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)

Cortical spreading depression (CSD) has been shown to have neuroprotective effects when administered in advance of cerebral ischemia. The mechanism by which CSD induces its neuroprotective effect however remains to be elucidated. Since MAP kinases have been shown to impart neuroprotection in ischemic preconditioning paradigms, we attempted to determine the role CSD may have in the activation of MAPK. We show that CSD is capable of increasing the phosphorylation of ERK in a MEK-dependent manner. This phosphorylation is, however, transient, as phosphorylated ERK levels return to control levels 45 min after 2 h of CSD elicitation. Immunohistochemical analysis reveals that the phosphorylated form of ERK is located ubiquitously in cells of the CSD-treated cortex while CSD-elicited MEK phosphorylation resides solely in the nuclei. These data suggest that CSD may act via the MAP kinase pathways to mediate preconditioning.
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PMID:Cortical spreading depression transiently activates MAP kinases. 1186 11

Transforming growth factor beta1 (TGF-beta1) induces long-term synaptic facilitation and long-term increases in excitability in Aplysia. Here we report that this growth factor has acute effects as well. Treatment of pleural-pedal ganglia with TGF-beta1 for 5 min activated mitogen-activated protein kinase (MAPK) and stimulated the phosphorylation of synapsin in a MAPK-dependent manner. This phosphorylation appeared to modulate synapsin distribution in cultured sensory neurons. Control neurons exhibited a punctate distribution of synapsin along neurites, which appeared to represent high concentration aggregates of synapsin. TGF-beta1-treated sensory neurons showed a significant reduction in the number of these puncta, an effect that was blocked by the MAP/ERK kinase inhibitor U0126. The functional consequence of TGF-beta1 was tested by examining its effects on synaptic transmission at the sensorimotor synapse. Application of TGF-beta1 reduced the magnitude of synaptic depression. This effect was dependent on MAPK, consistent with the hypothesis that TGF-1 mobilizes synaptic vesicles through the phosphorylation of synapsin.
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PMID:Transforming growth factor beta1 alters synapsin distribution and modulates synaptic depression in Aplysia. 1197 61

The effects of sea snake venom (SSV) on renal function were studied in two groups of anesthetized experimental dogs pretreated with intravenous infusion of 4.2 gm% NaHCO3 solution. Animals were envenomated by intramuscular injection of SSV at a dosage of 0.34 mg/kg. Systemic hemodynamics showed no significant changes except for a tendency of decrease in cardiac output (CO). The glomerular filtration rate (GFR), the rate of urine flow (V) and effective renal plasma flow (ERPF), and effective renal blood flow (ERBF) significantly decreased, while filtration fraction (FF) significantly increased at 180 min after envenomation. Envenomated animals showed a reduction in renal fraction (RF), while renal vascular resistance (RVR) increased stepwise throughout the experimental periods. Animals pretreated with sodium bicarbonate showed no significant changes of CO, TPR MAP, HR, and packed cell volume (PCV) while receiving sea snake venom. Animals pretreated with sodium bicarbonate showed no changes in GFR, ERPF, ERBF, RF, and RVR after envenomation. The rate of urine flow markedly increased in envenomated animals which received pretreatment with bicarbonate. After envenomation alone, there were no differences in the plasma concentration of sodium (PNa) and chloride (PCl) as compared to the control value, whereas the plasma concentration of potassium (PK) increased at 180 min after envenomation. Animals pre-treated with bicarbonate showed a stepwise increase in both UNaV, FE(NA), U(Cl)V, and FE(Cl) accompanying SSV injection. Neither PNa nor PCl were affected, while PK significantly decreased in animals given SSV with bicarbonate loading. UKV and FEK increased stepwise in envenomated animals treated with bicarbonate throughout the period of study. All groups of animals given SSV, with or without NaHCO3 infusion, showed a marked elevation of the concentration of urinary myoglobin (U(Mb)), plasma lactate dehydrogenase (LDH), and plasma creatine phosphokinase (CPK) throughout experimental periods. The urinary myoglobin excretion markedly increased in animals after SSV injection accompanied by NaHCO3 infusion. It can be concluded that large amounts of myoglobin present in the renal tubules in envenomated animals can precipitate, particularly under acidic conditions, resulting in increased intratubular pressure and subsequently decreased renal hemodynamics including GFR and ERBF. An infusion of NaHCO3 to render urine more alkaline could have a protective role against depression of renal function following sea snake venom administration.
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PMID:Renal function following sea snake venom (Lapemis hardwicki) administration in dogs treated with sodium bicarbonate solution. 1200 11

