TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain.

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain can be so severe that it limits dose and choice of chemotherapy and has significant negative consequences on the quality of life of survivors. Current treatment options for CIPNP are limited and unsatisfactory.

Mimicking Sampson's Retrograde Menstrual Theory in Rats: A New Rat Model for Ongoing Endometriosis-Associated Pain.

Endometriosis is a prevalent gynecologic disease, defined by dysfunctional endometrium-like lesions outside of the uterine cavity. These lesions are presumably established via retrograde menstruation, i.e.

Technical Verification and Assessment of Independent Validation of Biomarker Models for Endometriosis.

There is a great need for a noninvasive diagnosis for endometriosis. Several biomarkers and biomarker panels have been proposed. Biomarker models consisting of CA-125, VEGF, Annexin V, and glycodelin/sICAM-1 were previously developed by our group.

Functional Expression of TRP Ion Channels in Endometrial Stromal Cells of Endometriosis Patients.

Endometriosis is a common gynecological disease that is characterized by the presence of functional endometrial-like lesions in the abdominal cavity. Aside from epithelial cells, these lesions consist of stromal cells that have the capacity to migrate, adhere, proliferate, and induce neuro- and lymphangiogenesis, which allows them to survive at ectopic locations. However, the exact underlying mechanisms that regulate these changes are yet to be elucidated.

Acute Drug Effects on the Human Placental Tissue: The Development of a Placental Murine Xenograft Model.

Objective: A pilot study was conducted to establish a human placental xenograft, which could serve as a model to evaluate the effect of toxic exposures during pregnancy.

Study Design: The protocol consisted of engraftment of third-trimester human placental tissue in immunocompromised mice, after induction of a pseudo-pregnancy state by ovariectomy and progesterone supplementation. To validate the model, the placental tissue before and after engraftment was examined by immunohistochemistry, fluorescence-activated cell sorting (FACS), single-nucleotide polymorphism (SNP) genotyping, and whole transcriptome sequencing (WTSS).

Increased expression of placental growth factor in high-grade endometrial carcinoma.

Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models.

Oxidant balance markers at birth in relation to glycemic and acid-base parameters.

In diabetic pregnancies, suboptimal glycemic control is a risk factor for fetal acidemia and stillbirth. We hypothesized that the diabetic intrauterine milieu (hyperglycemia, hyperinsulinemia, changes in acid-base status) might predispose to oxidative stress. We studied 70 newborns whose mothers had pregestational diabetes (58 with type 1 diabetes mellitus) and 71 control newborns from nondiabetic mothers.

Oxidative stress after antenatal betamethasone: acute downregulation of glutathione peroxidase-3.

Background: Human and experimental data show that antenatal exposure to glucocorticoids (GC) temporarily reduces fetal well-being and impairs the fetal response to hypoxemia.

Aims: We tested the hypothesis that antenatal betamethasone provokes transient oxidative stress, which may be triggered directly by the GC or indirectly by metabolic signals such as increased glucose and free fatty acid (FFA) concentrations.

Study Design: Prospective (single center, 18 months) cohort study in newborns <34 weeks gestational age at birth.

Amniotic fluid markers of fetal cardiac dysfunction in twin-to-twin transfusion syndrome.

Objective: The objective of the study was to determine whether cardiac troponin T (cTnT) and natriuretic peptides can be isolated from the amniotic fluid (AF) of pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) and whether they correlate with fetal echocardiographic findings and recipient survival.

Study Design: AF samples from the recipient sac were obtained in 52 TTTS cases and 16 controls. Samples were assayed for cTnT and natriuretic peptides.

Insulin-like growth factor-II regulates maternal hemodynamic adaptation to pregnancy in rats.

The relationship between maternal plasma volume (PV) expansion and fetal growth is well established, but the underlying mechanisms remain unclear. Here, we examined the influence of maternal body weight and fetoplacental mass on gestational PV increment in the rat. Because IGF-I and IGF-II have growth-promoting and vasoactive properties, their relationship to PV expansion and fetoplacental growth was also studied.

Adverse adipose phenotype and hyperinsulinemia in gravid mice deficient in placental growth factor.

Pregnancy-induced metabolic changes are regulated by signals from an expanded adipose organ. Placental growth factor (PlGF), acting through vascular endothelial growth factor receptor-1, may be among those signals. There is a steep rise in circulating PlGF during normal pregnancy, which is repressed in gravidas who develop preeclampsia.

Diet-induced obesity in gravid rats engenders early hyperadiposity in the offspring.

Exposure to a dysmetabolic in utero environment may be one of the mechanisms to explain why individuals with high birth weight are more likely to remain overweight. We explored this hypothesis in an animal model of diet-induced obesity (DIO). We studied adipose tissue development and glucose tolerance in the offspring of rat dams fed a diet rich in milk and sugar from early adulthood until day (d) 2 postpartum.

