Browsing by Author "Rossouw, D. J."
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- ItemThe adult respiratory distress syndrome in association with diabetic keto-acidosis: A case report(Health & Medical Publishing Group, 1987-04) Botha, J.; Van Niekerk, D. J. T.; Rossouw, D. J.; Stewart, R. I.ENGLISH ABSTRACT: A 41-year-old man presented in stupor, with ketoacidosis and acute severe respiratory failure. He had a history of alcohol abuse and had been on insulin therapy for diabetes secondary to chronic pancreatitis for 11 years. The condition was rapidly progressive and the patient died within 5 hours of presentation of profound hypoxia and hypotension despite aggressive therapy. Autopsy confirmed the clinical diagnosis of 'shock lung'. None of the more commonly associated precipitating factors of adult respiratory distress syndrome could be detected clinically or at autopsy and the pathogenesis of the condition remains elusive.
- ItemThe effect of oxygen and paraquat on the 14C-glucose oxidation of rabbit alveolar macrophages and lung slices(Health & Medical Publishing Group, 1979) Rossouw, D. J.; Engelbrecht, F. M.In this study, we measured the effects of different concentrations of paraquat (0.01 mM and 1.0 mM) on the 1-14CO2 and 6-14CO2 production of rabbit lung slices and isolated alveolar macrophages, in 20% and 95% oxygen phases respectively. A 95% oxygen phase induced an increase in the 6-14C-glucose oxidation of control lung slices over a 3-hour period, while the increased activity of the pentose pathway over the first 2 hours started to decline during the third hour of incubation. Paraquat (1.0mM) in 20% oxygen caused a consistent increase in the 6-14CO2 production by lung slices, but in a 95% oxygen phase gradually inhibited the 6-14C-glucose oxidation over a period of 3 hours. The pentose phosphate pathway was highly significantly stimulated by 1.0 mM paraquat in 20% and 95% oxygen over 3 hours. When isolated alveolar macrophages (viability 95%) were incubated in a 20% and a 95% oxygen phase respectively, both the 6-14C-glucose oxidation rates were significantly inhibited by 1.0 mM paraquat after 1 hour. Our results confirmed the initial increase in glycolytic metabolism induced by paraquat, but also indicated that the 6-14CO2 production was significantly inhibited by paraquat when lung slices were incubated in a 95% oxygen phase. The fact that the glucose metabolism in alveolar macrophages is more sensitive to paraquat exposure than that of cells in lung slices may be related to the genesis of the intra-alveolar pulmonary lesions described in the literature.
- ItemThe effect of paraquat on the in vitro activity of cytosol, mitochondrial and microsomal enzyme systems(Health & Medical Publishing Group, 1984) Rossouw, D. J.; Chase, C. C.; Engelbrecht, F. M.Subcellular fractions (mitochondria, microsomes and cytosol) were prepared from the lungs of rabbits and rats to investigate the effects of paraquat (Aldrich Laboratories) on the activity of cytosol and mitochondrial dehydrogenases and on the microsomal respiration and reduced pyridine nucleotide oxidation rate. The normal basal oxygen consumption of rabbit lung microsomes was 1.9 ± 0.3 nmol O2/mg microsomal protein/min, and the oxidation rates of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) and reduced nicotinamide-adenine dinucleotide (NADH) were 4.29 ± 0.53 and 4.0 ± 0.55 nmol/mg microsomal protein/min respectively. One molecule of oxygen can therefore oxidize two molecules of NADPH and NADH, and the generated hydrogen peroxide is probably immediately broken down by the catalase activity of the normal lung microsomal preparation. When Aldrich paraquat (1.0 mM) was added to microsomes metabolizing NADPH (0.5 - 0.75 mM), both the rate of oxygen consumption and the generation of nicotinamide-adenine dinucleotide phosphate (NADP) were significantly (P < 0.001) stimulated over the first 5 minutes, and thereafter returned to within basal limits. When microsomes were preincubated with 1.0 mM paraquat before NADPH was added, the oxygen consumption was substantially lower (10.01 ± 1.01 nmol oxygen/mg microsomal protein/min), while the NADPH oxidation rate was almost similar to the basal rate in the absence of paraquat. This resulted in a striking dissociation in the H/O ratio under these circumstances. The addition of potassium cyanide (KCN) (5.0 mM) prior to paraquat pre-incubation and followed by the addition of NADPH restored the stimulatory effect of paraquat on microsomal respiration and on NADPH oxidation rate. Paraquat (0.01 mM) had no effect on the reaction rates of the following enzyme systems, glucose-6-phosphate dehydrogenase (G-6-PD), glyceraldehyde-3-phosphate