Corydaline and l-tetrahydropalmatine attenuate morphine-induced conditioned place preference and the changes in dopamine D2 and GluA1 AMPA receptor expression in rats.

Corydalis is a Chinese herb that has been used in China for hundreds of years for analgesic and other purposes. Corydaline and l-tetrahydropalmatine (l-THP) are the main active ingredients of Corydalis. This study was aimed to study the potential utility of corydaline and l-THP in the treatment of opioid abuse and addiction and explore the possible mechanisms underlying their pharmacological actions. Conditioned place preference (CPP) was used to evaluate the rewarding effects of morphine and Western-blot immunoreactive assays were used to evaluate morphine-induced changes in dopamine D2 receptor and GluA1 AMPA receptor and GluA2 AMPA receptor expression in the brain of rats. Systemic administration of corydaline (5 mg/kg, i.p.) or l-THP (1.25, 2.5,5 mg/kg) significantly inhibited the acquisition and expression of morphine-induced CPP in a dose-dependent manner. Corydaline or l-THP alone, at the same doses, failed to produce CPP or conditioned place aversion, and didn't affect locomotor activity. We then examined the expression of dopamine D2 receptor and GluA1 AMPA receptor and GluA2 AMPA receptor subunit expression in rats after acquisition of morphine-induced CPP. We found that repeated administration of morphine produced a significant reduction in dopamine D2 receptor expression in the prefrontal cortex, hippocamps, and striatum, while an increase in the striatal GluA1 AMPA receptor expression. Pretreatment with corydaline or l-THP blocked morphine-induced dopamine D2 receptor down-regulation and GluA1 AMPA receptor up-regulation in these brain regions. Corydaline and l-THP may have therapeutic potential in prevention and treatment of opioid abuse and addiction. The underlying mechanisms may be related to their antagonism on morphine-induced changes in dopamine and glutamate transmission in the brain.

Protective Effects of Chaihu Shugan San () on Nonalcoholic Fatty Liver Disease in Rats with Insulin Resistance.

OBJECTIVE: To investigate the protective effects of Chinese medicine formulation Chaihu Shugan San (, CHSGS) on nonalcoholic fatty liver disease (NAFLD) in rats with insulin resistance (IR) and its molecular mechanisms. METHODS: Male Sprague-Dawley rats were randomly divided into six groups: the control group, the model group, Dongbao Gantai group (, DBGT, 0.09 g methionine/kg), CHSGS high-dose group (CHSG-H, 12.6 g crude drug/kg), CHSGS medium-dose group (CHSG-M, 6.3 g crude drug/kg), and CHSGS low-dose group (CHSG-L, 3.15 g crude drug/kg). After establishing the NAFLD rat model and treatment for 8 weeks, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), fasting blood glucose (FBG), fasting insulin (FINS) contents in blood serum, and TC, TG contents in the hepatic homogenate were measured by an automatic biochemical analyzer, and a homeostasis model assessment was applied to assess the status of IR, insulin sensitivity index (ISI), and homeostasis model assessment for insulin secretion (HOMA-IS). The expression levels of adiponectin and leptin mRNA in liver tissue were analyzed by reverse transcription polymerase chain reaction. Pathological changes of livers were observed by hematoxylin-eosin staining of paraffin section. RESULTS: Compared with the model group, the serum levels of TC, TG, FFA, FBG, FINS, IRI, ISI, and the liver levels of TC and TG in CHSG-H, CHSG-M, CHSG-L groups showed significant declines (P<0.01 or P<0.05); the serum levels of HDL-C, HOMA-IS were significantly increased (P<0.01 or P<0.05); the expression of leptin mRNA was dramatically decreased and the expression of adiponectin mRNA was increased in the hepatic tissue (P<0.01 or P<0.05). The fatty deposition of liver cells could also be alleviated. CONCLUSION: CHSGS could up-regulate the expression of adiponectin mRNA and down-regulate the expression of leptin mRNA on the liver, suggesting the CHSGS had positive therapeutic effect on NAFLD in rats with IR.

