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)

Chromosomal aberrations resulting from the exposure of Chinese hamster lung fibroblast cells to 95% oxygen have been used to investigate the protective effect of three steroids. Hydrocortisone had little useful effect. However, dosage of both methylprednisolone and dexamethasone could be increased to a level at which damage by oxygen was reduced to 50% of nuclei compared with 90% damaged in cells unprotected by steroids. There was no appreciable impairment of cell growth. Concentrations of steroids required for this effect were respectively 100 and 10 mumol litre-1, which corresponds to the high dosage regimen currently used to protect the lungs against the effects of endotoxic shock, haemorrhage and other conditions. The steroids did not protect against the depression of cell growth caused by 95% oxygen.
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PMID:Protective effect of steroids on cultured cells damaged by high concentrations of oxygen. 742 27

Enhanced production of nitric oxide has been implicated in cardiac and vascular dysfunction associated with septic and endotoxic shock. To test this hypothesis, conscious rats were administered endotoxin. 6 h later, the rats were anesthetized, arterial pressure was measured, and hearts were removed for Langendorff perfusion in the absence and presence of .01 microM isoproterenol. Left ventricular developed pressure was 61 +/- 6 mmHg in control rats 39 +/- 5 mmHg in endotoxin-treated rats. Inotropic responses to isoproterenol were unaffected by endotoxin treatment. Administration of nitric oxide synthase (NOS) inhibitors (NG-nitro-L-arginine and aminoguanidine) prior to endotoxin did not improve left ventricular function in endotoxin-treated rats. Dexamethasone pretreatment, however, prevented endotoxin-induced cardiac depression. These results suggest that cardiac depression during endotoxemia is not caused by NOS activation and increased nitric oxide production. Furthermore, the cardioprotectant actions of dexamethasone are not related to its ability to inhibit inducible NOS expression.
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PMID:Nitric oxide synthase inhibition does not prevent cardiac depression in endotoxic shock. 753 6

Endotoxin (lipopolysaccharide, LPS) can induce shock, multiple organ failure, and death. A recombinant N-terminal fragment of bactericidal/permeability increasing protein, rBPI23, binds with high affinity to gram-negative bacterial LPS and neutralizes its biological activity. We sought to determine the effect of rBPI23 on LPS-induced respiratory dysfunction and cardiovascular depression in conscious rabbits. Rabbits were injected with Escherichia coli O113 LPS (6 micrograms/kg) and treated with rBPI23 (2 mg/kg), vehicle, or control protein after recovery from surgery performed to implant catheters for hemodynamic assessments and intravenous injections. LPS challenge caused respiratory dysfunction including tachypnea, significant decreases in arterial O2 tension (PO2), arterial oxygen content, and an increase in alveolar-arterial O2 gradient (A-aDO2). LPS administration also resulted in profound and prolonged decreases in mean arterial blood pressure and cardiac index. Treatment with rBPI23 prevented LPS-induced respiratory dysfunction and significantly ameliorated the cardiovascular depression. 5 of 16 LPS-challenged animals died of respiratory failure and acidosis, whereas none died in the rBPI23 treated group (p = .11). The results demonstrate that rBPI23 protects animals against LPS-induced cardiopulmonary depression in endotoxic shock.
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PMID:Protective effects of a recombinant N-terminal fragment of bactericidal/permeability increasing protein on endotoxic shock in conscious rabbits. 774 57

A shock model was experimentally produced by intravenous injection of a lethal dose (3 mg/kg) of endotoxin under general anesthesia induced by pentobarbital sodium using 7 beagles. The effect of this endotoxic shock on the reticuloendothelial function was investigated. The blood endotoxin concentration peaked immediately after administration and decreased subsequently. However, the value still remained on an increased level (1,051 pg/ml) even at 360 min after endotoxin treatment. The lipid emulsion test as an index of reticuloendothelial phagocytotic activity and the arterial ketone body ratio as an index of the energy charge in the liver decreased after endotoxin treatment and failed to recover during the experiment. Fibronectin, one of opsonic proteins, tended to decrease after injection of the endotoxin and was significantly (p < 0.01) low at 180 and 360 min compared with the value before injection of the endotoxin. These results suggested the depression of the reticuloendothelial function during endotoxin-induced shock.
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PMID:Changes in reticuloendothelial function in dogs with endotoxin-induced shock. 839 41

