Effect of monoamine oxidase A and B inhibition on the uptake and metabolism of serotonin within serotonergic neurons of rat brain

The effects of inhibiting monoamine oxidase (MAO) A and B on metabolism and uptake of serotonin (5-HT) in serotonergic synaptosomes were studied. To avoid contamination by extrasynaptosomal MAO, synaptosomes were separated from other components of rat brains by discontinuous sucrose density gradient centrifugation. Kinetic analysis of 5-HT uptake demonstrated that 5-HT was selectively transported into serotonergic synaptosomes through the high affinity 5-HT uptake process. Selectivity of the uptake and subsequent deamination of 5-HT within serotonergic synaptosomes were confirmed using selective and non-selective 5-HT and norepinephrine (NE) uptake inhibitors. MAO inhibitor analysis of 5-HT deamination occurring within serotonergic synaptosomes indicated that, at physiologically relevant concentrations of 5-HT, MAO A deaminates 5-HT, maintaining a low cytoplasmic concentration of 5-HT. When the cytoplasmic concentration of 5-HT is increased above physiologically relevant levels by the inhibition of MAO A, MAO B becomes active. [( 14)C] 5-HT uptake into synaptosomes was reduced by decreasing the V( max) of [(14)C] 5-HT uptake. One mechanism for a decrease in the V(max) could be the increase in the cytoplasmic concentration of 5-HT.     

Postoperative adjuvant therapy for stage II non-small-cell lung cancer

BACKGROUND: Stage II non-small-cell lung cancer is regarded as one of the early lung cancers. Although resection, including the mediastinal lymph nodes, is currently regarded as the standard treatment, the survival rate of this disease is not encouraging. It is well known that the most common causes of death are locoregional recurrences or distant metastases, or both. However, the best adjuvant treatment to improve survival is as controversial an issue as ever. METHODS: This study was designed as a randomized, blinded, two-armed study with operation and adjuvant radiotherapy in one arm, versus operation and adjuvant mitomycin C (10 mg/m2), vinblastine (6 mg/m2), and cisplatin (100 mg/m2) (MVP) chemotherapy in the other arm. We assigned 57 resected patients with pathologic proven stage II non-small cell lung cancer to the groups according to our eligibility criteria. RESULTS: The most common pattern of recurrence was distant metastases, and nearly all the recurrences (17 of 18 patients) in both groups were found within 2 years after operation. The rates of the locoregional and distant metastases were 3.6% and 46.4% in the adjuvant radiotherapy group and 6.9% and 10.3% in the adjuvant chemotherapy group (p = 0.018). The 5-year disease-free survival rates were 52.0% in the adjuvant radiotherapy group and 74.0% in the adjuvant chemotherapy group (p = 0.16, log-rank test). The 2-year, 5-year, and 6-year survival portions were 60.3%, 56.5%, and 28.3% in the adjuvant radiotherapy group, and 82.8%, 70.1%, and 60.1% in the adjuvant chemotherapy group (p = 0.01, p = 0.17, and p = 0.03, Z-test). The difference of the actuarial survival between these two groups was somewhat significant (p = 0.09, log-rank test). CONCLUSIONS: Our results suggest that the addition of adjuvant MVP chemotherapy may reduce the distant metastasis rates and prolong the survival of the surgically resected stage II non-small-cell lung cancer patients.     

Fifteen years' experience with an antirefluxing biliary drainage valve

PURPOSE: The aim of this study was to examine the efficacy of the antirefluxing, mucosal-flap valve (AMFV) for biliary drainage relative to technical feasibility, surgical complications, and incidence of ascending cholangitis (AC). METHODS: Twenty-seven infants requiring biliary tract reconstruction underwent valve construction. Twenty biliary atresia (BA) patients received the Kasai procedure, and 7 choledochal cyst (CC) infants had cystectomy and hepatoenterostomy. A retrospective review of all patients was performed including radiographic evaluation of the current valve function in 10 patients. RESULTS: Construction was successful in all cases, and no morbidity was incurred by incorporation of the valve. Of 7 CC patients, there have been no known episodes of AC with mean follow-up of 4.4+/-4.2 years. Of 20 BA patients, there have been 5 deaths (25%), 7 liver transplants (35%), 2 (10%) lost to follow-up, and 6 (30%) survivors. Nine BA patients (45%) have had AC, with patients in all 4 outcome categories represented. Ten patients (5 CC and 5 BA) have been evaluated with barium small bowel radiographs, with no reflux to the liver hilum in all cases. CONCLUSIONS: The AMFV has caused no morbidity and continues to prevent reflux to the liver hilum. Despite functioning as designed, it does not appear to influence the occurrence of AC. Because CC patients had no AC, we feel that infection is related to the underlying atresia rather than to reflux.     

