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)

Glibenclamide was administered to five non insulin dependent diabetic (NIDD) patients, whose hyperglycaemia was not controlled by diet alone. The plasma glucose and insulin porfile was determined under strictly standardised conditions before, after the first administration and after 6 months of treatment with glibenclamide. A rapid and satisfactory lowering of plasma glucose was observed in all patients after the first administered dose and a very similar response was seen after 6 months of therapy, when glibenclamide was administered once a day. Despite a consistent plasma glucose lowering effect a very variable plasma insulin response was evident between the patients. This difference may be of relevance in the long term prognosis of these patients with respect to atherogenesis. For the period of the study weight gain was minimal, no episodes of hypoglycaemia or alcohol induced flushing were recorded.
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PMID:The effect of glibenclamide on the glucose and insulin profile in maturity onset diabetics following both acute and long term treatment. 677 11

In this report we review the pharmacology of the hypoglycemic sulfonylurea drugs. The early work with sulfonylureas is briefly described. The pharmacokinetics of first-generation sulfonylureas, such as tolbutamide, chlorpropamide, acetohexamide and tolazamide, are described. The first-generation sulfonylureas are compared with second-generation sulfonylureas such as glyburide, glipizide and glibornuride. These latter drugs have a more nonpolar or lipophilic side chain, which results in a marked increase in their hypoglycemic potency. Because of the low serum concentration required for effective therapy, it is necessary to measure the serum concentration of second-generation sulfonylureas by gas-liquid chromatography or radioimmunoassay. The second-generation sulfonylureas do not produce facial flushing after ethanol ingestion (Antabuse effect) and are not uricosuric. Glyburide (but not glipizide or glibornuride) has been evaluated for its effect on water excretion. Glyburide not only does not increase water retention but in fact also increases free water clearance. The second-generation sulfonylureas bind to human serum albumin by nonionic forces in contrast with tolbutamide and chlorpropamide which bind by ionic forces. Thus, anionic drugs such as phenylbutazone, warfarin and salicylate do not displace glyburide from albumin as they displace tolbutamide and chlorpropamide. Therefore, it may be safer to administer the second-generation sulfonylureas than the more polar sulfonylureas when concurrent administration of other pharmacologic agents is likely. The sulfonylurea drugs lower plasma glucose concentrations in diabetic patients by stimulating insulin secretion and by potentiating the biologic effect of the insulin on such tissues as skeletal muscle, fat and liver. The mechanism of the latter so-called extra-pancreatic effect may be activated by increasing the deficient numbers of insulin receptors on muscle, fat or liver cells.
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PMID:The pharmacology of sulfonylureas. 678 41

Twelve maturity-onset diabetic subjects were treated with chlorpropamide once daily, glibenclamide once daily, or glibenclamide twice daily in a crossover design study. Doses were increased until the fasting blood glucose concentrations became less than 6 mmol/L (108 mg/dl), at which time the patients were admitted for a 24-h study period. There was little difference between the plasma glucose and insulin responses to chlorpropamide or glibenclamide given twice daily (mean doses 489 and 11 mg/day, respectively). When glibenclamide was given once daily (mean dose 9 mg/day), similar plasma glucose concentrations during the day were obtained with slightly higher plasma glucose concentrations during the night. Four patients had chlorpropamide-induced flushing with alcohol, and six patients had postprandial hypoglycemia on glibenclamide. Chlorpropamide once daily or glibenclamide twice daily are suitable for control based on fasting blood glucose measurements.
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PMID:Comparison of chlorpropamide and glibenclamide treatment of maturity-onset diabetes: control assessed by fasting plasma glucose concentrations. 678 74

The results of seven segmental pancreas transplantations in diabetic patients, using a jejunal Roux-en-Y loop for drainage of digestive enzymes, are presented. An initial case with pancreatic duct ligation is also included. The patients ranged in age from 30 to 45 yr, with duration of diabetes from 8 to 24 yr, and were incapacitated but not uremic. Immunosuppression was attempted with azathioprine, prednisone, and antilymphocyte globulin, and, in one patient, thoracic duct drainage was added. The pancreas tolerated at least 16 min of warm ischemia and at least 4 h of cold storage; flushing with a balanced electrolyte solution was optimal. Six of the grafts provided control of blood glucose for 7--51 days, and, in one patient, an intravenous glucose tolerance test was normal at 7 and 21 days. Five of the grafts failed due to rejection 7--51 days after transplantation, and one was removed at 14 days, while still functioning, due to bleeding. In one case, early detection of rejection by a rise in post-prandial blood glucose was treated and reversed by corticosteroid administration. Two failed in the immediate postoperative period from vascular thrombosis. Drainage of pancreatic secretions from a fistula was a common problem.
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PMID:Segmental pancreatic transplantation with duct ligation or drainage to a jejunal Roux-en-Y loop in nonuremic diabetic patients. 698 9

