Microneedles: A novel clinical technology for evaluating skin characteristics.

BACKGROUND: Current methods for evaluating efficacy of cosmetics have limitations because they cannot accurately measure changes in the dermis. Skin sampling using microneedles allows identification of skin-type biomarkers, monitoring treatment for skin inflammatory diseases, and evaluating efficacy of anti-aging and anti-pigmentation products. MATERIALS AND METHODS: Two studies were conducted: First, 20 participants received anti-aging treatment; second, 20 participants received anti-pigmentation treatment. Non-invasive devices measured skin aging (using high-resolution 3D-imaging in the anti-aging study) or pigmentation (using spectrophotometry in the anti-pigmentation study) at weeks 0 and 4, and adverse skin reactions were monitored. Skin samples were collected with biocompatible microneedle patches. Changes in expression of biomarkers for skin aging and pigmentation were analyzed using qRT-PCR. RESULTS: No adverse events were reported. In the anti-aging study, after 4 weeks, skin roughness significantly improved in 17 out of 20 participants. qRT-PCR showed significantly increased expression of skin-aging related biomarkers: PINK1 in 16/20 participants, COL1A1 in 17/20 participants, and MSN in 16/20 participants. In the anti-pigmentation study, after 4 weeks, skin lightness significantly improved in 16/20 participants. qRT-PCR showed significantly increased expression of skin-pigmentation-related biomarkers: SOD1 in 15/20 participants and Vitamin D Receptor (VDR) in 15/20 participants. No significant change in TFAP2A was observed. CONCLUSION: Skin sampling and mRNA analysis for biomarkers provides a novel, objective, quantitative method for measuring changes in the dermis and evaluating the efficacy of cosmetics. This approach complements existing evaluation methods and has potential application in assessing the effectiveness of medical devices, medications, cosmeceuticals, healthy foods, and beauty devices.

SARS-CoV-2 spike trimer vaccine expressed in Nicotiana benthamiana adjuvanted with Alum elicits protective immune responses in mice.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has spurred rapid development of vaccines as part of the public health response. However, the general strategy used to construct recombinant trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) proteins in mammalian cells is not completely adaptive to molecular farming. Therefore, we generated several constructs of recombinant S proteins for high expression in Nicotiana benthamiana. Intramuscular injection of N. benthamiana-expressed Sct vaccine (NSct Vac) into Balb/c mice elicited both humoral and cellular immune responses, and booster doses increased neutralizing antibody titres. In human angiotensin-converting enzyme knock-in mice, two doses of NSct Vac induced anti-S and neutralizing antibodies, which cross-neutralized Alpha, Beta, Delta and Omicron variants. Survival rates after lethal challenge with SARS-CoV-2 were up to 80%, without significant body weight loss, and viral titres in lung tissue fell rapidly, with no infectious virus detectable at 7-day post-infection. Thus, plant-derived NSct Vac could be a candidate COVID-19 vaccine.

The peripheral dopamine 2 receptor antagonist domperidone attenuates ethanol enhancement of dopamine levels in the nucleus accumbens.

BACKGROUND: Dopamine neuron firing in the ventral tegmental area (VTA) and dopamine release in the nucleus accumbens have been implicated in reward learning. Ethanol is known to increase both dopamine neuron firing in the VTA and dopamine levels in the nucleus accumbens. Despite this, some discrepancies exist between the dose of ethanol required to enhance firing in vivo and ex vivo. In the present study we investigated the effects of peripheral dopamine 2 subtype receptor antagonism on ethanol's effects on dopamine neurotransmission. METHODS: Plasma catecholamine levels were assessed following ethanol administration across four different doses of EtOH. Microdialysis and voltammetry were used to assess the effects of domperidone pretreatment on ethanol-mediated increases in dopamine release in the nucleus accumbens. A place conditioning paradigm was used to assess conditioned preference for ethanol and whether domperidone pretreatment altered this preference. Open-field and loss-of-righting reflex paradigms were used to assess the effects of domperidone on ethanol-induced sedation. A rotarod apparatus was used to assess the effects of domperidone on ethanol-induced motor impairment. RESULTS: Domperidone attenuated ethanol's enhancement of mesolimbic dopamine release under non-physiological conditions at intermediate (1.0 and 2.0 g/kg) doses of ethanol. Domperidone also decreased EtOH-induced sedation at 2.0 g/kg. Domperidone did not alter ethanol conditioned place preference nor did it affect ethanol-induced motor impairment. CONCLUSIONS: These results show that peripheral dopamine 2 receptors mediate some of the effects of ethanol on nonphysiological dopamine neurotransmission, although these effects are not related to the rewarding properties of ethanol.

