Biphasic solitary fibrous tumour: a report of two cases with epithelioid features

We present two cases of solitary fibrous tumour (SFT) showing biphasic morphology with a spectrum of malignant epithelioid components. Slides prepared from formalin-fixed and paraffin-embedded tissue from both cases were stained with haematoxylin and eosin and by immunohistochemistry. Interphase fluorescent in situ hybridisation studies were performed in both cases using paraffin-embedded tissue to look for the t(X;18) translocation, thereby to exclude synovial sarcoma. Both cases showed biphasic morphology with some areas having typical benign spindled SFT morphology (including CD34 expression) and other areas having a malignant epithelioid appearance. In one of the cases, the epithelioid area, which was well circumscribed and showed packeting of cell groups, demonstrated expression of cytokeratin and epithelial cadherin but not of CD34. In the second case, the immunophenotype of the epithelioid component was similar to that of the benign SFT component. These findings suggest that epithelioid change in SFT shows a range of differentiation at one end, similar to that of a standard SFT, and at the other end, possibly acquiring epithelial characteristics.     

Coenzyme Q10 Supplementation and Heart Failure

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Western world. Oxida-tive stress appears to play a pivotal role in atherosclerosis. Coenzyme Q10 (CoQ10), one of the most important antioxidants, is synthesized de novo by every cell in the body. Its biosynthesis decreases with age and its deficit in tissues is associated with degenerative changes of aging, thus implicating a possible therapeutic role of CoQ10 in human diseases. There is evidence to support the therapeutic value of CoQ10 as an adjunct to standard medical therapy in congestive heart failure. However, much further research is required, especially in the use of state-of-the-art techniques to assess functional outcomes in patients with congestive heart failure.     

Inhibition of enteropathogenic Escherichia coli adhesion on host epithelial cells by Holarrhena antidysenterica (L.) WALL.

Bacterial adhesion is the first step in the sequence of events leading to infection. Previous data are available on the effect of Holarrhena antidysenterica on antidiarrhoeal and antibacterial action, but there is little information on the mechanism of action of the various aspects of EPEC‐induced diarrhoea, namely adherence and translocation of the effector molecule to intestinal epithelial cells. The aim of the present study was to investigate the effects of alkaloids of Holarrhena antidysenterica (AHA) on interference in the mechanism of enteropathogenic Escherichia coli (EPEC) adhesion on host epithelial cells (INT 407 and HEp2). To determine the impact of AHA on epithelial cells, cytotoxicity (LDH), adherence, apoptotic and ultrastructural studies were performed. To analyse the effect of AHA on EPEC secreted proteins, especially EspD, INT 407 monolayers were infected with EPEC and AHA‐treated EPEC, followed by immunoblotting, probed with anti EspD antisera. The maximum percentage of LDH leakage was reduced in AHA‐treated EPEC (400 µg/mL) in both cell lines. Reduced bacterial adherence was observed under light microscopy and altered apoptotic changes were visualized using propidium iodide staining in conjunction with fluorescence microscopy, in both cell lines infected with AHA‐treated EPEC and these results were confirmed with transmission electron microscope images. The suppression of type III secretory proteins (TTSPs), EspD (～40 kDa), was detected in INT 407 cells infected with AHA‐treated EPEC. In conclusion, AHA reduces initial bacterial adhesion to intact epithelial cells and it may exert an antiadherence effect against the pathogenesis of EPEC in host epithelial cells. Thus, the investigations provide a rational basis for the treatment of EPEC‐mediated diarrhoea with AHA. Copyright © 2009 John Wiley & Sons, Ltd.     