We investigated the mechanisms by which endotoxic shock induces intrinsic myocardial depression by studying cardiac myocytes isolated from 10 anesthetized instrumented rabbits given 172 +/- 42 (mean +/- SD) micrograms/kg IV endotoxin. Left ventricular (LV) depression developed 4 +/- 1 hours after endotoxin administration, with a 15 +/- 4% increase in LV internal end-systolic diameter, measured with sonomicrometers at a matched LV end-systolic pressure of 65 +/- 10 mm Hg. Normal LV pressure, arterial PO2, and pH were maintained to minimize confounding effects of ischemia, hypoxia, and acidosis. Cardiac myocytes from endotoxin-exposed rabbits had less unloaded cell shortening and lower peak rates of cell shortening (-dL/dt) and lengthening (+dL/dt) at [Ca2+] levels ranging from 0.5 to 16 mM when compared with myocytes isolated from normal rabbits or rabbits undergoing an identical protocol but without exposure to endotoxin. At 2 mM [Ca2+], cell shortening was depressed by approximately 25% because of a decrease in action potential duration (207 +/- 70 versus 375 +/- 64 milliseconds). In contrast, there was only mild impairment of sarcoplasmic reticulum (SR) function. When myocytes were restimulated after rest periods of 4 to 480 seconds, the decrement in cell shortening (rest decay), peak -dL/dt and peak +dL/dt, and the recovery from rest decay were similar in myocytes from endotoxin-treated and normal rabbits. There was a greater decrement in cell shortening in the second beat of postrest recovery in myocytes from endotoxin-treated rabbits than in normal myocytes. This was partly due to a 12% decrement in action potential duration with rest decay, which did not occur in normal myocytes. The SR Ca2+ content assessed by contractures in 10 mM caffeine was similar in the two groups. We conclude that endotoxic shock produces a LV depression in vivo that persists in isolated myocytes studied in vitro. This intrinsic myocardial depression is largely related to endotoxin-mediated sarcolemmal alterations, which shorten action potential duration, and is not due to alterations in SR function.
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PMID:Cellular mechanisms of endotoxin-induced myocardial depression in rabbits. 850 24

To evaluate the relationship between cardiovascular injury and the pathological significance of endothelial constitutive nitric oxide synthase (ecNOS) and inducible nitric oxide synthase (iNOS) in endotoxic shock, Wistar rats were injected intraperitoneally with 10 mg/kg Escherichia coli endotoxin and the resulting cardiovascular changes observed using immunohistochemistry, immunoelectron microscopy, the reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization at 4, 6, 8 and 10 h after endotoxin administration. Immunohistochemical and electron microscopic observations showed that ecNOS was localized in the cytoplasmic vesicles and rough endoplasmic reticulum of the endothelium of coronary arteries and intermyocardial capillaries in both control and endotoxin-treated rats. iNOS was localized in the cytoplasmic vesicles and endoplasmic reticulum of vascular endothelial cells, vascular smooth muscle cells and cardiomyocytes after endotoxin administration. The RT-PCR study confirmed the expression of ecNOS and iNOS mRNA in the heart tissues of all animals including controls. In situ hybridization showed that ecNOS mRNA was expressed in the cytoplasm of vascular endothelial cells in control and endotoxin-treated rats. After endotoxin administration, iNOS mRNA was strongly expressed in vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes and a small number of macrophages. Bacterial lipopoly-saccharide induces rapid release of nitric oxide in the microvasculature and cardiomyocytes resulting in the depression of cardiomyocyte contraction. These findings may describe the cardiac response after endotoxin treatment.
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PMID:Differential distribution of ecNOS and iNOS mRNA in rat heart after endotoxin administration. 929 May 78

Injection of guinea pigs with a single dose of Escherichia coli lipopolysaccharide (3.2 mg/100 g) induces a reversible endotoxic shock that was evaluated by measuring plasma glucose levels and aspartate aminotransferase activity at 24 h after lipopolysaccharide injection. The hypoglycaemia and the increase in plasma aminotransferase activity observed, correlated with the alterations found during the recovery phase of endotoxic shock. When lipid peroxidation and some antioxidant systems were measured in lungs from treated animals, we only found differences in ascorbic acid content, that was decreased by 50%. Lipopolysaccharide treatment results in a depression of pulmonary phosphatidylcholine synthesis, that correlates with the surfactant deficiencies associated with respiratory illnesses in septic shock. Guinea pigs fed on a diet with a low content in ascorbic acid were more sensitive to endotoxin. In these animals we found no detectable levels of ascorbic acid in lung, whereas both vitamin E lung levels and pulmonary phosphatidylcholine synthesis were significantly decreased. Our results point out the significance of ascorbic acid in the protection against oxidative lung injury associated to endotoxaemia, and validate our shock model for further studies on the mechanisms of this pathological condition.
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PMID:Impaired phosphatidylcholine biosynthesis and ascorbic acid depletion in lung during lipopolysaccharide-induced endotoxaemia in guinea pigs. 935 41