Previous studies have suggested that a cationic bactericidal/permeability-increasing protein (BPI) present in both rabbit and human polymorphonuclear leukocytes is the principal O2-independent bactericidal agent of these cells toward several strains of Escherichia coli and Salmonella typhimurium (1978. J. Biol. Chem. 253: 2664--2672; 1979. J. Biol. Chem. 254: 11000--11009). To further evaluate the possible role of this protein in the killing of gram-negative bacteria by polymorphonuclear leukocytes, we have measured the bactericidal activity of intact rabbit peritoneal exudate leukocytes under aerobic or anaerobic conditions and of intact human leukocytes from a patient with chronic granulomatous disease. Anaerobic conditions were created by flushing the cells under a nitrogen stream. Effective removal of oxygen was demonstrated by the inability of nitrogen-flushed leukocytes to mount a respiratory burst (measured as increased conversion of 1-[14C]glucose leads to 14CO2 or by superoxide production) during bacterial ingestion. At a bacteria/leukocyte ratio of 10:1, killing of gram-positive, BPI-resistant, Staphylococcus epidermidis is markedly impaired in the absence of oxygen (76.4 +/- 3.3% killing in room air, 29.2 +/- 8.2% killing in nitrogen). Essentially all increased bacterial survival is intracellular. In contrast, both a nonopsonized rough strain (MR-10) and an opsonized smooth strain (MS) of S. typhimurium 395 are killed equally well in room air and nitrogen. A maximum of 70--80 MR-10 and 30--40 MS are killed per leukocyte either in the presence or absence of oxygen. There is no intracellular bacterial survival in either condition indicating that intracellular O2-independent bactericidal system(s) of rabbit polymorphonuclear leukocytes can at least match the leukocyte's ingestive capacity. Whole homogenates and crude acid extracts manifest similar bactericidal capacity toward S. typhimurium 395. This activity can be accounted for by the BPI content of these cell fractions and is virtually eliminated by immune (anti-BPI), but not by preimmune goat IgG-rich fractions. Opsonization of smooth MS, required for bacterial killing by intact leukocytes, does not alter bacterial sensitivity to BPI in crude or purified form. Leukocytes of a patient with chronic granulomatous disease killed ingested S. typhimurium 396 MS nearly as well as did normal leukocytes. The bactericidal activity toward E. coli (J5) of crude acid extracts of the CGD and normal human leukocytes was virtually the same and was nearly completely inhibited by anti-BPI IgG-rich fractions, but not by preimmune IgG-rich fractions. These findings suggest that the killing of gram-negative bacteria such as S. typhimurium by intact polymorphonuclear leukocytes may also be attributed to the action of BPI.
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PMID:Killing of gram-negative bacteria by polymorphonuclear leukocytes: role of an O2-independent bactericidal system. 704 58

A microassay method sensitive enough to analyze the enzyme activities in one oocyte was developed using enzymatic cycling for amplifying the reaction product to 10,000 fold. An oil-well technique was applied in the assay for achieving the reaction in the medium as small as 1.0 to 5.0 microliter. Immature Wistar rats were superovulated by PMS-hCG administration. Oocytes were collected by the puncture of the follicle and the flushing of the tube. They were freeze-dried after washing to remove cumulus cells. The dry weight was about 50ng on a quartz fiber fishpole balance. The activity of hexokinase was 1.75 +/- 0.14 picomol/oocyte/hr corresponding to one-tenth of the ovarian homogenate as control, indicating low capacity of glucose utilization in the oocyte. The activities of G6PD, LDH, and MDH were 8.41 +/- 0.34, 35.7 +/- 2.89. 11.1 +/- 2.5 picomol/oocyte/min, respectively. High activity of G6PD suggests the pentose phosphate shunt concerned with steroidogenesis is active in the oocyte. HCG increased the activities of hexokinase and MDH and decreased that of G6PD. The activity of LDH remained unchanged.
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PMID:[Study of energy metabolism in the oocyte by cycling method]. 717 80

