Depuration of geosmin- and 2-methylisoborneol-induced off-flavors in recirculating aquaculture system (RAS) farmed European whitefish Coregonus lavaretus.

European whitefish Coregonus lavaretus has increasingly become an important species for aquatic food production, especially in the Nordic countries. Whitefish is produced in traditional cage and pond operations, and in recirculating aquaculture system (RAS) in which, unfortunately, off-flavors and odors, mostly caused by geosmin (GSM) and 2-methylisoborneol (MIB), can accumulate in fish flesh from the circulating water. GSM and MIB have very low human sensory detection limits and, therefore, often disliked by consumers even at low concentrations. In this study, concentrations of GSM and MIB in RAS farmed European whitefish were studied by an analytical method based on headspace solid phase microextraction and gas chromatography-mass spectrometry. Concentrations were determined in different parts of fish: fillet, neck, belly, and tail during a depuration period and in depuration water. The highest initial concentrations were on average 32 ng g-1 (GSM) and 24 ng g-1 (MIB) in European whitefish fillet and 128 ng L-1 (GSM) and 94 ng L-1 (MIB) in water, respectively. After a depuration period of 16 days, concentrations decreased to below the detection limits, indicating the importance of the depuration period.

Preoperative levosimendan infusion in combined aortic valve and coronary bypass surgery.

BACKGROUND: Cardiopulmonary bypass may have detrimental effects on intestinal function and decrease the concentrations of the active, long-acting metabolites of levosimendan, an inodilator used to improve cardiac function. The aim of this study was to evaluate the haemodynamic effects of preoperative levosimendan in patients undergoing high-risk cardiac surgery. METHODS: Twenty-four patients were randomized to receive levosimendan (12 µg bolus followed by an infusion of 0.2 µg kg(-1) min(-1)) or a placebo 24 h before surgery. The inclusion criteria were left ventricular ejection fraction (LVEF) <50% or LV hypertrophy indicated by a wall thickness of >12 mm. Haemodynamics were recorded every hour for 24 h (pulmonary artery catheter) and daily until postoperative day 4 (whole-body impedance cardiography). Doppler echocardiography with tissue Doppler imaging was used to assess systolic and diastolic cardiac function. RESULTS: The cardiac index (CI) and stroke volume index (SI) were higher in the levosimendan group (LG) for the 4 day postoperative period (P<0.05); on the fourth postoperative day, the CI was 3.0 litre m(-2) min(-1) in the LG compared with 2.4 litre m(-2) min(-1) in the control group (CG) and the SI was 30 vs 25 ml m(-2), respectively. The LVEF measured at baseline and on the fourth postoperative morning decreased in the CG, but was maintained in the LG. CONCLUSIONS: Levosimendan improved haemodynamics compared with a placebo in patients undergoing high-risk cardiac surgery. The concentrations of levosimendan's metabolites were higher compared with earlier studies using perioperative dosing.

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme.

UNLABELLED: AIMS/HYPOTHESIS; The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance. METHODS: A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity. RESULTS: During the first year, weight loss in the first 212 study subjects was 4.7 +/- 5.5 vs 0.9 +/- 4.1 kg in the intervention and control group, respectively (p < 0.001). The plasma glucose concentrations (fasting: 5.9 +/- 0.7 vs 6.4 +/- 0.8 mmol/l, p < 0.001; and 2-h 7.8 +/- 1.8 vs 8.5 +/- 2.3 mmol/l, p < 0.05) were significantly lower in the intervention group after the first year of intervention. Favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group. CONCLUSION/INTERPRETATION: The interim results show the efficacy and feasibility of the lifestyle intervention programme.

The effect of pH on the in-vitro dissolution of three second-generation sulphonylurea preparations: mechanism of antacid-sulphonylurea interaction.

