Postpartum acute myometritis suppresses expression of contraction-associated proteins in the gravid uterus.

Uterine atony is a major contributor to postpartum hemorrhage. We previously proposed the novel histological concept of postpartum acute myometritis (PAM) to elucidate the pathophysiology of uterine atony. This concept involves the infiltration of macrophages and neutrophils, as well as mast cell and complement activation in the myometrium. However, the pathological mechanism underlying uterine atony in the context of PAM remains unclear. Herein, we focused on uterine contraction-associated proteins (CAPs) including connexin 43 (Cx43), oxytocin receptors (OXR), prostaglandin receptors EP1, EP3, FP, and protease-activated receptor (PAR)-1. This follow-up study aimed to compare CAP expression between PAM and control groups. We selected 38 PAM subjects from the cases enrolled in our amniotic fluid embolism registry between 2011 and 2018. Control tissues from 10 parturients were collected during cesarean section. We stained the myometrial tissues with the following CAP markers, inflammatory cell markers, and other markers: Cx43, OXR, EP1, EP3, FP, PAR-1, C5a receptor, tryptase, neutrophil elastase, CD68, ß-actin, and Na+/K+-ATPase. The immunostaining-positive areas of Cx43, OXR, EP1, EP3, and FP standardized by ß-actin in the PAM tissue were significantly smaller than in the control group, whereas those of PAR-1 and Na+/K+-ATPase increased significantly in the PAM group. The Cx43- and OXR-positive areas correlated negatively with the immunostaining-positive cell numbers of CD68 and tryptase with halo, respectively. PAM may impair individual and synchronized myocyte contraction, leading to uterine atony refractory to uterotonics. Further cell-based studies are needed to elucidate the molecular mechanism by which inflammatory cells suppress CAP expression.

Continuous training in young athletes decreases hepcidin secretion and is positively correlated with serum 25(OH)D and ferritin.

Background: Iron deficiency is known to impair muscle function and reduce athletic performance, while vitamin D has been reported to induce iron deficiency. However, the mechanism underlying exercise-induced changes in iron metabolism and the involvement of vitamins in this mechanism are unclear. The present study examined changes in biological iron metabolism induced by continuous training and the effects of vitamin D on these changes. Methods: Diet, physical characteristics, and blood test data were collected from 23 female high school students in a dance club on the last day of each of a 2-month continuous training period and a 2-week complete rest periods. Results: Serum hepcidin-25 levels were significantly lower during the training period than the rest period (p = 0.013), as were the red blood cell count, hemoglobin, and hematocrit (all p < 0.001). Serum erythropoietin was significantly higher (p = 0.001) during the training period. Significant positive correlations were observed between 25(OH)D levels and serum iron, serum ferritin, and transferrin saturation during the training period. Multiple regression analysis with serum 25(OH)D level as the dependent variable and serum ferritin and iron levels as independent variables during the training period revealed a significant association with serum ferritin. Conclusion: Continuous training may promote hemolysis and erythropoiesis, contributing to the suppression of hepcidin expression. The relationship between serum 25(OH)D and iron in vivo may be closely related to metabolic changes induced by the exercise load.

Skeletal muscle metabolic dysfunction with circulating carboxymethyl-lysine in dietary food additive-induced leaky gut.