Nicotine Rather Than Non-Nicotine Substances in 3R4F WCSC Increases Behavioral Sensitization and Drug-Taking Behavior in Rats.

INTRODUCTION: Nicotine increases reinforcing effects of cigarette smoking by upregulating glutamate and dopamine releases via stimulation of nicotinic acetylcholine receptors (nAChRs) in the dorsal striatum (CPu). The present study was conducted to evaluate whether non-nicotine substances in cigarette smoke potentiate nicotine-induced behaviors by increasing glutamate and dopamine concentrations in the CPu. AIMS AND METHODS: Changes in the levels of glutamate and dopamine in the CPu were analyzed using a glutamate colorimetric assay and dopamine enzyme-linked immunosorbent assay, respectively, after repeated administration of nicotine or whole cigarette smoke condensate (WCSC) in male Sprague-Dawley rats. Changes in locomotion and drug-taking behavior were analyzed using the measurements of locomotor activity and self-administration under a fixed ratio 1 schedule in response to repeated administration of nicotine or WCSC. RESULTS: Repeated subcutaneous (s.c.) injections of nicotine (0.25 mg/kg/day) for 7 consecutive days significantly increased the levels of glutamate and dopamine in the CPu. Similar results were obtained from repeated injections of WCSC (0.25 mg/kg nicotine/day, s.c.) extracted from 3R4F Kentucky reference cigarettes. Parallel with the increases in the neurotransmitter levels in the CPu, both nicotine and WCSC increased locomotor activity and self-administration (0.03 mg/kg nicotine/infusion). However, repeated injections of WCSC did not change the nicotine-induced increases in neurotransmitter levels, locomotor activity, and self-administration. CONCLUSIONS: Nicotine rather than non-nicotine substances in WCSC play a major role in potentiating behavioral sensitization and drug-taking behavior via elevation of glutamate and dopamine concentrations in the CPu of rats. IMPLICATIONS: WCSC does not augment the nicotine-induced increases in behavioral sensitization, drug-taking behavior, and glutamate and dopamine concentrations, suggesting that non-nicotine substances do not potentiate the nicotine-induced behaviors by increasing the concentrations of the neurotransmitters in the CPu. These findings imply that nicotine, but not non-nicotine substances in WCSC, may be a major contributor that induces tobacco dependence in rats.

Modulation of dopamine release by ethanol is mediated by atypical GABAA receptors on cholinergic interneurons in the nucleus accumbens.

