It has been suggested that superoxide radicals play an important role in the pathogenesis of gastric mucosal lesions after ischemia. To prove a participation of O-2 in gastric mucosal lesion formation, diethyldithiocarbamate (DDC), an inhibitor of Cu, Zn-super-oxide dismutase (SOD), was injected into rats and its ulcerogenicity was examined. Subcutaneous injection of DDC was employed, because of high mortality after intraperitoneal injection of the drug. At 7h after the injection of the drug, many ulcers appeared in the stomach, with suppression of SOD activities in the gastric mucosa, suggesting the participation of O-2 in ulcer formation in the stomach.
4-Aminopyrazolopyrimidine (4-APP)-induced fatty livers were analyzed biochemically and immunohistochemically. Biochemically, lipid peroxide levels measured by thiobarbituric acid method in the rat liver homogenates were markedly increased following 4-APP administration. However, glutathione peroxidase (GSH-PO) activity in the same homogenates was decreased. In addition, immunohistochemical localization of GSH-PO in 4-APP-treated rat liver was also decreased. Based on our data, we strongly suggested that pathogenesis of 4-APP induced-fatty liver may be due to uncontrolled free radical formation, peroxidation of lipids, and an associated lipid accumulation in the liver.
Effect of administration of active vitamin D3 on the histological changes of intestinal mucosa was studied in normal rats treated with 0.25 to 0.5μg of 1α(OH)D3 or 1α, 25(OH)2D3. Mucosal thickness, cell count and volume, mucosal mass, and nuclear size were morpho-metrically measured in the villi and crypts. In the villi, both 1α(OH)D3 and 1α, 25(OH)2D3 significantly increased the cell counts, moderately increased the thickness, and slightly increased the cell volume, compared with the control group. Neither agent had any effect on the crypts. Nuclear size in villi was increased only in the 1α, 25(OH)2D3 group.
Neurons containing CCK-8-like immunoreactive substance are present in the lateral part of the dorsal parabrachial nucleus (PBD) and project fibers to the ventromedial hypothalamus (VMH). The role of these neurons was examined by studies on the effect of electrical stimulation of the lateral part of the PBD on glucose metabolism in female Sprague-Dawley rats in the light and dark periods. PBD stimulation caused hyperglycemia, and the response was greater in the light period than in the dark. PBD stimulation also induced hypoinsulinemia and hyperglucagonemia, but only the hyperglucagonemic response differed in the light and dark periods like the hyperglycemic response. Thus the neural fibers from the PBD to the VMH may be involved in regulation of glucose metabolism by relaying messages to the VMH to control the reciprocal secretions of insulin and glucagon from the pancreas. Possible reasons why the hyperglycemic response to PBD stimulation was greater in the light period are discussed.
To understand the relevance of peptide release and absorption during protein digestion to its quality, digestibility of a few animal (AP) and plant proteins (PP) was studied in trained rats. Some differences were observed between proteins in their digestion in vivo and absorption (as assessed by recovery of fed nitrogen). We observed that rats fed AP diets had a greater proportion of peptides (total, large (P1) and small (P2) including dipeptides) in their jejunal luminal supernatants than those fed PP diets, which had a greater proportion of free amino acids (AA). AA fractions always had a higher essential amino acid (EAA) content than peptide fractions; and among peptide fractions, the P1 fraction had a greater content of EAAs than the P2 fraction. Protein quality was correlated positively with the proportion of peptides (total, P1, P2, and dipeptides) in the jejunal luminal supernatants and negatively with that of AAs. Incorporation of some of these in vivo digestion indices increased the correlation between chemical and animal growth indices of protein quality, suggesting their relevance to protein nutritional quality.
Lipid peroxide levels in rat hippocampus and cortex were determined at 6, 24, and 48h following ischemia for a period of 20min. A significant (p<0.05) but transient increase in lipid peroxide formation was found in the hippocampus at 24h following ischemia. Regional iron concentration determined by inductively coupled plasma (ICP) emission spectrometry revealed that the concentration of iron in the hippocampus was also significantly elevated at 24h following ischemia, suggesting that in the hippocampus the increase in the concentration of iron resulted in promotion of lipid peroxidation. Though lipid peroxide and iron levels were reversed at 48h following ischemia, iron-dependent lipid peroxidation was possibly involved in the onset of delayed neuronal death in the rat hippocampus.
