Associations of perceived prenatal stress and adverse pregnancy outcomes with perceived stress years after delivery

Archives of Women's Mental Health - Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal...     

An Israeli Arab patient with a de novo TNFRSF1A mutation causing tumor necrosis factor receptor-associated periodic syndrome

OBJECTIVE: To investigate genetic susceptibility to recurrent fevers, generalized severe myalgia, and migratory erythema in an Israeli Arab child with no family history of similar disease. METHODS: DNA sequencing of exons 1-6 of the TNFRSF1A gene (formerly TNFR1) was performed in the patient and his parents to determine the presence of the autosomal-dominant tumor necrosis factor receptor-associated periodic syndrome (TRAPS); informative markers spanning the TNFRSF1A locus were used to genotype all available members of the patient's family. The TNFRSF1A gene was subsequently screened in 69 healthy Arab controls and 96 Caucasian controls. Formal forensic paternity testing was performed on the child. RESULTS: We found a de novo missense mutation in exon 3 of the TNFRSF1A gene, involving a novel C-->T transition encoding a Cys70Arg (C70R) variant, in the Israeli Arab patient. Eight of the common familial Mediterranean fever (FMF) gene MEFV mutations were excluded. This mutation was not present in the parents or siblings, or among the 69 healthy Arab controls. However, another TNFRSF1A variant, Pro46Lys (P46L), was present in 1 of the Arab controls. CONCLUSION: We have identified a TNFRSF1A mutation associated with periodic fever in an Arab patient, and a TNFRSF1A variant, which is variably pathogenic in Caucasians, in an Arab control. This is the first report of a de novo mutation in periodic fevers in general, and also of TRAPS in the Arab population. These findings demonstrate the need to include TRAPS in the differential diagnosis of recurrent fevers in this population.     

Interferon‐α treatment of female (NZW × BXSB)F1 mice mimics some but not all features associated with the Yaa mutation

Objective

Male (NZW × BXSB)F₁ mice develop antiphospholipid syndrome (APS) and proliferative glomerulonephritis that is markedly accelerated by the Yaa locus encoding an extra copy of Tlr7. Female (NZW × BXSB)F₁ mice with only 1 active copy of Tlr7 develop late‐onset glomerulonephritis but not APS. Because a major function of Toll‐like receptor 7 is to induce type I interferons (IFNs), our goal was to determine whether IFNα can induce or accelerate the manifestations of systemic lupus erythematosus (SLE) in female (NZW × BXSB)F₁ mice.

Methods

Eight‐week‐old female (NZW × BXSB)F₁ mice were injected with a single dose of adenovirus expressing IFNα. Mice were monitored for the development of thrombocytopenia and proteinuria. Sera were tested for anticardiolipin and anti‐Sm/RNP antibodies. Mice were killed at 17 or 22 weeks of age, and their kidneys and hearts were examined histologically and by immunohistochemistry. Spleen cells were phenotyped, and enzyme‐linked immunospot assays for autoantibody‐producing B cells were performed.

Results

IFNα markedly accelerated nephritis and death in female (NZW × BXSB)F₁ mice. A significant increase in spleen cell numbers associated with a striking increase in the number of activated B and T cells was observed. Marginal‐zone B cells were retained. IFNα‐induced increased titers of autoantibodies were observed, but thrombocytopenia was not observed. Cardiac damage was milder than that in male mice.

Conclusion

IFNα accelerates the development of renal inflammatory disease in female (NZW × BXSB)F₁ mice but induces only mild APS and does not induce thrombocytopenia. The effect of IFNα on SLE disease manifestations is strain dependent. These findings are relevant to our understanding of the physiologic significance of the IFN signature.

     

Moderate Amounts of Fructose Consumption Impair Insulin Sensitivity in Healthy Young Men: A randomized controlled trial

OBJECTIVE

Adverse effects of hypercaloric, high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly. The implications of fructose in amounts close to usual daily consumption, however, have not been well studied. This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism.

RESEARCH DESIGN AND METHODS

Nine healthy, normal-weight male volunteers (aged 21–25 years) were studied in this double-blind, randomized, cross-over trial. All subjects consumed four different sweetened beverages (600 mL/day) for 3 weeks each: medium fructose (MF) at 40 g/day, and high fructose (HF), high glucose (HG), and high sucrose (HS) each at 80 g/day. Euglycemic-hyperinsulinemic clamps with [6,6]-²H₂ glucose labeling were used to measure endogenous glucose production. Lipid profile, glucose, and insulin were measured in fasting samples.

