as a marker of lung cell injury in SH rats. BALF neutrophils, but not macrophages, were significantly increased in the PM-exposed WKY and SH rats. SH rats showed a greater PMN increase than WKY rats. Similarly, BALF protein and LDH levels were also increased following PM exposure but to a significantly greater extent in SH rats. Plasma fibrinogen was increased only in SH rats exposed to PM. The increased inflammation seen in PM-exposed SH rats was accompanied by a significant increase in TLR4 protein in the lung tissue, which was primarily localized in alveolar macrophages and epithelial cells. CD14 was also increased by PM exposure in both SH and WKY rats but was significantly greater in the SH rats. These increases were associated with greater translocation of NF-kappa B in the lungs of SH rather than WKY rats. This was accompanied by increased macrophage inhibitory protein (MIP)-2 mRNA expression at 24 h of exposure. These data suggest that the increased inflammation in the lungs of PM-exposed SH rats compared to WKY rats is accompanied by an increase in TLR4-mediated cell signaling. Thus, one of the mechanisms for greater susceptibility of SH rats to PM exposure may involve an increased activation of the TLR4 signaling pathway.

Air Pollutants↗

PubMed2003

Metals mimic airway epithelial injury induced by in vitro exposure to Utah Valley ambient particulate matter extracts.

Epidemiologic studies have shown positive associations between changes in ambient particulate matter (PM) levels in Utah Valley during 1986-1988, and the respiratory health of the local population. Ambient PM reductions coincided with closure of an open-hearth steel mill, the major industrial source of particulate emissions in the valley. In this report, water extracts of PM filters from steel mill operational (UE-86, UE-88) and closure (UE-87) periods were analyzed for their elemental composition. Their relative toxicity was determined by exposing primary rodent airway epithelial cultures to equal masses of extracted material. To elucidate extract subcomponents mediating the effects observed, cells were also exposed to surrogate metal mixtures. Potential interactions between the two predominant metals in the UE-86/88 samples, zinc (Zn) and copper (Cu), were further investigated. Data indicated that, relative to the UE-87 (plant closed) sample, UE-86/88 samples contained more sulfate, calcium, potassium,magnesium and, although present in much lower amounts, a variety of metals including Zn,Cu, iron, lead, strontium, nickel, manganese, and vanadium (V). Cell exposure to UE-86 and UE-88, but not UE-87, resulted in time- and concentration-dependent epithelial injury based on biochemical and light/electron microscopic changes. Cell injury induced by metal mixtures containing equivalent amounts of Zn + Cu + V was commensurate with that induced by the corresponding extract, although divergent antioxidant responses were observed. Exposure to Zn + Cu resulted in significantly greater epithelial toxicity and stress (c-Jun N-terminal protein kinase activation) responses than did exposure to Zn or Cu individually. The parallel epithelial injury induced by the extracts and their surrogate Zn + Cu + V mixtures suggests that these metals are mediating the acute airway epithelial effects observed; however, metal interactions appear to play a critical role in the overall cellular effects induced by the PM-derived extracts. These experimental findings are in good accord with epidemiologic reports of adverse airway and respiratory health health effects in Utah Valley residents.

Air Pollutants, Occupational↗

PubMed2003

Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations.

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.

Abnormalities, Drug-Induced↗

PubMed2003

Oxalate deposition on asbestos bodies.

We report on a deposition of oxalate crystals on ferruginous bodies after occupational exposure to asbestos demonstrated in 3 patients. We investigated the mechanism and possible significance of this deposition by testing the hypothesis that oxalate generated through nonenzymatic oxidation of ascorbate by asbestos-associated iron accounts for the deposition of the crystal on a ferruginous body. Crocidolite asbestos (1000 microg/mL) was incubated with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C. The dependence of oxalate generation on iron-catalyzed oxidant production was tested with the both the metal chelator deferoxamine and the radical scavenger dimethylthiourea. Incubation of crocidolite, H(2)O(2), and ascorbate in vitro generated approximately 42 nmol of oxalate in 24 hours. Oxalate generation was diminished significantly by the inclusion of either deferoxamine or dimethylthiourea in the reaction mixture. Incubation of asbestos bodies and uncoated fibers isolated from human lung with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C resulted in the generation of numerous oxalate crystals. We conclude that iron-catalyzed production of oxalate from ascorbate can account for the deposition of this crystal on ferruginous bodies.

Asbestos, Crocidolite↗

PubMed2003

Oxidative stress mediates air pollution particle-induced acute lung injury and molecular pathology.

