UMLS:C0020473 - FACTA Search

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

Query: UMLS:C0020473 (hyperlipidemia)
15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.
...
PMID:Small bowel review: normal physiology part 1. 1176 47

Effect of coconut protein in rats fed high fat cholesterol containing diet on the metabolism of lipids and lipid peroxides was studied. In addition, effect of coconut protein were compared with rats fed L-arginine. The results indicate that those fed coconut protein and those fed L-arginine showed significantly lower levels of total cholesterol, LDL+ VLDL cholesterol, Triglycerides and Phospholipids in the serum and higher levels of serum HDL cholesterol. The concentration of total cholesterol, triglycerides and phospholipids in the tissues were lower in these groups. There was increased hepatic cholesterogenesis which is evident from the higher rate of incorporation of labeled acetate into free cholesterol. Increased conversion of cholesterol to bile acids and increased fecal excretion of bile acids were observed. Feeding coconut protein results in decreased levels of Malondialdehyde in the heart and increased activity of Superoxide dismutase and Catalase. Supplementation of coconut protein causes increased excretion of urinary nitrate which implies higher rate of conversion of arginine into nitric oxide. In the present study, the arginine supplemented group and the coconut protein fed group produced similar effects. These studies clearly demonstrate that coconut protein is able to reduce hyperlipidemia and peroxidative effect induced by high fat cholesterol containing diet and these effects are mainly mediated by the L-arginine present in it.
...
PMID:Hypolipidemic and antiperoxidative effect of coconut protein in hypercholesterolemic rats. 1188 11

Common complications of diabetes are accelerated atherosclerosis and vascular disturbances. We investigated whether the simultaneous insult of hyperlipemia-hyperglycemia affects the reactivity of the resistance arteries to bradykinin (BK), and if so, what are the mechanisms responsible for this disturbance. Experiments were conducted on male Golden Syrian hamsters rendered hyperlipemic (H) by a fat-rich diet, diabetic (D) by streptozotocin injection, or simultaneously hyperlipemic-diabetic (HD). Normal age-matched animals were used as controls (C). At 24 weeks after the induction of disease(s) the vascular reactivity of the mesenteric resistance arteries to BK (10(-8)-10(-4) M) was assayed by the myograph technique. To explore the role of nitric oxide (NO) in modulating the endothelium-dependent BK-induced relaxation, two experimental approaches were employed: (i) in vivo administration of L-arginine (622.14 mg/kg bw) to H, D, and HD hamsters (for 12 weeks); (ii) in vitro blockage of nitric oxide synthase by N(omega)-nitro- L-arginine methyl ester (10(-4) M). To evaluate the contribution of Ca2+-activated K+ channel(s) to BK-induced relaxation, the resistance arteries were exposed to 10(-3) M tetraethylammonium. Comparatively, the endothelium-independent relaxation was assayed using sodium nitroprusside (10(-8)-10(-4) M). The results showed that compared to the H and D groups, the HD hamsters exhibited the most reduced vasodilation of the resistance arteries to BK (34.09 +/- 1.5%). The diminished vasodilation was found to be due to a dual mechanism: an L-arginine:NO pathway and a NO-independent process, mediated via Ca2+-activated K+ channels. In vivo administration of L-arginine had favourable effects especially in the HD group, which manifested (i) an; 30% improvement of attenuated BK relaxation, (ii) an increase in sensitivity of the response to BK, (iii) a 3-fold diminishment of plasma hyperglycemia. Collectively, these data explain in part, the mechanisms and possible ways to correct the arterial endothelial dysfunction when diabetes is complicated with hyperlipemia.
...
PMID:Mechanisms of decreased bradykinin- induced vasodilation in experimental hyperlipemia-hyperglycemia: contribution of nitric oxide and Ca2+-activated K+ channels. 1190 2

