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Biomedical subjects

J F Blickle

Publications and source records attributed to J F Blickle.

At least 19 recordsLinked to original sources
PubMed2000

[Pharmacological treatment of postprandial hyperglycemia].

Every diabetes treatment contributes to the control of postprandial blood glucose, yet some agents more specifically target this goal. Alpha-glucosidase inhibitors, led by acarbose, mainly address postprandial glucose control. These agents inhibit intestinal disaccharidases through a competitive effect and can be used either as the sole treatment or in combination with other antidiabetic drugs. Other agents improve insulin secretion kinetics. This is the case for repaglinide et nateglinide, which are efficient in controlling postprandial blood glucose, and to a lesser degree, fasting blood glucose. These agents shortly and quickly stimulate insulin secretion and should be available soon. In oral therapy secondary failures, trials are currently being conducted to clarify the role of fast-acting insulin analogs, as monotherapy or in combination. Finally, insulin sensitizing agents are being investigated as a way to improve postprandial glucose efflux by potentiating insulin effects. The optimal strategy for the use of these different therapeutic agents remains to be established, as well as their long-term effects on diabetic complications.

Diabetes Mellitus, Type 2↗
PubMed1998

Short-term variations of serum glycated apolipoprotein B.

Serum glycated apolipoprotein B (apo B-G) levels were determined in 31 non-insulin-dependent diabetic patients and 13 control subjects by an enzyme-linked immunosorbent assay. Apo B-G was increased in diabetic patients compared to non-diabetic subjects, whether expressed as a serum concentration (57.7 vs 36.1 mg/l) or a percentage of total apolipoprotein B (4.42 vs 3.14%). Apo B-G, together with other markers (mean daily plasma glucose, serum fructosamines, triglycerides, total cholesterol, glycated haemoglobin), was measured before and after 5 days of therapeutic adjustment in diabetic patients. In 20 patients with a favourable course of glycaemic control, the mean decrease of apo B-G concentration reached nearly 16%. In 11 patients with an unfavourable course, the increase of apo B-G concentration was about 14%. Therefore, variation of serum apo B-G concentration could serve as an additional short-term marker for glycaemic control, although possible concomitant variations of serum triglycerides or total apolipoprotein B concentrations should also be considered.

Aged↗
PubMed1996

[Refsum disease].

Refsum's disease, firstly described almost 50 years ago by the Norvegian neurologist Sigvald Refsum, is an autosomic recessive disease affecting mostly the Scandinavians and the populations originating from Northern Europe. The disease results from a specific enzyme deficiency of the first step of phytanic acid catabolism pathway. This deficiency leads to an accumulation of this C20 fatty acid in the serum and the tissues with a preference for adipose tissue, liver and kidneys. The clinical picture includes retinitis pigmentosa, peripheral neuropathy, ataxia and elevated cerebrospinal fluid protein concentration. Other less frequent manifestations include cranial nerves deficiency, myocardiopathy, renal tubular dysfunction and ichtyosis. The diagnosis relies on serum phytanic acid measurement. The treatment consists of a phytanic-acid free diet sometimes associated with plasmapheresis. This treatment is generally effective on neuropathy but not on cranial nerves dysfunction and retinitis pigmentosa.

Humans↗
PubMed1994

Biliary elimination and hepatic disposition of an association of piperacillin and tazobactam: experimental evaluation.