At a symposium on "Controversies in Contraception" at Wayne State University (Detroit), Dr. C. Alvin Paulsen outlined 3 separate trends in using drugs in men to prevent conception: 1) Danazol--a male "pill"; 2) Provera (medroxyprogesterone acetate) as a pill or injection plus monthly testosterone injections; and 3) a combination of the 1st and 2nd methods. The mechanism of action of the pill methods is blocking the ability of the testes to make hormones and the depression of signals coming from the pituitary gland. Advantages of a successful male contraceptive pill include its use as an alternative to sterilizaiton as well as an effective contraceptive with no adverse effects for the female.
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PMID:Interest increasing for male contraceptive pill. 1226 43

Finding the most appropriate contraceptive method for retarded or developmentally delayed young people poses a tremendous challenge to family planning nurse practitioners. Retarded young people have the same sex drive and are influenced by the same pressures affecting sexual decision making as every adolescent. The crucial difference is the retarded person's lack of appropriate information about physical and emotional changes of adolescence, sexuality, and birth control. Since retarded teenagers struggle to be accepted, they tend to be compliant and thus vulnerable to sexual exploitation. Parents are generally more concerned about sexuality in retarded daughters than sons, and many request to have their child sterilized. Mentally retarded teens usually lack the motor skills and motivation to use barrier methods consistently. Long-acting injectable contraceptives such as Depo-Provera offer the greatest protection against pregnancy and have the highest satisfaction rate among parents and caretakers of retarded young people; however, side effects can include depression and weight gain. If hormonal contraception is selected, its effects on seizure activity must be carefully evaluated. In addition, may epileptic teens may be on anticonvulsants or other medications that interfere with the effectiveness of hormonal methods. Sterilization must be approved by the courts and is difficult to obtain if a young woman demonstrates enough comprehension and competence to one day marry and have a family.
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PMID:Physically, mentally disabled teens require special contraceptive care. 1226 27

In a recent survey of 655 women in New Zealand on family planning practices, it was found that 61% were using a contraceptive. The method most used was sterilization (28%); 44% of those using contraceptives had side effects; and 14% experienced contraceptive failure resulting in pregnancy. Dissatisfaction was highest with the pill (24%) and the IUD (23%), while only 3% were dissatisfied a partner's vasectomy. The ages of those surveyed ranged form 18-60 and all were contacted through their physicians. 81% reported pill use in the past but this has dropped to 16%. Side effects such as headaches (21%), depression (17%), irritability (14%), nausea (13%), weight gain (23%), and loss of libido (13%) probably caused this drop in usage, and a 5% pregnancy rate also contributed. Those who used Depo-provera injection had similar effects on a lesser scale but heavy bleeding was common (18%). The IUD had few side effects but heavy bleeding (26%), and pain (19%); also 2.6% needed surgery after IUD insertion. Effects from using other methods such as the diaphragm, sheath, foam or rhythm are not discussed since their use was so small, but pregnancy was high for these methods (16%). In comparing a 1976 study with this one, pill usage changed from 23.1%-15.9%, IUD 2.6%-8.1%, injection 0-3.1%, tubal ligation 6.5%-12.1%, vasectomy 5.1%-15.4%, condom 4.9%-3.1%, rhythm .8-1.4%, other 4.9%-1.6%, which shows that vasectomy has become the most common method of contraception.
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PMID:Contraceptive use and experience amongst a sample of women attending their GP. 1228 68

