Exposure to low-dose bisphenol A induces spleen damage in a murine model: Potentially through oxidative stress?

Background: During early life, exposure to environmental toxicants, including endocrine disruptor bisphenol A (BPA), can be detrimental to the immune system. To our knowledge, a few researches have looked at the effects of developing BPA exposures on the spleen. Aim: The murine model was developed to investigate the underlying molecular mechanisms and mode of BPA actions on the spleen subsequent to prolonged early-life exposure to BPA. Methods: Immature (3-week-old) male and female Swiss Albino mice were intraperitoneally injected with 50 µg/kg BPA in corn oil or corn oil alone for 6 weeks. Mouse spleens were harvested and examined histologically at 10 weeks old (adulthood). Results: We observed neurobehavioral impairments and a significant increase in peripheral monocyte and lymphocyte counts in mice (males and females). Moreover, several spleen abnormalities in both male and female mice were observed in adulthood. BPA-treated mice's histopathological results revealed toxicity in the form of significantly active germinal centers of the white pulp and a few apoptotic cells. There was also a notable invasion of the red pulp by eosinophils and lymphocytes that were significantly higher than normal. Agarose gel electrophoresis provided further evidence of internucleosomal DNA fragmentation and apoptosis in the splenic tissues of BPA-treated mice compared to controls. In addition, there were increased levels of the lipid peroxidation malondialdehyde end-product, a marker of oxidative lipid damage, in the spleens of BPA-treated mice compared to controls. Conclusion: Our study provides evidence that oxidative stress injury induced by early-life exposures to BPA could contribute to a range of splenic tissue damages during adulthood.

Real world use of oral treatments in interstitial cystitis/bladder pain syndrome in the UK: Outcome of a cross sectional study.

BACKGROUND: To describe the oral treatments people living with interstitial cystitis/bladder pain syndrome (IC/BPS) are using to treat their urologic condition in the UK. METHOD: A questionnaire hyperlink encompassing current and previous medications taken for IC/BPS with other sociodemographic and diagnostic indices was available to the Bladder Health UK website. Interested and fully consented individuals accessed and completed the survey. RESULTS: A total of 601 accessed the questionnaire of whom 173 participants responded (response rate: 28.7%) with a mean ± SD O'Leary/Sant scores of 20.12 ± 9.38. A sample size of 171 was estimated to be used in the survey. A fifth of the participants were not on any treatment at all. Amitriptyline was the most prevalent medication in use both alone and in combination. A shift in the use of unapproved (for IC/BPS) antidepressant, smooth muscle relaxant, opioids, gabapentenoids, and antibiotics was observed in the sample. There were no significant differences between the mean (SD) O'Leary/Sant scores of cohorts currently taking oral medications and those not taking it. More than two-thirds of the participants had been diagnosed with the disease more than 5 years. Just under a half (47.4%) of participants reported a history of allergy. CONCLUSION: Our study provides contemporary evidence that the treatments used for managing IC/BPS encompass a broad range of medications both recommended and not recommended by current guidelines. The latter suggests patients are willing to try novel treatments when more conventional ones are ineffective.

The relationship between illness perception and worsening of interstitial cystitis/painful bladder syndrome symptoms: A cross-sectional study.

OBJECTIVE: To evaluate disease perception in a cohort of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) using the Brief Illness Perception-Questionnaire (BIP-Q) and to evaluate how this might relate to disease severity. MATERIALS AND METHODS: The study is a cross-sectional survey amongst members of Bladder Health UK who had previously received a clinical diagnosis of IC/PBS. A hyperlink containing the questionnaire was sent to the patient group's website and interested members accessed and completed the survey. Participants' inclusion was based on a prior clinical diagnosis of IC/PBS, current O'Leary Sant scores supportive of the diagnosis, and age between 18 and 80. A sample size of 171 was used in the study. The Brief Illness Perception Questionnaire (BIP-Q) and the O'Leary/Sant symptoms and problem indices questionnaire were used to collect data. A multivariable logistic regression analysis was used to test the relationship between items of BIP-Q and severity of IC/PBS. Content analysis was used for the causal domain and subsequently analysed as percentages. RESULTS: Six hundred and one members accessed the questionnaire of whom 159 returned completed questionnaires. One hundred and twenty-two of 159 (≥75%) respondents believe that their illness will continue indefinitely. The majority of the respondents indicated that IC/PBS had a negative impact on their daily lives, caused them worry and made them emotionally unstable. Of the 8 BIP-Q items, those most predictive of disease severity were (adjusted odd ratio and confidence intervals): consequence 0.094 (0.023-0.386); treatment control 2.702 (1.256-5.812); identity 0.141 (0.033-0.600); concern 9.363 (1.521-57.632). CONCLUSIONS: Our findings show that IC/PBS negatively impacts participant's quality of life and emotional wellbeing. Higher expectation for treatment benefit and increasing levels of patient concern are predictive for severity of IC/PBS.

