Central nervous system penetration of oxycodone after intravenous and epidural administration.

BACKGROUND: Despite being increasingly used for pain management, only two studies, with controversial results, have evaluated the epidural use of oxycodone. METHODS: Twenty-four women, aged 26-64 yr, undergoing elective gynaecological surgery were enrolled in this randomized, double-blinded, parallel group study. The subjects were administered either i.v. oxycodone and epidural placebo (IV group; n=12) or epidural oxycodone and i.v. placebo (EPI group; n=12) after operation. Oxycodone was administered as a single dose of 0.1 mg kg(-1). An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for cerebrospinal fluid (CSF) sampling at L3/4. Plasma and CSF were frequently collected for the analysis of oxycodone and its major metabolites. The primary outcomes were the peak concentration (C(max)), time to peak concentration (T(max)), and the exposure (AUC(last)) of oxycodone in CSF and plasma. The secondary outcome was the analgesic efficacy, measured as the total dose of rescue fentanyl during the first four postoperative hours. RESULTS: In the EPI group, the median oxycodone Cmax and AUC(last) in the CSF were 320- and 120-fold higher, respectively, compared with the IV group. The total dose of rescue fentanyl was significantly lower in the EPI group (seven subjects needed 16 doses) than in the IV group [12 subjects needed 71 doses (P=0.001)]. No serious or unexpected adverse events were reported. CONCLUSIONS: Epidural oxycodone provides much higher CSF concentrations and possibly better analgesic efficacy than does i.v. oxycodone. CLINICAL TRIAL REGISTRATION: EudraCT reference number: 2011-000125-76.

Event-related EEG desynchronization and synchronization during an auditory memory task.

Event-related desynchronization (ERD) and synchronization (ERS) of the lower (8-10 Hz) and upper (10-12 Hz) alpha bands of background EEG were studied in 10 subjects during an auditory memory scanning paradigm. Each experimental trial started with the presentation of a visual warning signal, after which an auditory 4-vowel memory set was presented for memorization. Thereafter the probe, a fifth vowel, was presented and identified by the subject as belonging or not belonging to the memorized set. In 50% of the cases, the probe was among the previously presented memory set. The presentation of the memory set elicited a significant ERS in the both alpha frequency bands. In contrast, the presentation of the probe elicited a significant bilateral ERD in both alpha frequency bands studied. The results suggest that the ERD phenomenon is closely associated with higher cortical processes such as memory functions rather than with auditory stimulus processing per se. Event-related desynchronization provides a potentially valuable tool for studying cortical activity during cognitive processing in the auditory stimulus modality.

Cortical processing of vowels and tones as measured by event-related desynchronization.

Event-Related Desynchronization (ERD) and Synchronization (ERS) were studied in 20 normal subjects during a Sternberg-type auditory memory-scanning paradigm. Half of the subjects performed the experiment with vowels and the other half with tones as stimuli. The stimuli consisted of 100 msec long synthesized vowels and 100 msec long tones produced by eight different synthesized instruments. In this paradigm each trial started with the presentation of a visual warning signal, after which a four-stimulus set was presented for memorization whether after a probe stimulus was presented and identified by the subject as belonging or not belonging to the memorized set. The ERD/ERS of the lower (8-10 Hz) and upper (10-12 Hz) alpha frequency bands differed in their reactivity to stimulus type; the differences between the two frequency bands reached statistical significance only in the case of vowels. The presentation of the memory set elicited ERS which was more pronounced in the 10-12 Hz frequency band and greater for vowels than for tones. On the other hand, the presentation of the probe elicited ERD which was greater for vowels than for tones, especially in the upper alpha frequency band. The results of this exploratory study suggest that ERD is closely related to memory process and that the ERD/ERS-technique might provide a valuable tool for future research encompassing more complex auditory stimulation like speech and music.

Immunocytochemical detection of actin and 53 kDa polypeptide in the epididymal spermatozoa of rat and mouse.

