Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: DrugBank:APRD00627 (MAP)
15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 58 patients undergoing orthotopic liver transplantation, aged 42 +/- 10 years (mean +/- SD), and weighing 65 +/- 14 kg. Anesthesia was maintained with fentanyl, midazolam, and vecuronium. Serum bicarbonate, serum potassium, serum ionized calcium and pH did not change significantly throughout the study. Usual hemodynamic parameters were recorded. Hemodynamic tolerance was assessed by a trial of clamping of the inferior vena cava, above and below the liver and the portal vein; patients were allocated to two groups: the group without venovenous bypass (NBP, n = 29) consisted of patients whose MAP did not decrease by more than 30% and/or cardiac output did not decrease by more than 50%; the group with venovenous bypass (BP, n = 29) consisted of patients whose MAP decreased by more than 30% and/or cardiac output decreased by more than 50% or required venovenous bypass for easier surgical dissection. After clamping of the vena cava and the portal vein, the cardiac index (CI) and mean pulmonary arterial pressure (MPAP) decreased significantly, whereas systemic vascular resistances (SVR) increased. After unclamping the inferior vena cava suprahepatically and infrahepatically, no hemodynamic change was observed. After unclamping the portal vein, MAP decreased, despite the increase in the CI, because of an significant decrease in SVR; in addition MPAP increased despite the decrease in pulmonary vascular resistances. The decrease in MAP of more than 30% during at least 1 min occurred in 6 patients (20%) in the NBP group and in 6 patients (20%) in the BP group. We concluded that the occurrence of the syndrome of cardiovascular collapse following liver reperfusion was similar whether venovenous bypass was used or not.
...
PMID:The failure of venovenous bypass to prevent graft liver postreperfusion syndrome. 163 49

Serum concentrations of progesterone begin to rise just before the midcycle gonadotropin surge that leads to ovulation. To examine the role of progesterone in the regulation of these events, we evaluated the effects of a low dose (1 mg/day, orally) of the antiprogesterone RU 486 on the timing of the gonadotropin surge and ovulation in normally cycling women. The drug or a placebo was given for 5 or 15 days, starting when the dominant follicle reached 14-16 mm. RU 486 consistently delayed the timing of the midcycle gonadotropin surge and the subsequent collapse of the dominant follicle, despite rising estradiol concentrations and normal follicular development. Unexpectedly, RU 486 also delayed the emergence of the periovulatory progesterone rise. The addition of progesterone (5-10 mg/day, im, for 2 days) to a 5-day course of RU 486 after the emergence of a mature follicle readily induced LH and FSH surges and completely reversed the effects of RU 486 at midcycle. Our results suggest that RU 486 delays the midcycle gonadotropin surge and ovulation by suppressing or antagonizing an ovarian progestational signal. Progesterone may, thus, represent the ultimate ovarian signal to the estrogen-primed hypothalamic-pituitary unit to trigger the gonadotropin surge that leads to ovulation.
...
PMID:Evidence for a critical role of progesterone in the regulation of the midcycle gonadotropin surge and ovulation. 174 Apr 91

The effects of endothelin-1 (ET-1) administered i.v. or intracerebroventricularly (i.c.v.) on arterial pressure (MAP), heart rate and cardiac output were studied in the conscious rat. Systemic injection of ET-1 (0.1 to 1 nmol/kg i.v.) increased dose-dependently MAP and decreased heart rate. The doses of 0.3 and 1 nmol/kg produced initially transient hypotension and tachycardia which were accompanied by a decrease in total peripheral resistance index (TPRI). Cardiac output was significantly reduced and TPRI increased during the pressor response to 0.3 and 1 nmol/kg ET-1. ET-1 i.c.v. (30 pmol/kg) produced a profound pressor and vasoconstrictor response which was followed by cardiovascular collapse and death within 20 min after i.c.v. injection. Low doses (1 to 10 pmol/kg) of ET-1 i.c.v. had no effect on the cardiovascular system. The present data are in accordance with the studies demonstrating biphasic blood pressure and heart rate responses to i.v. ET-1 in the rat. Profound cardiac depressor and peripheral vasoconstrictor responses were found to accompany the pressor phase. Our results also showed for the first time direct central pressor and vasoconstrictor effects of ET-1 insinuating that endothelin might be a neuropeptide participating in the central cardiovascular control.
...
PMID:Hemodynamic effects of endothelin after systemic and central nervous system administration in the conscious rat. 269 55