Adipocyte-Specific Fatty Acid-Binding Protein (AFABP) and Chemerin in Association with Gestational Diabetes: A Case-Control Study.

BACKGROUND: Adipocytokines participate in regulating the inflammatory response in glucose homeostasis and type 2 diabetes. However, among these peptides, the role of adipocyte-specific fatty-acid-binding protein (AFABP), chemerin, and secreted protein acidic and rich in cysteine (SPARC) in gestational diabetes (GDM) has not been fully investigated. METHOD: The maternal fasting level of adipocytokines of 53 subjects with GDM and 43 normal pregnant (NGDM) was measured using multiplex immunoassay at 24-28 weeks, before delivery, immediate postpartum, and 2-6 months postpuerperium. RESULTS: Higher levels of AFABP were associated with a 3.7-fold higher risk of GDM. Low chemerin levels were associated with a 3.6-fold higher risk of GDM. Interleukin-10 (IL-10) was inversely associated with the risk of GDM. SPARC had no association with GDM. AFABP was directly correlated to interleukin-6 (r = 0.50), insulin resistance index (r = 0.26), and body mass index (r = 0.28) and inversely correlated to C-reactive protein (r = -0.27). Chemerin levels were directly and strongly correlated with IL-10 (r = 0.41) and interleukin-4 (r = 0.50) and inversely correlated to insulin resistance index (r = -0.23) in GDM but not NGDM. In the longitudinal assessment, there were no significant differences in AFABP and chemerin concentrations of both studied groups. CONCLUSION: AFABP and chemerin were associated with a higher risk of GDM. These adipocytokines were related to insulin resistance, body mass index, and inflammation in pregnant women diagnosed with GDM.

Paternal bisphenol A exposure induces testis and sperm pathologies in mice offspring: Possibly due to oxidative stress?

Bisphenol A (BPA), an endocrine and metabolic disruptor, is widely used to manufacture polycarbonate plastics and epoxy resins. Accumulating evidence suggests that paternal BPA exposure adversely affects male germlines and results in atypical reproductive phenotypes that might persist for generations to come. Our study investigated this exposure on testicular architecture and sperm quality in mouse offspring, and characterised underlying molecular mechanism(s). A total of 18 immature male Swiss albino mice (3.5 weeks old) were randomly divided into three groups and treated as follows: Group I, no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 µg/kg) in sterile corn oil. At 9.5 weeks old, F0 males were mated with unexposed females. F0 offspring (F1 generation) were monitored for postnatal development for 10 weeks. At 11.5 weeks old, the animals were sacrificed to examine testicular architecture, sperm parameters, including DNA integrity, and oxidative stress biomarkers. Results showed that BPA significantly induced changes in the body and testis weights of the F0 and F1 generation BPA lineages compared to F0 and F1 generation control lineages. A decrease in sperm count and motility with further, increased sperm abnormalities, no or few sperm DNA alterations and elevated levels of MDA, PC and NO were recorded. Similar effects were found in BPA exposed F0 males, but were more pronounced in the F0 offspring. In addition, BPA caused alterations in the testicular architecture. These pathological changes extended transgenerationally to F1 generation males' mice, but the pathological changes were more pronounced in the F1 generation. Our findings demonstrate that the biological and health BPA impacts do not end in paternal adults, but are passed on to offspring generations. Hence, linking observed testis and sperm abnormalities in the F1 generation to BPA exposure of their parental line was evident in this work. The findings also illustrate that oxidative stress appears to be a molecular component of the testis and sperm pathologies.

