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Biomedical subjects

S Jönsson

Publications and source records attributed to S Jönsson.

At least 19 recordsLinked to original sources

Determination of 2,4,6-trichloroanisole and 2,4,6-tribromoanisole on ng L-1 to pgL-1 levels in wine by solid-phase microextraction and gas chromatography-high-resolution mass spectrometry.

A gas chromatography-high-resolution mass spectrometry (GC-HRMS) method using solid-phase microextraction (SPME) for the determination of 2,4,6-trichloroanisole (TCA) and 2,4,6-tribromoanisole (TBA) in wine at low ng L(-1) levels was developed. A robust SPME method was developed by optimizing several different parameters, including type of fiber, salt addition, sample volume, extraction and desorption time. The quantification limit for TCA and TBA in wine was lowered substantially using GC-HRMS in combination with the optimized SPME method and allowed the detection of low analyte concentrations (ng L(-1)) with good accuracy. Limits of quantification for red wine of 0.3 ng L(-1) for TCA and 0.2 ng L(-1) for TBA with gas chromatography-negative chemical ionization mass spectrometry and 0.03 ng L(-1) for TCA and TBA were achieved using GC-HRMS. The method was applied to 30 wines of which 4 wines were sensorically qualified as cork defected. TCA was found in three of these wines with concentrations in the range 2-25 ng L(-1). TBA was not detected in any of the samples.

Anisoles↗

Lactational exposure and neonatal kinetics of methylmercury and inorganic mercury in mice.

The concentration of mercury in milk and the distribution pattern in the sucking pup was followed over time after administration of a single iv injection of 0.5 mg/kg body wt of 203Hg-labeled methylmercuric chloride or mercuric chloride to lactating mice on Day 10 of lactation. Mercury concentrations in milk of the dams and in whole body, blood, plasma, GI-tract, liver, kidneys, and brain of the offspring were followed up to 11 days after dosing (until lactational Day 21). Following the inorganic mercury dose to the dams, most of the mercury in milk was delivered to the pups during the first 24 h, but the maximum mercury concentration in plasma and tissues of pups was not reached until 7 days after dosing, indicating a prolonged absorption of inorganic mercury in the sucking pup. Pups of dams given methylmercury were exposed to a much lower and constant mercury concentration in milk. The estimated accumulated mercury dose via milk per pup of dams given methylmercury was less than half of that estimated after the inorganic mercury dose. When the accumulated dose via milk from methylmercury-exposed dams was compared to the amount of mercury in pup's carcass (whole body minus GI-tract including content), it was revealed that almost all mercury delivered via milk was absorbed, and that the suckling pups had a very low elimination of mercury until lactational Day 17. Lactational exposure following a maternal methylmercury or inorganic mercury dose resulted in almost similar mercury concentrations in liver, kidneys, and plasma of the suckling, but higher concentrations in brain (as most 14 times) and also twice as high mercury body burden in the methylmercury group. Thus, differences in kinetics indicate that lactational exposure of methylmercury is a greater hazard for the breast-fed infant than inorganic mercury.

Animals↗

Kinetics of methylmercury and inorganic mercury in lactating and nonlactating mice.

The elimination of mercury was followed for 9 days (Days 10-19 of lactation) in milk and/or 21 days in blood and plasma of lactating and nonlactating mice administered a single iv injection of either 203Hg-labeled methylmercuric chloride or 203Hg-labeled mercuric chloride (0.5 mg Hg/kg body wt). Demethylation of methylmercury to inorganic mercury was taken into consideration by analyzing the data with a combined pharmacokinetic model based on the assumption of constant blood plasma ratios for methylmercury and inorganic mercury. A three-compartment model fitted the blood and plasma concentrations vs time profiles for both compounds. Plasma clearance and volume of distribution at steady state for methylmercury were 95. 3 ml/h/kg and 18,500 ml/kg, respectively, in lactating mice, and significantly higher than in nonlactating mice with values of 47.1 ml/h/kg and 9400 ml/kg, respectively. The terminal half-lives of methylmercury in plasma were similar, 170 h in lactating and 158 h in nonlactating mice. No differences were observed between the pharmacokinetic parameters in lactating and nonlactating mice administered inorganic mercury. The lactational transfer of mercury was more efficient following administration of inorganic mercury than after administration of methylmercury, with a five times higher peak concentration in milk, higher milk:plasma concentration ratios, and 8% of the administered dose excreted in milk compared with 4% for methylmercury. Mercury concentrations in milk following an iv dose of inorganic mercury decreased with a terminal half-life of 107 h, whereas after administration of methylmercury, the concentration of total mercury in milk remained at an almost constant level during the whole period of investigation. There was a nonlinear relationship between mercury in milk and plasma following inorganic mercury administration. It is suggested that inorganic mercury enters the mammary gland by a carrier-mediated transport system, which is saturated at high plasma levels of inorganic mercury. The present study shows that physiological changes during lactation alter the pharmacokinetics for methylmercury in mice but not for inorganic mercury.

