Absorption of tetrahydropyranyl adriamycin administered intravesically immediately after transurethral resection of bladder carcinoma

Absorption of tetrahydropyranyl adriamycin (THP) administered immediately after transurethral resection of bladder carcinoma (TUR-Bt) has not been reported. In this study, we have examined the absorption of THP and the systemic toxicity in the early post-TUR period. Of 21 patients with bladder carcinoma, 10 had a solitary tumor and 11 multiple tumors. Twenty mg THP in 40 ml of sterile water was intravesically administered on days 1, 3, 5, 7, 14 and 28, and then every 4th week. The THP solution was retained for 2 hours. The blood THP concentration was measured 30 minutes and 2 hours after the intravesical administration on days 1, 7 and 28. No systemic side effects were observed. Thirteen of the 38 (34%) samples contained a detectable level (more than 1 ng/ml) of THP on the post-TUR-Bt on day 1, 8, of 42 (19%) on day 7, and 3 of 18 (17%) on day 28. Altogether, 24 of the 98 (24%) samples contained more than 1 ng/ml THP. The highest blood THP level was 23 ng/ml on day 1. The differences between frequency of detection of blood THP in the samples at 30 minutes and 2 hours were not statistically significant. The difference between average concentration of blood THP of patients with solitary and multiple tumors also was not significant. These results indicate that intravesical THP administration starting within 24 hours after TUR-Bt can not result in significant systemic absorption of THP, and the systemic toxicity can be avoided.     

Oral squamous cell carcinoma: electron microscopic and immunohistochemical characteristics

Oral squamous cell carcinoma is the most common oral malignancy, and we performed electron microscopic and immunohistochemical investigation of the tumor. In patients with cervical metastasis, microvilli were developed and a small number of desmosomes were found, regardless of the width of the intercellular spaces. In patients without the metastasis, few microvilli were found in relatively wide intercellular spaces, or numerous microvilli were found in narrow intercellular spaces, and a large number of desmosomes were shown. However, these findings were different from those of tumors that had received radiotherapy, in which numerous microvilli and a small number of desmosomes were found in the nonmetastatic cases. Transferrin receptor, which is a marker of cell proliferation, was localized on the cell membrane, especially in microvilli. Ultrastructural similarity between the primary tumor and the metastatic tumor was recognized, however, the features of microvilli, desmosomes, and the intercellular spaces differed between them in most cases. It is suggested that microvilli might be related to the metastasis of oral squamous cell carcinoma cells. Immunohistochemically, the protein expression of p53 and pRb2/p130 was related to the clinical course of the patients with oral squamous cell carcinoma; the mechanism of the synthesis of these proteins should be investigated in order to understand the biological behavior of the tumor.     

Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity

Camostat mesilate (CM), an oral protease inhibitor, has been used clinically for the treatment of chronic pancreatitis in Japan. However, the mechanism by which it operates has not been fully understood. Our aim was to evaluate the therapeutic efficacy of CM in the experimental pancreatic fibrosis model induced by dibutyltin dichloride (DBTC), and we also determined the effect of CM on isolated monocytes and panceatic stellate cells (PSCs). In vivo, chronic pancreatitis was induced in male Lewis rats by single administration of 7 mg/kg DBTC and a special diet containing 1 mg/g CM was fed to the DBTC+CM-treated group from day 7, while the DBTC-treated group rats were fed a standard diet. At days 0, 7, 14 and 28, the severity of pancreatitis and fibrosis was examined histologically and enzymologically in both groups. In vitro, monocytes were isolated from the spleen of a Lewis rat, and activated with lipopolysaccharide stimulation. Thereafter, the effect of CM on monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) production from monocytes was examined. Subsequently, cultured rat PSCs were exposed to CM and tested to see whether their proliferation, MCP-1 production and procollagen alpha1 messenger RNA expression was influenced by CM. In vivo, the oral administration of CM inhibited inflammation, cytokines expression and fibrosis in the pancreas. The in vitro study revealed that CM inhibited both MCP-1 and TNF-alpha production from monocytes, and proliferation and MCP-1 production from PSCs. However, procollagen alpha1 expression in PSCs was not influenced by CM. These results suggest that CM attenuated DBTC-induced rat pancreatic fibrosis via inhibition of monocytes and PSCs activity.     