Biliary elimination and hepatic disposition of tazocillin, an association of a highly bile-excreted ureido-penicillin, piperacillin, with a beta-lactamase inhibitor, tazobactam, have been assessed applying an isolated perfused rabbit liver experimental model. Six investigations were performed, each during a 3 h period, using reconstituted blood circulating in a closed circuit. Piperacillin and tazobactam concentration in all specimens were determined by high performance liquid chromatography. Blood samples and cumulative bile secretion were collected every 30 min, and liver fragments were isolated at the end of each experiment for dosage purposes. Following the simultaneous administration of piperacillin 80 mg and tazobactam 10 mg (dose ratio 8/1) in the perfusion device, theoretical initial serum concentrations were respectively 414 micrograms/ml and 32.1 micrograms/ml. Maximal biliary concentrations of 4431 +/- 1541 (s.d.) of piperacillin and 21.3 +/- 7.8 micrograms/ml of tazobactam were reached between 0.5-1 h and 2.5-3 h, respectively. Cumulative biliary excretion (0-3 h) amounted to 37.6 +/- 17.7% of the administered dose for piperacillin and 1.5% for tazobactam. At the end of the perfusion, respectively 22.1% and 50.7% of piperacillin and tazobactam doses remained in the circulating blood, while 1.1% and 5.6% were found in the liver. On the basis of these data, the calculated percentages of piperacillin and tazobactam doses having undergone hepatic biotransformation, were 6.5% and 1.2%, respectively. Under such experimental conditions, concentrations and excretion of piperacillin in bile prove to be substantial. Of note, tazobactam concentrations turn out to be stable both in serum and in bile whereas they stay at a relatively constant level of 20 micrograms/ml during nearly all the perfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Glycated immunoglobulin M in diabetic patients.

Measurement of glycation levels on isolated immunoglobulin M (IgM), a short half-life protein, could be an index of glycaemic control. We determined glycated IgM levels in a diabetic patients population as compared to control non-diabetic subjects in a cross-sectional and longitudinal study. For that purpose we developed a precipitation method for IgM purification, measured glycation on the purified protein by a nitroblue tetrazolium assay and correlated glycated IgM, glycated haemoglobin (HbA1c) and fructosamine rates. The purification method we developed comprises dextran sulfate-CaCl2, ammonium sulfate and polyethylene glycol precipitations and it allows extraction of IgM free of contaminants as shown by immunoelectrophoresis. Glycated IgM levels were 8.65 +/- 0.15 nmol deoxymorpholinofructose (DOMF) equivalents/mg protein for non-diabetic subjects (n = 30) and 12.08 +/- 0.60 nmol DOMF equivalents/mg protein (n = 67) for diabetic patients. Diabetic patients had then a 40% rise in glycated IgM (p < 0.0005). In a longitudinal study with patients undergoing treatment aimed at improving their metabolic control, glycated IgM levels decreased significantly (p < 0.001) between the day of admission and the fifth day. Average rate of fall was 13% with a range of 3.0 to 22.0% (n = 28). Glycated IgM clearly responds more rapidly than fructosamines which fell by 7.0% and than HbA1c, which showed a rate of fall of 3.9% in the same period. A significant positive correlation was found between these parameters, being stronger between glycated IgM and fructosamines. This method could provide an alternative approach as a short-term marker of glycaemic control for clinical trials.

Diabetes Mellitus, Type 1↗
PubMed1992

Evaluation of cefixime biliary disposition in the isolated perfused rabbit liver model and in humans.

Cefixime is a new orally effective third-generation cephalosporin. It inhibits a wide variety of Gram-positive and Gram-negative bacteria, especially most of the Enterobacteriaceae. Since extrarenal excretion processes have been reported to account for 60% of cefixime systemic clearance we have endeavoured to determine the place taken up by biliary excretion of unchanged cefixime in this pattern. We initially used the isolated perfused rabbit liver technique. Six perfusions were performed. Cefixime concentrations were measured by HPLC chromatography. After addition of a single 10-mg dose of cefixime to the circulating blood, biliary elimination of the drug proved to be very low, since only 0.28 +/- 0.15% of the dose was recovered during the 3-h perfusion period. The rate of cefixime biotransformation in the liver was found to be 16.2%. In contrast, the data obtained in humans highlight substantial biliary excretion of the drug. In six healthy volunteers submitted to duodenal aspiration and receiving a single 200-mg i.v. dose of cefixime, drug levels in duodenal fluid were at least fivefold greater than the simultaneous concentrations in serum. Biliary excretion of cefixime was further investigated in ten cholecystectomized patients provided with T-tube drainage: following a single 200 mg oral dose of cefixime, Cmax in bile reached 56.9 +/- 70 mg/l, that is about 25 times as high as Cmax in serum, 2.3 +/- 0.85 mg/l. Drug levels in choledochal bile proved to be sustained, since a concentration of 4.3 +/- 3.7 mg/ml was still observed 20 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Biliary excretion and hepatic disposal of cefixime: experimental and clinical study].

