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Biomedical subjects

F M Engelbrecht

Publications and source records attributed to F M Engelbrecht.

At least 19 recordsLinked to original sources

Beneficial effects of adenosine triphosphate-MgCl2 administered intravenously to rabbits subjected to haemorrhagic shock.

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.

Adenosine Triphosphate

Beneficial effect of naloxone on in vitro tissue metabolism after hemorrhagic shock.

A rabbit model of hemorrhagic shock is used in assessing the use of naloxone as an adjunct in the treatment of hemorrhagic shock. In vitro oxidation rates of labelled glucose are used as parameters of early tissue damage. Naloxone, given as an adjunct to volume replacement, significantly improves the in vitro capabilities of lung and liver tissues, but has no effect on kidney cortex. Changes in MABP are not affected by naloxone in this rabbit model, and serum lysosomal enzyme activity is not significantly improved. It is proposed that naloxone exerts some of its beneficial effect at the cellular level.

Animals

Experimental evaluation of the prophylactic and therapeutic effects of hydrocortisone in haemorrhagic shock.

The prophylactic and therapeutic effects of hydrocortisone (50 mg/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 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.

Animals

Experimental paraquat poisoning--histological, electron microscopic and autoradiographic changes in the lung.

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: signs of disruption of the alveolar wall; type II alveolar epithelial hyperplasia; mobilization of mononuclear cells, and 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.

Animals

Shock lung--experimental studies on a haemorrhagic hypovolaemic rabbit model.

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 beta-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 beta-glucuronidase and acid phosphatase contents of the plasma increased with time; beta-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 beta-glucuronidase activity and the retarded metabolic capacity of the lung tissue.

Acid Phosphatase

The effect of oxygen and paraquat on the 14C-glucose oxidation of rabbit alveolar macrophages and lung slices.

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 contorol 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 (1,0 mM) 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 and 1-14C-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 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-aveolar pulmonary lesions described in the literature.

Animals

The effect of paraquat on the aerobic metabolism of rabbit alveolar macrophages and lung fibroblasts.

In this study the effects of paraquat on the aerobic metabolism and viability of isolated rabbit alveolar macrophages and lung fibroblasts were investigated, and compared with the effects of other known metabolic inhibitors, i.e. sodium fluoride (NaF) and potassium cyanide (KCN). The manometrically and polarographically determined endogenous oxygen consumption of lavaged alveolar macrophages compared very well (180,9 +/- 35,8 and 169,3 +/- 26,8 nmol per 10(6) viable cells per hour respectively). Exogenous glucose (10 mM) and autologous serum (1:3 v/v) added to the medium had no significant effect on the basal respiration rate. The mean cell protein content, determined by the micro-Kjeldahl and Lowry techniques, amounted to 242,6 +/- 37,6 microgram/10(6) macrophages. Paraquat (2 mM), like NaF (20mM) and KCN (5 mM), decreased the viability of the macrophages far less than it did the oxygen utilization of the viable cells, and resulted in an 80% inhibition of oxygen uptake. In contrast, paraquat (1 mM) induced a marked stimulation (230%) of the cyanide-insensitive respiration of alveolar macrophages. The concentrations of paraquat (nmol/10(3) cells) which reduce macrophage metabolism to almost zero were virtually non-toxic to fibroblasts, as measured by their oxygen consumption.

Animals

The effect of paraquat on the respiration of lung cell fractions.

The in vitro effects of paraquat on the aerobic metabolism of lung and liver homogenates, as well as on the oxygen consumption of isolated rat and rabbit lung mitochondria, were investigated. It was found that the endogenous oxygen uptake of a 40% lung homogenate was similar to that of a 10% liver homogenate, and that succinate (20 mM) was well oxidized by both homogenates. About 14% of the basal respiration rate was due to cyanide-insensitive oxidative systems in lung and liver homogenates. Paraquat (1 mM and higher concentrations) induced an acute and highly significant increase in the cyanide-insensitive oxygen utilization. We were able to recover about 5% of the protein in the supernatant (1,000 g) of the original homogenate as mitochondrial protein. Only results obtained from mitochondrial preparations with a respiratory control ratio between 2,7 and 3,3 were used in the final analyses, and the normal state 3 respiration values of rabbit and rat lung mitochondria were 45,2 +/- 5,3 and 38,7 +/- 2,9 nmol oxygen per mg protein per minute respectively. Paraquat in concentrations up to 0.5 mM had no significant effect, but higher concentrations up to 1 mM induced a highly significant inhibition of mitochondrial oxygen consumption. When slices were pre-incubated with 1 mM and with 0,01 mM paraquat in the incubation medium, the oxygen consumption of the mitochondria isolated after 2 hours and 4 hours respectively, was significantly reduced.

Aerobiosis

The influence of paraquat on the in vitro oxygen consumption of rabbit lung.

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-hour 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 that 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.

Animals

The adrenal cortex in hypercholesterolaemic rabbits: histochemical and electron microscopical changes.

The adrenals of rabbits on a cholesterol-rich diet for 35 days show histopathological changes, a marked increase in weight and a lowering in the ascorbate content. A focal increase in the neutral lipid and cholesterol content was noted mostly in the inner cortical zones; and a characteristic acid phosphatase-positive pattern in areas of infiltrating cells, and an alkaline phosphatase-positive reaction in heterophils in the infiltrated areas. Electron microscopy confirmed that the zona glomerulosa cells were relatively normal in hypercholesterolaemic rabbits, while necrosis and fibrosis were very obvious in the inner two zones. The cellular infiltrate was shown to consist of large, granular mononuclear cells, heterophils, eosinophils, stromal phagocytes, lymphocytes and plasma cells. The possibility that the reaction was of an immunological nature is considered. The morphology of the adrenals of rabbits which were on a cholesterol-rich diet for 35 days and on a normal diet for 6 weeks afterwards, was indistinguishable from that of those rabbits killed after 35 days on a cholesterol-rich diet.

Acid Phosphatase

Serum cholesterol and dietary data in middle-aged white males.

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 less than 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.

Adult

The histochemical localization of cholesterol in formalin-fixed and fresh frozen sections.

The premixed cholesterol reagent (acetic acid, sulphuric acid, ferric chloride and phosphoric acid) employed in a spectrophotometric method for serum cholesterol determinations was applied to frozen sections of various rat and rabbit tissues. The histochemical reaction was compared with the results obtained by the classical Schultz reaction. The same bluish-green color was observed after treatment of formalin-fixed and fresh cryostat sections incubated in 2.5% iron alum at 37 C for 3 days. The premixed cholesterol reagent is stable for years at room temperature if stored in a brown bottle and is thus readily available for routine use.

Adrenal Glands

Mesothelial reaction of asbestos and other irritants after intraperitoneal injection.

Ten groups of rats were injected intraperitoneally with one of the following suspensions; (i) standard reference crocidolite; (ii) acid-treated crocidolite (iii) crocidolite plus iron oxide; (iv) crocidolite plus silica; (v) iron oxide; (vi) silica; (vii) long fibre crocidolite; (viii) short fibre crocidolite; (ix) long fibre glass and (x) short fibre 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 or mechanical irritation theory in the pathogenesis of peritoneal mesotheliomas could be found, although all the suspensions except iron oxide caused a reactive mesothelium.

Animals