Prospective analysis of patient reported symptoms and quality of life in patients with incurable lung cancer treated in a rapid access clinic.

INTRODUCTION: The Vancouver Rapid Access (VARA) clinic was designed to provide palliative radiotherapy and holistic care to patients with incurable lung cancer. Analysis of the pilot phase demonstrated improved radiotherapy wait-times and access to supportive services compared to standard practice. This study aims to prospectively assess the impact of the clinic on patient reported symptoms and quality of life. MATERIALS AND METHODS: Patient assessments are completed at baseline and by a telephone follow up four-weeks later using Likert scales adapted from the Edmonton Symptom Assessment System (scale 0-10) and European Organization for Research and Treatment of Cancer questionnaires (scale 1-4). Patient reported outcomes at follow-up are compared to baseline using wilcoxon signed-rank test for categorical variables and paired sample t-test for continuous variables. RESULTS: Baseline data was collected on 125 patients, 109 received palliative radiotherapy (87%). At the 4 week follow up, 22 patients had died. Seventy-one of the remaining 103 patients completed the follow-up questionnaire, resulting in a 69% response rate among survivors. The mean patient reported overall health score, improved from 4.8 to 6.1 (p<0.01). All respiratory symptoms except chest pain (p=0.06) were associated with a statistically significant improvement after the clinic, whereas all respiratory symptoms improved post radiotherapy. Mean bone pain scores decreased from 5.5 to 2.7 (p<0.01). Assessment of symptoms secondary to brain metastases is limited by small patient numbers. CONCLUSION: The VARA clinic provides timely access to palliative radiotherapy and supportive services resulting in improved patient reported outcomes. Despite a high symptom and disease burden, patients report improved overall health and palliation of respiratory symptoms and bony pain. The studies completed on the VARA clinic to date, continue to support its value in our center.

Incidence of second malignancies in prostate cancer patients treated with low-dose-rate brachytherapy and radical prostatectomy.

PURPOSE: To compare the second malignancy incidence in prostate cancer patients treated with brachytherapy (BT) relative to radical prostatectomy (RP) and to compare both groups with the cancer incidence in the general population. METHODS AND MATERIALS: From 1998 to 2010, 2418 patients were treated with Iodine 125 prostate BT monotherapy at the British Columbia Cancer Agency, and 4015 referred patients were treated with RP. Cancer incidence was compared with the age-matched general population using standardized incidence ratios (SIRs). Pelvic malignancies included invasive and noninvasive bladder cancer and rectal cancer. Cox multivariable analysis was performed with adjustment for covariates to determine whether treatment (RP vs BT) was associated with second malignancy risk. RESULTS: The median age at BT was 66 years and at RP 62 years. The SIR comparing BT patients with the general population was 1.06 (95% confidence interval [CI] 0.91-1.22) for second malignancy and was 1.53 (95% CI 1.12-2.04) for pelvic malignancy. The SIR comparing RP patients with the general population was 1.11 (95% CI 0.98-1.25) for second malignancy and was 1.11 (95% CI 0.82-1.48) for pelvic malignancy. On multivariable analysis, older age (hazard ratio [HR] 1.05) and smoking (HR 1.65) were associated with increased second malignancy risk (P<.0001). Radical prostatectomy was not associated with a decreased second malignancy risk relative to BT (HR 0.90, P=.43), even when excluding patients who received postprostatectomy external beam radiation therapy (HR 1.13, P=.25). Older age (HR 1.09, P<.0001) and smoking (HR 2.17, P=.0009) were associated with increased pelvic malignancy risk. Radical prostatectomy was not associated with a decreased pelvic malignancy risk compared with BT (HR 0.57, P=.082), even when excluding postprostatectomy external beam radiation therapy patients (HR 0.87, P=.56). CONCLUSIONS: After adjustment for covariates, BT patients did not have an increased second malignancy risk compared with RP patients. Further follow-up of this cohort is needed given the potential latency of radiation-induced malignancies.