Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Information from clinical and pharmacokinetic studies of angiotensin-converting enzyme inhibitors (ACEIs) has come from subjects who are mostly male and Caucasian, but the use of ACEIs extends to populations worldwide. Significant differences between Chinese in general and male Caucasians have been demonstrated in the pharmacokinetics/dynamics of other drug classes that could have implications for the use of ACEIs in the Chinese population. These include: significant Chinese/Caucasian genetic variation in the renin-angiotensin system based on an insertion/deletion (O/D) polymorphism of the ACE gene; the genetic determination of plasma ACE activity in the Chinese population; and genetic factors involving the disease substrate which may also influence the response to treatment. Oral and IV pharmacokinetic data from various studies of Chinese and Caucasian subjects are available for cilazapril, fosinopril, and perindopril, and pharmacodynamic data are available for eight different ACEIs. Based on these data, there are few differences among the pharmacokinetics of ACEIs between Chinese and Caucasians. Most ACEIs showed good blood pressure lowering efficacy in Chinese (benazepril, enalapril, fosinopril and spirapril), with perhaps less blood pressure lowering with cilazapril or a relatively shorter-term effect with cilazapril or perindopril compared to Caucasions. Chinese experience more cough from ACEIs (captopril and enalapril) than Caucasians. Data suggest that fosinopril may not induce cough in as many subjects as other ACEIs, and this seems to be true of Chinese as well. The mechanism, currently unknown, could involve fosinopril's dual elimination pathway (hepatic and renal). Pharmacokinetic data also support the use of fosinopril in congestive heart failure where elimination pathways may be impaired. In conclusion, ethnic differences between Chinese and Caucasians with respect to ACE and AGT gene polymorphism, which might be expected to differentially affect the action of ACEIs in these two ethnic groups, do not, in fact, have such an effect. Rather, differences among the ACEIs appear to be more important. Journal of Human Hypertension (2000) 14, 163-170.
 ...
PMID:Does Chinese ethnicity affect the pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors? 1069 29

Hypertension is often associated with corpulence, an increased total and abdominal fatty mass. The fact of being corpulent exposes to the risk of error of measurement of the blood pressure which may be overestimated by 10 to 16 mmHg and lead to the unnecessary prescription of antihypertensive drugs. In order to analyse the nature of the corpulence, it is useful to define the condition as an increase in fatty and/or lean body mass. It is also useful to quantify the distribution of body fat. Hypertensive patients of increased corpulence, obese (BMI > 30) with an abdominal distribution of adipose tissue, have an increased risk of cardiovascular morbidity-mortality, especially from coronary artery disease: their cardiovascular risk factors consist not only of hypertension and corpulence, but also of metabolic abnormalities and the haemodynamic consequences of corpulence, that is to say diabetes, hypertriglyceridaemia, hypercholesterolaemia, left ventricular hypertrophy and increased glomerular filtration. In hypertension with increased corpulence, the nutritional objective is to decrease the corpulence, decrease the fatty mass without reducing the lean mass. Therefore, it is important to proceed by a progressive, even small, loss of weight with a realistic target because loss of weight is beneficial for the hypertension and its complications (cardiovascular and renal), all other risk factors and for cardiovascular mortality.
 ...
PMID:[Hypertension and obesity]. 1119 Feb 91

The clinician, Franz Volhard, and the pathologist, Theodor Fahr, worked closely together in Mannheim from 1909 until 1915 and introduced a novel classification of renal diseases. In the monograph entitled 'Die Bright'sche Nierenkrankheit, Klinik, Pathologie und Atlas' (1914) they differentiated between degenerative (nephroses), inflammatory (nephritides) and arteriosclerotic (scleroses) diseases. Nephrosclerosis was divided into the benign and malignant form, of which the latter stood the test of time as a new disease entity. Fahr further divided benign nephrosclerosis into the compensated and decompensated form--depending on the presence or absence of glomerular injury. In the pathogenesis of malignant nephrosclerosis, Volhard stressed the decisive role of severe blood pressure elevation, while Fahr postulated an inflammatory mechanism, a concept later confirmed by Adalbert Bohle for at least a minority of patients. A very far reaching concept of Franz Volhard was his idea that pale (renal) hypertension results from a pressor substance released from ischaemic kidney(s) contributing--via a vicious circle--to a further rise in blood pressure with subsequent renovascular injury and aggravation of hypertension. This hypothesis was supported in 1930 by initial experiments of his collaborator, Hartwich (demonstrating in dogs a mild rise in blood pressure after ligation of branches of the renal artery) and definitively proven by Goldblatt (1934) in dogs by induction of severe and persistent hypertension after clamping of both renal arteries. The consequent detection of the renin angiotensin system was the final confirmation of Volhard's postulated renal pressor substance. In the pathogenesis of red (essential) hypertension, Volhard stressed the role of hereditary factors, age, obesity and potentially of severe alcoholism. He emphasised a premature reduction of vascular distensibility (due to elastosis of the prearterioles), a high cardiac output as well as a dampening of baroceptor function. Additionally, Volhard made crucial advances in cardiology and pneumology. Journal of Human Hypertension (2001) 15, 5-16
 ...
PMID:Franz Volhard and Theodor Fahr: achievements and controversies in their research in renal disease and hypertension. 1122 97

