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

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maternal lung edema due to the use of beta-mimetic tocolytic agents is a well-documented complication. The risk increases if several other factors are present: infectious diseases, the use of inhaled anesthetics, EPH gestosis, hydramnios, twin gestation and preexisting cardiovascular disease. The complications induced by beta-mimetic tocolytic agents can be reduced by remembering their side effects and contraindications and restricting fluid intake. During obstetric general anesthesia in patients undergoing tocolysis, the infusion of large amounts of saline, as is widely practised today, is strictly contraindicated.
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PMID:[Maternal pulmonary edema as an anesthesia complication after intravenous tocolysis and stimulating of lung maturation]. 135 38

While there is still much debate in the literature regarding the specific MET levels at which there are differences in survival, the following points have become clear with the growing body of reports in the literature. Exercise capacity seems to be an independent predictor of mortality, and when it is combined with other clinical, exercise, or angiographic data, it becomes very powerful in this regard. This relates to both overall mortality and to that from cardiovascular disease. There is still a need for the establishment of mortality data related to MET levels adjusted for age and activity status. A low exercise capacity of less than 6 METs indicates a higher mortality group, probably regardless of the underlying extent of coronary disease or left ventricular function. Analysis of the CASS data has indicated that these patients benefit from coronary artery bypass surgery with respect to survival. An exercise capacity of greater than 10 METs designates an excellent survival group, again despite the extent of coronary artery disease or left ventricular function. If 10 METs truly exerts a "protective effect" that obviates any survival benefit from coronary artery bypass surgery, this has enormous implications for cost containment and medical care. It is nonetheless important to remember that this level of exercise capacity does not imply the absence of either coronary disease or triple-vessel coronary disease. Exercise capacity is related to more than just cardiovascular fitness and integrity. It is dependent upon a combination of other physiologic components as well, including pulmonary function, health status of other organ systems, nitrogen balance, nutritional status, medications, orthopedic limitations, and others.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The prognostic value of exercise capacity: a review of the literature. 195 Oct 7

Cardiovascular disease in all its clinical manifestations progresses significantly as age advances and takes its heaviest toll in the elderly. Hypertension becomes the dominant risk factor for cardiovascular disease in this age group because of its high incidence. Traditionally, diastolic rather than systolic blood pressure has been regarded as the main risk factor for cardiovascular complications in hypertension, although it is becoming clearer that the risk of cardiovascular complications is likely to be associated mainly with systolic pressure in the elderly. Various intervention drug trials in elderly patients seem to indicate that hypotensive drug treatment can decrease cardiovascular mortality, mainly by decreasing cerebrovascular mortality. The EWPHE used a diuretic combination with methyldopa, and the HEP study used atenolol with a thiazide diuretic. The multicenter Systolic Hypertension in the Elderly Program (SHEPS) currently underway in the United States is likely to also provide some answers. The place of newer agents such as ACE inhibitors or calcium antagonists is still undetermined. Calcium antagonist drugs have been reported to be effective, and possibly more so in the elderly than in a younger population, although this assumption is not proven and may not be valid. Pharmacokinetic studies in the elderly are very few, although the studies reported indicate a reduced clearance. Studies also indicate that Nifedipine Retard tablets are effective, with a low incidence of adverse effects. There are no trials, however, looking at the long-term benefit of treating elderly hypertensive patients with either nifedipine tablets or other calcium-channel blockers.
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PMID:Hypertension in the elderly. 207 5

Several studies have demonstrated an increased risk of cardiovascular disease (CVD) in relation to high blood pressure in elderly patients aged below 70-75, whereas the risk seemed to decline with age in the older elderly. Early studies on the effect of treatment of mild to moderate hypertension in the elderly indicated (but did not convincingly show) a reduction of CVD. In the 1980s, both the EWPHE trial (European Working Party on High Blood Pressure in the Elderly) and the HEP study (The Randomised Trial of the Treatment of Hypertension in Elderly Patients in Primary Care) provided evidence of the benefit of treating high blood pressure in the elderly, at least up to the age of 70-74. These results have lately been confirmed by three major trials SHEP (Systolic Hypertension in the Elderly Program), STOP (Swedish Trial in Old Patients with Hypertension) and MRC (Medical Research Council), also including older patients (STOP) and those with isolated systolic hypertension (SHEP). This satisfactory effect was not impaired by a low tolerability of the drugs used (beta-blockers and diuretics). In conclusion, drug treatment with beta-blockers and diuretics in hypertensive men and women aged 70 and above confers highly significant and clinically relevant reductions in cardiovascular (especially stroke) morbidity and mortality. The clinical implication of this is that blood pressure lowering therapy should be considered in elderly hypertensives, at least up until they are 80. It should also be remembered that elderly hypertensives often have other diseases as well and that the drug treatment should be adjusted accordingly.
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PMID:Hypertension in the elderly. 826 94