In our previous work thyroidectomy significantly improved survival in canine hemorrhagic shock. This finding, coupled with the reported beneficial hemodynamic effects of thyrotropin-releasing hormone (TRH) in circulatory collapse, led to the present study. Anesthetized, heparinized dogs were bled rapidly into a reservoir until MAP = 40 mm Hg. After 60 min of hypotension (E60) the reservoir line was clamped for 30 min (E90). In 10 dogs three doses of TRH (2 mg/kg) were administered iv at 10-min intervals during clamping. In 11 other animals equivalent volumes of saline were given. At E90 the reservoir line was unclamped, and shed blood was reinfused over 30 min. After 1 hr of monitoring (E180) the dogs were returned to the kennel and observed for at least 3 days. Among 11 control dogs, 6 died. In the TRH group only 1 of 10 dogs died (P less than 0.05). During uncompensated shock (E60-E90), TRH-treated dogs had significantly higher mean arterial pressure, cardiac index, stroke index, and right and left ventricular stroke work indexes, and arterial pH than control animals. At the conclusion of the acute experiment (E180) there were few intergroup hemodynamic-metabolic differences. The significant enhancement of 3-day survival by TRH in canine hemorrhagic shock might be related to hemodynamic improvement at a critical stage of circulatory collapse (E60-E90). Direct or indirect neuromodulatory actions of TRH on the CNS could also explain our results. These findings lend further support to the potentially key role of hypothalamic-pituitary-thyroid interrelationships in shock.
...
PMID:Thyrotropin-releasing hormone increases survival in canine hemorrhagic shock. 307 47

The splanchnic circulation constitutes a major portion of the total capacitance vasculature and may affect venous return and subsequently cardiac output during low output states. This study assessed the effects of rapid (10 microg/kg over 5 min) and slow (10 microg/kg over 60 min) induction of endotoxin (Escherichia coli) shock on splanchnic blood volume in 8 farm swine. Blood volume was measured by using Tc99m-labeled erythrocytes and radionuclide imaging. Baseline arterial pressure (MAP), central venous pressure (CVP), and liver, splenic, mesenteric and total splanchnic volumes were stable during the 30-min baseline. Approximately 30 min after the rapid endotoxin infusion, splenic volume decreased by 45%, whereas liver volume increased by 40% and MAP decreased by 60% (P < 0.01). The reduction in splenic volume occurred within 10 min of the endotoxin infusion, whereas liver volume changes occurred after MAP reduction. The slow endotoxin infusion also reduced splenic volume by approximately 50% (P = 0.05), whereas MAP declined by 30% (P < 0.05). However, the slow endotoxin infusion lowered liver volume (P < 0.05). Mesenteric volume was unaffected by the fast or slow endotoxin infusion. Total splanchnic volume was unaffected by the fast infusion but decreased by 37% in the slow infusion group (P < 0.05). In summary, E. coli endotoxin reduces splenic blood volume and increases liver blood volume after acute hypotension ensues. Endotoxin does not increase total splanchnic blood volume and may actually decrease total splanchnic volume in the absence of circulatory collapse. This endotoxin shock model is not associated with blood volume pooling in the splanchnic capacitance circulation.
...
PMID:Endotoxemia alters splanchnic capacitance. 1090 96

