Reduced recurrence of late hemorrhagic radiation cystitis by WF10 therapy in cervical cancer patients: a multicenter, randomized, two-arm, open-label trial.

BACKGROUND AND PURPOSE: To evaluate the efficacy and the safety of WF10 as adjunct to standard treatment in the management of late hemorrhagic radiation cystitis compared to standard treatment alone. PATIENTS AND METHODS: Cervical cancer patients with Grade 2 or 3 late hemorrhagic radiation cystitis, were randomized and treated with WF10 0.5 ml/kg body weight, diluted in physiological saline or 5% dextrose water 250 ml, intravenous infusions over 2 h on 5 consecutive days, every 3 weeks for 2 cycles plus standard treatment (WF10 group) or standard treatment alone (control group). Fifty patients in each group were evaluated by questioning; urinalysis and cystoscopy during a 1 year follow up. RESULTS: At week 7, 37 patients (74%) in the WF10 group and 32 patients (64%) in the control group showed complete resolution in objective hematuria (P = 0.28). Significantly lower use of antibiotics (P = 0.002) and antispasmodics (P < 0.001) was found in the WF10 group. Among the responders, 24 patients (77%) in the control group experienced recurrent objective hematuria, whereas in the WF10 group only 17 patients (47%) experienced a recurrence (P = 0.01). Recurrence of objective hematuria occurred significantly faster in the control group as evidenced by Kaplan-Meier and log-rank statistics (P = 0.004), suggesting a long-term effect of WF10. Cystoscopy, at the end of the treatment period and after the one year follow up showed overall improvement without significant difference between two groups. No severe toxicity was monitored. CONCLUSIONS: WF10 therapy is a safe, non-invasive and convenient method in the management of late hemorrhagic radiation cystitis. WF10 therapy, as adjunct to standard treatment, has significantly reduced recurrence of objective hematuria, compared to standard treatment alone, during a one year follow up.     

Diarylheptanoid 1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-one enhances C2C12 myoblast differentiation by targeting membrane estrogen receptors and activates Akt-mTOR and p38 MAPK-NF-κB signaling axes

Journal of Natural Medicines - Diarylheptanoid, 1-(4-hydroxyphenyl)-7-phenyl(6E)-6-hepten-3-one (HPPH), has been reported to enhance myoblast differentiation via estrogen receptor (ER). However,...     

Antimycobacterial anthraquinone-chromanone compound and diketopiperazine alkaloid from the fungus Chaetomium globosum KMITL-N0802

Investigation of the fungus Chaetomium globosum KMITL-N0802 led to the isolation of a novel anthraquinone-chromanone compound named chaetomanone along with seven known compounds, ergosterol, ergosteryl palmitate, chrysophanol, chaetoglobosin C, alternariol monomethyl ether, echinuline and isochaetoglobosin D. These compounds were characterized by spectroscopic methods. Chaetomanone and echinulin exhibited activity towards Mycobacterium tuberculosis.     

Prohormone convertase furin has a role in gastric cancer cell proliferation with parathyroid hormone-related peptide in a reciprocal manner

We investigated the expression of parathyroid hormone-related peptide (PTHrP) and the relationship between PTHrP and its endoprotease furin in gastric cancer. PTHrP was colocalized with furin in 75% of gastric cancer tissues (six of eight) from patients with high serum PTHrP levels. PTHrP mRNA expression was confirmed in 67% of gastric cancer cell lines (four of six), whereas furin mRNA was detected in all six gastric cancer cell lines. In a cultured gastric cancer cell line, MKN28, mature PTHrP protein expression was markedly increased by transfection of furin cDNA. Furin cDNA-transfected MKN28 cells grew faster than did the mock controls. Moreover, furin mRNA expression in cultured gastric cancer cells was enhanced when PTHrP was added to the culture medium. These results suggest a link between PTHrP and furin in the regulation of gastric cancer cell growth. Furin might be involved not only in the production of the mature form of PTHrP, but also in promoting growth in gastric cancer cells.     

Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro

The effects of stevioside and steviol (a product of enzymatic hydrolysis of stevioside) on intestinal glucose absorption were examined in hamster jejunum. By using the everted sac technique, we found that stevioside (1 and 5 mM) had no inhibitory effect on glucose absorption. In contrast, glucose absorption was inhibited 29% by 1 mM steviol. The inhibition of glucose absorption by steviol was related to steviol concentration and incubation time. The possible mechanism of steviol inhibitory action of glucose absorption was also investigated. Reductions in the intestinal mucosal ATP content and absorptive surface area were responsible for the inhibition of glucose absorption by steviol. The decrease in the intestinal mucosal ATP content was accompanied by a decrease in the activities of mitochondrial NADH cytochrome c reductase and cytochrome oxidase. Morever, no inhibitory effects of steviol on the activity of intestinal Na⁺,K⁺-ATPase and glucose uptake in the intestinal brush-border membrane vesicles were seen. These results suggest that inhibition of intestinal glucose absorption by steviol in hamsters is due to the reduction in mucosal ATP content and an alteration of the morphology of the intestinal absorptive cells.     

