The accumulation of putrescine into slices of rat lung and brain and its relationship to the accumulation of paraquat.
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Biomedical subjects
Publications and source records attributed to L L Smith.
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In an attempt to reduce the toxicity of paraquat several compounds were examined for their ability to increase the rate of efflux of paraquat from the lung. The compounds were selected because they were known, from in vitro studies, to reduce the accumulation of paraquat into the lung. Histamine (100 MicroM), promethazine (100 microM), putrescine (100 microM), bromthymol blue (300 microM) and the metabolic inhibitors iodoacetate (1 mM), rotenone (100 microM) and KCN (1 mM) have been shown to reduce the accumulation of paraquat into rat lung slices, as did the incubation of slices under nitrogen. The efflux of paraquat from lung slices prepared from rats dosed intravenously with paraquat was biphasic, having a very fast component and a slow component. The slow component was first order and was characterised by a t1/2 of 17 h. This half life is similar to that seen in vivo (24 h) following intravenous dosing. When lung slices prepared from rats dosed intravenously with paraquat were incubated in the presence of iodoacetate (1 mM) or under nitrogen, the half life of paraquat in the slices was reduced to approximately 3 h. In the presence of rotenone (100 microM) it was reduced to approximately 9 h. Histamine (100 microM) and promethazine (100 microM) did not affect the efflux of paraquat from lung slices. Bromthymol blue, a dye which forms "ion pair" complexes with paraquat, also significantly increased the efflux of paraquat from lung slices. The effect of bromthymol blue, however, decreased with time and thus paraquat efflux in the presence of bromthymol blue did not obey first order kinetics. In order to measure cellular viability of lung slices, oxygen consumption, glucose oxidation and the rate of the efflux of protein from the slices into the incubation medium were determined. Iodoacetate (1 mM) and rotenone (100 mM) almost abolished oxygen consumption and glucose oxidation whereas these activities were inhibited to a lesser extent by bromthymol blue (300 microM) (18% and 30%, respectively). During the first 30 min of incubation in the presence of KCN (1 mM) oxygen consumption was almost abolished but between 30 min and 4 h returned to control levels. The effect of KCN could therefore be divided into 2 phases. Over 4 h incubation glucose oxidation was inhibited by 36%. Iodoacetate (1 mM) and incubation under nitrogen caused the most pronounced increases in the rate of protein efflux from slices. KCN (1 mM) and rotenone (100 microM) also increased the rate of protein efflux but to a lesser extent. We have therefore suggested that the effect of KCN (1 mM) on cellular viability, while severe, may be less than that of iodoacetate (1 mM) or incubation under nitrogen...
Tabulation of the diagnostic evaluation and operative treatment of 16 patients with aldosterone-producing adrenal adenomas is presented. The diagnosis of primary aldosteronism was confirmed in all patients by biochemical and radiologic studies. Selective venous sampling of adrenal vein aldosterone localized the adenoma in 14 patients and proved to be the single most helpful diagnostic procedure. Computed tomography was used recently to confirm the localization of these interesting lesions and may become the initial noninvasive diagnostic study. Confidence in the accuracy of preoperative localization has led to the choice of the posterior approach to the involved adrenal gland. Postoperative morbidity has been low regardless of the operative approach; however, subjective patient acceptance of posterior adrenalectomy suggests a more comfortable convalescence and a more rapid return to normal activity.
There is an important and necessary distinction to be made between the delivery of medical services and the furnishing of comprehensive health care. Both medical service (or that which makes life possible) and comprehensive health care (or that which makes life worthwhile) directly enhance the self-esteem and functional ability of elderly patients. In programs of care for the elderly, practitioners must develop an understanding of the impact that various body systems as well as the social system have on the patient if the programs are to be effective. This study has attempted to provide a comprehensive understanding of the functional capacity of elderly patients seen in the General Medicine Outpatient Clinic at the University of Utah Medical Center, Salt Lake City. Implications drawn from this multidimensional functional assessment have led to recommendations for appropriate service delivery along with a better understanding of how the elderly function and what they need. Assessment techniques such as OARS questionnaire used in this study are invaluable in helping caregivers understand and plan for the comprehensive health care needs of the elderly. As more programs make use of data derived from assessment procedures like the one described here, the overall quality of life for the elderly should improve.