Previous studies indicate that moderate-to-high ethanol (EtOH) concentrations enhance dopamine (DA) neurotransmission in the mesolimbic DA system from the ventral tegmental area (VTA) and projecting to the nucleus accumbens core (NAc). However, voltammetry studies demonstrate that moderate-to-high EtOH concentrations decrease evoked DA release at NAc terminals. The involvement of γ-aminobutyric acid (GABA) receptors (GABAA Rs), glycine (GLY) receptors (GLYRs) and cholinergic interneurons (CINs) in mediating EtOH inhibition of evoked NAc DA release were examined. Fast scan cyclic voltammetry, electrophysiology, optogenetics and immunohistochemistry techniques were used to evaluate the effects of acute and chronic EtOH exposure on DA release and CIN activity in C57/BL6, CD-1, transgenic mice and δ-subunit knockout (KO) mice (δ-/-). Ethanol decreased DA release in mice with an IC50 of 80 mM ex vivo and 2.0 g/kg in vivo. GABA and GLY decreased evoked DA release at 1-10 mM. Typical GABAA R agonists inhibited DA release at high concentrations. Typical GABAA R antagonists had minimal effects on EtOH inhibition of evoked DA release. However, EtOH inhibition of DA release was blocked by the α4 ß3 δ GABAA R antagonist Ro15-4513, the GLYR antagonist strychnine and by the GABA ρ1 (Rho-1) antagonist TPMPA (10 µM) and reduced significantly in GABAA R δ-/- mice. Rho-1 expression was observed in CINs. Ethanol inhibited GABAergic synaptic input to CINs from the VTA and enhanced firing rate, both of which were blocked by TPMPA. Results herein suggest that EtOH inhibition of DA release in the NAc is modulated by GLYRs and atypical GABAA Rs on CINs containing δ- and Rho-subunits.

Effects of ß-Phenylethylamine on Psychomotor, Rewarding, and Reinforcing Behaviors and Affective State: The Role of Dopamine D1 Receptors.

Beta-phenylethylamine (ß-PEA) is a well-known and widespread endogenous neuroactive trace amine found throughout the central nervous system in humans. In this study, we demonstrated the effects of ß-PEA on psychomotor, rewarding, and reinforcing behaviors and affective state using the open-field test, conditioned place preference (CPP), self-administration, and ultrasonic vocalizations (USVs) paradigms. We also investigated the role of the dopamine (DA) D1 receptor in the behavioral effects of ß-PEA in rodents. Using enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting, we also determined the DA concentration and the DA-related protein levels in the dorsal striatum of mice administered with acute ß-PEA. The results showed that acute ß-PEA increased stereotypic behaviors such as circling and head-twitching responses in mice. In the CPP experiment, ß-PEA increased place preference in mice. In the self-administration test, ß-PEA significantly enhanced self-administration during a 2 h session under fixed ratio (FR) schedules (FR1 and FR3) and produced a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement in rats. In addition, acute ß-PEA increased 50-kHz USV calls in rats. Furthermore, acute ß-PEA administration increased DA concentration and p-DAT and TH expression in the dorsal striatum of mice. Finally, pretreatment with SCH23390, a DA D1 receptor antagonist, attenuated ß-PEA-induced circling behavior and ß-PEA-taking behavior in rodents. Taken together, these findings suggest that ß-PEA has rewarding and reinforcing effects and psychoactive properties, which induce psychomotor behaviors and a positive affective state by activating the DA D1 receptor in the dorsal striatum.

The potent psychomotor, rewarding and reinforcing properties of 3-fluoromethamphetamine in rodents.

3-fluoromethamphetamine (3-FMA), a derivative of methamphetamine (METH), produces behavioral impairment and deficits in dopaminergic transmission in the striatum of mice. The abuse potential of 3-FMA has not been fully characterized. The aim of this study was to evaluate the effects of 3-FMA on locomotor activity as well as its rewarding and reinforcing properties in the conditioned place preference (CPP) and self-administration procedures. Intravenous (i.v.) administration of 3-FMA (0.5 and 1.0 mg/kg) significantly increased locomotor activity in a dose-dependent manner in rats. In the CPP procedure, intraperitoneal administration of 3-FMA (10 and 30 mg/kg) produced a significant alteration in place preference in mice. In the self-administration paradigms, 3-FMA showed drug-taking behavior at the dose of 0.1 mg/kg/infusion (i.v.) during 2 hr sessions under fixed ratio schedules and high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion (i.v.) during 6 hr sessions under progressive ratio schedule of reinforcement in rats. A priming injection of 3-FMA (0.4 mg/kg, i.v.), METH (0.2 mg/kg, i.v.), or cocaine (2.0 mg/kg, i.v.) reinstated 3-FMA-seeking behavior after an extinction period in 3-FMA-trained rats during 2 hr session. Taken together, these findings demonstrate robust psychomotor, rewarding and reinforcing properties of 3-FMA, which may underlie its potential for compulsive use in humans.

