DA-9701 on gastric motility in patients with Parkinson's disease: A randomized controlled trial.

INTRODUCTION: To evaluate the effect of DA-9701, a novel prokinetic drug, on gastric motility evaluated by magnetic resonance imaging in patients with Parkinson's disease (PD). METHODS: Forty PD patients were randomly allocated to receive either domperidone or DA-9701. Their gastric functions were evaluated using magnetic resonance imaging before and after 4-week treatment period. Information on levodopa daily dose, disease duration, and Unified PD Rating Scale scores was collected. In 18 patients (domperidone: 9, DA-9701: 9), plasma levodopa concentrations were determined. Primary outcome was assessed by a one-sided 95% confidence interval to show non-inferiority of DA-9701 vs. domperidone with a pre-determined non-inferiority margin of -10%. RESULTS: Thirty-eight participants (19 men and 19 women; mean age, 67.1 years) completed the study protocol (domperidone: DA-9701 = 19:19). Gastric emptying rate at 120 min (2-hr GER) was comparable between the 2 groups; it was not correlated with levodopa daily dose or disease duration or Unified PD Rating Scale scores (all p > 0.05). DA-9701 was not inferior to domperidone in changes of 2-hr GERs before and after the treatment (absolute difference, 4.0 %; one-sided 95% confidence interval, - 3.7 to infinity). However, a significant increase in 2-hr GER was observed only in DA-9701 group (54.5% and 61.8%, before and after treatment, respectively, p < 0.05). Plasma levodopa concentration showed an insignificant but increasing trend in DA-9701 group. There were neither adverse reactions nor deteriorations of parkinsonian symptoms observed in the study participants. CONCLUSION: DA-9701 can be used for the patients with PD to enhance gastric motility without aggravating PD symptoms (ClinicalTrials.gov number: NCT03022201).

Therapeutic effect of microcurrent on calf muscle atrophy in immobilized rabbit.

INTRODUCTION: Immobilization causes significant muscle loss. In this study we assessed the regenerative effect of microcurrent electrical stimulation (MES) on gastrocnemius muscle (GCM) atrophy induced by immobilization by cast (IC) in rabbits. METHODS: Fifteen rabbits were divided into 3 groups: IC (group 1); IC and free re-ambulation for 2 weeks after cast removal (CR) (group 2); and IC and MES for 2 weeks after CR (group 3). We evaluated clinical parameters (calf circumference, compound muscle action potential of tibial nerve, and thickness of GCM by ultrasound), histomorphometric data (muscle composition and cross-sectional area), and immunohistochemistry. RESULTS: Mean atrophic changes in clinical parameters in group 3 were significantly less than those in groups 1 and 2 (P < 0.05). Histomophometric and immunohistochemical parameters in group 3 were significantly greater than those in groups 1 and 2, respectively (P < 0.05). DISCUSSION: MES prevents muscle atrophy and facilitates regeneration of muscle. Muscle Nerve 58: 270-276, 2018.

Sentinel node mapping of VX2 carcinoma in rabbit thigh with CT lymphography using ethiodized oil.

OBJECTIVE: To assess the feasibility of computed tomography (CT) lymphography using ethiodized oil for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh. MATERIALS AND METHODS: This experiment received approval from the institutional animal use and care administrative advisory committee. Twenty-three rabbits with VX2 carcinoma in the thigh underwent CT before and after (1 hour, 2 hour) peritumoral injection of 2 mL ethiodized oil. After the CT examination, sentinel nodes were identified by peritumoral injection of methylene blue and subsequently removed. The retrieved sentinel and non-sentinel lymph nodes were investigated with radiographic and pathologic examinations. Based on the comparison of CT findings with those of radiographic and pathologic examinations, the diagnostic performance of CT for sentinel node identification was assessed. RESULTS: All 23 rabbits showed 53 ethiodized oil retention nodes on post-injection CT and specimen radiography, and 52 methylene blue-stained nodes at the right femoroiliac area. Of the 52 blue-stained sentinel nodes, 50 nodes demonstrated ethiodized oil retention. Thus, the sentinel node detection rate of CT was 96% (50 of 52). On pathologic examination, 28 sentinel nodes in 17 rabbits (nodes/rabbit, mean ± standard deviation, 1.7 ± 0.6) harbored metastasis. Twenty seven of the 28 metastatic sentinel nodes were found to have ethiodized oil retention. CONCLUSION: Computed tomography lymphography using ethiodized oil may be feasible for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh.

