Sporidesmin toxicity in rabbits: biochemical and morphological changes

The earliest lesion in rabbits dosed orally with 2 mg of sporidesmin per kg of body weight was necrosis of occasional hepatocytes 1 day after dosing. The most consistent lesion was a severe necrotizing cholangitis of medium and large-sized intrahepatic and extrahepatic bile ducts, first seen 2 days after dosing. Similar lesions were also present in the gall bladder of some rabbits. Expansion of portal triads with fibrous tissue and proliferating bile ductules progressed to pseudo-lobulation by 21 days. Other hepatic changes observed irregularly included large infarcts at the periphery of some lobes, and multiple small foci of coagulation necrosis in midzonal and periportal regions. Vascular necrosis and thrombosis, invariably adjacent to necrotic bile ducts, was presumably responsible for the hepatic necrosis. Serum cholesterol and total bilirubin concentrations and GGT activity reached peaks 15 days after dosing and were useful indicators of the severity of biliary lesions. Serum ID activity was the most useful indicator of hepatic necrosis following oral dosing with sporidesmin. The similarity between hepatobiliary lesions observed in sheep and rabbits with experimental sporidesmin toxicity suggests that the rabbit would be a useful model for studying methods of treatment and prevention of "facial eczema" in ruminants.     

Aging of liver: morphological and biochemical changes

Light-microscopically there are no significant age-dependent changes in the liver, due to the slight increase in biochemically determined connective tissue components. Electron-microscopical comparison of young and old animals show a larger size and decreased numbers of liver cell mitochondria in older animals. Collagen synthesis in liver is accelerated during growth, as demonstrated by assay of the [3H] proline incorporation rates and of the specific activity of hydroxyproline, corresponding to a decrease in the prolyl hydroxylase activity with age. The neutral salt-soluble collagen fraction may be regarded as a parameter for collagen synthesis, which is activated during the growth period and then remains constant without age and sex differences. Not much is known about the significance of these changes with increasing age or about their initiating factors, although there are parallel findings for liver intoxication and inflammation.     

Articular cartilage changes in experimental osteoarthritis in rabbits: MRI and morphological findings

The objective of the present study was to determine the magnetic resonance imaging (MRI) and gross pathological findings of articular cartilage in osteoarthritis experimentally induced in rabbit as an animal model. Ten adult Dutch male rabbits were randomly divided into two equal groups. In group one, in the left knee (stifle), the cranial (anterior) cruciate ligament (CCL) was sectioned [transected group (TG)], and in the second group, only arthrotomy was performed through the same approach, but the CCL was left intact [arthrotomy group (AG)]. In both groups, the right knees were considered as controls. Thirty days after operation, MRI was performed under general anesthesia, and then the animals were sacrificed for gross pathological study. MRI was performed by a 1.5-T scanner with a wrist coil to evaluate the coronal and sagittal gradient echo T2-weighted proton density and T1- and T2-weighted sequences. A magnification loupe was used to inspect the menisci, femoral and tibial cartilages, and synovium. The results revealed that the measured mean articular cartilage thickness by MRI was less in TG in comparison to AG and control groups (p < 0.05), whereas the difference between AG and control was not significant. Statistical analysis of the results revealed that the measured mean articular cartilage thickness by MRI was less in TG than those of AG and control groups, whereas the difference between AG and control was not significant. There were no significant differences in meniscal degeneration, joint effusion, and MRI overall grades between AG and the control groups. The difference was significant between TG with AG and the controls in relation to MRI findings. The gross examination revealed that there were no gross abnormalities in AG but there were also significant differences between the TG and AG, and between TG and the controls. Changes were localized primarily to the distal aspect of the medial femoral condylar cartilage. It was concluded that the MRI findings in early osteoarthritis process consisted of articular cartilage loss and meniscal degeneration. The quantitative alterations in articular cartilage thickness measured by MRI can be a noninvasive way to predict osteoarthritis. The MRI findings were also well correlated with the results of pathological study.     