Insight into the mechanism(s) by which ambient air particulate matter (PM) mediates adverse health effects is needed to provide biological plausibility to epidemiological studies demonstrating associations between PM exposure and increased morbidity and mortality. Although in vitro PM studies provide an understanding of mechanisms by which PM affects pulmonary cells, it is difficult to extrapolate from in vitro to in vivo mechanisms of PM-induced lung injury. We examined in vivo mechanisms of lung injury generated by oil combustion particles. Rats were pretreated with dimethylthiourea (DMTU) before intratracheal instillation of residual oil fly ash (ROFA). Animals were examined by bronchoalveolar lavage for biomarkers of lung injury, and lung tissues were examined by immunohistochemical, biochemical, and molecular approaches to identify ROFA-induced alterations in intracellular signaling pathways and proinflammatory gene expression. Significant increases in pulmonary inflammation, cytotoxicity, activation of ERK mitogen-activated protein kinase (MAPK), and increases in mRNA levels encoding macrophage inflammatory protein (MIP)-2, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, MCP-1 and matrilysin were observed. DMTU pretreatment inhibited ROFA-induced pulmonary inflammation, cytotoxicity, ERK MAPK activation, and cytokine gene expression. Our findings provide coherence with in vitro PM mechanistic information, allow direct in vitro to in vivo extrapolation, and demonstrate a critical role for oxidative stress in ROFA-induced lung injury and associated molecular pathology.

Air Pollutants↗

PubMed2003

Iron and iron-related proteins in the lower respiratory tract of patients with acute respiratory distress syndrome.

OBJECTIVE: An increased oxidative stress in the lower respiratory tract of individuals with acute respiratory distress syndrome is considered to be one mechanism of lung injury in these patients. Cell and tissue damage resulting from an oxidative stress can ultimately be the consequence of a disruption of normal iron metabolism and an increased availability of catalytically active metal. Using bronchoalveolar lavage fluid, we quantified concentrations of iron and iron-related proteins in the lower respiratory tract in patients with acute respiratory distress syndrome and healthy volunteers. DESIGN: A clinical study to quantify iron and iron-related proteins in the lower respiratory tract in patients with acute respiratory distress syndrome and healthy volunteers. PATIENTS: We studied 14 patients with acute respiratory distress syndrome and 28 healthy volunteers. MAIN RESULTS: Comparable to previous investigation, protein, albumin, and cytokine concentrations in the bronchoalveolar lavage fluid were significantly increased in acute respiratory distress syndrome patients. The concentrations of total and nonheme iron were also increased in the lavage fluid of patients. Concentrations of hemoglobin, haptoglobin, transferrin, transferrin receptor, lactoferrin, and ferritin in the bronchoalveolar lavage fluid were all significantly increased in acute respiratory distress syndrome patients. CONCLUSIONS: We conclude that bronchoalveolar lavage fluid indices reflect a disruption of normal iron metabolism in the lungs of acute respiratory distress syndrome patients. Increased concentrations of available iron in acute respiratory distress syndrome may participate in catalyzing oxidant generation destructive to the tissues of the lower respiratory tract. However, increased metal availability is also likely to elicit an increased expression of transferrin receptor, lactoferrin, and ferritin in the lower respiratory tract which will function to diminish this oxidative stress.

Adult↗

PubMed2002

Iron-binding and storage proteins in sputum.

Induced sputum (IS) and bronchoalveolar lavage (BAL) sample different lung compartments, with IS obtaining secretions from the surfaces of the bronchial airways and BAL sampling secretions from the alveolar airspaces. Deposition of iron-containing particulate matter occurs preferentially in the bronchial airways compared to the distal airspaces. Iron-binding and storage proteins have been measured in BAL in healthy humans, where they act to sequester and detoxify available iron; however, their comparative levels in the airways are not well defined. Seventeen (n = 17) healthy, nonsmoking volunteers underwent sputum induction and fiber-optic bronchoscopy with lavage in order to measure and compare the levels of iron and iron-binding and storage proteins in BAL, bronchial lavage (BL), and IS. Relative to BAL and BL specimens, concentrations of total iron, ferritin, lactoferrin, and total iron binding capacity (TIBC) were significantly increased and transferrin decreased in IS. Immunohistochemical staining showed increased ferritin, lactoferrin, and TIBC in IS. Constitutive levels of iron and iron-binding and storage proteins (except for transferrin) are in greatest concentration in the bronchial airways relative to the alveolar airspaces in healthy humans. We speculate that these proteins reflect activated antioxidant defense mechanisms resulting from the preferential deposition of iron-containing particulate matter in the airways. The finding of decreased transferrin with increased ferritin suggests a local cellular response via iron-response elements (IRE) associated with the mRNAs for these two iron-binding proteins.

Adolescent↗

PubMed2002

Pulmonary and systemic effects of zinc-containing emission particles in three rat strains: multiple exposure scenarios.