The capillary filtration coefficient (Kf) is one of the most accurate measures of change in pulmonary vascular permeability and has been used in various models of acute lung injury. To evaluate the isolated effects of ischemia on Kf, we have developed an ex vivo rabbit lung model in which the influences of reperfusion are eliminated. The current study was designed to validate this model by determining the effect of cold flushing with low-potassium-dextran solution containing 1% glucose (LPDG), ischemic time, temperature, and inspired oxygen fraction on Kf. On completion of the ischemic period, the ventilated lungs, with the heart still attached, were suspended from a strain-gauge force transducer. After the lungs were flushed with 50 mL hetastarch solution (6% hetastarch solution with physiologic saline solution), the left atrial drainage cannula was occluded and the pulmonary artery pressure was incrementally increased by elevation of the reservoir. The Kf was calculated as the slope of the line relating the weight gain rate and pulmonary capillary pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in vascular permeability with ischemic time, temperature, and inspired oxygen fraction in isolated rabbit lungs. 751 84

In previous experimental liver transplant studies, it was possible to extend cold ischaemic time (CIT) by using a flush/storage solution combining histidine, lactobionate and raffinose (HLR). In this study, energy metabolism, glycolytic substrate (glucose) and anaerobic end-product (lactate) were examined in rat liver over 24 h of cold storage to determine the mechanism of action of the HLR solution. In livers subjected to simple flush and storage with the HLR solution, levels of ATP and ADP were considerably higher than livers stored with modified UW throughout 24 h of storage; at 4 h of storage, ATP and ADP levels were 1.1 and 3.1 mumol/g for HLR solution versus 0.18 and 0.81 mumol/g for UW solution. Total adenylate contents (TA = ATP + ADP + AMP) also remained 1-2 mumol/g higher in HLR-treated livers than those preserved in UW; TA values ranged from 3.8 to 5.7 mumol/g. Glucose increased to 20-35 mumol/g by 10-24 h of storage (similar to the UW group). Lactate rose to almost twice that in livers stored in UW; total lactate accumulation was approximately 10.0 mumol/g. This study demonstrated that the combined HLR solution is able to prolong the maximum 'safe' CIT by increasing anaerobic metabolism and consequently preserving liver energetics. The second part of the experiment examined the effect of continuous perfusion (with/without O2) over the 1st h of cold ischaemia. Under current methods of liver flushing and excision, the 1st h of cold storage may be the critical time of metabolic 'adjustment' since most of the pH and ATP changes occur during this period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An underlying mechanism for improved liver preservation with a combined histidine-lactobionate-raffinose flush solution. 757 19

We describe herein a new experimental model in which an isolated rat lung was ventilated with a mixture of 95% nitrogen and 5% carbon dioxide to decrease the oxygen and increase the carbon dioxide in the perfused blood to create and maintain a gas composition similar to that of venous blood. By utilizing this system as a "deoxygenator," pulmonary functions, including gas exchange, could be measured for at least 60 min in isolated and preserved lungs on reperfusion. When the effects of glucose in the flushing and storage solution were examined, 5 mM glucose in the solution resulted in better preservation of the lung, as shown by a higher uptake of oxygen and a lower intratracheal pressure, than when no glucose was given. However, the presence of 50 mM glucose was not beneficial, but rather increased the wet/dry weight ratio of the tissue.
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PMID:Effects of glucose on rat lung preservation: report of a study conducted on an isolated lung reperfusion model utilizing. Another isolated lung as a "deoxygenator". 757 63

We evaluated the effect of urokinase on pulmonary microthrombi formation of the donor lung using a canine cadaver left lung allotransplantation model. Donor animals were sacrificed with an intravenous injection of potassium chloride without heparinization and were divided into three groups. In group 1 (n = 6), cadavers were left at room temperature for 1 hour, and lung retrieval was then performed after flushing the lung block with low potassium-dextran-glucose solution. Donor lungs were stored for 3 hours at 8 degrees C. In group 2 (n = 6), donor lungs were treated as in group 1 except that the cadavers were left at room temperature for 2 hours instead of 1 hour before lung retrieval. In group 3 (n = 6), donor lungs were treated as in group 2 except that high-dose urokinase (120,000 IU) was injected into the main pulmonary artery after flushing with low-potassium-dextrose-glucose solution. In all groups after left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 6 hours after reperfusion. The fibrin degradation product level in the donor lung tissue was also measured. All recipient animals in group 1 survived the 6-hour observation period with excellent gas exchange and stable hemodynamics. Group 3 had significantly better gas exchange than group 2 and similar cardiopulmonary function as group 1. The fibrin degradation product level in the donor lungs before transplantation was significantly higher in group 3 than in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved lung function by urokinase infusion in canine lung transplantation using non-heart-beating donors. 777 33


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