Animals↗

Pharmacokinetics of bambuterol in healthy subjects.

AIMS: To study the pharmacokinetics and bioavailability of the prodrug bambuterol and its bronchodilator moiety terbutaline in healthy subjects. METHODS: Eight healthy subjects (four women) received intravenous doses of bambuterol and terbutaline. On a third occasion, they, plus another four subjects, ingested oral bambuterol as a single dose followed by repeated doses once daily for 7 days. Plasma concentrations and urinary excretion of bambuterol and terbutaline were measured. RESULTS: After intravenous administration, renal clearances of bambuterol and terbutaline were similar (about 140 ml min(-1)), but there was a five-fold difference in total clearance (bambuterol 1.25 l min(-1), terbutaline 0.23 l min(-1)). Volume of distribution (Vss) was 1.6 l kg(-1) b.w. for both substances. A similar renal clearance of bambuterol was found during oral administration but that of terbutaline decreased (to about 120 ml min(-1)). Mean terminal half-life of bambuterol was 2.6 h after intravenous and 12 h after oral administration, implying that uptake was rate-limiting. Mean residence time of terbutaline generated from oral bambuterol was 34 h compared with 8.0 h when terbutaline as such was infused. Generated terbutaline had a bioavailability of 36% (28-46) after intravenous and 10.2% (6.1-13.2) after oral administration of the prodrug. Bambuterol was well tolerated. The mean activity of plasma cholinesterase, an enzyme catalyzing bambuterol metabolism, was inhibited between 30-60% during repeated oral dosing. It virtually regained original activity within 48 h after the last dose. CONCLUSIONS: The plasma concentration ofterbutaline fluctuated little during repeated oral administration (mean peak: trough ratio 1.9), as a result of prolonged absorption of bambuterol and slow formation of terbutaline. Thus, the pharmacokinetic properties of bambuterol make it suitable for oral once-daily dosage.

Administration, Oral↗

Continuous long-term measurements of the middle ear pressure in subjects without a history of ear disease.

A new method was used for continuous measurement of the middle ear (ME) pressure during a 24-h period. In 10 subjects without a history of ear disease a small perforation was made through the tympanic membrane. A tight rubber stopper containing a small polyethylene tube was fitted into the external ear canal. Conventional tubal function tests were performed. The equipment was then carried by the subjects for 24 h of normal activity to monitor any slow or rapid dynamic pressure change in the ME. Body position was found to be the most important factor affecting ME pressure variation, during the 24-h continuous pressure measurements. A significant pressure rise occurred in the recumbent position in all but one subject. Few rapid pressure equilibrations were seen during the recordings, indicating few tubal openings. This implies that the pressure changes in the ME seen in this study were mainly the result of gas exchange over the mucosa. The investigation might be a base for reference when investigating different kinds of pathologic conditions in the ear.

Adult↗

Toxicokinetics of lead in lactating and nonlactating mice.

Toxicokinetics of lead in lactating and nonlactating mice were studied after a single intravenous injection of 0.05 mg of lead (2.5 mCi 203Pb)/kg. Lead concentrations in blood, plasma, and milk were measured for 10 days following dosing. The volume of distribution based on plasma lead was more than two times larger in lactating than in nonlactating mice, 133 and 58 liter/kg, respectively. Plasma lead clearance in lactating mice was 4.25 liter/hr/kg compared with 1.07 liter/hr/kg in nonlactating mice. However, no such pronounced difference in blood lead clearance was found between the two groups, indicating that this parameter does not reveal the kinetic characteristics during lactation. Milk was found to be an additional route of excretion for lead. About 1/3 of the administered dose of lead was excreted in milk. Accordingly, milk clearance contributed to 1/3 of the total plasma clearance in the mice. The relationships of lead in plasma to lead in whole blood as well as lead in milk to lead in whole blood were nonlinear, with a relatively higher increase in plasma and in milk lead levels at higher blood lead levels. This nonlinearity may be explained by a reduced uptake of lead in erythrocytes as the lead binding sites of these cells become saturated. In lactating mice, the maximum binding capacity of lead in red blood cells was even lower than in nonlactating mice. Similar nonlinear relationship have have also been found in human studies although at much higher levels of lead in blood. The milk:plasma concentration ratio for lead was found to be between 50 and 100 after 24 hr, demonstrating a much more efficient excretion of lead into milk than what is known from human studies. Differences in the milk composition may be one explanation for the species differences in milk excretion of lead. The present study shows that physiological changes during lactation alter the pharmacokinetics of lead in mice.