The mechanisms responsible for the accelerated cardiovascular disease in diabetes, as well as the increased hypertrophic effects of angiotensin II (Ang II) under hyperglycemic conditions, are not very clear. We examined whether the culture of vascular smooth muscle cells (VSMC) under hyperglycemic conditions to simulate the diabetic state can lead to increased activation of key growth- and stress-related kinases, such as the mitogen-activated protein kinases (MAPKs), in the basal state and in response to Ang II. Treatment of porcine VSMC for short time periods (0.5 to 3 hours) with high glucose (HG; 25 mmol/L) markedly increased the activation of the extracellular signal-regulated kinase (ERK1/2) and c-Jun/N-terminal kinase (JNK) relative to cells cultured in normal glucose (NG; 5.5 mmol/L). p38 MAPK also was activated by HG, and this effect remained sustained for several hours. Ang II treatment increased the activity of all 3 families of MAPKs. Ang II-induced ERK activation was potentiated nearly 2-fold in cells treated with HG for 0.5 hour. However, Ang II-induced JNK was not altered. In VSMC cultured for 24 hours with HG, Ang II and HG displayed an additive response on p38 MAPK activity. MAPKs can lead to activation of transcription factors such as activator protein-1 (AP-1). HG alone significantly increased AP-1 DNA-binding activity. Furthermore, Ang II and HG combined had additive effects on AP-1 activity. These results suggest that increased activation of specific MAPKs and downstream transcription factors, such as AP-1, may be key mechanisms for the increased VSMC growth potential of HG alone and of Ang II under HG conditions.
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PMID:Angiotensin II signaling in vascular smooth muscle cells under high glucose conditions. 993 Nov 33

Crosstalk between the cyclic AMP-dependent protein kinase (PKA) and growth factor receptor signaling is one of many emerging concepts of crosstalk in signal transduction. Understanding of PKA crosstalk may have important implications for studies of crosstalk between other, less well known, signaling pathways. This review focuses on PKA crosstalk in arterial smooth muscle. Proliferation and migration of arterial smooth muscle cells (SMCs) contribute to the thickening of the blood vessel wall that occurs in many types of cardiovascular disease. PKA potently inhibits SMC proliferation by antagonizing the major mitogenic signaling pathways induced by growth factors in SMCs. PKA also inhibits growth factor-induced SMC migration. An intricate crosstalk between PKA and the mitogen-activated protein kinase (MAPK/ERK) pathway, the p70 S6 kinase pathway and cyclin-dependent kinases has been described. Further, PKA regulates expression of growth regulatory molecules. The result of PKA activation in SMCs is the potent inhibition of cell cycle traverse and SMC migration. In this review, we discuss recent advances in our understanding of the crosstalk between PKA and signaling pathways induced by growth factor receptors in SMCs, and where relevant, in other cell types in which interesting examples of PKA crosstalk have been described.
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PMID:Crosstalk between protein kinase A and growth factor receptor signaling pathways in arterial smooth muscle. 1040 57

As part of a 60-week, open-label, nonrandomized, parallel, controlled study comparing a monthly contraceptive injection containing medroxyprogesterone acetate (MPA) 25 mg and estradiol cypionate (E(2)C) 5 mg (Lunelle Monthly Contraceptive Injection) and a norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE) triphasic oral contraceptive (Ortho-Novum(R) 7/7/7), a longitudinal examination of lipid profiles was conducted. Lipid parameters were assessed at screening and at weeks 20, 40, and 60 (or the final visit) in 114 women using MPA/E(2)C and 93 using NET/EE (lipid analysis population). Extra blood samples were obtained at weeks 21, 22, and 23 in 61 MPA/E(2)C users and 51 NET/EE users (index-cycle analysis population) to investigate lipid changes during one cycle of use. In the index-cycle population, median changes from screening to week 60 showed a decrease in apolipoprotein (apo) A-I and apo A-II in both groups. MPA/E(2)C users had a decrease in total cholesterol (C), total triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with maintenance of the total C/HDL-C ratio. NET/EE users showed an increase in total C and LDL-C, with no change in HDL-C or the total C/HDL-C ratio. Within the index cycle (weeks 20 to 23), median changes in lipid values in both MPA/E(2)C and NET/EE users were generally greatest during the first week after the injection or the start of the pill pack. The results of this first longitudinal examination of serum lipids in US women using MPA/E(2)C confirm earlier findings in women in other countries. However, a direct comparison of the effects of MPA/E(2)C and NET/EE on lipid profiles was not possible in this study because of its design and because of the baseline and pharmacokinetic/pharmacodynamic differences between the two contraceptive groups. The results of this analysis showed that, although overall lipid values decreased, including a significant decrease in HDL cholesterol, the maintenance of the total-C/HDL-C ratio suggests that the effect of MPA/E(2)C on lipid parameters may not negatively affect CVD risk over 1 year of use. However, these results warrant further investigation, given the nature of this trial.
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PMID:Comparative effects of Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension) and ortho-Novum 7/7/7 oral contraceptive (norethindrone/ethinyl estradiol triphasic) on lipid profiles. Investigators from the Lunelle Study Group. 1074 70

