The influence of inflammatory disease on the pharmacokinetics of atenolol and metoprolol was investigated after administering single oral 100 mg doses of the drugs to six subjects. Each subject had a respiratory tract infection with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour and a body temperature of at least 38.5 degrees. Since the subjects subsequently received atenolol and metoprolol when they were healthy, each person acted as his own control. Inflammatory disease had no influence on the kinetics of metoprolol. In contrast, mean peak plasma levels and AUC for atenolol were significantly lower, both by about 40 per cent, during infectious disease compared to the healthy state (p less than 0.05), where as renal clearance of atenolol slightly increased from 110.8 +/- 14.7 ml min-1 in the healthy state to 128 +/- 21.6 ml min-1, when the ESR's were elevated. The elimination half-life of atenolol, about 10 h, was not affected by the health status of the subjects. Reduced absorption in the gastro-intestinal tract and enhanced elimination of atenolol from plasma might account for the decreased AUC and peak plasma levels of the drug during inflammatory disease.

Adult↗

PubMedDate not supplied

Reduction of cisplatin toxicity in cultured renal tubular cells by the bioflavonoid quercetin.

Quercetin (QC), a polyphenolic compound widely distributed in fruits and vegetables has recently gained interest due to its cisplatin (CP) sensitizing properties in cancer cells. It is currently unknown, whether quercetin also increases the susceptibility of the kidneys to cisplatin toxicity. We studied the effects of various bioflavonoids on CP toxicity in an in vitro model of cultured tubular epithelial cells (LLC-PK1). Viability of LLC-PK1 cells, as assessed by lactate dehydrogenase (LDH) release and MTT-test, was affected by CP (100-400 microM) in a time and dose dependent fashion. Pretreatment of cells with QC for 3 h significantly reduced the extent of cell damage. The protective activity of QC was concentration dependent, starting at 10-25 microM and reaching a plateau between 50 and 100 microM. Other bioflavonoids (catechin, silibinin, rutin) did not diminish cellular injury, even at higher concentrations (100-500 microM). Quercetin itself showed some intrinsic cytotoxicity at concentrations exceeding 75 microM. Our data indicate that quercetin reduces cisplatin toxicity in cultured tubular epithelial cells. The exact mechanism of protection is unclear, though scavenging of free oxygen radicals may play an important role.

Animals↗

PubMedDate not supplied

[The vitamin A requirement of fattening cairina].

In two experiments with 420 male cairina (Cairina moschata domestica L.) semisynthetic rations were used with vitamin A supplements between 0 and 10,000IU per kg feed. Clinical deficiency symptoms, such as coordination disturbances or horny growths at the oesophagus glands, could be prevented in the starter period up to 3rd week with 500IU vitamin A and in the fattening period between the 4th and 10th/11th weeks with a 250IU vitamin A supplement per kg feed. Cairina achieved an optimal fattening performance under the conditions tested with 1,000 IU in the starter period and with 500 IU vitamin A supplement in the fattening period. Under consideration of the vitamin A storage in the liver and a safety supplement of 4000 IU vitamin A per kg start feed (0-3 weeks) and 2,000 IU vitamin A per kg fattening feed (4-11 weeks) is suggested as requirement norm and mixed feed supplement.

Animal Feed↗

PubMedDate not supplied

LC-MS determination of oxydemeton-methyl and its main metabolite demeton-S-methylsulfon in biological specimens--application to a forensic case.

A sensitive method for the identification and quantitation of the organophosphate insecticide oxydemeton-methyl and its metabolite demeton-S-methylsulfon from human blood and various tissue samples has been established. After solid-phase extraction using C18 cartridges the extracts were analyzed by high-performance liquid chromatography with mass selective detection (Finnigan MAT LCQ). The method was completely validated. The limit of detection is 1 ng/g blood for the parent substance oxydemeton-methyl and 2 ng/g blood for the metabolite demeton-S-methylsulfon. This method was applied for the analysis of blood and tissue samples of a 58-year-old man who died after the intake of Metasystox R-Spezial, a product from Bayer containing oxydemeton-methyl. Because of a prolonged interval between the ingestion and death, the concentrations of oxydemeton-methyl and demeton-S-methylsulfon were very low. Although the body was already putrefied when the autopsy was performed, the chromatograms of blood and tissue samples were free of interfering peaks.

Autopsy↗

PubMedDate not supplied

Studies of the influence of ochratoxin A on immune and defense reactions in the mouse model.

In the mouse model, the mycotoxin ochratoxin A has a non-selective suppressive effect on various immune and defence reactions. Apart from weight depression, lymphopenia, neutrophilia and eosinophilia, antibody-producing cells, antibody titres in blood serum and phagocytosis of Escherichia coli by blood phagocytes become suppressed. Moreover, immunized animals show a lower survival rate after experimental infection with Pasteurella multocida as well as an increase in oxygen radicals in blood cells.

Animals↗

PubMedDate not supplied

Effects of acidosis on acute phase protein metabolism in liver cells.