This study focuses on certain aspects of the renal structure of the giraffe, with some implications as to its function. About 4,000 collecting ducts open at the truncated end of a curved crest that juts into the renal pelvis as the inner medulla (IM). Extensions of the pelvis pass between the medullary (MP) and vascular (VP) processes almost to the corticomedullary border. The MPs contain an IM and an outer medulla (OM) containing clusters of capillaries (vascular bundles). The VPs contain the interlobar arteries and veins. All of the IM and almost all of the OM, with its vascular bundles, are bathed with pelvic urine. The cortex comprises 63% of the parenchyma. The OM has nine times the mass of the IM. The IM comprises 4% of the parenchyma. The ratio of mass of the adult cortex to the medulla is 1.7:1.0, and the number of glomeruli per kidney is 6.6 x 10(6). Glomerular mass is 6.2-6.7% of renal mass in the adult and 5.2% in the 6-month-old calf. The dimensions of the glomerular capsules are the same across the thickness of the cortex. Every terminal collecting duct drains an estimated 1,650 nephrons. In the adult giraffe the ratio of thickness of the muscularis of the main renal artery (RA) to its diameter is 0.117 (right RA) and 0.132 (left RA). These ratios are close to those in rhinoceros and ox but greater than in man. The visceral arteries (celiac, anterior mesenteric, and renal) have about the same muscularis : diameter ratio. Giraffes have arterial hypertension, but atherosclerosis is apparently absent and serum lipid fractions are low.
 ...
PMID:Kidney of giraffes. 1199 78

(1) Sirolimus, an immunosuppressant, is chemically related to tacrolimus but has a different mechanism of action. (2) In a double-blind trial in patients also treated with ciclosporin and a steroid, sirolimus was more effective than azathioprine at preventing acute rejection during the first three months, but caused more adverse effects (especially renal). (3) An unblinded trial compared ciclosporin + steroid + sirolimus with steroid + sirolimus for maintenance treatment. Ciclosporin was withdrawn gradually from the steroid + sirolimus group. Side effects from ciclosporin were therefore reduced (mainly nephrotoxicity and arterial hypertension), but rates of acute rejection, hepatotoxicity, and thrombocytopenia went up. (4) Sirolimus has numerous adverse effects, including hyperlipidemia, thrombocytopenia, hepatic disorders and opportunistic infections. The adverse effects of long term treatment are unknown. Sirolimus is metabolised by the cytochrome P450 isoenzyme CYP3A4, so may induce drug interactions. (5) In practice, sirolimus offers no advantage over existing immunosuppressive treatments for people with renal transplants.
 ...
PMID:Sirolimus: new preparation. No tangible advance in renal transplantation. 1246 93

The adequate dosage of peritoneal dialysis (PD) has been defined (using unrandomized and uncontrolled studies) asKt/V = 2, with a total (peritoneal + renal) creatinine clearance = 60 mL/min. The recent prospective, randomized ADEMEX study, suggests targets of 1.8 and 54 mL/min respectively. Dialysis must also be adequate to control fluid removal, phosphate levels, nutritional status, and hypertension. The targets for automated PD (APD) should be either 10% more than CAPD or similar, depending on the time of blood sample collection either immediately at the end of the automated exchanges or 6 to 8 hours after. A peritoneal equilibration test should be done 1 to 2 months after the start of PD, yearly, and when peritoneal permeability or ultrafiltration changes occurr. Residual renal function must be protected as long as possible by avoiding nephrotoxic drugs and excessive dehydration. Every effort must be taken in the attempt to maintain a good nutritional status and to diagnose as soon as possible any changes toward malnutrition. Hypertension has a high prevalence in PD patients and has negative effects on both cardiovascular status and patient survival. However, anti-hypertensive therapy should avoid hypotension, mainly in older patients, who are more at risk for cerebrovascular accident. Hyperparathiroidism must be controlled by diet, phosphate binders, and calcitriol supplement, but attention must be paid to avoid cardiac and vascular calcifications. Peritonitis and exit-site infection should be prevented by all means available. In the case of infection, empiric antibiotic therapy should be started as soon as possible and then adapted according to the antibiogram.
 ...
PMID:[Guidelines of the Italian Society of Nephrology. Peritoneal dialysis Guidelines]. 1466 7

