Dietary trans and saturated fatty acids effects on semen quality,hormonal levels and expression of genes related to steroid metabolism in mouse adipose tissue

Our objectives were to assess sperm alteration and adipose tissue (AT) genes expression related to steroid metabolism subsequent to fatty acids consumption. Twenty‐nine mature male mice were divided into: fat diet (FD; n = 15) and the control group (n = 14). FD group was fed with low level of trans and saturated fatty acids source for 60 days. Sperm parameters, levels of hormones and the mRNA abundance of the target genes in AT were assessed. The sperm concentration, total and progressive motilities were lower in FD group compared to that of control (p < 0.01). Blood estradiol levels increased in FD (p < 0.001), whereas no significant difference was observed in testosterone. The mRNA levels of StAR, CYP11A1, CYP17A1, 17βHSD7 and 17βHSD12 in AT of FD were higher than those of the control (p < 0.05). In contrast, mRNA level of Cyp19a1 in FD was significantly (p < 0.05) lower than that of control. 17βHSD12 and 17βHSD7 (as oestrogenic genes) increased, while 17βHSD5 and 17βHSD3 (as androgenic genes) remained unchanged, indicating that dietary trans/saturated fatty acids affect AT genes expression. Probably, sperm parameters were altered by increment of expression level of genes involved in oestrogenic metabolism rather than those engaged in androgenic metabolism after fatty acids consumption.     

The impact of using defined criteria for adequacy of fine needle aspiration cytology of the thyroid in routine practice

The fine needle aspiration cytology (FNAC) of the thyroid is the predominant method of preoperative tissue diagnosis of thyroid lesions. The routine use of FNAC has reduced the rate of unnecessary surgery for thyroid nodules. However, there are overlaps in the existing criteria for defining adequacy in thyroid aspirates. In this study, we aimed to explore the reasons for high percentage of inadequate thyroid FNAC samples and to reevaluate those samples by applying clearly defined criteria suggested in the literature to reduce the proportion of inadequate aspirates. The results of 550 smears reported as inadequate FNAC samples are presented over a period of 15 years extending from 1986 to 2000 (18.8%). For the purpose of the study, only those patients with subsequent histological or cytological analysis were included (279). The original FNA samples were reviewed by two cytopathologists, unaware of the subsequent repeat cytology or histology results. Specific criteria for adequacy of specimens were used which include the presence of six or more groups of follicular cells, each having more than 10 discernable viable cells or 60 isolated viable follicular cells. Out of 279, 82 (29%) FNAC samples originally reported as inadequate met our criteria and were considered adequate on review. Of these 82 cases, subsequent surgical excision showed malignancy in 5 cases (6%), adenoma in 7 (9%), and benign hyperplasia and thyroiditis in 70 cases (85%). In addition, 16 (5%) cases were classified as cysts. The slide preparation error was noticed in 26 (14%) and the sampling error was observed in 160 (86%) cases. The use of well‐defined criteria for adequacy is helpful because it improves the diagnostic efficiency of thyroid FNA and avoids unnecessary surgery for benign nonneoplastic thyroid lesions. However, since application of these criteria has also resulted in an increase in the false‐negative diagnoses, they should be applied in the multidisciplinary context. Diagn. Cytopathol. 2011;39:81–86. © 2010 Wiley‐Liss, Inc.     

Grafting of dermatan sulfate on polyethylene terephtalate to enhance biointegration

The aim of the present study was to achieve the immobilization of dermatan sulfate (DS) on polyethylene terephthalate (PET) surfaces and to evaluate its biocompatibility. DS obtained from the skin of Scyliorhinus canicula shark was immobilized via carbodiimide on knitted PET fabrics, modified with carboxyl groups. PET-DS characterization was performed by SEM, ATR-FTIR and contact angle measurements. Biocompatibility was evaluated by investigating plasma protein adsorption and endothelial cell proliferation, as well as by subcutaneous implantations in rats. The results indicated that DS immobilization on PET was achieved at ~8 μg/cm2. ATR-FTIR evidenced the presence of sulfate groups on the PET surface. In turn, contact angle measurements indicated an increase in the surface wettability. DS immobilization increased albumin adsorption on the PET surface, whereas it decreased that of fibrinogen. In vitro cell culture revealed that endothelial cell proliferation was also enhanced on PET-DS. Histological results after 15 days of subcutaneous implantation showed a better integration of PET-DS samples in comparison to those of nonmodified PET. In summary, DS was successfully grafted onto the surface of PET, providing it new physicochemical characteristics and biological properties for PET, thus enhancing its biointegration.     

Cheminformatics-based selection and synergism of herbal extracts with anticancer agents on drug resistance tumor cells-ACHN and A2780/cp cell lines

The treatment of cancer usually involves lethal effect on normal body cells as side effects. Cheminformatics methodology can play a significant role in biomed/clinical scientific research. Similarity searching is a standard cheminformatics tool in drug discovery area and database design. In this study, five novel herbal extracts in combination with doxorubicin and cisplatin have been used to sensitize ACHN and A2780/cp cells. These herbal extracts have been selected on the basis of novel cheminformatics methodology and assayed for the first time. The findings confirmed predicted outcomes from the in silico research and the results introduced may bring to use the effects of these herbs in reversing of multidrug resistance (MDR) phenomenon.     

Pilot study of a pediatric metronomic 4-drug regimen

Background

Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC is gaining interest as an alternative strategy to fight resistant cancer.

Objective

to assess the safety of 4 drug MC regimen in pediatric patients with refractory or relapsing various tumors types.

Setting

From November 2008 to December 2010, in three academic pediatric oncology centers, 16 children (median age 12 years old; range 5.5-20) were included in this pilot study. This treatment was proposed to children with refractory disease for whom no further effective treatments were available. Most frequent diagnosis were medulloblastoma/cerebral PNET (5) osteosarcoma (5), and one case each of nephroblastoma, high grade glioma, Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma and kidney rhabdoid tumour. The MC regimen consisted in cycles of 56 days (8 weeks) with weekly vinblastine 3 mg/m² (week 1-7), daily cyclophosphamide 30 mg/m² (days 1-21), and twice weekly methotrexate 10 mg/m²; (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days1-56) followed by a 2-weeks chemotherapy break. Adverse events were determined through laboratory analysis and investigator observations.

Results

One objective response was observed in a patient with Hodgkin lymphoma, and 4 patients experienced disease stabilization and continued their treatment for 3 cycles (24 weeks) or more. At last follow-up, 7 patients (43%) are alive including 1 still undergoing treatment. During the overall 36 cycles of treatments received by patients, 4 grade IV toxicities and 24 grade III toxicities were observed in 11 cycles in only 10 different patients.

Conclusion

The metronomic regimen we report here was well tolerated and associated with disease stabilization. This regimen is currently being evaluated in a national multicenter phase II study.