Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present investigation was undertaken to discover whether repeated doses of dimethylnitrosamine (DMNA) could produce a cumulative toxic effect on the rat liver. For this purpose doses were selected at a level just too low to produce cytopathological changes, as indicated by depression of glucose-6-phosphatase and induction of autophagic vacuoles (AV) in hepatocytes, when given once only. Single subcutaneous injections of 10 or 3 mg/kg induced these cytopathological changes in the centrilobular (CLB) hepatic cells but when the dose was reduced to 1 mg/kg no such changes were seen. After daily administration of 1 mg/kg for 4 or 8 weeks we observed both glucose-6-phosphatase depression and autophagy, and in addition there was marked hypertrophy of the rough endoplasmic reticulum, nucleolar microsegregation and the appearance of distorted, often ring-shaped mitochondria with shortened cristae. Kupffer cells exhibited a marked increase in lysosomal activity. With the exception of mitochondrial changes and Kupffer cell activity this same picture was observed, although in milder form, when the dose administered was 0.3 or 0.1 mg/kg daily for the same period. When treatment was continued for 12 weeks, however, the only differences from control rats were the presence of hypertrophied rough endoplasmic reticulum (RER) at all three dose levels, nucleolar microsegregation at the upper two dose levels, and pronounced Kupffer cell activity at the top dose. These findings indicate that cumulative cytopathologic effects occur only up to 8 weeks at the dose levels studied but hypertrophy of RER and increased Kupffer cell activity persist up to 12 weeks.
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PMID:Reversibility of lysosomal and glucose 6-phosphatase changes produced in the rat liver by dimethylnitrosamine. 16 89

Neutrophils from healthy volunteers were isolated and incubated with varying concentrations of albumin-bound long chain free fatty acids. Standard in vitro function tests including phagocytosis, bactericidal activity, and chemotaxis were performed after the incubation. It was found that unsaturated fatty acid (oleic acid) caused no changes in bactericidal activity and only moderate decreases in phagocytosis and chemotaxis at very high concentrations. Saturated fatty acid (palmitic acid) produced, at high concentrations, virtually complete inhibition of chemotaxis and moderate depression of phagocytosis and bactericidal ability. Most significantly, lower concentrations of saturated free fatty acids, within the range reported clinically in various diseases, caused a marked inhibition of chemotaxis. These functional disturbances were associated with ultrastructural alterations. Neutrophils treated with oleic acid contained numerous cytoplasmic neutral lipid droplets. Neutrophils incubated with palmitic acid showed elongated cleftlike dilations of the endoplasmic reticulum and degenerative degranulated cytoplasmic areas. It is postulated that these represent crystallization of excess saturated free fatty acids or triglyceride which interfere with chemotaxis, either mechanically or by causing cell injury.
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PMID:The effects of long chain free fatty acids on human neutrophil function and structure. 17 17

The synapses between the lateral giant axon and the giant motor axon found in the abdominal ganglia of the ventral nerve cord of the crayfish Procambarus clarkii are electronic. The junctional membrane rectifies, favoring impulse transmission from lateral giant fiber to giant motor fiber. This rectifying electronic junction consists of closely apposed membranes indistinguishable from ordinary arthropod gap junctions. The apposed membranes contain intramembrane particles that are approximately 12.5 nm in width. These particles have a central depression and are arranged in a loosely ordered array with a center-to-center spacing of about 20 nm. The only obvious morphological evidence of asymmetry is the presence of vesicles (about 80 nm in diameter) in the cytoplasm adjacent to the junctional region of the presynaptic lateral giant fiber. Vesicles are not present in the adjacent cytoplasm of the postsynaptic giant motor fiber; however, mitochondria and smooth tubular endoplasmic reticulum are more frequent in the cytoplasm of the giant motor fiber.
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PMID:The fine structure of a rectifying electrotonic synapse. 73 Jul 67

Young male rats (100-130 g) were fed diets of equal energy content containing o.5, 1,2,3,5, and 18% lactalbumin consumed either freely or in restricted amounts. The rats receiving low protein diets failed to grow and mature. Those consuming the 0.5 and1% protein diets given freely developed the characteristic features of kwashiorkor including edema, while those receiving the diets in restricted amounts developed the characteristic features of marasmus. The rats fed low protein diets had low plasma levels of essential amino acids; however, the lysine level was well maintained. The plasma levels of nonessential amino acids, especially glycine, alanine, and aspartic and glutamic acids were raised in marasmic rats but were reduced in rats fed low protein diets ad libitum. Young and severly malnourished rats appeared to have limited ability to synthesize urea. Therefore, they excreted more ammonia and other nitrogenous substances such as ethanolamine, and when given an amino acid load, intermediary metabolites of the ingested amino acids. Rats fed low protein diets showed diminution of total liver DNA, RNA, and protein. In addition to the reduction of protein synthesis resulting from decreased cellular RNA, ribosomes from the livers of protein-deficient rats had reduced ability to synthesize proteins. This defect was associated with the detatchment of the ribosomes from endoplasmic reticulum membrane and the elevation of the proportion of monosomes to polyribosomes. Malnutrition did not produce any change in the turnover rate of liver RNA. Protein deficiency caused significant depression of serum insulin, thyroxine, and corticosterone levels. Theoverall conclusion is that mammalian metabolism is well adapted to dietary intake and that this adaptation is achieved through dietary control of synthesis and release of key metabolic hormones.
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PMID:Experimental protein and energy in the rat. 80 70

