Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Usual risk factors for coronary artery disease account for only 25-50% of increased atherosclerotic risk in diabetes mellitus. Other obvious risk factors are hyperglycemia and dyslipidemia. However, hyperglycemia is a very late stage in the sequence of events from insulin resistance to frank diabetes, whereas lipoprotein abnormalities are manifested during the largely asymptomatic diabetic prodrome and contribute substantially to the increased risk of macrovascular disease. The insulin-resistant diabetes course affects virtually all lipids and lipoproteins. Chylomicron and very-low-density lipoprotein (VLDL) remnants accumulate, and triglycerides enrich high-density lipoprotein (HDL) and low-density lipoprotein (LDL), leading to high levels of potentially atherogenic particles and low levels of HDL cholesterol. Hyperglycemia eventually impairs removal of triglyceride-rich lipoproteins, the accumulation of which accentuates hypertriglyceridemia. As triglycerides increase-still within the so-called normal range-abnormalities in HDL and LDL became more apparent. Thus, when triglycerides are >200 mg/dL, LDL particles are small and dense (when they are <90 mg/dL, the particles are of the large, buoyant variety). The atherogenicity of small, dense LDL particles is attributed to their increased susceptibility to oxidation, but in many patients they may be a marker for insulin resistance or the presence of atherogenic VLDL. Hypertriglyceridemia is associated with atherosclerosis because (1) it is a marker for insulin resistance and atherogenic metabolic abnormalities; and (2) the small size of triglyceride-enriched lipoproteins enables them to infiltrate the blood vessel wall where they are oxidized, bind to receptors on macrophages, and ingested, leading to the development of the atherosclerotic lesion. Various studies (primary prevention with gemfibrozil: Helsinki Heart Study; secondary prevention with simvastatin and pravastatin: Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events [CARE], respectively) have demonstrated that lipid-lowering therapy in type 2 diabetes is effective in decreasing the number of cardiac events. Risk reduction was 22% to 50% (statins) and approximately 65% (fibrate) relative to placebo. It was also noted (in 4S and CARE) that the risk of major coronary events in untreated diabetic patients was 1.5-1.7-fold greater than in untreated nondiabetic patients. Although gemfibrozil (fibric acid derivative) is more effective in decreasing triglycerides and increasing HDL cholesterol in diabetic patients than the statins, it does not change and may even increase LDL-cholesterol levels (fenofibrate may be an exception, decreasing LDL cholesterol by 20-25% in some studies). However, gemfibrozil does increase LDL particle size. Nevertheless, the statins are the current lipid-lowering drugs of choice because the change in LDL-cholesterol-to-HDL-cholesterol ratio is better than with gemfibrozil. Moreover, the diabetic patient may be more likely to benefit from statin therapy than the nondiabetic patient. It should be noted that, in theory, nicotinic acid can correct or improve all lipid or lipoprotein abnormalities in patients with type 2 diabetes. Unfortunately, it is relatively contraindicated because it causes insulin resistance and may precipitate or aggravate hyperglycemia (in addition to its other well-known side effects such as flushing, gastric irritation, development of hepatotoxicity, and hyperuricemia). It is unknown at present whether newer formulations such as once-daily Niaspan may be better tolerated in diabetes. In any case, most patients with type 2 diabetes have risk factors for coronary artery disease and qualify for aggressive LDL cholesterol-lowering therapy. At the same time, it is presently unknown whether improved glycemic control decreases coronary artery disease risk in such patients.
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PMID:Diabetic dyslipidemia. 991 65

Recent studies have demonstrated the importance of insulin-like growth factors (IGF) in mouse preimplantation development. We examined IGF-1 and IGF-1 receptor (IGF-1R) gene expression in a single blastomere of an early mouse embryo and compared it with subsequent embryo development in culture. Fertilized eggs and 2-cell embryos were obtained by tubal flushing in superovulated and mated female mice. Single cells were removed from embryos at cleavage stage between 3 and 8 cells using the standard embryo biopsy techniques. Individual blastomeres from each embryo were then assayed for the presence of IGF-1 and IGF-1R mRNA using reverse transcription-polymerase chain reaction. The biopsied embryos were washed in medium and placed in co-culture with murine endometrial cells. Embryonic development in culture was assessed and blastocyst grading was performed. IGF-1 gene expression was then examined for an association with in-vitro development. Eighty-seven embryos were biopsied. IGF-1R gene expression was detected in the majority of embryos tested and IGF-1 gene expression was detected in 34 of 81 (42%) embryos. A significant association between IGF-1 expression and blastocyst formation in vitro was found (P < 0.01). There was no association between IGF-1R expression and subsequent embryo development. We conclude that IGF-1 gene expression could potentially be used as a marker of embryo quality.
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PMID:Expression of the insulin-like growth factor-1 gene and its receptor in preimplantation mouse embryos; is it a marker of embryo viability? 1046 Feb 25

