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At least 19 recordsLinked to original sources
PubMed1995

Stability, tissue metabolism, tissue distribution and blood partition of azosemide.

Stability of azosemide after incubation in various pH solutions, human plasma, human gastric juice, and rat liver homogenates, metabolism of azosemide after incubation in 9000 g supernatant fraction of various rat tissue homogenates in the presence of NADPH, tissue distribution of azosemide and M1 after intravenous (i.v.) administration of azosemide, 20 mg kg-1, to rats, and blood partition of azosemide between plasma and blood cells from rabbit blood were studied. Azosemide seemed to be stable for up to 48 h incubation in various pH solutions ranging from two to 13 at an azosemide concentration of 10 micrograms mL-1; more than 93.4% of azosemide was recovered, and a metabolite of azosemide, M1, was not detected. However, the drug was unstable in pH1 solution: 75.8% of azosemide was recovered and 2.16 micrograms mL-1 of M1 (expressed in terms of azosemide) was formed after 48 h incubation in pH 1 solution at an azosemide concentration of 10 micrograms mL-1. Azosemide was stable in both human plasma and rat liver homogenates for up to 24 h incubation at an azosemide concentration of 1 microgram mL-1, and in human gastric juice for up to 4 h incubation at an azosemide concentration of 10 micrograms mL-1. However, all rat tissues studied had metabolic activity for azosemide in the presence of NADPH, with heart having a considerable metabolic activity: approximately 22% of azosemide disappeared and 9.32 micrograms of M1 was formed per gram of heart (expressed in terms of azosemide) after 30 min incubation of 50 micrograms of azosemide in 9000 g supernatant fraction of heart homogenates. The tissue to plasma ratios of azosemide (T/P) were greater than unity only in the liver (1.26) and kidney (1.74); however, M1 showed high affinity for all tissues studied except the brain and spleen when each tissue was collected at 30 min after i.v. administration of azosemide to rats. The equilibrium plasma to blood cell concentration ratios of azosemide were independent of azosemide blood concentrations: the values were 2.78-4.25 at azosemide blood concentrations of 1, 10, and 20 micrograms mL-1 in three rabbits. There was negligible 'blood storage effect' of azosemide, especially at low blood concentrations of azosemide, such as 1 and 10 micrograms mL-1.

Animals↗
PubMed1995

Stability, tissue metabolism, tissue distribution, and blood partition of DA-1131, a new carbapenem.

The stability of DA-1131 after incubation in various pH solutions, human plasma, human urine, human gastric juice, rat liver homogenates and rat whole blood, the disappearance of DA-1131 after incubation in the 9000g supernatant fraction of various rat tissue homogenates in the presence of NADPH, the tissue distribution of DA-1131 after intravenous (i.v.) administration of DA-1131, 50 mg/kg, to rats, and the blood partition of DA-1131 between plasma and blood cells from rabbit blood were studied. DA-1131 was unstable when incubated in various pH solutions, especially at low and high pHs at the DA-1131 concentration of 10 micro g/ml; the degradation half-lives of DA-1131 were 0.260, 1.23, 2.20, 7.16, 14.2, 10.5, 31.3, 21.3, 0.262, 0.241, and 1.45 hr for pH solutions of 1-11, respectively. DA-1131 was also unstable after incubation in human plasma, rat liver homogenates, and human gastric juice. However, DA-1131 seemed to be sable in human plasma for up to 12 hr storage at -20 degrees C. The spleen, kidney, liver, lung, mesentery, and stomach homogenates from rats showed metabolic activity to DA-1131. The tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied except kidney when each tissue was collected at 30 min after i.v. administration of DA-1131 to rats. The tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied except kidney when each tissue was collected at 30 min after i.v. administration of DA-1131 to rats. The plasma-to-blood cell concentration ratios of DA-1131 were independent of DA-1131 blood concentrations when the whole blood was incubated up to 120 min; the mean values were 5.56 +/- 1.47, 5.80 +/- 2.19, and 4.61 +/- 1.82 at DA-1131 blood concentrations of 2, 10, and 20 microgram/ml, respectively, rabbits A-C. There was also considerable in vivo and in vitro blood storage effect in the plasma concentration of DA-1131 in rabbits.

Animals↗
PubMed1991

Effects of early pregnancy on regional adipose tissue metabolism.