The decline of residual renal function (RRF) in peritoneal dialysis (PD) patients was analysed and assessed, and risk factors affecting its decline were identified. Residual glomerular filtration rate (GFR) was calculated from averaging the urea and creatinine clearance by 24-h urine collection, and peritoneal solute removal was evaluated by creatinine clearance calculated from 24-h effluent collection. Both GFR and peritoneal solute removal were chronologically examined in 34 PD patients from the time of initiation, and risk factors associated with rapid GFR decline were investigated. The RRF contributed to 43.1 +/- 17.6% of total (peritoneal and renal) weekly creatinine clearance at 1 month after initiation of PD. Residual GFR, however, declined continuously with time (-0.19 +/- 0.14 mL/min per month), and the reduction rate was high with a higher GFR, higher normalized dietary protein intake, higher urine volume and higher urine protein excretion at the initiation of PD. Other factors related to the rapid decline of GFR were: being older than 60 years of age, automated peritoneal dialysis (APD) rather than continuous ambulatory peritoneal dialysis, mean blood pressure higher than 110 mmHg, and serum human atrial natriuretic peptide level higher being than 60 pg/dL. These data suggest that while RRF plays an important role in the removal of uraemic solute in PD patients, they show a significant decrease over 2 years. The factors related to the rapid decline of GFR corresponded to older age, modality of PD (APD), higher GFR and higher amount of urine protein at initiation, higher dietary protein intake, and inadequate control of hypertension and body fluid volume.
 ...
PMID:Preservation of residual renal function and factors affecting its decline in patients on peritoneal dialysis. 1501 19

Olmesartan medoxomil (Belsar, Olmetec) developed by Sankyo Pharma and proposed by Sankyo Pharma but also Menarini is a new angiotensin II ATI receptor blocker. Its indication is the treatment of hypertension. Olmesartan is indeed an antihypertensive agent with an efficacy dependent on the dose from 10 to 40 mg. It is taken once a day, because of a long duration of action. This prodrug has a dual elimination pathway (biliary and renal). The contraindications are the same as for the other sartans. One of its main advantage, besides its rapidly observed efficacy to lower high blood pressure, is its relatively low cost within this family. It has also cardiovascular and renal protective effects. The recommended usual dosage is 20 mg/day.
 ...
PMID:[The drug of the month: Olmesartan medoxomil]. 1562 83

Until relatively recently, depression has been considered a purely "mental" disorder and therefore in the natural domain of psychologists and psychiatrists. However, recent epidemiological studies have revealed that aging, physical and psychological stress, chronic pain, several metabolic disorders such as insulin resistance and established diabetes, alcoholism, inflammatory conditions, and vascular disorders such as arterial hypertension all may be associated with depression. The present review examines some of these depression-associated factors and the mechanisms by which they might give rise to vascular disorders such as atherosclerosis, microcirculation endothelial dysfunction, and interstitial disturbances leading to organ damage. A number of disorders involving the circulation can lead progressively and insidiously to large artery rigidity, remodeling of peripheral arteries, and alterations of the microcirculation of large blood vessels. Perturbations in vasa vasorum blood flow may contribute to atherogenesis, in addition to the influence of numerous cellular events involved in inflammation (tumor necrosis factor alpha, interleukin 1 beta, etc). Since Hans Selye first described the neuroendocrine cascade generated by experimentally induced stress half a century ago, phenomena such as the axonal release of neurotransmitters (including serotonin), accumulation of metabolites such as homocysteine, platelet-activating factor, and nitric oxide also have been implicated in the pathogenesis of depression. Moreover, vascular consequences of depression such as heart rate and pulse pressure variations may lead to endothelial dysfunction in critical microcirculation networks (cerebral, myocardial, and renal) and initiate physicochemical alterations in interstitial compartments adjacent to vital organs. The appropriate use of ambulatory monitoring of vascular parameters, such as heart rate and pulse pressure, and eventually, early identification of genetic and metabolic markers may prove helpful in the early detection of events preceding and predicting the clinical manifestations of depression.
 ...
PMID:Depression and cardiovascular disease: a reciprocal relationship. 1587 13

Adrenal myelolipoma is a rare, benign and biochemically inactive tumor. It is usually diagnosed incidentally by radiological methods and is known to be associated with obesity, hypertension, endocrinological disorders and some malignancies. We report herein the association of a myelolipoma with a gastrointestinal stromal tumor. To our knowledge this is the first report of such an association to date. A 67-year-old male patient admitted to our clinic with abdomimal pain and fever; he had a history of hypertension and diabetes mellitus. In physical examination, a mass involving the right quadrants was palpated. Computerized tomography revealed a right retroperitoneal mass, probably originating from the kidney or cecum. In laparotomy, the tumor (12 cm radius and 1500 g) localized on the superior of right kidney was excised. Abdomen exploration revealed another mass with 10 cm radius 100 cm distal to the ligamentum of Treitz and segmental jejunal resection and anastomosis were applied. The pathological diagnosis was reported as myelolipoma for the retroperitoneal mass and leiomyosarcoma for the jejunal mass. Myelolipoma is a benign tumor, involving mature fat and hematopoietic stem cells. Pathogenesis is still not clear and the microscopical characteristics are hematopoietic, lipoid, and reticuloid cells and megakaryocytes. Myelolipomas are reported to be associated with some other malignancies (especially renal), but this is the first report showing the association with a leiomyosarcoma. Therefore, leiomyosarcoma should also be one of the possible associations kept in mind by the physician in the diagnosis and treatment of myelolipomas.
 ...
PMID:Giant adrenal myelolipoma associated with small bowel leiomyosarcoma: a case report. 1683 Feb 97


<< Previous 1 2 3 4 5 Next >>