Impaired intestinal permeability induces systemic inflammation and metabolic disturbance. The effect of a leaky gut on metabolism in skeletal muscle, a major nutrient consumer, remains unclear. In this study, we aimed to investigate the glucose metabolic function of the whole body and skeletal muscles in a mouse model of diet-induced intestinal barrier dysfunction. At Week 2, we observed higher intestinal permeability in mice fed a titanium dioxide (TiO2)-containing diet than that of mice fed a normal control diet. Subsequently, systemic glucose and insulin tolerance were found to be impaired. In the skeletal muscle, glucose uptake and phosphorylation levels in insulin signaling were lower in the TiO2 group than those in the control group. Additionally, the levels of pro-inflammatory factors were higher in TiO2-fed mice than those in the control group. We observed higher carboxymethyl-lysin (CML) levels in the plasma and intestines of TiO2-fed mice and lower insulin-dependent glucose uptake in CML-treated cultured myotubes than those in the controls. Finally, soluble dietary fiber supplementation improved glucose and insulin intolerance, suppressed plasma CML, and improved intestinal barrier function. These results suggest that an impaired intestinal barrier leads to systemic glucose intolerance, which is associated with glucose metabolism dysfunction in the skeletal muscles due to circulating CML derived from the intestine. This study highlights that the intestinal condition regulates muscle and systemic metabolic health.

Effects of Laurus nobilis Leaf Extract (LAURESH®) on Oral and Gut Microbiota Diversity in Mice.

BACKGROUND/AIM: The leaves of Laurus nobilis have been used for culinary purposes for many years and have recently been shown to have beneficial effects on human health by altering microbiota composition. However, the effects of L. nobilis on the diversity of microbiomes in the oral cavity and gut remain unknown. Therefore, in this study, we examined the effects of an extract of L. nobilis on the diversity of microbiomes in the oral cavity and gut in mice. MATERIALS AND METHODS: C57BL/6J mice were randomly divided into two groups and fed a standard diet (SD) and a standard diet containing 5% LAURESH®, a laurel extract (SDL). After 10 weeks, oral swabs and fecal samples were collected. The bacterial DNA extracted from the oral swabs and feces was used for microbiota analysis using 16S rRNA sequencing. The sequencing data were analyzed using the Quantitative Insights into Microbial Ecology 2 in the DADA2 pipeline and 16S rRNA database. RESULTS: The α-diversity of the oral microbiome was significantly greater in the SDL group than in the SD group. The ß-diversity of the oral microbiome was also significantly different between the groups. Moreover, the taxonomic abundance analysis showed that five bacteria in the gut were significantly different among the groups. Furthermore, the SDL diet increased the abundance of beneficial gut bacteria, such as Akkermansia sp. CONCLUSION: Increased diversity of the oral microbiome and proportion of Akkermansia sp. in the gut microbiome induced by L. nobilis consumption may benefit oral and gut health.

Dietary characteristics associated with the risk of non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease in non-obese Japanese participants: A cross-sectional study.

Background and Aim: Dietary characteristics associated with non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) in non-obese patients remain to be elucidated. This study examined the association of NAFLD and MASLD with dietary characteristics according to obesity status. Methods: We performed a cross-sectional study of 15 135 participants (n = 7568 men and 7567 women) aged 35-74 years using data of annual health checks between 2008 and 2020. Obesity was defined as BMI ≥ 25 kg/m2. Diagnosis of fatty liver was based on abdominal ultrasonography. Fatty-liver-related dietary characteristics were assessed using a self-administered questionnaire. Results: For non-obese participants, NAFLD was found in 31.0% of men and 19.4% of women. Non-obese MASLD was found in 27.6% of men and 18.1% of women. Multivariable-adjusted stepwise logistic regression analysis indicated that, in males, both non-obese NAFLD and non-obese MASLD were significantly and negatively associated with "often eat sesame/nuts", and positively associated with "often eat noodles/rice bowl" and "often eat evening meal" (P < 0.05). For non-obese women, both NAFLD and MASLD were significantly and positively associated with "often eat sweet buns/bread with fillings" (P < 0.05). Adjusted analyses showed that all dietary characteristics were not significantly associated with the risk of NAFLD/MASLD in obese men and women. Conclusion: This cross-sectional study indicates the existence of sex and obesity differences in the association of NAFLD and MASLD with dietary characteristics. Our findings suggest that some dietary characteristics are associated with NAFLD and MASLD prevalence in non-obese Japanese participants.

High-intensity exercise impairs intestinal barrier function by generating oxidative stress.