Network analysis of the depressive symptom profiles in Asian patients with depressive disorders: Findings from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD).

AIM: We aimed to estimate the network structures of depressive symptoms using network analysis and evaluated the geographic regional differences in theses network structures among Asian patients with depressive disorders. METHODS: Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), the network of the ICD-10 diagnostic criteria for depressive episode was estimated from 1174 Asian patients with depressive disorders. The node strength centrality of all ICD-10 diagnostic criteria for a depressive episode was estimated using a community-detection algorithm. In addition, networks of depressive symptoms were estimated separately among East Asian patients and South or Southeast Asian patients. Moreover, networks were estimated separately among Asian patients from high-income countries and those from middle-income countries. RESULTS: Persistent sadness, fatigue, and loss of interest were the most centrally situated within the network of depressive symptoms in Asian patients with depressive disorders overall. A community-detection algorithm estimated that when excluding psychomotor disturbance as an outlier, the other nine symptoms formed the largest clinically meaningful cluster. Geographic and economic variations in networks of depressive symptoms were evaluated. CONCLUSION: Our findings demonstrated that the typical symptoms of the ICD-10 diagnostic criteria for depressive episode are the most centrally situated within the network of depressive symptoms. Furthermore, our findings suggested that cultural influences related to geographic and economic distributions of participants could influence the estimated depressive symptom network in Asian patients with depressive disorders.

The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4'-F-PCP) in Rodents.

The dissociative anesthetic phencyclidine (PCP) and PCP derivatives, including 4'-F-PCP, are illegally sold and abused worldwide for recreational and non-medical uses. The psychopharmacological properties and abuse potential of 4'-F-PCP have not been fully characterized. In this study, we evaluated the psychomotor, rewarding, and reinforcing properties of 4'-F-PCP using the open-field test, conditioned place preference (CPP), and self-administration paradigms in rodents. Using Western immunoblotting, we also investigated the expression of dopamine (DA)-related proteins and DA-receptor-mediated downstream signaling cascades in the nucleus accumbens (NAc) of 4'-F-PCP-self-administering rats. Intraperitoneal administration of 10 mg/kg 4'-F-PCP significantly increased locomotor and rearing activities and increased CPP in mice. Intravenous administration of 1.0 mg/kg/infusion of 4'-F-PCP significantly enhanced self-administration during a 2 h session under fixed ratio schedules, showed a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement, and significantly altered the expression of DA transporter and DA D1 receptor in the NAc of rats self-administering 1.0 mg/kg 4'-F-PCP. Additionally, the expression of phosphorylated (p) ERK, pCREB, c-Fos, and FosB/ΔFosB in the NAc was significantly enhanced by 1.0 mg/kg 4'-F-PCP self-administration. Taken together, these findings suggest that 4'-F-PCP has a high potential for abuse, given its robust psychomotor, rewarding, and reinforcing properties via activation of DAergic neurotransmission and the downstream signaling pathways in the NAc.

Development and comparison of two H5N8 influenza A vaccine candidate strains.