The axially chiral ligands 2-(diphenylphosphanyl)-2'-methoxy-1,1'-binaphthalene (MOP; 6) and 2'-dimethylamino-2-(diphenylphosphanyl)-1,1'-binaphthalene (MAP; 7) coordinate to a cationic allylpalladium fragment in an unusual bidentate (P,C)-mode through the triarylphosphane and ipso-carbon atom (C1'). The readily prepared MAP and MOP complexes [Pd[(P,C)-(L)](n3-allyl)][OTf] (9 (L = 7) and 10 (L = 6)) have been characterised in solution (NMR), in which two diastereoisomeric rotamers are observed. The stereochemical identity of the rotamers is established by one- and two-dimensional NMR spectroscopy experiments. In both the solid state and in solution, the allyl unit is shown to coordinate in a slightly distorted n3-mode that results in a more alkene-like character at the allyl terminus trans to phosphane ligand. The opposite allyl terminus, which is trans to the ipsocarbon atom (C1'), is more strongly bound and the dominant allyl stereodynamic process involves C-C bond rotation in an n'-allyl intermediate bound through this carbon. Palladium complexes of MAP and MOP are very efficient catalysts for allylic alkylation of racemic cyclopentenyl pivalate with [NaCH(CO2Me)2] in THF. Isotopic desymmetrisation revealed that the reaction occurs with powerful stereochemical memory effects and consequently with low global ee values. The memory effect is suggested to arise through selective generation of diastereoisomeric [Pd[(P,C)-L](n3-cyclopentenyl)]+ ions (L = MAP or MOP) and subsequent capture by nucleophile before ion-pair collapse or equilibration occurs.
...
PMID:Diastereoisomeric cationic pi-allylpalladium-(P,C)-MAP and MOP complexes and their relationship to streochemical memory effects in allylic alkylation. 1114 Sep 64

Big MAP kinase 1 (BMK1 or ERK5) is a key mediator of endothelial cell (EC) function as shown by impaired embryonic angiogenesis and vascular collapse in BMK1 knockout mice. Hypoxia inducible factor 1alpha (HIF1alpha), a potent mediator of angiogenesis, is positively regulated by the MAP kinases, ERK1/2. Because BMK1 deficiency is associated with impaired angiogenesis we hypothesized that BMK1 might regulate HIF1alpha. To test this hypothesis, bovine lung microvascular ECs (BLMECs) were transfected with HIF1alpha and BMK1 cDNAs, and stimulated by hypoxia. HIF1alpha activity was measured by a reporter gene assay in which luciferase expression was driven by HIF1alpha activation. Hypoxia (1% O2, 24 hours) stimulated HIF1alpha activity by 5.1+/-0.6 fold. In the presence of dominant negative (DN)-BMK1, which inhibited BMK1 activity, hypoxia induced HIF1alpha activity was enhanced significantly to 6.4+/-0.4 fold. BMK1 activation by constitutively active (CA)-MEK5 inhibited HIF1alpha activity by 46+/-4%, suggesting BMK1 functions as a negative regulator of HIF1alpha activation. Activation of BMK1 reduced HIF1alpha protein levels. Ubiquitination inhibitors (30 micromol/L ALLN, 2 micromol/L lactacystin, or 100 nmol/L MG132) reduced the BMK1-mediated effect on HIF1alpha expression by >80%, suggesting that BMK1 stimulated HIF1alpha proteolysis. The negative effect of BMK1 on HIF1alpha was functionally important because transfection with CA-MEK5 significantly decreased EC migration by 68+/-10%, and inhibited angiogenesis (in vitro Matrigel assay) by 76+/-7%. In summary, BMK1 is a novel negative regulator of HIF1alpha and angiogenesis by increasing HIF1alpha ubiquitination and inhibiting HIF1alpha activity in endothelial cells.
...
PMID:BMK1/ERK5 is a novel regulator of angiogenesis by destabilizing hypoxia inducible factor 1alpha. 1587 8