The intestine functions as a barrier preventing the entry of extrinsic factors into the body. This barrier function is disrupted by oxidative damage along with an impaired mucosal layer. Excessive exercise can generate oxidative stress in the intestinal tissue; however, the effect of exercise-induced oxidative stress on intestinal permeability is unclear. In this study, we examined the involvement of oxidative stress in barrier function of the ileum of mice following high-intensity exercise. Male ICR mice (12-week-old) were divided into sedentary and exercise groups. Mice in the exercise group underwent a single bout of treadmill running, and the ileum was collected for histological and biochemical analyses. Plasma fluorescence intensity level after oral administration of fluorescein isothiocyanate-dextran gradually increased until 30 min after exercise in response to intensity of exercise. Relatively high levels of oxidative proteins and low level of claudin-1, a tight-junction protein, were observed in the exercise group. Treatment with a xanthine oxidase inhibitor suppressed exercise-induced increases in intestinal permeability. Moreover, excessive exercise training for two weeks led to relatively high intestinal permeability at rest. These results suggest that high-intensity exercise increases intestinal permeability and tight junction damage, which may be mediated by oxidative stress.

Ilex paraguariensis A.St.-Hil. improves lipid metabolism in high-fat diet-fed obese rats and suppresses intracellular lipid accumulation in 3T3-L1 adipocytes via the AMPK-dependent and insulin signaling pathways.

Background: Obesity is closely associated with several chronic diseases, and adipose tissue plays a major role in modulating energy metabolism. Objective: This study aimed to determine whether Mate, derived from I. paraguariensis A.St.-Hil., ameliorates lipid metabolism in 3T3-L1 adipocytes and high-fat diet (HFD)-fed obese Sprague-Dawley (SD) rats. Design: 3T3-L1 adipocytes were cultured for 7 days, following which intracellular lipid accumulation and expression levels of lipid metabolism-related factors were examined. Dorsomorphin was used to investigate the potential pathways involved, particularly the adenosine monophosphate-activated protein kinase (AMPK)- dependent pathway. Mate was administered to rat HFD-fed obese SD models for 8 consecutive weeks. The expression of lipid metabolism-related factors in the organs and tissues collected from dissected SD rats was evaluated. Results: Mate suppressed intracellular lipid accumulation in 3T3-L1 adipocytes, increased the protein and gene expression levels of AMPK, hormone sensitive lipase (HSL), calmodulin kinase kinase (CaMKK), liver kinase B1 (LKB1), protein kinase A (PKA), CCAAT/enhancer binding protein ß (C/EBPß), insulin receptor b (IRß), and insulin receptor substrate 1 (IRS1) (Tyr465), and decreased those of sterol regulatory element binding protein 1C (Srebp1c), fatty acid synthase (FAS), peroxisome-activated receptor γ (PPARγ), and IRS1 (Ser1101). Furthermore, an AMPK inhibitor abolished the effects exerted by Mate on intracellular lipid accumulation and HSL and FAS expression levels. Mate treatment suppressed body weight gain and improved serum cholesterol levels in HFD-fed obese SD rats. Treatment with Mate increased the protein and gene expression levels of AMPK, PKA, Erk1/Erk2 (p44/p42), and uncoupling protein 1 and reduced those of mammalian target of rapamycin, S6 kinase, Srebp1c, ap2, FAS, Il6, Adiponectin, Leptin, and Fabp4 in rat HFD-fed obese SD models. Discussion and conclusions: Mate suppressed intracellular lipid accumulation in 3T3-L1 adipocytes and improved lipid metabolism in the epididymal adipose tissue of HFD-fed obese SD rats via the activation of AMPK-dependent and insulin signaling pathways.

Comparative analysis of hyperfibrinolysis with activated coagulation between amniotic fluid embolism and severe placental abruption.