Increased plasma CD14 levels 1 year postpartum in women with pre-eclampsia during pregnancy: a case-control plasma proteomics study.

Epidemiological data suggest that pre-eclampsia (PE) is associated with an increased risk of post-delivery metabolic dysregulation. The aim of the present case-control observational study was to examine the global plasma proteomic profile 1 year postpartum in women who developed PE during pregnancy (n = 5) compared to controls (n = 5), in order to identify a novel predictive marker linking PE with long-term metabolic imbalance. Key findings were verified with enzyme-linked immunosorbent assay (ELISA) in a separate cohort (n = 17 women with PE and n = 43 controls). One hundred and seventy-two proteins were differentially expressed in the PE vs. control groups. Gene ontology analysis showed that Inflammatory|Immune responses, Blood coagulation and Metabolism were significantly enriched terms. CD14, mapping to the inflammatory response protein network, was selected for verification based on bibliographic evidence. ELISA measurements showed CD14 to be significantly increased 1 year postpartum in women with PE during pregnancy compared to controls [PE group (median ± SD): 296.5 ± 113.6; control group (median ± SD): 128.9 ± 98.5; Mann-Whitney U test p = 0.0078]. Overall, the identified proteins could provide insight into the long-term disease risk among women with PE during pregnancy and highlight the need for their postpartum monitoring. CD14 could be examined in larger cohorts as a predictive marker of insulin resistance and type II diabetes mellitus among women with PE.

Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

AIMS: To identify the presence and geographical distribution of mast cell (MC) subtypes: MCT (tryptase positive-chymase negative) and MCTC (tryptase positive-chymase positive) in bladder tissue. METHODS: Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MCT and MCTC) and anti-MC chymase (for MCTC). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. RESULTS: There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MCTC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. CONCLUSIONS: Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MCTC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis.

Systemic lupus erythematosus: disease activity may influence the release of endothelial microparticles?

: To evaluate blood-borne endothelial microparticles (EMPs) in women with SLE and correlated these to disease activity as defined by the SLEDAI-2K score. The study takes cross-sectional design. A total of 90 age-matched women were recruited including: G1 (healthy volunteers, n = 30), G2 (women with SLE and low disease activity (SLEDAI-2K score ≤4; n = 30) and G3 (women with SLE and moderate/high disease activity (SLEDAI-2K score >4; n = 30). Blood was collected in 3.2% sodium citrate. Subsequently, the microparticles were purified by ultracentrifugation and labeled with anti-CD51/61 and anti-Annexin-V antibodies. Quantification and phenotyping were performed using flow cytometry. The number of EMPs was significantly higher in SLE patients compared with controls (P = 0.0178). When SLE patients were stratified according to disease activity, the number of EMPs was significantly increased in women with moderate-to-high disease activity compared with controls (P = 0.0074). We observed a correlation between the number of EMPs and age (r = -0.34; P = 0.0123) and between the number of EMPs and SLEDAI-2K score (r = 0.30; P = 0.04). Our results suggest that the SLE causes increased EMPs release, especially in patients with SLEDAI-2K score greater than 4. Although measurement of the EMPs could be useful in distinguishing patients with SLE from health controls, they have limited value in differentiating between SLE subtypes.

Honey is potentially effective in the treatment of atopic dermatitis: Clinical and mechanistic studies.

INTRODUCTION: As manuka honey (MH) exhibits immunoregulatory and anti-staphylococcal activities, we aimed to investigate if it could be effective in the treatment of atopic dermatitis (AD). METHODS: Adult volunteers with bilateral AD lesions were asked to apply MH on one site overnight for seven consecutive days and leave the contralateral site untreated as possible. Three Item Severity score was used to evaluate the response. Skin swabs were obtained from both sites before and after treatment to investigate the presence of staphylococci and enterotoxin production. In addition, the ability of MH and its methanolic and hexane extracts to down regulate IL4-induced CCL26 protein release from HaCaT cells was evaluated by enzyme linked immunosorbent assay. Also, the ability of MH to modulate calcium ionophore-induced mast cell degranulation was assessed by enzyme immunoassay. RESULTS: In 14 patients, AD lesions significantly improved post MH treatment versus pre-treatment as compared to control lesions. No significant changes in the skin staphylococci were observed after day 7, irrespective of honey treatment. Consistent with the clinical observation, MH significantly down regulated IL4-induced CCL26 release from HaCaT cells in a dose-dependent manner. This effect was partially lost, though remained significant, when methanolic and hexane extracts of MH were utilized. In addition, mast cell degranulation was significantly inhibited following treatment with MH. CONCLUSIONS: MH is potentially effective in the treatment of AD lesions based on both clinical and cellular studies through different mechanisms. This needs to be confirmed by randomized and controlled clinical trials.