Various amounts of paraquat (10(-5) to 10(-12) g) in 0.1 ml saline were instilled directly into the left bronchus of male adult rats. Gravimetric, macroscopic, and microscopic studies on the left lobe of the lung showed that 10(-5) g of paraquat produced lung oedema and macroscopic lesions two and 14 days after doing. The pathology of the lung was similar to that seen after systemic poisoning. When 10(-6) g of paraquat was instilled, some animals developed lung oedema and macroscopic lesions. Microscopic examination showed subtle changes in the parenchyma of the lung. With amounts of paraquat equal to or less than 10(-7) g (doses as little as 10(-12) g were used), no changes in the lung were seen. This is contrary to published accounts in which amounts as low as 10(-12) g (1 Pg) were reported to cause acute damage to the rabbit lung. When 3H paraquat was instilled into the left lobe (doses of 10(-5) to 10(-10) g were used), the loss of paraquat from the lung was biphasic. The initial half-life was less than one hour. The secondary phase obeyed first-order kinetics, and the half-life was dependent on the dose of paraquat instilled. This half-life was as short as 11 hours when 10(-5) g paraquat was instilled and was 76 hours after the instillation of 10(-10) g paraquat. The decrease in the half-life of the secondary phase with increasing doses of paraquat is possibly associated with the production of oedema or lung cell damage, or both. After the instillation of 10(-8) g 3H paraquat, the initial half-life was less than 15 minutes, and paraquat was detected in the urine and plasma at that time. This suggests that 50% of the instilled paraquat was rapidly absorbed from the lung into the plasma.
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True aneurysms have developed in nonreinforced, expanded polytetrafluoroethylene (PTFE). We report our experience in arterial reconstructions with PTFE in the legs of patients having symptomatic occlusive disease. Fifty-four femoropopliteal or femorotibial bypass operations were performed in 51 patients between January 1975 and December 1976. An unsuitable saphenous vein for a vascular conduit was found in 14 patients, and reconstruction was done with PTFE (IMPRA-graft). Two of the 14 PTFE grafts were composite and used a segment of saphenous vein. Aneurysmal dilation developed in five PTFE grafts (36%) in four patients three to 36 months following placement. Nonreinforced PTFE conduits as manufactured during 1975 and 1976 are unsatisfactory for use as limb arterial bypass grafts because of the high incidence of aneurysmal change. Those that are implanted must be followed up indefinitely because of late aneurysmal formation and rupture. Newer PTFE graft modifications should be used with caution.
High concentrations of oxygen are known to enhance the toxic effects of paraquat in the lung. We have examined the effects of paraquat (2.5 mg/kg or 20 mg/kg subcutaneously) and diquat (10 mg/kg or 20 mg/kg subcutaneously) on mortality and lung pathology in rats exposed to air or to an atmosphere of 85% oxygen. Our results show a 10-fold increase in mortality when paraquat is given to rats placed in 85% oxygen rather than air, but only a 2-fold increase in the lethality of diquat. Lung damage typical of early paraquat intoxication is seen following 20 mg/kg paraquat in air or oxygen, with damage to type I and type II alveolar cells. Selective damage to the type II cell is produced by lower levels of paraquat (2.5 mg/kg) and by 20 mg/kg diquat, both in 85% oxygen, other cell types showed little change. Lung damage is minimal following 2.5 mg/kg paraquat or 20 mg/kg diquat in air, or exposure to 85% oxygen alone. It is suggested that the type II cell may be the primary target cell for paraquat and diquat in the lung.
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Paraquat accumulation into rat lung slices was unaffected by hypoxia (PO2 = 645 mm Hg) but was inhibited by hypoxia. The IC50 (IC50 = partial pressure of O2 resulting in a 50% inhibition of paraquat accumulation) for paraquat accumulation was P02 = 50 mm Hg; significant accumulation could be observed after 1 or 2 hr of incubation at PO2 = 10 mm Hg. The hypoxic inhibition was due to oxygen limitation of the accumulation mechanism and not to a diffusion limitation of oxygen or to cell death. Incubation of lung slices for up to 2 hr in 100% N2 (PO2 = 0 mm Hg) did not decrease paraquat accumulation or metabolism of glucose to CO2 when the slices were returned to room air. However, under the same conditions total tissue oxygen consumption was decreased by 50%. Paraquat accumulation and glucose metabolism are oxygen dependent but are resistant to the damaging effects of cellular anoxia.
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A means of determination of a ctive hydrogen of hydroxyl, carboxyl, sulfhydryl, amino, amido and sulfonamido groups by chemical ionization mass spectrometry using ammonia and trideuterioammonia as reagent gases is described. The method is based on exchange of active hydrogen for deuterium occurring during the chemical ionization process using trideuterioammonia, with comparison of m/z for ammonium adduct [M + NH1]+ and trideuterioammonium adduct [M--nH + nD + ND4]+, or of protonated molecular ion [M + H]+ and deuteronated molecular ion [M--nH + nD + D]+ yielding the number of active hydrogens. Applications have been made to several classes of biologically important compounds.
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Naturally air-aged commercial samples of USP or reagent-grade cholesterol contain components which are mutagenic towards Salmonella typhimurium strains TA1537, TA1538 and TA98. These mutagenic components are associated with the polar cholesterol autoxidation products, but identity of the mutagenic components has not been achieved. Pure crystalline nonmutagenic cholestrol free from autoxidation products becomes mutagenic towards these strains upon heating at 70 degrees in air or following exposure to 60 Co gamma-radiation.