Amniotic fluid embolism (AFE) and placental abruption (PA) are typical obstetric diseases associated with disseminated intravascular coagulation (DIC). AFE is more likely to be complicated with enhanced fibrinolysis than PA. AFE may have an additional mechanism activating fibrinolytic cascade. We aimed to compare the coagulation/fibrinolysis factors among AFE, PA, and peripartum controls. We assessed AFE cases registered in the Japanese AFE Registry, and PA cases complicated with DIC (severe PA) and peripartum controls recruited at our hospital. The following factors in plasma were compared: prothrombin fragment 1 + 2 (PF1 + 2), plasmin α2-plasmin inhibitor complex (PIC), tissue factor (TF), tissue plasminogen activator (tPA), annexin A2 (AnnA2), total thrombin activatable fibrinolysis inhibitor (TAFI) including its activated form (TAFIa), and plasminogen activator inhibitor-type 1 (PAI-1). PF1 + 2 and PIC were markedly increased in both AFE (n = 27) and severe PA (n = 12) compared to controls (n = 23), without significant difference between those disease groups; however, PIC in AFE showed a tendency to elevate relative to PF1 + 2, compared with severe PA. AFE had significantly increased tPA and decreased total TAFI levels compared with severe PA and controls, which might be associated with further plasmin production in AFE and underlie its specific fibrinolytic activation pathway.

Favorable Dietary Patterns Associated with Lower Incidence of Metabolic Syndrome in Middle-Aged Japanese Men: A Prospective Cohort Study.

Dietary patterns, such as selecting what food to regularly eat, may play role in reducing the incidence of metabolic syndrome (MetS). This study examined the causal relationships of Japanese dietary patterns and the relationship with the risk of MetS onset using a prospective cohort design. Data of annual health checks between 2008 and 2017 were analyzed, and middle-aged men and women (n=3,298 and 3,925, respectively) were followed up for 15,498 and 19,459 person-years, respectively. We investigated six dietary patterns using a questionnaire, and the participants were divided into low, middle, and high dietary score groups. During the follow-up period, cases of new-onset MetS were found in 698 men (21.2%) and 350 women (8.2%). Covariate-adjusted Cox proportional hazard models revealed that the risk of new-onset MetS was significantly lower in the male participants who responded that they "often eat vegetables" (HR: 0.77, 95% CI: 0.66-0.91). For dietary score, the male participants had significantly lower adjusted HRs of MetS onset in the middle-score group (HR: 0.80, 95% CI: 0.69-0.94) and high-score group (HR: 0.54, 95% CI: 0.41-0.72) compared to the low-score group. On the other hand, there was no association of each dietary pattern and dietary score with new-onset MetS among the female participants. This study found that favorable dietary patterns are associated with a lower risk of MetS; thus, education that aims to encourage a favorable diet may have an important role in reducing the incidence of MetS in middle-aged men.

Matcha green tea beverage moderates fatigue and supports resistance training-induced adaptation.

BACKGROUND: Resistance training adaptively increases muscle strength and mass, contributing to athletic performance and health promotion. Dietary intervention with natural foods provides nutrients that help accelerate muscle adaptation to training. Matcha green tea contains several bioactive factors such as antioxidants, amino acids, and dietary fibers; however, its effect on muscle adaptation is unclear. In this study, we aimed to investigate the effects of matcha beverage intake on muscle adaptation to resistance training. METHODS: Healthy, untrained men were randomized into placebo and matcha groups. Participants consumed either a matcha beverage containing 1.5 g of matcha green tea powder or a placebo beverage twice a day and engaged in resistance training programs for 8 (trial 1) or 12 weeks (trial 2). RESULTS: In trial 1, maximum leg strength after training tended to increase more in the matcha group than that in the placebo group. In the matcha group, subjective fatigue after exercise at 1 week of training was lower than that in the placebo group. Gut microbe analysis showed that the abundance of five genera changed after matcha intake. The change in Ruminococcus, Butyricimonas, and Oscillospira compositions positively correlated with the change in maximum strength. In trial 2, the change in skeletal muscle mass in response to training was larger in the matcha group. In addition, the salivary cortisol level was lower in the matcha group than that in the placebo group. CONCLUSION: Daily intake of matcha green tea beverages may help in muscle adaptation to training, with modulations in stress and fatigue responses and microbiota composition.

