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

Experiments were carried out to determine whether the growth of tumors could be influenced by local inflammatory reactions induced by mitogens; Gram-negative bacterial lipopolysaccharide (LPS), concanavalin A (Con A) and phytohemagglutinin (PHA). Mice received injections, beneath the footpad or subcutaneously in the flank, of cells of syngeneic chemically induced fibrosarcomas with or without varying doses of mitogen. In the footpad (a) LPS caused a dose-dependent increase in the size; (b) Con A caused a decrease in the size of one of the three tumors, the decrease being inversely related to the dose of Con A; (c) PHA caused a dose-dependent decrease in the size of all three tumors: (d) PHA caused much smaller macroscopic inflammatory reactions than LPS or Con A. Subcutaneously injected tumor growth was inhibited by all three agents. Subcutaneous tumors contained a higher proportion of host inflammatory cells when mitogens had been mixed with the tumor inoculum. It is concluded that mitogens that can induce inflammatory reactions in mice can also bring about some suppression of tumor growth but that the depression is site-dependent and not clearly related to the apparent intensity of inflammation.
 ...
PMID:II. Tumor growth at sites of inflammation induced by mitogens in mice. 725 99

There is growing evidence that an oxidant stress contributes to the deleterious effects of bacterial lipopolysaccharide (LPS). The present study evaluated the ability of the antioxidant, U74389, to prevent the depression of vascular reactivity caused by LPS. Aortic rings taken from rats given LPS showed a depression of maximum force in response to phenylephrine that was reversed by an inhibitor of nitric oxide synthase. Pretreatment of animals with U74389 attenuated this depression of vascular reactivity. U74389 did not limit the increase in serum tumor necrosis factor levels caused by LPS. These results show that U74389 can ameliorate the depression of vascular reactivity caused by LPS possibly by interfering with the induction of nitric oxide synthase.
 ...
PMID:The antioxidant, U74389, ameliorates the depression of vascular reactivity caused by lipopolysaccharide. 747 27

To determine the role that vasoactive neuropeptides, calcitonin gene-related peptide, and substance P play in tissue-blood flow regulation during early septic shock, we examined the responsiveness of arteries removed from pigs 3 h after administration of Escherichia coli lipopolysaccharide or saline vehicle. The carotid, cranial mesenteric, and left anterior descending coronary arteries were excised, and rings were cut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstricted and challenged with acetylcholine, substance P, calcitonin gene-related peptide, and nitroglycerin. Lipopolysaccharide significantly increased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. This enhancement of responses to nitroglycerin suggests augmented smooth-muscle responsiveness to an exogenous source of nitric oxide, possibly associated with early depression of basal endothelial function. Depression of agonist-induced nitric oxide release may mask such enhancement with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.
 ...
PMID:Early endotoxic shock results in enhanced vasodilator responses to nitroglycerin but unaltered responses to neuropeptides calcitonin gene-related peptide and substance P. 753 18

The depression of vasoconstrictor responsiveness caused by bacterial lipopolysaccharide (LPS) is mediated, in part, by the induction of nitric oxide synthase (NOS) and the resultant increase in nitric oxide production by vascular smooth muscle. The present study evaluated the ability of the antioxidant, diethyldithiocarbamate (DDTC), to attenuate the LPS-stimulated induction of NOS in cultured vascular smooth muscle cells (VSMC) and the depression of in vitro vascular reactivity caused by LPS administration to rats. The LPS-stimulated increase in nitrite production by cultured VSMC was inhibited 85% by DDTC (100 microM). When VSMC were stimulated with a combination of LPS, interferon-gamma (INF) and tumor necrosis factor (TNF) nitrite production was 5-fold greater than with LPS alone. DDTC inhibited 49% of the increase caused by LPS plus INF and TNF. Aortic rings taken from animals injected with LPS showed a depression of maximum force in response to phenylephrine which was reversed by inhibition of NOS activity. Pretreatment of animals with DDTC attenuated this depression of vascular reactivity. The DDTC treatment did not reduce the increase in serum TNF levels caused by LPS. These results suggest that DDTC can attenuate the LPS-stimulated induction of NOS in vascular smooth muscle and may thereby ameliorate the impairment of vascular reactivity.
 ...
PMID:Diethyldithiocarbamate ameliorates the effect of lipopolysaccharide on both increased nitrite production by vascular smooth muscle cells and decreased contractile response of aortic rings. 754 1