dehydrogenase (GAPD), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), and isocitrate dehydrogenase (IDH). However, 0.1 mM paraquat slightly inhibited the mitochondrial IDH system, and 1.0 mM paraquat significantly inhibited all the enzymes tested except for mitochondrial and cytosol MDH. The addition of KCN 5.0 mM led to a total inhibition of the LDH and MDH enzyme systems in vitro, but did not affect the IDH, GAPD and G-6-PD systems. However, when KCN was added before or after the addition of 1.0 mM paraquat to the test systems for IDH, GAPD or G-6-PD the inhibitory effect of paraquat was reversed and the reaction rates returned to normal or almost normal. Paraquat (1.0 mM) had no effect on the nicotinamide-adenine dinucleotide-dependent microsomal respiration, and no basic differences were noted between the responses of rat and rabbit lung microsomes exposed to paraquat in vitro.
- ItemThe effect of paraquat on the incorporatipon of 14C-leucine and 14C-palmitate into lung proteins and lung lipids of rats and rabbits(Health & Medical Publishing Group, 1981) Engelbrecht, F. M.; Rossouw, D. J.; Nienaber, M. W. P.The results of this comparative study show that paraquat added in vitro inhibited lipid and protein biosynthesis by lung slices from rats and rabbits during the first 2 hours of incubation. This inhibition was maintained in spite of an increased oxygen uptake and pentose pathway activity during this period. Paraquat (1 mM) added in vitro caused significant inhibition of 14C-leucine and 14C-palmitate incorporation into the soluble proteins and total lipids respectively of rat and rabbit lung slices. The effect of paraquat (27 mg/kg) administered intraperitoneally to rats and rabbits and assessed on the rate of 14C-leucine incorporation in vitro 24 hours after injection, also showed a significant inhibition. However, after 48 hours, protein synthesis was stimulated in rat lungs, whereas paraquat had no effect on rabbit lungs. A highly significant suppression of the rate of14C-palmitate incorporation 24 hours after intraperitoneal injection of paraquat was found with rat lung slices, whereas with rabbit lung slices the degree of inhibition was not significant. Forty-eight hours after injection a highly significant inhibition was maintained in rat lung slices while rabbit lung slices showed no inhibition. This finding points to a species difference in the effect of paraquat on metabolic processes and may explain the resistance of rabbit lung to damage by paraquat.
- ItemDie effek van steroied-terapie op die sitologiese en histopatologiese veranderinge tydens eksperimentele ekstrinsieke allergiese alveolitis (hipersensitiwiteitspneumonitis)(Health & Medical Publishing Group, 1981) Rossouw, D. J.; Chase, C. C.; Scheepers, J. C. E.Acute extrinsic allergic alveolitis was experimentally induced in rabbits using horseradish peroxidase (HRP) as antigen. Bronchoalveolar lavage was performed on the excised lungs and total and differential cellular yields determined, and correlated with the histopathological changes in the lungs as well as the total and differential white blood cell counts. After a single parenteral immunization with HRP without adjuvants, and weekly aerosol challenges with nebulized HRP solution for 3 consecutive weeks, a 3-fold increase in the total cell count as well as very pronounced rise in the percentage of lymphocytes was noticed. Histopathologically, the bronchi-associated lymphoid tissue dw-3 (BALT) became more prominent, an increase in the number of foreign body giant cells was noticed and a focal interstitial and intra-alveolar accumulation of lymphocytes, granulocytes and macrophages could be demonstrated, as well as a mild hyperplasia of type 2 alveolar epithelial cells. Intramuscular injections of methylprednisolone acetate (Depo-Medrol) every 72 hours induced a pronounced peripheral lymphopenia, thymic involution and an almost complete disappearance of the BALT in both the control and HRP-challenged rabbits. Similarly, a marked decrease in the total cell count and percentage of lymphocytes was noticed in the broncho-alveolar fluid of the animals with hypersensitivity pneumonitis. No signs of interstitial or intra-alveolar reactions were seen in the lungs of the experimental animals after 3 weeks of aerosol antigen challenge when treated with steroids. Collectively, these data suggest that the development of hypersensitivity pneumonitis was, at least in part, due to a cell-mediated immunological reaction in the lung. This animal model in which steroid suppression of experimental allergic alveolitis has been demonstrated, may be employed to elucidate the cellular pathogenesis of this disease process.
