[First case of thrombolysis with non-immunogenic staphylokinase in a patient with ischemic stroke receiving dabigatran etexilate followed by thrombectomy]. / Pervyi sluchai tromboliticheskoi terapii pri pomoshchi neimmunnogennoi stafilokinazy u patsientki s ishemicheskim insul'tom, poluchayushchei dabigatrana eteksilat, s posleduyushchei trombektomiei.

Currently, five oral anticoagulants have been shown to be effective in preventing recurrent ischemic stroke and/or systemic embolism in patients with non-valvular atrial fibrillation. However, 1.1-2.2% of patients taking oral anticoagulants develop ischemic strokes. The use of oral anticoagulants limits the possibility of systemic thrombolytic therapy, as this is associated with an increased risk of symptomatic hemorrhagic transformation. The exception is cases when, with the help of a specific antagonist, it is possible to neutralize the effect of the anticoagulant in the shortest possible time and achieve normocoagulation. Currently, the Russian Federation allows two drugs for systemic thrombolytic therapy in patients with ischemic stroke in the «therapeutic window¼ up to 4.5 hours from the onset of the disease - recombinant tissue plasminogen activator and non-immunogenic staphylokinase, which showed no less efficacy and safety in the FRIDA study compared to recombinant tissue plasminogen activator. This article describes a clinical case of the first systemic thrombolytic therapy with a non-immunogenic staphylokinase after the use of idarucizumab in a patient taking dabigatran etexilate, followed by thrombectomy.

The absence of brain-specific link protein Bral2 in perineuronal nets hampers auditory temporal resolution and neural adaptation in mice.

Brain-specific link protein Bral2 represents a substantial component of perineuronal nets (PNNs) enwrapping neurons in the central nervous system. To elucidate the role of Bral2 in auditory signal processing, the hearing function in knockout Bral2(-/-) (KO) mice was investigated using behavioral and electrophysiological methods and compared with wild type Bral2(+/+) (WT) mice. The amplitudes of the acoustic startle reflex (ASR) and the efficiency of the prepulse inhibition of ASR (PPI of ASR), produced by prepulse noise stimulus or gap in continuous noise, was similar in 2-week-old WT and KO mice. Over the 2-month postnatal period the increase of ASR amplitudes was significantly more evident in WT mice than in KO mice. The efficiency of the PPI of ASR significantly increased in the 2-month postnatal period in WT mice, whereas in KO mice the PPI efficiency did not change. Hearing thresholds in 2-month-old WT mice, based on the auditory brainstem response (ABR) recordings, were significantly lower at high frequencies than in KO mice. However, amplitudes and peak latencies of individual waves of click-evoked ABR did not differ significantly between WT and KO mice. Temporal resolution and neural adaptation were significantly better in 2-month-old WT mice than in age-matched KO mice. These results support a hypothesis that the absence of perineuronal net formation at the end of the developmental period in the KO mice results in higher hearing threshold at high frequencies and weaker temporal resolution ability in adult KO animals compared to WT mice.

Effect of noise exposure on gap detection in rats.

The effects of intense (110-120 dB) noise exposure (broadband noise for one hour) on temporal resolution was estimated in rats by measuring the behavioural gap detection threshold (GDT). Changes in GDT after 120 dB noise exposure were compared with changes in the threshold and amplitude of middle latency responses (MLR) recorded in response to tone stimuli. GDT values increased from 1.6 to 4.3 or 7.8 ms after exposure to 110 or 115 dB SPL, respectively; GDT recovered to pre-exposure values in 3-7 days. Three main types of noise-induced changes were observed after 120 dB SPL exposure: (I) GDT changes similar to those following noise exposure to 115 dB SPL and maximal hearing threshold shifts (TSs) at high frequencies of about 45 dB; (II) more pronounced changes in GDT (up to 60 ms) with maximal hearing threshold shifts of about 65 dB and (III) a lack of reliable responses to gap during the first weeks post-exposure with maximal hearing threshold shifts of about 80 dB. An increased GDT was present two months after noise exposure in animals with types II and III post-exposure changes; enhanced MLR amplitudes were also found in most of these in the first post-exposure week. The pronounced deficit in gap detection in some rats after 120 dB SPL noise exposure may signal the presence of a noise-induced tinnitus.

