Effects of 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS) and chlorpromazine on NO3- transport via anion exchanger in erythrocytes: inertness of DIDS in whole blood

We examined the effects of chlorpromazine on NO(3)(-) transport between erythrocytes (RBCs) and extracellular fluid. Chlorpromazine (10 microg/ml) did not influence NO(3)(-) movement in both whole blood and RBC suspension. Though an anion exchanger (AE1) inhibitor DIDS (4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, 100 microM) did not alter NO(3)(-) movement in whole blood, it inhibited the movement in a concentration-dependent manner in the RBC suspension. The inhibition was abrogated by plasma and albumin concentration-dependently. Our results indicated that chlorpromazine had no effect on NO(3)(-) transport through AE1 and that the inertness of DIDS on AE1 in whole blood is due to interference by albumin in plasma.     

A case responding to weekly paclitaxel (TXL) therapy as third line chemotherapy for scirrhous type gastric cancer

A 67-year-old female was admitted to our hospital in May, 2001 for examination. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal dissemination. Seventeen courses of sequential MTX and 5-FU therapy, and 2 courses of TS-1 plus CDDP were carried out. A partial response (PR) and prolonged NC were obtained after these chemotherapies. However, pleural effusion and ascites appeared again, and we diagnosed progressive disease. As a third line chemotherapy for this patient, paclitaxel (TXL) was administered. Treatment consisted of two 3-week courses of paclitaxel 70 mg per m2 on day 1 of each week, with a 1-week break between the courses. Two weeks after the start of this therapy, pleural effusion and ascites had completely disappeared. Paclitaxel is considered to be promising for advanced gastric cancers, as second or third line chemotherapy with paclitaxel for patients with inoperable gastric cancer seems to be effective in improving QOL.     

A case of adenoid cystic carcinoma (acc) of the Breast and review of the utility of preoperative imaging diagnose

A case of adenoid cystic carcinoma (ACC) of the breast in a 66-year-old woman is reported herein. ACC accounts for about 0.1% of all breast cancers. Our patient presented with a small, elastic and hard mass, measuring 2.0x2.0 cm, between both outer quadrants of the right breast. Although physical examination, ultrasonography and magnetic resonance (MR) mammography suggested a benign tumor, aspiration biopsy cytology (ABC) was performed twice, and the second ABC specimen was evaluated as suspicious for breast carcinoma. Breast conserving surgery with a level II lymph node dissection was subsequently performed. There was no lymph node metastases and estrogen receptor (ER) status was negative. Light microscopy revealed various growth patterns, with the cells showing biphasic cellularity. According to immunohistochemical analyses, CEA, actin and vimentin were positive, S-100 protein was negative, and the cytokeratin reaction was partially positive. Therefore, ACC of the breast was diagnosed. Although ACC of the breast is a rare neoplasm, it should be considered in the differential diagnosis even if various diagnostic imaging studies suggest a benign tumor of the breast. Awareness of this tumor will help prevent misdiagnosis.     

TZT-1027, an Antimicrotubule Agent, Attacks Tumor Vasculature and Induces Tumor Cell Death

TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with potent antitumor activity both in vitro and in vivo. In this study, we performed biochemical and histopathological examinations, and evaluated TZT-1027-induced tumoral vascular collapse and tumor cell death in an advanced tumor model, murine colon 26 adenocarcinoma. In addition, we studied the effects of TZT-1027 on cultured human umbilical vein endothelial cells (HUVEC). Tolerable doses of TZT-1027 induced tumor-selective hemorrhage within 1 h. This hemorrhage occurred mainly in the peripheral area of the tumor mass. Measurements of tumoral hemoglobin content and dye permeation revealed that the hemorrhage occurred firstly and tumor blood flow stopped secondarily. The vascular damage was followed by continuous induction of apoptosis of the tumor cells, tumor tissue necrosis, and tumor regression. In cultured HUVEC, TZT-1027 induced marked cell contraction with membrane blebbing in 30 min. These cell changes were completely inhibited by K252a, a broad-spectrum inhibitor of protein kinases. These effects of TZT-1027 on both tumor vasculature and HUVEC were greater than those of vincristine. In conclusion, TZT-1027 quickly attacked the well-developed vascular system of advanced tumors by a putative protein kinase-dependent mechanism, and then blocked tumor blood flow. Therefore, TZT-1027 has both a conventional antitumor activity and a unique anti-tumoral vascular activity, making it a potentially powerful tool for clinical cancer therapy.     

