Distribution of components of the glutathione detoxification system across the human placenta after uncomplicated vaginal deliveries

The function of the glutathione-related detoxification system plays an important role to ensure an uncomplicated pregnancy outcome. This study was performed to investigate whether the components of the glutathione-related detoxification system are equally distributed among the different cotelydons in the human placenta. We measured glutathione, cysteine, glutathione S-transferase (GST) isoenzyme levels (GSTA1+A2, GSTP1, GSTM1 and GSTT1), enzyme activities of glutathione S-transferase and glutathione peroxidases, protein carbonyl levels, and antioxidant capacities at twelve different standardized positions in six placentae from healthy women after uncomplicated pregnancy and vaginal delivery. Data were statistically evaluated with a Friedman two-way ANOVA with Bonferroni correction. 'Foetal'-side values were not significantly different from those at the 'maternal'-side. Except for GSTA1+A2, no significant differences were found between different sampling sites indicating that the distribution of all parameters measured was homogenous throughout the placenta. Since levels of GSTA1+A2 were minor compared to those of GSTP1 and GSTT1, the clinical relevance of this heterogeneity may be limited. These results implicate that the location of sampling is not important as long as biopsies are taken from physiological cotelydons.     

Polymorphisms of the glutathione S-transferase P1 gene and head and neck cancer susceptibility

BACKGROUND: Factors determining the individual susceptibility to head and neck squamous cell carcinoma (HNSCC) are still largely unknown. An imbalance between enzymes involved in the toxification and detoxification of (pre)-carcinogens closely related to HNSCC, which may appear during smoking and alcohol consumption, may play a role. Genetic polymorphisms in glutathione S-transferases (GSTs) often result in altered detoxification, which may contribute to individual susceptibility to HNSCC. METHODS: We studied the frequencies of polymorphic variants in the GSTP1 gene in 235 patients with HNSCC and 285 healthy controls. In addition, data on exposure to alcohol and tobacco consumption were recorded. DNA was extracted from whole blood, and polymerase chain reaction-based methods were used to detect genetic polymorphisms. RESULTS: In patients with HNSCC and control groups, the homozygous GSTP1 BB genotype was observed in 12.3% and 13.6%, respectively. No statistical differences were found for the GSTP1 AA and GSTP1 AB/GSTP1BB genotypes. CONCLUSIONS: Our study showed that genetic polymorphisms of GSTP1 are not associated with altered susceptibility to HNSCC.     

Immunohistochemical Localization of Glutathione S-Transferase α and π in Human Esophageal Squamous Epithelium, Barrett's Epithelium and Carcinoma

High tissue levels of glutathione S-transferases (GSTs), a family of detoxification enzymes, are inversely correlated with cancer risk in the human gastrointestinal tract. Patients with Barrett's esophagus, wherein squamous epithelium is replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma. Biochemical analyses revealed that Barrett's epithelium contains lower levels of GST enzyme activity as well as some GST isoforms, as compared with squamous epithelium. So far, little information on the immunohistochemical distribution of the GST α and π isoforms in normal squamous epithelium, in Barrett's metaplastic epithelium or in adeno- and squamous cell carcinomas of the esophagus is available. Tissues were fixed in formalin and embedded in paraffin. Three 4 μm thick sections were used for hematoxylin and eosin staining and for immunostaining with antibodies against GST α and π. GST α and π were seen in normal squamous epithelium (0% and 75%, respectively), Barrett's epithelium (75% and 100%), adenocarcinoma (25% and 100%) and squamous cell carcinoma (27% and 91%). Staining was mainly cytoplasmic, though some nuclear staining with the GST π antibody was apparent. The varying expression of GST α and π in normal and (pre)neoplastic esophagus may have consequences for the treatment of these diseases and may contribute to an understanding of the development of these esophageal disorders.     

Phytochemical screening of a Warao pharmacopoeia employed to treat gastrointestinal disorders.

A three-year medical-ethnobotanical investigation among the Warao of the Orinoco Delta in eastern Venezuela documented a pharmacopoeia of 100 plant species representing 45 families. Warao phytotherapists manipulate these plants in diverse manners to produce 259 remedies of various complexities to treat 52 classes of diseases/disorders. National health statistics indicate that gastrointestinal disease ranks as a principal cause of morbidity and mortality in this part of the country. Ten plant species, specifically employed by the Indians against these disorders, were subjected to phytochemical screening. Test results are listed together with the ethnoepidemiological protocol that governs the selection and administration of these medicinal plants in Warao society.     

Intra-fractional uncertainties in cone-beam CT based image-guided radiotherapy (IGRT) of pulmonary tumors.

PURPOSE: Intra-fractional variability of tumor position and breathing motion was evaluated in cone-beam CT (CB-CT) based image-guided radiotherapy (IGRT) of pulmonary tumors. MATERIALS AND METHODS: Twenty-four patients (27 lesions: prim. NSCLC n=6; metastases n=21) were treated with stereotactic body radiotherapy (SBRT) (one to eight fractions). Prior to every treatment fraction (n=66) and immediately after treatment a CB-CT was acquired. Patient motion, absolute drift and drift of the tumor relative to the bony anatomy were measured. Tumor motion was investigated based on the density distribution in the CB-CT. RESULTS: Absolute intra-fractional drift (3D vector) of the tumor position was 2.8 mm+/-1.6 mm (mean +/- SD), maximum 7.2 mm. Poor correlation between patient motion and absolute tumor drift was observed. Changes of the tumor position due to patient motion and due to drifts independently from the bony anatomy were of similar magnitude with 2.1 mm +/- 1.4 mm and 2.3 mm +/- 1.6 mm, respectively. No systematic increase or decrease of breathing motion was seen. The intra-fractional change of breathing motion was more than 2 mm and 3 mm in 39% and 16%, respectively. CONCLUSION: Intra-fractional tumor position and breathing motion were stable. In IGRT of pulmonary tumors we suggest an ITV-to-PTV margin of 5 mm to compensate intra-fractional changes.