A paracrine pathway for the regulation of cardiac contractile function by nonmuscle cells is documented in the heart. Coronary and endocardial endothelium release several diffusible agents, such as prostaglandins, endothelin-1, and nitric oxide, with an action on cardiac myocyte function. Cardiac diseases involving an immune or inflammatory mechanism, such as endotoxic shock, are now seen as conditions in which cross-talk between different cell types in the heart is clearly implicated. The potential biological relevance of inducible nitric oxide synthase in the myocardium, and the subsequent production of nitric oxide has been proposed as a mechanism of the cardiac depression observed in septic shock. In addition to cardiac myocytes, activated microvascular endothelial cells and cardiac endothelial cells may contribute to nitric oxide generation and, ultimately, to the depression of myocardial contractile activity during sepsis. This article reviews the local intercellular communication between cardiac myocytes and endothelial cells in the normal heart and discusses some of the mechanisms potentially claimed to depress heart function in sepsis.
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PMID:Paracrine regulation of cardiac myocytes in normal and septic heart. 955 26

Although cardiac function is depressed during endotoxic shock, it remains controversial whether the ventricular contractility and structure are altered during sepsis. To resolve this issue, rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). At 2, 5, and 10 h after CLP (i.e., the early, hyperdynamic stage of sepsis) or 20 h after CLP (the late, hypodynamic stage of sepsis, based on the depressed tissue perfusion), in vivo left ventricular contractility parameters such as maximal rate of the left ventricular pressure increase (+dP/dtmax) and decrease (-dP/dtmax), maximal rate of "pressure-normalized" change in ventricular pressure (dP/dtmax/P), and ventricular peak systemic pressure were determined using a Digi-Med Heart Performance Analyzer. In additional groups of animals, ultrastructure of the cardiac muscle in the left ventricle was examined at 5, 10, or 20 h after CLP, using a transmission electron microscope. The results indicate that +dP/dtmax and dP/dtmax/P increased significantly at 2-10 h after CLP. The values of -dP/dtmax and ventricular peak systemic pressure increased significantly at 2 and 5 h after the onset of sepsis, respectively. These in vivo ventricular contractility parameters, however, were not significantly different from shams at 20 h after CLP. Ultrastructural examination showed that enlarged T-tubules were prominent during the hyperdynamic stage of sepsis, which was correlated with the increased cardiac contractility. Although focal and moderate hypertrophy as well as expanded intermyocyte junctions could be observed occasionally, myocardial cells did not appear to be compromised at 20 h after CLP. Thus, the transition from the hyperdynamic to hypodynamic circulation during sepsis does not appear to be due to any depression in myocardial function because cardiac contractility and structure are not compromised even during the late, hypodynamic stage of sepsis. However, further investigation is required to determine whether cardiac function is depressed at the terminal stage of polymicrobial sepsis.
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PMID:Cardiac contractility and structure are not significantly compromised even during the late, hypodynamic stage of sepsis. 992 20

Sixteen cases of acute idiopathic toxaemic colitis developed in a veterinary hospital over a period of three years. Before the onset of colitis, 15 horses had received antibiotics, 11 had undergone general anaesthesia and various surgical procedures, and 10 had been treated with non-steroidal anti-inflammatory drugs. The horses had acute onset, profuse watery diarrhoea, profound depression, mild to moderate abdominal pain, reduced intestinal borborygmi, tachycardia, dehydration and endotoxic shock. Leucopenia, neutropenia and pyrexia were common early indicators of impending colitis. Metronidazole appeared to be an effective treatment; eight horses treated with metronidazole survived whereas five of seven horses that received other treatments, but no metronidazole, died or had to be euthanased. The aetiology of the colitis could not be determined, but the clinicopathological features resembled those of colitis attributed to an intestinal overgrowth of Clostridium perfringens type A. No Salmonella species were isolated from 52 samples of faeces, colonic contents and colonic mucosa which were collected from the horses antemortem and postmortem.
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PMID:Use of metronidazole in equine acute idiopathic toxaemic colitis. 967 Apr 51


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