Lack of metformin effect on mouse embryo AMPK activity: implications for metformin treatment during pregnancy.

Background: Adenosine monophosphate-activated protein kinase (AMPK) is stimulated in embryos during diabetic pregnancy by maternal hyperglycaemia-induced embryo oxidative stress. Stimulation of AMPK disrupts embryo gene expression and causes neural tube defects. Metformin, which may be taken during early pregnancy, has been reported to stimulate AMPK activity.

Alternative models in developmental toxicology.

In light of various pressures, toxicologists have been searching for alternative methods for safety testing of chemicals. According to a recent policy in the European Union (Regulation, Evaluation Authorisation and Restriction of Chemicals, REACH), it has been estimated that over the next twelve to fifteen years, approximately 30,000 chemicals may need to be tested for safety, and under current guidelines such testing would require the use of approximately 7.2 million laboratory animals [ Hofer et al.

Novel mitochondria-targeted antioxidant peptide ameliorates burn-induced apoptosis and endoplasmic reticulum stress in the skeletal muscle of mice.

This study tested the hypothesis that a novel mitochondria-targeted SS-31 peptide attenuates the burn injury-induced apoptosis and endoplasmic reticulum stress and improves insulin sensitivity in the skeletal muscle. Following 30% total body surface area burn or sham burn, mice were injected daily with SS-31 peptide (5 mg/kg body weight), and the rectus abdominis muscles collected on postburn days 1, 3, and 7. The tissues were subjected to various biochemical and immunohistochemical analyses.

Assessment of research models for testing gene-environment interactions.

Throughout the last century, possible effects of exposure to toxicants, nutrients or drugs were examined primarily by studies of groups or populations. Individual variation in responses was acknowledged but could not be analyzed due to lack of information or tools to analyze individual genetic make-ups and lifestyle factors such as diet and activity. The Human Genome, Haplotype Map, 1000Genomes, and Human Variome Projects are identifying and cataloging the variation found within humans.

Cardiac outflow tract septation failure in Pax3-deficient embryos is due to p53-dependent regulation of migrating cardiac neural crest.

During neural tube closure, Pax3 is required to inhibit p53-dependent apoptosis. Pax3 is also required for migration of cardiac neural crest (CNC) from the neural tube to the heart and septation of the primitive single cardiac outflow tract into the aorta and pulmonary arteries. Whether Pax3 is required for CNC migration and outflow tract septation by inhibiting p53-dependent apoptosis is not known.

The effects of blocking the actions of estrogen and progesterone on the rates of proliferation and apoptosis of cervical epithelial and stromal cells during the second half of pregnancy in rats.

Serum levels of the ovarian hormones relaxin, estrogen, and progesterone are elevated during the second half of 23-day rat pregnancy when dramatic growth of the cervix occurs. Recently, we demonstrated that relaxin contributes to cervical growth by both promoting cell proliferation and inhibiting apoptosis of cervical cells during late pregnancy. The objective of this study was to determine the influence of estrogen and progesterone on the rates of proliferation and apoptosis of cervical cells at 3-day intervals during the second half of rat pregnancy.

Clinical use of relaxin to facilitate birth: reasons for investigating the premise.

In the United States, both medical and nonmedical factors have driven the cesarean section rate to over 26% of all deliveries. In addition to questions of increased cost associated with operative delivery, some have questioned the ethics of performing cesarean section for nonmedical reasons. Reduction of both the duration and the pain associated with vaginal delivery would likely bring about a decline in the rate of both medical and nonmedical cesarean sections.

Porcine and human relaxin bioactivity: bioactivities of porcine relaxin and human relaxin do not differ in mice and rats.

This study compares the bioactivity of porcine relaxin-1 to that of recombinant human relaxin-2 in mice and rats. The effects of the two hormone preparations on elongation of the mouse interpubic ligament and both the wet weight and the extensibility of the rat cervix were compared. No difference in bioactivity was detected between porcine relaxin-1 and recombinant human relaxin-2 in either rodent.

The extent to which relaxin promotes proliferation and inhibits apoptosis of cervical epithelial and stromal cells is greatest during late pregnancy in rats.

Relaxin promotes marked growth of the cervix during the second half of rat pregnancy, and this growth is accompanied by an increase in both epithelial and stromal cells. The objective of this study was to test the hypothesis that the extent to which relaxin promotes proliferation and inhibits apoptosis of cervical cells is greatest during late pregnancy in rats. The influence of neutralization of circulating relaxin by iv injection of 5 mg monoclonal antibody against rat relaxin (MCA1) was examined at 3-d intervals throughout the second half of pregnancy.