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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of endotoxin with cultured fibroblasts resulted in a depression of cellular proliferation and an increased synthesis of macromolecules, namely collagenous and non-collagenous proteins. The collagen salt-soluble fraction was increased at the expense of the insoluble fraction, and both the salt-soluble fraction and collagen secreted into the medium was underhydroxylated.
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PMID:Stimulation of macromolecular synthesis by endotoxin-treated 3T6 fibroblasts. 624 93

Severe copper deficiency was induced in rats by rearing nursing dams and their offsprings on a semisynthetic diet comprising all the requisite nutrients and trace metals except copper. The copper-deprived rats exhibited growth retardation, severe anaemia, loss of caeruloplasmin, decrease of cytochrome oxidase, accumulation of salt-soluble collagen and a drastic decrease in iron in plasma and liver. Apart from these characteristic signs of deficiency, a marked inhibition of protein synthesis was found to occur both in vivo and in cell-free liver preparations. The curtailed ability to carry out endogenously coded amino acid incorporation into protein contrasted with the unimpaired poly(U)-acid-directed phenylalanine polymerization. This inhibition pattern, as well as the attendant disaggregation of the liver polyribosomes, suggested that the primary biosynthetic lesion was located at the stage of peptide-chain initiation. Concurrently with this alteration there was a pronounced depletion of the hepatic ATP content, associated with a parallel depression of mitochondrial respiration and an enhancement of ATPase activity. Supplementation of the copper-deficient diet with a 2-4-fold excess of iron (relative to the standard diet) prevented growth retardation and anaemia and restored normal energy metabolism, as well as unimpaired protein-synthesizing capacity. The conclusion that these disturbances were primarily determined by the secondary iron deficiency was also borne out by the finding that similar alterations occurred in rats maintained on a copper-sufficient but iron-deficient diet. On the other hand, the iron-fortified diet failed to reverse the other signs of copper deficiency, namely the loss of caeruloplasmin, the diminished rate of cytochrome oxidase and the increase of soluble collagen. The interrelations between the various biochemical lesions induced by deprivation of copper or iron are discussed and the possible role of ATP depletion in determining the derangement of protein synthesis is considered.
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PMID:Biochemical lesions in copper-deficient rats caused by secondary iron deficiency. Derangement of protein synthesis and impairment of energy metabolism. 625 58

Ther are several main mechanisms that allow us to understand a number of the hepatic and metabolic effects of ethanol. Ethanol is oxidized in the liver to two products (hydrogen and acetaldehyde), to which many of the effects of ethanol can be attributed. The hydrogen generated alters the redox state, and though this effect is attenuated after chronic ethanol consumption, it may still be sufficient to explain alterations in lipid metabolism, possibly increased collagen deposition, and, under special circumstances, depression of protein synthesis. Acetaldehyde impairs microtubules, decreases protein secretion, and causes protein retention and ballooning of the hepatocyte. Acetaldehyde exerts toxicity also with regard to other key cellular functions, particularly in the mitochondria, and it may promote peroxidation of the cellular membranes. It is noteworthy that after chronic consumption of ethanol, there is increased acetaldehyde, in part because of decreased disposition in the mitochondria and partly because of induction of an alternative pathway of ethanol metabolism, namely the microsomal ethanol-oxidizing system. Indeed, this MEOS increases in activity after chronic ethanol consumption, with cross induction and acceleration of the metabolism of other drugs and increased lipoprotein production with hyperlipemia. There is also increased microsomal activation of hepatotoxic compounds (including drugs and possibly vitamin A). Fibrosis and cirrhosis can develop despite an associated adequate diet and even in the absence of alcoholic hepatitis. They are preceded by myofibroblasts and fibroblast proliferation. What eventually causes the increased number of myofibroblasts and promotes fibrosis is unclear, nor do we know the relative role of hepatocytes or mesenchymal cells in the process of fibroplasis. Possibly selective roles in this process of specific nutritional factors remain to be elucidated.
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PMID:Alcohol, protein nutrition, and liver injury. 634 74