Avian influenza viruses circulating in birds have caused outbreaks of infection in poultry and humans, thereby threatening public health. Recently, a highly pathogenic avian influenza (HPAI) virus (H5N8) of clade 2.3.4.4 emerged in Korea and other countries and caused multiple outbreaks in domestic and wild birds, with concerns for human infection. To combat HPAI viral infections, novel vaccines are likely to be the most effective approach. Therefore, in this study, we generated H5N8 vaccine candidate viruses based on a Korean isolate (A/broiler duck/Korea/Buan2/2014). The vaccine candidate viruses were 2:6 reassortants expressing the two surface glycoproteins of A/broiler duck/Korea/Buan2/2014 on an A/Puerto Rico/8/34 (PR8) backbone generated by using an eight-plasmid-based reverse genetics system with or without replacement of the multi-basic amino acid cleavage motif (MBCM, a crucial pathogenic factor in HPAI virus) with a bi-basic amino acid cleavage motif (BBCM) in their HA. An H5N8 vaccine candidate virus containing the BBCM showed attenuated pathogenesis in embryonated eggs and exhibited less virulence in the infected mice compared with the wild H5N8 virus containing an MBCM. Vaccination with an inactivated preparation of the vaccine candidate virus protected mice from lethal H5N8 viral challenge. This is the first report of the development and evaluation of H5N8 vaccine strains (with an MBCM or BBCM) of HA clade 2.3.4.4 as vaccine candidates. Our findings suggest that H5N8 strains with a BBCM instead of an MBCM might be considered for H5N8 vaccine seed virus development or as a reference vaccine against H5N8 viral strains.

Acupuncture inhibition of methamphetamine-induced behaviors, dopamine release and hyperthermia in the nucleus accumbens: mediation of group II mGluR.

Methamphetamine (METH) increases metabolic neuronal activity in the mesolimbic dopamine (DA) system and mediates the reinforcing effect. To explore the underlying mechanism of acupuncture intervention in reducing METH-induced behaviors, we investigated the effect of acupuncture on locomotor activity, ultrasonic vocalizations, extracellular DA release in the nucleus accumbens (NAcs) using fast-scan cyclic voltammetry and alterations of brain temperature (an indicator of local brain metabolic activity) produced by METH administration. When acupuncture was applied to HT7, but not TE4, both locomotor activity and 50-kHz ultrasonic vocalizations were suppressed in METH-treated rats. Acupuncture at HT7 attenuated the enhancement of electrically stimulated DA release in the NAc of METH-treated rats. Systemic injection of METH produced a sustained increase in NAc temperature, which was reversed by the DA D1 receptor antagonist SCH 23390 or acupuncture at HT7. Acupuncture inhibition of METH-induced NAc temperature was prevented by pre-treatment with a group II metabotropic glutamate receptors (mGluR2/3) antagonist EGLU into the NAc or mimicked by injection of an mGluR2/3 agonist DCG-IV into the NAc. These results suggest that acupuncture reduces extracellular DA release and metabolic neuronal activity in the NAc through activation of mGluR2/3 and suppresses METH-induced affective states and locomotor behavior.

Bacterial indoleacetic acid-induced synthesis of colloidal Ag2O nanocrystals and their biological activities.

The biosynthesis and biological activity of colloidal Ag2O nanocrystals have not been well studied, although they have potential applications in many fields. For the first time, we developed a reducing agent free, cost-effective technique for Ag2O biosynthesis using Xanthomonas sp. P5. The optimal conditions for Ag2O synthesis were 50 °C, pH 8, and 2.5 mM AgNO3. Using these conditions the yield of Ag2O obtained at 10 h was about five times higher than that obtained at 12 h under unoptimized conditions. Ag2O was characterized by FESEM-EDS, TEM, dynamic light scattering, XRD, and UV-Visible spectroscopy. Indoleacetic acid produced by the strain P2 was involved in the synthesis of Ag2O. Ag2O exhibited a broad antimicrobial spectrum against several human pathogens. Furthermore, Ag2O exhibited 1,1-diphenyl-2-picrylhydrazyl (IC50 = 25.1 µg/ml) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate (IC50 = 16.8 µg/ml) radical scavenging activities, and inhibited collagenase (IC50 = 27.9 mg/ml). Cytotoxicity of Ag2O was tested in fibroblast cells and found to be non-toxic, demonstrating biocompatibility.

