Cu isotope ratios are meaningful in ovarian cancer diagnosis.

BACKGROUND: Ovarian cancer diagnosis is currently based on imaging and circulating CA-125 concentrations with well-known limits to sensitivity and specificity. New biomarkers are required to complement CA-125 testing to increase effectiveness. Increases in sensitivity of isotopic separation via multi collector inductively coupled plasma-mass spectrometry have recently allowed highly accurate measurement of copper (Cu) isotopic variations. Studies in breast cancer patients have revealed changes of serum copper isotopic composition demonstrating the potential for development as a cancer biomarker. Evaluating 65Cu/63Cu ratios (δ65Cu) in serum samples from cancer patients has revealed a strong correlation with cancer development. In this study blood samples from forty-four ovarian cancer patients, and 13 ovarian biopsies were investigated. RESULTS: Here we demonstrate that changes in Cu isotopes also occurs in ovarian cancer patients. Copper composition determined by multiple collector inductively coupled plasma mass spectrometry revealed that the copper isotopic ratio δ65Cu in the plasma of 44 ovarian cancer patient cohort was significantly lower than in a group of 48 healthy donors, and indicated that serum was enriched for 63Cu. Further analysis revealed that the isotopic composition of tumour biopsies was enriched for 65Cu compared with adjacent healthy ovarian tissues. CONCLUSIONS: We propose that these changes are due to increase lactate and Cu transporter activities in the tumour. These observations demonstrate that, combined with existing strategies, δ65Cu could be developed for use in ovarian cancer early detection.

Direct monitoring of breast and endometrial cancer cell epigenetic response to DNA methyltransferase and histone deacetylase inhibitors.

DNA methylation and histone deacetylation are key epigenetic processes involved in normal cellular function and tumorigenesis. Therapeutic strategies based on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors are currently in use and under development for the treatment of cancers. Genome-wide DNA methylation profiling has been proposed for use in disease diagnosis, and histone modification profiling for disease stratification will follow suit. However, whether epigenome sequencing technologies will be feasible for rapid clinic diagnosis and patient treatment monitoring remains to be seen, and alternative detection technologies will almost certainly be needed. Here we used electrochemical impedance spectroscopy (EIS) employing a graphene-based screen-printed electrode system to directly measure global DNA methylation and histone H3 acetylation to compare non-cancer and breast cancer cell lines. We demonstrated that whilst global methylation was not useful as a differential marker in the cellular systems tested, histone H3 acetylation was effective at higher chromatin levels. Using breast and endometrial cancer cell models, EIS was then used to monitor cellular responses to the DNMT and HDAC inhibitors 5-Aza-2'-deoxycytidine and suberoylanilide hydroxamic acid in vitro, and proved very effective at detecting global cellular responses to either treatment, indicating that this approach could be useful in following treatment response to epigenetic drugs. Moreover, this work reports the first combined analysis of two epigenetic markers using a unified graphene-based biosensor platform, demonstrating the potential for multiplex analysis of both methylation and acetylation on the same sample.

MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis.

CONTEXT: Endometrium of fertile women expresses progesterone-regulated Mucin 1 (MUC1) that carries selectin ligands recognized by the human blastocyst. Altered MUC1 expression at the time of implantation may contribute to endometrial infertility. OBJECTIVE: The aim was to assess the expression of MUC1 in the endometrium from polycystic ovary syndrome (PCOS), endometriosis, and fertile women in comparison with other hormone-regulated proteins [hydroxysteroid dehydrogenase (HSD) 1, HSD2, estrogen receptor (ER) and progesterone receptor (PR)]. DESIGN AND PATIENTS: Endometrial samples were obtained from 33 fertile patients, 26 ovulatory PCOS patients, 15 anovulatory PCOS patients, and 25 endometriosis patients. MAIN OUTCOME MEASURE: Immunohistochemistry assessed the expression of MUC1 subunits ER, PR, HSD1, and HSD2 in endometrial epithelium. Endometrial MUC1 expression was quantified by immunoblots and RT-PCR. HSD1 and HSD2 expression was assayed by RT-PCR. RESULTS: MUC1ND expression was significantly higher in ovulatory PCOS than in fertile and anovulatory PCOS patients, even after progesterone stimulation. MUC1ND and -CD expression was lower in anovulatory PCOS than in fertile patients. Only MUC1CD expression was lower in endometriosis patients. Endometrial ER expression was significantly higher in PCOS and endometriosis patients, whereas PR expression was significantly higher in PCOS than in fertile patients. The expression of HSD1 was significantly higher in anovulatory PCOS than in fertile patients. Expression of HSD2 was significantly higher in PCOS patients and lower in endometriosis patients. CONCLUSION: Expression of MUC1 subunits in the infertile endometrium is significantly different from fertile and appears to be a component of altered gene expression that potentially contributes to endometrial insufficiency.

Fractionation of persistent organic pollutants in fish oil by high-performance liquid chromatography on a 2-(1-pyrenyl)ethyl silica column.

The analysis of persistent organic pollutants in foodstuffs has become necessary for control of their levels in products for human and animal consumption. These analytical procedures usually require a fractionation step in order to separate the different families of pollutants to avoid interferences during the instrumental determination. In this study the separation was carried out on a 2-(1-pyrenyl)ethyl silica column, where analyte fractionation was based on differences in planarity and aromaticity. The fractionation of several types of persistent organic pollutants found in fish oil samples was studied; the pollutants included polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated biphenyls, polybrominated diphenyl ethers, and some organochlorine pesticides. Fractions were analyzed by high-resolution gas chromatography with electron-capture detection and high-resolution gas chromatography-high resolution mass spectroscopy. Finally, the whole method (including the purification, fractionation, and instrumental determination steps) was validated and successfully applied to the analysis of several samples of fish oil.

