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)

Cytotoxicity of triethylene glycol dimethacrylate (TEGDMA), a co-monomer of dental resinous restorative materials, is firmly established in vitro, but the molecular mechanisms are unknown. Here we examined apoptosis and necrosis induced by TEGDMA in human primary pulp cells. The levels of apoptotic and necrotic cell populations differentially increased after exposure to increasing concentrations of TEGDMA. A two-fold increase in the percentage of apoptotic cells was induced by 1 mmol/L TEGDMA. However, a population shift among cells in apoptosis and necrosis was detected when cell cultures were exposed to 2 mmol/L TEGDMA. Inhibition of the MAP Kinase/ERK pathway had no influence on cell survival, but inhibition of phosphatidylinositol 3 kinase (PI3-Kinase; Akt/protein kinase B) by LY294002 amplified TEGDMA-induced apoptosis. Moreover, Akt phosphorylation was inhibited in the presence of TEGDMA. These results suggest that depression of PI3K signaling may be a primary target in TEGDMA-induced apoptosis.
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PMID:Inhibition of phosphatidylinositol 3-kinase amplifies TEGDMA-induced apoptosis in primary human pulp cells. 1532 76

Increased oxidative stress and reduced nitric oxide (NO) bioactivity are key features of diabetes mellitus that eventually result in cardiovascular abnormalities. We assessed whether N-acetylcysteine (NAC), an antioxidant and glutathione precursor, could prevent the hyperglycaemia induced increase in oxidative stress, restore NO availability and prevent depression of arterial blood pressure and heart rate in vivo in experimental diabetes. Control (C) and streptozotocin-induced diabetic (D) rats were treated or not treated with NAC in drinking water for 8 weeks, initiated 1 week after induction of diabetes. At termination, plasma levels of free 15-F2t-isoprostane, a specific marker of oxygen free radical induced lipid peroxidation, was increased while the plasma total antioxidant concentration was decreased in untreated diabetic rats as compared to control rats (P<0.05). This was accompanied by a significant reduction of plasma levels of nitrate and nitrite, stable metabolites of NO, (P<0.05, D vs. C) and a reduced endothelial NO synthase protein expression in the heart and in aortic and mesenteric artery tissues. Systolic, diastolic and mean arterial blood pressures (SBP, DBP and MAP) and heart rate (HR) were reduced in diabetic rats (P<0.05 vs. C) and NAC normalised the changes that occurred in the diabetic rats. The protective effects may be attributable to restoration of NO bioavailability in the circulation.
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PMID:Antioxidant N-acetylcysteine restores systemic nitric oxide availability and corrects depressions in arterial blood pressure and heart rate in diabetic rats. 1639 Aug 27

Bupropion has been used to treat psychic depression and as a therapy for smoking cessation, the latter mainly in association with nicotine. However, there have been no detailed studies of the hemodynamic effects of the association of bupropion with nicotine during replacement therapy. In this study, we evaluated the effects of such an association on the cardiovascular parameters in anesthetized dogs. Bupropion, either alone or together with nicotine, had no significant effect on the cardiac index (CI; 4.7 +/- 0.2 vs 4.3 +/- 0.1 and 3.5 +/- 0.3 vs 3.4 +/- 0.3 L x min(-1) x m(2), respectively; mean +/- SEM) and mean arterial pressure (MAP; 134 +/- 5.0 vs 145 +/- 11.0 and 118 +/- 5.0 vs 133 +/- 10.5 mmHg, respectively). There was a slight but significant increase in the systemic vascular resistance index (SVRI; 2,165 +/- 93 vs 2,645 +/- 126 and 2,335 +/- 100 vs 2,737 +/- 200 dyn x cm(-5)m(-2), respectively). However, there was a significant increase in the mean pulmonary artery pressure (MPAP; 20 +/- 0.8 vs 25 +/- 1.6 and 18 +/- 1.3 vs 25 +/- 1.6 mmHg, respectively; p < 0.05) and pulmonary vascular resistance index (IRVP; 194 +/- 11 vs 272 +/- 21 and 206 +/- 32 vs 307 +/- 42 dyn x cm-5m(-2), respectively; p < 0.05). These results show that bupropion alone or in association with nicotine does not markedly affect most hemodynamic parameters of the systemic circulation, although the significant increase in MPAP and IRVP can elevate the pulmonary pressure.
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PMID:Hemodynamic effects of a combination of bupropion and nicotine in anesthetized dogs. 1684 83

