The supposition of the mechanism of escitalopram makes a dopamine nerve activity rise by inhibiting corticotropinreleasing factor to the non-organic-pain ～A SSRI application is desirable for a non-organic-pain～

Although escitalopram (ESC) is no having dopamine (DA) transporter (DAT) inhibitory-action, having dopamine nerve (A10 nerve) stimulus operation by the ESC used basic experiment is reported. We supposed the mechanism that the DA increases and it supposed the mechanism that makes a non-organic pain disappear with ①5-HT reinforcement of the descending pain modulatory system, ②the opioid receptor activation with the descending pain modulatory system, ③negative emotion block from the amygdala and the hippocampus to the nucleus accumbens, ④5-HT1A receptor stimulation from the activation of the amygdala, ⑤DA-phasic activity activation. As a result ④ and ⑤ two items were an operation with a main restraint mechanism of a nonorganic-pain. ESC is different from other SSRIs, and we know that ESC make a DA increase at the VTA. We supposed amygdala that a functional depression declined by corticotropin-releasing factor (CRF) is improved with ④ and ③. After DA stimulate by A10 nerve, DA is undergone metabolic change to, and the endogenous opioid peptide (βendorphin) is made

Positron Annihilation Study of Irradiated HOPG-type Graphite

Positron annihilation angular correlation measurements (ACAR : angular correlation of annihilation radiation) were made for HOPG (highly oriented pyrolytic graphite) and PGCCL (HOPG-type graphite, Le Carbone-Lorraine) irradiated by various particles, such as electrons, neutrons and deuterium particles. The ACAR measurements made under the condition of P_Z//c-axis for unirradiated specimens showed a clear minimum at θ=0°, but P_Z⊥c-axis measurement did not show this minimum. This minimum is considered to be due to the annihilation of positrons with π electrons the momentum distribution of which is extended to the direction parallel to c-axis. On the other hand, by neutron irradiation this minimum disappeared, which suggests that positrons are trapped at radiation-induced defects, probably vacancy sites, and the probability of the annihilation with π electrons was decreased to the large extent. But, in the case of hydrogen irradiation the minimum was not affected so much, which suggests hydrogen atoms do not disturb the π electrons, probably because hydrogen atoms are trapped at boundary regions, such as those between adjacent crystallites or region of stacking disorder

Preferred Conditions for SrtA Transpeptidation for Creating a DDS Tool

Background/Aim: This study aimed to determine the preferred conditions for the transpeptidase reaction of sortase A from Staphylococcus aureus, for the purpose of creating functional liposomes useful for a drug-delivery system (DDS). Materials and Methods: His-tagged recombinant sortase A with 59 amino acids deleted from the N-terminus (His-ΔN59SrtA) was prepared using an Escherichia coli expression system. The pH dependency and sorting signal sequence dependency of the transpeptidase reaction of His-ΔN59SrtA were analyzed by monitoring the transfer of model donor-substrates (i.e. His-tagged mutant green fluorescent proteins with a C-terminal LPxTG sorting signal) to model acceptor-beads with a GGGGGC peptide. In addition, using preferred conditions, the sortase A reaction was used to modify liposome surface. Results and Discussion: The transpeptidase reaction of His-ΔN59SrtA was enhanced under weakly acidic conditions. Transfer efficiency, based on sorting signal recognition by His-ΔN59SrtA, was similar to or higher than that obtained using several substrates with amino acids other than Glu in the sorting signal position “x”. Furthermore, liposomes containing GGGGGC peptide-linked dipalmitoylphosphatidylethanolamine were successfully modified using the preferred conditions for His-ΔN59SrtA determined in this study. Conclusion: Preferred conditions for the transpeptidase reaction of His-ΔN59SrtA, especially in a weakly acidic environment to enhance reaction, was established and successfully used to create functional liposomes applicable to DDS

The shape of the emotion

　The emotion is an active reaction with being eloquent of the emotions such as the change of the look with the physiological reaction which is strong in the automatic nerves system, the immune system, the endocrine system which occurs with the organolepty which the creature felt.However, the definition of the emotion is ambiguous.　It is different roughly every learning field and for it, there is not a strict distinction of the emotion and the feelings.　The handling depends on the interval of the research area and the researcher.There seems to be possibility to complicate the discussion of the concerning with anxiety, theamygdala which is the nucleus of the fear and a cerebral limbic system for the ambiguousness of the definition and to make difficult.　Therefore, we made a chart with the emotion , feelings and the mood, placing as the differentreaction. In the tunnel of the tube-like of the comparatively gently long lasting mood, the feelings were wavering but supposed that doing of the eloquent of the emotion which is a physiological reaction and an active reaction didn\u27t accompany.　On the other hand, it supposed that an emotion was accompanied by the reaction which is physiological which is strong in the automatic nerves system, the immune system, the endocrine system and doing of the eloquent of the emotion physiological strong, deviating from the feeling control by the ventromedial prefrontal cortex.　Moreover, it considered about the relation, too, about the amygdala which is the existence like a nucleus of the experience like an emotion and the chronic pain