Correlation between morphological heterogeneity and genetic alteration within one tumor in adenocarcinomas of the lung

In some human cancers, multistep carcinogenesis has been advocated on the basis of morphological and genetic analysis. In adenocarcinoma of the lung, a carcinogenetic process from atypical adenomatous hyperplasia (AAH) to bronchiolo-alveolar carcinoma (BAC) and/or more malignant adenocarcinoma has been recently suggested. In the present study, we selected 13 lung tumors which had AAH-like or BAC-like areas at the periphery, and poorly differentiated areas at other sites, and examined their loss of heterozygosity (LOH) on chromosome 3p, 9p and 17p and point mutation of the p53 gene. A heterogeneous pattern of LOH and/or point mutation of the p53 gene was detected in five of 13 cases, and genetic alterations were frequent in the areas of poorer differentiation. These findings suggest that some adenocarcinomas of the lung occur through multistep carcinogenesis.     

Correlation among lung damage after radiation, amount of lipid peroxides, and antioxidant enzyme activities

The correlation between lipid peroxidation and morphologic changes was examined in Sprague-Dawley rat lungs after 30 Gy single thoracic radiation. The rats were sacrificed every week until the end of the fifth week after radiation. The left lungs were used for the measurement of lipid peroxides and antioxidant enzymes activities. The right lungs were examined by light and electron microscopy. Amounts of lung lipid peroxides were within normal limits, and no cellular degenerative changes were observed in the lungs except for subendothelial and interstitial edema 2 weeks after radiation. Lipid peroxides drastically increased and marked degenerative cellular changes such as edematous swelling, vacuolation, and destruction of cell membranes occurred in the alveolar septa following the third week after radiation. The activities of catalase were significantly higher during the period from the second to the fifth week and those of superoxide dismutase and glutathione peroxidase increased at the end of the fifth week. Our results demonstrated that the acceleration of lipid peroxidation was well correlated with the morphologic expression of cell injury in the irradiated lungs.     

Rheumatoid arthritis cells and biochemical changes in turpentine-induced pleuritis in rabbits

When turpentine was instilled into the right pleural cavity in rabbits a pleural effusion developed in half of the animals, with a low pH, low glucose concentration, high lactic dehydrogenase activity and the constant presence of rheumatoid arthritis cells in the affected pleural cavity. The biochemical values in the pleural fluid were significantly different from the values for normal pleural fluid obtained by a special microtechnique. These changes resulting from the experimentally induced, simple, irritative turpentine pleuritis are similar to the findings in the pleural effusion in human rheumatoid pleuritis; this implies that such changes are probably non-specific and without evidence of an immunological background.     

Severe acute oxidant exposure: morphological damage and aerobic metabolism in the lung

Groups of male rats were exposed to acute doses of oxygen, ozone, or paraquat which produced equivalent mortality (25-30%) over a 28 day post-exposure period. Quantitative evaluation of morphological changes indicated the primary response to be edema and inflammation with only slight fibrosis being apparent by the end of the observation period. Aerobic pulmonary metabolism was inhibited in lungs from animals exposed to oxygen and ozone as evidenced by decreased oxygen consumption; however, this was transient and O2 consumption returned to normal within 24 hours after removal from the exposure chamber. Conversely, treatment with paraquat caused an immediate, transient stimulation of O2 consumption. Glucose metabolism was unaltered by the gas exposures and, as previously reported, was initially stimulated by paraquat treatment. In vitro, only paraquat altered both O2 consumption and glucose metabolism when added to lung slice preparations; ozone had no effect. Oxygen did not alter O2 consumption but caused a slight biphasic response in glucose metabolism. Aerobic metabolism is relatively unchanged by these doses of oxygen and ozone which result in the death of 25-30% of all treated animals. Even though paraquat produces similar morphologic changes, it may represent a more severe metabolic insult than "equivalent" doses of oxygen or ozone. Also, if interstitial pulmonary fibrosis is a desired result of experimental exposure, rats may not be a suitable model for oxidant induced lung injury.     

Correlation between biochemical tests, parameters of drug elimination and hepatic enzyme induction in chronic liver diseases

The biochemical liver function tests form an integral part of diagnostic practice in hepatology. In this study the parameters suited for the estimation of drug elimination and of the induced state of the liver, thus the excretion of D-glucaric acid, of menthol glucuronide and the parameters of antipyrine and sulphadimidine kinetics were correlated with the results of biochemical laboratory tests in patients with chronic liver disease. The aim was to establish universally valid quantitative correlations between the above results. Multiple relationships were revealed, but generally valid correlations for the group of liver diseases occurred only in special relationships (serum albumin level and antipyrine T1/2; serum bilirubin level and sulphadimidine T1/2). The results have been evaluated from the methodological aspect to work out an appropriate dosage regime in liver diseases.     

