Periconceptional multivitamin folic acid use,dietary folate,total folate and risk of neural tube defects in South Carolina

PURPOSE: To investigate whether dietary folate or multivitamin folic acid taken 3 months before conception and during the first 3 months of pregnancy reduces the risk of isolated occurrent neural tube defect (NTD)-affected pregnancies. METHODS: This population-based case control study conducted between 1992 and 1997 included 179 women with NTD-affected pregnancies and 288 randomly selected controls. Women completed a food frequency questionnaire and were interviewed about lifestyle behaviors, pregnancy histories and use of multivitamins. RESULTS: Use of 0.4 mg or more of multivitamin folic acid at least 3 times per week during the periconceptional period showed no statistically significant reduction in NTD risk [adjusted odds ratio (AOR) = 0.55, 95% confidence interval (CI) = 025, 1.22]. After adjusting for covariates, protective effects for NTDs were observed at the highest quartiles of dietary folate and total folate (daily dietary folate plus daily multivitamin folic acid); the respective odds ratios were 0.40 (95% CI = 0.19, 0.84) and 0.35 (95% CI = 0.17, 0.72). CONCLUSIONS: This study illustrates some of the difficulties in determining effects of folic acid and dietary folate in a population where the consumption of foods rich in folate and the use of multivitamins are increasing and the rate of NTDs is declining. Studies are needed to monitor future changes in folate levels and their effect on health.     

Inhibition of markers of hepatic stellate cell activation by the hormone relaxin

Hepatic fibrosis results from excess extracellular matrix produced primarily by hepatic stellate cells (HSC). In response to injury, HSC differentiate to a myofibroblastic phenotype expressing smooth muscle actin and fibrillar collagens. Relaxin is a polypeptide hormone shown to have antifibrotic effects in fibrosis models. In this study, activated HSC from rat liver were treated with relaxin to determine if relaxin can reverse markers of HSC activation. Relaxin treatment resulted in a decrease in the expression of smooth muscle actin, but had no effect on cell proliferation rate. The levels of total collagen and type I collagen were reduced, while the synthesis of new collagen was inhibited. Furthermore, relaxin caused an increase in the expression and secretion of rodent interstitial collagenase (MMP-13), but there was no effect on the gelatinases MMP-2 or MMP-9. Relaxin also increased secretion of TIMP-1 and TIMP-2. The effective concentration of relaxin to induce these effects was consistent with action through the relaxin receptor. In conclusion, relaxin reversed markers of the activated phenotype of HSC including the production of fibrillar collagen. At the same time, the activity of a fibrillar collagenase was increased. These data suggest that relaxin not only inhibits HSC properties that contribute to the progression of hepatic fibrosis, but also promotes the clearance of fibrillar collagen. Therefore, relaxin may be a useful approach in the treatment of hepatic fibrosis.     

Chronic ethanol consumption impairs receptor-mediated endocytosis of MAA-modified albumin by liver endothelial cells

Alcoholic liver disease has been associated with abnormalities in receptor-mediated endocytosis (RME) which results in abnormal degradation of metabolically altered proteins. Model systems using formaldehyde-modified albumin (f-Alb) have shown an impairment in RME following chronic alcohol consumption utilizing both in situ perfused rat livers and isolated rat liver endothelial cells (LECs). The discovery that alcohol metabolite derived aldehydes can modify proteins prompted a study to determine if malondialdehyde-acetaldehyde-modified albumin (MAA-Alb) would be degraded similar to that reported for f-Alb, and whether ethanol-fed rats would demonstrate an impaired RME with respect to this ligand which occurs as a consequence of chronic ethanol consumption. MAA-Alb was degraded slightly more than f-Alb in both in situ perfused livers and at the single cell level. This degradation was completely inhibited with 100x unlabeled f-Alb, which suggests the use of a similar receptor. Following alcohol consumption there was a 50-60% decrease in MAA-Alb degradation in whole livers and isolated LECs. Utilizing isolated LECs it was determined that impairment in internalization was the most likely mechanism for the decrease in the amount of MAA-Alb that was degraded. These data show that chronic alcohol consumption by rats does in fact impair RME of alcohol metabolite-derived adducted proteins, and this impairment is due to a defect in the post-internalization step rather than the binding or degradation of the modified protein.     

Effect of acute drought stress and time of harvest on phytochemistry and dry weight of St. John's wort leaves and flowers

The phytochemistry and dry weight of cultivated St. John's wort are significantly influenced by acute drought stress and time of harvest. In this study, plants subjected to brief drought stress during both flower and seed development periods exhibited increased concentrations in 8 of the 10 phytochemicals examined in this study, including hypericin, pseudohypericin, chlorogenic acid, rutin, hyperoside, isoquercitrin, quercitrin, and quercetin. Increases ranged from 5% to 36% (hyperoside and rutin, respectively). Conversely, the concentrations of hyperforin and adhyperforin in flowers were decreased by an average of 10% in drought-stressed plants as compared to well-watered control plants. Acute drought stress decreased flower dry weight significantly during both drydown periods, although vegetative parameters (height, leaf dry weight and stem dry weight) were not adversely affected. While acute drought stress significantly altered the chemical yield in the leaves and flowers (phytochemical content x harvested dry weight), the time of harvest was the predominant factor determining phytochemical concentration in the organs of H. perforatum.     