Hyperhomocysteinemia is a well established risk factor for cardiovascular disease, and multiple factors likely lead to abnormal regulation of plasma homocysteine in patients with diabetes. To examine a possible role for insulin and glucose in homocysteine metabolism, we examined the activity of two important enzymes of homocysteine metabolism in hepatocytes. In various tissues of six mice, methylene tetrahydrofolate reductase (MTHFR) activity was present in all tissues tested and the highest concentration (per gram) was in the brain. In contrast, cystathionine beta-synthase (CBS) activity appeared to be present only in the liver and to a small extent in the kidney. Using HEP G2 cells in culture, MTHFR activity was 3.3+/-0.8 nmol/h when the glucose concentration in the medium was 100 mg/dl and fell to 2.3+/-0.3 nmol/h when glucose was increased to 300 mg/dl. MTHFR activity was 3.4+/-0.3 nmol/h when cells were exposed to an insulin concentration of 5 mU/ml and fell to 2.8+/-0.3 nmol/h when insulin concentration was increased to 200 mU/ml (P<0.01). In contrast CBS activity increased from 0.017 to 0.13 U/ml by increasing the glucose concentration in the medium (P<0.01), but decreased from 0.04 to 0.02 (P<0.01) when the insulin concentration was increased from 5 to 200 mU/ml, respectively. We conclude that CBS and MTHFR have different tissue distributions, with CBS being present predominantly in liver and kidney, and MTHFR found in many tissues. In addition, both insulin and glucose affect the activity of the two enzymes when added to hepatocytes in vitro. If such effects occur in humans with hyperglycemia and hyperinsulinemia, then alterations in homocysteine metabolism may contribute to the accelerated macrovascular disease associated with insulin resistance or type 2 diabetes.
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PMID:The effect of glucose and insulin on the activity of methylene tetrahydrofolate reductase and cystathionine-beta-synthase: studies in hepatocytes. 1158 7

Mesenchymal tumors of the appendix are very rare, and specific stromal tumors (i.e., gastrointestinal stromal tumors, GISTs) have not been reported in this location to date. Four GISTs were identified in the review of primary mesenchymal tumors of the appendix from the files of the Armed Forces Institute of Pathology from 1970 to 1998. There were also one benign schwannoma, one diffuse neurofibroma with neurofibromatosis 1, one leiomyosarcoma in a child with HIV infection, and one inflammatory fibroid polyp. The four appendiceal GISTs occurred in adult males 56-72 years of age (mean 63 years). Two tumors occurred in patients who had surgery for appendicitis-like symptoms: one was an incidental finding during surgery for a malignant gastric epithelioid GIST and one was an incidental autopsy finding. Only one of the two appendices operated for symptoms had acute inflammation, and a polypoid GIST projected outward from the proximal part of appendix. Three tumors were partially obliterating nodules, eccentrically expanding the appendiceal wall. All four were spindle cell tumors, and three of them contained extracellular collagen globules (skeinoid fibers); none had atypia or mitotic activity (<1/50 high power fields). Immunohistochemically, two tumors studied were positive for CD117 (KIT), and two were positive for CD34. The tumors were negative for alpha-smooth muscle actin and S-100 protein. Follow-up revealed death from cardiovascular disease in one case (4 years after appendectomy) and liver failure because of malignant gastric epithelioid GIST metastatic to liver in another case 15 years after the appendectomy. This report documents the rare occurrence of CD117-positive GISTs as primary appendiceal tumors.
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PMID:Gastrointestinal stromal tumors in the appendix: a clinicopathologic and immunohistochemical study of four cases. 1622 28

45 women aged 27-37 participated in a 6-month study of the effects of 3 kinds of oral contraceptives (OC), (DSG, LNG, and NET) on changes in lipoprotein and apolipoprotein metabolism. The women took each of the 3 kinds of OC for 3 cycles sequentially and had blood tests after taking each kind of OC. The results of the blood tests showed that DSG was associated with an increased level of HDL-C, TG, TC, apo AI, and apo AII; and reduced the ratio of LDL-C/HDL-C. Compared with DSG, LNG was associated with a reduction in HDL-C level, the changes in other parameters were smaller than DSG. The comparison of LNG and NET was similar to that of DSG and LNG. Comparing NET with DSG, the increase of HDL-C and apo AI induced by NET was not as high as that of DSG; nevertheless, the changes in other parameters induced by DSG and NET were similar. The LDL-C/HDL-C ratio and apo AI/apo B ratio induced by DSG were the most favorable. Using DSG or NET can result in an increase of serum protein levels. LNG reduced the HDL-C level, but its changes in other serum protein levels were not significant. An increase in the HDL-C level is protective of the cardio vascular system and is beneficial to women who have a low level of HDL-C. Alternating the use of different kinds of OCs could reduce the side effects of changing serum lipoprotein metabolism. As the subjects of the study were healthy young women, the association of OCs with the risk of cardiovascular disease (CVD) other studies could not be proved, but the possibility of higher risk of CVD in OC users may be present in view of the increased TC/HDL-C and LDL-C/HDL-C ratios in OC users.
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PMID:[Comparative study of the effects of three different kinds of oral contraceptives on lipoprotein and apolipoprotein metabolism]. 1231 81


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