Gold nanoparticle interactions in human blood: a model evaluation.

In this study, we investigated gold nanoparticle (AuNP) interactions in blood using thromboelastography as a rapid screening tool to monitor their influence on blood coagulation. 1.2 nM colloidal AuNPs ranging from 12 to 85 nm have no effect in the blood, however, 5 nM AuNPs demonstrate pro-thrombogenic concentration dependent effects with a reduction in clot formation. Size effects exhibit a non-linear trend with 45 and 85 nm particles resulting in a faster pro-thrombotic response. Clot strength decreased with AuNP size with the greatest reduction with 28 nm particles. We assessed AuNP interactions in the blood focusing on their biological activity. AuNP-RGD possessed pro-coagulant activities, while PEG-thiol, human fibrinogen and clopidogrel prevented blood clot formation and influenced platelet activity, and were more efficient when bound to nanocarriers than unbound ligands. Such tests could fill the knowledge gaps in thrombogenicity of NPs between in vitro test methods and predict in vivo haemocompatibility.

Diluted honey inhibits biofilm formation: potential application in urinary catheter management?

AIMS: Biofilms are ubiquitous and when mature have a complex structure of microcolonies in an extracellular polysaccharide and extracellular DNA matrix. Indwelling medical devices harbour biofilms which have been shown to cause infections and act as reservoirs for pathogens. Urinary catheters are often in place for considerable periods of time and are susceptible to both encrustation and biofilm formation. Strategies for minimising biofilm occurrence underpin an active research area in biomedicine. Manuka honey has, inter alia, well-established antibacterial properties. This study aims to assess the influence of honey on early biofilm formation in an established in vitro model. METHODS: An established model of early biofilm formation using static bacterial cultures in vinyl 96-well plates was used to grow Escherichia coli, strain ATC 25922 and Proteus mirabilis, strain 7002. Planktonic cells were removed and the residual biofilm was stained with crystal violet, which were subsequently eluted and quantified spectrophotometrically. Manuka honey (Unique Manuka Factor 15+) was added either with the bacteria or up to 72 hours after. RESULTS: Biofilms in this model was developed over 3 days, after which growth stalled. Mixed (1:1) cultures of E. coli and P. mirabilis grew slower than monocultures. In mixed cultures, honey gave a dose-dependent reduction in biofilm formation (between 3.3 and 16.7%w/v). At 72 hours, all concentrations inhibited maximally (p<0.001). Application of honey to cultures after 24 and 48 hours also reduced the adherent bacterial biomass (p<0.05-p<0.01). CONCLUSION: Manuka honey at dilutions as low as 3.3% w/v in some protocols and at 10% or above in all protocols tested significantly inhibits bacterial attachment to a vinyl substrate and reduces further early biofilm development. No augmentation of growth over untreated controls was observed in any experiment.

Artemisinins as potential anticancer agents: uptake detection in erythrocytes using Fourier transform infrared spectroscopy and cytotoxicity against bladder cancer cells.

