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J Hoidal

Publications and source records attributed to J Hoidal.

11 recordsLinked to original sources
PubMed1997

Selective O-desulfation produces nonanticoagulant heparin that retains pharmacological activity in the lung.

Heparin has potential use as an antiinflammatory treatment in many lung diseases but its therapeutic use is limited by inherent anticoagulant activity. The anticoagulant nature of heparin can be eliminated by a number of chemical treatments, but often not without loss of other important pharmacological activities. Lyophilization of porcine mucosal heparin under extreme alkaline conditions (pH > or = 13) produces a nonanticoagulant heparin remarkable for the selective loss of only 2-O and 3-O sulfates, leaving 6-O and N-sulfates intact. In contrast to the commonly used nonanticoagulant analog N-desulfated, N-reacetylated heparin, selectively O-desulfated heparin retains potent activity as an inhibitor of the cationic neutrophil proteases human leukocyte elastase and cathepsin G, both in vitro and in vivo. Selectively O-desulfated heparin also inhibits complement lysis of erythrocytes, prevents ischemia-reperfusion injury of the lung, remains a potent antiproliferative treatment for cultured airway smooth muscle and normalizes altered neuronal M2 muscarinic receptor sensitivity and bronchial hyperreactivity after antigen challenge. These retained pharmacologic properties suggest possible use of this new nonanticoagulant heparin for the treatment of a variety of lung disorders.

Animals↗
PubMed1990

Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters.

Oxidants from cigarette smoke or those produced by phagocytes are implicated in the pathogenesis of emphysema. We reasoned that augmentation of antioxidant enzymes in cigarette smokers may be important in restricting direct and indirect oxidant damage to alveolar structures. Accordingly, we studied the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx), in alveolar macrophages (AM) from cigarette smokers and from smoke-exposed hamsters. The activities of these antioxidant enzymes were compared with the activities found in AM from nonsmoking control subjects. The activities of SOD and CAT from AM of smokers and smoke-exposed hamsters were twice that found in control subjects (p less than 0.01), but there was no change in the activity of GSHPx. Using the hamster model, we found that filtration of smoke attenuated the increase in antioxidant activities, and that after smoking cessation, the increased activities had returned to those found with control subjects. An adaptive response was further suggested by prolonged survival of smoke-exposed hamsters in normobaric hyperoxia (O2 greater than 95%). Chronic smoke exposure in humans or hamsters causes increased SOD and CAT activities in AM. This augmented activity may serve as a mechanism to limit oxidant-mediated damage to alveolar structures.

Animals↗
PubMed1989

Characterization of scavenger receptor activity in resident human lung macrophages.

We characterized scavenger receptor pathways of human alveolar macrophages and cultured monocytes using radiolabeled maleylated bovine serum albumin (MAL-BSA) and acetylated low-density lipoprotein (Ac-LDL) as ligands. Human alveolar macrophages and cultured human monocytes degraded both MAL-BSA and Ac-LDL. Both ligands were bound and degraded in a specific and saturable fashion. Specificity of degradation was tested using excess MAL-BSA and Ac-LDL, polyanionic compounds, and alpha-casein as inhibitors. Alveolar macrophages utilized the classical scavenger receptor pathway to degrade MAL-BSA and Ac-LDL. In contrast, cultured monocytes utilized two receptor pathways to degrade MAL-BSA: the classical scavenger receptor pathway and a secondary alpha-casein-inhibitable pathway. These results demonstrate differences in the activities of receptor systems in cultured monocytes compared to alveolar macrophages.

Humans↗
PubMed1988

Leukocyte function and chronic bronchitis.

Chronic bronchitis is a condition of mucous hypersecretion. It represents an interface between airway structures, cigarette smoke, and inflammatory cells. Chronic bronchitis is a late complication of smoking, typically occurring after 30 pack years. Stable patients have mucous hypersecretion and little evidence of acute inflammation. In contrast, during acute attacks of bronchitis, an intense accumulation of neutrophils occurs in the airways. Mechanisms of injury to airway structures include chemicals and reactive oxygen species within cigarette smoke, and secreted products of recruited neutrophils. Recent studies demonstrate that secreted products of polymorphonuclear leukocytes (PMNs) can cause secretory cell metaplasia and increase mucous production. Thus, the role of the PMN in chronic mucous hypersecretion appears to be a significant one. Cessation of cigarette smoking remains a most important aspect of caring for patients with chronic mucous hypersecretion.

Animals↗
PubMed1986

Size and filterability of human and hamster pulmonary macrophages exposed to cigarette smoke.

