13^th World Congress on Pharmacology and Toxicology November 14-15, 2018 | Mercure Albert Park | Melbourne, Australia

Our research goal is to understand the synaptic mechanisms involved in the pathophysiology of chronic pain and psychiatric disorders. We try to understand how brain circuit modulates neuronal transmission in midbrain periaqueductal gray, which is an critical region of midbrain for controlling of pain and emotion. We also try to understand how the analgesic compounds and antidepressants regulate pain and depression leads to therapeutic efficacy in the brain, especially in the periaqueductal gray.

Statement of the Problem: Major depressive disorder affecting more than 100 million people worldwide every year is a heterogeneous illness. To date, current pharmacotherapies require prolonged administration from several weeks to months for an appreciable response. This is particularly concerning given that suicide risk is elevated in subjects with depression. Methodology & Theoretical Orientation: It is still unclear that whether ketamine metabolite (2R,6R-hydroxynorketamine; 2R,6R-HNK) rescues chronic stress-elicited depression-like behavior. Depression-like behavior in the rats were induced by learned helplessness (LH) procedure. Forced swim test (FST) and sucrose preference test (SPT) were used to study the depression-like behavior. Findings: Rats receiving learned helplessness procedure exhibited high failure rate in the escapable footshock test compared to control group. LH rats exhibited an increase in immobile time during the FST and a reduction in sucrose consumption. Intraperitoneal ketamine metabolite, 2R,6R-HNK, injection decreased immobile time during the FST and increased sucrose consumption in LH rats. Conclusion & Significance: Ketamine metabolite 2R,6R-HNK rescues LH-induced depression-like behavior including despair behavior and anhedonia. These results may pave the foundation for a critical issue that ketamine metabolite, 2R,6R-HNK plays crucial roles in stress-induced depression-like behaviors and provides a new insight into depression management and development of antidepressants.

Yuhong Guo, who received a bachelor's degree from Hunan Medical Sciences University (1994-1999), has his expertise in studying traditional Chinses herbal medicines on ICU diseases. She also engaged in pathogenesis of sepsis, psoriasis, and inflammatory diseases. She is now continuing her research work in Beijing Hospital of Traditonal Chinese Medicine and Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases.

Sepsis is reported to be an unusual systemic reaction to infection, accompanied by multiple-organ failure. Sepsis-induced cardiomyopathy, defined as damages and dysfunction of the heart, is essential in the pathogenesis of sepsis. Traditional Chinese formula, which has long been used to improve the situation of patients through multitarget regulation, is now gradually being used as complementary therapy. The present study aimed to investigate the effect of Qiang-Xin 1 (QX1) formula, a traditional Chinese herbal medicine designed for cardiac dysfunction, on cecal ligation puncture (CLP)-induced heart damage and its underlying mechanisms in mice. Survival test first showed that an oral administration of QX1 formula significantly increased the 7-day survival of septic mice from 22% to 40%. By estimating the secretion of serum cytokines, QX1 treatment dramatically inhibited the excessive production of interleukin-1β and tumor necrosis factor-α. Immunohistochemical staining illustrated that the expression of c-Jun N-terminal kinase, caspase-12, and high-mobility group box 1 was downregulated in cardiomyocytes of the QX1-treated group compared with that of the CLP surgery group. Western blotting confirmed that the activation of essential caspase family members, such as caspase-3, caspase-9, and caspase-12, was prohibited by treatment with QX1. Moreover, the abnormal expression of key regulators of endoplasmic reticulum and mitochondria-associated apoptosis in cardiomyocytes of septic mice, including CHOP, GRP78, Cyt-c, Bcl-2, Bcl-XL, and Bax, was effectively reversed by treatment with QX1 formula. This study provided a new insight into the role of QX1 formula in heart damage and potential complementary therapeutic effect of traditional Chinese medicine on sepsis.