The effects of alpha- and gamma-interferons (IFNs) on collagen production by confluent human diploid fibroblasts in culture were examined. It was found that partially purified alpha-IFNs and affinity purified gamma-IFNs caused greater than 50% inhibition of collagen synthesis by these cells independently of their effect on cell proliferation. Recombinant alpha-IFNs showed a similar effect (38.8% inhibition), indicating that collagen synthesis inhibition was a constitutive property of IFNs. Collagen synthesis inhibition by IFNs was concentration dependent. Gel filtration chromatography of the newly synthesized proteins from the media of fibroblasts incubated with partially purified alpha-IFNs demonstrated a selective depression of molecules eluting in the region of procollagen. No detectable increase in collagen degradation products or underhydroxylation of procollagen was observed. Short-term kinetic studies further demonstrated that the major effect of IFNs was due to a net decrease in fibroblast collagen production rather than to impairment of secretion or increased extracellular degradation of the newly synthesized molecules. These results indicate that alpha- and gamma-IFNs are potent inhibitors of human fibroblast collagen production and suggest that they may play an important role in the regulation of normal and pathologic fibrogenesis.
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PMID:Selective inhibition of human diploid fibroblast collagen synthesis by interferons. 643 46

Recombinant gamma-interferon (rec gamma-IFN) caused potent inhibition of collagen synthesis by cultured confluent human diploid fibroblasts in a dose-dependent manner. Gel electrophoresis of the newly synthesized proteins from the culture media of rec gamma-IFN-treated fibroblasts demonstrated a selective depression of procollagen without a significant change in non-collagenous proteins. Dot blot hybridization to a Type I procollagen cDNA probe showed that the inhibition of collagen production was accompanied by a decrease in the levels of collagen mRNA. These results indicate that rec gamma-IFN is capable of exerting transcriptional modulation of collagen biosynthesis and suggest that it may play an important role in regulation of normal and pathologic fibrogenesis.
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PMID:Transcriptional control of human diploid fibroblast collagen synthesis by gamma-interferon. 643 19

Platelet-rich plasma was incubated with mithramycin in vitro. This diminished platelet aggregation by ADP and adrenaline, but did not interfere with collagen-induced aggregation. Platelet factor 4 release was diminished by ADP and delayed when induced by adrenaline but normal when induced by collagen. Platelet factor 3 availability was not significantly impaired. Reptilase clot retraction was diminished when induced by ADP but normal when induced by collagen. Uptake of 14C-serotonin and 14C-adenine was slightly inhibited. There was no depression in platelet adhesion or release of serum aggregating activity.
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PMID:Influence of mithramycin on some platelet functions in vitro. 644 52

The differentiation of precardiac mesoderm into beating heart tissue was examined during explant culture. Explanted tissue forms tubular heart-like vesicles and initiates rhythmic contractility within 18-24 h in vitro, a developmental time-course approximating that observed during in vivo development. Electron-microscopic observations reveal that beating heart cells are rich in cytoplasmic myofibrils in varying degrees of order, with some regions containing highly organized myofibrillar arrays. The analysis of actin-isotype biosynthesis, using metabolic labeling with [35S]-methionine and isoelectric-focusing resolution of the synthesized radioactive polypeptides, demonstrates that the initiation of cardiac alpha-actin synthesis and the pattern of transition in the synthesis of alpha-, beta-, and gamma-actin isotypes is equivalent to the initiation time and pattern observed in vivo. A possible collagen involvement in the differentiation process was investigated by assessing the effects of collagen-synthesis inhibitors on the development of the explant cultures. Two different agents, alpha, alpha'-dipyridyl and L-azetidine-2-carboxylic acid, exhibited a dose-dependent ability to inhibit the formation of beating heart tissue. When examined by electron microscopy, the nonbeating tissue exhibited a drastic depression of myofibrillogenesis, but otherwise appeared healthy. Further examination of the effect of L-azetidine-2-carboxylic acid demonstrated that the inhibition of myofibril formation and heartbeat was correlated with a 60% inhibition of native collagen synthesis; however, the time-course and pattern of actin-isotype biosynthesis was completely unaffected. The data suggest a possible involvement in heart differentiation that is necessary for either the synthesis of non-actin cardiac contractile proteins or the assembly of cardiac contractile proteins into myofibrils.
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PMID:Precardiac mesoderm differentiation in vitro. Actin-isotype synthetic transitions, myofibrillogenesis, initiation of heartbeat, and the possible involvement of collagen. 651 68

