Gestational hypercalciuria causes pathological urine calcium oxalate supersaturations

Gestational hypercalciuria causes pathological urine calcium oxalate supersaturations. Although normal pregnant women are more hypercal-ciuric than women with calcium oxalate nephrolithiasis (243 ± 23 mg/day vs. 194 ± 5 mg/day), pregnancy is not an established stone-forming state and pregnant women do not exhibit pathological crystalluria. One hypothesis to explain their lack of overt stone formation and pathological crystalluria is that pregnancy does not raise urine supersaturation with respect to stone forming salts such as calcium oxalate or calcium monohydrogen phosphate (brushite) to levels as high as in stone forming women. To test this hypothesis, we studied eleven normal women during each trimester of pregnancy, and between six and eight weeks post-partum. During pregnancy, hypercalciuria occurs with unchanged urine volume, citrate and magnesium excretions do not increase proportionally with calcium excretion, and urine pH increases. Supersaturations with respect to calcium oxalate (CaOx) and brushite (Br) are as high as those of women with calcium nephrolithiasis. The lack of pathological crystalluria and stones during pregnancy is not due to a failure of supersaturations to increase; urinary potential for crystallization is as high as in patients with established stone disease

Soluble fms-Like Tyrosine Kinase 1 (sFlt1), Endoglin and Placental Growth Factor (PlGF) in Preeclampsia among High Risk Pregnancies

Background: Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. Methods: This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. Results: The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2- fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. Conclusions: The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women

Effect of Smoking on Circulating Angiogenic Factors in High Risk Pregnancies

Objective: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia. Study Design: We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']). Smoking status was determined by self-report. Results: sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups. Conclusions: In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Sodium- and potassium-activated adenosine triphosphatase in kidneys of Fundulus heteroclitus adapted to fresh and salt

reabsorption of sodium and renal microsomal sodiumand potassium-activated adenosine triphosphatase (Na-K-ATPase) was evaluated in hypothyroid and hyperthyroid rats and in age-matched euthyroid controls. Tubular sodium reabsorption per gram of kidney was lower in thyroidectomized rats than in controls (186±14 vs. 246±+12 Leq/min; P < 0.005) and was accompanied by a quantitatively similar reduction in Na-K-ATPase specific activity (49.4+2.4 vs. 65.8+2.3,umol inorganic phosphate (Pi)/mg protein, per h; P < 0.001). This decrement was present in both cortex and outer medulla, and was limited to Na-K-ATPase since other representative enzymes not involved in sodium transport (magnesium-dependent adenosine triphosphatase [Mg-ATPase], glucose-6-phosphatase, 5'-nucleotidase) remained unchanged or increased in the hypothyroid animals. Conversely, Na-K-ATPase rose when sodium reabsorption increased in euthyroid rats treated with triiodothyronine. Subsequent experiments were performed to determine to what extent the decrease in Na-K-ATPase is due to lack of thyroid hormone per se or to an adaptive response to decreased reabsorptive sodium load. Triiodothyronine in concentrations of 1012 to 10 ' M had no effect in vitro on microsomal Na-K-ATPase of either thyroidectomized or euthyroid rats. When hypothyroid rats were uninephrectomized or treated with methylprednisolone, sodium reabsorption per gram kidney increased markedly and was similar to that of intac