- ItemExperimental paraquat poisoning : histological, electron microscopic and autoradiographic changes in the lung(Health & Medical Publishing Group, 1984) Rossouw, D. J.; Chase, C. C.; Engelbrecht, F. M.Paraquat is a potent and widely used herbicide which acts as a specific pulmonary toxin and causes lung fibrosis in man and animals. Some controversy still exists concerning the details of the morphogenesis of the pulmonary lesions. The lungs of rats exposed to intravenous injections of paraquat and sacrificed 6 - 24 days later were examined by light and electron microscopy. Autoradiography was used to detect possible paraquat accumulation in the lung 5 hours after a single intravenous injection. The findings on microscopy suggested an acute phase of damage to alveolar lining epithelium followed by epithelial regeneration. The most pronounced light and electron microscopic findings were: (1) signs of disruption of the alveolar wall; (ii) type II alveolar epithelial hyperplasia; (iii) mobilization of mononuclear cells, and (iv) migration and accumulation of fibroblast-like cells in the intra-alveolar and interstitial spaces. After three equally spaced intravenous injections of paraquat signs of interstitial connective tissue proliferation could be seen. Autoradiography showed low-grade radioactivity over the alveolar wall, indicating possible active uptake of paraquat by alveolar epithelium; this coincides with in vitro evidence of an active transport mechanism for paraquat by alveolar epithelial cells.
- ItemThe influence of paraquat on the in vitro oxygen consumption of rabbit lung(Health & Medical Publishing Group, 1978) Rossouw, D. J.; Engelbrecht, F. M.The effects of paraquat on the aerobic metabolism of rabbit lung slices were investigated. The oxygen consumption of lung slices was examined at different oxygen tensions and in the presence or absence of glucose as substrate in a Krebs-Ringer phosphate medium. In an air phase, the oxygen consumption of control lung tissue with glucose in the medium was practically the same as the oxygen consumption without glucose over a 3-hr period. In a 100% oxygen phase, glucose induced a marked increase in oxygen uptake, which persisted for about 2 hours. Thereafter, a decrease occurred in oxygen consumption which was notably faster than of lung tissue without added glucose. With 10 mM glucose in the medium, paraquat (10-5 M and 10-3 M) immediately stimulated the oxygen consumption of lung slices. Although the initial increase in aerobic metabolism seemed to be glucose-dependent, the secondary inhibitory effect of paraquat appeared to be of the same magnitude in the presence or absence of glucose. Both the initial stimulation as well as the secondary inhibition were much more pronounced in a 100% oxygen atmosphere than in an air phase. These results indicate that the rabbit lung is sensitive to paraquat toxicity in vitro, and confirm that oxygen and paraquat supplement each other's toxicity in the lung.
