Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers

The effects of single oral doses of ketoconazole 400 mg and terbinafine 500 mg on the hepatic microsomal system have been investigated in 8 healthy male volunteers. Microsomal activity caffeine was assessed by following the metabolism of 3 mg/kg bodyweight i.v. administered 1 h after the drug. The inhibitory effect of terbinafine was more pronounced than that of ketoconazole: clearance was decreased from 1.34 ml.kg-1.min-1 in controls to 1.06 and 1.21 ml.kg-1.min-1, respectively, and the corresponding half-life was increased from 5.8 h in controls to 7.6 and 6.7 h, respectively. The apparent volume of distribution remained unchanged. The serum levels of the antimycotics were within the therapeutic range in each subject. Although all three substances are metabolised by microsomes, the kinetic parameters (Cmax, half-life, elimination constant) of the antimycotics were poorly if at all correlated with the elimination of caffeine.     

Immediate ultrastructural effects of endothelin-1 on rabbit basilar artery

Summary In this study intra-arterial Endothelin-1 was applied to rabbit basilar arteries and morphological findings were compared between two groups who were either perfusion fixed or immersion fixed. We planned to establish the quantitative dimension of the drug-induced morphological alterations, independent of the fixation technique's effect.There was an abundance of collagenous fibres deposited among the smooth muscle cells which was not observed in control arteries and after immersion fixation. These degenerative changes are similar to the finding following subarachnoid haemorrhage. The only fixation-related difference was the fact that lamina elastica interna was not corrugated in the perfusion fixation group.It is concluded that, the observed changes in the connective tissue of the arterial wall alter the passive elastic properties and so affect the degree of the response to the vasoactive messengers.     

Absence ofHelicobacter pylori in dental plaques inHelicobacter pylori positive dyspeptic patients

To test the validity of reports on detection ofHelicobacter pylori in the mouth, samples were obtained simultaneously from the gastric mucosa and dental plaques for culture in 94 patients examined consecutively by endoscopy. Histological examinations and serological tests were also performed.Helicobacter pylori was not found in the mouth of any of the patients including 52 who had culture-positive gastric biopsies. Thus earlier results could not be confirmed, however, other techniques such as the polymerase chain reaction might give different results.     

Molecular characterisation of two mumps virus genotypes circulating during an epidemic in Lithuania from 1998 to 2000

Summary.  An epidemic of mumps in Lithuania started in December 1998 and continued until May 2000. The total registered number of cases was about 11.000 of a total of 3,7 million inhabitants in Lithuania (29,7 cases/10000). Virus- containing samples were collected from 80 patients treated at the hospital of Kaunas from October 1999 until the end of the epidemic. Out of the 80 patients with parotitis, meningitis was observed in 11 patients and orchitis in 22 of 69 male patients. Twenty-seven virus strains were genotyped by nucleotide sequencing of the small hydrophobic (SH) protein gene, and the 57 amino acid sequences of the gene were deduced. Twenty-five virus strains belonged to the C genotype and two were of the D genotype. By phylogenetic analysis the virus strains causing meningitis grouped in a separate cluster, designated C1, within the C genotype. Another group of ten of the 25 genotype C strains exhibited an amino acid triplet at amino acid positions 28 to 30 of the protein, consisting of valine, alanine and serine, instead of the previously recognised valine, valine and serine combination of genotype C. The amino acid alanine at position 29 was found in combination with the amino acid serine at position 48. This variant was designated C2 and it was associated with parotitis. The amino acid alanine at position 29 and serine in position 48 of the C2 genotype may constitute a marker of low neurovirulence compared to other genotype C strains. Received July 9, 2001 Accepted October 23, 2001     

Microcirculation in the upper trapezius muscle during varying levels of static contraction,fatigue and recovery in healthy women —a study using percutaneous laser-Doppler flowmetry and surface electromyography