The syndrome that is characterized by obesity, insulin resistance, and hyperlipidemia is increasingly prevalent in all prosperous societies. It is now recognized as a major contributor to cardiovascular disease. Vascular dysfunction in the form of hypercontractility and impaired nitric oxide-mediated relaxation is a significant component of cardiovascular disease, predisposing to ischemic events. The JCR:LA-cp strain of rats exhibits all major aspects of the obesity/insulin resistance syndrome, including vascular dysfunction and ischemic lesions of the heart. Dietary lipid intake may have a marked effect on plasma lipid levels and, potentially, on vascular disease. We have investigated the effects of a novel preparation, ONC101 (a phytosterol esterified with fish oil), on plasma lipids and vascular function in the insulin-resistant JCR:LA-cp rat. Treatment of obese male rats with ONC101 from 8 to 12 wk of age resulted in no change in plasma lipid concentrations at 0.5 g/kg body weight. At the higher dose of 2.6 g/kg, plasma TG fell 50% (1.26 vs. 2.59 mmol/L, P < 0.002) and cholesterol esters were significantly reduced (1.34 vs. 1.61 mmol/L, P < 0.002). Food intake and body weights were unaffected by ONC101 treatment. At the low dose of 86 mg/kg, the hypercontractility of aortic rings in response to phenylephrine was normalized and the relaxant response to acetylcholine was significantly improved. The results indicate that ONC101 at high doses has significant hypolipidemic effects and, at very low doses, has beneficial effects on endothelial and vascular smooth muscle cell function.
...
PMID:Improvement of vascular dysfunction and blood lipids of insulin-resistant rats by a marine oil-based phytosterol compound. 1191 Nov 16

Management of the conventional cardiovascular risk factors is insufficient to prevent the dramatic increase in atherosclerotic cardiovascular morbidity and mortality in patients with renal failure. Folate recently received attention as a potential alternative treatment option to decrease the excess cardiovascular risk in the uremic population. Folate administration is the principal treatment modality for hyperhomocysteinemia. Hyperhomocysteinemia is prevalent in more than 85% of patients with end-stage renal disease (ESRD) and is independently associated with increased odds for atherosclerotic cardiovascular disease. Several attempts have been made to normalize homocysteine levels in uremic patients with folate-based vitamin regimens. Although supraphysiologic doses of folic acid afford greater reductions in homocysteine levels than standard doses, the response to treatment is generally only partial and the large majority of ESRD patients have residual hyperhomocysteinemia. Several defects in folate metabolism have been described in uremia, which may explain the relative folate resistance in patients with renal failure, but their clinical relevance remains uncertain. It appears unlikely that the hyperhomocysteinemia in ESRD can be cured solely with folic acid supplements, since folate does not affect the prolonged plasma elimination of homocysteine, which is the primary defect in homocysteine metabolism in uremia. Folate restores endothelial dysfunction, associated with hyperlipidemia, diabetes and hyperhomocysteinemia. The beneficial effect appears to be independent of its homocysteine-lowering capacity and is possibly related to an improved bioavailability of nitric oxide. However, folate has failed to improve endothelial dysfunction in uremic patients. In the ESRD population, multiple metabolic and hemodynamic abnormalities adversely affect endothelial function. In addition, irreversible structural vascular disease already may be present. Folate should, therefore, probably be an integral part of an "endothelial protective regimen," consisting of lipid-lowering agents, antihypertensives and antioxidant vitamins and started very early in patients with renal failure. Before large-scale folate administration can be recommended, effects on hard endpoints of cardiovascular disease need to be demonstrated in randomized trials. Such trials are currently underway in patients with normal renal function at high risk for cardiovascular disease, and one trial has recently been initiated in stable renal transplant recipients.
...
PMID:Is folate a promising agent in the prevention and treatment of cardiovascular disease in patients with renal failure? 1263 Nov 53

