17 research outputs found
First-Trimester Follistatin-Like-3 Levels in Pregnancies Complicated by Subsequent Gestational Diabetes Mellitus
Objective: To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies complicated by subsequent gestational diabetes mellitus (GDM). Research Design and Methods: This was a nested case-control study of subjects enrolled in a prospective cohort of pregnant women with and without GDM (2 abnormal values on a 100-g glucose tolerance test at ~28 weeks of gestation). We measured FSTL3 levels in serum collected during the first trimester of pregnancy. Logistic regression analyses were used to determine the risk of GDM. Results: Women who developed GDM (n = 37) had lower first-trimester serum levels of FSTL3 compared with women who did not (n = 127) (median 10,789 [interquartile range 7,013-18,939] vs. 30,670 [18,370-55,484] pg/ml, P < 0.001). When subjects were divided into tertiles based on FSTL3 levels, women with the lowest levels demonstrated a marked increase in risk for developing GDM in univariate (odds ratio 11.2 [95% CI 3.6-35.3]) and multivariate (14.0 [4.1-47.9]) analyses. There was a significant negative correlation between first-trimester FSTL3 levels and ~28-week nonfasting glucose levels (r = -0.30, P < 0.001). Conclusions: First-trimester FSTL3 levels are associated with glucose intolerance and GDM later in pregnancy
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Cardiac Angiogenic Imbalance Leads to Peripartum Cardiomyopathy
Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM
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PGC1α-dependent NAD biosynthesis links oxidative metabolism to renal protection
The energetic burden of continuously concentrating solutes against gradients along the tubule may render the kidney especially vulnerable to ischemia. Indeed, acute kidney injury (AKI) affects 3% of all hospitalized patients.1,2 Here we show that the mitochondrial biogenesis regulator, PGC1α,3,4 is a pivotal determinant of renal recovery from injury by regulating NAD biosynthesis. Following renal ischemia, PGC1α−/− mice developed local deficiency of the NAD precursor niacinamide (Nam), marked fat accumulation, and failure to re-establish normal function. Remarkably, exogenous Nam improved local NAD levels, fat accumulation, and renal function in post-ischemic PGC1α−/− mice. Inducible tubular transgenic mice (iNephPGC1α) recapitulated the effects of Nam supplementation, including more local NAD and less fat accumulation with better renal function after ischemia. PGC1α coordinately upregulated the enzymes that synthesize NAD de novo from amino acids whereas PGC1α deficiency or AKI attenuated the de novo pathway. Nam enhanced NAD via the enzyme NAMPT and augmented production of the fat breakdown product beta-hydroxybutyrate (β-OHB), leading to increased prostaglandin PGE2, a secreted autocoid that maintains renal function.5 Nam treatment reversed established ischemic AKI and also prevented AKI in an unrelated toxic model. Inhibition of β-OHB signaling or prostaglandins similarly abolished PGC1α-dependent renoprotection. Given the importance of mitochondrial health in aging and the function of metabolically active organs, the results implicate Nam and NAD as key effectors for achieving PGC1α-dependent stress resistance
INHIBITION OF SALIVARY AMYLASE ACTIVITY
Cigarette smoke (CS) is a leading known cause of cancer and cardiovascular diseases worldwide. The mechanisms by which CS produces its damaging effects seem to be multifactorial. Among others, CS toxicity is due also to several compounds like α,β-unsaturated aldehydes (acrolein, crotonaldehyde) and saturated aldehydes (acetaldehyde). Aldehydes could interact with thiol compounds of salivary proteins, leading to structural and functional alterations of these molecules. Prior in vitro studies have shown that there is a significant decrease in several known enzymatic activities following exposure to CS. Additionally, it was found that glutathione (GSH) has protective effect against the damaging role of CS to salivary enzymes, emphasizing the role of thiol groups in the mechanism of inactivation of these enzymes. In this study, salivary amylase activity showed a significant inhibition following exposure to CS, and to external addition of purified aldehydes known to be present in CS, due probably to the interaction between aldehydes and -SH groups of the enzyme. Our results indicate that although saturated aldehydes are the chief aldehydes present in CS, a significant decrease in amylase activity was due to unsaturated aldehydes, reacting, probably, through their double bond with the thiol group of proteins by the Michael addition reaction
Recovery of 177Lu from Irradiated HfO2 Targets for Nuclear Medicine Purposes
A new method of production of one of the most widely used isotopes in nuclear medicine, 177Lu, with high chemical purity was developed; this method includes irradiation of the HfO2 target with bremsstrahlung photons. The irradiated target was dissolved in HF and then diluted and placed onto a column filled with LN resin. Quantitative sorption of 177Lu could be observed during this process. The column later was rinsed with the mixture of 0.1 M HF and 1 M HNO3 and then 2 M HNO3 to remove impurities. Quantitative desorption of 177Lu was achieved by using 6 M HNO3. The developed method of 177Lu production ensures high purification of this isotope from macroquantities of hafnium and zirconium and radioactive impurities of carrier-free yttrium. The content of 177mLu in 177Lu in photonuclear production was determined. Due to high chemical and radionuclide purity, 177Lu obtained by the developed method can be used in nuclear medicine
Yields of Photo-Proton Reactions on Nuclei of Nickel and Separation of Cobalt Isotopes from Irradiated Targets
Nowadays, cobalt isotopes 55Co, 57Co, and 58mCo are considered to be promising radionuclides in nuclear medicine, with 55Co receiving the most attention as an isotope for diagnostics by positron emission tomography. One of the current research directions is dedicated to its production using electron accelerators (via photonuclear method). In our work, the yields of nuclear reactions occurring during the irradiation of natNi and 60Ni by bremsstrahlung photons with energy up to 55 MeV were determined. A method of fast and simple cobalt isotopes separation from irradiated targets using extraction chromatography was developed