Summary Microcirculation in the upper portion of the trapezius muscle was measured percutaneously by continuous laser-Doppler flowmetry (LDF) during two 10-min series of alternating 1-min periods of static contraction and rest determined electromyographically (EMG). Stepwise increased contraction was induced by keeping the arms straight and elevated at 30, 60, 90 and 135°, which was repeated with a 1-kg load carried in each hand. Thereafter, fatigue and recovery were recorded while the subject kept her arms straight and elevated at 45° carrying the 1-kg hand load as long as possible, followed by rest with arms hanging and no load. A group of 16 healthy women of different ages was studied. Signal processing was done on line using a 386 SX computer. The LDF- and root-mean-square (rms) EMG signals were normalized. Spectrum analyses of EMG mean power frequency (MPF) and median spectrum frequency were performed. The rms-EMG increased significantly with an increase in the calculated shoulder torque (r=0.75). Accumulated local fatigue was indicated by a decrease in MPF with increased shoulder angle and added load (r = –0.54). Blood flow increased with increased shoulder angle (r=0.82, with hand loadr=0.62) and with increased shoulder torque (r=0.72), and also showed a significant increase with increased EMG activity (r=0.74). The LDF showed a negative correlation to MPF (r= –0.67), with increased values when MPF was lowered. During the endurance test, a moderate increase of LDF occurred which reached its maximum during the 1st min of recovery. Then, a slow return to the base level was recorded. The ability to increase the flow in the microcirculation with increasing muscle load was not diminished with age.     

Accumulation of very long-chain fatty acids does not affect mitochondrial function in adrenoleukodystrophy protein deficiency

X-linked adrenoleukodystrophy (X-ALD, OMIM 300100) is a severe inherited neurodegenerative disease, associated with the accumulation of very long-chain fatty acids (VLCFA). The recent unexpected observation that the accumulation of VLCFA in tissues of the Abcd1-deficient mouse model for X-ALD is not due to a deficiency in VLCFA degradation, led to the hypothesis that mitochondrial abnormalities might contribute to X-ALD pathology. Here, we report that in spite of substantial accumulation of VLCFA in whole muscle homogenates, normal VLCFA levels were detected in mitochondria obtained by organellar fractionation. Polarographic analyses of the respiratory chain as well as enzymatic assays of isolated muscle mitochondria revealed no differences between X-ALD and control mice. Moreover, analysis by electron microscopy, revealed normal size, structure and localization of mitochondria in muscle of both groups. Similar to the results obtained in skeletal muscle, the mitochondrial enzyme activities in brain homogenates of Abcd1-deficient and wild-type animals also did not differ. Finally, studies on mitochondrial oxidative phosphorylation in permeabilized human skin fibroblasts of X-ALD patients and controls revealed no abnormalities. Thus, we conclude that the accumulation of VLCFA per se does not cause mitochondrial abnormalities and vice versa-mitochondrial abnormalities are not responsible for the accumulation of VLCFA in X-ALD mice.     

Number Magnitude Processing and Verbal Working Memory in Children with Mild Intellectual Disabilities

ABSTRACT

This study examined if children (M_age = 14.60) with Mild Intellectual Disabilities (MID) display weaknesses in number processing and verbal working memory. An age-matched and mental age-matched (MA, M_age = 6.17) design extended by a group of 9–10-year-olds, and a group of 11–12-year-olds were used. The MID children’s working memory was equal to the MA group but poorer than the other groups. On number tasks, the MID group was faster than the MA group but slower than the other groups. All groups obtained equal Weber fraction scores and distance effects on the number comparison tasks. The MID group performed subitizing and counting faster than the MA group, but slower than the 11–12-year-olds. The results demonstrate that number processing and working memory in children with MID is characterized by a developmental delay, not a deficit. Their main problem is to access the quantitative meaning of Arabic numerals. The development of different types of cognitive abilities is differently affected by educational experience and intellectual ability. The innate number system appears to be unaffected by intellectual capacity or educational experience, while the innate working memory ability is affected by intellectual capacity but not by educational experience. Culturally acquired symbolic number abilities are strongly affected by educational experience.     

Adaptive Wiener Filtering for Improved Acquisition of Distortion Product Otoacoustic Emissions

An innovative acoustic noise canceling method using adaptive Wiener filtering (AWF) was developed for improved acquisition of distortion product otoacoustic emissions (DPOAEs). The system used one microphone placed in the test ear for the primary signal. Noise reference signals were obtained from three different sources: (a) pre-stimulus response from the test ear microphone, (b) post-stimulus response from a microphone placed near the head of the subject and (c) post-stimulus response obtained from a microphone placed in the subjects nontest ear. In order to improve spectral estimation, block averaging of a different number of single sweep responses was used. DPOAE data were obtained from 11 ears of healthy newborns in a well-baby nursery of a hospital under typical noise conditions. Simultaneously obtained recordings from all three microphones were digitized, stored and processed off-line to evaluate the effects of AWF with respect to DPOAE detection and signal-to-noise ratio (SNR) improvement. Results show that compared to standard DPOAE processing, AWF improved signal detection and improved SNR. © 1998 Biomedical Engineering Society. PAC98: 4364Jb, 4360-c, 8790+y