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Biomedical subjects

C Tschanz

Publications and source records attributed to C Tschanz.

At least 19 recordsLinked to original sources

Negligible changes in piglet serum clinical indicators or organ weights due to dietary single-cell long-chain polyunsaturated oils.

Single-cell oils are currently included in human infant formula as sources of the long-chain polyunsaturates (LCP) docosahexaenoic acid (DHA) and arachidonic acid (AA) in many countries, but have not yet been approved for use in the USA. We prepared four bovine-milk-based formulas with AA/DHA=0, 34/17, 68/34 and 170/85 (mg per 100 kcal formula) provided by two commercial single-cell oils. These levels correspond approximately to 0, 1, 2 and 5 times the concentrations used in infant formulas and, due to greater consumption of formula per unit body weight, resulted in daily consumption of approximately 0, 3, 6 and 16 times those anticipated for human infants. All other dietary fat (47% of calories) was provided by a vegetable oil blend used in commercial human infant formulas. Domestic piglets were allowed to nurse with the sow for 24 h after parturition, then removed to individual cages and maintained on one of the four diets. At 30 days of age the piglets were sacrificed, and serum collected and organs weighed. With litters treated as a blocked variable, no significant differences among groups were found by analysis of variance for the following serum assays: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, albumin, glucose, cholesterol, triglycerides, and total protein. No significant differences were found for hematocrit or body weight. No significant differences were found among groups for weights of liver, brain, heart, lung, spleen, kidneys or lung, analyzed as absolute weight and as a fraction of body weight. Hematoxylin/eosin liver sections examined by light microscopy showed no abnormalities as evaluated by an independent pathologist. DHA content in liver and heart and AA content in heart showed significant dose-related accumulation (P<0.05) and confirmed enhanced tissue accretion of DHA and AA from both oils. We conclude that single-cell oils in formula consumed for 1 month in amounts up to 16-fold greater than proposed for human infants in the USA did not result in clinical chemistry or histopathologic indications of toxic effects in neonatal pigs.

Animals↗

Vulvodynia after CO2 laser treatment of the female genital mucosa.

We have observed 3 cases of vulvodynia after CO2 laser (pulse or scan) treatment of condylomata acuminata (n = 1) or bowenoid papulosis (n = 2) of the female genital mucosa. Laser treatment was associated with a considerable delay in healing (3-4 months) and chronic pain. The histology of the treated areas showed a scar tissue and severe mucosal atrophy. The occurrence of painful scars following CO2 laser treatment could be related to an inadequate laser technique considering the morphology of the vagina.

Adult↗

Postmarketing surveillance of food additives.

Postmarketing surveillance of consumption and of anecdotal reports of adverse health effects has been recognized by a number of regulatory authorities as a potentially useful method to provide further assurance of the safety of new food additives. Surveillance of consumption is used to estimate more reliably actual consumption levels relative to the acceptable daily intake of a food additive. Surveillance of anecdotal reports of adverse health effects is used to determine the presence of infrequent idiosyncratic responses that may not be predictable from premarket evaluations. The high-intensity sweetner, aspartame, is a food additive that has been the subject of extensive evaluation during the postmarketing period and is thus used as an example to discuss postmarketing surveillance.

Aspartame↗

Evaluation of clinical and biochemical parameters in children after consumption of microparticulated protein fat substitute (Simplesse).

OBJECTIVE: The objective of this randomized, double-blind, two-way crossover study in healthy children was to evaluate whether microparticulated protein (MPP, Simplesse) fat substitute had any effects on various clinical and biochemical parameters when compared to super premium ice cream (approximately 16% butterfat). METHODS: Twenty-four children (12 males, 12 females), 7-10 years of age, received their normal diet plus two consecutive 7-day treatment regimens consisting of one serving (approximately 196 mL) per day of either ice cream or a frozen dessert made with MPP. Three-day food diaries, routine hematologies, clinical chemistries, urinalyses, fasting plasma lipids and amino acids, vital signs and adverse experiences were compared between treatments. RESULTS: There were no clinically significant effects on any of the parameters following either treatment, although there were statistically significant increases in fasting plasma cholesterol and high-density lipoprotein cholesterol following ice cream when compared to MPP. There were no statistically significant differences between the two treatments in regard to macronutrient consumption. The only adverse experience related to treatment was one episode of vomiting following the ice cream. The children ingested more than five times the amount of MPP than that found in the 90th percentile of frozen dessert consumption by this age group. The protein intake (5.5 g/day) from MPP at this level of consumption would only modestly increase the total daily protein intake. CONCLUSION: Children ingesting approximately 196 mL/day of frozen dessert made with MPP did not show any clinically significant changes in various clinical and biochemical parameters.