Gap detection threshold in the rat before and after auditory cortex ablation.

Gap detection threshold (GDT) was measured in adult female pigmented rats (strain Long-Evans) by an operant conditioning technique with food reinforcement, before and after bilateral ablation of the auditory cortex. GDT was dependent on the frequency spectrum and intensity of the continuously present noise in which the gaps were embedded. The mean values of GDT for gaps embedded in white noise or low-frequency noise (upper cutoff frequency 3 kHz) at 70 dB sound pressure level (SPL) were 1.57+/-0.07 ms and 2.9+/-0.34 ms, respectively. Decreasing noise intensity from 80 dB SPL to 20 dB SPL produced a significant increase in GDT. The increase in GDT was relatively small in the range of 80-50 dB SPL for white noise and in the range of 80-60 dB for low-frequency noise. The minimal intensity level of the noise that enabled GDT measurement was 20 dB SPL for white noise and 30 dB SPL for low-frequency noise. Mean GDT values at these intensities were 10.6+/-3.9 ms and 31.3+/-4.2 ms, respectively. Bilateral ablation of the primary auditory cortex (complete destruction of the Te1 and partial destruction of the Te2 and Te3 areas) resulted in an increase in GDT values. The fifth day after surgery, the rats were able to detect gaps in the noise. The values of GDT observed at this time were 4.2+/-1.1 ms for white noise and 7.4+/-3.1 ms for low-frequency noise at 70 dB SPL. During the first month after cortical ablation, recovery of GDT was observed. However, 1 month after cortical ablation GDT still remained slightly higher than in controls (1.8+/-0.18 for white noise, 3.22+/-0.15 for low-frequency noise, P<0.05). A decrease in GDT values during the subsequent months was not observed.

Susceptibility to noise exposure during postnatal development in rats.

Susceptibility to noise-induced hearing loss was studied during maturation in 20 female pigmented rats (strain Long-Evans). Young rats, 3, 4, 5 and 6-7 weeks old, were exposed for 1 h to a broad-band noise with an intensity of 120 dB SPL. The thresholds and amplitudes of middle latency responses (MLR) recorded from electrodes implanted on the surface of the auditory cortex were analyzed before and after noise exposure. The results were compared with data from our previous study, in which the effects of broad-band noise exposure on MLR were investigated in adult rats [Syka, J. and Rybalko, N. (2000) Hear. Res. 139, 59-68]. The hearing thresholds of 3-7 week old rats before noise exposure were within the normal adult range. Noise exposure in young rats produced an adult-like pattern with an elevation of hearing thresholds. One-two weeks post-exposure a recovery of MLR thresholds was observed, though full recovery only occurred in the low frequency range. Recovery of hearing thresholds in the high frequency range depended on the age of the animal at the time of exposure. In all animals aged less that 6-7 weeks, exposure resulted in a permanent threshold shift in the range of 4-32 kHz. The mean values of permanent threshold shifts at 16 kHz (the frequency of maximal hearing loss) were 53.0+/-4.5, 47.6+/-9.6, 37.5+/-7.5 and 27+/-10 dB for rats exposed at 3, 4, 5 and 6-7 weeks of age, respectively. Similar to adult rats, young rats exposed to noise exhibited an enhancement of MLR amplitudes. This amplitude enhancement was more pronounced in the high frequency range. In several rats exposed at 3-5 weeks of age, the recovery period to normal amplitudes was substantially prolonged and lasted 4-8 weeks in comparison with 1-2 weeks in adult rats. These results demonstrate a greater susceptibility to noise exposure in rats during the first 5 postnatal weeks.

[An analysis of 3H-tamoxifen binding with the cell plasma membranes of the rat uterus]. / Analiz sviazyvaniia 3H-tamoksifena s plazmaticheskimi membranami kletok matki krys.