Objective: To report a case of ceftazidime-induced encephalopathy. The occurrence of this adverse drug reaction is rare. Case summary: An 85-year-old female with hypertensive cardiovascular disease, dyslipidemia, and uremia under hemodialysis (twice a week) was admitted. Patient suffered from coronary heart disease before admission and being maintained hemodialysis on 19 Dec, 2017. During hospitalization, Augmentin (amoxicillin sodium 1000mg +clavulanate 200mg) 1.2gm once daily was initiated due to suspected infection on 24 Dec, 2017. After consulting the infection specialist for better infectious control, he recommended ceftazidime 2gm once daily instead of Augmentin on 26 Dec, 2017. Consequently, the patient presented inability to stand and to repeat what other people said, and her left limb was involuntarily shaking on 29 Dec, 2017. Hyperammonemia and hyperureaemia could be ruled out for the patient was not noted to have liver disease or regular hemodialysis. The physician suspected that the cause might be stroke or drug-related encephalopathy, followed by arrangement of MRI and discontinuation of ceftazidime on 31 Dec, 2017. The patient still showed confusion and delirium, as a result, the nephrologist set up extra hemodialysis for toxin removal on 1 Jan, 2018. Two days later, the patient returned to normal on 3 Jan, 2018. Magnetic resonance imaging (MRI) report indicated that the infarction was obsolete, therefore, the neurologist excluded the possibility of stroke on 5 Jan, 2018. The assessment was 6 points by Naranjo Score and the ceftazidime-related encephalopathy was highly suspected after the overall assessment. Eventually, the patient was discharged on 16 Jan, 2018. Discussion: Ceftazidime is a third-generation Cephalosporin antibiotic that is commonly used in hospitals to treat pneumonia and urinary tract infection due to its broad spectrum of antibacterial activity. In this case, the dosage and frequency of ceftazidime did not address overdose. The neuro-related adverse reaction of ceftazidime was seizure (frequency not defined) instead of encephalopathy recorded in UpToDate database. However, we still could not exclude the possibility of encephalopathy because ceftazidime can penetrate the cerebrospinal fluid to impair the neurological function Conclusion: We should pay more attention to the unusual behavior of patients and be cautious about the risk of ceftazidime-induced encephalopathy despite its rarity.

Objective: Taiwan's Disease Control Department invests a lot of effort in flu epidemic prevention. The reason is that the influenza outbreak has a rapid spread and spread. Widespread and severe complications may lead to viral or bacterial pneumonia leading to higher medical expenditures. Aim : We want to analyze the patient use of publicly-funded anti-viral drugs to understand the regional epidemic and people's ways of seeking medical care. Through this statistics we want to provide professional services from pharmacists. Method: Retrospective analysis of patients receiving publicly-funded antiviral agents (just Tamiflu) from November 2017 to May 2018 after attending out-patient clinics. Patients are divided into the following categories base on the date of administration, age, and the conditions of the subjects to be used. 1. Flu-like patients with danger signs；2. Flu-like patients with incomplete immunity, or heart and lung vascular disease, liver, kidney, and diabetes；3. Pregnant women are evaluated for prompt use；4. Influenza patients under the age of 5 and over 65；5. Family/colleagues/classmates with flu-like illness；6. Diagnosed or suspected suffering from influenza and need hospitalization. We collect those data to analyze and discuss. Result: The public antiviral treatment were received total 836 people. Patients’ aged below 10 years old was the highest number , with a total of 311 people (37.2%)；The second highest age group is 11-20 years old, a total of 168 people (20%).The major indicate for using publicly-funded antiviral agents is「Family/colleagues/classmates with flu-like illness」, with a total of 570 people (68.1%). The second highest category is 「Diagnosed or suspected suffering from influenza and need hospitalization」 , with a total of 216 people (25.8%). Conclusion: From the data analysis ,the major using public antiviral drugs were under 20 years of age .We seems need do more effort on communicating influenza vaccines’ benefit to increase the willingness of taking vaccine. Pharmacists can provide more information about influenza vaccines in patient education. Let people understand the role of vaccines and antivirus drug using timing in order to achieve the goal of prevention.

