Memory-specific correlated neuronal activity in higher-order auditory regions of a parrot.

Male budgerigars (Melopsittacus undulatus) are open-ended learners that can learn to produce new vocalisations as adults. We investigated neuronal activation in male budgerigars using the expression of the protein products of the immediate early genes zenk and c-fos in response to exposure to conspecific contact calls (CCs: that of the mate or an unfamiliar female) in three subregions (CMM, dNCM and vNCM) of the caudomedial pallium, a higher order auditory region. Significant positive correlations of Zenk expression were found between these subregions after exposure to mate CCs. In contrast, exposure to CCs of unfamiliar females produced no such correlations. These results suggest the presence of a CC-specific association among the subregions involved in auditory memory. The caudomedial pallium of the male budgerigar may have functional subdivisions that cooperate in the neuronal representation of auditory memory.

[Survey of the Efficacy of Long-term and Successive Pharmaceutical Care in Outpatient Chemotherapy by Oncology Pharmacy Specialists].

It is important that pharmacists ensure safe chemotherapy implementation. In addition to inspecting chemotherapeutic prescriptions according to patient condition and drug-drug interactions, the management of chemotherapy-induced adverse effects and associated pharmaceutical intervention is one of the most important responsibilities of pharmacists in medical care teams. In May 2016, an oncology pharmacist was set responsible for the specialized, long-term, and successive pharmaceutical care, including instructions about appropriate use of medication at an outpatient chemotherapy center. We evaluated the effectiveness of the continuous pharmaceutical care. The number of medication counseling and associated pharmaceutical interventions increased with time. Specifically, the number of pharmaceutical interventions (prescription questions and pharmaceutical proposals) was 745 (459 and 286, respectively) in the surveillance period, which significantly increased compared to that observed within the same duration before posting an oncology pharmacist. The adoption rate was approximately 70% for prescription questions and 98% for pharmaceutical proposals. We also found that approximately 70% of the proposals attenuated the painful symptoms. Furthermore, approximately 60% of all pharmaceutical interventions were established after the third visit; in particular, approximately 20% of the pharmaceutical proposals were suggested after the sixth visit, indicating that continuous medication counseling results in an increase in pharmaceutical proposals. In conclusion, long-term and successive pharmaceutical care by oncology pharmacy specialists in outpatient chemotherapy contributes to a safe and less onerous chemotherapy implementation, as it has been highly adopted, is effective in many cases, and has been proven to be important for risk management in chemotherapy.

Validating the Effectiveness of Switching the Vancomycin TDM Analysis Software Based on the Predictive Accuracy.

Based on the predictive performance in our previous study, we switched the therapeutic drug monitoring (TDM) analysis software for dose setting of vancomycin (VCM) from "Vancomycin MEEK TDM analysis software Ver2.0" (MEEK) to "SHIONOGI-VCM-TDM ver.2009" (VCM-TDM) in January 2015. In the present study, our aim was to validate the effectiveness of the changing VCM TDM analysis software in initial dose setting of VCM. The enrolled patients were divided into two groups, each having 162 patients in total, who received VCM with the initial dose set using MEEK (MEEK group) or VCM-TDM (VCM-TDM group). We compared the rates of attaining the therapeutic range (trough value; 10-20 µg/mL) of serum VCM concentration between the groups. Multivariate logistic regression analysis was performed to confirm that changing the VCM TDM analysis software was an independent factor related to attaining the therapeutic range. Switching the VCM TDM analysis software from MEEK to VCM-TDM improved the rate of attaining the therapeutic range by 21.6% (MEEK group: 42.6% vs. VCM-TDM group: 64.2%, p<0.01). Patient age ≥65 years, concomitant medication (furosemide) and the TDM analysis software used VCM-TDM were considered to be independent factors for attaining the therapeutic range. These results demonstrated the effectiveness of switching the VCM TDM analysis software from MEEK to VCM-TDM for initial dose setting of VCM.

Sex differences in behavioural and neural responsiveness to mate calls in a parrot.

Vocalisation in songbirds and parrots has become a prominent model system for speech and language in humans. We investigated possible sex differences in behavioural and neural responsiveness to mate calls in the budgerigar, a vocally-learning parrot. Males and females were paired for 5 weeks and then separated, after which we measured vocal responsiveness to playback calls (a call of their mate versus a call of an unfamiliar conspecific). Both sexes learned to recognise mate calls during the pairing period. In males, but not females, mate calls evoked significantly fewer vocal responses than unfamiliar calls at one month after separation. Furthermore, in females, there was significantly greater molecular neuronal activation in response to mate calls compared to silence in the caudomedial mesopallium (CMM), a higher-order auditory region, in both brain hemispheres. In males, we found right-sided dominance of molecular neuronal activation in response to mate calls in the CMM. This is the first evidence suggesting sex differences in functional asymmetry of brain regions related to recognition of learned vocalisation in birds. Thus, sex differences related to recognition of learned vocalisations may be found at the behavioural and neural levels in avian vocal learners as it is in humans.