The sulphonylurea drugs have been the mainstay of oral treatment for patients with diabetes mellitus since they were introduced. In general, they are well tolerated, with a low incidence of adverse effects, although there are some differences between the drugs in the incidence of hypoglycaemia. Over the years, the drugs causing the most problems with hypoglycaemia have been chlorpropamide and glibenclamide (glyburide), although this is a potential problem with all sulphonylureas because of their action on the pancreatic beta cell, stimulating insulin release. Other specific problems have been reported with chlorpropamide that occur only rarely, if at all, with other sulphonylureas. Hyponatraemia secondary to inappropriate antidiuretic hormone activity, and increased flushing following the ingestion of alcohol, have been well described. The progressive beta cell failure with time results in eventual loss of efficacy, as these agents depend on a functioning beta cell and are ineffective in the absence of insulin-producing capacity. Differences in this secondary failure rate have been reported, with chlorpropamide and gliclazide having lower failure rates than glibenclamide or glipizide. The reasons for this are unclear, but the more abnormal pattern of insulin release produced by glibenclamide may be partly responsible and, indeed, may explain the increased risk of hypoglycaemia with this agent. Previously reported increased mortality associated with tolbutamide therapy has not been substantiated, and more recent data have shown no increased mortality from sulphonylurea treatment. Indeed, benefit from glycaemic control, regardless of the agent used--insulin or sulphonylurea--was reported by the United Kingdom Prospective Diabetes Study. Nevertheless, there is still ongoing controversy in view of the experimental evidence, mainly from animal studies, of potential adverse effects on the heart from sulphonylureas, but these are difficult to extrapolate into clinical situations. Most of these studies have been carried out with glibenclamide, which makes comparison of possible risk difficult. Other cardiovascular risk factors may be modified by gliclazide, which seems unique among the sulphonylureas in this respect. Its reported haemobiological and free radical scavenging activity probably resides in the azabicyclo-octyl ring structure in the side chain. Reduced progression or improvement in retinopathy has been reported in comparative trials with other sulphonylureas, and the effect is unrelated to improvements in glycaemia. There are differences between the sulphonylureas in some adverse effects, risk of hypoglycaemia, failure rates and actions on vascular risk factors. As a group of drugs, they are very well tolerated, but differences in overall tolerability can be identified.
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PMID:Comparative tolerability of sulphonylureas in diabetes mellitus. 1078 25

Gastroenteropancreatic (GEP) neoplasms originate from any of the various cell types belonging to the neuroendocrine system. A general characteristic of GEP endocrine tumours is that the vast majority produce and secrete a multitude of peptide hormones and amines. Many patients with malignant metastasising tumours present clinical symptoms related to hormone hyperproduction. These include the so-called carcinoid syndrome, characterised by flushing, diarrhoea, wheezing and right heart disease, which is predominantly associated with the serotonin- and tachykinins-producing carcinoids of the midgut. Several types of syndrome associated with GEP endocrine tumors are caused by overproduction of a specific hormone. For instance, the well-known Zollinger-Ellison syndrome is gastrin-mediated. The so-called 'insulinoma syndrome' depends on excessive production of insulin and proinsulin, resulting in hypoglycemia. The 'glucagonoma syndrome' is characterised by necrolytic migratory erythema, diabetes and diarrhoea. The Verner-Morrison syndrome, which is brought about by high circulating levels of vasointestinal peptide (VIP). produces severe secretory diarrhoea. Finally the 'somatostatinoma syndrome' involves gallbladder dysfunction and gallstones, diarrhoea with or without steatorrhea, and impaired glucose tolerance. The biochemical diagnosis of endocrine digestive tumors is based on general and specific markers. The best general markers are chromogranin A (CgA) and pancreatic polypeptide (PP). Specific markers for endocrine tumors include insulin, gastrin, glucagon, vaso intestinal polypeptide (VIP), somatostatin and the primary cathabolic product of serotonin, 5-hydroxyndoleacetic acid (5-HIAA). Localisation procedures commonly applied, in the diagnosis of endocrine tumours include ultrasound (US), computed tomography (CT) and somatostatin receptor scintigraphy (SRS).
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PMID:Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours. 1176 60