Simultaneously administered magnesium hydroxide or sodium bicarbonate can increase the rate and extent of absorption of non-micronized glibenclamide and glipizide. To clarify the mechanism of this interaction we have studied the effect of pH on the dissolution of two different formulations of glibenclamide (micronized and non-micronized) and one formulation of glipizide. One tablet of each sulphonylurea preparation was placed in a dissolution chamber containing continuously mixed dissolution medium at pH 2, pH 6 or pH 9; 5 mL of the medium was replaced every 2 min. The amount of glibenclamide dissolved from the non-micronized formulation within 2 h, was 1.2, 4.5 and 76% at pH 2, pH 6 and pH 9, respectively (P < 0.01), whereas 21, 29 and 100% was dissolved from the micronized formulation (P < 0.01). The amount of glipizide dissolved within 2 h at pH 2, pH 6 and pH 9 was 3.9, 24 and 92%, respectively (P < 0.01). We conclude that the elevated pH of the gastric contents is the most likely explanation for the interactions previously demonstrated between antacids and sulphonylureas after their concomitant ingestion.

Effects of milk and food on the absorption of enoxacin.

The effects of milk and a standard breakfast on the oral absorption of enoxacin were evaluated in eight healthy volunteers in a randomized, balanced, four-way crossover study. After an overnight fast, 400 mg enoxacin was given with water, milk, a breakfast or with a breakfast and milk. The extent of enoxacin absorption was not affected by any of the three treatments, and no statistically significant changes were found with respect to peak plasma enoxacin concentration or time to peak. We conclude that enoxacin can be taken together with food and dairy products.

Different effects of products containing metal ions on the absorption of lomefloxacin.

The effects of different cation containing products on the absorption of lomefloxacin were evaluated in eight healthy volunteers in a five-way randomized crossover study. The treatments were lomefloxacin alone, lomefloxacin with milk (300 ml), lomefloxacin with calcium carbonate (corresponding to 500 mg calcium), lomefloxacin with ferrous sulfate (corresponding to 100 mg elemental iron), and lomefloxacin with sucralfate (1 gm). Treatments were separated by a 7-day washout period. The bioavailability of lomefloxacin was significantly reduced when it was given with sucralfate; the area under the plasma drug concentration-time curve (AUC) from 0 to 24 hours was reduced by 51% (p < 0.05). Ferrous sulfate reduced the maximum plasma concentration of lomefloxacin by 26% (p < 0.05), the total amount of lomefloxacin recovered in urine by 15% (p < 0.05), and the AUC by 13% (p = 0.26). Calcium carbonate and milk had no significant effects on the bioavailability of lomefloxacin. We conclude that concomitant use of lomefloxacin and sucralfate should be avoided. It may also be advisable not to take lomefloxacin with ferrous sulfate, although this interaction is probably of no clinical significance. Calcium carbonate and milk do not affect lomefloxacin absorption.

Effect of sucralfate on absorption of norfloxacin and ofloxacin.

The effect of sucralfate on the pharmacokinetics of norfloxacin and ofloxacin was assessed in two separate crossover studies with healthy volunteers. In both studies, eight subjects were randomized to one of the following three regimens: a 400-mg dose of norfloxacin or ofloxacin alone, norfloxacin or ofloxacin given simultaneously with sucralfate (1 g), or norfloxacin or ofloxacin given 2 h before sucralfate. Coadministration of sucralfate reduced the bioavailability of norfloxacin and ofloxacin by 91% (P < 0.001) and 61% (P < 0.001), respectively. However, when norfloxacin and ofloxacin were given 2 h before sucralfate, there were no significant alterations in the pharmacokinetics of either fluoroquinolone. Similar results were obtained when the cumulative amount of each fluoroquinolone recovered in the urine was used to calculate bioavailability. To avoid these interactions and potential therapeutic failures, norfloxacin and ofloxacin should not be used concurrently with sucralfate. The interaction can be minimized by maximizing the time between the fluoroquinolone dose and the previous sucralfate dose and giving the fluoroquinolone at least 2 h before another sucralfate dose.

The effect of ferrous sulphate on the absorption of norfloxacin, ciprofloxacin and ofloxacin.

