Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.
Rats ; Animals ; Rats, Sprague-Dawley ; Stress Disorders, Post-Traumatic ; Receptors, AMPA ; 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology* ; Receptors, Glutamate/metabolism* ; Amygdala ; Weight Gain ; Medulla Oblongata/physiology* ; Blood Pressure

OBJECTIVE: To investigate effects of physiological hypoxic conditions on suspension and adherence of embryoid bodies (EBs) during differentiation of human induced pluripotent stem cells (hiPSCs) and explore the underlying mechanisms. METHODS: EBs in suspension culture were divided into normoxic (21% O₂) and hypoxic (5% O₂) groups, and those in adherent culture were divided into normoxic, hypoxic and hypoxia + HIF-1α inhibitor (echinomycin) groups. After characterization of the pluripotency with immunofluorescence assay, the hiPSCs were digested and suspended under normoxic and hypoxic conditions for 5 days, and the formation and morphological changes of the EBs were observed microscopically; the expressions of the markers genes of the 3 germ layers in the EBs were detected. The EBs were then inoculated into petri dishes for further culture in normoxic and hypoxic conditions for another 2 days, after which the adhesion and peripheral expansion rate of the adherent EBs were observed; the changes in the expressions of HIF-1α, β-catenin and VEGFA were detected in response to hypoxic culture and echinomycin treatment. RESULTS: The EBs cultured in normoxic and hypoxic conditions were all capable of differentiation into the 3 germ layers. The EBs cultured in hypoxic conditions showed reduced apoptotic debris around them with earlier appearance of cystic EBs and more uniform sizes as compared with those in normoxic culture. Hypoxic culture induced more adherent EBs than normoxic culture (P < 0.05) with also a greater outgrowth rate of the adherent EBs (P < 0.05). The EBs in hypoxic culture showed significantly up-regulated mRNA expressions of β-catenin and VEGFA (P < 0.05) and protein expressions of HIF-1 α, β-catenin and VEGFA (P < 0.05), and their protein expresisons levels were significantly lowered after treatment with echinomycin (P < 0.05). CONCLUSION Hypoxia can promote the formation and maturation of suspended EBs and enhance their adherence and post-adherent proliferation without affecting their pluripotency for differentiation into all the 3 germ layers. Our results provide preliminary evidence that activation of HIF-1α/β-catenin/VEGFA signaling pathway can enhance the differentiation potential of hiPSCs.
Echinomycin/metabolism* ; Embryoid Bodies/metabolism* ; Humans ; Hypoxia/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; beta Catenin/metabolism*

timolol, brimonidine, and latanoprost) to lower their IOP, which subsequently was changed to double maximum medical therapy (DMT, fixed drug combinations of tafluprost/timolol and brinzolamide/brimonidine). The rate of IOP change and adverse drug reactions were compared amongst the three age groups.RESULTS: The mean IOP change at three months after converting from TMT to DMT was −0.65 ± 1.42 mmHg (−3.84% ± 9.31%) among the overall study group, but this finding was not statistically significant (p = 0.108). In the 40 to 54 years and 55 to 69 years groups, the mean IOP change rates were +0.29 ± 0.96 mmHg (+2.40% ± 6.85%, p = 0.087) and −0.50 ± 0.99 mmHg (−3.05% ± 6.40%, p = 0.084) respectively. In the 70 years or older group, the mean IOP change, interestingly, was −1.80 ± 1.46 mmHg (−11.29% ± 9.31%, p < 0.001) and nine (47.4%) of the 19 subjects showed additional IOP reductions of 10% or more after converting from TMT to DMT. In all three age groups, the incidence rate of dry eye was significantly lower for DMT than for TMT (p = 0.031).CONCLUSIONS: In POAG patients, DMT was proven to be both effective and safe for lowering the IOP, especially in those 70 years or older group, when compared with the TMT protocol.]]>
Brimonidine Tartrate ; Disease Management ; Drug Combinations ; Drug-Related Side Effects and Adverse Reactions ; Glaucoma, Open-Angle ; Humans ; Incidence ; Intraocular Pressure ; Retrospective Studies