Puerperal and parental experiences alter rat preferences for pup odors via changes in the oxytocin system.

In the rat, induction of maternal behavior depends on the parity of the female. For example, nulliparous (NP) females need longer exposure to pups than multiparous (MP) or lactating (L) females to exhibit similar maternal behavior. In this study, we investigated the role of brain oxytocin in the approaching behavior of these female rats. Olfactory preferences for pup odors were examined for 8 consecutive days. Each preference test was followed by direct overnight exposure to pups. On the 8th day, MP and L, but not NP females showed robust pup-odor preferences. After the behavioral test, half of the females were exposed to pups for 2 h, whereas the other half were not. The females were then sacrificed to analyze brain oxytocin (OXT) and vasopressin (AVP) activities by cFos immunohistochemistry and to quantify their receptor mRNA expression using real-time PCR. In the paraventricular nucleus (PVN), the percentage of cFos-positive OXT neurons was significantly larger in MP and L females than in NP females after pup exposure. No significant differences were found in cFos expression in OXT neurons of the supraoptic nucleus (SON) or in AVP neurons of either the PVN or SON. Expression of OXT receptor mRNA in the medial preoptic area and amygdala of the control groups was also higher in MP females than in NP females. Finally, we demonstrated that infusion of OXT into the lateral ventricle of NP females promoted preferences for pup odors. These results indicate that puerperal and parental experiences enhance the responsiveness of OXT neurons in the PVN to pup stimuli and establish olfactory preferences for these odors in a parity-dependent manner.

The effect of androgen on the retention of extinction memory after conditioned taste aversion in mice.

Conditioned taste aversion (CTA) induced by the application of a novel taste such as sodium saccharin (Sac) as the conditioned stimulus (CS) and a malaise-inducing agent as the unconditioned stimulus (US), results in acquisition of CTA memory to Sac. In contrast, CTA is extinguished by repeated presentations of the CS without the US, resulting in acquisition of the extinction memory. We examined the effects of androgenic hormones on acquisition and retention of extinction memory in mice. We gonadectomized sexually immature mice and continuously administered androgens to these animals. After sexual maturation, the mice underwent a conditioning period followed by an extinction period. Retrieval tests revealed that the androgen-treated group showed significantly greater retention of extinction memory than the non-treated group 5 weeks later, whereas such significant difference was not observed in acquisition of extinction memory. These results demonstrate the enhancing effect of androgens on retention of extinction memory.

Novel splicing events and post-transcriptional regulation of human estrogen receptor α E isoforms.

Expression of the estrogen receptor α (ERα) gene is subject to complex regulation. To elucidate the mechanisms of this regulation, the genomic organization and the physiological role of the multiple 5'-untranslated regions (5'-UTRs) must be determined. Here, we investigated the expression and splicing patterns of the human ERα E isoforms. We identified two novel untranslated exons, N1 and N2, in the 5'-region of the human ERα gene and multiple E isoform mRNA variants generated by alternative usage of non-coding internal exons. Expression of the N1-containing variants was observed only in the human breast adenocarcinoma cell line, MCF7, while the N2-containing variants were expressed in the adult liver and MCF7 cells. We examined post-transcriptional regulation of the variant mRNAs using luciferase reporter assays and quantitative PCR. The insertion of untranslated internal exons into the 5'-UTRs of the E isoforms reduced their translation efficiency, but barely influenced mRNA turnover. Our results indicate that the genomic organization of the human ERα gene and the splicing profiles of the human ERα E isoforms are more complicated than previously reported. Furthermore, the 5'-UTRs of the E isoforms post-transcriptionally control human ERα expression mainly through translational repression.

Attempt to develop taste bud models in three-dimensional culture.