Dialysis patients constitute a high-risk subset of patients for developing cardiovascular disease, which accounts for nearly 50% of deaths. After stratification for age, race and gender, cardiovascular mortality is 10-20 times higher in dialysis patients than in the general population. Cardiovascular disease in this population cannot be fully explained by the high prevalence of classical cardiovascular risk factors (age, hypertension, diabetes, hyperlipidemia, smoking, etc.). Thus, the involvement of "new" cardiovascular risk factors (hyperhomocysteinemia, hyperfibrinogenemia, high lipoprotein (a) levels, oxidative stress, inflammation, etc.), and uremia-related factors (anemia, impaired calcium-phosphorus metabolism, hyperparathyroidism, accumulation of endogenous inhibitors of nitric oxide synthesis, etc.) has been also invoked to play a role in the increased cardiovascular risk in these patients. Endothelial dysfunction is the initial event in the development of atherosclerosis. Uremic patients exhibit an endothelial dysfunction, even before starting dialysis, which persists o is even aggravated under dialysis treatment. Uremic patients must be considered at high risk of developing cardiovascular disease. Thus cardiovascular risk factors in these patients should be managed early, aggressive and multifactorially in order to reduce their high cardiovascular morbidity and mortality.
...
PMID:[Cardiovascular risk in patients with chronic renal failure. Patients in renal replacement therapy]. 1198 73

Nitric oxide (NO) plays a pivotal role in the pathophysiology of coronary artery disease. The roles of NO are not only physiological but also pathological in the cardiovascular system. An inappropriate release of NO has been linked to the pathogenesis of CAD. The authors investigated whether serum NOx (nitrate and nitrite), a stable end product of NO, level was related to patients with coronary artery disease. The blood chemistry, such as cholesterol, triglyceride, LDL-C, HDL-C and blood sugar, was also measured in comparison with serum NOx. Serum NOx was measured in samples from 20 healthy controls, 20 angina patients without angiographic evidence of coronary lesions (CAG) and 20 angina patients with angiographic evidence of coronary lesions (CAD) by using modified Griess reaction. The mean serum NOx levels in the CAD groups was higher than CAG and control groups (41.3 +/- 5.5, 32.7 +/- 3.9 and 25.7 +/- 3.5 micromol/L, respectively). NOx levels in the CAD group was only significantly higher than the control groups (p < 0.05) but not the CAG groups. There were no significant differences of NOx levels in all age groups. In the CAD group, women showed significantly higher NOx levels than men (64.0 +/- 7.5 and 29.0 +/- 4.7 microl/L, respectively, p < 0.05). Interestingly, the mean serum NOx levels in the CAD groups was significantly higher in a group of abnormal lipid profiles (cholesterol, triglyceride, LDL-C) and blood sugar than in a group of normal profiles. The results suggested that there was an increased NOx levels in patients with coronary artery disease and much higher in patients with multiple underlying conditions such as hyperlipidemia and hyperglycemia. Thus, the measurement of the NOx levels at different times may help to monitor the state and severity of coronary artery disease.
...
PMID:Serum nitric oxide levels in patients with coronary artery disease. 1200 15

The objective of this study was to evaluate whether administration of L-arginine, the substrate for nitric oxide synthesis, was able to ameliorate the endothelial dysfunction and the morphological changes induced by the combined insult of hyperlipemia and hyperglycemia. To this purpose, golden Syrian hamsters were rendered simultaneously hyperlipemic and diabetic (HD group) for 24 weeks, and then orally treated with 622.14 mg/kg per day L-arginine, for 12 weeks (HD + L-arg group). The following assays were carried out: (1) spectrophotometric: concentrations of circulating glucose, cholesterol, and creatinine, the activity of angiotensin-converting enzyme (ACE), and the osmotic fragility of erythrocyte plasmalemma; (2) myographic: the endothelium-dependent and -independent relaxation of the resistance arteries (i.d. 210-250 microm) to 10(-8) to 10(-4) M acetylcholine (ACh) or sodium nitroprusside (SNP); and (3) electron-microscopic: the ultrastructure of the resistance arteries, myocardium, and kidney glomeruli, which are main targets of hypertensive complications. The results showed that oral supplementation with L-arginine in simultaneous hyperlipemia-hyperglycemia induced in hamsters had favorable effects on: (1) homeostasis, i.e., diminished the concentration of circulating glucose (by ~63%) and cholesterol (by approximately 10%), reduced the ACE activity (by approximately 45%), and lowered the osmotic fragility of erythrocyte plasmalemma (as marker for the oxidative stress in plasma); (2) mesenteric resistance arteries, which showed (in 10(-4) M ACh) an improved endothelium-dependent relaxation (72.40+/-4.6% in the HD + L-arg group vs 61.90+/-1.45% in the HD group) and a reduced thickness (approximately 1.32-fold) of the smooth muscle cells' extracellular matrix; and (3) the heart, which displayed approximately 16% diminishing of the thickness of the left ventricular wall, and an apparently normal structure of the myocardium; the restoration of the thickness of the pericapillary extracellular matrix to almost normal dimensions was also observed. Administration of L-arginine did not modify the high level of plasma creatinine determined for the HD group (approximately 48% increased vs control group) and had no effect on the thickened, nodular basal lamina of the kidney capillaries. The results indicate that endothelial dysfunction established in combined hyperlipemia-diabetes is distinctive for each vascular bed (mesenteric arterioles, heart capillaries, kidney glomerular capillaries), and there is a reversible stage of the dysfunction in which L-arginine oral supplementation induced beneficial effects.
...
PMID:Beneficial effects of L-arginine supplementation in experimental hyperlipemia-hyperglycemia in the hamster. 1201 11

