Gene/Protein Disease Symptom Drug Enzyme Compound
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 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High blood pressure during pregnancy (BP > or = 140/90 mmHg) is sometimes already noted before conception, with usually a good prognosis (although it could predispose to preeclampsia). alpha-methyldopa is the best treatment when needed (agents blocking the renin angiotensin system are not recommended). Preeclampsia, a form of hypertension noted after 20 weeks of gestation with proteinuria is a more serious condition (BP > or = 140/90 mmHg or increase in BP from the 1st trimester > or = 25/15 mmHg). It is generated by placental ischemia and creates maternal endothelial lesions which in turn decrease the blood flow to placenta leading to maternal and fetal syndromes. Hospitalisation is mandatory. No measure other than delivery is known to attenuate or reverse its progression. Treating hypertension during pregnancy (when blood pressure > or = 170/110 mmHg) aims at preventing maternal risk (stroke or eclampsia) but has few effect on foetal lesions. Prevention of this syndrome, which represents the first secondary cause of hypertension, is until now disappointing.
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PMID:[Hypertension at pregnancy]. 1039 40

Diabetes mellitus and hypertension is often associated, but with a different type of development in type 1 and type 2 diabetes. Type 1 diabetes, renal disease, starting with microalbuminuria, is associated with increasing blood pressure or hypertension, whereas the patient without renal disease is most often normotensive. Poor metabolic control is a predictor of microalbuminuria or incipient nephropathy, but with microalbuminuria hypertension is an important risk factor for progression along with poor glycemic control. The same is the case for overt renal disease, and metabolic control is important in all stages of renal disease in type 1 diabetes. It has also been shown that good metabolic control as well as antihypertensive treatment, especially with ACE-inhibitors, often combined with other agents is quite effective in preventing progression in renal disease in all its stages. In type 2 diabetes, blood pressure elevation is often found as early as at the actual diagnosis, and blood pressure significantly increases according to the degree of albuminuria, normo-microalbuminuria and clinical proteinuria (macroalbuminuria). Elevated blood pressure is an important risk for renal disease but more importantly so also for cardiovascular disease. Several studies document that antihypertensive treatment in particular with ACE-inhibitors is important in preventing microalbuminuria, in treating microalbuminuria and thus preventing progression, also in overt renal disease. Near-normalization of blood pressure is vital. Regarding cardiovascular disease, a series of studies now document that antihypertensive treatment with various antihypertensive agents is able to significantly reduce a number of major cardiovascular complications in diabetes, such as cardiac disease, stroke, and also microvacular disease, including retinopathy. Several studies show that antihypertensive treatment should be started at a level higher than 140-150/90. The blood pressure to be achieved during treatment is probably around 140/85 mmHg or even 130/80 mmHg as a pragmatic goal. However, there is no sign of a J-shaped curve in any of the studies, and therefore even lower blood pressure could be advantageous. Even mortality, at least from diabetes-related causes can be effected by antihypertensive treatment. With more advanced renal disease, normalization of blood pressure is increasingly difficult, especially systolic blood pressure, and therefore it is recommendable to screen patients much earlier on with focus on blood pressure recordings and measurements of albuminuria, including microalbuminuria, and to treat early.
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PMID:Drug treatment for hypertensive patients in special situations: diabetes and hypertension. 1042 11

Antiphospholipid antibodies (APA) were studied in 30 women with a history of recurrent fetal losses. An increased level of anticardiolipin antibodies was found in 7(23.3%) of them, being high and moderate in 4 women. Lupus anticoagulant was present in 9(30.0%) examinees. None cases of SLE were diagnosed. Diagnostically significant APA levels were associated with moderate symptomless thrombocytopenia. 12 of 13 women with antiphospholipid syndrome markers had definite (livedo reticularis, damage of cardiac valves, recurrent thrombophlebitis, leg ulcers, stroke, migraine) and possible (moderate arterial hypertension, proteinuria, retina angiopathy) extragenital features of this disorder. The most serious vascular complications took place in the group with high and moderate levels of anticardiolipin antibodies IgG.
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PMID:[Antiphospholipid syndrome in females with recurrent fetal losses]. 1048 65

We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.
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PMID:Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin. 1060 99