Animals↗

Kinetic observations in neonatal mice exposed to lead via milk.

The absorption and disposition of lead in blood was examined in 10-day-old suckling mice exposed via milk. Lactating dams were administered a single intravenous injection of 0.05 mg Pb (2.5 mCi 203Pb)/kg body wt. Lead concentrations in blood of the suckling offspring were measured for 10 days after administration to the dams. Maximum blood lead concentrations in the pups were recorded between 50 and 74 hr after dams' administration despite the fact that the majority of the lead dose to the sucklings was delivered within 24 hr after dams' administration. Kinetic analysis of pups' blood lead data revealed a rate-limited absorption in the suckling pups with an absorption half-life of approximately 17 hr in the pups. This delayed absorption is most likely due to a retention of casein-bound lead in the ileal mucosa which has a high pinocytotic activity of dietary proteins in infant rodents. The present results also indicated that the distribution of lead to the peripheral tissues in the suckling mice was different than that of adults. The conflicting evidence on whether milk enhances or inhibits the absorption of lead in infant rodents may thus be explained by measurements of lead absorption at different time periods after administration to the animals. It is also suggested that the milk diet is one reason for the increased absorption of lead seen in immature rodents.

Animals↗

Impairment of the blood-CSF barrier in suicide attempters.

In a patient group of 90 suicide attempters, 18% showed an impaired blood-CSF barrier; of these 16 patients, all but one were younger than 45 years. When compared with 105 healthy controls, a significant difference in impairment of the blood-CSF barrier, between patients and controls, was seen only in those younger than 45 years (z = -2.66; P < 0.01). Paracetamol intoxication was more common among those with an impaired blood-CSF barrier than among those without an impairment (Fisher's exact test, P = 0.00029). Paracetamol intoxication was the most common method of suicide attempt in patients with adjustment disorders. There was no significant association between alcohol and/or drug abuse and an impaired blood-CSF barrier (Fisher's exact test, P = 0.91977). There were no differences in IgG index between patients and controls. The hypothesis that a blood-CSF barrier leakage may be a confounding factor when assessing the levels of monoamine metabolites in the CSF did not receive any support.

Adult↗

Conformationally constrained analogues of (Z)-5-decenyl acetate, a pheromone component of Agrotis segetum.

Conformationally constrained analogues of (Z)-5-decenyl acetate (1), a pheromone component of the turnip moth, Agrotis segetum, have been synthesized and tested by using electrophysiological single-cell recordings. In the constrained analogues the terminal alkyl chain in 1 has been incorporated in a six-membered (3 and 4) or five-membered (6) ring system. These cycli compounds are also conformationally constrained analogues of the previously deduced bioactive conformations of the corresponding chain-elongated analogues 2 and 5. The electrophysiological activities of the constrained analogues are found to be significantly lower than that of the natural pheromone component 1, most probably due to steric repulsive interactions between the analogue and the receptor, and also lower than the activities of the corresponding chain-elongated analogues of 1. It is concluded that the flexibility of the terminal chains in 2 and 5 is essential for the possibility of the receptor to accommodate these parts of the chain-elongated analogues in their bioactive conformations.

Acetates↗

Interleukin (IL)-6 and IL-8 in children with febrile urinary tract infection and asymptomatic bacteriuria.

Urine and serum interleukin (IL)-6 and IL-8 responses were higher in children with febrile urinary tract infection (n = 61) than in those with asymptomatic bacteriuria (n = 39). By univariate analysis, cytokine levels were related to age, sex, reflux, renal scarring, urine leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and bacterial properties (P fimbriae but not hemolysin). Multivariate modeling showed that urine IL-6 responses were higher in girls than boys, increased with age, and were positively associated with CRP, ESR, serum IL-6, and urine leukocyte counts. The urine IL-8 response was not influenced by age, but it was influenced by P fimbriae and was associated with ESR, CRP, urine leukocytes, and female sex. The results show that cytokine responses to urinary tract infection vary with the severity of infection and that cytokine activation is influenced by a variety of host and bacterial variables.