Acupuncture reduces relapse to cocaine-seeking behavior via activation of GABA neurons in the ventral tegmental area.

There is growing public interest in alternative approaches to addiction treatment and scientific interest in elucidating the neurobiological underpinnings of acupuncture. Our previous studies showed that acupuncture at a specific Shenmen (HT7) points reduced dopamine (DA) release in the nucleus accumbens (NAc) induced by drugs of abuse. The present study was carried out to evaluate the effects of HT7 acupuncture on γ-aminobutyric acid (GABA) neuronal activity in the ventral tegmental area (VTA) and the reinstatement of cocaine-seeking behavior. Using microdialysis and in vivo single-unit electrophysiology, we evaluated the effects of HT7 acupuncture on VTA GABA and NAc DA release and VTA GABA neuronal activity in rats. Using a within-session reinstatement paradigm in rats self-administering cocaine, we evaluated the effects of HT7 stimulation on cocaine-primed reinstatement. Acupuncture at HT7 significantly reduced cocaine suppression of GABA release and GABA neuron firing rates in the VTA. HT7 acupuncture attenuated cocaine-primed reinstatement, which was blocked by VTA infusions of the selective GABAB receptor antagonist 2-hydroxysaclofen. HT7 stimulation significantly decreased acute cocaine-induced DA release in the NAc, which was also blocked by 2-hydroxysaclofen. HT7 acupuncture also attenuated cocaine-induced sensitization of extracellular DA levels in the NAc. Moreover, HT7 acupuncture reduced both locomotor activity and neuronal activation in the NAc induced by acute cocaine in a needle-penetration depth-dependent fashion. These results suggest that acupuncture may suppress cocaine-induced DA release in the NAc and cocaine-seeking behavior through activation of VTA GABA neurons. Acupuncture may be an effective therapy to reduce cocaine relapse by enhancing GABAergic inhibition in the VTA.

Improved biosynthesis of silver nanoparticles using keratinase from Stenotrophomonas maltophilia R13: reaction optimization, structural characterization, and biomedical activity.

In the present study, keratinase from Stenotrophomonas maltophilia R13 was used for the first time as a reducing agent for the eco-friendly synthesis of AgNPs. The keratinase produced by strain R13 was responsible for the reduction of silver ions and the subsequent formation of AgNPs. Maximum AgNP synthesis was achieved using 2 mM AgNO3 at pH 9 and 40 °C. Electron microscopy and dynamic light scattering analysis showed AgNPs were spherical and of average diameter ~ 8.4 nm. X-ray diffraction revealed that AgNPs were crystalline. FTIR indicated AgNPs were stabilized by proteins present in the crude enzyme solution of strain R13. AgNPs exhibited a broad antimicrobial spectrum against several pathogenic microorganisms, and the antimicrobial mechanism appeared to involve structural deformation of cells resulting in membrane leakage and subsequent lysis. AgNPs also displayed 1,1-diphenyl-2-picrylhydrazyl (IC50 = 0.0112 mg/ml), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate radical scavenging (IC50 = 0.0243 mg/ml), and anti-collagenase (IC50 = 23.5 mg/ml) activities.

Mycophenolic mofetil, an alternative antiviral and immunomodulator for the highly pathogenic avian influenza H5N1 virus infection.