OBJECTIVE: To explore the effect and possible mechanism of PI3K/mTOR inhibitor XL765 on KG-1 cells in vitro. METHODS: The effect of XL765 on cell proliferation was detected by CCK-8 assay. The colony formation test (200 cells were plated in a plate for 9 days) was used to detect the effect of XL765 on the colony forming ability of KG-1 cells. The apoptosis was assessed by flow cytometry with Annexin V-FITC/PI double staining. Quantitative real-time polymerase chain reaction (q-PCR) was used to detect the expression of cell apoptosis-related genes BCL-2, BAX and caspase-3, Western blot was performed to detect the expression levels of BCL-2, BAX, Caspase-3, and the phosphorylation change of p-PI3K, p-AKT and p-S6K. RESULTS: XL765 effectively inhibited the proliferation and the colony formation of KG-1 cells (P=0.0002). XL765 (150 nmol/L) induced KG-1 cell apoptosis (31.87±1.376%), very statistically significant different from (3.533±0.4179% ) in the control group (P＜0.01). Treatment with 150 nmol/L XL765 could in a significantly increase the expression levels of BAX and active caspase-3, and decreases expression level of the BCL-2 (P＜0.01). In accordance with these results, the Western blot further confirmed the expression decrease of BCL-2 protein along with the increase BAX and cleaved caspase-3 activity. XL765 statistically significantly down-regulated the phosphorylation levels of PI3K, AKT and S6K. CONCLUSION PI3K/mTOR inhibitor XL765 substantially suppresses KG-1 cell proliferation and induces apoptosis by inhibiting the activation of PI3K-AKT-mTOR signaling pathway, and regulating the apoptosis-related proteins.
Apoptosis ; Cell Line, Tumor ; Humans ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Quinoxalines ; Signal Transduction ; Sulfonamides ; TOR Serine-Threonine Kinases

BACKGROUND: Although the number of medical institutions running a smoking cessation clinic is on the rise, there remains a paucity of research on the long- and short-term success rates of smoking cessation programs, as well as on smoking relapse rates, before and after project implementation. This study assessed the general characteristics of patients visiting the smoking cessation clinic, success rate of smoking cessation in the short term, and risks of relapse. METHODS: Medical records from March 2015 to April 2017 were analyzed and telephone surveys were conducted with 151 smokers who visited a hospital smoking cessation clinic from March 2015 to April 2017. RESULTS: Of the 139 smokers who were eligible for follow-up, 22 (15.8%) failed to quit smoking initially. The clinic's 6-month success rate of smoking cessation was 64.83%. Those with higher medication compliance had a lower risk of primary failure (odds ratio, 0.056; 95% confidence interval, 0.005–0.609), whereas those with higher age (hazard ratio [HR], 0.128; P=0.0252) and a greater number of visits to the clinic (HR, 0.274; P=0.0124) had a lower risk of relapsing. CONCLUSION: The risk of primary failure to quit was higher with low medication compliance, and that of relapsing was higher with lower age and fewer number of clinic visits. Various evaluation and analysis methods can be carried out in the future based on the accumulated data for maintenance of smoking cessation and relapse prevention.
Ambulatory Care ; Follow-Up Studies ; Humans ; Medical Records ; Medication Adherence ; Recurrence ; Running ; Secondary Prevention ; Smoke ; Smoking Cessation ; Smoking ; Telephone ; Varenicline

OBJECTIVES: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. METHODS: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. RESULTS: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/ varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. CONCLUSION: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.
Antidepressive Agents ; Antipsychotic Agents ; Aripiprazole ; Benzodiazepines ; Cholinergic Antagonists ; Clinical Decision-Making ; Clozapine ; Consensus ; Depression ; Dihydroergotamine ; Drug Therapy ; Humans ; Injections, Intramuscular ; Metformin ; Naltrexone ; Propranolol ; Psychiatry ; Schizophrenia ; Serotonin Uptake Inhibitors ; Substance-Related Disorders ; Suicide ; Varenicline

Quitting smoking helps smokers maintain their health and extend their lifespan by 10 or more years. Treatment strategies for smoking cessation should be tailored to individual smokers with special needs based on their specific circumstances. It is recommended that pregnant women adopt smoking cessation through counseling and behavioral interventions because the safety of medications has yet to be established. Counseling is the main strategy for smoking cessation in adolescents and nicotine replacement therapy can be used with caution in individuals with serious nicotine dependence. It is important for smokers with psychiatric diseases to quit smoking following accurate assessment of their depression status. Nicotine replacement therapy, varenicline, and bupropion can be used for smoking cessation in smokers with psychiatric disorders. The incidence of cardiovascular disease decreased according to the smoking status and the duration of smoking cessation. In smokers with chronic obstructive pulmonary disease (COPD) who used a combination of counseling and pharmacotherapy the quitting rate was more than twice as high as subjects who used behavioral interventions alone. Varenicline can be used as the most effective anti-smoking drug by most smokers including those with psychiatric disorders, cardiovascular disease, and COPD.
Adolescent ; Bupropion ; Cardiovascular Diseases ; Counseling ; Depression ; Drug Therapy ; Female ; Humans ; Incidence ; Nicotine ; Pregnant Women ; Pulmonary Disease, Chronic Obstructive ; Smoke* ; Smoking Cessation* ; Smoking* ; Tobacco Use Disorder ; Varenicline