RESULTS

Hepatic suppression of glucose production during the clamp was significantly lower after HF (59.4 ± 11.0%) than HG (70.3 ± 10.5%, P < 0.05), whereas fasting glucose, insulin, and C-peptide did not differ between the interventions. Compared with HG, LDL cholesterol and total cholesterol were significantly higher after MF, HF, and HS, and free fatty acids were significantly increased after MF, but not after the two other interventions (P < 0.05). Subjects’ energy intake during the interventions did not differ significantly from baseline intake.

CONCLUSIONS

This study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose.In the U.S., the consumption of fructose increased by more than 25% between 1970 and 1997 as the total sugar intake of the population rose (1). During the same period, the prevalence of obesity rose dramatically, paralleling the increase in fructose consumption and the introduction of high-fructose corn syrup (2). Whether there is a causal relationship between those developments, however, remains unclear. Total fructose consumption from natural and added sources, estimated from food disappearance data, was estimated to be 97 g/person/day in 1997 in the U.S. (1) and 83 g/person/day in 1998 in Switzerland (3).Epidemiologic and intervention studies of fructose and other caloric sweeteners have shown detrimental effects on health. In a cross-sectional study in U.S. adults, for example, the consumption of caloric sweeteners was associated with increased dyslipidemia (4) and in the Health Professionals Follow-up Study, high intakes of sugar-sweetened beverages (SSB) increased the risk for type 2 diabetes (5). Intervention trials have provided evidence that high- to very high–fructose doses led to increases in de novo lipogenesis, blood triglycerides, and hepatic insulin resistance (6–8).Not all of these studies found consistent effects for all parameters, however. In the study by Lê et al. (6), where 1.5 g fructose/kg body weight were consumed during a 4-week period, fasting lipids and glucose were affected, but insulin resistance, as determined by a euglycemic-hyperinsulinemic clamp, did not change. However, their study only tested fructose, without comparison with other sugars. Furthermore, relatively high amounts of fructose were consumed in most of these studies, reaching up to 25% of total energy intake. In a recent intervention study in healthy Swiss men, we found adverse effects of low to moderate amounts of fructose—but also glucose and sucrose—on fasting glucose and inflammatory markers, whereas only beverages containing fructose seemed to negatively affect LDL particle size. Even though fasting glucose was altered, none of the interventions showed any effect on glucose tolerance or on indices of insulin sensitivity calculated during an oral glucose tolerance test (9).The aim of the current study was therefore to assess the effect of moderate amounts of fructose and sucrose, compared with the same amounts of glucose, specifically on hepatic insulin sensitivity but also on lipid profiles of healthy human subjects using euglycemic-hyperinsulinemic clamps with [6,6]-²H₂ labeled glucose.     

Hydrogen sulfide protects colon cancer cells from chemopreventative agent β-phenylethyl isothiocyanate induced apoptosis

AIM: Hydrogen sulfide (H2S) is a prominent gaseous constituent of the gastrointestinal (GI) tract with known cytotoxic properties. Endogenous concentrations of H2S are reported to range between 0.2-3.4 mmol/L in the GI tract of mice and humans. Considering such high levels we speculate that, at non-toxic concentrations, H2S may interact with chemical agents and alter the response of colonic epithelium cells to such compounds. The GI tract is a major site for the absorption of phytochemical constituents such as isothiocyanates, flavonoids, and carotenoids, with each group having a role in the prevention of human diseases such as colon cancer. The chemopreventative properties of the phytochemical agent β-phenyethyl isothiocyanate (PEITC) are well recognized. However, little is currently known about the physiological or biochemical factors present in the GI tract that may influence the biological properties of ITCs. The current study was undertaken to determine the effects of H2S on PEITC mediated apoptosis in colon cancer cells.METHODS: Induction of apoptosis by PEITC in human colon cancer HCT116 cells was assessed using classic apoptotic markers namely SubG1 population analysis,caspase-3 like activity and nuclear fragmentation and condensation coupled with the MTT (3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl tetrasodium bromide) viability assay and LDH leakage.RESULTS: PEITC significantly induced apoptosis in HGT116cells as assessed by SubG1 population formation, nuclear condensation, LDH leakage and caspase-3 activity after 24 h, these data being significant from control groups (P＜0.01). In contrast, co-treatment of cells with physiological concentrations of H2S (0.1-1 mmol/L) prevented PEITC mediated apoptosis as assessed using the parameters described.CONCLUSION: PEITC effectively induced cell death in the human adenocarcinoma cell line HCT116 in vitro through classic apoptotic mechanisms. However, in the presence of H2S, apoptosis was abolished. These data suggest that H2S may play a significant role in the response of colonic epithelial cells to beneficial as well as toxic agents present within the GI tract.