Taste buds are the end organs of taste located in the gustatory papillae, which occur on the surface of the oral cavity. The goal of the present study was to establish a culture model mimicking the lingual taste bud of the mouse. To this end, three cell lines were employed: taste bud-derived cell lines (TBD cell lines), a lingual epithelial cell-derived cell line (20A cell line), and a mesenchymal cell-derived cell line (TMD cell line). TBD cells embedded in collagen gel formed three-dimensional clusters, which had an internal cavity equipped with a tight junction-like structure, a microvilluslike structure, and a laminin-positive layer surrounding the cluster. The cells with this epitheliumlike morphology expressed marker proteins of taste cells: gustducin and NCAM. TBD cells formed a monolayer on collagen gel when they were co-cultured with TMD cells. TBD, 20A, and TMD cell lines were maintained in a triple cell co-culture, in which TBD cells were pre-seeded as aggregates or in suspension on the collagen gel containing TMD cells, and 20A cells were laid over the TBD cells. TBD cells in the triple cell co-culture expressed NCAM. This result suggests that co-cultured TBD cells exhibited a characteristic of Type III taste cells. The culture model would be useful to study morphogenesis and functions of the gustatory organ.

Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans.

We investigated the effect of the intravenous infusion of atrial natriuretic peptide (ANP) on the response of plasma arginine vasopressin (AVP) levels to intravenous infusion of angiotensin II (ANG II) in healthy individuals. Intravenous infusion of ANP (10 ng·kg(-1)·min(-1)) slightly but significantly decreased plasma AVP levels, while intravenous infusion of ANG II (10 ng·kg(-1)·min(-1)) resulted in slightly increased plasma AVP levels. ANG II infused significant elevations in arterial blood pressure and central venous pressure (CVP). Because the elevation in blood pressure could have potentially inhibited AVP secretion via baroreceptor reflexes, the effect of ANG II on blood pressure was attenuated by the simultaneous infusion of nitroprusside. ANG II alone produced a remarkable increase in plasma AVP levels when infused with nitroprusside, whereas the simultaneous ANP intravenous infusion (10 ng·kg(-1)·min(-1)) abolished the increase in plasma AVP levels induced by ANG II when blood pressure elevation was attenuated by nitroprusside. Thus, ANG II increased AVP secretion and ANP inhibited not only basal AVP secretion but also ANG II-stimulated AVP secretion in humans. These findings support the hypothesis that circulating ANP modulates AVP secretion, in part, by antagonizing the action of circulating ANG II.

[Appropriate use of antibiotics--practice we should employ now: appropriate use of antibiotics by pharmacists at university hospitals].

Various elements, such as a quick response, effectiveness, economy, mobility (inside and outside the hospital) are needed for today's in-hospital infection control. An infection control group was established, consisting of a doctor, dentist, pharmacist, nurse, medical technologist, and an administer for the purpose of and swiftness was mobile, and being active about the establishment of investigation/a study of the prevention of in-hospital infection and measures in March, 2001. As duties to play a key role of the infection control that a pharmacist made use of professional ability in, the making of enlightenment, Therapeutic Drug Monitoring, for use situation grasp and the proper use of antimicrobial/the disinfectant and the medication guideline by the participation in planning, PK/PD characteristic to the administration plan is given. There are a lot of cases to become the fatal injury not only in-hospital infection by resistant bacteria becomes the obstruction of the treatment including MRSA, multidrug resistance Pseudomonas aeruginosa in the House. It is to support treatment by reasonable medication to be born to we pharmacist and keeps it in mind therefore to load the study of the specialty domain as a member of the team medical care.

Effects of midazolam on acquisition and extinction of conditioned taste aversion memory in rats.

Some intravenous anesthetic agents such as midazolam are known to induce anterograde and retrograde amnesia. We analyzed the effect of midazolam by the conditioned taste aversion (CTA) acquisition and retention. After the rats were offered 0.1% sodium saccharin (Sac) as conditioned stimulus (CS), an intraperitoneal (i.p.) injection of several concentrations (5-30mg/kg) of midazolam was followed by an i.p. injection of 0.15M LiCl (2% of body weight) as unconditioned stimulus (US). The rats, which acquired CTA by every CS-US paradigm, strongly avoided Sac on the 1st test day after conditioning and maintained the avoidance for 3 days. We have already reported that Sac intake abruptly increased on the 2nd test day and the almost complete extinction occurred on the 3rd test day after conditioning by injection of subhypnotic dose of propofol before LiCl-injection. In contrast, we found that subhypnotic dose of midazolam suppressed not only CTA acquisition, but also CTA retention. On the other hand, an alpha2-adrenergic blocker, yohimbin (1mg/kg) suppressed only the CTA retention. These results suggest that the subhypnotic doses of midazolam firstly affect the acquisition mechanism of the CTA memory (CTAM), resulting the suppression of the retention of CTAM.

Does infusion of ANG II increase muscle sympathetic nerve activity in patients with primary aldosteronism?