Cefixime is a new oral cephalosporin with in vitro activity similar to that of third-generation cephalosporins. Renal excretion accounts for only 40% of systemic clearance of cefixime, suggesting that biliary excretion of the drug may be significant. This study was designed to determine to what extent nonrenal clearance of cefixime is due to biliary excretion of the parent compound. In an isolated perfused rabbit liver model, biliary excretion of cefixime was very low, with only 0.28 +/- 0.15% of a single 10 mg dose injected in the system being recovered in the bile after three hours perfusion. The liver biotransformation rate for cefixime was found to be 16.2%. These results are in striking contrast with those obtained in human studies. Cefixime levels in duodenal juice aspirates collected over four hours following an intravenous injection of 200 mg cefixime in six healthy volunteers were at least fivefold concomitant serum levels. Studies of bile collected by external biliary drainage during 24 hours following an oral dose of 200 mg cefixime in ten cholecystectomized patients showed that the Cmax was 56.9 +/- 70 mg/l, i.e., 25-fold the serum Cmax (2.3 +/- 0.85 mg/l). The bile AUC/serum AUC ratio was 20.4 +/- 20.3. Mean bile level of cefixime was still as high as 4.3 +/- 3.7 mg/l 20 hours after dosing. The amount of cefixime excreted in the bile over 24 hours was 10.0 +/- 12.3 mg i.e., 5% of the dose administered. Twenty-four hour renal excretion of cefixime was 53.3 +/- 26.2 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

[Experimental study on the hepatobiliary kinetics and excretion of temafloxacin. Evidence for production of active metabolites by the rabbit liver].

Temafloxacin is a new fluoroquinolone derivative currently under evaluation. Its hepatobiliary disposition remains undefined as yet. The present study represents an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for three hours with reconstituted and oxygenated blood in a closed circuit. A the onset of the procedures, temafloxacin 10 mg were added to the circulating blood. Both bile and blood were sampled throughout the perfusion time, and liver fragments were taken at the end of the experiments. Temafloxacin levels were measured by HPLC in serum and hepatic tissue, and by both HPLC and microbiological assay in bile. The percentage of drug undergoing hepatic biotransformation appeared to be high, i.e. 58.3%. This finding is substantiated by the comparison of temafloxacin levels in bile, as provided by HPLC and microbiological assay, the latter yielding concentrations twice as high (biliary peak: 33.5 +/- 2.8 micrograms/ml versus 19.3 +/- 3.1 micrograms/ml by HPLC assay) as those obtained by HPLC (p less than 0.05). Consistently, the average amount of temafloxacin excreted into the bile (0-3 h) was, respectively, 92 micrograms (0.9% of the dose) and 204 micrograms (2.0%) as determined by HPLC and microbiological methods (p less than 0.05); this statistically significant difference suggests the presence of active metabolites in bile. The presented results bring out evidence for substantial biotransformation of temafloxacin by Rabbit liver. Extrapolation to other species, however, would be hazardous; further pharmacokinetic studies are needed in order to assess the relevance of these findings in humans.

4-Quinolones↗
PubMed1990

[Consequences of hyperglycemia on glucose and nitrogen metabolism in liver cirrhosis. A study using a hyperglycemic clamp].

To study the consequences of hyperglycemia on glucose and nitrogen metabolism in cirrhosis, an hyperglycemic clamp was performed in 5 cirrhotic patients and 5 normal controls during two subsequent periods of 90 min, at 7.78 and then at 13.89 mmol/l. In the first period, glucose infusion and metabolic clearance rates were decreased in cirrhotics vs controls (p less than 0.05). In the second period, this difference between the two groups disappeared because of a more important enhancement in cirrhotics. Baseline plasma C peptide levels and those during hyperglycemia were the same during hyperglycemia in both groups, but plasma insulin level rose more in cirrhotics (p less than 0.05). Baseline insulin secretion following IV glucagon was reduced in cirrhotics vs controls (p less than 0.05), but became normal in the hyperglycemic state. Plasma glucagon levels were enhanced at all times in cirrhotics vs controls (p less than 0.01), but dropped more in cirrhotics vs controls (p less than 0.05). Insulin responsiveness, defined as the "glucose consumption: plasma insulin concentration" ratio was reduced in cirrhotics at 7.78 mmol/l (p less than 0.01), but was the same in both groups at 13.80 mmol/l because of a more important enhancement in cirrhotics, reflecting an improvement of insulin action probably at the post-receptor level and of non-insulin-mediated glucose transport. Hyperglycemia induced a drop in plasma concentration and muscular release of all aminoacids, excepted alanine, between the basal state and the end of the study. Aminoacid concentration rose only in cirrhotics, without any change in muscular output. In the same time, blood ammonia level rose only in cirrhotics, without reduction of muscular uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Biliary pharmacokinetic profile of piperacillin: experimental data and evaluation in man.