BACKGROUND: Presence of immunocytochemically detectable actin in the rat and mouse sperm head has been enigmatic for years. In this study, we demonstrate actin in the perinuclear theca and show that the detection of actin epitopes in the rat and mouse epididymal spermatozoa can effectively be enhanced by pre-extraction of sperm cells with SDS. METHODS: The study with one monoclonal and one polyclonal anti-actin antibody was carried out at conventional and confocal fluorescence and electron microscope level, and by immunoblotting of proteins isolated from the head and tail fractions. RESULTS: In the head of the control methanol-acetone fixed rat spermatozoa, the polyclonal antibody gave a stronger immunostaining in the postacrosomal area and in the perforatorium than the monoclonal antibody. In the mouse sperm head, the monoclonal antibody labeled the ventral edge of the postacrosomal area and slightly the perforatorium, whereas the polyclonal antibody stained the entire perinuclear space. In the SDS-extracted spermatozoa, an intense postacrosomal and perforatorial labeling was obtained with both antibodies but, in particular in the rat spermatozoa, the middle lateral portion of the postacrosomal segment remained unlabeled. Sonication seemed to cause structural modifications which specifically impeded staining with the monoclonal antibody. Both antibodies detected actin in the basal plate and the monoclonal antibody in the neck. Amorphous matrix of the connecting piece showed immunogold labeling. In the tail, the monoclonal antibody recognized actin and a relatively basic 53 kDa polypeptide, whereas the polyclonal antibody reacted with several protein bands. SDS-soluble actin of the tail was addressed to the midpiece and the SDS-insoluble 53 kDa protein profoundly to the outer dense fibers of the principal piece. CONCLUSIONS: Intense labeling of actin in the SDS-extracted rat and mouse spermatozoa was presumably due to the generated demasking of actin epitopes embedded in the perinuclear cytoplasm. The results are important in confirming that actin in the rat and mouse sperm head is not lost during spermiogenesis but apparently contributes to the three-dimensional packing of the mature perinuclear cytoplasm. This study further demonstrates the importance of the methods used in sample preparation and advantages of confocal microscopy when attempting to detect cytoskeletal proteins which, as in spermatozoa, may occur in small quantities.

Event-related desynchronization evoked by auditory stimuli.

Event-Related Desynchronization (ERD) and Synchronization (ERS) of several EEG alpha frequencies was studied in 19 subjects during the presentation of linguistic and/or melodic auditory stimuli. The stimulus length was 1300 msec (+/-100 msec) and the interstimulus interval was 2000 msec. A significant ERD was found during auditory stimulation in the 8-10 Hz and 10-12 Hz alpha frequency bands, and there were also significant differences in the spatiotemporal pattern of the ERD between these frequency bands. Significant ERD was elicited also in the 10-11 and 11-12 Hz frequency bands by auditory stimulation. There were no significant differences between these one-hertz frequency bands. The subjects were assigned to two analysis groups according to their individual alpha peak frequency (10-11 or 11-12 Hz) at rest. The ERD in these groups reached statistical significance and there were significant differences between the groups. The ERD of the two groups differed significantly also when their EEG data was studied in the 10-12 Hz frequency band. The results from this study show that ERD is not modality-specific, i.e., it can be elicited also by auditory stimuli. Moreover, they indicate that it is important to control over interindividual variation in the EEG when studying the ERD phenomenon.

Effect of dietary fish powder on intestinal flora and development of arthritis in the pig.

In 1971 Månsson et al. reported that a 20% dry fish powder diet fed to young pigs induced arthritis and increases in faecal Clostridium perfringens counts. To confirm this interesting finding we have repeated their experiment by following their regimen as closely as possible. Twelve piglets of Finnish landrace were divided at 8 weeks of age into two groups according to litter, sex and initial weight. The control group received a cereal-based diet. In the experimental group 20% of cereal in the diet was replaced by fish meal. Stool samples were cultured for Cl. perfringens and subjected to direct gas-liquid chromatography (GLC) to provide bacterial cellular fatty acid profiles. Development of arthritis was monitored macroscopically, and synovial samples were taken at autopsy for microscopical examination. Faecal Cl. perfringens counts increased 10-40 times more in the fish diet group than in the control group. GLC revealed a significant difference in bacterial florae between the groups. No arthritis was observed and only slight synovial inflammation in four experimental pigs and in one control pig. We conclude that fish diet changed faecal flora significantly, but did not induce arthritis.