Patients with primary aldosteronism (PA) were shown to have suppressed muscle sympathetic nerve activity (MSNA) in our previous study. Although baroreflex inhibition probably accounts in part for this reduced MSNA in PA, we hypothesized that the lowered activity of the renin-angiotensin system in PA may also contribute to the suppressed SNA. We recorded MSNA in 9 PA and 16 age-matched normotensive controls (NC). In PA, the resting mean blood pressure (MBP) and serum sodium concentrations were increased, and MSNA was reduced. We examined the effects of infusion of a high physiological dose of ANG II (5.0 ng.kg(-1).min(-1)) on MSNA in 6 of 9 PA and 9 of 16 NC. Infusion of ANG II caused a greater pressor response in PA than NC, but, in spite of the greater increase in pressure, MSNA increased in PA, whereas it decreased in NC. Simultaneous infusion of nitroprusside and ANG II, to maintain central venous pressure at the baseline level and reduce the elevation in MBP induced by ANG II, caused significantly greater increases in MSNA in PA than in NC. Baroreflex sensitivity of heart rate, estimated during phenylephrine infusions, was reduced in PA, but baroreflex sensitivity of MSNA was unchanged in PA compared with NC. All the abnormalities in PA were eliminated following unilateral adrenalectomy. In conclusion, the suppressed SNA in PA depends in part on the low level of ANG II in these patients.

Biophysical properties of voltage-gated Na+ channels in frog parathyroid cells and their modulation by cannabinoids.

The membrane properties of isolated frog parathyroid cells were studied using perforated and conventional whole-cell patch-clamp techniques. Frog parathyroid cells displayed transient inward currents in response to depolarizing pulses from a holding potential of -84 mV. We analyzed the biophysical properties of the inward currents. The inward currents disappeared by the replacement of external Na+ with NMDG+ and were reversibly inhibited by 3 micromol l-1 TTX, indicating that the currents occur through the TTX-sensitive voltage-gated Na+ channels. Current density elicited by a voltage step from -84 mV to -24 mV was -80 pA pF-1 in perforated mode and -55 pA pF-1 in conventional mode. Current density was decreased to -12 pA pF-1 by internal GTPgammaS (0.5 mmol l-1), but not affected by internal GDPbetaS (1 mmol l-1). The voltage of half-maximum (V1/2) activation was -46 mV in both perforated and conventional modes. V1/2 of inactivation was -80 mV in perforated mode and -86 mV in conventional mode. Internal GTPgammaS (0.5 mmol l-1) shifted the V1/2 for activation to -36 mV and for inactivation to -98 mV. A putative endocannabinoid, 2-arachidonoylglycerol ether (2-AG ether, 50 micromol l-1) and a cannabinomimetic aminoalkylindole, WIN 55,212-2 (10 micromol l-1) also greatly reduced the Na+ current and shifted the V1/2 for activation and inactivation. The results suggest that the Na+ currents in frog parathyroid cells can be modulated by cannabinoids via a G protein-dependent mechanism.

Sexual dimorphism of acoustic signals in the oriental white stork: non-invasive identification of sex in birds.

Identification of the sex of birds is important for captive breeding of endangered species. In the oriental white stork (Ciconia boyciana), an endangered species, both sexes produce an acoustic signal called "clatter" by rattling their mandibles together to generate sounds. We examined the structure of male and female clatter to determine whether clatter is sexually dimorphic. The acoustic structure of the clatter of the two sexes proved to be dimorphic with respect to the fundamental frequency; female clatter had higher fundamental frequencies. The fundamental frequency correlated significantly and positively with bill length, suggesting that bill morphology contributes to the sexual dimorphism of clatter. Sexing can be done by acoustic signals without capturing birds, and thus is useful as a non-invasive sexing method for ecological and conservation studies of birds.

Subhypnotic doses of propofol accelerate extinction of conditioned taste aversion.