Twenty-three women with premenstrual dysphoric disorder (PMDD) and 29 non-PMDD controls were compared for plasma progesterone (P) and its neuroactive steroid metabolite allopregnanolone (ALLO), as well as the ALLO/P ratio following the double-blind, placebo controlled administration of 300 mg oral micronized progesterone. Approximately half of each group had prior depression (DEP) (13 PMDD, 12 non-PMDD), though all were free of current depression. Progesterone and ALLO were sampled 160, 190, 225, and 255 min after progesterone administration. Changes over time in plasma concentrations and the ALLO/P ratio were assessed using area under the curve analyses. Women with prior DEP had lower ALLO levels (p=0.05) and marginally lower P levels (p<0.07) following progesterone administration compared to never depressed women, and this was especially evident in the non-PMDD women (p<0.01). PMDD women with no prior DEP had higher pre-progesterone ALLO/P ratios than all other groups (Ps<0.05) and higher ratios than the never depressed, non-PMDD women following oral progesterone (p<0.05). Results could not be accounted for by group differences in steroid hormone binding protein concentrations. For all women, progesterone administration was associated with increased confusion, fatigue, and with reduced confidence (Ps<0.01), even after controlling for placebo-associated mood change. These results suggest a persistent effect of prior DEP on P and ALLO concentrations following oral progesterone and that PMDD women, especially those with no prior DEP, may have alterations in the metabolic pathways underlying the conversion of P to ALLO.
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PMID:Associations of histories of depression and PMDD diagnosis with allopregnanolone concentrations following the oral administration of micronized progesterone. 1704 66

Increased blood pressure induces functional and structural changes of the vascular endothelium. Depression of endothelium-dependant vasodilatation is an early manifestation of endothelial dysfunction due to hypertension. It can be demonstrated by pharmacological or physiological tests. Decreased availability of nitric oxide (NO) is a major determinant of the depression of vasodilatation. It may be caused by a reduction in the activity of NO-endothelial synthase (NOSe) related to: 1) a deficit in substrate (L-arginine), 2) an inhibition by asymmetrical dimethylarginine, 3) a deficit in the cofactor tetrahydrobiopterin (BH4). However, the increase in oxidative stress, a producer of superoxide radicals which combine with NO to form peroxynitrates (ONOO-), is the determining factor. It is related to activation of membranous NAD(P)H oxidases initiated by the stimulation of activating mecanosensors of protein C kinase. The message is amplified by oxidation of BH4 which transforms the NOSe into a producer of superoxide radicals. A cascade of auto-amplification loops leading to atherosclerosis and its complications is then triggered. The superoxide radicals and the peroxynitrates oxidise the LDL-cholesterol. They activate the nuclear factor-kappaB which controls the genes stimulating the expression of many proteins: angiotensinogen and AT1 receptors which stimulate the sympathetic system, receptors of oxidised LDL, adhesion and migration factors (ICAM-1, VCAM-1, E-selectin and MCP-1), pro-inflammatory cytokins (interleukines and TNF-alpha), growth factors (MAP kinases), plasminogen activator inhibitor 1. The monocytes and smooth muscle cells produce metalloproteinases and pro-inflammatory cytokins which destabilise the atheromatous plaque and favourise vascular remodelling. Inshort, the endothelial dysfunction due to hypertension plays a role in a complex physiopathological process and is a marker of future cardiovascular events.
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PMID:[Hypertension, endothelial dysfunction and cardiovascular risk]. 1710 Jan 43

Pharmaceutically induced metabolic down-regulation may be a useful therapeutic adjunct when tissue oxygen supply is restricted. We hypothesized that protein synthesis inhibition in a non-hibernating species should lower oxygen demand, resulting in aerobic metabolic rate depression at the whole animal level. We compared metabolic responses and measures of systemic oxygenation of conscious catheterized rats given either protein synthesis inhibition (PSI) agents or carrier controls (normal saline and DMSO). Core temperature was measured by implanted transmitters, and VO2 was determined in an open flow-through metabolic chamber at 25 degrees C. Mean arterial pressure MAP and heart rate HR were determined from arterial pressure transducer tracings; arterial blood gases and lactate were sampled every 15 min. PSI rats exhibited an immediate transient decline in VO2, followed by a secondary decline to new resting levels; VO2 for the first hour was significantly lower than that for rats receiving DMSO vehicle. Unlike controls, PSI rats showed an overall 3.5 degrees C decline in core temperature, coupled with increased arterial lactate. There were no differences in MAP and HR of PSI rats compared to controls. Although hypothermic response to toxic agents typical of rodents cannot be ruled out completely, the mild hypothermia and reduced VO2 exhibited by PSI rats may be partially attributed to the action of protein synthesis agents.
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PMID:Pharmaceutical metabolic down-regulation by protein synthesis inhibition in a conscious rat model. 1729 27

Cardiovascular dysfunction in septic shock (SS) is ascribed to the release of inflammatory mediators. Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. This effect can be blocked in an in vitro preparation by chitobiose, a competitive inhibitor of Lzm-S. In the present study, we examined whether chitobiose treatment can reverse myocardial depression and obviate NE requirements in two respective canine E. coli preparations. In a 6-h study, we administered chitobiose after 3.5 h of E. coli bacteremia and compared stroke work (SW) and MAP at 6 h with a sepsis control group. In a 12-h study, we determined whether chitobiose treatment can reduce the need for NE requirements during 12 h of bacteremia. In the latter study, either chitobiose or NE was given when MAP decreased approximately 20% from the presepsis value in respective groups. In anesthetized, mechanically ventilated dogs, we monitored hemodynamic parameters during continuous E. coli infusion. In the 6-h study, chitobiose improved SW and MAP at the 6-h period as compared with the nontreated sepsis group. In the 12-h study, SW and MAP increased after chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.
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PMID:N,N'-diacetylchitobiose, an inhibitor of lysozyme, reverses myocardial depression and lessens norepinephrine requirements in Escherichia coli sepsis in dogs. 1788 42