Adipose tissue metabolism was studied in needle biopsies from femoral and abdominal subcutaneous depots, in 12 healthy young women, during early (9-11 weeks) pregnancy, and 6 weeks after a legal abortion. Both during pregnant and non-pregnant conditions, a higher lipoprotein lipase (LPL) activity was seen in the femoral compared to the abdominal region, but the LPL activity was not influenced by early pregnancy. Rates of fatty acid esterification and acylglyceride synthesis were not different between regions, nor affected by pregnancy. The stimulatory effect of norepinephrine (10(-7) M) on lipolysis was significantly greater in the abdominal than in the femoral region in both the pregnant and non-pregnant condition. This difference was apparently due to higher alpha-adrenergic activity in the femoral region. Pregnancy per se had no effect on lipolytic response to norepinephrine. These findings indicate that lipid accumulation is favoured in the femoral region in young women both during pregnant and non-pregnant conditions.

Abdomen↗
PubMed1993

Long-Term Anaerobic Metabolism in Root Tissue (Metabolic Products of Pyruvate Metabolism).

The onset of anaerobiosis in barley root tissue (Hordeum vulgare L. cv Himalaya) results in the following metabolic responses. There are rapid increases in the levels of pyruvate, lactate, and ethanol. Malate and succinate concentrations increase over the first 12 h, after which they return to the levels found in oxygenated root tissue. Alanine concentration increases over the first 12 h, and this is matched by a corresponding decrease in aspartate. The initial stoichiometric decline in aspartate and increase in alanine suggests that the amino group of aspartate is conserved by transaminating pyruvate to alanine. Aspartate catabolism also probably provides the initial source of carbon for reduction to succinate under anoxic conditions. Under long-term anaerobiosis (>24 h), there is no further accumulation of any of the fermentative end products other than ethanol, which also represents the major metabolic end product during long-term anaerobiosis. Although a number of the enzymes involved in fermentative respiration have been found to be induced under anaerobic conditions, neither aspartate amino-transferase nor malate dehydrogenase is induced in barley root tissue. The observations suggest that the long-term adaptations to hypoxic conditions may be quite different than the more well-characterized short-term adaptations.

Journal Article↗
PubMed2000

Concordance of in vivo microdialysis and in vitro techniques in the studies of adipose tissue metabolism.

BACKGROUND: Adipose tissue metabolism can be investigated directly in vivo by microdialysis and indirectly in vitro using isolated adipocytes. The in vitro studies are relatively easy to make and they give information about specific tissue metabolism. The in vivo studies, on the other hand, are supposed to give relevant data about tissue physiology interacting with other metabolic systems at the body level. OBJECTIVE: To investigate the concordance between the results on responsiveness to stimulation of lipolysis from in vivo microdialysis and in vitro isolated adipocytes. SUBJECTS: Altogether 22 massively obese otherwise healthy subjects (seven men and 15 women, age 41 (26-55) y, BMI 51.5 (37.5-73.9)kg/m2, mean (range)) going through the gastric banding operation participated in the study. METHODS: The microdialysis study was done after an overnight fast at rest. Lipolysis was stimulated with isoprenaline that was perfused into the subcutaneous abdominal adipose tissue. Local blood flow was estimated by ethanol dilution method. Adipose tissue biopsy for the in vitro study was taken from subcutaneous abdominal region during the operation. Lipolysis in freshly isolated adipocytes was stimulated with different concentrations of adrenaline or isoprenaline. RESULTS: Significant positive correlations were observed between the values of relative stimulation of lipolysis in isolated adipocytes and in the microdialysis study. These correlations improved after correcting for cell size or fat mass. CONCLUSION: The microdialysis study in vivo and lipolysis assay with isolated adipocytes in vitro provide concordant and complementary information of adipose tissue metabolism in the same individual.

Adipocytes↗
PubMed2005

Influences of AT1 receptor blockade on tissue metabolism in obese men.