Continued lodging of retinal emboli in a patient with internal carotid artery and ophthalmic artery occlusions

Internal carotid artery or ophthalmic artery occlusions are devastating ophthalmological events which lead to severe impairment of vision. A case of multiple branch retinal artery occlusions in a 63-year-old male with internal carotid artery and ophthalmic artery occlusions on brain angiography is presented. Emboli lodging in branches of the retinal arteries were bright, glistening, yellow or orange in appearance. Such a distinctive ophthalmoscopic appearance led to the diagnosis of cholesterol emboli. Fluorescein and indocyanine green angiography disclosed delayed filling of the retinal vessels and choroid, and showed multiple hypofluorescence distal to the vessels in which the emboli were lodged. At the time of initial examination, the number of emboli lodged in retinal arteries was estimated at more than 20. As time passed, a few of the previous emboli disappeared and new emboli appeared in other sites on fundus examination. We think that the lodging of new emboli in other sites is due to the continued break-up of atheromatous tissue through the collateral circulation associated with the occlusion of the internal carotid and ophthalmic arteries.     

Studies on constituents of Korean basidiomycetes (L)

To find antitumor metabolites in Korean basidiomycetes, the shake-cultured mycelia of eight of the higher fungi were extracted with hot water and the extracts, after being partially purified, were subjected toin vivo antitumor test. When administeredi.p. at the dose of 30mg/kg/day for ten consecutive days into the female ICR mice, which had been implanted with 1×10⁵ cells of sarcoma 180 twenty-four hours before the first injection, the extracts ofAgaricus campestris, Lyophyllum decastes, Lyophyllum ulmarium, Armillaria tabescence andCalvatia exipulitormis respectively showed inhibition ratios of 64.1%, 65.4%, 60.0%, 53.0% and 49.3%. These five species were selected for further study, whereas the extracts ofPhallus impudicus, Coprinus comatus andPholiota squarrosa which showed the inhibition ratios of 31.2%, 33.5% and 19.0% were discontinued.     

Value of lying-down nystagmus in the lateralization of horizontal semicircular canal benign paroxysmal positional vertigo.

BACKGROUND: Horizontal canal benign paroxysmal positional vertigo is characterized by horizontal direction-changing nystagmus induced by lateral head turning in supine position. According to Ewald's second law, the direction of head turning that creates a stronger response represents the affected side in geotropic nystagmus and the healthy side in apogeotropic nystagmus. However, it may not always be possible to lateralize the involved ear only by comparing the intensity of the nystagmus. We studied the values of nystagmus induced by position change from sitting to supine in the lateralization of horizontal canal benign paroxysmal positional vertigo. METHODS: A retrospective study of 54 patients who had been diagnosed as having horizontal canal benign paroxysmal positional vertigo at the Dizziness Clinic of Seoul National University Bundang Hospital from May 2003 to February 2004 was performed. The directions of the nystagmus induced by lying down were compared with those determined by Ewald's second law. RESULTS: Of the 54 patients, 32 (20 apogeotropic and 12 geotropic) showed horizontal nystagmus induced by lying down. The nystagmus tended to be ipsilesional in apogeotropic patients (80%) and contralesional in their geotropic counterparts (75%). CONCLUSION: In horizontal canal benign paroxysmal positional vertigo, lying-down nystagmus mostly beats toward the involved ear in the apogeotropic type and directs to the healthy ear in the geotropic type. The direction of lying-down nystagmus may help lateralizing the involved ear in horizontal canal benign paroxysmal positional vertigo.     

Primary tumors and mediastinal lymph nodes after neoadjuvant concurrent chemoradiotherapy of lung cancer: serial CT findings with pathologic correlation

PURPOSE: The purpose of this work was to describe the changes of primary tumor and mediastinal lymph nodes on CT after neoadjuvant concurrent chemoradiotherapy and to correlate the CT findings with pathology. METHOD: Twenty-one consecutive patients [N2 disease (n = 19) or resectable T4 and N2 disease (n = 2)] with non-small cell lung cancer underwent neoadjuvant concurrent chemoradiotherapy. Changes of primary tumor and mediastinal nodes before and after the therapy were assessed using CT. The CT findings were correlated with pathologic findings. RESULTS: With neoadjuvant therapy, decrease in T stage was achieved in 9 of 21 (43%) patients on CT. On pathology, the remaining tumor consisted mostly of fibrosis and necrosis with little proportion of viable tumor cells (mean volume 17%, range 0-55%). Decrease in nodal stage was achieved in 14 of 21 (67%) patients on pathologic examination. Seven patients had cancer cells in mediastinal lymph nodes: in 6 of 9 (67%) patients with adenocarcinoma and 1 of 12 (8%) patients with squamous cell carcinoma (p = 0.016). CONCLUSION: With neoadjuvant concurrent chemoradiotherapy, the remaining tumor consists mostly of fibrosis or necrosis. Decreased nodal stage on pathology is achieved especially in patients with N2 disease of squamous cell carcinoma. The CT findings of the tumor and mediastinal nodes are not helpful in predicting the pathology after the therapy.     

Cytotoxic polyacetylenes from the marine sponge Petrosia sp

Three C46 (1-3) and three C30 (4-6) polyacetylenic alcohols with cytotoxic activity against a small panel of human solid-tumor cell lines have been isolated from the marine sponge Petrosia sp. Although compound 1 was identified as the stereoisomer of petrocortyne A, the structures of compounds 2-5 have not been previously reported and were established by spectral methods. Compound 6 was identified as the known compound petrosiacetylene D. The stereochemistry of compounds 1-5 was determined by the modified Mosher's method.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).