As a common component of ambient particulate matter (PM), zinc has been proposed to play a role in PM-induced adverse health effects. Although occupational exposures to high levels of zinc-fume have been associated with metal-fume fever accompanied by pulmonary inflammation and injury, the effects of PM-associated zinc are unclear. We hypothesized that an oil combustion emission PM (EPM) containing bioavailable zinc would induce pulmonary injury and systemic hematological changes attributable to the leachable zinc following acute as well as longer-term exposures in a rat strain-specific manner. In order to initially characterize the pulmonary response to EPM, male Sprague-Dawley (SD) rats were intratracheally (IT) instilled with 0.0, 0.8, 3.3, or 8.3 mg/kg EPM in saline. To further determine if the pulmonary injury was associated with the EPM leachable zinc, subsequent studies included IT instillation of SD rats with either saline, whole EPM suspension, the saline leachable fraction of EPM, the particulate fraction of EPM (all at 8.3 mg/kg, soluble Zn = 14.5 microg/mg EPM), or ZnSO(4) (0.0, 33.0, or 66.0 microg/kg Zn). Finally, to ascertain the cumulative impact of inhaled EPM in the causation of acute pulmonary and systemic effects as well as long-term fibrotic responses, we exposed three rat strains of differential susceptibility to PM. Male SD, normotensive Wistar-Kyoto (WKY), and spontaneously hypertensive (SH) rats (90 days old) were exposed nose-only to either filtered air or EPM: 2, 5, or 10 mg/m(3) (6 h/day x 4 days/week x 1 week); or 10 mg/m(3) (6 h/day x 1 day/week for 1, 4, or 16 weeks) and assessed at 2 days postexposure. IT exposures to whole EPM suspensions were associated with a dose-dependent increase in protein/albumin permeability and neutrophilic inflammation. Pulmonary protein/albumin leakage and neutrophilic inflammation caused by the leachable fraction of EPM and ZnSO(4) were comparable to the effect of whole suspension. However, protein/albumin leakage was not associated with the particulate fraction, although significant neutrophilic inflammation did occur following instillation. With EPM nose-only inhalation, acute exposures (10 mg/m(3) only) for 4 days resulted in small increases in bronchoalveolar lavage fluid (BALF) protein and n-acetyl glucosaminidase activities (approximately 50% above control). Surprisingly, unlike IT exposures, no neutrophilic influx was detectable in BALF from any of the inhalation groups. The only major effect of acute and long-term EPM inhalation was a dose- and time-dependent increase in alveolar macrophages (AM) regardless of the rat strain. Histological evidence also showed dose- and time-dependent accumulations of particle-loaded AM. Particles were also evident in interstitial spaces, and in the lung-associated lymph nodes following the inhalation exposures (SH > WKY = SD). There were strain-related differences in peripheral white blood cell counts and plasma fibrinogen with no major EPM inhalation effect. The present study demonstrated the critical differences in pulmonary responsiveness to EPM between IT and inhalation exposures, probably attributable to the dose of bioavailable zinc. EPM IT exposures, but not acute and long-term inhalation of up to 10 mg/m(3), caused neutrophilic inflammation. Inhalation exposures may result in particle accumulation and macrophage recruitment with potential strain differences in EPM clearance.

Administration, Inhalation↗

PubMed2002

Partitioning of benzene in blood: influence of hemoglobin type in humans and animals.

Earlier studies have shown that air/blood partition coefficients (PCs) for many volatile organic chemicals (VOCs) are much higher in rat blood than in human blood. It has been suggested that the discrepancy could be attributed to the fact that hemoglobin (Hb) in rat blood exists in a quasi-crystalline form of hydrophobicity greater than that of normal human Hb (HbA) and thus has a higher carrying capacity for VOCs. In the present study, we used benzene as a prototypic VOC to examine its relative partitioning into human and animal blood. Additionally, we sought to ascertain whether the water-insoluble form of hemoglobin (HbS) found in subjects with homozygous sickle cell (SC) disease has a greater VOC-carrying capacity than does HbA blood. At a low-O(2) tension, HbS switches to water-insoluble polymers, which physically deforms the red blood cells (RBCs) to the sickle shape. We equilibrated HbA, HbS, Hartley guinea pig, CD1 mouse, and rat (F-344, Wistar, and Sprague-Dawley) blood and their respective fractions with benzene vapor (80 or 400 ppm) for 3 hr at 37 degrees C in air-tight vials. We introduced benzene vapor into the vial head space that contained air or respiratory mixtures of venous-type (low-O(2)) or arterial-type (high-O(2)) gases. The blood measurements included the PC, Hb, partial pressures of O(2)(pO(2)) and CO(2)(pCO(2), pH, and percentage of SCs. The benzene concentration had no effect on these parameters, and the high- and low-O(2) gas mixtures produced the expected changes in pO(2), pCO(2), and pH. At equilibrium, the low-O(2) HbS blood had approximately 85% SCs compared with roughly 15% with air or high-O(2) gas. PCs for rat and mouse blood were about 100% higher than those for human and guinea pig blood, but the PC for deoxygenated HbS blood was only slightly higher than that for HbA or oxygenated HbS blood. Benzene showed higher affinities for RBCs in the deoxygenated HbS, rat, and mouse blood and higher affinity for plasma in the guinea pig blood. There was no evidence of disproportionate partitioning of benzene into oxygenated HbS or into HbA blood forms. These data suggest that the water solubility of Hb alone appears to have little effect on the VOC-carrying capacity of blood and that the influence of species is large in comparison. These latter differences in partitioning may depend on the number of hydrophobic sites on the surface of the plasma/heme proteins and thus be unique to the species.

Animals↗