Eclampsia is defined as the occurrence of seizures in pregnancy or within 10 days of delivery, accompanied by at least two of the following features documented within 24 hours of the seizure: hypertension, proteinuria, thrombocytopenia or raised aspartate amino transferase. Eclampsia complicates approximately one in 2,000 pregnancies in the United Kingdom and it remains one of the main causes of maternal death. Up to 38% of cases of eclampsia can occur without premonitory signs or symptoms of pre-eclampsia-that is, hypertension, proteinuria, and oedema. Only 38% of eclamptic seizures occur antepartum; 18% occur during labour and a further 44% occur postpartum. Rare cases of eclampsia have occurred over a week after delivery. Outcome is poor for mother and child. Almost one in 50 women suffering eclamptic seizures die, 23% will require ventilation and 35% will have at least one major complication including pulmonary oedema, renal failure, disseminated intravascular coagulation, HELLP syndrome, acute respiratory distress syndrome, stroke, or cardiac arrest. Stillbirth or neonatal death occurs in approximately one in 14 cases of eclampsia. Up to one third of eclamptic seizures occur out of hospital. For this reason, initial management may involve accident and emergency departments. Early involvement of senior obstetric staff is crucial. Optimal emergency management of seizures, hypertension, fluid balance and subsequent safe transfer is essential to minimise morbidity and mortality.
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PMID:Management of eclampsia in the accident and emergency department. 1065 82

This study was undertaken to find the significant parameters associated with hyperuricaemia in patients with Type 2 diabetes, and hence to determine if hyperuricaemia is associated with poor control of diabetes or increased coronary heart disease. All the diabetic patients seen at a Family Medicine Teaching Clinic within the period January to September 1997 were recruited into the study. In 273 Type 2 diabetics, serum uric acid was analysed against basic demographic data (age, sex, smoking and alcohol habits, body mass index, number of years since the diagnosis of diabetes), present medications, control of diabetic state (attending physician's estimation of the patient's diet compliance, fasting serum sugar, HbA1c), and complications (serum creatinine, total cholesterol, triglyceride, urine proteinuria, retinopathy, last blood pressure readings, history of hypertension, coronary heart disease, stroke). Serum uric acid was significantly associated with body mass index, history of hypertension, serum triglyceride and serum creatinine, but was not related to coronary heart disease, stroke or control of the diabetic state. Female diabetics were more likely to have elevated uric acid. There is not enough evidence for monitoring serum uric acid or for intervention to lower asymptomatic hyperuricaemia in Type 2 diabetic patients.
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PMID:Hyperuricaemia in Type 2 diabetes mellitus. 1078 55

Fenofibrate, a commonly used lipid lowering drug, induces the expression of the gene coding for cytochrome P450-4A, whose major product is 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a potassium channel antagonist, could increase or decrease blood pressure (BP). We studied the effects of four weeks of oral fenofibrate on BP, urine output (UVol), plasma renin activity (PRA), and urine protein excretion in young (4-5 weeks) stroke prone spontaneously hypertensive rats (SHRSP), older (25 weeks) SHRSP, Dahl salt sensitive rats (Dahl S) on a high salt diet, Dahl S rats on a normal salt diet, and normotensive Sprague-Dawley (SD) rats. Fenofibrate prevented the increase in BP in 4-5 week old SHRSP, reduced BP in 25 week old SHRSP, but had no effect on BP in normotensive SD rats. Similarly, fenofibrate prevented the increase in BP in Dahl S rats on a high salt diet, but had no effect in Dahl S rats on a low salt diet. Fenofibrate increased UVol (and reduced weight gain) in young SHRSP and tended to increase it in other groups. It also increased PRA 2 to 5-fold in all groups except older SHRSP. Young SHRSP receiving fenofibrate excreted significantly less urine protein than control rats. The drug reduced proteinuria in Dahl S rats on high salt diet, but had no significant effect on proteinuria in other groups. In summary, fenofibrate reduced blood pressure and weight gain, increased UVol and PRA, and reduced urine protein excretion in young SHRSP. Other groups of animals showed these changes to a variable, but directionally similar extent. These findings are consistent with a natriuretic effect of fenofibrate.
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PMID:Fenofibrate lowers blood pressure in two genetic models of hypertension. 1084 31