Infection with the highly pathogenic avian influenza H5N1 virus results in a high incidence of mortality in humans. Severe complications from infection are often associated with hypercytokinemia. However, current neuraminidase inhibitors (NAIs) have several limitations including the appearance of oseltamivir-resistant H5N1 virus and the inability to completely ameliorate hyper-immune responses. To overcome these limitations, we evaluated the anti-viral activity of mycophenolic mofetil (MMF) against A/Vietnam/1194/2004 (H5N1) virus infection using MDCK cells and mice. The IC50 of MMF (0.94 µM) was comparable to that of zanamivir (0.87 µM) in H5N1 virus-infected MDCK cells based on ELISA. Time-course assays demonstrated that MMF completely inhibited H5N1 viral mRNA replication and protein expression for approximately 8 h after the initiation of treatment. In addition, MMF treatment protected 100% of mice, and lung viral titers were substantially reduced. The anti-viral mechanism of MMF against H5N1 virus infection was further confirmed to depend on the inhibition of cellular inosine monophosphate dehydrogenase (IMPDH) by exogenous guanosine, which inhibits viral mRNA and protein expression. Moreover, IL-1ß, IFN-ß, IL-6, and IP-10 mRNA expression levels were significantly downregulated in MDCK cells with MMF treatment. These results indicated that MMF could represent a novel inhibitor of viral replication and a potent immunomodulator for the treatment of H5N1 virus infection.

The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens.

Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. METH-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are implicated in behavior changes and DA release in the nucleus accumbens (NAc) following cocaine administration. The aim of this study was to evaluate the involvement of ROS in METH-induced locomotor activity, self-administration and enhancement of DA release in the NAc. Systemic administration of a non-specific ROS scavenger, N-tert-butyl-α-phenylnitrone (PBN; 0, 50 and 75 mg/kg, IP) or a superoxide-selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL; 0, 50 and 100 mg/kg, IP), attenuated METH-induced locomotor activity without affecting generalized behavior in METH-naïve rats. PBN and TEMPOL significantly attenuated METH self-administration without affecting food intake. Increased oxidative stress was found in neurons, but not astrocytes, microglia or oligodendrocytes, in the NAc of METH self-administering rats. In addition, TEMPOL significantly decreased METH enhancement of DA release in the NAc. Taken together, these results suggest that enhancement of ROS in the NAc contributes to the reinforcing effect of METH.

Effect of acupuncture on Lipopolysaccharide-induced anxiety-like behavioral changes: involvement of serotonin system in dorsal Raphe nucleus.

BACKGROUND: Acupuncture has been used as a common therapeutic tool in many disorders including anxiety and depression. Serotonin transporter (SERT) plays an important role in the pathology of anxiety and other mood disorders. The aim of this study was to evaluate the effects of acupuncture on lipopolysaccharide (LPS)-induced anxiety-like behaviors and SERT in the dorsal raphe nuclei (DRN). METHODS: Rats were given acupuncture at ST41 (Jiexi), LI11 (Quchi) or SI3 (Houxi) acupoint in LPS-treated rats. Anxiety-like behaviors of elevated plus maze (EPM) and open field test (OFT) were measured and expressions of SERT and/or c-Fos were also examined in the DRN using immunohistochemistry. RESULTS: The results showed that 1) acupuncture at ST41 acupoint, but neither LI11 nor SI3, significantly attenuated LPS-induced anxiety-like behaviors in EPM and OFT, 2) acupuncture at ST41 decreased SERT expression increased by LPS in the DRN. CONCLUSIONS: Our results suggest that acupuncture can ameliorate anxiety-like behaviors, possibly through regulation of SERT in the DRN.

In Vitro Effects of Polyphosphate against Prevotella intermedia in Planktonic Phase and Biofilm.

Polyphosphate (polyP) has gained a wide interest in the food industry due to its potential as a decontaminating agent. In this study, we examined the effect of sodium tripolyphosphate (polyP3; Na5P3O10) against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. The MIC of polyP3 against P. intermedia ATCC 49046 determined by agar dilution method was 0.075%, while 0.05% polyP3 was bactericidal against P. intermedia in time-kill analysis performed using liquid medium. A crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that sub-MICs of polyP3 significantly decreased biofilm formation. Under the scanning electron microscope, decreased numbers of P. intermedia cells forming the biofilms were observed when the bacterial cells were incubated with 0.025% or higher concentrations of polyP3. Assessment of biofilm viability with LIVE/DEAD staining and viable cell count methods showed that 0.05% or higher concentrations of polyP3 significantly decreased the viability of the preformed biofilms in a concentration-dependent manner. The zone sizes of alpha-hemolysis formed on horse blood agar produced by P. intermedia were decreased in the presence of polyP3. The expression of the genes encoding hemolysins and the genes of the hemin uptake (hmu) locus was downregulated by polyP3. Collectively, our results show that polyP is an effective antimicrobial agent against P. intermedia in biofilms as well as planktonic phase, interfering with the process of hemin acquisition by the bacterium.