An Evaluation of the Protein Requirements of Japanese Young Men by Consuming Two Types of Dairy Proteins Using the Indicator Amino Acid Oxidation Method.

The indicator amino acid oxidation method is a relatively new method for determining protein requirements. Our hypothesis was that the protein requirement of the casein-whey protein mixture (70% casein and 30% whey protein) was lower than the protein requirement of plain casein, because casein and whey proteins compensate for the lack of the first-limiting amino acids. The optimal mixing ratio was determined based on the amino acid scoring pattern which is used to calculate the digestible indispensable amino acid score. In this study, digestibility was not considered to determine the optimal mixing ratio because dairy protein is a good source of digestible protein. This study aimed to evaluate the protein requirements of Japanese young men by consuming casein and casein-whey protein mixture. Ten healthy young men (22±0.2 y old) participated in 12 experiments according to a graded protein intake (0.5, 0.7, 0.9, 1.0, 1.2, 1.4 g/kg/d) of casein and casein-whey protein mixture. The mean protein requirement was calculated as the breakpoint of breath 13CO2 enrichment using change-point regression models. The mean protein requirements of Japanese young men by consuming casein and casein-whey protein mixture were estimated to be 1.00 g/kg/d and 0.90 g/kg/d, respectively. These estimated requirements were consistent with the protein quality expected from the amount of the first-limiting amino acids. The indicator amino acid oxidation method may be useful to evaluate protein quality.

Household Income Is Related to Dietary Fiber Intake and Dietary Acid Load in People with Type 2 Diabetes: A Cross-Sectional Study.

Household income was related to habitual dietary intake in general Japanese people. This cross-sectional study investigated the relationship between household income and habitual dietary intake in people with type 2 diabetes mellitus (T2DM). Household income was evaluated using a self-reported questionnaire and categorized into high and low household income. Nutritional status was assessed using a brief-type self-administered diet history questionnaire. Among 128 men and 73 women, the proportions of participants with low household income were 67.2% (n = 86/128) in men and 83.6% (n = 61/73) in women. Dietary fiber intake (11.3 ± 4.2 vs. 13.8 ± 6.0 g/day, p = 0.006) was lower, and dietary acid load, net endogenous aid production score (NEAP) (51.7 ± 10.5 vs. 46.8 ± 10.4 mEq/day, p = 0.014) and potential renal acid load score (PRAL) (9.5 ± 10.7 vs. 3.7 ± 14.1 mEq/day, p = 0.011) were higher in men with low household income than in those without. Multivariable linear regression analyses demonstrated that log (dietary fiber intake) in men with low household income was lower than that in those with high household income after adjusting for covariates (2.35 [2.26−2.44] vs. 2.52 [2.41−2.62], p = 0.010). Furthermore, NEAP (54.6 [51.7−57.4] vs. 45.8 [42.5−49.2], p <0.001) in men with low household income were higher than in those with high household income after adjusting for covariates. Contrastingly, household income was not related to diet quality in women. This study showed that household income was related to dietary fiber intake and dietary acid load in men but not in women.

Comparative Analysis of Gene Expression Profiles in the Adipose Tissue of Obese Adult Mice With Rapid Infantile Growth After Undernourishment In Utero.