ANG II applied to the interstitial space influences carbohydrate and lipid metabolism in a tissue-specific fashion. Thus endogenous ANG II may have a tonic effect on tissue metabolism that could be reversed with ANG II type 1 (AT1) receptor blockade, particularly during adrenergic stimulation. We studied 14 obese men. They were treated for 10 days with the AT1 receptor blocker irbesartan or with placebo in a double-blind and crossover fashion. At the end of each treatment period, we assessed skeletal muscle and adipose tissue metabolism using the microdialysis technique. The ethanol dilution technique was applied to follow changes in tissue blood flow. Measurements were obtained at baseline and during application of incremental isoproterenol concentrations through the microdialysis catheter. Blood pressure decreased from 133 +/- 3/84 +/- 3 to 128 +/- 3/79 +/- 2 mmHg for systolic and diastolic blood, respectively (P = 0.02 and 0.006, respectively) with AT1 receptor blockade. Isoproterenol perfusion caused a dose-dependent increase in dialysate glycerol in adipose tissue and in skeletal muscle. Irbesartan slightly reduced the isoproterenol-induced glycerol response in adipose tissue (P < 0.05 by ANOVA). Ethanol ratio, interstitial glucose supply, and lactate production in adipose tissue and skeletal muscle were similar with placebo and irbesartan. We conclude that AT1 receptor blockade in obese men does not reveal a major tonic ANG II effect on interstitial glucose supply, lipolysis, or glycolysis in skeletal muscle, either at rest or during beta-adrenergic stimulation. Endogeneous ANG II may slightly increase adipose tissue lipolysis. The mechanism may promote the redistribution of triglycerides from adipose tissue toward other organs.

Adipose Tissue↗
PubMed2002

Differences in adipose tissue metabolism between postmenopausal and perimenopausal women.

Changes in adipose tissue metabolism may contribute to the changes in body fat distribution seen during the menopause transition. We compared in vitro abdominal and gluteal sc adipose tissue metabolism [basal and stimulated lipolysis and activity of adipose tissue lipoprotein lipase (AT-LPL)] in postmenopausal and perimenopausal women (n = 12/group), matched for race, body mass index (29.5 +/- 3.8 kg/m(2); mean +/- SD), and percentage body fat (42 +/- 6%). The postmenopausal women were older (54 +/- 3 vs. 48 +/- 3 yr; P < 0.01) and had higher FSH (55.5 +/- 26.4 vs. 16.6 +/- 22.5 IU/ml; P < 0.01) and lower estradiol (33.8 +/- 14.9 vs. 97.4 +/- 61.7 pmol/liter; P < 0.05) concentrations than the perimenopausal women. Despite similar fat cell size and beta-adrenergic receptor and postreceptor (dibutyryl-cAMP)-stimulated lipolysis, basal lipolysis was 77% lower in gluteal adipose cells from postmenopausal compared with perimenopausal women (P < 0.05). Within each group, AT-LPL activity in the gluteal region was significantly higher than in the abdominal region (P < 0.05). In addition, AT-LPL activity was significantly higher in the postmenopausal compared with perimenopausal women in both gluteal (4.9 +/- 3.6 vs. 2.0 +/- 1.4 nmol free fatty acid/g.min; P < 0.05) and abdominal (3.2 +/- 2.6 vs. 1.3 +/- 0.9 nmol free fatty acid/g.min; P < 0.05) adipose cells. The results of this study suggest that menopause status is associated with differences in adipose tissue metabolism in both the abdominal and gluteal fat depots. The lower lipolysis and higher AT-LPL activity in postmenopausal women may predispose them to gain body fat after menopause.

Abdomen↗
PubMed2003

Anti-glucocorticoid effects of progesterone in vivo on rat adipose tissue metabolism.

Steroid hormones seem to be important for adipose tissue metabolism and accumulation. As progesterone has been suggested to modulate the glucocorticoid effects, the interactions between glucocortioid and progesterone on adipose tissue metabolism were investigated.Forty-eight male Wistar rats were adrenectomized and divided into four groups; controls (treated with vehicle only), dexamethasone treated (10 micro g per rat), progesterone treated (5mg per rat) and the last group received both dexamethasone and progesterone. The dexamethasone-treated group had a significant loss of body weight and smaller intra-abdominal fat depots compared to the control group in addition, dexamethasone increased LPL-activity and increased catecholamine stimulated lipolysis. When progesterone was given concomitantly the dexamethasone effects on adipose tissue mass, LPL-activity and lipolysis were blocked. When given alone progesterone had no influence on body weight, amount of adipose tissue, lipolysis or LPL-activity. These data indicate that progesterone acts as an anti-glucocorticoid in adipose tissue in vivo, thus attenuating the glucocorticoid effect on adipose tissue metabolism.

Adipose Tissue↗
PubMed1998

Adipose tissue metabolism in the postprandial period: microdialysis and arteriovenous techniques compared.