The mechanical, enzymatic and morphological changes in acute pulmonary insufficiency following the production of a haematoma in rabbits.

The production of a haematoma in the hindleg of rabbits represents a simplification of post-traumatic models. The lungs, one of the target organs, show similar micromorphological alterations to those described in traumatised human beings. The lungs of rabbits, bearing a hindleg haematoma for 24 hr, showed a significantly increased incidence of micromorphological lung alterations compared to the control group. Moreover, measurement revealed a significantly decreased lung compliance within the haematoma groups. It was demonstrated that whether the haematoma was subcutaneous or intramuscular, similar alterations were seen in lung histology, and in lung compliance values. Studies on the activity of superoxide dismutase in lung tissue homogenates demonstrated a significant decrease in those rabbits having had a haematoma intramuscularly for 24 hr.     

Regulation of erythrocyte antioxidant enzyme activities in athletes during competition and short-term recovery

We have determined "in vivo" the influence of strenuous prolonged exercise and short-term recovery on erythrocyte antioxidant enzyme activities. We have also determined the "in vitro" effects of the xanthine/xanthine-oxidase-generating superoxide anion system on catalase activity in haemolysed erythrocytes. Haematological parameters and erythrocyte superoxide dismutase (SOD), glutathione peroxidases and catalase activities were measured in nine healthy duathlon athletes under basal conditions, at the finish of a competition and after 1 h of recovery. We also measured catalase activity in haemolysed erythrocytes--obtained from four overnight-fasted well-trained sportsmen before and after an 80% submaximal exercise test on a cycle-ergometer--prior to and after incubation for 3 min with the superoxide-anion-generating system. Duathlon competition and/or short-term recovery produced a slight haemolysis and increased the activity of catalase and peroxidases but not SOD enzymes. The observed changes in catalase activity were mimicked "in vitro" by the superoxide-anion-generating system.     

The relationships between ethnicity, gender, and short-term changes in energy balance following smoking cessation

Although weight gain is a well-established consequence of quitting smoking, the energy balance mechanisms responsible for postcessation weight gain are not clear. Furthermore, although gender and ethnicity are important predictors of postcessation weight gain, no studies have evaluated the effects of these variables on changes in energy balance. This study investigated short-term changes in energy balance following smoking cessation in 95 smokers. In as little as 2 weeks, smoking cessation was associated with a significant increase in body weight (1.05 kg). Smoking cessation was also associated with an increase in energy intake (1440 kJ/day), and no changes in energy expenditure (physical activity; resting energy expenditure, REE) were observed. Changes in body weight and energy balance did not differ by gender or ethnicity. Predictors of weight gain included baseline carbon monoxide (CO) level, baseline REE per kg of body weight, and changes in energy intake. These findings provide valuable information about the mechanisms responsible for at least the early stages of postcessation weight gain. Support for this study was providedby Grant No. HL46352 from the National Heart, Lung and Blood Institute.     

Comparison between developmental and senescent changes in enzyme activities linked to energy metabolism in rat heart

The developmental and senescent patterns of a number of heart enzyme activities linked to energy metabolism have been studied in rats aged between 4 days and 21 months. A morphometric study of mitochondrial volume fractions and numbers has been also carried out. Developmental changes result in a rise of most mitochondrial enzymes (NADP⁺-isocitrate dehydrogenase, malic enzyme, succinate dehydrogenase, citrate synthase) and mitochondrial volume fractions. Exceptions are NAD⁺-isocitarte dehydrogenase, which declines from 4 days onwards, and NAD⁺-malate dehydrogenase, which declines and then rises over the same period. Senescent changes follow two different trends. While pyruvate kinase and those mitochondrial enzymes lying between citrate formation and isocitrate oxidation (citrate synthase, NADP⁺- and NAD⁺-isocitrate dehydrogenases) decline to some degree, mitochondrial succinate dehydrogenase and NAD⁺-malate dehydrogenase activities increase over the same period. This could point towards a partial impairment of Krebs cycle function, and a reduced energy-producing capacity in the aged rat heart.