Browsing by Author "Engelbrecht, F. M."
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- ItemBeneficial effects of adenosine triphosphate-MgC12 administered intravenously to rabbits subjected to haemorrhagic shock(Health & Medical Publishing Group, 1986-10) Engelbrecht, F. M.; Mattheyse, F. J.ENGLISH ABSTRACT: The beneficial effects of adenosine triphosphate (ATP)-MgCl2 administered as a bolus following fluid infusion or in combination with the infusion fluid were investigated in rabbits subjected to severe but reversible haemorrhagic shock. ATP-MgCl2 treatment led to a significant improvement of the metabolic functions of lung and liver tissue. Kidney tissue showed the same tendency, but the improvement did not reach significant levels. The release of lysosomal enzymes in vivo was retarded after treatment but not stopped. The mean arterial pressure was kept at a relatively constant level when ATP-MgCl2 was infused slowly. Administration as a bolus resulted in an immediate dramatic drop in pressure, followed by recovery and then a gradual decrease to levels which appeared to be incompatible with survival.
- 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 incorporation of radiolabelled proline into acid-extractable lung proteins and collagens(Health & Medical Publishing Group, 1982) Engelbrecht, F. M.; Windt, M.-L.; Maree, E.; Nienaber, M. W. P.In this comparative study the authors describe the influence of paraquat on the rate of L-2,3-3H proline incorportion into the acid-extractable proteins and into newly synthesized protropocollagen molecules from the lungs of rats and rabbits. Exposure to paraquat took two forms: (a) addition of paraquat in vitro to lung tissue taken from rats and rabbits, and (b) intraperitoneal injection of paraquat prior to death. Paraquat (0,5-1,0 mM) added in vitro significantly slowed the rates of 3H-proline incorporation into the acid-extractable proteins and into newly synthesized protropocollagen in both rat and rabbit lung tissue. Paraquat administered intraperitoneally (27 mg/kg) to rabbits did not markedly influence the rate of 3H-proline incorporation into acid-extractable proteins and collagen assessed in vitro 24, 48 and 96 hours after injection. Paraquat injected intraperitoneally into rats induced no significant difference in synthesis rates of acid-soluble proteins up to 48 hours after injection. During the same period, the collagen synthesis rate of rat lung tissue was reduced. At 96 hours an increase was found when the rate of synthesis was expressed as cpm/mg DNA and as cpm/μg hydroxyproline.
- 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.
- ItemExperimental evaluation of the prophylactic and therapeutic effects of hydrocortisone in haemorrhagic shock(Health & Medical Publishing Group, 1985) Engelbrecht, F. M.; Mattheyse, F. J.; Mouton, W. L.The prophylactic and therapeutic effects of hydrocortisone (50mg/kg) in severe haemorrhagic shock were evaluated by metabolic, biochemical and haematological investigations in a rabbit model. It was found that administration of hydrocortisone prior to severe haemorrhage had no beneficial effect on any of the values measured. Owing to haemoconcentration and marked mobilization of leucocytes it would appear that in pretreated animals the magnitude of the hypoxia was increased and led to greater tissue damage and higher levels of lysosomal enzymes than in rabbits which had not received pretreatment with hydrocortisone. On the other hand, hydrocortisone therapy combined with volume replacement 1 hour after the haemorrhagic insult had several beneficial effects. The metabolic capacity of liver and kidney tissues was improved, the lysosomal concentration remained within normal limits, and normal limits, and the mean blood pressure and pulse pressure were maintained better than in controls. However, it would appear that this beneficial effect is only exerted on tissue still in a reversible state of shock. There is therefore no beneficial effect on lung tissue metabolism, the lungs being more sensitive to hypoxic damage than either liver or kidney tissue. Administration of hydrocortisone results in the immediate release of endotoxins into the circulation. This might be due to its vasodilatory action on the microcirculation of the intestinal viscera.
- 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.
- ItemHaemorrhagic shock : metabolic parameters for the assessment of damage in lung, liver and kidney tissue(Health & Medical Publishing Group, 1984) Engelbrecht, F. M.; Mattheyse, F. J.; Mouton, W. L.Changes in catabolic and biosynthetic parameters measured in vitro were used as criteria to assess the degree of damage in tissues after an animal was exposed to severe haemorrhagic shock for periods of 1 and 2 hours (blood loss 36.8%, blood pressure 30 ± 5 mmHg). The biosynthetic capacity of lung tissue, as determined by the incorporation of 1-14C-palmitate into total lung lipids, declined significantly with time. This reduction correlates well (r = 0.99) with the rate of decline in 14CO2 production from 1-14C- and 6-14C-glucose oxidation as well as with the decline in the rate of oxygen uptake. Any one of these parameters could therefore be used as an index of the degree of tissue damage due to haemorrhagic shock. Comparing the rates of decline in 14CO2 production from 1-14C-glucose by lung, liver and kidney tissue from the same animal after haemorrhagic insult for 1 hour, lung tissue appeared to be the most sensitive to hypoxia and kidney the least so. However, 2 hours after severe haemorrhage, i.e. near the terminal phase, the rate of 14CO2 production from 6-14C-glucose by liver tissue decreased dramatically by more than 53% of the control value. Apart from kidney and lung dysfunction, irreparable liver damage probably plays a major role in the fatal course of severe haemorrhage.