Rapid infantile growth (RG) markedly increases the risk of obesity and metabolic disorders in adulthood, particularly among neonates born small. To elucidate the molecular mechanisms by which RG following undernourishment in utero (UN) contributes to the deterioration of adult fat deposition, we developed a UN mouse model using maternal energy restriction, followed by RG achieved by adjustments to 4 pups per litter soon after birth. A high-fat diet (HFD) was fed to weaned pups treated or not (Veh) with tauroursodeoxycholic acid (TU). UN-RG pups showed the deterioration of diet-induced obesity and fat deposition, which was ameliorated by TU. We performed a microarray analysis of epididymal adipose tissue and two gene enrichment analyses (NN-Veh vs UN-RD-Veh and UN-RG-Veh vs UN-RG-TU). The results obtained identified 4 common gene ontologies (GO) terms of inflammatory pathways. In addition to the inflammatory characteristics of 4 GO terms, the results of heatmap and principal component analyses of the representative genes from 4 GO terms, genes of interest (GOI; Saa3, Ubd, S100a8, Hpx, Casp1, Agt, Ptgs2) selected from the 4 GO terms, and immunohistochemistry of macrophages collectively suggested the critical involvement of inflammation in the regulation of fat deposition in the responses to UN and TU. Therefore, the present results support the 'Developmental Origins of Metaflammation', the last word of which was recently proposed by the concept of metabolic disorders induced by low-grade systemic inflammation.

Placental pathology predicts infantile neurodevelopment.

The aim of present study was to investigate the association of placental pathological findings with infantile neurodevelopment during the early 40 months of life. 258 singleton infants were enrolled in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) whose placentas were saved in our pathological division. To assess the infantile neurodevelopment, we used Mullen Scales of Early Learning (gross motor, visual reception, fine motor, receptive language, expressive language) at 10, 14, 18, 24, 32, and 40 months. For obtaining placental blocks, we carried out random sampling and assessed eleven pathological findings using mixed modeling identified 'Accelerated villous maturation', 'Maternal vascular malperfusion', and 'Delayed villous maturation' as significant predictors of the relatively lower MSEL composite scores in the neurodevelopmental milestones by Mullen Scales of Early Learning. On the other hand, 'Avascular villi', 'Thrombosis or Intramural fibrin deposition', 'Fetal vascular malperfusion', and 'Fetal inflammatory response' were significant predictors of the relatively higher MSEL composite scores in the neurodevelopmental milestones by Mullen Scales of Early Learning. In conclusion, the present study is the first to report that some placental pathological findings are bidirectionally associated with the progression of infantile neurodevelopment during 10-40 months of age.

Developmental Origins of Metaflammation; A Bridge to the Future Between the DOHaD Theory and Evolutionary Biology.

Metabolic syndrome refers to obesity-associated metabolic disorders that increase the risk of type 2 diabetes, coronary diseases, stroke, and other disabilities. Environmental imbalance during the early developmental period affects health and increases susceptibility to non-communicable diseases, including metabolic syndrome, in later life; therefore, the Developmental Origins of Health and Disease (DOHaD) theory was established. According to the DOHaD theory, the hypothesis of the energy-saving 'Thrifty Phenotype' in undernourished fetuses is one of the well-accepted schemes as a risk of developing metabolic syndrome. This phenotype is evolutionarily advantageous for survival of the fittest in a hangry environment after birth, a strong selection pressure, but increases the risk of developing metabolic syndrome under an obesogenic diet according to the 'Mismatch' hypothesis. Increasing evidences support that chronic inflammation pathophysiologically connects obesity to metabolic disorders in metabolic syndrome, leading to the concept of 'Metaflammation'. 'Metaflammation' in humans is proposed to originate from the evolutionary conservation of crosstalk between immune and metabolic pathways; however, few studies have investigated the contribution of evolutionary maladaptation to the pathophysiology of 'Metaflammation'. Therefore, it is promising to investigate 'Metaflammation' from the viewpoint of selective advantages and its 'Mismatch' to an unexpected environment in contemporary lifestyles, in consideration of the principal concept of evolutionarily conserved nutrient sensing and immune signaling systems.

A nutritional intervention that promotes increased vegetable intake in Japanese with non-alcoholic fatty liver disease: a six-month trial.

