The goal of the study was to determine whether defects in intracellular Ca(2+) signaling contribute to cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. Depression in cardiac systolic and diastolic function was traced from live diabetic rats to isolated individual myocytes. The depression in contraction and relaxation in myocytes was found in parallel with depression in the rise and decline of intracellular free Ca(2+) concentration ([Ca(2+)](i)). The sarcoplasmic reticulum (SR) Ca(2+) store and rates of Ca(2+) release and resequestration into SR were depressed in diabetic rat myocytes. The rate of Ca(2+) efflux via sarcolemmal Na(+)/Ca(2+) exchanger was also depressed. However, there was no change in the voltage-dependent L-type Ca(2+) channel current that triggers Ca(2+) release from the SR. The depression in SR function was associated with decreased SR Ca(2+)-ATPase and ryanodine receptor proteins and increased total and nonphosphorylated phospholamban proteins. The depression of Na(+)/Ca(2+) exchanger activity was associated with a decrease in its protein level. Thus it is concluded that defects in intracellular Ca(2+) signaling caused by alteration of expression and function of the proteins that regulate [Ca(2+)](i) contribute to cardiomyopathy in STZ-induced diabetic rats. The increase in phospholamban, decrease in Na(+)/Ca(2+) exchanger, and unchanged L-type Ca(2+) channel activity in this model of diabetic cardiomyopathy are distinct from other types of cardiomyopathy.

Objective To test the hypothesis that a combination of PP13, PAPP-A and first-trimester uterine artery Doppler would improve the prediction of preeclampsia. Methods This is a prospective cohort study of pregnant women followed from the first-trimester to delivery. PP13 and PAPPA were determined by immunoassay of maternal serum at 11 – 14 weeks’, when uterine artery Doppler measurements were assessed. Cases identified with any form of preeclampsiawere compared with a control group without preeclampsia. The sensitivity of each marker or their combinations in predicting preeclampsia for different fixed false positive rates was calculated from the ROC curves. Results Forty two women were diagnosed with preeclampsia and 410 women with pregnancies not complicated by preeclampsia were used as controls. For a fixed false positive rate (FPR) of 20%, PP13, PAPP-A and mean uterine artery pulsatility index identified 49%, 58% and 62% respectively, of women who developed any form of preeclampsia. PP13 was best in predicting early onset preeclampsia with a sensitivity of 79% at a 20% FPR.Combinations of the three first trimester assessments did not improve the prediction of preeclampsia in later pregnancy. Conclusion First-trimester PP13, PAPP-A and uterine artery PI are reasonable, individual predictors of women at risk to develop preeclampsia. Combinations of these assessments do not further improve the prediction of preeclampsia

Autism is a disorder of neurobiological origin characterized by problems in communication and social skills and repetitive behavior. After more than six decades of research, the etiology of autism remains unknown, and no biomarkers have been proven to be characteristic of autism. A number of studies have shown that the cytokine levels in the blood, brain, and cerebrospinal fluid (CSF) of autistic subjects differ from that of healthy individuals; for example, a series of studies suggests that interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) are significantly elevated in different tissues in autistic subjects. However, the expression of some cytokines, such as IL-1, IL-2, transforming growth factor-β (TGF-β), and granulocyte-macrophage colony-stimulating factor (GM-CSF), is controversial, and different studies have found various results in different tissues. In this review, we focused on several types of proinflammatory and anti-inflammatory cytokines that might affect different cell signal pathways and play a role in the pathophysiological mechanism of autistic spectrum disorders.

The goal of this study was to examine whether alteration of sarcoplasmic reticulum (SR) protein levels is associated with early-onset diastolic and late-onset systolic dysfunction in streptozotocin (STZ)-induced diabetic rat hearts. Four-week diabetic rat hearts exhibited slow relaxation, whereas 6-wk diabetic rat hearts exhibited slow and depressed contraction. Total phospholamban level was increased, and phosphorylated level was decreased in 4- and 6-wk diabetic rat hearts. Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) protein level was unchanged in 4-wk but decreased in 6-wk diabetic rat hearts. Only the apparent affinity of SR Ca2+ uptake for Ca2+ was decreased in 4-wk diabetic rat hearts, but the apparent affinity and the maximum rate was decreased in 6-wk diabetic rat hearts. Insulin treatment of the diabetic rats normalized SR protein expression and function. It was concluded that an increase in nonphosphorylated phospholamban and a decrease in the apparent affinity of SR Ca2+ pump for Ca2+ are associated with early-onset diastolic dysfunction and decreases in SERCA2 protein level and apparent affinity and maximum velocity of SR Ca2+ pump are associated with late-onset systolic dysfunction in diabetic rats.

Preeclampsia and intrauterine growth restriction (IUGR) are major contributors to perinatal mortality and morbidity worldwide. Both are characterized by impaired trophoblastic invasion of the maternal spiral arteries and their conversion from narrow muscular vessels to wide non-muscular channels. Despite improvement in the understanding of the pathophysiology of these conditions, ability to accurately identify pregnant woman who will develop them is limited. This greatly impairs the development and testing of preventive interventions. While different measures of placental dysfunction have been associated with increased risk for adverse pregnancy outcomes, the ability of any single one to accurately predict these outcomes is poor. Developing predictive tests is further challenged by difficulty in the timing of the measurements, as both the structural and biochemical characteristics of the placenta change with increasing gestational age. The ideal screening test would accurately predict the development of adverse pregnancy outcomes early enough to provide a window for preventive interventions. Improvement in ultrasound technology provides potentially useful novel tools for evaluating placental structure, but measuresments need to be standardized in order to be useful. Maternal serum analyte screening is a noninvasive test of placental biochemical function, but present serum marker alone is not sufficiently accurate to suggest its routine use in clinical practice. The use of first trimester biochemical markers in combination with uterine artery Doppler screening is promising as a potential screening tool. Prospective longitudinal studies using standardized methodology are necessary to further evaluate the choice of parameters and strategies of combination to achieve the best predictive models.