The non-insulin-dependent DIABetes, HYpertension, microalbuminuria or proteinuria, CARdiovascular events, and Ramipril (DIABHYCAR) study is a randomized, prospective, double-blind, placebo-controlled, multicenter international trial of the ACE inhibitor ramipril (1.25 mg/day) in patients with type II diabetes and micro- or macroalbuminuria. The main outcome of the study is the time to first occurrence of either death from a cardiovascular origin, including sudden death, nonfatal myocardial infarction, stroke, or congestive heart failure, or requirement of hemodialysis or renal transplantation. The study was launched in France in early 1995 with the participation of general practitioners only, but had to be extended to 15 other countries in 1997 due to difficulties in recruitment. Since 2.5 years after the beginning of the trial the observed event rate was much less than anticipated, it was decided to increase recruitment and follow-up duration and to include congestive heart failure in the definition of the main outcome to keep the study power at a satisfactory level. Recruitment ended on April 1, 1998 with 4937 randomized patients. Following the early discontinuation for efficacy of another study of ramipril in high cardiovascular risk patients, the Heart Outcomes Prevention Evaluation study (HOPE), the second interim analysis of DIABHYCAR was performed early (when 406 instead of 500 patients presented a main outcome) and the Data Safety and Monitoring Board recommended that the study continue. Follow-up is planned to end on March 31, 2001.
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PMID:The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and ramipril (DIABHYCAR) study: design, organization, and patient recruitment. DIABHYCAR Study Group. 1091 14

In previous articles, we have shown that the combination of the angiotensin-converting enzyme (ACE) inhibitor delapril (12 mg/kg/day) and the diuretic indapamide (1 mg/kg/ day) was able to prolong the life span significantly in salt-loaded stroke-prone spontaneously hypertensive rats (SHRsp). Because this finding was partly dependent on the antagonism of salt-loading effects by pharmacologic induction of diuresis, which prevented any increase in blood pressure values, we decided to evaluate whether lower doses of the combination could be equally protective without changing the progression of hypertension. Thus, we studied several treatments with progressively lower doses of delapril (6, 3, or 1.5 mg/kg/day) combined with indapamide (0.5, 0.25, or 0.125 mg/kg/day) or hydrochlorothiazide (2.5, 1.25, or 0.625 mg/kg/day) in salt-loaded SHRsp. Salt-loaded untreated animals were considered to be the control group. In agreement with previous experiments, control rats reached 50% mortality approximately 7 weeks after the beginning of salt loading. The combination of delapril and hydrochlorothiazide at the two lowest doses was not able to delay animal death significantly, whereas treatment with delapril and indapamide at the lowest dose was effective (50% survival rate, 15 weeks). The groups treated with the highest dose of delapril and hydrochlorothiazide or with the intermediate or highest dose of delapril and indapamide did not reach 50% mortality by the end of the experiment, at 44 weeks of treatment (i.e., when animals reached age 1 year). Only the highest delapril and indapamide doses were able to increase diuresis, but for a relatively short period. None of the treatments was able to lower or control blood pressure levels adequately. Therefore, blood pressure levels by themselves were not predictive of rat mortality. In contrast, the maximal value of proteinuria in the weeks preceding death was inversely correlated with the survival time. In conclusion, this study shows that low doses of an ACE inhibitor in combination with a diuretic can be effectively protective in a model of severe hypertension, independent of any change in blood pressure levels.
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PMID:Protective effects of delapril combined with indapamide or hydrochlorothiazide in spontaneously hypertensive stroke-prone rats: a comparative dose-response analysis. 1097 89

Despite reduction of stroke and coronary mortality rates, progression of renal disease to end stage continues to occur with increasing frequency. Recent studies emphasize common pathways of elevated arterial pressures that produce increased glomerular capillary pressures and increase filtered proteins in the urinary space. Such proteinuria, along with activation of the intrarenal renin-angiotensin system, endothelin, and inflammatory cytokines, magnifies progressive renal injury and fibrosis. Malignant forms of hypertension with severe arteriolar injury and proteinuria can be treated effectively with current antihypertensive regimens with improved patient survival. Several recent studies indicate improved renal outcomes in proteinuric diseases, generally regardless of the specific antihypertensive agent. Recent trials of hypertensive subjects with minimal proteinuria demonstrate slower rates of disease progression than that seen in subjects with proteinuria above 1 gram per day. Reduction of arterial pressures, particularly when it leads to reduced proteinuria, can slow the progression of many renal diseases.
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PMID:Importance of blood pressure reduction for prevention of progression of renal disease. 1098 Nov 1


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