The aim of this study was to investigate whether a nutritional intervention motivating increased vegetable consumption would be an effective treatment and diet therapy for patients with non-alcoholic fatty liver disease. We examined 15 patients with this disease (5 men and 10 women). During the 6-month intervention period, all participants received a small amount of vegetables twice a month as a nutritional education tool aimed at increasing vegetable consumption. They also received nutritional counseling and underwent ultrasound and blood biochemical examinations at baseline and 3 and 6 months after initiation of the intervention. Moreover, they were requested to submit dietary records for any 2 days. Green, white, and total vegetable intakes were significantly higher at 3 and 6 months than at baseline in 8 patients. These patients had significantly lower alanine amino-transferase and triglyceride concentrations than those whose vegetable intake did not increase. Additionally, green vegetable intake significantly negatively correlated with weight at 3 and 6 months (r = -0.617, p = 0.032 and r = -0.848, p = 0.008, respectively). These results suggest that our nutritional approach effectively increased vegetable consumption in at least some patients with non-alcoholic fatty liver disease, consequently improving their condition.

Inhibitory effects of amniotic fluid on the activated protein C anticoagulation system in maternal plasma.

Pulmonary thromboembolism (PTE) is one of the leading causes of maternal mortality. We previously reported that possible contamination of amniotic fluid (AF) into maternal circulation accelerated thrombin production and activated platelet function in maternal blood through the extrinsic pathway, which may be associated with the high incidence of PTE in early puerperium. However, it remains unclear whether the maternal anticoagulation system, e.g., the activated protein C (APC) pathway, contributes to the hypercoagulable condition induced by AF. Our previous study using an endogenous thrombin potential (ETP)-based assay revealed that sensitivity to APC was reduced during the postpartum first day, i.e., immediately after delivery, when parturients were supposed to be exposed to AF. Our aim is to investigate the susceptibility of maternal plasma to APC when mixed with AF. We collected plasma from 51 pregnant females and mixed with AF as well as APC. APC-sensitivity ratio (APC-sr) was calculated using the ETP-based assay. Addition of AF to maternal plasma showed a significant increase of ETP in the presence of APC. APC-sr was significantly increased, indicating decreased sensitivity to APC, after AF mixture to maternal plasma. The present APC-sr difference with AF contamination was smaller than that we reported previously in venous thromboembolism cases. The inhibitory effects of AF on the APC anticoagulation pathway may contribute, at least partly, to further promotion of thrombin production induced by AF. Combined with other classical thrombophilic risk factors, the present findings support possible involvements of AF exposure in the high incidence of PTE in early puerperium.

Cystine supplementation sustains plasma mercaptalbumin levels in rats fed low-protein diets more effectively than methionine.

We recently reported that dietary cystine maintained plasma mercaptalbumin levels in rats fed low-protein diets. The present study aimed to compare the influence of low-protein diets supplemented with cystine and methionine, which is another sulfur amino acid, on plasma mercaptalbumin levels in rats. Male Sprague-Dawley rats were fed a 20% soy protein isolate diet (control group), 5% soy protein isolate diet (low-protein group) or 5% soy protein isolate diet supplemented with either methionine (low-protein + Met group) or cystine (low-protein + Cyss group) for 1 week. The percentage of mercaptalbumin within total plasma albumin of the low-protein + Met group was significantly lower than that of the control and low-protein + Cyss groups. No significant differences in the mRNA levels of tumor necrosis factor-α, interleukin-6, interleukin-1ß, and cyclooxygenase 2 in blood cells were observed between the low-protein + Met and low-protein + Cyss groups. Treatment with buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, did not influence the percentage of mercaptalbumin within total plasma albumin in rats fed the low-protein diet supplemented with cystine. These results suggest that supplementation with cystine may be more effective than that with methionine to maintain plasma mercaptalbumin levels in rats with protein malnutrition. Cystine might regulate plasma mercaptalbumin levels via the glutathione-independent pathway.