Subhypnotic doses of propofol accelerate extinction of conditioned taste aversion. Some intravenous anesthetic agents including propofol is known to induce anterograde and retrograde amnesia. We evaluated whether propofol affect the long-term memory formed by the conditioned taste aversion (CTA) paradigm. Rats were allowed a 4h access to water through the experiments. After preconditioning water intake, the rats were offered 0.1% sodium saccharin (Sac) as conditioned stimulus (CS) for 20 min. An intraperitoneal (i.p.) injection of several concentrations (0.5-100 mg/kg) of propofol 10 min after Sac exposure was followed by an i.p. injection of 0.15M LiCl (2% of body weight) as unconditioned stimulus (US) 30 min after CS-exposure. The volumes of intake of Sac for 20 min were measured on the successive 4 days. The rats, which acquired CTA by every CS-US paradigm, strongly avoided Sac on the first test day after conditioning and maintained the avoidance for 3 days. However, when subhypnotic dose of propofol was injected before LiCl-injection, Sac intake abruptly increased on the second test day and the almost complete extinction occurred on the third test day after conditioning. The extinction process of CTA was barely affected by hypnotic dose of propofol. These results suggest that propofol affects the retention mechanism of the CTA memory in a dose-dependent manner. Subhypnotic dose of propofol may affect the sub-cellular process of the memory consolidation in CTA.

Dopamine modulates a voltage-gated calcium channel in rat olfactory receptor neurons.

Dopamine D2 receptors exist in the soma of rat olfactory receptor neurons. Actions of dopamine on the voltage-gated Ca(2+) channels in the neurons were investigated using the perforated whole-cell voltage-clamp. In 10 mM Ba(2+) solution, rat olfactory receptor neurons displayed the inward currents elicited by the voltage ramp (167 mV/s) and depolarizing step pulses from a holding potential of -91 mV. The inward Ba(2+) currents were greatly reduced by 10 microM nifedipine (L-type Ca(2+) channel blocker). The Ba(2+) currents were inhibited by the external application of dopamine. The IC(50) for the inhibition was about 1 microM. Quinpirole (10 microM, a D2 dopamine agonist) also inhibited the Ba(2+) currents. Quinpirole did not affect the activation and inactivation kinetics of the Ba(2+) currents. The results suggest that dopamine modulates the L-type Ca(2+) channels in rat olfactory receptor neurons via the mechanism independent of voltage.

Serotonin differentially modulates the electrical properties of different subsets of taste receptor cells in bullfrog.

Serotonin (5-hydroxytryptamin, 5-HT) is localized in taste bud cells of vertebrates. Effects of the external application of 5-HT on the membrane currents of frog taste receptor cells (TRCs) were investigated using patch-clamp technique in whole-cell configuration. The 5-HT (0.1-1 micro m) and 5-HT1A receptor agonist (+/-)-8-OH-2-(D1-n-propyl-amino)tetralin (8-OH-DPAT) (1-20 micro m) inhibited both voltage-gated sodium current (INa) and voltage-gated potassium current (IK) in 50% of TRCs, but potentiated IK without any significant effect on INa in another subset of 18% of TRCs. Voltage-gated currents in the residual TRCs were not affected by 5-HT or 8-OH-DPAT. External application of 10 micro m forskolin and 300 micro m 8-cpt cAMP [8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate] mimicked the inhibitory effect of 5-HT and 8-OH-DPAT on IK and INa while internal dialysis with 50 micro m protein kinase A inhibitor prevented the 5-HT-mediated inhibitory effects on IK and INa in TRCs. Internal dialysis of TRCs with high Ca2+-pipette solution (1 micro m) increased the IK in 58% of TRCs. The 5-HT reversibly increased the [Ca2+]i in 17% of TRCs when measured by Ca2+-imaging using a Ca2+-sensitive dye (fura-2 AM). These results suggest that 5-HT differentially modulates the voltage-gated membrane currents in different subsets of TRCs.

Slow potentials in taste cells induced by frog glossopharyngeal nerve stimulation.

Intracellular recordings were made from the taste cells of atropinized bullfrogs while the glossopharyngeal (GP) nerve fibres were electrically stimulated. Two types of slow potential, slow hyperpolarizing potentials (HPs) and slow depolarizing potentials (DPs), were induced in the taste cells. The slow HPs appeared when the lingual capillary blood flow was kept above 0.7 mm/s, whereas the slow DPs appeared when the blood flow was slowed down below 0.7 mm/s. The membrane resistance of a taste cell increased during the generation of a slow HP, but decreased during the generation of a slow DP. The reversal potentials for the slow HPs and the slow DPs were recorded at the same membrane potential (-11 to approximately -13 mV). Activation of non-selective cation channels possibly induced the slow DP and inactivation of those channels possibly induced the slow HP in the taste cell membrane. Electrical stimulation of the GP nerve activated a population of C fibres in the nerve and possibly released neurotransmitters from the nerve terminals. Released neurotransmitters might cause modulation of the membrane conductance in taste cells that leads to generation of the slow potentials. The present data suggest that slow HPs and slow DPs evoked in the taste cells of atropinized frogs by GP nerve stimulation are induced by putative neurotransmitters in the taste disc.