The injection of aethimizol to rats (10 mg/kg) causes an irregular widening of cisternae of the granular endoplasmic reticulum in "light" pyramidal neurons of zone CA1 of dorsal hippocampus, which is considered as a depression of the neuronal apparatus of protein synthesis. A 1 mg/kg dose causes, in some synapses, a complex of changes supposed to express the activation of synapses. No essential changes were revealed in the heart neurons. Aethimizol acts selectively on the ultrastructure of central nervous system and does not exert a pronounced action on autonomic neurons.
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PMID:[Effect of etimizol on the ultrastructure of the dorsal hippocampus and autonomic ganglia of the rat heart]. 88 24

A target-organ study of the effects of the phthalate ester di-(2-ethylhexyl) phthalate (DEHP) has been conducted in mature male albino ferrets. DEHP treatment caused a loss of body weight when administered as a 1% (w/w) diet for 14 months. Additionally marked liver enlargement with associated morphological and biochemical changes was observed. These changes consisted of liver cell enlargement, lysosomal changes, dilatation of the endoplasmic reticulum and the depression of a number of marker enzyme activities. The only other tissue observed to be affected by DEHP treatment was the testes where histological evidence of tissue damage was observed in some animals. Studies on the metabolism of [14C]DEHP in the ferret indicated that the diester was metabolised to derivatives of mono-(2-ethylhexyl) phthalate which were excreted in the urine both unconjugated and as glucuronides. The results obtained have been compared with previous studies in the rat and it is concluded that DEHP is hepatotoxic in both species.
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PMID:Studies on the effects of orally administered Di-(2-ethylhexyl) phthalate in the ferret. 99 79

The postphagocytic effect on mouse, rabbit, and guinea pig peritoneal macrophages of a petrol-ether lipid extract from Corynebacterium ovis (C. pseudotuberculosis) representing the surface coat of the organism external to the cell wall was investigated by examing three parameters of cytotoxicity, viability assayed by dye exclusion, glycolytic activity, and ultrastructural morphology. The viability test demonstrated a lethal effect on normal and immune mouse macrophages but not on those of the rabbit or guinea pig. Measurement of glycolsis indicated a significant degree of cytotoxicity in normal mouse macrophages ingesting lipid, a nonsignificant depression of activity in cells from immune mice, and no alteration in the activities of rabbit and guinea pig macrophages. Electron microscopy demonstrated that C. ovis surface lipid caused acute lethal injury in normal and immune mouse macrophages. The early stages of degeneration were typified by dilatation of the cisternae of rough endoplasmic reticulum, Golgi lamellae, and nuclear envelope, proceeding to focal disruption of various cell membranes, particularly those of the lipidcontaining phagolysosomes and nucleus. In contrast, over the 3-h period of study, no cytotoxic change was evident in rabbit or guinea pig macrophages. The results add further support to previous observations that the surface lipid of C. ovis plays a major role in the pathogenesis of the organism in mice, but they do not explain the guinea pig's marked susceptibility to infection.
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PMID:Comparative toxic effect of the surface lipid of Corynebacterium ovis on peritoneal macrophages. 120 21

The parathion analogue O, O-diethyl, O-phenyl phosphorothionate (SV1) is hepatotoxic when given in large intraperitoneal doses (400 mg/kg body weight) to male rats that have been treated previously with phenobarbitone. The lesion produced at 24 h after dosing is a periacinar hydropic degeneration which appears identical to that caused by carbon disulphide (CS2) in similarly pretreated rats. Both lesions are characterized by a marked depression in hepatic microsomal cytochrome P-450 levels, no change in the concentrations of Na+, K+ and Ca++ in liver water, in contrast to the periacinar necrogenic lesion caused by tccl4 in which Na+ and Ca++ levels markedly increase while that of K+ decreases. The similarity of the SV1 and CS2 induced liver changes, the fact that both chemicals undergo a similar oxidative desulphuration in the liver microsomes and that prior induction of the latter enzymes is necessary in order to produce the injury suggest a similar mechanism for both lesions. A reactive form of sulphur released from the metabolism of CS2 and phosphorothionates in the liver may become covalently bound to constituents of the endoplasmic reticulum of the liver cell and in this way initiate the toxic liver changes. Drugs and chemicals which contain P=S or C=S bonds and which undergo oxidative desulphuration in the liver could thus be similarly hepatotoxic.
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PMID:The hepatotoxicity of O,O-diethyl, O-phenyl phosphorothionate (SV1) for the rat. 126 38

Sixty-four rabbits were used in this study, experimental bone defects were made in notch of the mandibular bone angle. Dan sheng was used in experimental groups. A pieces of bone at the edge of the defect was taken and observed by electron microscope in different period. The results were as follows: 1. The amount of osteoblast increase clearly. 2. The synthesis of protein was vigorous in fibroblast appeared as nuclear depression, nucleoli locating at one side and formation of endoplasmic reticulum bubble. as Therefore, we think that dan shen would take a role of improving the mandibular bone fracture healing.
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PMID:[An experimental study of dan sheng improving the mandibular bone fracture healing]. 130 31

The effects of a short-term in vivo administration of two liver tumour promoters (phenobarbital and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane on rat liver endoplasmic reticulum Ca(2+)-ATPase were investigated. The specific activity values of this membrane-bound enzyme significantly decreased (P less than 0.01) by 51% for phenobarbital-treated rats and by 48% for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane-treated rats compared with control animals. The depression of liver endoplasmic reticulum Ca(2+)-ATPase appears to be a manifestation of the toxicological effect of tumour promoters.
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PMID:Depression of the Ca(2+)-ATPase activity of the rat liver endoplasmic reticulum by the liver tumour promoters, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane and phenobarbital. 134 71


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