- 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.
- ItemDie kliniese belang van fosfolipiede longpatologie(Health & Medical Publishing Group, 1981) Van Papendorp, D. H.; Engelbrecht, F. M.The phospholipid composition of 35 human lungs with pathological lesions was analysed by means of thin-layer chromatography and densitometric scanning. The pathological conditions studied were: bronchopneumonia, myocardial infarction, chronic heart failure, chronic obstructive airway disease and tuberculosis. The phospholipid composition was compared with that of a control group consisting of sudden death cases (due to unnatural causes), i.e. relatively normal lungs. The phospholipid composition of the lungs in a specific pathological group showed the same pattern. However, significant differences were observed between corresponding phospholipid fractions from lungs in the various pathological groups. Compared with the lipid fractions from relatively normal lungs, these differences were even more marked. From the results it would appear that the abnormal composition of the phosholipid fractions might possibly be a cause of lung pathology. The increase and/or decrease in individual fractions and abnormal ratios between fractions might indicate abnormalities in the biosynthesis and catabolism of the lung phospholipids. Further research is necessary to elucidate the association of phospholipids with lung pathology. Phospholipid analysis of lung lavages and lung biopsies could be helpful in the diagnosis of lung diseases. Phospholipids in aerosol form could perhaps be used in treating certain lung disorders.
- ItemMesothelial reaction to asbestos and other irritants after intraperitoneal injection(Health and Medical Publishing Group (HMPG), 1975) Engelbrecht, F. M.; Burger, B. F.Ten groups of rats were injected intraperitoneally with one of the following suspensions; standard reference crocidolite; acid treated crocidolite; crocidolite + iron oxide; crocidolite + silica; iron oxide; silica; long fiber crocidolite; short fiber crocidolite; long fiber glass and short fiber glass. Two rats from each group were killed at 45, 90, 150, 240 and 330 days respectively, and the pathology induced by the different suspensions was studied histologically at each time interval. No evidence in support of the chemical induction theory of mechanical irritation theory in the pathogenesis of peritoneal mesotheliomas could be found, although all the suspensions except iron oxide caused a reactive mesothelium.
- ItemMetabolic changes in the lungs after ischaemia(Health & Medical Publishing Group, 1980) Engelbrecht, F. M.; Edwards, I. J.; De Beer, D. P.The effects of variable periods of ischaemia on the isolated lungs of rats and rabbits, stored for up to 6 hours at 4°C, 21°C and 37°C under standardized conditions, were investigated in vitro in terms of oxygen consumption, the rate of 1-14C-leucine incorporation into soluble proteins, and 1-14C-palmitate incorporation into total phospholipids and lipid fractions. The endogenous oxygen uptake of rat lung slices in an air phase, from tissues stored at 4°C and 21°C under ischaemic conditions for 6 hours and at 37°C for 4 hours, was significantly different from the control values. The oxygen uptake of lungs from animals anaesthetized with pentobarbitone prior to exsanguination and stored for only 2 hours at 37°C differed significantly from control values. Judged by the rate of incorporation of radiolabelled leucine into soluble proteins and that of palmitate into total lipids and phospholipids of lungs after storage for increasing periods at 4°C and 37°C, significant differences were already found after 1 1/2 hours. From this observation it would appear that these parameters are very sensitive indicators for assessing irreversible lung damage due to ischaemia.
- 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.
- ItemShock lung : experimental studies on a haemorrhagic hypovolaemic rabbit model(Health & Medical Publishing Group, 1983) Engelbrecht, F. M.; Mouton, W. L.; Van Schalkwyk, L. J.An experimental model of haemorrhagic hypotension was standardized using rabbits to investigate the shock lung syndrome over a period of 120 minutes. Acute hypovolaemia was induced by withdrawal of blood under anaesthesia to a mean arterial pressure of 30 ± 5 mmHg within 10 minutes. The mean leucocyte counts and the release of lysosomal enzymes (acid phosphatase and β-glucuronidase) in the blood and in lung tissue, as well as the metabolic capacities of lung tissue in terms of protein and lipid biosynthesis, were investigated at set intervals after 30, 60, 90 and 120 minutes. The results indicate a progressive decline in leucocyte numbers over 120 minutes to about 40% of the original. An immediate granulocytopenia was observed with a relative lymphocytosis within 30 minutes. The β-glucuronidase and acid phosphatase contents of the plasma increased with time; β-glucuronidase activity increased progressively as leucocytes disappeared from the circulation. Concomitantly, the capacity of the lung tissue to synthesize protein and lipids was retarded with time, becoming significantly lower than baseline values after 60 minutes of hypovolaemia. The decline in leucocyte numbers in the circulation correlated well with the increase in β-glucuronidase activity and the retarded metabolic capacity of the lung tissue.