Chronopharmacokinetics of sumatriptan in healthy human subjects

Rhythms in the onset and symptoms of several diseases are well established. Migraine is a disorder that exhibits periodicity in its symptoms and so chronotherapy may be beneficial in treating the problem. Designing a chronotherapeutic schedule requires chronopharmacokinetic and chronopharmacodynamic data of the drugs prescribed. We have studied the chronopharmacokinetics of sumatriptan, a drug of choice in migraine treatment. Twelve healthy male volunteers were treated with 100 mg sumatriptan orally at 0700, 1300, 1900 and 0100 h in a randomized 4 x 4 Latin square crossover design, with a wash-out period of one week. Serum samples were analysed by high performance liquid chromatography with an electrochemical detector. Pharmacokinetic parameters were calculated using noncompartmental methods. The pharmacokinetic parameters were analysed using analysis of variance and a two-tailed paired t-test at the probability of 95%. The mean peak serum concentration following the 0700 h administration (Cmax; 59.09 +/- 10.53 ng mL(-1)) was significantly (P < 0.05; n = 12) higher than after the 1900 h administration (Cmax 41.88 +/- 12.21 ngmL(-1)). The mean area under the serum concentration-time curve from time zero to the last time-point (AUCo-t), the area under the serum concentration-time curve from zero to infinity (AUC 0-infinity), and the area under the first moment curve (AUMC) were significantly (P < 0.05; n = 12) higher following the 0700 and 0100 h administrations than after the 1900 h administration. Following administration at 0700 h, the mean oral clearance (CLs/f; 781 +/- 186 mL h(- 1) kg(-1)) and the apparent volume of distribution (Vd/f; 2,379 +/- 684) were significantly lower (P < 0.05; n = 12) than after the 1900 h administration (CLs/f 1,208 +/- 458 mL h(-1) kg(-1), Vd/f 4,655 +/- 2,096 mL kg(-1)). The mean Vd/f value was again lower after the 1300h administration than after the 1900 h administration (2,763 +/- 1,417 vs 4,655 +/- 2,096 mL kg(-1); P < 0.05; n = 12). The variations may be due to the time dependent changes in the extent of absorption and/or circadian variations in hepatic blood flow.     

Correlation of serum and salivary levels of pentoxifylline

Twelve healthy volunteers were treated with 400 mg pentoxifylline at 1000 and 2200 hours in a randomized crossover design with a washout period of 1 week. Serum and saliva samples were analyzed for unchanged pentoxifylline by high-performance liquid chromatography. Saliva to serum ratios and pharmacokinetic parameters of pentoxifylline were calculated. Significant (p < 0.05) correlation between serum and salivary levels of pentoxifylline was observed for the treatments at 1000 and 2200 hours. Although the mean saliva/serum ratios of pentoxifylline in the postabsorption phase were found to be higher for the 2200-hour treatment than the 1000-hour treatment, this difference was not statistically significant (p > 0.05). Further, no significant (p > 0.05) difference was noted between the mean pharmacokinetic parameters of pentoxifylline whether computed through serum or through salivary levels for either treatment. Hence, saliva can be used in place of serum/plasma in pharmacokinetic and interaction studies of pentoxifylline.     

Enzyme-linked PNA lectin-binding assay of serum T-antigen in patients with SCC of the uterine cervix

The expression of Thomsen-Friendenreich antigen (T-Ag) is associated with enhanced metastatic potential, poor prognosis and decreased survival rate in a variety of malignancies, and their detection and quantification can be used in serologic diagnosis. T-antigen expressions were measured by the enzyme-linked lectin assay (ELLA) with peanut agglutinin (PNA) in the sera of patients with squamous cell carcinoma (SCC) of the uterine cervix from 286 patients. This study has a sensitivity of 80%, specificity of 82% and a positive predictive value of 93%. Quantification of the T-antigen may provide useful biochemical indices for clinical assessment of the tumor spread and invasiveness of disease in SCC of the uterine cervix. Moreover, the ELLA assay is cheap, easy to perform and reproducible in the prognosis and diagnosis of SCC of the uterine cervix.     

Serum alpha-N-acetylgalactosaminidase is associated with diagnosis/prognosis of patients with squamous cell carcinoma of the uterine cervix

Serum alpha-N-acetylgalactosaminidase (NaGalase) is responsible for the deglycosylation of vitamin D(3)-binding protein (Gc protein). The deglycosylated Gc protein cannot be converted into major macrophage-activating factor (MAF), leading to immunosuppression. NaGalase is universally detected in a variety of cancer patients, but not in healthy individuals (Cancer Res. 56 (1997) 2827-2831). However, the diagnostic/prognostic utility of NaGalase in squamous cell carcinoma (SCC) of the uterine cervix is not known. To address this issue, the serum NaGalase was quantitatively determined in 210 patients with different stages of SCC of the uterine cervix. NaGalase levels were increased with the progression of the cancer. After radiotherapy, the increased levels returned toward or to normal levels in early stages (FIGO stage I-IIB) but not in advanced stages (FIGO stage III-IV). The present study revealed that the amount of NaGalase in the patient's bloodstream reflects the tumor burden and aggressiveness of the disease. We conclude that NaGalase is an independent predictor of diagnosis/prognosis in SCC of the uterine cervix, and therefore suggest that quantitative NaGalase alteration may reflect important differences in the immunological functions of these neoplasms.