The decreased contraction amplitude of isolated cardiac myocytes from guinea pigs exposed to lipopolysaccharide (LPS) was reported to be partially reversed by nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) [Brady, et al., Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1963-H1966, 1992]. We have tested the potential involvement of NO formation in LPS-induced cardiac depression in the intact heart. Isolated perfused hearts of LPS-treated guinea pigs (4 mg/kg 4 h before organ removal) displayed a greatly decreased left ventricular pressure (LVP) when compared with untreated controls (48 +/- 11 vs. 93 +/- 18 mmHg, n = 6 hearts each), whereas heart rate and coronary flow were similar. Perfusion of LPS-treated hearts with L-NMMA or L-NAME (100 microM each) at constant flow did not increase LVP (50 +/- 14 and 44 +/- 11, respectively, vs. 52 +/- 14 mmHg). However, coronary resistance increased significantly. There was no difference between LPS-treated and control hearts in venous adenosine release (104 +/- 58 vs. 133 +/- 86 pmol.min-1.g-1). Measurement of the activities of the induced (iNOS) and constitutive forms of NOS revealed that there was no difference in total NOS activity (237 +/- 82 vs. 181 +/- 97 fmol.min-1.mg protein-1. There was no measurable induction of iNOS in the LPS-treated hearts either. Finally, cardiac energy status was studied by 31P nuclear magnetic resonance spectroscopy. There was no difference between LPS-treated and control hearts in myocardial ATP, creatine phosphate, pH, and free ADP (59 +/- 20 vs. 50 +/- 27 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Endotoxin-induced contractile dysfunction in guinea pig hearts is not mediated by nitric oxide. 754 61

The aim of the present study was to determine whether two classical macrophage activators, bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) could affect the accumulation of the second messenger cAMP in cultured rat microglia and astrocytes. Purified microglia and astrocyte secondary cultures obtained from the neonatal rat were grown for 3 days in basal medium Eagle (BME) + 10% fetal calf serum (FCS). Exposure of microglia to LPS resulted into a dose- and time-dependent decrease in the accumulation of cAMP induced by receptor-mediated (isoproterenol or prostaglandin E2) or direct (forskolin) activation of adenylate cyclase. The inhibitory effect of LPS was rapid (a 10 min preincubation was sufficient to approach a maximal effect), occurred at low doses (IC50 = 1.2 ng/ml), and was not abrogated by pertussis toxin. A selective inhibitor of type IV phosphodiesterase (rolipram, 100 nM) prevented the effect of LPS on cAMP accumulation, while inhibitors of other forms of phosphodiesterase were unable to do so. IFN-gamma (100 u/ml) also caused a depression of the evoked cAMP accumulation in microglia after a 10 min preincubation, and its effect was prevented by rolipram, as in the case of LPS. Astrocytes differed from microglia in that LPS (1-100 ng/ml) did not inhibit the accumulation of cAMP induced by either isoproterenol or forskolin; on the other hand, IFN-gamma did have an inhibitory effect (though less pronounced than in microglia) that could be prevented by rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interferon-gamma and lipopolysaccharide reduce cAMP responses in cultured glial cells: reversal by a type IV phosphodiesterase inhibitor. 755 45

The modulatory role of endogenous corticoids in the behavioral effects of lipopolysaccharide (LPS) and recombinant human interleukin-1 beta (IL-1 beta) was studied in mice. Adrenalectomy enhanced the depression of social exploration induced by subcutaneous injection of 200 ng of IL-1 beta or 2 micrograms of LPS. This effect was mimicked by an acute injection of the progesterone antagonist RU-38486 (0.25-1 mg). Chronic replacement with a 15-mg corticosterone pellet abrogated the enhanced susceptibility of adrenalectomized animals to 200 ng of IL-1 beta but had only partial protective effects on their response to 400 ng of IL-1 beta and LPS. These results suggest that the pituitary-adrenal response to cytokines exerts an inhibitory feedback on the cell targets that mediate the behavioral effects of LPS and IL-1 beta.
 ...
PMID:Corticosterone regulates behavioral effects of lipopolysaccharide and interleukin-1 beta in mice. 763 87