AIMS: Semisynthetic derivatives of the antimalarial drug artemisinin may also possess anticancer properties. The ability to detect artemisinin uptake and distribution in cells would facilitate live cell imaging without labelling. This study describes mid-range infrared absorption spectra for three artemisinin variants and attempts to detect their presence in a simple cell model (erythrocytes). Cytotoxicity assays assess potential anticancer properties against bladder cancer cells. METHODS: Mid-range Fourier transform infrared spectra were obtained from dry preparations of dihydroartemisinin (DHA), artesunate (ART) and artemether (ARTE). Erythrocytes were prepared from normal blood and incubated for 30 min at 37°C with the three artemisinin derivatives. Cytospin preparations were prepared on aluminium foil for spectroscopy. Potential for growth inhibition in the RT112 bladder carcinoma cell line was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide residual viable biomass method. RESULTS: Spectra were obtained from the three native compounds. Repeat scans after 8 weeks showed ART and ARTE to be stable, stored under manufacturer's recommendations. DHA exhibited marked changes over the same period. It was possible by subtraction to detect DHA in cytospins, but not ART or ARTE. The fit between the subtraction spectrum and that of the native compound was >80%. DHA and ART showed strong cytotoxic potential against RT112 cells. CONCLUSIONS: The artemisinin derivatives tested exhibit unique mid-range infrared absorption spectra which can be used to monitor degradation and, for DHA, can be detected by subtraction in loaded erythrocytes rendering future imaging studies feasible. Its cytotoxic efficacy against RT112 cells suggests bladder cancer as a possible target disease.

Tissue factor-dependent pathway in severe preeclampsia revisited: a Brazilian cohort study.

Previously we investigated the tissue factor (TF)-dependent coagulation pathway and key haemostatic cofactors in white women with preeclampsia (P-EC) and suggested that plasma factor VII (FVII) levels can differentiate women with P-EC from healthy nonpregnant women or normal pregnant women, at the same trimester, with high sensitivity, specificity, positive and negative predictive values. Here we re-examine the TF-dependent pathway in a large cohort of Brazilian women. A total of 240 women were studied. These included healthy nonpregnant women (n = 79), normotensive pregnant women (n = 80) and women with severe P-EC (n = 81). Commercially available enzyme-linked immunosorbent assays were used to measure plasma FVII, activated factor VII (FVIIa), TF and tissue factor pathway inhibitor (TFPI). All study participants were matched for age. Pregnant women (with/without P-EC) were matched for gestational age and parity. Plasma levels of FVII, FVIIa and TFPI were significantly increased in women with severe P-EC compared with healthy nonpregnant women (P < 0.01) or normotensive pregnant women (P < 0.01). FVIIa was also higher in normotensive pregnant women compared with nonpregnant women (P < 0.01). However, no such significant trends were observed for plasma TF levels (P = 0.074). In conclusion, circulating FVII, FVIIa and TFPI were significantly elevated in women with severe P-EC in the absence of comparable changes in plasma TF levels. The present work is in agreement with our previous report on FVII levels in white women with P-EC. Thus, this lends further support to the notion that plasma FVII levels are potentially valuable diagnostic marker for P-EC, irrespective of ethnicity.

Homeostasis of Hemostasis: The Role of Endothelium.

Forming an interface with virtually every other organ, endothelium has a strategic role in modulating vascular homeostasis. While its miscellany of functions includes regulation of vasomotor tone, promotion, and prevention of vascular growth, and modulation of inflammatory and hemostatic processes, it functions critically in maintaining the balance of hemostasis in health. Whereas endothelium has been recognized to influence all stages of hemostasis, new evidence suggests it to have a primary role for thrombin generation. Endothelial dysfunction is being increasingly appreciated in several pathological states and particularly, by virtue of its critical role in hemostasis, in causing thrombosis in a multitude of diseases.

Postsurgical Inflammation as a Causative Mechanism of Venous Thromboembolism.

Surgery is associated with an increased risk of venous thromboembolic events (VTE) including deep vein thrombosis and pulmonary embolism. Although the current treatment regiments such as mechanical manipulation and administration of pharmacological prophylaxis significantly reduced the incidence of postsurgical VTE, they remain a major cause of postoperative morbidity and mortality worldwide. The pathophysiology of venous thrombosis traditionally emphasizes the series of factors that constitute Virchow triad of factors. However, inflammation can also be a part of this by giving rise to a hypercoagulable state and endothelial damage. The inflammatory response after surgery, which is initiated by a cytokine "storm" and occurs within hours of surgery, creates a prothrombotic environment that is further accentuated by several cellular processes including neutrophil extracellular traps formation, platelet activation, and the generation of tissue factor-bearing microparticles. Although such inflammatory markers are elevated in undergoing surgery, the precise mechanism by which they give rise to venous thrombosis is poorly understood. Here, we discuss the potential mechanisms linking inflammation to thrombosis, and highlight strategies that may minimize surgical inflammation and reduce the incidence of postoperative VTE.