Cognitive-existential group psychotherapy for women with primary breast cancer: a randomised controlled trial

BACKGROUND: We conducted a randomised, controlled trial of cognitive-existential group therapy (CEGT) for women with early stage breast cancer receiving adjuvant chemotherapy with the aim of improving mood and mental attitude to cancer. METHODS: Women were randomised to 20 sessions of weekly group therapy plus 3 relaxation classes or to a control arm receiving 3 relaxation classes. Assessments, independently done at baseline, 6 and 12 months, included a structured psychiatric interview and validated questionnaires covering mood, attitudes to cancer, family relationships, and satisfaction with therapy. RESULTS: Three hundred and three of 491 (62%) eligible patients participated over 3 years. Distress was high pre-intervention: 10% were diagnosed as suffering from major depression, 27% from minor depression and 9% from anxiety disorders. On an intention-to-treat analysis, there was a trend for those receiving group therapy (n=154) to have reduced anxiety (p=0.05, 2-sided) compared to controls (n=149). Women in group therapy also showed a trend towards improved family functioning compared to controls (p=0.07, 2-sided). The women in the groups reported greater satisfaction with their therapy (p<0.001, 2-sided), appreciating the support and citing better coping, self-growth and increased knowledge about cancer and its treatment. They valued the CEGT therapy. Overall effect size for the group intervention was small (d=0.25), with cancer recurrence having a deleterious effect in three of the 19 therapy groups. Psychologists as a discipline achieved a moderate mean effect size (d=0.52). CONCLUSION: CEGT is a useful adjuvant psychological therapy for women with early stage breast cancer. Interaction effects between group members and therapists are relevant to outcome. Group-as-a-whole effects are powerful, but the training and experience of the therapist is especially critical to an efficacious outcome.     

Genetics: Direct Comparison of Detection Systems Used for the Development of Single-Cell Genetic Tests in Preimplantation Genetic Diagnosis

Purpose: Single-cell polymerase chain reaction (PCR) requires efficient amplification and accurate detection. We compare the accuracy of heteroduplex, fluorescent-fragment, and fluorescent single-strand conformation polymorphism (F-SSCP) analysis as detection systems for analysis of a PCR assay developed for preimplantation genetic diagnosis. Methods: A single-cell, fluorescent multiplex PCR assay was developed for the cystic fibrosis F508 mutation and the short tandem repeat, D21S11. Detection systems were compared by analyzing blinded PCR products. Results: Amplification rates for cystic fibrosis were 89% by heteroduplex and 91% by fragment analysis, while it was 72% for D21S11 by fragment analysis. No difference in allele dropout was detected for cystic fibrosis by any method (2%). Overall accuracy was high, >97%, although SSCP was the least accurate. Conclusions: Heteroduplex and fragment analysis proved equal in the diagnosis of a single amplified locus. We determined that fragment analysis allows maximal accuracy of detection and permits analysis of a second loci, controlling for DNA contamination and allelic dropout.     

Quality assurance in gynecologic cytology. The value of cytotechnologist-cytopathologist discrepancy logs

We describe a simple method for displaying and evaluating the concordance or discordance between cytotechnologists (CTs) and cytopathologists (CPs) on gynecologic cases. The provisional diagnoses made by the CTs and the final diagnoses of the CPs are captured by the laboratory information system; data generated for specified periods are displayed as a 10 x 10 matrix that classifies each possible diagnosis made by the CT and CP into 1 of 10 major categories. Matrices are generated for the entire laboratory and for individual CTs; individual CTs are evaluated based on their deviation from the laboratory average. Three statistical measures are generated: percentage of discordant diagnoses, a kappa statistic, and a weighted measure. During a 2.5-year period, approximately 4,200 cases were referred to a CP for review every 6 months. The median discordance in diagnoses increased during 2 years from 21% to 34%, and the kappa value fell from 0.69 to 0.38. This was attributed primarily to 1 CT, whose performance, as well as that of the entire laboratory, improved after remedial action. Measures of CT-CP diagnostic concordance are a useful and efficient measure of CT performance and can be incorporated into mandatory semiannual performance evaluations.     

Human Mast Cell Apoptosis Is Regulated Through Bcl-2 and Bcl-XL

It is well established that human mast cell proliferation and maturation are regulated by kit ligand (stem cell factor). Little is known, however, about how these two processes are negatively regulated and thus, how mast cell number is controlled in normal and pathologic conditions. We therefore first hypothesized that SCF-dependent human mast cells would undergo programmed cell death (apoptosis) on removal of SCF as has been shown for growth factor-dependent rodent mast cells. We then examined whether SCF acts as a survival factor through the regulation of the bcl-2 family of apoptosis-regulatory genes. As hypothesized, elimination of SCF from primary peripheral blood-derived human mast cell cultures resulted in a significant apoptotic process. During apoptosis, down-regulation of the two apoptosis-regulatory proteins Bcl-2 and Bcl-X_Lwas observed. Moreover, a deregulated expression of these two proteins was found in two human mast cell lines which are SCF-independent. Thus, SCF functions as a survival factor by repressing apoptosis of human mast cells through Bcl-2 and Bcl-X_L. Deregulated expression of these antiapoptotic proteins may contribute to proliferation and accumulation of mast cells in certain forms of systemic mast cell disorders.