Stimulatory effect of centrally injected capsaicin, an agonist of vanilloid receptors, on gastric acid secretion in rats.

Capsaicin, the main pungent ingredient in chilli peppers, acts through specific vanilloid receptors on sensory neurons. The vanilloid receptors have been localized in the brain. We describe here a stimulatory effect of centrally injected capsaicin on gastric acid secretion in urethane-anesthetized rats. Injection of capsaicin (10-30 nmol per rat) into the lateral cerebroventricle markedly stimulated the secretion. Injection of capsazepine (30 nmol) or ruthenium red (30 nmol), antagonists for vanilloid receptors, into the lateral cerebroventricle inhibited the secretion induced by capsaicin, although these antagonists alone significantly stimulated the secretion. Injection of capsaicin into the fourth cerebroventricle also stimulated gastric acid secretion. The effects of centrally injected capsaicin into the lateral and fourth cerebroventricle were mediated via the vagus cholinergic nerve, because the effects were abolished by bilateral vagotomy at the cervical level. The present findings showed that central injection of capsaicin stimulated gastric acid secretion, via vanilloid receptors in the central nervous system (CNS), and through vagus nerve mechanisms in the perfused stomach of urethane-anesthetized rats.

Detection and quantitation of thymidylate synthase mRNA in human colon adenocarcinoma cell line resistant to 5-fluorouracil by competitive PCR.

BACKGROUND: Thymldylate synthase (TS) is an important target of cancer chemotherapeutic agents, such as 5-fluorouracil (FU). To investigate mechanisms of resistance to FU, we tried to detect TS mRNA in the human colon adenocarcinoma cell lines. MATERIALS AND METHODS: SNU-C1 (C1) and its FU-resistant cell line, SNU-C1/FU (C1/FU) were used for this study. Total RNA was isolated by the AGPC method, then competitive PCR and northern blot were done to detect TS mRNA. RESULTS: Using sets of primers covering the 3'-untranslated region of TS mRNA, PCR products were amplified from cDNA prepared from both C1 and C1/FU in their logarithmic growth phases. However, only cDNA prepared from C1/FU was amplified in the stationary phase. The amount of mRNA was quantified by competitive PCR technique in both cell lines, using another set of primer to amplify the product in the stationary phase. The amount of TS mRNA in C1/FU was found to be four times more than that found in C1. In addition, TS catalytic activity of C1/FU was approximately 2-times higher than that of C1. Southern blot analysis revealed that no TS gene amplification or rearrangement in genomic DNA was detected in these cell lines. CONCLUSIONS: This PCR technique is applicable for detecting TS mRNA, and the TS mRNA level was found to be increased 1.5-fold (as detected by northern blot analysis) and 4-fold (measured by competitive PCR), leading to enhanced TS catalytic activity in C1/FU in contrast to its parent cell line, C1; thus accounting for one possible resistant mechanism to FU.

[Long-term follow-up study of children with minimal change nephrotic syndrome].

We conducted a long-term follow-up study of 37 children with biopsy-proved minimal change nephrotic syndrome during a period of over 6 years from onset to adulthood. These patients were classified into 4 groups of 13 infrequent relapsers, 17 frequent relapsers, 3 non-responders and 4 no-relapsers according to the International Study of Kidney Disease in Children (ISKDC). All patients were treated with conventional prednisolone therapy. Two cases of infrequent relapsers, 7 cases of frequent relapsers and 1 case of non responders relapsed in adult life. Two cases of infrequent relapsers and 1 case of frequent relapsers relapsed in adult life after remission for 5 or more years. We concluded that minimal change nephrotic syndromes in childhood should be followed up over a long duration in adult life, evenly in cases with good steroid responsiveness.

[Exercise-induced acute renal failure observed in a boy with idiopathic renal hypouricemia caused by postsecretary reabsorption defect of uric acid].

Acute renal failure without oliguria developed in an 11-year boy after running exercise. With improvement of his renal function, marked hypouricemia became apparent (0.8-0.9 mg/dl). Increased excretion of uric acid into the urine, increased clearance ratio of uric acid against creatinine (CUA/CCr), normal concentration of plasma xanthine and hypoxanthine, and suppression of CUA/CCr ratio by pyrazinamide loading but not by probenecid, were observed in the patient and his two siblings, suggesting that hereditary abnormalities of reabsorption of uric acid after secretion from the renal tubules resulted in the hypouricemia. The mechanism of acute renal failure in this disease remains unknown.

[Detection of thymidylate synthase mRNA in 5-fluorouracil resistant human colon adenocarcinoma cells].

To investigate the resistance against 5-fluorouracil (FU), thymidylate synthase (TS) mRNA level was measured by reverse transcription PCR (RT-PCR) technique and quantitated by a competitive-PCR method in human colon adenocarcinoma cell line, SNU-C1 and its FU resistant cell line, C1/FU. Using a set of primers covering 3'-untranslated region of mRNA, PCR products were amplified from cDNAs prepared from both SNU-C1 and C1/FU. However, only a cDNA extracted from C1/FU was amplified in a stationary growth phase. Then, the amount of mRNA was quantitated by competitive-PCR technique in both cell lines using another set of primer enable to amplify product in both stationary and logarithmic cell growth phase. The amount of mRNA in C1/FU was four times more than that of C1. The gene level in TS gene in genome DNA in these cell lines were not different incidentally. These data suggest that TS mRNA was more increased and can be more stable in C1/FU, accounting for FU resistance.