L-selectin ligands in human endometrium: comparison of fertile and infertile subjects.

BACKGROUND: L-selectin ligands, localized to the luminal epithelium at the time of implantation, may support the early stages of blastocyst attachment. We have assessed the expression of two L-selectin ligands, defined by MECA-79 and HECA-452 monoclonal antibodies, and the sulfotransferase GlcNAc6ST-2, involved in generation of L-selectin ligand epitopes, in the secretory phase of the endometrium from fertile and infertile patients. METHODS: Endometrial samples were obtained from 33 fertile, 26 PCOS, 25 endometriosis and 33 patients diagnosed with unexplained infertility. L-selectin ligands and GlcNAc6ST-2 expression was assessed by immunohistochemistry and immunoblotting. RESULTS: Immunohistochemical staining of uterine epithelium, from fertile and infertile women, demonstrated differential expression of MECA-79 and HECA-452 epitopes. In fertile women in the secretory phase MECA-79 was more strongly expressed, particularly on the lumen, than in infertile women. HECA-452 staining was significantly stronger in the glands in PCOS and endometriosis patients than in fertile women. GlcNAc6ST-2 expression was reduced in infertile patients, correlating with MECA-79 expression. CONCLUSIONS: This study demonstrated significant differences in expression of L-selectin ligands between fertile and infertile women in natural cycles, and could contribute to patient assessment prior to initiating fertility treatment.

A survey of methods used to measure symphysis fundal height.

Symphysis fundal height (SFH) is currently used in the UK as a screening test to identify which pregnancies may require additional investigations including the use of ultrasound fetal biometry. The routine use of SFH has been subjected to extensive research assessing its sensitivity and also inter and intraobserver variation. This study's aim was to assess the current UK practice of SFH measurement and particularly looked at methods used in its measurement. A total of 250 healthcare professionals (doctors and midwives) were asked to complete a structured anonymous questionnaire of which 211 health professionals agreed to participate. The results revealed that SFH is used less frequently by the professionals with less than 10 years clinical experience compared to professionals with more than 10 years clinical experience. In addition there was significant variance in the methods used to measure SFH that would increase the interobserver error.

Amniotic fluid endothelin levels and the incidence of premature rupture of membranes.

Objective. The purpose of this prospective study was to record Endothelin 1 (ET1) concentrations in the second trimester amniotic fluid and in women who develop premature rupture of membranes (PROM), preterm premature rupture of the membranes (PPROM) and in women with uneventful pregnancies. Method. Amniotic fluid was retrieved by amniocentesis from 125 women in the second trimester of pregnancy. The levels of Endothelin were measured by a sensitive and specific radioimmunoassay. Results. From the 125 women included in the study 20 developed PROM and preterm PROM (13 PPROM and 7 PROM). The ET1 concentration was significantly higher (P<0.001) in PROM and PPROM than in normal pregnancy (96.4 vs. 43 pg/ml). The sub-analysis of the two rupture of membranes groups found that the concentration of ET1 was higher in the PPROM than in PROM (118 vs. 72 pg/ml). Conclusion. The amniotic fluid concentration of ET1 is elevated by the second trimester in women who later develop preterm PROM or term PROM.

Second trimester amniotic fluid endothelin concentration. A possible predictor for pre-eclampsia.

The mechanism of pre-eclampsia is still an enigma. There is now some evidence that amniotic concentrations of endothelin is elevated in pregnancies associated with pre-eclampsia. The aim of this prospective observational study was to record the concentration of amniotic fluid endothelin and compare this in women who develop pre-eclampsia and women who do not develop pre-eclampsia. Amniotic fluid concentration of endothelin is elevated by the second trimester in women who later develop pre-eclampsia.

[Myxoma of the left ventricle: a cause of syncope in an adolescent]. / Mixoma de ventrículo izquierdo como causa de síncope en adolescente.

Clinical diagnosis of cardiac tumours is often difficult. We present the case of a 17 year-old boy in whom a left ventricular tumour was discovered during on diagnostic work-up for a syncope. The tumour was removed and histology confirmed the diagnosis of myxoma.

[Transmyocardial revascularization with laser]. / Revascularización transmiocárdica con láser.

Patients with severe angina pectoris, refractory to medical treatment, in which conventional revascularization (PTCA or bypass surgery) is not possible because they present advanced coronary artery disease with a poor distal bed, account for an important clinical problem due to an increasing incidence, combined with poor quality of life, an elevated risk of severe complications, repeated hospital admissions and high mortality rate. Laser transmyocardial revascularization provides a new therapeutic alternative for these patients. Although up to now there are only a few published series, with a small number of patients, the results obtained in the two ongoing multicentric studies in Europe and the United States (including more than 500 patients at present) are quite promising. It is a simple surgical procedure, but its associated mortality is not to be dismissed (in the beginning 12% and currently 5%), because patients are in an advanced evolutionary stage. In Spain this procedure has been available since April 1996 and the results have been encouraging. In our small series we have noted a significant symptomatic improvement and better quality of life.

[Resection with removal of a primary fibrosarcoma of the left auricle. Value of two-dimensional echocardiography in the clinical diagnosis]. / Resección con éxito de un fibrosarcoma primario de aurícula izquierda. Valor del ecocardiograma bidimensional en el diagnóstico clínico.

A primary fibrosarcoma was removed from the left atrium in a 58-year-old woman. We comment on the rareness of this cardiac neoplasm, the usefulness of two-dimensional echocardiogram in the clinical diagnosis of all cardiac tumors, and also the necessity for surgical treatment.