This paper reviews some important links between nutrition and reproduction in a seasonal breeder, the mink (Mustela vison). The energetic costs of reproduction in mink are partly covered by mobilization of body fat reserves. A reduced food supply before the breeding season is detrimental to reproductive performance, and release of LH and ovulation may not occur in animals in extremely poor body condition. Nutritional flushing comprising a 2 week period of slightly restricted feeding, followed by ad libitum feeding for 4-5 days before the start of the mating season can influence reproductive performance positively. Reproductive endocrinology, ovulation and implantation rate, and early embryo development are affected by the modification of important metabolic signals including insulin, insulin-like growth factor I (IGF-I) and the thyroid hormones.
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PMID:Links between nutrition and the reproductive axis in a seasonal breeder, the mink (Mustela vison). 1178 96

Automated sampling and fluorogenic derivatization of islet proteins (insulin, proinsulin, c-peptide) are separated and analyzed by a novel lab-on-valve capillary electrophoresis (LOV-CE) system. This fully integrated device is based on a micro sequential injection instrument that uses a lab-on-valve manifold to integrate capillary electrophoresis. The lab-on-valve manifold is used to perform all microfluidic tasks such as sampling, fluorogenic labeling, and CE capillary rejuvenation providing a very reliable system for reproducible CE separations. Fluorescence detection was coupled to an epiluminescence fluorescence microscope using a customized capillary positioning plate. This customized plate incorporated two fused-silica fiber optic probes that allow for simultaneous absorbance and fluorescence detection, extending the utility of this device. Derivatization conditions with respect to the sequence of addition, timing, injection position, and volumes were optimized through iterative series of experiments that are executed automatically by software control. Reproducibility in fluorogenic labeling was tested with repetitive injections of 3.45 mM insulin, yielding 1.3% RSD for peak area, 0.5% RSD for electromigration time, and 2.8% RSD for peak height. Fluorescence detection demonstrated a linear dynamic range of 3.43 to 6.87 microM for insulin (r2 = 0.99999), 0.39 to 1.96 pM for proinsulin (r2 = 0.99195) and 260 to 781 nM for c-peptide (r2 = 0.99983). By including hydrodynamic flushing immediately after the detection of the last analyte, the sampling frequency for islet protein analysis was increased. Finally, an in vitro insulin assay using rat pancreatic islet excretions was tested using this lab-on-valve capillary electrophoresis system.
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PMID:Micro sequential injection: automated insulin derivatization and separation using a lab-on-valve capillary electrophoresis system. 1452 18

Dexamethasone-cyclophosphamide pulse (DCP) is the prefered mode of therapy in pemphigus in India because it is relatively free from the side effects seen with heavy doses of daily oral steroids. One hundred forty-six pemphigus patients treated with DCP were observed for side effects of this regimen. One hundred forty mg of dexamethasone was administered IV in 200 ml of 5% dextrose over a period of 60-90 minutes on 3 consecutive days. Five hundred mg of cyclophosphamide was added on first day of the pulse and 50 mg given orally daily in the intervening period. DCP was repeated every 4 weeks and continued for 6 months after subsidence of the disease (no new lesions). Flushing over the face was the most common event recorded during the adiministration in 78 subjects followed by palpitations in 11, hiccups in 9, and numbness of feet in 6. Fourteen patients had polyurea, and 3 developed skin rash. Shivering, shooting pains along thighs, breathlessness, seizure and unilateral limb edema were observed in one patient each. Generalized weakness/malaise was the most troublesome delayed side effect in 81 (55.4%) patients; it lasted for 8-15 days after the pulse. Thirty-six (24.6%) had inadequate sleep syndrome, 23 (15.7%) had headache, 21 (14.3%) complained of arthralgias, 19 (13%) experienced alteration in taste, and 13 (9%) had diffuse hair loss. 28 females developed menstrual disturbances, and 14 (9.5%) had blurring of vision (glaucoma in 3 and posterior subcapsular cataract in 1). Thirteen of eighteen diabetics had an increase in blood sugar requiring higher doses of insulin. Five NIDDM patients needed insulin. Four (2.7%) developed hypertension. Pulse therapy is not absolutely free from side effects. Hypertension and diabetes occur less frequently as compared to conventional steroid therapy. Generalized weakness, flushing, headache and taste alteration occur exclusively with pulse therapy.
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PMID:Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP) therapy. 1468 52