The Activation of Complement and Its Role in the Pathogenesis of Thromboembolism.

It is well established that inflammation and thrombosis are intricately linked processes, and there is increasing evidence of the importance of their roles in activated complement in the pathogenesis of thromboembolism. The two systems are activated by similar stimuli simultaneously and interact, either directly or through biochemical mediators, to protect the host from microbial invasion. Diseases characterized by complement hyperactivity such as paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome have high rates of thrombosis. This review describes how disease processes where there is excessive complement activation leads to thrombosis, and the specific interactions between the complement and coagulation systems that lead to pathological thrombus formation.

Cytotoxicity of gemcitabine enhanced by polyphenolics from Aronia melanocarpa in pancreatic cancer cell line AsPC-1.

AIMS: Extending work with brain tumours, the hypothesis that micronutrients may usefully augment anticancer regimens, chokeberry (Aronia melanocarpa) extract was tested to establish whether it has pro-apoptotic effects in AsPC-1, an established human pancreatic cell line, and whether it potentiates cytotoxicity in combination with gemcitabine. Pancreatic cancer was chosen as a target, as its prognosis remains dismal despite advances in therapy. METHODS: An MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was used to assess the growth of the single pancreatic cancer cell line AsPC-1, alone and in comparison or combination with gemcitabine. This was backed up by flow cytometric DRAQ7 cell viability analysis. TUNEL assays were also carried out to investigate pro-apoptotic properties as responsible for the effects of chokeberry extract. RESULTS: Chokeberry extract alone and its IC75 value (1 µg/mL) in combination with gemcitabine were used to assess the growth of the AsPC-1 cell line. Gemcitabine in combination with chokeberry extract was more effective than gemcitabine alone. TUNEL assays showed apoptosis to be a mechanism occurring at 1 µg/mL concentration of chokeberry, with apoptotic bodies detected by both colourimetric and fluorometric methods. CONCLUSIONS: The implication of this study, using single cancer cell line, is that chemotherapy (at least with gemcitabine) might be usefully augmented with the use of micronutrients such as chokeberry extract.

Tissue factor and tissue factor pathway inhibitor in women with a past history of preeclampsia: implication for a hypercoagulable state postpregnancy.

Preeclampsia (P-EC) is a multisystem disorder of pregnancy whose cause and pathogenesis remain poorly understood. However, abnormal haemostasis and endothelial dysfunction are thought to be implicated. Women with a past medical history of P-EC have a baseline hypercoagulable state postpregnancy. The aim of this study is to examine the relationship between tissue factor (TF) and TF pathway inhibitor (TFPI) in women who have had P-EC within the last 3 years (more than 6 months postpartum) and their normal counterparts. Blood specimens were collected from women known to have had P-EC within the last 3 years (n = 26) and aged-matched healthy women without past history of P-EC in previous pregnancy (n = 26). Plasma TF and TFPI levels were measured using ELISAs. Women who have had P-EC showed increased TF levels compared with their normal counterparts, whereas TFPI levels were reduced. Neither parameter differed significantly when the groups were tested against each other. Interestingly, the TF/TFPI ratio was significantly increased (P = 0.024) when the two groups were compared. In summary, there was a trend towards increased TF and reduced TFPI levels in the P-EC group. Such a tendency was not statistically significant. However, the TF/TFPI ratio was significantly increased when the groups were compared. Our findings suggest an imbalance between TF/TFPI levels in women with past history of P-EC postpregnancy. This may contribute to the development of maternal hypercoagulable states and may predispose women with a history of P-EC to cardiovascular risks later in life.

Gastrointestinal bleeding and aortic stenosis (Heyde syndrome): the role of aortic valve replacement.

Heyde syndrome (the combination of iron deficiency anemia and aortic stenosis) has been a controversial entity. The proposed mechanisms between aortic valve disease and iron deficiency anemia are examined in this article along with impact valve replacement on iron deficiency anemia.