Prevalence and symptomatic correlates of interpersonal trauma in South Korean outpatients with major depressive disorder.

BACKGROUND: There is growing evidence that exposure to severe interpersonal trauma (IPT) has a pivotal role in the development and manifestation of depression. However, it is not clearly understood whether patients with major depressive disorder (MDD) have specifically increased prevalence of IPT than other non-interpersonal traumatic events and whether those with IPT have unique symptom profile within depressed groups. In this study, we investigated the prevalence of past traumatic events and symptomatic features of treatment-seeking outpatients with MDD. METHODS: A consecutive sample of 111 South Korean outpatients with MDD was recruited on their first visit to a psychiatric department of a university-affiliated hospital. Participants completed the Life Events Checklist (LEC), the Symptom Checklist-90-Revised (SCL-90-R), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Dissociative Experience Scale (DES) and Impact of Event Scale-Revised (IES-R). The prevalence of past traumatic events on LEC was compared to medical outpatients. RESULTS: Compared to medical outpatients, MDD patients had significantly higher rates of IPT (physical and sexual) but not other traumatic events of non-interpersonal origin such as accidents or disaster. Compared to MDD patients without IPT (n=44, 40%), those with IPT (n=67, 60%) had higher subscale scores on hostility in SCL-90-R, as well as greater depressive and post-traumatic symptoms. However, multivariate analysis revealed that the best model to discriminate those with IPT was interaction of depressive and posttraumatic symptoms. LIMITATIONS: Limitations include sample characteristics (treatment-seeking outpatients) and possible effects of comorbid conditions, which were not investigated. CONCLUSIONS: Clinicians managing individuals with depressive disorder need to include the assessment of lifetime IPT and its impact on presenting symptoms.

Decreased hemoglobin levels, cerebral small-vessel disease, and cortical atrophy: among cognitively normal elderly women and men.

BACKGROUND: Decreased hemoglobin levels increase the risk of developing dementia among the elderly. However, the underlying mechanisms that link decreased hemoglobin levels to incident dementia still remain unclear, possibly due to the fact that few studies have reported on the relationship between low hemoglobin levels and neuroimaging markers. We, therefore, investigated the relationships between decreased hemoglobin levels, cerebral small-vessel disease (CSVD), and cortical atrophy in cognitively healthy women and men. METHODS: Cognitively normal women (n = 1,022) and men (n = 1,018) who underwent medical check-ups and magnetic resonance imaging (MRI) were enrolled at a health promotion center. We measured hemoglobin levels, white matter hyperintensities (WMH) scales, lacunes, and microbleeds. Cortical thickness was automatically measured using surface based methods. Multivariate regression analyses were performed after controlling for possible confounders. RESULTS: Decreased hemoglobin levels were not associated with the presence of WMH, lacunes, or microbleeds in women and men. Among women, decreased hemoglobin levels were associated with decreased cortical thickness in the frontal (Estimates, 95% confidence interval, -0.007, (-0.013, -0.001)), temporal (-0.010, (-0.018, -0.002)), parietal (-0.009, (-0.015, -0.003)), and occipital regions (-0.011, (-0.019, -0.003)). Among men, however, no associations were observed between hemoglobin levels and cortical thickness. CONCLUSION: Our findings suggested that decreased hemoglobin levels affected cortical atrophy, but not increased CSVD, among women, although the association is modest. Given the paucity of modifiable risk factors for age-related cognitive decline, our results have important public health implications.