The effect of phencarol, ranitidine, propranolol, atropine, and diethylstilbestrol (known as modulators of the tamoxifen-binding sites in plasma membranes) on the 3H-tamoxifen binding to the plasma membrane fraction of white rat uterine cells was studied by determining the amounts of estradiol and H1- and H2-receptors. The interaction of tamoxifen with various receptors of uterine cells may be significant for evaluation of the tumor activity of this compound.

Threshold shifts and enhancement of cortical evoked responses after noise exposure in rats.

The effect of exposure to various types of noise (broadband, high-frequency or low-frequency) was studied in adult pigmented rats. Thresholds and amplitudes of middle latency responses (MLR) recorded from electrodes implanted on the surface of the auditory cortex were analyzed before and after noise exposure. Exposure to noise with intensities ranging from 105 to 120 dB for 1 h produced only temporary threshold shifts (TTS). Exposure to broadband noise produced TTS throughout the whole frequency range of the rat's hearing, mostly expressed at frequencies of maximal hearing sensitivity (16-32 kHz). Hearing loss produced by high- or low-frequency noise exposure was related to the spectral characteristics of the noise. The exposure to high-intensity noise may also result in amplitude enhancement of the MLR. This phenomenon was seen mainly after broadband noise exposure and occurred in response to both low-frequency and high-frequency test stimuli. High-frequency and low-frequency noise produced amplitude enhancement mainly at frequencies which corresponded to the maximum exposure energy. In contrast to the relatively similar values of TTS obtained in different rats under the same conditions of noise exposure, great inter-individual variability was found in the MLR amplitude enhancement. In all rats the dynamics of recovery functions for amplitude enhancement were different from those for MLR thresholds. The data indicate that whereas post-exposure TTS are related to peripheral changes, the post-exposure MLR amplitude enhancement is most probably connected with a change in the processing of auditory information in the central nervous system.

Auditory frequency and intensity discrimination in pigmented rats.

Auditory function was investigated in seven pigmented hooded rats (strain Long-Evans) with the aid of an operant conditioning procedure. Frequency difference limen was measured at frequencies from 0.5 to 64 kHz at 50 dB sensation level (SL). Weber ratios (frequency difference limen/frequency) in this range varied between 3.7 and 7.3%. The decline in the intensity of the stimulus from 50 to 10 dB SL was accompanied by a slight increase in the frequency difference limen. The frequency difference limen values were similar for frequency shifts upwards or downwards. Intensity discrimination was measured at 50 dB SL at frequencies of 2, 8 and 32 kHz. Intensity difference limen was frequency independent and amounted to 2.9 +/- 0.5 dB in conditions of upward intensity shift. The values of intensity difference limen measured in conditions of downward intensity shift were significantly larger and amounted to 6.5 +/- 1.6 dB. The characteristics of hearing function found in these experiments correspond with those described by other authors in albino rats and indicate that albinism in the rat has no significant influence on auditory frequency and intensity discrimination.

Enhancement of the auditory cortex evoked responses in awake guinea pigs after noise exposure.

In a previous paper [Popelár et al., Hear. Res. 26, 239-247 (1987)] we have shown that amplitudes of the auditory cortex evoked responses (AC-ER) in awake guinea pigs were enhanced for several hours after 1 h of noise exposure whereas amplitudes of the compound potential of the auditory nerve (CAP) and of the inferior colliculus evoked responses (IC-ER) declined. The present study demonstrates that the duration of the AC-ER amplitude increase is related to the intensity of the noise exposure (white noise, for 30 min or 1 h, intensity range 105-125 dB). The AC-ER amplitude as well as the threshold shift increased linearly with increasing intensity of the noise. The maximum AC-ER increase occurred when clicks served as stimuli; amplitude enhancement was smaller for 1 kHz tone pips and was absent when 20 kHz tone pips were used. The amplitude enhancement was specific for the auditory cortex since the amplitude of visually evoked responses, recorded in the occipital cortex, was unchanged after noise exposure. It is suggested that the postexposure amplitude enhancement of the AC-ER is produced by temporary exhaustion of inhibitory processes in the auditory cortex.