We report fluorescence studies of phototriggered changes in spectral position and shape for two azobenzene-functionalized poly(p-phenylenevinylene) derivatives, poly(2-methoxy-5-(4-phenylazophenyl-4'-(1,10-dioxydecyl))-1,4-phenylenevinylene) (MPA-10-PPV) and poly(2-hexyloxy-5-(4-phenylazophenyl-4'-(1,10-dioxydecyl))-1,4-phenylenevinylene) (HPA-10-PPV). Upon trans --> cis azobenzene photoisomerization, small (ca. 1 nm) blue shifts in spectral position are observed for MPA-10-PPV in 100% toluene, a good solvent for this polymer. These shifts are reversed upon visible irradiation and can be cycled many times. To probe the dependence of these shifts on initial polymer conformation, a dichloromethane-methanol cosolvent study was performed in which the solvent quality was decreased incrementally to induce a reduction in polymer coil dimensions. Unirradiated dichloromethane solutions of both MPA-10-PPV and HPA-10-PPV showed a red shift and reduction in quantum yield with increasing methanol concentration as expected based on literature results for other poly(p-phenylenevinylene) derivatives. These changes have been attributed to a dramatic conformational collapse by others and occur for these azo polymers over the 30-60% (v/v) methanol range. While little or no light-induced spectral shifting was observed at low (<or=20%) and high (>or=70%) methanol concentrations, significant spectral shifts were observed for both polymers upon azobenzene photoisomerization in solutions with 30-60% methanol, the same range over which the polymer undergoes collapse to a highly coiled state. The largest shifts are visible to the eye, with a 65:35 (v/v) dichloromethane-methanol solution of HPA-10-PPV showing yellow-orange fluorescence when the azobenzenes are trans, green fluorescence when they are cis, and yellow-orange again after the azobenzenes are returned to the trans state. We attribute these color changes to a reversible UV-phototriggered expansion of polymer coil dimensions that occurs as a result of trans --> cis azobenzene side chain isomerization and provide temperature data to support this conclusion.
...
PMID:Phototriggered fluorescence color changes in azobenzene-functionalized conjugated polymers. 1633 27

Slits mediate multiple axon guidance decisions, but the mechanisms underlying the responses of growth cones to these cues remain poorly defined. We show here that collapse induced by Slit2-conditioned medium (Slit2-CM) in Xenopus retinal growth cones requires local protein synthesis (PS) and endocytosis. Slit2-CM elicits rapid activation of translation regulators and MAP kinases in growth cones, and inhibition of MAPKs or disruption of heparan sulfate blocks Slit2-CM-induced PS and repulsion. Interestingly, Slit2-CM causes a fast PS-dependent decrease in cytoskeletal F-actin concomitant with a PS-dependent increase in the actin-depolymerizing protein cofilin. Our findings reveal an unexpected link between Slit2 and cofilin in growth cones and suggest that local translation of actin regulatory proteins contributes to repulsion.
...
PMID:Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth cones. 1642 96

Following the induction of DNA damage, a prominent route of cell inactivation is apoptosis. During the last ten years, specific DNA lesions that trigger apoptosis have been identified. These include O6-methylguanine, base N-alkylations, bulky DNA adducts, DNA cross-links and DNA double-strand breaks (DSBs). Repair of these lesions are important in preventing apoptosis. An exception is O6-methylguanine-thymine lesions, which require mismatch repair for triggering apoptosis. Apoptosis induced by many chemical genotoxins is the consequence of blockage of DNA replication, which leads to collapse of replication forks and DSB formation. These DSBs are thought to be crucial downstream apoptosis-triggering lesions. DSBs are detected by ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3 related) proteins, which signal downstream to CHK1, CHK2 (checkpoint kinases) and p53. p53 induces transcriptional activation of pro-apoptotic factors such as FAS, PUMA and BAX. Many tumors harbor mutations in p53. There are p53 backup systems that involve CHK1 and/or CHK2-driven E2F1 activation and p73 upregulation, which in turn transcribes BAX, PUMA and NOXA. Another trigger of apoptosis upon DNA damage is the inhibition of RNA synthesis, which leads to a decline in the level of critical gene products such as MKP1 (mitogen-activated protein kinase phosphatase). This causes sustained activation of JNK (Jun kinase) and, finally, AP-1, which stimulates death-receptor activation. DNA damage-triggered signaling and execution of apoptosis is cell-type- and genotoxin-specific depending on the p53 (p63 and p73) status, death-receptor responsiveness, MAP-kinase activation and, most importantly, DNA repair capacity. Because most clinical anti-cancer drugs target DNA, increasing knowledge on DNA damage-triggered signaling leading to cell death is expected to provide new strategies for therapeutic interventions.
...
PMID:DNA damage-induced cell death by apoptosis. 1689 8


1 2 Next >>

---