We investigated whether two different methods of studying metabolism in adipose tissue, microdialysis and the arteriovenous technique, produced comparable results during the postprandial period. Interstitial glycerol concentrations measured by microdialysis are usually used as an index of intracellular lipolysis, and it is not known whether they also reflect the intravascular action of lipoprotein lipase in the postprandial period. The two techniques were compared in 10 healthy subjects fed mixed meals. Interstitial glycerol concentrations reflected those measured in adipose tissue venous plasma. However, the calculation of the rate of glycerol release from adipose tissue using the microdialysis data differed systematically from that using arteriovenous difference measurement. The former method gave, on average, 40% lower values than the latter one. The difference is probably due to the assumptions that had to be made for the calculation of glycerol release. The two techniques have complementary places in the study of postprandial adipose tissue metabolism, with microdialysis reflecting intracellular hormone-sensitive lipase action rather than intravascular lipoprotein lipase.

Adipose Tissue↗
PubMed1988

Experimental diabetes and the lung. II. In vivo connective tissue metabolism.

In vivo lung connective tissue and DNA synthesis, following intraperitoneal injection of [14C]proline and [3H]thymidine, were studied in streptozotocin-induced diabetic rats fed ad libitum. Insulin-treated diabetic and normal rats similarly fed, and undernourished rats weight-matched to the untreated diabetics, served as comparison groups. The ratio of unbound [14C]hydroxyproline to total [14C]hydroxyproline in the lung was used to assess connective tissue degradation. Compared to the normal group, the untreated diabetic animals showed similar synthesis of collagen and elastin, reduced synthesis of total protein and DNA, and decreased degradation of connective tissue. When compared with the normal group, the undernourished animals showed diminished synthesis of total protein, collagen, elastin, and DNA, and increased degradation of connective tissue. In comparison to the undernourished group, the untreated diabetic animals indicated increased synthesis of collagen and elastin, and diminished degradation of connective tissue; total protein and DNA syntheses were similar. The insulin-treated diabetic animals showed increased collagen and DNA synthesis. We conclude that experimental diabetes has a profound effect on lung connective tissue metabolism, supporting previous observations of connective tissue abnormalities and morphometric changes. The increase in lung collagen and elastin in diabetes is in part due to reduced breakdown of the connective tissue proteins.

Animals↗
PubMed1993

Subcutaneous adipose tissue metabolism studied by local catheterization.

Adipose tissue is a metabolically active tissue which plays a key role in regulating the concentrations of circulating lipid fuels. In recent years, two new techniques have become available for the study of human adipose tissue metabolism in vivo: microdialysis, and catheterization of the venous drainage from the subcutaneous abdominal adipose tissue. Blood obtained by the latter method shows all the characteristics expected of adipose tissue drainage. The characteristics of this tissue are quite distinct from those of the superficial (mainly skin) or the deep (mainly muscle) tissues of the forearm. The depot studied appears to be typical of adipose tissue as a whole in terms of non-esterified fatty acid release. In comparison with the microdialysis technique, the arterio-venous difference technique allows easier quantification of substrate uptake and release, and allows the study of hydrophobic molecules (e.g. fatty acids, triacylglycerol). On the other hand, it does not allow the study of more than one depot, nor the local introduction of effectors of metabolism (e.g. adrenergic agents). The two techniques are clearly complementary.

Adipose Tissue↗
PubMed1986

Adipose tissue metabolism in sheep: response to season and its modulation by reproductive state.

Seasonal changes in subcutaneous adipose tissue metabolism and serum metabolite and hormone concentrations are described in virgin ewes fed a fixed amount of a cereal mixture plus hay ad libitum. Body weight, adipocyte mean cell volume, the rates of fatty acid and acylglycerol glycerol synthesis, and lipoprotein lipase activity increased from October to May and then decreased over the following five months. These changes are probably due to an increase in voluntary food intake leading to increased availability of acetate for fatty acid synthesis and also a probable rise in serum insulin concentration. Seasonal changes in adipose tissue metabolism in sheep are modulated by pregnancy and lactation, possibly mediated in part by changes in the serum insulin: growth hormone ratio. Although seasonal changes in adipose tissue metabolism are paralleled by changes in serum prolactin concentration, prolactin probably does not have a direct effect on adipose tissue metabolism.

Adipose Tissue↗