The Supposition of the Mechanism of SSRI to the glossodynia as Non-Organic-Pain in the Mouth and Face Area

These contents obtain the approval of Japanese Red Cross Takayama Hospital Ethics Committeeand it is considering sufficiently about the ethical models such as the protection of the privacy.There is not a state of the conflict of interests (COI)

An Improved DDS Tool with Versatile Cell-targeting Ability

Background/Aim: The aim of this study was to develop an improved drug delivery system (DDS) tool with enhanced versatility in the cell-targeting step using as Z-domain, a modified IgG binding domain of protein A from Staphylococcus aureus, as an IgG adapter domain. Materials and Methods: The chimera protein expression system composed of the Z-domain and chimeric cholesterol-dependent cytolysin mutant named His-Z-CDC(ss)IS was constructed in Escherichia coli. His-Z-CDC(ss)IS was purified by Ni-affinity chromatography, and its abilities for controlled pore formation, membrane binding, IgG binding, and target cell-specific delivery of liposomes carrying medicine were investigated. Results and Discussion: His-Z-CDC(ss)IS purified by Ni-affinity chromatography indicated pore-forming activity only under disulfide bond reducing conditions. His-Z-CDC(ss)IS also demonstrated an ability to bind both IgG and cholesterol-embedded liposomes via its Z-domain and domain 4, respectively. Furthermore, anticarcinoembryonic antigen (CEA) IgG-bound His-Z-CDC(ss)IS indicated effective delivery of liposomes carrying drugs to CEA-expressing cells. Conclusion: His-Z-CDC(ss)IS was revealed to be an improved DDS tool with enhanced versatility in cell targeting

Application of Pore-forming Toxin as a DDS Tool

Background/Aim: Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins from Gram-positive bacteria. The aim of this study was to investigate the potential of a CDC, intermedilysin, as a drug-delivery system (DDS) for clinical application. Materials and Methods: Intermedilysin was modified by the addition of a disulfide bridge to regulate pore formation, by swapping domain 4 to provide cholesterol-binding capacity, and by the introduction of a targeting domain. The resultant chimera protein, His-LTBP-CDC(ss)IP, was investigated for its use as a DDS tool in vitro. Results: His-LTBP-CDC(ss)IP exhibited a regulated pore-forming capacity under reducing conditions. This chimera protein was able to deliver a drug-carrier liposome specifically to the target cell, to be endocytosed into the cell with subsequent release of the components into the cytoplasm. Conclusion: A chimera protein derived from the bacterial pore-forming toxin intermedilysin (His-LTBP-CDC(ss)IP) forms the basis for a novel DDS tool

The Early Effect Onset of SSRI to the Non-Organic-Pain in the Mouth and Face Area

These contents obtain the approval of Japanese Red Cross Takayama Hospital Ethics Committeeand it is considering sufficiently about the ethical models such as the protection of the privacy.There is not a state of the conflict of interests (COI )

Development of SrtA-mediated Peptide-labeled Liposome

Background/Aim: In order to develop an efficient drug-delivery system (DDS), a lipopeptide-loaded liposome that functions as a platform for the transpeptidase reaction mediated by sortase A (SrtA) was constructed and its stability, as well as cell-specific targeting were evaluated in the present study. Materials and Methods: Several lipopeptides possessing an acceptor peptide sequence (oligoglycine ≥ three residues) or donor peptide sequence (LPETG) for the SrtA-mediated reaction were chemically synthesized and then inserted into the liposome membrane composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol (DPPC-Chol-lipo) to obtain the lipopeptide-loaded liposomes. The transpeptidase reaction mediated by recombinant SrtA (His-ΔN59SrtA) was employed to modify the peptide moiety on the liposomal surface using a fluorescently-labeled substrate peptide corresponding to the species of each loaded lipopeptide. Furthermore, lung tumor-binding peptide (LTBP)-labeled liposomes, prepared by this transpeptidase reaction, were investigated for selective targeting to lung cancer cells in vitro. Results and Discussion: The His-ΔN59SrtA-mediated transpeptidation of fluorescently-labeled peptide on the lipopeptide-loaded DPPC-Chol-lipo was confirmed. The selective targeting of LTBP-labeled liposomes to the lung cancer cell line A549 was also observed in vitro. These results suggest that the labeling of acceptor or donor lipopeptide-loaded liposomes with the transpeptidase SrtA could be a useful method for developing a platform applicable to a cancer-targeting DDS