Early gastric cancer: feasibility of CT lymphography with ethiodized oil for sentinel node mapping.

PURPOSE: To evaluate the feasibility of CT lymphography with ethiodized oil for sentinel node mapping in porcine stomachs and in patients with early gastric cancer. MATERIALS AND METHODS: Approval for the animal study was obtained from the authors' institutional animal use and care administrative advisory committee, the clinical study was approved by the institutional review board, and informed consent was obtained from each participant. Five pigs underwent CT lymphography 1 hour after gastric subserosal injection of 1 mL ethiodized oil and sentinel node mapping with injection of 1 mL methylene blue. Ethiodized oil retention nodes were identified on the radiographic images of the gastric specimen and removed for histopathologic examination. In addition, 10 patients with early gastric cancer underwent CT lymphography with peritumoral injection of 1 mL ethiodized oil, followed by sentinel basin extirpation with CT and routine nodal dissection. The removed sentinel basins were examined by radiography. Histopathologic examination was performed for dissected nodes, including sentinel nodes. RESULTS: In each of the five pigs, CT showed one perigastric ethiodized oil retention node. After harvesting the ethiodized oil retention node, blue-stained areas were identified in the five removed nodes and intranodal ethiodized oil was detected on histopathologic examination. In all 10 patients, CT lymphography with ethiodized oil successfully defined the sentinel basin with ethiodized oil retention nodes. CT lymphography revealed 20 ethiodized oil retention nodes. After basin extirpation, 28 and 46 nodes were detected on radiographic and histopathologic examinations. Histopathologic examination revealed that one patient had micrometastases at two sentinel nodes and another patient had isolated tumor cells at one sentinel node. No patient had metastasis in nonsentinel nodes. CONCLUSION: CT lymphography with ethiodized oil may be a feasible method for sentinel node mapping in patients with early gastric cancer.

Berberine inhibits human colon cancer cell migration via AMP-activated protein kinase-mediated downregulation of integrin ß1 signaling.

Colon cancer is associated with a poor prognosis, motivating strategies to prevent its development. An encouraging preventative strategy is the use of nutraceuticals; however, scientific verification of therapeutic functions and mechanisms of biological activity are necessary for the acceptance of dietary supplements in cancer treatment. Berberine is a benzylisoquinoline alkaloid extracted from many kinds of medicinal plants that has been extensively used as a Chinese traditional medicine. Recently, berberine has been reported to possess antitumoral activities. Among the various cellular targets of berberine is AMP-activated protein kinase (AMPK), which regulates tumor progression and metastasis. However, the specific role of berberine-induced AMPK activation and its effects on the metastatic potential of colon cancer remain largely unknown. The present study investigated berberine-induced activation of AMPK and its effects on colon cancer cell migration. Berberine decreased the migration of SW480 and HCT116 cells. We found that berberine activated AMPK in human colon cancer cell lines. Notably, berberine-induced activation of AMPK reduced the integrin ß1 protein levels and decreased the phosphorylation of integrin ß1 signaling targets. Knockdown of AMPKα1 subunits using small interfering RNA significantly attenuated berberine-induced downregulation of integrin ß1 and inhibition of tumor cell migration. Collectively, our results suggest that berberine-induced AMPK activation inhibits the metastatic potential of colon cancer cells by decreasing integrin ß1 protein levels and downstream signaling.