Amino Acids↗

Aspartame and sucrose produce a similar increase in the plasma phenylalanine to large neutral amino acid ratio in healthy subjects.

Aspartame (L-aspartyl-L-phenylalanine methyl ester) consumption has been postulated to increase brain phenylalanine levels by increasing the molar ratio of the plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids (Phe/LNAA). Dietary manipulations with carbohydrate or protein can also produce changes in the Phe/LNAA value. To compare the effects of aspartame and carbohydrate on Phe/LNAA, beverages sweetened with aspartame, sucrose, and aspartame plus sucrose, and unsweetened beverage were ingested by 8 healthy, fasted subjects in a randomized, four-way crossover design. The beverages were sweetened with an amount of aspartame (500 mg) and/or sucrose (100 g) approximately equivalent to that used to sweeten 1 liter of soft drink. The baseline-corrected plasma Phe/LNAA values did not differ significantly following ingestion of aspartame or sucrose. Following aspartame alone, the high mean ratio increased 26% over baseline 1 h after ingestion. Following sucrose alone, the high mean ratio increased 19% at 2.5 h. Sucrose increased the Phe/LNAA value due to an insulin-mediated decrease in the plasma LNAA, while aspartame increased the ratio by increasing the plasma Phe concentration. These findings indicate that similar increases in plasma Phe/LNAA occur when healthy, fasting subjects ingest amounts of equivalent sweetness of sucrose or aspartame.

Adult↗

Production of superoxide during the metabolism of nitrazepam.

Nitrazepam is metabolized in both humans and rats to 7-amino-nitrazepam OFFicating that this drug is reduced to a number of metabolic intermediates including several free radical species. When rat-hepatic microsomes are incubated with NADPH in the presence of nitrazepam, its nitro anion free radical was observed under anaerobic conditions. In the presence of oxygen, this free radical reduced oxygen giving nitrazepam and superoxide. 7-Nitroxyl-nitrazepam was produced by the chemical oxidation of 7-amino-nitrazepam using m-chloroperbenzoic acid. Reaction of this reactive free radical with hepatic microsomes led to the covalent spin labelling of microsomal protein. This phenomenon was also observed by the enzymic oxidation of 7-amino-nitrazepam with hepatic microsomes, obtained from a phenobarbital-induced rat, in the presence of a NADPH-generating system. With the generation of superoxide and hydrogen peroxide (arising from the dismutation of superoxide), it is not surprising that nitrazepam-enhanced lipid peroxidation was demonstrated by monitoring the production of lipid peroxyl radicals using spin-trapping techniques.

Animals↗

Effect of oxygen-carrying resuscitation fluids on the pharmacokinetics of antipyrine, diazepam, penicillin, and sulfamethazine in rats.

The effects of exchange transfusion with an oxygen-carrying resuscitation fluid, Fluosol DA 20% or stroma-free hemoglobin, on the pharmacokinetics of antipyrine, diazepam, penicillin, and sulfamethazine were studied in rats. After transfusion with Fluosol DA 20% or stroma-free hemoglobin the pharmacokinetics of antipyrine, diazepam, and penicillin were unchanged when compared to control animals. After transfusion with Fluosol DA 20%, the t 1/2 of sulfamethazine was increased from 3.15 +/- 0.56 to 7.65 +/- 2.41 hr (p less than 0.05) and the Vd was increased from 60.7 +/- 17.5 to 152 +/- 16 ml (p less than 0.05). In contrast, after transfusion with stroma-free hemoglobin, the AUC of sulfamethazine was decreased from 129 +/- 28 to 80.5 +/- 27.7 micrograms X h X ml-1 (p less than 0.05) and there was an increase in Cl from 12.2 +/- 3.4 to 20.2 +/- 6.0 ml X h-1 (p less than 0.05) and Vd from 60.1 +/- 11.8 to 132 +/- 49 ml (p less than 0.05). The reason for these alterations is not clear. Fluosol DA 20% and stroma-free hemoglobin may alter the acetylation of sulfamethazine.