When 17β-estradiol was administered intraperitoneally to female mice, serum and liver lipid peroxide levels were significantly decreased, while in the case of male mice they only tended to decrease. On the other hand, the intraperitoneal administration of 2-hydroxyestradiol, a major metabolite of 17β-estradiol in the liver, brought about a decrease in liver lipid peroxide levels in both male and female mice. Accordingly, the remarkable effect of 17β-estradiol found in female mice seems to be ascribable to the 2-hydroxyestradiol formed in them.
Specimens were prepared from autopsied and biopsied human liver and lymph nodes and from Thorotrast granulomas surgically removed from patients who had been injected with this colloidal thorium dioxide. The lattice images of Thorotrast particles in the liver, lymph nodes, and Thorotrast granuloma, and in the Thorotrast solution, were observed by high-resolution electron microscopy. The fringe spacing of 0.32nm corresponding to the (111) atomic plane of ThO2 was determined. The mean particle sizes in the tissues and solution were estimated to be 10.8 and 8.1nm, respectively. Two kinds of recrystallization pattern were observed at the boundaries of particles in granular aggregates. Calcium needles coexisted with Thorotrast particles only in Thorotrast granulomas. The atomic rearrangement was more remarkable in the tissues than in the Thorotrast solution. Based on these experimental data, a model is proposed to explain the mechanism for the growth of granular aggregates of Thorotrast in human tissues; macrophages may take up Thorotrast particles and those particles may then unite tightly through atomic rearrangement.
We developed a simplified intravenous fat emulsion tolerance test (FETT) by administering 0.25ml/kg body weight of Intralipid® 10% fat emulsion in order to study the pathogenesis of hyperlipidemia. The fractional removal rate (K2) of fat emulsion was determined by nephelometry. FETT was performed on male and female normolipidemic subjects and on patients who had primary and secondary hyperlipidemia (except types I and V of W.H.O. classification). The K2 value of normolipidemic subjects ranged from 4.0 to 27.6%/min, with a mean value of 11.5±4.7 (SD) %/min, (n=77). The K2 value of hyperlipidemic patients ranged from 1.8 to 18.6%/min, and the mean value was 8.2±3.3 (SD)%/min, (n=150). Compared with the data in the literature, the values and range of K2 by this simplified FETT were higher and greater, respectively, than those obtained by the earlier method of administering a higher loading dose such as 1ml/kg body weight of Intralipid® 10% fat emulsion. Good reliability and high reproducibility of K2 by the present FETT were also demonstrated. We suggest that the simplified FETT is a good tool for the study of hyperlipidemia and lipid metabolism.
Indicators of iron status and protein status as well as markers of inflammatory processes were determined in 164 apparently healthy children 4 years old (±3 months) undergoing a free medical check-up in a Parisian Children's Health Examination Center. Biochemical evidence of inflammatory syndrome (without clinical signs) was observed in 32 children. Among the indicators of protein status, only the mean thyroxine-binding prealbumin was significantly lower in the group of children with inflammation than in the inflammation-free group. Among indicators of iron status, mean serum iron and transferrin saturation were significantly lower, and mean serum ferritin, significantly higher, in children with inflammatory processes. Seventy-eight percent of children with biochemical inflammatory processes had serum ferritin levels higher than 50μg/liter, and 42% had serum ferritin levels higher than 80μg/liter. Our study shows that mild inflammatory processes are not uncommon in young, apparently healthy children and may affect the capacity of prealbumin to reflect protein status as well as the capacity of most iron parameters to assess iron status. Serum ferritin, serum iron, and transferrin saturation seem to be most affected by the presence of a mild inflammatory reaction.
Levels of anti-acetylcholine receptor (AChR) antibodies were investigated in sera of 272 patients with myasthenia gravis (MG) and 75 patients with other autoimmune diseases by the immunoprecipitation method (RIA) using rat denervated muscle AChR as an antigen. Anti-AChR antibodies were found in over 70% of the MG patients but not in those with other autoimmune diseases except for only 2 cases with border-line titer. Most patients with ocular MG without thymoma had insignificant levels of antibody titers. In patients with generalized MG, both the mean values of antibody titer and percentages positive for the antibody were roughly correlated with clinical seventies. Antibody titers and clinical features were estimated for a long-term period on MG patients who underwent thymectomy (24 cases with thymoma and 48 cases without thymoma). After the operation, anti-AChR antibody levels tended to decrease significantly, corresponding to the clinical improvement; moreover, patients with thymic hyperplasia showed better clinical improvement than those with thymoma.