- ItemA nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part III. Clinical pathology and pathogenesis(Health & Medical Publishing Group, 1985) Joubert, J. R.; King, J. B.; Rossouw, D. J.; Cooper, R.Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in 8 patients; 7 were staff members at Tygerberg Hospital who had been infected by a patient in whom the disease had not initially been diagnosed. Two patients, the initial case and a staff member, died and 4 became seriously ill. The immunopathogenesis of CCHF appears to be multifactorial. Certain features were common to all patients - leucopenia, thrombocytopenia, elevated liver enzyme values and low serum total protein levels. Ultrastrucutral changes in and around skin capillaries, including intracytoplasmic endothelial tuboreticulated bodies, were found. Virus-like particles were found on electron microscopy. Important individual factors related to prognosis were identified. The patients who survived all mounted a good antibody response, and manifested no coagulation defect extensive enough to explain the haemorrhagic tendency. In the patients who died no evidence of antibody production was detected; both developed diffuse intravascular coagulation and in 1 evidence of immune complex formation and complement consumption was found. Hepatorenal failure and cardiovascular collapse characterized the terminal period. Early clinical recognition of CCHF with specific attention to factors amenable to treatment may vastly improve the prognosis.
- ItemThe role of the endothelium in the reduction of restenosis following balloon angioplasty(Clinics Cardive Publishing, 1998-10) Davids, MR; Page, C.; Muller, C. J.; Rossouw, D. J.; Doubell, A. F.Objective. Coronary angioplasty is complicated in one-third of cases by restenosis due to intimal hyperplasia. This is the result of the migration and proliferation of vascular smooth-muscle cells (SMCs) and correlates with the extent of endothelial stripping. To study the effect of rapid re-endothelialisation on preventing intimal hyperplasia, a model of vessel injury is needed which allows for the retention and adhesion of cultured vascular endothelial cells (VECs) in the injured segment. Methods. The abdominal aortas of BD9 rats were injured with an embolectomy catheter and the response to injury assessed on days 1, 3, 7, 14 and 28. Cultured vascular endothelial cells (VECs) were then placed into injured vessels. Introduction of 51Cr-labelled cells was used first-to confirm adhesion, and then unlabelled cells were used to study the effect on intimal hyperplasia. Results. Medial necrosis and complete stripping of the endothelium was seen on days 1 and 3. By day 7 all rats had VECs lining part of the lumen. Intimal hyperplasia was present by day 14. Complete restitution of the endothelium was present at day 28 and medial SMC numbers were also back to normal at this time. Cells producing the intimal hyperplasia were identified as SMCs by staining for smooth-muscle actin and electron microscopy. Re-endothelialisation was confirmed by autoradiography following introduction of 51Cr-labelled VECs. In animals receiving VECs after injury (N = 15), intimal hyperplasia involved a smaller percentage of the lumen circumference compared with controls (N = 15), where only medium was introduced (52.00 ± 6.83% v. 63.47 ± 6.39%; P = 0.03). Conclusion. The response to balloon-induced injury in the rat aorta has been well characterised. This model enabled us to repopulate a damaged vessel with cultured VECs, resulting in a decrease in intimal hyperplasia.
- ItemSerum cholesterol and dietary data in middle aged white males(Health & Medical Publishing Group, 1977) Rossouw, D. J.; Engelbrecht, F. M.; Fourie, J. J.; Van Heerden, L. E.The mean daily dietary intake of normocholesterolaemic subjects (serum cholesterol less than 250 mg/100 ml) was compared with that of hypercholesterolaemic subjects (250 mg/100 ml or higher). Apart from a higher polyunsaturated fatty acid (PUFA) intake in the hypercholesterolaemic group, no other significant differences could be demonstrated between the two groups. Simple linear correlation coefficients (r) were calculated for the total sample, and the positive correlation (r = 0,29) between the serum cholesterol and the percentage of kilojoules derived from PUFA, was the only dietary variable to reach a statistically significant value (P<0.05). A stepwise regression analysis was used to calculate a multiple regression relationship (R2) between the dependent variable and the dietary variables. The results showed PUFA, total protein and saturated fatty acids (SFA) to have the highest cumulative influence on the serum cholesterol concentration. Only 29% of the variation in the serum cholesterol could be explained by the first 6 of 30 dietary variables tested in this survey. It was concluded that the small differences in the nutritional status among individuals from homogenous sample populations as well as the fact that non linear relationships would not be reflected in the correlation coefficient, make it difficult to establish significant relationships between the dietary data and serum cholesterol concentration.