Thromboxane A2 (TxA2) may aggravate myocardial ischemia by inducing vasoconstriction and platelet aggregation in small coronary vessels, whereas prostacyclin (PGI2) counteracts these effects. Acetylsalicylic acid (ASA) inhibits the formation of TxA2 as well as PGI2, whereas dazoxiben, a thromboxane synthetase inhibitor, reduces TxA2 formation selectively. In 25 patients with coronary artery disease, 2 identical atrial pacing stress tests were performed: before and after the administration of dazoxiben (200 mg) in 15 patients and before and after ASA (250 mg) in 10. The ischemic response, quantified by coronary sinus and aortic lactate levels and by ST depression, was significantly reduced after administration of dazoxiben (p less than 0.02) but not after ASA. Heart rate at rest, myocardial extraction of free fatty acids and the arteriovenous oxygen difference was unaffected by medication. Both drugs reduced TxB2 levels to the same extent, whereas collagen-induced aggregation was more reduced after ASA than after dazoxiben. The effect of dazoxiben on ischemia was probably a result of inhibited TxA2 and preserved PGI2 production, which increased blood flow to ischemic regions.
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PMID:Effects of a selective thromboxane synthetase inhibitor, dazoxiben, and of acetylsalicylic acid on myocardial ischemia in patients with coronary artery disease. 653 40

Bilateral medial meniscectomy was performed in 12 mature greyhounds. One knee joint of half the group was immobilized by a Kirschner splint for a period of 5 weeks immediately following meniscectomy, after which the device was removed and the animals were allowed free movement for a further 21 weeks before sacrifice. Three greyhounds served as controls. While the collagen levels of articular cartilage from the femoral condyles and tibial plateaus of meniscectomized animals were the same as that of controls, differences were found for proteoglycan (PG) content and extractability using nondissociative conditions (0.5 M guanidinium hydrochloride (GuHCl) but not dissociative conditions (4.0 M GuHCl). With nondissociative conditions, twice as much PG was extracted from medial femoral condyle of meniscectomized animals encouraged to bear weight on joints immediately after surgery compared to that from controls or animals in whom joints were immobilized after surgery. Proteoglycans from medial tibial plateau cartilage of the free contralateral joints of the immobilized group were more readily extracted using 0.5 M GuHCl and also showed a statistically significant depression of uronic acid levels relative to both controls and tissues of other surfaces. The data suggest that postoperative management of meniscectomy in the human may be more important than has hitherto been recognized.
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PMID:The effects of postoperative joint immobilization on articular cartilage degeneration following meniscectomy. 665 36

ADP and collagen-induced platelet aggregation and parameters related to the fibrinolytic system were studied in groups of healthy persons who had ingested 500 mg of diflunisal. A single dose of diflunisal resulted in a depression of platelet function in most cases. However, the effect was limited and only of clinical relevance in patients with a defective platelet function. A frequent finding was an enhanced fibrinolytic activity in plasma and saliva 2 h after ingestion of diflunisal. In approximately one-third of the cases studied, the fibrinolytic activity in saliva rose to levels that induced clot lysis within a few minutes. This could explain the clinical observation that administration of diflunisal prior to dental surgery is followed by dry socket symptoms in one-third of the patients.
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PMID:Platelet function and fibrinolytic activity after a single dose of diflunisal (Donobid). 678 75


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