Bridge devices-dialysis catheters and subcutaneous access devices-play a critical role in increasing the placement of arteriovenous (AV) fistulas by providing hemodialysis vascular access while AV fistulas mature. The LifeSite Hemodialysis Access System (Vasca Inc, Tewskburg, MA), a fully implantable, subcutaneous dual valve access system, has been shown to have lower complication rates, higher blood flow rates, and better long-term device survival than conventional tunneled hemodialysis catheters, indicating it may better meet the requirements for optimally bridging to a fistula. This case study of a 48-year-old black man undergoing chronic hemodialysis for renal failure because of insulin-dependent diabetes describes a simple approach for resolving localized pocket infections associated with the LifeSite System by drip irrigation of the valves and tissue pockets with an antibiotic solution. Eight weeks after implantation of the LifeSite System, the patient exhibited symptoms of infection of the lateral LifeSite valve tissue pocket, which on culture was shown to be caused by Staphylococcus aureus. Flushing the LifeSite valve and tissue pocket with a large volume of kanamycin solution, in conjunction with intravenous vancomycin and routine irrigation of the valve with isopropyl alcohol, resolved the infection after 1 treatment. The LifeSite System successfully bridged the patient to a transposed basilic vein fistula created through a 2-stage surgical procedure. The LifeSite System provided uninterrupted access for hemodialysis over a period of 6 months while the fistula matured. The LifeSite System should allow surgeons to attempt fistula construction in more patients, including diabetics, access-challenged patients, and patients with small vessels, who may benefit from a nontraditional surgical approach toward fistula creation.
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PMID:Successful treatment of a LifeSite Hemodialysis Access System pocket infection with large-volume kanamycin solution irrigation. 1470 81

Two or three different solutions may be used to preserve thoracic and abdominal organs during a single procurement. The aim of this prospective, multi-center, noncomparative study was to evaluate the safety and efficacy of Celsior (study solution, solution S) as a flushing and cold storage solution for both thoracic and abdominal organs. Between August 1999 and July 2000, 72 consecutive multiple-organ procurements were performed using solution S as the sole solution for flushing out and cold-storing thoracic and abdominal grafts. Two hundred and sixty-four grafts were implanted into 245 recipients (131 kidneys, 9 kidney-pancreases, 69 livers, 34 hearts and 6 heart-lungs). The mean cold ischemia time was 21 h for kidneys (26%>24 h); 11 h 26 min for pancreases, 9 h 16 min for livers (23%>12 h), and 2 h 58 min for hearts and lungs. No cardiac failure or arrhythmia occurred on graft reperfusion. Fourteen percent of kidney recipients had delayed graft function. The mean serum creatinine level at 3 months was 123 +/- 41 micromol/l. All pancreas recipients were insulin-free at 3 months. Primary graft nonfunction occurred in one liver recipient. Complete hepatic artery thrombosis occurred in six liver recipients during the first month; four of these patients had a risk factor for thrombosis. All but three of the heart recipients were in sinus rhythm on day 1, and 65% were extubated on day 1. Inotropic drugs were necessary during the first 72 h in 25% of heart recipients. Twelve-month patient and graft survival rates were, respectively, 100% and 96% (kidney), 100% and 89% (pancreas), 88% and 83% (liver), 77.5% (heart) and 67% (heart-lung). These results suggest that Celsior, a ready-to-use solution, is safe and effective for multiple organ procurement and preservation.
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PMID:A single solution for multiple organ procurement and preservation. 1591 Feb 89

The suitability of noncovalently bilayer-coated capillaries for the analysis of proteins by capillary electrophoresis (CE) at medium pH was investigated. Fused-silica capillaries were coated simply by successively flushing with a polybrene (PB) and a poly(vinyl sulfonate) (PVS) solution. A protein test mixture was used to evaluate the performance of the coated capillaries. Comparisons with bare fused-silica capillaries were made. Several background electrolytes (BGEs) were tested in combination with the PB-PVS coating, showing that optimum performance was obtained for the proteins using high BGE concentrations. With a 300 mM Tris phosphate buffer (pH 7.0), good plate numbers (150,000-300,000), symmetrical peaks, and favorable migration-time repeatabilities (RSDs below 0.8%) were obtained for the proteins. Using bare fused-silica capillaries, the protein peaks were significantly broadened and the migration-time RSDs often exceeded 5%. It is concluded that the PB-PVS coating effectively minimizes adverse protein adsorption and provides a very stable electroosmotic flow (EOF). We also investigated the potential of a commercially available bilayer coating (CEofix) for protein analysis. It is demonstrated that with this coating, good plate numbers and peak symmetries for proteins can be achieved when the CEofix BGE ("accelerator") is replaced by a common BGE such as sodium or Tris phosphate. Apparently, the negatively charged polymer present in the "accelerator" interacts with the proteins causing band broadening. The utility of the bilayer coatings is further illustrated by the separation of proteins such as interferon-alpha 2b, myoglobin and carbonic anhydrase, by the analysis of a degraded insulin sample in time, and by the profiling of the glycoprotein ovalbumin. In addition, it is demonstrated that even in the presence of concentrations of human serum albumin in the sample of up to 60 mg/mL, the PB-PVS coating still provides reproducible protein separations of good performance.
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PMID:Noncovalently bilayer-coated capillaries for efficient and reproducible analysis of proteins by capillary electrophoresis. 1607 6


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