Hemodynamic effects of benazepril,an angiotensin-converting enzyme inhibitor,as studied in conscious normotensive dogs

Hemodynamic effects and inhibitory effects on the pressor response to exogenous angiotensin I of benazepril (CGS 14824A), a new angiotensin-converting enzyme (ACE) inhibitor, were examined in conscious chronically instrumented normotensive dogs in comparison with those of captorpil. Oral administration of benazepril (1-10 mg/kg) and captopril (3 and 10 mg/kg) reduced the blood pressure and inhibited the pressor response to angiotensin I dose-dependently. The blood-pressure-lowering effect of benazepril was as potent as that of captopril. The onset of effects of benazepril was slower and the duration longer than that of captopril. There was no close correlation between the attenuation of pressor response to exogenous angiotensin I and the blood-pressure-lowering effect of these two agents. These results indicate that benazepril is a potent ACE inhibitor with a slow onset and a long duration. The slow onset of action may be explained by the necessity of prior conversion of this compound to an active metabolite. A mechanism or mechanisms other than that responsible for the inhibition of pressor response to exogenous angiotensin I must be taken into consideration to explain the blood-pressure-lowering effects of benazepril and captopril.     

Development of Sentinel LN Imaging with a Combination of HAase Based on a Comprehensive Analysis of the Intra-lymphatic Kinetics of LPs

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Stimulatory action of itopride hydrochloride on colonic motor activity in vitro and in vivo

We investigated the effects of itopride hydrochloride (itopride, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride), a gastroprokinetic agent, on the colonic motor activity in vitro and in vivo, in comparison with benzamides, cisapride hydrate (cisapride), and mosapride citrate (mosapride). Itopride stimulated both peristaltic and segmental motility induced by applying intraluminal pressure to the isolated guinea pig colon. Although cisapride and mosapride enhanced the segmental motility, they markedly reduced the peristaltic motility. In conscious dogs with implanted strain gauge force transducers, itopride stimulated contractile activity in the gastrointestinal tract from the stomach to the colon. Cisapride stimulated contractile activity in the gastric antrum, ileum, and ascending colon. Mosapride stimulated contractile activity only in the gastric antrum and ileum. In guinea pigs and rats, itopride accelerated colonic luminal transit. On the other hand, cisapride and mosapride failed to enhance colonic transit. These results demonstrate that itopride has a stimulatory action on colonic peristalsis, propelling colonic luminal contents, different from that of cisapride and mosapride. Therefore, itopride may be a useful drug for the treatment of functional bowel disorders such as functional constipation.     

Umbilical appearance and patient/parent satisfaction over 5 years of follow-up after umbilical hernia repair in children

Background/purpose

We evaluated the long-term umbilical appearance and patient/parent satisfaction at follow-up after umbilical hernia repair (UHR).

Primary carcinoid tumor of the liver: report of a case with an emphasis on contrast-enhanced ultrasonographic findings

We report the case of a 82-year-old man with primary carcinoid tumor of the liver. Abdominal ultrasonography (US) showed 2 well-demarcated, round tumors in the right lobe (4 x 4 cm and 1 x 1 cm). The lesions were both markedly echogenic with many small cystic areas. Contrast-enhanced US showed the whole tumor to be quickly and highly enhanced, suggesting the highly vascular nature of the lesion, and the findings corresponded well with hepatic angiographic results. The patient underwent a US-guided needle biopsy, which yielded histological results consistent with a carcinoid tumor. Considering his age, we selected radiofrequency ablation (RFA) for treatment. After treatment, contrast-enhanced US demonstrated complete disappearance of blood flow signals, indicating satisfactory treatment. Our case showed that US and contrast-enhanced US findings can lead to a high suspicion of carcinoid tumor.     

Assessing nitrate metabolism in the intestinal tract by measuring breath nitric oxide and nitrous oxide, and its clinical significance

BACKGROUND: The toxicity of dietary nitrate (NO3-) is controversial. One reason is nitrate metabolism in the intestine is so complicated that it is far from fully understood. There is no study measuring breath nitric oxide (NO) and nitrous oxide (N2O) after ingesting vegetables and high-nitrate food at the same time. METHODS: Breath samples from 10 healthy young and 10 healthy old subjects were collected at 15-min intervals for 5 h after ingestion of 100 g of lettuce and during fasting (control). Breath NO and N2O were analyzed by a chemiluminescence and an IR-PAS analyzer respectively. RESULTS: N2O maximum concentration and excretions increased significantly after ingesting lettuce in each group [303 (30) vs. 750 (81) ppb, 771 (72) vs. 1668 (146) microg in young; 442 (52) vs. 1092 (109) ppb, 1088 (125) vs. 2100 (183) microg in old subjects; mean (SE), P<0.01], while NO did not. In addition, breath NO was strongly influenced by ambient NO, which varied greatly. N2O maximum level in old subjects after ingesting lettuce was higher than that of young subjects (750 vs. 1092 ppb, P<0.05), and significantly higher N2O concentration levels were seen at 30, 45, 60, and 105 min in old subjects. CONCLUSIONS: A large amount of N2O produced in the intestine and normal nitrate intake do not influence the breath NO concentration, probably due to its relatively small production. Higher maximum N2O concentration after ingesting lettuce in old subject is probably because more bacteria, which rapidly reduce dietary nitrate in the upper intestinal tract, inhabit the gut in old age. Our results suggested that breath N2O is a useful noninvasive maker to estimate dietary nitrate reduction in the intestinal tract.