Animals↗

Decreased rate of creatinine production in patients with hepatic disease: implications for estimation of creatinine clearance.

Serum creatinine concentration is commonly used in conjunction with individual patient characteristics (e.g., age, sex, and body weight) in order to estimate creatinine clearance. Such estimates of creatinine clearance are widely used as a parameter for individualization of dosages of drugs excreted primarily via the kidneys in patients with diminished renal function. However, estimation of creatinine clearance in patients with concurrent hepatic disease tends to result in substantial overprediction of observed creatinine clearance in this patient population. This report suggests that a diminished rate of creatinine production in patients with hepatic disease is a likely explanation for this anomaly. This postulated mechanism is based on a presentation of the biology of creatinine formation.

Adult↗

Kinetics of R andS warfarin enantiomers.

A method is reported for simultaneous measurement of the kinetics of R and S warfarin enantiomers. Pure pentadeuterated R and S enantiomers were each combined with unlabeled enatiomers to form "pseudo"-racemic mixtures which were given (0.75 mg/kg) to 5 healthy subjects. Plasma R and S enantiomer levels were measured by gas chromatography--mass spectrometry. Elimination half-lifes (t1/2S) and volumes of distribution (VdS) of the enantiomers were not altered by the presence of the other.

Adult↗

Topical application of lindane cream (Kwell) and antipyrine metabolism.

The transcutaneous absorption of a 1% lindane cream (Kwell) was determined after application according to the official label. By 3 days after application the plasma lindane level increased from nondetectable to 10.3 +/- 2.2 ng/ml. Sufficient lindane was absorbed to increase the plasma clearance of antipyrine from 0.027 +/- 0.009 to 0.037 +/- 0.011 1/kg/hr (p less than 0.05). these findings indicate significant transcutaneous absorption of lindane occurs following a single application and are compatible with the neurological toxicity reported following the topical application of lindane cream.

Administration, Topical↗

Quantitation of lidocaine and its deethylated metabolites in plasma and urine by gas chromatography-mass fragmentography.

A sensitive, precise and accurate method for simultaneous quantitation of lidocaine and its deethylated metabolites by gas chromatography-mass fragmentography has been developed. Propyl derivatives of the deethylated metabolites are formed directly in either plasma or urine by treatment with propionaldehyde and sodium cyanoborohydride. The propyl derivatives and unchanged lidocaine are extracted, separated by gas chromatography and quantitated by mass fragmentography using mepivacaine as the internal standard. Quantitation of these compounds to levels as low as 50 ng/ml body fluid has been achieved with coefficients of variation less than 10%.

Chromatography, Gas↗

Metabolic disposition of antipyrine in patients with lung cancer.

The metabolism of antipyrine (10 mg/kg i.v.) was studied in nine patients with cancer of the lung and in a cancer-free control group matched for age, sex, drug intake, and smoking and drinking history. The mean plasma clearance of antipyrine was 0.0475 +/- 0.009 liter/kg/hr in the tumor group and 0.0557 +/- 0.007 liter/kg/hr in the control group (p greater than 0.05). The antipyrine plasma elimination half-life was longer in the group with tumors (9.5 +/- 1.3 hr) compared to the control group (7.7 +/- 1.3 hr), but the difference was not statistically significant (p greater than 0.05). There was no difference between the groups in the excretion of two major antipyrine metabolites, 4-hydroxyantipyrine and N-demethylantipyrine, in a 48-hr urine sample. Thus, the presence of lung cancer in humans does not significantly alter antipyrine elimination.

Adult↗

Quantitation of N-demethylantipyrine in biological samples and isolation and characterization of its glucuronic acid conjugate.

An improved method for quantitating N-demethylantipyrine (N-DEM-AP) in urine by gas chromatography or gas chromatography-mass spectrometry has been developed. Recovery of greater than 90% of N-DEM-AP was achieved by extraction of the sample at pH 1 after addition of 3-amino-1-phenyl-2-pyrazolin-5-one. The coefficient of variation of replicate analyses was 8%. N-DEM-AP was excreted in the urine as a glucuronic acid conjugate. This conjugate was isolated from the urine of an individual receiving antipyrine and purified. The NMR and mass-spectral data are consistent with the conjugate being an O-glucuronide of N-DEM-AP in its enol form.

Antipyrine↗