Postprandial hyperlipidemia is frequently associated with diabetes mellitus and considered to be an independent coronary risk factor. Nitric oxide (NO) is a key regulator of glucose uptake in skeletal muscle. The goal of this study was to examine the effects of chronic in vivo competitive antagonism of NO synthase (NOS) by the administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) on glucose and lipid metabolism in diabetic (Otsuka Long-Evans Tokushima Fatty [OLETF]) and nondiabetic rats. Chronic administration of L-NAME to rats induced reduced NO production and hypertension in both strains of rats. No detectable impairment of plasma levels of postprandial triglyceride (TG) or insulin sensitivity in nondiabetic rats was detected by chronic treatment of L-NAME, but significant impairment was observed in the cases of diabetic rats. These results suggest that diabetes, when associated with endothelial dysfunction, results in greater abnormalities in lipid, as well as glucose metabolism.
...
PMID:Chronic feeding of a nitric oxide synthase inhibitor induces postprandial hypertriglyceridemia in type 2 diabetic model rats, Otsuka Long-Evans Tokushima Fatty rats, but not in nondiabetic rats. 1203 22

Modifications by hyperlipidemia of endothelium-dependent and -independent relaxations were evaluated in cerebral and temporal arteries from control and hyperlipidemic (high cholesterol-fed) monkeys. Histologically atherosclerotic lesions were not observed in either group. Relaxations induced by histamine, abolished by N(G)-nitro->L-arginine (>L-NA), were significantly potentiated in the hyperlipidemic monkey cerebral arteries, compared with those in the arteries from control monkeys. Treatment with superoxide dismutase did not affect the histamine-induced relaxation. Conversely, endothelium-dependent relaxations induced by A23187, Ca2+ ionophore, in cerebral arteries did not differ between control and hyperlipidemic monkeys. In temporal arteries, relaxations by acetylcholine and A23187 did not differ between control and hyperlipidemic monkeys. Endothelium-dependent and -independent relaxations by adenosine diphosphate in cerebral and temporal arteries were not affected by hyperlipidemia. Endothelium-independent relaxations by exogenously applied nitric oxide did not differ in the arteries from control and hyperlipidemic monkeys. Nicotine-induced relaxations in cerebral arteries, which were mediated with nitric oxide released from nitroxidergic (nitrergic) nerves, and the contractions caused by nicotine in temporal and mesenteric arteries treated with >L-NA did not differ between control and hyperlipidemic monkeys. It is concluded that long exposure to hyperlipidemia did not affect endothelial functions of monkey middle cerebral and temporal arteries but enhanced nitric oxide-mediated relaxations caused by histamine, possibly due to upregulation of endothelial histamine receptor-mediated functions in the cerebral arteries. The nitroxidergic (nitrergic) and adrenergic nerve functions do not seem to be affected by hyperlipidemia.
...
PMID:Endothelial and neuronal functions in cerebral and temporal arteries from monkeys fed a high-cholesterol diet. 1219 32

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>