M. tuberculosis, the aetiological agent of tuberculosis readily infects and multiplies within the macrophages of the host. Macrophage activation is known to occur through a series of stages, which results in the production of biologically active molecules such as the reactive oxygen and nitrogen intermediates. The following study was conducted on 20 patients with pulmonary tuberculosis, before and after initiation of antituberculous therapy, and on 10 normal healthy controls. The macrophages were isolated from peripheral blood of the patients and controls at a concentration of 1 x 10(6) cells ml-1. The generation of reactive oxygen intermediates was measured by a chemiluminescence technique. Reactive nitrogen intermediates, were measured following stimulation of macrophages with latex, lipopolysaccharide (LPS) and purified protein derivative-S (PPD-S). Citrulline levels and electron transport chain activity were also determined in the cell cultures. It was observed that there was a significant depression (p < 0.05) in the respiratory burst response in the patient group (0.46 x 10(3) +/- 0.11 cpm per 10(6) cells) compared with the controls (7.12 x 10(3) +/- 2.31 cpm per 10(6) cells). On the other hand, reactive nitrogen intermediates (671.03 +/- 2.18 nmol) and citrulline levels (193.07 +/- 2.38 nmol) were significantly (p < 0.001) higher before initiation of therapy compared with control values (24.36 +/- 2.81 and 18.91 +/- 2.12 nmol respectively). Their levels declined, during the post-therapy period of 3 months, to 60.81 +/- 2.03 and 38.17 +/- 2.13 nmol respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Release of reactive oxygen and nitrogen intermediates from monocytes of patients with pulmonary tuberculosis. 766 9

The effects of dexamethasone (DEX) were studied on early and delayed hyporesponsiveness to noradrenaline (NA) induced by Escherichia coli lipopolysaccharide (LPS) in pentobarbitone-anesthetized rats, and in aortic rings, which were either removed from LPS-treated rats or exposed to LPS in vitro. In all three preparations, the LPS-impaired responses to NA were restored by N omega-nitro-L-arginine methyl ester. In addition, delayed depression of NA-induced aortic contractions was enhanced by L-arginine (1 mM). In control conditions, DEX had no effect on responses to NA. When administered before LPS, or before hyporeactivity was fully developed, DEX (5-10 mg/kg or 10 microM) entirely prevented both the early decline in responses to NA or its progression, and the delayed impaired aortic contraction induced by LPS. However, DEX did not prevent the transient drop in mean arterial blood pressure (which was maximal at 20 min after the onset of LPS infusion) observed before the full development of impaired reactivity to NA (reached after 55 min). Neither did DEX modify the responses to NA, in vivo or in vitro, once LPS-induced hyporesponsiveness was fully established. These results indicate that DEX inhibits both the onset of impaired responsiveness to NA, which probably involves the early stimulation of the constitutive nitric oxide (NO) synthase, and persistent vascular hyporeactivity resulting from the delayed induction of NO-synthase by LPS. In addition, they show that DEX has no effect on hyporeactivity to NA once fully established.
 ...
PMID:Effect of dexamethasone on the onset and persistence of vascular hyporeactivity induced by E. coli lipopolysaccharide in rats. 769 12

The effect of lipopolysaccharide (LPS) on cardiac protein kinase C (PKC) activation and cardiac depression was evaluated. Guinea pigs (n = 44) received intraperitoneal injections of saline or Escherichia coli LPS (2 mg/kg). Left atria were harvested 16 h later and suspended in oxygenated low calcium (1 mM) (n = 24) or high calcium (5 mM) (n = 20) 30 degrees C Krebs-Henseleit buffer. Atria were treated with H-7 (n = 23), a PKC inhibitor, or vehicle (n = 21). Contractile responses to changes in preload and stimulating frequency, in the resting and potentiated states, and to escalating doses of phenylephrine were measured. PKC activation in ventricular muscle was also determined. LPS activated ventricular PKC (p < .05) but treatment with H-7 failed to reverse LPS-induced atrial dysfunction in the low calcium buffer. Contractile function in the potentiated state indicated that LPS appears to interfere with calcium release from the sarcoplasmic reticulum (SR). The contractile response to phenylephrine was markedly attenuated in atria harvested from endotoxic animals. These data indicate that LPS-induced cardiac depression is mediated, in part, by alterations in SR calcium release. LPS activates cardiac PKC but a causal relationship among LPS, PKC, and cardiac dysfunction remains to be established.
 ...
PMID:The role of protein kinase C in lipopolysaccharide-induced myocardial depression in guinea pigs. 773 71


<< Previous 1 2 3 4 5 6 7 8 9 10