Pulmonary alveolar macrophages (PAM) obtained from healthy human cigarette smokers generated greater pressure in filtration through small cylindrical pores than PAM from nonsmoking controls. A well standardized hamster smoking model was employed to study the structural basis for the impaired PAM filtration accompanying cigarette smoke exposure. Hamsters also demonstrated increased PAM filtration pressure through cylindrical pores less than half a cell diameter in size after inhalation of cigarette smoke, but not after exposure to vapor phase smoke that had been strained through a particle filter. Cigarette smoker PAM were equally filterable as control through larger diameter channels, and showed comparable improvements in filterability with cytochalasin B treatment. Altered PAM filtration was associated with the formation of characteristic cytoplasmic smoker inclusions, an increase in cell size, and loss of redundant, ruffled surface membrane. The study of smoker and control PAM separated into different sizes on the basis of variations in cell density suggested that discrepancies in cell size were insufficient to explain the filtration disparity. A loss of availability of surface membrane for deformation appeared to be the most important factor responsible for the impaired filtration.

Animals↗
PubMed1985

Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: role of red cell glutathione.

Intact erythrocytes placed into the tracheobronchial tree of hyperoxic rats dramatically improved their chances for survival. Over 70 percent of the animals so treated survived more than 12 days during continuous exposure to 95 percent oxygen, whereas all of the control animals died within 96 hours. Lungs from erythrocyte-protected rats showed almost none of the morphologic damage suffered by untreated animals. Erythrocytes containing cyanomethemoglobin were as beneficial as normal erythrocytes, but cells in which glutathione was partially blocked were significantly less protective. Analogous results were obtained in vitro: 51Cr-labeled target cells released 70 to 90 percent of their label when exposed briefly to hydrogen peroxide or to toxic oxygen species generated by phorbol ester-stimulated neutrophils. Addition of intact erythrocytes decreased release by approximately 75 percent, but significantly less than this if red blood cell glutathione was partially blocked. These results suggest that insufflated erythrocytes, through their recyclable glutathione, protect rats from toxic oxygen species engendered by hyperoxia.

Animals↗
PubMed1985

Effects of elastase and cigarette smoke on alveolar epithelial permeability.

To determine whether instilled porcine pancreatic elastase (PPE) increases alveolar epithelial permeability, we measured alveolar epithelium permeability X surface area (PS) for [14C]sucrose and 125I-bovine serum albumin (125I-BSA) in isolated perfused lungs from hamsters previously exposed to PPE and/or cigarette smoke. Saline (0.5 ml) with 0, 5, or 20 units PPE was instilled intratracheally in anesthetized hamsters. Those exposed to smoke for 4-6 wk received 0 or 5 units; PS was measured 3 h later. Nonsmokers received 0, 5, or 20 units; PS was measured 3 h, 24 h, or 5 days later. Control PS values were (cm3/s X 10(-4), +/- SE) 0.84 +/- 0.11 for sucrose and 0.030 +/- 0.006 for BSA. Three and 24 h following 20 units PPE, (PS)sucrose was twice the control valve. (PS)BSA was four times control at 3 h but not significantly increased at 24 h. Five days after PPE both were back to control levels. Five units PPE or smoke exposure alone caused no PS changes. Smoke exposure and 5 units PPE caused (PS)sucrose to increase markedly (1.85 +/- 0.32); (PS)BSA was not significantly increased (0.076 +/- 0.026). Thus instilled PPE causes reversible increases in alveolar epithelial PS; cigarette smoking potentiates this effect.

Animals↗
PubMed1984

Insufflated red cells protect lungs from hyperoxic damage: role of red cell glutathione in scavenging toxic O2 radicals.

Hyperoxia-mediated pulmonary damage may involve formation of toxic oxygen species such as superoxide, hydrogen peroxide, and hydroxyl radical. Intact red cells evidently scavenge these when insufflated in small numbers into the tracheobronchial tree of rats. Such manipulation protects hyperoxic rats for prolonged periods of time and preserves normal pulmonary histology. Of several potential oxygen metabolite scavengers, a role for red cell glutathione seems particularly likely. It has not escaped our attention that an ironic, and previously unsuspected, connotation of our results emerges: namely, that a small degree of spontaneous alveolar bleeding, which is not an uncommon feature in respiratory distress situations, may actually be beneficial to patients--particularly those ventilated with excessive inspired oxygen concentrations. If confirmatory studies from other laboratories are forthcoming, the tracheal insufflation of autologous red cells in ventilated patients might be considered in the future.

Animals↗
PubMed1983

Bleomycin-induced changes in pulmonary microvascular albumin permeability and extravascular albumin space.

Pulmonary microvascular permeability to serum albumin and the extravascular albumin space (EAS) were measured in rat lungs 5 days after intratracheal instillation of bleomycin. The albumin permeability-surface area product (PS) was measured using a new method: lungs were removed and perfused with Ringer's solution; they were then perfused for 3 min with Ringer's containing [125I]albumin, followed by 3 min with plain Ringer's to clear the vascular space. The PS was calculated from the 125I activity in perfusate and homogenized lung tissue. In separate experiments the EAS was measured using standard methods. Compared with control rats, the injected animals showed a slight, but significant, increase in PS, and a doubling of the EAS. In previous work, using other techniques, the EAS increase was interpreted as an increased PS. Our new method for PS measurement is easy and more accurate than those previously used, and shows that the acute pulmonary response to intratracheally administered bleomycin involves significant interstitial changes with little alteration in the microvascular endothelium.

Animals↗