The toxicology of perfluorooctanoate

PFOA is a peroxisome proliferator (PPAR agonist) and exerts morphological and biochemical effects characteristic of PPAR agonists. These effects include increased beta-oxidation of fatty acids, increases in several cytochrome P-450 (CYP450)-mediated reactions, and inhibition of the secretion of very low-density lipoproteins and cholesterol from the liver. These effects on lipid metabolism and transport result in a reduction of cholesterol and triglycerides in serum and an accumulation of lipids in the liver. The triad of tumors observed (liver, Leydig cell, and pancreatic acinar-cell) is typical of many PPAR agonists and is believed to involve nongenotoxic mechanisms. The hepatocellular tumors observed in rats are likely to have been the result of the activation of the peroxisome proliferator activated receptor alpha (PPARalpha). The tumors observed in the testis (Leydig-cell) have been hypothesized to be associated with an increased level of serum estradiol in concert with testicular growth factors. The mechanism responsible for the acinar-cell tumors of the pancreas in rats remains the subject of active investigation. The mechanism resulting in the hepatocellular tumors in rats (PPARalpha activation) is not likely to be relevant to humans. Similarly, the proposed mechanism for Leydig-cell tumor formation is of questionable relevance to humans. Acinar tumors of the pancreas are rare in humans, and the relevance of the these tumors, as found in rats, to humans is uncertain. Epidemiological investigations and medical surveillance of occupationally exposed workers have not found consistent associations between PFOA exposure and adverse health effects.     

Evaluation of the Biocompatibility and Osteogenic Properties of Metal Oxide Coatings Applied by Magnetron Sputtering as Potential Biofunctional Surface Modifications for Orthopedic Implants

Biomaterials with adequate properties to direct a biological response are essential for orthopedic and dental implants. The surface properties are responsible for the biological response; thus, coatings with biologically relevant properties such as osteoinduction are exciting options to tailor the surface of different bulk materials. Metal oxide coatings such as TiO₂, ZrO₂, Nb₂O₅ and Ta₂O₅ have been suggested as promising for orthopedic and dental implants. However, a comparative study among them is still missing to select the most promising for bone-growth-related applications. In this work, using magnetron sputtering, TiO₂, ZrO₂, Ta₂O₅, and Nb₂O₅ thin films were deposited on Si (100) substrates. The coatings were characterized by Optical Profilometry, Scanning Electron Microscopy, Energy-Dispersive X-ray Spectroscopy, X-ray Photoelectron Spectroscopy, X-ray Diffraction, Water Contact Angle measurements, and Surface Free Energy calculations. The cell adhesion, viability, proliferation, and differentiation toward the osteoblastic phenotype of mesenchymal stem cells plated on the coatings were measured to define the biological response. Results confirmed that all coatings were biocompatible. However, a more significant number of cells and proliferative cells were observed on Nb₂O₅ and Ta₂O₅ compared to TiO₂ and ZrO_2. Nevertheless, Nb₂O₅ and Ta₂O₅ seemed to induce cell differentiation toward the osteoblastic phenotype in a longer cell culture time than TiO₂ and ZrO₂.     

Deoxyribonucleic acid-damaged sperm in cryopreserved-thawed specimens from cancer patients and healthy men

A similarity was found between the percentage of thawed, DNA-damaged spermatozoa in cancer patients and that in candidates to become sperm bank donors who had low sperm cryofreezability. Both groups were significantly different from the sperm bank donor group. It is suggested that the higher rate of DNA fragmentation in sperm from cancer patients compared with sperm bank donors is apparently a result of selecting donors by the level of sperm cryofreezability (i.e., high), rather than a direct effect of an existing malignancy.     

Accuracy of self-screening for contraindications to combined oral contraceptive use

OBJECTIVE: To estimate how well a convenience sample of women from the general population could self-screen for contraindications to combined oral contraceptives using a medical checklist. METHODS: Women 18-49 years old (N=1,271) were recruited at two shopping malls and a flea market in El Paso, Texas, and asked first whether they thought birth control pills were medically safe for them. They then used a checklist to determine the presence of level 3 or 4 contraindications to combined oral contraceptives according to the World Health Organization Medical Eligibility Criteria. The women then were interviewed by a blinded nurse practitioner, who also measured blood pressure. RESULTS: The sensitivity of the unaided self-screen to detect true contraindications was 56.2% (95% confidence interval [CI] 51.7-60.6%), and specificity was 57.6% (95% CI 54.0-61.1%). The sensitivity of the checklist to detect true contraindications was 83.2% (95% CI 79.5-86.3%), and specificity was 88.8% (95% CI 86.3-90.9%). Using the checklist, 6.6% (95% CI 5.2-8.0%) of women incorrectly thought they were eligible for use when, in fact, they were contraindicated, largely because of unrecognized hypertension. Seven percent (95% CI 5.4-8.2%) of women incorrectly thought they were contraindicated when they truly were not, primarily because of misclassification of migraine headaches. In regression analysis, younger women, more educated women, and Spanish speakers were significantly more likely to correctly self-screen (P<.05). CONCLUSION: Self-screening for contraindications to oral contraceptives using a medical checklist is relatively accurate. Unaided screening is inaccurate and reflects common misperceptions about the safety of oral contraceptives. Over-the-counter provision of this method likely would be safe, especially for younger women and if independent blood pressure screening were encouraged.     

Early risk factors for miscarriage: a prospective cohort study in pregnant women

Many pregnancies are lost during early gestation, but clinicians still lack tools to recognize risk factors for miscarriage. Thus, the identification of risk factors for miscarriage during the first trimester in women with no obvious risk for a pregnancy loss was the aim of this prospective cohort trial. A total of 1098 women between gestation weeks 4 and 12 in whom no apparent signs of a threatened pregnancy could be diagnosed were recruited. Demographic, anamnestic, psychometric and biological data were documented at recruitment and pregnancy outcomes were registered subsequently. Among the cases with sufficiently available data, 809 successfully progressing pregnancies and 55 subsequent miscarriages were reported. In this cohort, risk of miscarriage was significantly increased in women at higher age (>33 years), lower body mass index (< or =20 kg/ m(2)) and lower serum progesterone concentrations (< or =12 ng/ml) prior to the onset of the miscarriage. Women with subsequent miscarriage also perceived higher levels of stress/demands (supported by higher concentrations of corticotrophin-releasing hormone) and revealed reduced concentrations of progesterone-induced blocking factor. These risk factors were even more pronounced in the subcohort of women (n = 335) recruited between gestation weeks 4 and 7. The identification of these risk factors and development of an interaction model of these factors, as introduced in this article, will help clinicians to recognize pregnant women who require extra monitoring and who might benefit from therapeutic interventions such as progestogen supplementation, especially during the first weeks of pregnancy, to prevent a miscarriage.     

Utility of screening for other causes of infertility in women with "known" polycystic ovary syndrome

We investigated the prevalence of abnormal screening results (questionnaire and testing for other causes of oligo-ovulation, male or tubal factor infertility) in a group of 1,313 oligo-ovulatory women (included and excluded subjects) whose condition was screened for inclusion in the Pregnancy in Polycystic Ovary Syndrome trial, a multicenter clinical trial that was conducted at 13 sites in the United States. Other than failure to demonstrate laboratory evidence of hyperandrogenemia, the most common reasons for subject exclusion were persistent oligospermia and tubal factor infertility.