Botulinum toxin type A (BoNT/A) has been used therapeutically for various conditions including dystonia, cerebral palsy, wrinkle, hyperhidrosis and pain control. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) receive orofacial nociceptive information from primary afferents and transmit the information to higher brain center. Although many studies have shown the analgesic effects of BoNT/A, the effects of BoNT/A at the central nervous system and the action mechanism are not well understood. Therefore, the effects of BoNT/A on the spontaneous postsynaptic currents (sPSCs) in the SG neurons were investigated. In whole cell voltage clamp mode, the frequency of sPSCs was increased in 18 (37.5%) neurons, decreased in 5 (10.4%) neurons and not affected in 25 (52.1%) of 48 neurons tested by BoNT/A (3 nM). Similar proportions of frequency variation of sPSCs were observed in 1 and 10 nM BoNT/A and no significant differences were observed in the relative mean frequencies of sPSCs among 1–10 nM BoNT/A. BoNT/A-induced frequency increase of sPSCs was not affected by pretreated tetrodotoxin (0.5 µM). In addition, the frequency of sIPSCs in the presence of CNQX (10 µM) and AP5 (20 µM) was increased in 10 (53%) neurons, decreased in 1 (5%) neuron and not affected in 8 (42%) of 19 neurons tested by BoNT/A (3 nM). These results demonstrate that BoNT/A increases the frequency of sIPSCs on SG neurons of the Vc at least partly and can provide an evidence for rapid action of BoNT/A at the central nervous system.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Botulinum Toxins* ; Botulinum Toxins, Type A* ; Brain ; Central Nervous System ; Cerebral Palsy ; Dystonia ; Hyperhidrosis ; Mice* ; Neurons* ; Substantia Gelatinosa* ; Synaptic Potentials* ; Tetrodotoxin

Administration, Oral ; Anti-Bacterial Agents ; administration & dosage ; Brimonidine Tartrate ; administration & dosage ; Diagnosis, Differential ; Doxycycline ; administration & dosage ; Face ; physiopathology ; Female ; Humans ; Inflammation ; Middle Aged ; Rosacea ; diagnosis ; drug therapy ; Singapore ; Steroids ; administration & dosage ; Treatment Outcome

PURPOSE: To compare the allergy prevalence and clinical manifestations of 0.2% brimonidine/0.5% timolol fixed combination (BTFC) and 0.15% brimonidine in Korean patients with glaucoma. METHODS: We retrospectively analyzed the medical records of 196 glaucoma patients treated with BTFC and 234 glaucoma patients treated with 0.15% brimonidine. We compared sex, age, type of glaucoma, treatment period, allergy history, onset time of ocular allergy and clinical characteristics of allergy in the two groups. RESULTS: Ocular allergy percentages 10.14% in the BTFC group and 22.02% in the 0.15% brimonidine group, and the risk of allergy was approximately 0.4 times lower in patients using BTFC (hazard ratio = 2.5, p = 0.009). The BTFC group developed ocular allergy at a mean of 20.5 months (range: 1.7–51.1 months), and the 0.15% brimonidine group developed ocular allergy at a mean of 7.7 months (range: 0.4–50.8 months). In the BTFC group, 50% of the ocular allergy occurred within 15 months, and within 5 months in the 0.15% brimonidine group. Clinical characteristics of brimonidine allergy involved two types of conjunctival follicles and conjunctival papillae, but there were no significant differences in incidence according to allergy type (p = 0.566). CONCLUSIONS: The prevalence of ocular allergy in the BTFC group was lower than that in the 0.15% brimonidine group in Korean patients with glaucoma. The results of this study are expected to be useful for patient education and compliance improvement using brimonidine.
Brimonidine Tartrate ; Compliance ; Glaucoma ; Humans ; Hypersensitivity ; Incidence ; Medical Records ; Patient Education as Topic ; Prevalence ; Retrospective Studies ; Timolol