The purpose of the present experimental and clinical work is to revisit the biliary pharmacokinetic properties of piperacillin. Whereas the up to now published data result from microbiological assays, this work was realized by high performance liquid chromatography. In the isolated and perfused rabbit liver model (n = 5; 3 h), the biliary level peaked at 1,013 +/- 305 micrograms/ml between 30 and 60 min. During the experiments, 56.7% and 10.8% of the administered piperacillin (10 mg) were respectively eliminated in bile and submitted to hepatic biotransformation. In man, a single 2 g i.v. dose was administered to 6 volunteers. The excretion measured in the duodenal fluid was 1,681 +/- 601 micrograms in 4 h (0.08% of the administered dose). In cholecystectomized patients (n = 10) provided with a T-drain, the biliary peak concentration was 211 +/- 64 micrograms/ml during the 2nd h, and the 24 h biliary elimination was 12,963 +/- 3,332 micrograms, representing 0.65% of the administered dose. The hepato-biliary clearance was 0.80 ml/min. On per-operatively collected serum, choledocal bile, gallbladder bile and gallbladder wall samples (n = 10 patients), the concentrations of piperacillin simultaneously measured 1 h after the i.v. administration of 2 g were respectively, 81.7 +/- 20.5, 382 +/- 110, 30.8 +/- 2.5 micrograms/ml and 10.5 +/- 2.6 micrograms/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Biliary elimination and hepatic disposition of piperacillin: experimental evaluation].

The rate of biliary elimination and the hepatic disposition of piperacillin were studied by using an experimental model of a three hours perfusion of five isolated rabbit liver preparations. After addition of 10 mg of the antibiotic to the circulating blood, a mean biliary peak of 1,013 +/- 305 micrograms/ml was obtained between the 30th and 60th minute. The cumulated biliary elimination (0-3 hr) amounted to 5,665 +/- 389 micrograms (56.7% of the dose given). The hepatobiliary clearance was calculated to 134.2 ml/hr and the biliary elimination rate constant to 0.5 545 (h-1). After the procedure, 7.2 +/- 2.7% of the dose of piperacillin was still present in the circulating blood and 0.4 +/- 0.1% in the liver. The degradation of the antibiotic in the perfusion device concerned 24.9% of the dose. The percentage of piperacillin undergoing hepatic biotransformation, calculated by subtraction, was 10.8%. Under these conditions, the biliary elimination of piperacillin is much higher than that of the twenty other beta-lactams studied in our laboratory by the same experimental procedure.

Animals↗
PubMed1989

Clinical pharmacokinetics of cefotiam.

Cefotiam, a semisynthetic parenteral cephalosporin of the aminothiazole group, exhibits interesting properties: stability against hepatic metabolism and excellent solubility, accounting for an apparent volume of distribution 2 to 3 times higher than that of most other cephalosporins. Its degree of protein binding is about 40%. High concentrations of cefotiam are observed in several tissues (kidney, heart, ear, prostate and genital tract) as well as in fluids and secretions (bile, ascitic fluid). In healthy subjects, the serum elimination half-life is about 1 hour. The pharmacokinetics are linear only for doses lower than 1g. Cefotiam is mostly (and rapidly) eliminated in unchanged form in urine; 50 to 70% of the dose is recovered during the 12 hours following administration, and only severe renal failure, with creatinine clearance less than 5 ml/min, significantly alters the elimination half-life. Although the drug has no proven nephrotoxicity in man, a reduction of the dose is recommended when creatinine clearance is less than 30 ml/min.

Aging↗