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.     

PREVALENCE OF MICROALBUMINURIA IN NON-INSULIN-DEPENDENT DIABETES MELLITUS

The prevalence of microalbuminuria was assessed in 50 patients of non-insulin dependent diabetes mellitus. The mean age of patients was 52.1 ± 11.6 years and the duration of diabetes was 8.3 ± 6.8 years. Twenty (40%) patients had microalbuminuria. Microalbuminuria was more common in patients with a longer duration of diabetes (more than 5 years), a poor glycaemic control, and higher systolic blood pressure.KEY WORDS: Microalbuminuria, Diabetes mellitus, Diabetic nephropathy, Chronic renal failure     

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.     

Profile of non-compliance in lymphoblastic leukaemia

A nationwide study of intracellular drug metabolite concentrations in children prescribed 6-mercaptopurine for the treatment of lymphoblastic leukaemia was carried out to assess interpatient variability at a standardised dose. Nine children (2% of the total) had completely undetectable metabolites, indicative of non-compliance. Five were adolescents, but otherwise they had no obvious distinguishing characteristics. Not taking any 6-mercaptopurine at all is uncommon, but the problem cannot be predicted. The total number of children who do not comply cannot be determined from this study, but the nine children described represent only a fraction of these.