Elevation of serum transcobalamin II in patients with scrub typhus

Serum transcobalamin II levels were measured in scrub typhus patients. Eighteen out of fifty-two patients admitted to Maharat Nakhon Ratchasima Hospital were diagnosed with scrub typhus infection. The serum unsaturated vitamin B12 binding protein (UBBC) and total vitamin B12 binding protein (TBBC) levels in these patients were significantly higher than in normal subjects (p < 0.001). The mean serum transcobalamin II level in the typhus patients was also significantly higher than in the normal subjects (p=0.004). There was a significant correlation between serum TCII levels and typhus IgM or IgG titers (p < 0.05), but not to total IgM levels. These findings indicate that patients with scrub typhus had stimulation of the recticuloendothelial system as a result of a considerable increase in transcobalamin II levels.     

The hematological status, plasma vitamin B12 and folic acid levels, and intestinal pathology in rats infected with Giardia lamblia

The purpose of our study was to investigate the hematological status, vitamin B12 and folic acid absorption and intestinal pathology after Giardia lamblia infection in a rat model. Adult Wistar rats were assigned randomly to receive human giardia cysts orally in the amount of 5 x 10(5) or 1.0 x 10(6) cysts, or none in the controls. The results showed that all the rats injected with giardia cysts became infected. The cyst output in the infected rats varied considerably. In rats infected with 5.0 x 10(5) giardia cysts, the incubation period until cyst output was 10 days compared with 4 days in rats infected with the higher amount of 1.0 x 106 giardia cysts. The highest peaks for cysts output in these 2 groups were on days 4-33, which decreased gradually to days 40-58. The hematocrit and hemoglobin levels in the infected rats were statistically significantly lower than in the controls on days 16, 22, 33, and 37 post-infection (p < 0.05). A reverse relationship between giardia cyst output and hemoglobin concentration was found in the infected rats (p = 0.05). There were no significant differences in plasma vitamin B12 and folic acid levels between the infected rats and the control rats. No pathological changes were found in the small intestine of infected rats. These findings suggest that giardiasis did not affect the absorption of plasma vitamin B12 and folic acid but caused anemia in a rat model.     

Antimycobacterial activity and cytotoxicity of flavonoids from the flowers of<Emphasis Type="Italic">Chromolaena odorata</Emphasis>

From the flowers of Chromolaena odorata (Eupatorium odoratum) four flavanones, isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) (1), persicogenin (5,3'-dihydroxy-7,4'-dimethoxyflavanone) (2), 5,6,7,4'-tetramethoxyflavanone (3) and 4'-hydroxy-5,6,7-trimethoxyflavanone (4), two chalcones, 2'-hydroxy-4,4',5',6'-tetramethoxychalcone (5) and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (6), and two flavones, acacetin (5,7-dihydroxy-4'-methoxyflavone) (7) and luteolin (5,7,3',4'-tetrahydroxyflavone) (8) were isolated and identified. Compound 1 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with the MIC value of 174.8 microM, whereas compounds 4, 7, and 8 exhibited weak activity with the MIC values of 606.0, 704.2 and 699.3 microM respectively. Compound 7 showed moderate cytotoxicity against human small cell lung cancer (NCI-H187) cells with the MIC value of 24.6 microM, whereas compound 8 exhibited moderate toxicity against NCI-H187 cells and week toxicity against human breast cancer (BC) cells with the MIC values of 19.2 and 38.4 microM respectively.     

Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs

The purpose of this study was to elucidate the interactions of human organic anion transporters (hOATs) and human organic cation transporters (hOCTs) with nonsteroidal anti-inflammatory drugs (NSAIDs) using cells stably expressing hOATs and hOCTs. NSAIDs tested were acetaminophen, acetylsalicylate, salicylate, diclofenac, ibuprofen, indomethacin, ketoprofen, mefenamic acid, naproxen, piroxicam, phenacetin, and sulindac. These NSAIDs inhibited organic anion uptake mediated by hOAT1, hOAT2, hOAT3, and hOAT4. By comparing the IC(50) values of NSAIDs for hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions with NSAIDs than did hOAT2 and hOAT4. HOAT1, hOAT2, hOAT3, and hOAT4 mediated the uptake of either ibuprofen, indomethacin, ketoprofen, or salicylate, but not acetylsalicylate. Although organic cation uptake mediated by hOCT1 and hOCT2 was also inhibited by some NSAIDs, hOCT1 and hOCT2 did not mediate the uptake of NSAIDs. In conclusion, hOATs and hOCTs interacted with various NSAIDs, whereas hOATs but not hOCTs mediated the transport of some of these NSAIDs. Considering the localization of hOATs, it was suggested that the interactions of hOATs with NSAIDs are associated with the pharmacokinetics and the induction of adverse reactions of NSAIDs.