Oxidative-Nitrative Stress and Poly (ADP-Ribose) Polymerase Activation 3 Years after Pregnancy

Background: Oxidative-nitrative stress and poly (ADP-ribose) polymerase activation have been previously observed in healthy and gestational diabetic pregnancies, and they were also linked to the development of metabolic diseases. The aim of the present study was to examine these parameters and their correlation to known metabolic risk factors following healthy and gestational diabetic pregnancies. Methods: Fasting and 2 h postload plasma total peroxide level, protein tyrosine nitration, and poly (ADP-ribose) polymerase activation were measured in circulating leukocytes three years after delivery in women following healthy, "mild" (diet-treated) or "severe" (insulin-treated) gestational diabetic pregnancy during a standard 75 g OGTT. Nulliparous women and men served as control groups. Results: Fasting plasma total peroxide level was significantly elevated in women with previous pregnancy (B = 0.52 +/- 0.13; p < 0.001), with further increase in women with insulin-treated gestational diabetes (B = 0.36 +/- 0.17; p < 0.05) (R(2) = 0.419). Its level was independently related to previous pregnancy (B = 0.47 +/- 0.14; p < 0.01) and current CRP levels (B = 0.06 +/- 0.02; p < 0.05) (R(2) = 0.306). Conclusions: Elevated oxidative stress but not nitrative stress or poly (ADP-ribose) polymerase activation can be measured three years after pregnancy. The increased oxidative stress may reflect the cost of reproduction and possibly play a role in the increased metabolic risk observed in women with a history of severe gestational diabetes mellitus

Oxidative-Nitrative Stress and Poly (ADP-Ribose) Polymerase Activation 3 Years after Pregnancy

Background: Oxidative-nitrative stress and poly (ADP-ribose) polymerase activation have been previously observed in healthy and gestational diabetic pregnancies, and they were also linked to the development of metabolic diseases. The aim of the present study was to examine these parameters and their correlation to known metabolic risk factors following healthy and gestational diabetic pregnancies. // Methods: Fasting and 2 h postload plasma total peroxide level, protein tyrosine nitration, and poly (ADP-ribose) polymerase activation were measured in circulating leukocytes three years after delivery in women following healthy, “mild” (diet-treated) or “severe” (insulin-treated) gestational diabetic pregnancy during a standard 75 g OGTT. Nulliparous women and men served as control groups. // Results: Fasting plasma total peroxide level was significantly elevated in women with previous pregnancy (B = 0.52 ± 0.13; p < 0 001), with further increase in women with insulin-treated gestational diabetes (B=0 36 ± 0 17; p < 0 05) (R2 = 0 419). Its level was independently related to previous pregnancy (B=0 47 ± 0 14; p < 0 01) and current CRP levels (B=0 06 ± 0 02; p < 0 05) (R2 = 0 306). // Conclusions: Elevated oxidative stress but not nitrative stress or poly (ADP-ribose) polymerase activation can be measured three years after pregnancy. The increased oxidative stress may reflect the cost of reproduction and possibly play a role in the increased metabolic risk observed in women with a history of severe gestational diabetes mellitus

Gastrin: A Distinct Fate of Neurogenin3 Positive Progenitor Cells in the Embryonic Pancreas

Neurogenin3+ (Ngn3+) progenitor cells in the developing pancreas give rise to five endocrine cell types secreting insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. Gastrin is a hormone produced primarily by G-cells in the stomach, where it functions to stimulate acid secretion by gastric parietal cells. Gastrin is expressed in the embryonic pancreas and is common in islet cell tumors, but the lineage and regulators of pancreatic gastrin+ cells are not known. We report that gastrin is abundantly expressed in the embryonic pancreas and disappears soon after birth. Some gastrin+ cells in the developing pancreas co-express glucagon, ghrelin or pancreatic polypeptide, but many gastrin+ cells do not express any other islet hormone. Pancreatic gastrin+ cells express the transcription factors Nkx6.1, Nkx2.2 and low levels of Pdx1, and derive from Ngn3+ endocrine progenitor cells as shown by genetic lineage tracing. Using mice deficient for key transcription factors we show that gastrin expression depends on Ngn3, Nkx2.2, NeuroD1 and Arx, but not Pax4 or Pax6. Finally, gastrin expression is induced upon differentiation of human embryonic stem cells to pancreatic endocrine cells expressing insulin. Thus, gastrin+ cells are a distinct endocrine cell type in the pancreas and an alternative fate of Ngn3+ cells

Volatile and trace elements in basaltic glasses from Samoa : implications for water distribution in the mantle

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Earth and Planetary Science Letters 241 (2006): 932-951, doi:10.1016/j.epsl.2005.10.028.We report volatile (H2O, CO2, F, S, Cl) and trace element data for submarine alkalic basalt glasses from the three youngest Samoan volcanoes, Ta’u, Malumalu and Vailulu’u. Most samples are visibly sulfide saturated, so have likely lost some S during fractionation. Cl/K ratios (0.04 – 0.15) extend to higher values than pristine MORBs, but are suspected to be partly due to source differences since Cl/K roughly varies as a function of 87Sr/86Sr. There are no resolvable differences in the relative enrichment of F among sources, and compatibility of F during mantle melting is established to be nearly identical to Nd. Shallow degassing has affected CO2 in all samples, and H2O only in the most shallowly erupted samples from Vailulu’u. Absolute water contents are high for Samoa (0.63 – 1.50 wt%), but relative enrichment of water compared to equally incompatible trace elements (Ce, La) is low and falls entirely below normal MORB values. H2O/Ce (58 – 157) and H2O/La (120 – 350) correlate inversely with 87Sr/86Sr compositions (0.7045 – 0.7089). This leads us to believe that, because of very fast diffusion of hydrogen in mantle minerals, recycled lithospheric material with high initial water and trace element content will lose water to the drier ambient mantle during storage within the inner Earth. The net result is the counter-intuitive appearance of greater dehydration with greater mantle enrichment. We expect that subducted slabs will experience a two-stage dehydration history, first within subduction zones and then in the ambient mantle during long-term convective mixing

Identification of tissue-specific cell death using methylation patterns of circulating DNA

Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics

Hypertension Treatment Rates And Health Care Worker Density: An Analysis Of Worldwide Data

Elevated blood pressure is the leading cause of death worldwide; however, treatment and control rates for hypertension are low. Here, we analyze the relationship between physician and nurse density and hypertension treatment rates worldwide. Data on hypertension treatment rates were collected from the STEPwise approach to Surveillance country reports, individual studies resulting from a PubMed search for articles published between 1990 and 2010, and manual search of the reference lists of extracted studies. Data on health care worker density were obtained from the Global Atlas of the Health Workforce. We controlled for a variety of variables related to population characteristics and access to health care, data obtained from the World Bank, World Development Indicators, United Nations, and World Health Organization. We used clustering of SEs at the country level. Full data were available for 154 hypertension treatment rate values representing 68 countries between 1990 and 2010. Hypertension treatment rate ranged from 3.4% to 82.5%, with higher treatment rates associated with higher income classification. Physician and nurse/midwife generally increased with income classification. Total healthcare worker density was significantly associated with hypertension treatment rate in the unadjusted model (P\u3c0.001); however, only nurse density remained significant in the fully adjusted model (P=0.050). These analyses suggest that nurse density, not physician density, explains most of the relationship with hypertension treatment rate and remains significant even after adjusting for other independent variables. These results have important implications for health policy, health system design, and program implementation