There is growing evidence from neuroimaging and ostmortem studies that severe mood disorders, which have traditionally been conceptualized as neurochemical disorders, are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that recent preclinical studies have shown that critical molecules in neurotrophic signaling cascades (most notably cyclic adenosine monophosphate [cAMP] response element binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen activated protein [MAP] kinases) are long-term targets for antidepressant agents and antidepressant potentiating modalities. This suggests that effective treatments provide both trophic and neurochemical support, which serves to enhance and maintainnormal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal affective functioning. For many refractory patients, drugs mimicking "traditional" strategies, which directly or indirectly alter monoaminergic levels, may be of limited benefit. Newer "plasticity enhancing" strategies that may have utility in the treatment of refractory depression include N-methyl-D-aspartate antagonists, alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA) potentiators, cAMP phosphodiesterase inhibitors, and glucocorticoid receptor antagonists. Small-molecule agents that regulate the activity f growth factors, MAP kinases cascades, and the bcl-2 family of proteins are also promising future avenues. The development of novel, nonaminergic-based therapeutics holds much promise for improved treatment of severe, refractory mood disorders.
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PMID:Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. 1270 57

Activation of group 1 metabotropic glutamate receptors (mGluRs) induces long-term depression (LTD) of synaptic transmission that relies on dendritic protein synthesis. We investigated the signal transduction pathways required for mGluR-LTD to identify candidate mechanisms for mGluR regulation of synaptic protein synthesis. Our results demonstrate a role for extracellular signal-regulated protein kinase (ERK), a subclass of the mitogen-activated protein kinases (MAPKs), in mGluR-LTD in area CA1 of the rat hippocampus. Inhibitors of the upstream kinase of ERK, MAP/ERK kinase significantly reduce mGluR-LTD induced by the group 1 agonist dihydroxyphenylglycine (DHPG) and synaptic stimulation but do not affect NMDA receptor-dependent LTD. In contrast, inhibitors of p38 MAPK were ineffective against DHPG-induced LTD. Consistent with the role of ERK in mGluR-LTD, we observed that DHPG treatment of hippocampal slices (isolated CA1), at concentrations that induce LTD, results in a robust phosphorylation of ERK but not of p38 MAPK. These results point to ERK as an important regulator of mGluR-LTD and a potential mechanism for mGluR regulation of synaptic protein synthesis.
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PMID:Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1. 1515 46

The efficacy of Withania somnifera (Ws) to limit myocardial injury after ischemia and reperfusion was explored and compared to that of Vit E, a reference standard known to reduce mortality and infarct size due to myocardial infarction. Wistar rats (150-200 g) were divided into six groups and received orally saline (sham, control group), Ws-50/kg (Ws control and treated group) and Vit E-100 mg/kg (Vit E control and treated group) respectively for 1 month. On the 31st day, rats of the control, Vit E and Ws treated groups were anesthetized and subjected to 45 min occlusion of the LAD coronary artery followed by 60 min reperfusion. Hemodynamic parameters: systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), left ventricular peak (+)LVdP/dt and (-)LVdP/dt were monitored. Hearts were removed and processed for histopathological and biochemical studies: Myocardial enzyme viz, creatin phosphokinase (CPK), and antioxidant parameters: malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) were estimated. Postischemic reperfusion produced significant cardiac necrosis, depression of left ventricular functions (MAP, LVEDP, (+) and (-)LVdP/dt) and a significant fall in GSH (p < 0.01), SOD, CAT (p < 0.05), LDH and CPK (p < 0.01) as well as an increase in MDA level (p < 0.05) in the control group rats as compared to sham group. The changes in levels of protein and GPx was however, not significant. Ws and Vit E favorably modulated most of the hemodynamic, biochemical and histopathological parameters though no significant restoration in GSH, MAP (with Vit E) were observed. Ws on chronic administration markedly augmented antioxidants (GSH, GSHPx, SOD, CAT) while Vit E did not stimulate the synthesis of endogenous antioxidants compared to sham. Results indicate that Ws significantly reduced myocardial injury and emphasize the beneficial action of Ws as a cardioprotective agent.
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PMID:Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. 1522 84

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


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