Here we investigated the incidence of cortical spreading depolarizations (spreading depression and peri-infarct depolarization) after traumatic brain injury (TBI) and their relationship to systemic physiologic values during neurointensive care. Subdural electrode strips were placed on peri-contusional cortex in 32 patients who underwent surgical treatment for TBI. Prospective electrocorticography was performed during neurointensive care with retrospective analysis of hourly nursing chart data. Recordings were 84 hr (median) per patient and 2,503 hr in total. In 17 patients (53%), 280 spreading depolarizations (spreading depressions and peri-infarct depolarizations) were observed. Depolarizations occurred in a bimodal pattern with peak incidence on days 1 and 7. The probability of a depolarization occurring increased significantly as a function of declining mean arterial pressure (MAP; R(2) = 0.78; p < 0.001) and cerebral perfusion pressure (R(2) = 0.85; p < 0.01), and increasing core temperature (R(2) = 0.44; p < 0.05). Depolarization probability was 7% for MAP values of >100 mm Hg but 33% for MAP of < or =70 mm Hg. Temperatures of < or =38.4 degrees C were associated with a 21% depolarization risk, compared to 63% for >38.4 degrees C. Intracranial pressures were higher in patients with depolarizations (18.3 +/- 9.3 vs. 13.5 +/- 6.7 mm Hg; p < 0.001). We conclude that depolarization phenomena are a common cortical pathology in TBI. Their association with lower perfusion levels and higher temperatures suggests that the labile balance of energy supply and demand is an important determinant of their occurrence. Monitoring of depolarizations might serve as a functional measure to guide therapeutic efforts and their blockade may provide an additional line of defense against the effects of secondary insults.
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PMID:Spreading depolarizations and late secondary insults after traumatic brain injury. 1950 56

We describe the assessment and treatment of a mother who was a victim of domestic violence and of her 10-year-old son, both of whom were living in a domestic violence shelter. The Parent-Child Interaction Assessment-II Modifying Attributions of Parents intervention (PCIA-II/MAP; Bohr, 2005; Bohr et al., 2008; Bohr & Holigrocki, 2005) is a structured brief treatment using video recordings from a parent's play with his or her child. The play involves using toy people and animals to complete story stems related to a trip to the zoo (see Holigrocki, Kaminski, & Frieswyk, 1999, 2002). The therapist shows the parent video excerpts of the interaction, invites reflection and commentary, and collaborates with the parent to change how she makes sense of her child's behaviors. The pretreatment assessment revealed a depressed, fearful, highly stressed mother with a harsh parenting style. Her son experienced significant distress; had behavior problems; and viewed adults as harsh, fragile, irresponsible, and unavailable. Posttreatment gains were evident in the parent's reduced depression and greater parenting sensitivity; however, parenting stress and child behavior problems remained elevated. We emphasize the utility and application of a multimodal assessment that integrates rating scales, free response, and video-recorded interactions.
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PMID:Interventional use of the parent-child interaction assessment-II enactments: modifying an abused mother's attributions to her son. 1967 46

Human ovarian granulosa cells obtained from women undergoing in vitro fertilization were exposed to 15.6, 31.25, 62.5, 125, 250, 500, 1000 muM Ni(2+) for 48 h. To determine the site of action of Ni(2+), the granulosa cells were stimulated to produce progesterone (P) by using maximally stimulating amounts of human chorionic gonadotropin (0.1 IU/ml hCG) or dibutyryl cyclic adenosine monophosphate (1 mM db-cAMP). The luteinizing hormone (LH) analog hCG was chosen because resultant P production requires an intact membrane receptor and db-cAMP was used to test for post LH receptor defects caused by Ni(2+). Progesterone content of the culture medium was determined by radioimmunoassay (RIA), and viability of the cells was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction test. Concentration-dependent depression in both hGC and db-cAMP stimulated P production was seen at 15.625 muM or higher concentration of Ni(2+), which is not cytotoxic on human ovarian granulosa cells. The viability of cells was unaffected up to 31.25 muM and decreased significantly at 62.5 muM. Our results show a dose-related depression in stimulated P production of granulosa cells at a dose that does not induce significant cytotoxic action. These data indicate that the effect of Ni(2+) on P production is not due to cytotoxicity, and the cellular site(s) of inhibitory action appears to be subsequent to the membrane receptor and production of cAMP.
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PMID:Effect of nickel (ni(2+)) on primary human ovarian granulosa cells in vitro. 2002 Nov 8


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