Transient catabolic state with reduced IGF-I after antenatal glucocorticoids.

Glucocorticoid (GC) administration before preterm birth reduces neonatal morbidity but may restrain growth. Here we explored the effect of antenatal GC on nutrient substrates [glucose, FFA, amino acids (AA)], and on IGF-I and IGF-binding protein-1 (IGFBP-1). We analyzed umbilical vein (UV) plasma obtained at birth from 91 preterm newborns that received one course of GC (last exposure 1-1358 h before birth) and 49 newborns that did not.

Chronic tumor necrosis factor-alpha infusion in gravid C57BL6/J mice accelerates adipose tissue development in female offspring.

Objective: Tumor necrosis factor (TNF)-alpha is thought to mediate, in part, the link between obesity and insulin resistance, and women with gestational diabetes mellitus (GDM) have raised serum TNF-alpha concentrations. Our objective was to investigate whether systemic TNF-alpha administration into gravid C57BL6/J mice causes a GDM-like syndrome and affects growth and adipose tissue (AT) development in the offspring.

Methods: We assessed glucose tolerance and reproductive outcome in mice infused with saline, or 2 mug or 4 mug recombinant mouse (rm)TNF-alpha by subcutaneous mini-osmotic pumps between days (d)11.

Adipose tissue in offspring of Lepr(db/+) mice: early-life environment vs. genotype.

Gravidas with obesity and diabetes ("diabesity") may transmit this syndrome to their children through genetic and nongenetic mechanisms. Here, we used the Lepr(db/+) diabese mouse to examine the magnitude of these transmission modes, focusing on adipose tissue (AT). We compared the following six groups: wild-type (+/+) offspring from +/+ or db/+ dams (different early life environment) and db/+ offspring from db/+ dams, fed a standard or high-fat diet.

Aging does not aggravate the pregnancy-induced adaptations in glucose tolerance in rats.

Older age is an assumed risk factor for the development of gestational diabetes mellitus (GDM) in women. Here, we studied the effect of age and pregnancy on fat mass and glucose tolerance in rats. We performed intravenous glucose tolerance tests (IVGTTs) in 3- and 9-month-old rats, either nonpregnant or pregnant (day 20).

Maternal body size and birth weight: can insulin or adipokines do better?

Overweight gravidas and gravidas with a robust weight gain have an accrued risk of delivering a large-for-gestational age (LGA) baby. Here, we examined whether the measurement of insulin and adipokines--peptides secreted mainly by adipose tissue--at the glucose challenge test (GCT) improves the prediction of birth weight. We studied 631 singleton pregnancies at 24 to 29 weeks' gestational age (GA) with data on height, baseline body weight (BW), and BW change between baseline and the GCT.

Adipokine profile and C-reactive protein in pregnancy: effects of glucose challenge response versus body mass index.

Objective: To test the hypothesis that gravidas who have an abnormal response to glucose loading have dysfunctional adipose tissue cells that produce more insulin resistance-inducing and proinflammatory adipokines but less insulin-sensitizing adipokines.

Methods: We performed a nested case-control study within a larger sample of gravidas who had a glucose challenge test (GCT) at 24-29 weeks; we compared 73 cases with an abnormal GCT (>8.3 mM) and 146 controls with a strictly normal GCT (<7.

Exogenous corticosteroids and in utero oxygenation modulate indices of fetal insulin secretion.

Low birth weight has long-term effects on glucose-insulin homeostasis. Factors that could mediate intra-uterine "programing" of glucose homeostasis include endogenous and exogenous glucocorticoids, adipose tissue-secreted factors such as adiponectin, and in utero hypoxia. Here, we studied 123 fetuses with gestational age (GA) between 25 and 37 wk and birth weight sd score (BW SDS) between -2.

Pregnancy in mice lacking the vitamin D receptor: normal maternal skeletal response, but fetal hypomineralization rescued by maternal calcium supplementation.

Fetal mineralization appears to be driven by the pregnancy-induced stimulation of intestinal Ca absorption. We thus hypothesized that mineralization would be impaired in fetuses of mice that lack the vitamin D receptor (VDR). Here we report on the maternal response to pregnancy, and the fetal mineralization, in mice with a homozygous disruption of the VDR gene (VDR-/-) mated with wild-type (wt) males.

Is low-dose streptozotocin in rats an adequate model for gestational diabetes mellitus?

Objective: To examine the use of streptozotocin (SZ) in rats as a model for gestational diabetes mellitus (GDM).

Methods: We studied various doses of SZ, either as a single administration (30, 35, 40, or 50 mg/kg, intraperitoneally) on day 1 of pregnancy or as 2 low doses (30 and 20 or 30 and 30 mg/kg) administered 2 days before mating and on day 1 of pregnancy. We examined the effect on maternal and fetal glucose and insulin concentrations and on fetal weight on day 20 of pregnancy.