The effect of ferrous sulphate on the absorption of norfloxacin, ciprofloxacin and ofloxacin was studied in three separate, two-period crossover trials, each involving eight healthy volunteers. After an overnight fast, a single dose of norfloxacin (400 mg), ciprofloxacin (500 mg) or ofloxacin (400 mg) was administered with and without ferrous sulphate (corresponding to 100 mg elemental iron). The absorption of all the fluoroquinolones studied was significantly reduced when they were co-administered with ferrous sulphate. The reduction in the area under the plasma drug concentration-time curve from 0 to 24 h was most marked in the case of norfloxacin, while ofloxacin was least affected by ferrous sulphate. The AUC of norfloxacin was reduced by 73% (P < 0.001) and its peak plasma concentration by 75% (P < 0.01) by concomitant ingestion of ferrous sulphate. The AUC and peak plasma concentration of ciprofloxacin were reduced by 57% (P < 0.001) and 54% (P < 0.01), respectively, by ferrous sulphate. Concomitant ingestion of ferrous sulphate reduced the AUC and peak plasma concentration of ofloxacin by 25% (P < 0.01) and 36% (P < 0.01), respectively. Similar results were obtained with respect to the urinary recoveries of each fluoroquinolone. We recommend that norfloxacin and ciprofloxacin should not be taken together with ferrous sulphate. It would also be advisable not to take ofloxacin with ferrous sulphate, especially if the organism causing infection is only moderately susceptible.

The effects of different doses of sodium bicarbonate on the absorption and activity of non-micronized glibenclamide.

The effects of different doses of sodium bicarbonate on the absorption and activity of non-micronized glibenclamide were studied in six healthy volunteers, using a randomized crossover design with four phases. The subjects ingested a single dose of non-micronized glibenclamide (2.5 mg) with 150 ml of water or with 150 ml of water containing 0.3, 1.0 or 3.0 g of sodium bicarbonate. Plasma concentrations of glibenclamide, insulin and glucose were measured. Coadministration of 1.0 or 3.0 g of sodium bicarbonate with non-micronized glibenclamide increased the area under the plasma glibenclamide concentration-time curve (AUC) from 0 to 1 h 30-fold (p < 0.05) and 38-fold (p < 0.05), respectively. The 1.0- and 3.0-g doses of sodium bicarbonate also increased the AUC of plasma glibenclamide from 0 to 2 h, about 3-fold (p = 0.05 and 0.07, respectively). The peak plasma concentration, peak time and total extent of absorption of glibenclamide and the insulin and glucose responses were not significantly altered by any of the doses of sodium bicarbonate studied. Concomitant ingestion of 1.0 or 3.0 g of sodium bicarbonate and non-micronized glibenclamide greatly increased the early bioavailability of glibenclamide. However, this interaction did not alter the activity of glibenclamide.

Interference of dairy products with the absorption of ciprofloxacin.

The effects of milk and yogurt on the bioavailability of ciprofloxacin were studied in seven healthy volunteers in a randomized crossover trial. After an overnight fast, 500 mg ciprofloxacin was given with 300 ml water, milk, or yogurt. Plasma ciprofloxacin concentrations were significantly (p less than 0.05) lower during the milk and yogurt phases from 1/2 to 10 hours; at 1/2 hour the concentration was reduced by 70% by milk and by 92% by yogurt. Milk reduced the peak plasma concentration by 36% (p less than 0.05) and yogurt by 47% (p less than 0.05). The extent of bioavailability, measured as the total area under the plasma concentration-time curve and 24-hour urinary excretion of ciprofloxacin, was reduced by 30% to 36% by milk and yogurt (p less than 0.05). We conclude that the absorption of ciprofloxacin can be reduced by concomitant ingestion of milk or yogurt. To avoid therapeutic failures in infections where the causative organism is only moderately susceptible, ingestion of large amounts of dairy products in liquid form with ciprofloxacin is not recommended.