Dose- and time-dependent responses for micronucleus induction by X-rays and fast neutrons in gill cells of medaka (Oryzias latipes)

Medaka fish (Oryzias latipes) were exposed to various doses of X-rays or fast neutrons, and the frequency of micronucleated cells (MNCs) was measured in gills sampled at 12- or 24-hr intervals from 12 to 96 hr after exposure. The resulting time course of MNC frequency was biphasic, with a clear peak 24 hr after exposure, irrespective of the kind of radiation applied and the dose used. The half-life of MNCs induced in the gill tissues by the two exposures fluctuated around 28 hr, with no significant dose-dependent trend for either X-ray- or neutron-exposed fish. As assayed 24 hr after exposure, the MNC frequency increased linearly over the control level with increasing doses of both X-rays and fast neutrons. The relative biological effectiveness (RBE) of fast neutrons to X-rays for MNC induction was estimated to be 4.3 +/- 0.6. This value is close to the RBE value of 5.1 +/- 0.3 reported for fast neutron induction of somatic crossing-over mutations in Drosophila melanogaster that arise from recombination repair of DNA double-strand breaks. These results and other data support our conclusion that the medaka gill cell micronucleus assay is a reliable short-term test for detecting potential inducers of DNA double-strand breaks.     

Use of the genomic subtractive hybridization technique to develop a real-time PCR assay for quantitative detection of Prevotella spp. in oral biofilm samples

Genomic subtractive hybridization was used to design Prevotella nigrescens-specific primers and TaqMan probes. Based on this technique, a TaqMan real-time PCR assay was developed for quantifying four oral black-pigmented Prevotella species. The combination of real-time PCR and genomic subtractive hybridization is useful for preparing species-specific primer-probe sets for closely related species.     

Clinical effect of hypoallergenic rice (HRS-1) in atopic dermatitis. HRS-1 Research Group

The usefulness of hypoallergenic rice (HRS-1) was clinically evaluated in 43 patients with severe atopic dermatitis (AD), who were suspected of having rice allergy, in collaboration with 13 hospitals. The patients were fed with HRS-1 instead of eliminating both regular rice and wheat from their daily diet. AD area and severity index (ADASI) was calculated as an indicator of the degree of cutaneous symptoms. Significant decrease of ADASI were observed in the 2nd and 4th week and at the end of the replacement therapy (5.6 weeks on average). On final evaluation, 74% of the patients tested showed "moderate" to "remarkable" improvement, and in 53% of the patients HRS-1 resulted in a "moderate" to "remarkable" reduction in the dosage and the grade of potency of the steroid ointment concomitantly used for the treatment. Finally, HRS-1 was evaluated as "useful" to "very useful" as the elimination diet in 70% of the patients.     

Association of feces sign with prognosis of non-emergency adhesive small bowel obstruction

Background/Objective: The feces sign has been reported as a possible predictive factor for non-operative treatment of small bowel obstruction. However, its relationship with prognosis of non-emergency adhesive small bowel obstruction remains unclear. This study aimed to clarify the relationship between the feces sign and prognosis of non-emergency adhesive small bowel obstruction.MethodsNinety-two patients with non-emergency adhesive small bowel obstruction with the transitional zone visible on computed tomography were included. Patients were categorized into two groups: feces sign positive (n = 40) and negative (n = 52). Clinical features and prognosis were compared between the two groups. Cox proportional hazards regression models incorporating the feces sign were used to analyze odds of diet resumption and discharge.ResultsPatients with feces sign were younger (p = 0.015), had a higher body mass index (p = 0.027), and a lower white blood cell count (p = 0.019) on admission. More patients with feces sign were successfully treated with fasting and/or nasogastric tube placement (p < 0.001), and no patient with feces sign suffered from recurrent obstruction after diet resumption. Kaplan–Meier analysis showed that patients with feces sign took less time for diet resumption (p = 0.007) and discharge (p = 0.004) than those without it. Using Cox proportional hazards regression model, the feces sign was reported as an independent predictor of diet resumption (odds ratio 1.685, p = 0.018) and discharge (odds ratio 1.861, p = 0.007).ConclusionsThe feces sign is associated with improved odds for diet resumption and discharge.