Dysfunction of intestinal epithelial barrier is crucial in the pathological process of intestinal and systemic diseases. Ferulic acid (FA) has been well established to possess promising antioxidant activities. Our previous research demonstrated the potentially protective effects of FA against heat stress-induced intestinal epithelial barrier dysfunction in IEC-6 cells. However, the underlying mechanisms are unclear. This study aimed to elucidate whether FA protected IEC-6 cells from heat stress-induced intestinal epithelial barrier dysfunction via anti-oxidative mechanisms. IEC-6 cells were pretreated with FA prior to hyperthermia exposure at 42ï‚°C for 6 h, and the levels of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), nitrogen oxide (NO), and superoxide dismutase (SOD) activity were analyzed. The results showed FA suppressed heat stress-induced intestinal oxidative stress damage by reducing ROS, MDA and NO production, while enhancing SOD activity. Furthermore, FA treatment strengthened intestinal barrier function via increasing the phosphorylation levels of Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1) protein expression, which was reversed by zinc protoporphyrin (an HO-1 inhibitor). Additionally, LY294002, a specific PI3K/Akt inhibitor, significantly suppressed the FA-induced Nrf2 nuclear translocation and HO-1 protein expression, and inhibited FA-induced occludin and ZO-1 protein expression. FA protected IEC-6 cells against heat stress-induced intestinal epithelial barrier dysfunction via activating the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway.

Background: Benzbromarone is an uricosuric agent to control hyperuricemia. The hypouricemic effect of benzbromarone may be limited in patients with renal insufficiency. Objectives: This study try to determine if it is effective to the use of benzbromarone in patients with chronic kidney disease (CKD). Method: We retrospectively evaluated serum urate level and renal function changes in 133 patients with stage 3-5 CKD (120 patients in stage 3, 11 patients in stage 4, and 2 patients in stage 5) in a regional hospital between March 2012 and October 2017. They newly received 25-150 mg/day benzbromarone monotherapy for hyperuricemia. The main outcome such as serum urate level, serum creatinine level, and estimated glomerular filtration rate (eGFR) were measured before and after benzbromarone monotherapy. The statistical method we used was the paired sample t-test. Result: This study analyzed 96 men and 37 women aged from 38 to 91 years. Serum urate level significantly decreased from 9.30±1.39 to 5.94 ± 2.06 mg/dL (P<0.001) within the first 6 months. No significant changes in the renal function within the first 6 months: serum creatinine level was from 1.60±0.63 to 1.59 ±0.63 mg/dL (P=0.902); eGFR was from 46.00±10.83 to 46.22 ± 11.53 mL/minute/1.73 m2 (P=0.677). Conclusion: Although renal insufficiency was not improved by lowering serum urate level with benzbromarone, there was no significantrenal function deterioration. The results suggested that benzbromarone was applicable for hyperuricemic patients with CKD.

Jia-Yin Ma has completed her master’s from Chung Yuan Christian University. Her specialization is in Cancer Psychology and is also a Clinical Psychologist of Taipei City Hospital in Taiwan.

This study aims to consider the adaptation process of disease within breast cancer patients and their partners, including communication pattern, the perceived quality of the relationship and quality of life. This study is a cross-sectional design and 257 breast cancer patients and their partners are participated. As analysis methods, we applied correlation analysis,difference analysis, multiple regression analysis and dyadic data analysis through the Actor-Partner Interdependence Model(APIM). The results revealed the points as followed: (1) Not only patients but their partners perceived themselves are demanddiscussion and others are withdraw-discussion, they have worse satisfactory quality of relationship. (2) By using the APIM, the consequence revealed that the cancer-related communication pattern of each person is the strongest predictor of their own quality of relationship. The communication pattern of woman breast cancer patient’s perception also plays a significant role on their male partner’s quality of relationship. (3) Quality of relationship is a mediator variable between the cancerrelated communication patterns and quality of life. For patients, quality of relationship is consistent with full mediated between the cancer-related communication patterns and all domain of quality of life. In conclusion, disease does have an impact on relationship. Besides, for cancer patients and their partners, we encourage partners to accompany patients for medical treatment, be patient’s primary caregiver, and provide more assistance to patients. Clinicians should be aware of the communication between the patients and their partners in order to help them to improve their communication skills and the quality of their relationship.