Bacteriuria↗

Continuous 24-hour measurement of middle ear pressure.

A new method was developed for continuous measurement of the middle ear pressure during a 24-h period. The equipment consisted of a piezo-electric pressure device and a digital memory. To allow continuous pressure recordings during normal every-day activities the equipment was made light and portable. The measurement accuracy of the equipment as well as the base-line and temperature stability were tested and found to meet to our requirements satisfactorily. In 4 volunteers with different middle ear conditions, a small perforation was made through the tympanic membrane. A rubber stopper containing a small polyethylene tube was fitted into the external ear canal. Tubal function tests were made to establish the equipment's ability to monitor fast pressure changes. The tests were well in accordance with other methods of direct pressure measurements. The equipment was carried by the volunteers for 24 h to monitor any slow or rapid dynamic pressure changes in the middle ear. Four continuous 24-h measurements are presented. The method was found to be suitable for valid measurements of dynamic pressure changes in the middle ear during normal every-day activities. It may become a useful instrument in the search for a better understanding of the development of chronic middle ear disease.

Activities of Daily Living↗

Determination of bambuterol, a prodrug of terbutaline, in plasma and urine by gas chromatography/mass spectrometry.

(R,S)-Bambuterol was isolated from plasma and urine by solid-phase extraction and analysed as its trimethylsilyl derivative by gas chromatography/chemical ionization mass spectrometry with ammonia as the reagent gas. Deuterium-labelled bambuterol was used as internal standard. An esterase inhibitor was added to plasma to prevent hydrolysis of bambuterol in the plasma sample. Bambuterol could be measured in plasma down to 1 nmol l-1 with a within-day variation of less than 5% (coefficient of variation). The lower limit of measurement in urine was judged to be 8 nmol l-1, a concentration at which the within-day variation was 5.4% (coefficient of variation).

Bronchodilator Agents↗

Pharmacokinetic evaluation in man of terbutaline given as separate enantiomers and as the racemate.

1. The pharmacokinetics of the two enantiomers of terbutaline, (+)T and (-)T, and the racemate (+/-)T, have been evaluated after single intravenous and oral dosage to six healthy volunteers. 2. The mean systemic clearance, CL, was 0.19 and 0.13 l h-1 kg-1 for (+)T and (-)T, respectively. This difference was statistically significant. The mean clearance of (+/-)T was 0.20 l h-1 kg-1. Volumes of distribution were similar (1.9 l kg-1) after the three intravenous administrations. The differences in CL were reflected in values of the elimination half-life and MRT. 3. The difference in CL of the isomers could be explained by a corresponding difference in their renal clearance, CLR. Competition for stereoselective active reabsorption in the tubule might explain why (+)T seemed to enhance the CLR of (-)T when the drug was given as the racemate. 4. Oral bioavailability, calculated from plasma data, of (+)T was 7.5% and that of (-)T was 14.8%. This difference was statistically significant and was mainly due to a difference in absorption of (+)T and (-)T, but also to a difference in their subsequent first-pass metabolism. The bioavailability of (+/-)T was similar to that of (-)T. 5. (-)T appears to govern the absorption properties of the racemate, while (+)T determines its elimination behaviour. Systemic metabolism of the two enantiomers was similar and, therefore, a greater first-pass metabolism of (+)T would reflect a higher capacity of the gut wall to metabolise this isomer.

Absorption↗

Comparative pharmacokinetics of unlabeled and deuterium-labeled terbutaline: demonstration of a small isotope effect.

An equimolar mixture of terbutaline and [2H6]terbutaline was given as an oral solution to six healthy volunteers (three men and three women). Frequent blood samples were collected during a 24-h period and the plasma concentrations of unlabeled and deuterium-labeled terbutaline were measured by GC-MS. The overall geometric mean plasma concentration ratio of terbutaline to [2H6]terbutaline (isotope ratio) was 1.04 and differed significantly from unity. The difference can be explained by a difference in lipophilicity between the analogues, affecting their absorption. No trend in isotope ratio over the experimental time was observed. For unknown reasons, the isotope ratio was higher for women (1.07) than for men (1.00). Deuterium-labeled terbutaline can be used, intravenously or orally, as an absolute reference in bioavailability studies on terbutaline. If deuterium-labeled terbutaline is given orally in a single-day relative bioavailability study, a correlation should be made for the observed isotope effect.

Adult↗