Metabolic acidosis has been shown to act as a causative factor in muscle protein breakdown and negative nitrogen balance, as well as in decreased albumin synthesis. Albumin and other acute phase proteins (APP) are mainly synthesized in the liver following induction by interleukins, hormones and other mediators. Acute phase proteins have been shown to be predictors of cardiovascular mortality in the general population and in patients with end stage renal disease (ESRD). Clinical investigation gives evidence that albumin is reduced by acidosis in ESRD patients. The aim of our study was to investigate the role of the liver in acidosis, i.e. the influence of acidosis on metabolic activity and secretion of APP by liver cells (HepG2). Cells were cultured in a medium containing different amounts of bicarbonate. Metabolic activity was significantly diminished when the bicarbonate concentration of the extracellular medium was reduced (86.13+/-1.90% (pH 7.0) vs. 99. 53+/-90% (pH 7.4); p<0.01). While cellular release of negative APP was significantly decreased (albumin: 4.6+/-0.41 (pH 7.0) vs. 7.54+/-0.62 (pH 7.4) [ng/microg protein], p<0.001, transferrin: (0. 78+/-0.08 (pH 7.0) vs. 1.07+/-0.07 (pH 7.4) [ng/microg protein], p<0. 05), no significant influence of acidosis (pH 7.0) on the positive APP, alpha(1)-acid glycoprotein (AGP) (1.69+/-0.25) (pH 7.0) vs. 1.62+/-0.23 (pH 7.4) [ng/microg protein]), could be shown. Our data indicate that acidosis results in inhibition of liver cell metabolic activity and in reduced secretion of the negative acute phase proteins albumin and transferrin. In contrast, secretion of the positive acute phase protein AGP seems to be unchanged at pH 7.0 as compared to pH 7.4. We conclude that negative and positive APP in liver cells (HepG2) appear to be differently regulated by acidosis.

Acidosis↗

PubMedDate not supplied

High protein/energy vs. standard protein/energy nutritional regimen in the treatment of malnourished hemodialysis patients.

Although malnutrition is frequently encountered in maintenance hemodialysis (MHD) patients, a clear method of treating this complication is still lacking. Failure of nutritional support regimens may be due to inadequate support of dietary needs. Therefore, a high vs. standard or low protein/energy dietary regimen was studied in malnourished MHD patients. A total of 18 malnourished MHD patients selected according to subjective global assessment (SGA)-scores and biochemical indicators of malnutrition (serum albumin <40 g/l, cholesterol <200 mg/dl, prealbumin <30 mg/dl; two out of three) were assigned to three treatment groups: (A: 45 kcal/kg/d and 1.5 g protein/kg/d; B: 35 kcal/kg/d and 1.2 g protein/kg/d; C: spontaneous intake supplemented with 10% of mean protein and energy intake). A and B received food supplements at appropriate dosing to reach the targeted nutritional intake. During 3-month follow-up nutrient intake was assessed by repeated 4-day dietary diaries. Compliance and tolerance was good in each group. Weight gain (1.2+/-0.4 kg) was observed in group A, but not in B and C. Serum albumin levels increased by 1.0+/-0.5 g/l in group A, but not in B and C. Prealbumin and cholesterol levels were unaffected. Weight change correlated with mean dietary energy intake, but not with mean dietary protein intake. We conclude that prescription of 45 kcal/kg/d and 1.5 g protein/kg/d may be necessary to achieve weight gain and improvement of nutritional indices in malnourished MHD pts. Oral food supplements can be used safely and effectively to increase nutrient intake to high levels in these patients.

Aged↗

PubMedDate not supplied

Liver cell reactive components in peritoneal dialysis fluids.

Metabolic changes in peritoneal dialysis (PD) patients are an important aspect concerning long-term outcome. Liver plays the main role in regulating metabolism. The effects of peritoneal dialysis fluids (PDF) on liver cell function are scarcely investigated. Therefore, we investigated the effects of PDF, different in some components, on liver cell metabolism in vitro. Metabolic activity (MTT), cell integrity (LDH release), proliferation (BrdU incorporation) and synthesis of albumin and transferrin are measured by incubating HepG2 cells for 3 h and 24 h with six different PDFs: (a) lactate-buffered, pH5.5: PDF I (1.5% gluc.); PDF II (4.5% gluc. ); (b) bicarbonate-buffered, pH7.4: PDF III (1.5% gluc.), PDF IV (4. 5% gluc.); (c) amino acid-based solutions, pH 7.4: PDF V (low AA level) and PDF VI (high AA level). Metabolic activity of bicarbonate-treated cells is greatly enhanced in comparison to lactate-buffered PDFs. These findings are confirmed by proliferation data. Synthesis of albumin and transferrin is significantly enhanced by amino acid-based solutions. Our data demonstrate, that lactate-buffered PDF impair liver cells much stronger than bicarbonate-buffered PDF. pH is the parameter which contributes to cytotoxicity and impaired metabolism to a major extent. In contrast to glucose-containing solutions, amino acid-based PDF stimulate protein synthesis in liver cells.

Amino Acids↗

PubMedDate not supplied

The influence of renal function on plasma concentration, urinary excretion and antihypertensive effect of guanfacine.

18 hypertensive patients with a glomerular filtration rate (GFR) between 3.8 and 113ml/min received guanfacine as single intravenous and multiple oral dose treatment. Mean plasma concentrations of guanfacine on the fifth day or oral treatment ranged from 6.5 to 8.6ng/ml in patients with normal renal function (GFR > 90ml/min), as well as in those with a moderate degree of renal impairment (GFR 30 to 10ml/min) and in uraemic patients (GFR < 10ml/min). During guanfacine treatment plasma concentrations and fall in blood pressure did not differ in a statistically significant fashion among patients with varying degrees of renal function. Independent of renal function, in all investigated patients the elimination rate constant obtained from serum and urine values were close to 0.05h-1. Mean half-life of guanfacine was calculated to be 14h. The cumulative urinary excretion up to 48h fell from 57% in patients with normal renal function to 7.5% in uraemic patients. Thus, non-renal excretion plays an importat role in patients with impaired renal function.

Adult↗