The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Exploring associations of anthropometric parameters and serum triglycerides with serum thyroid hormones in young women.

Establishing links between serum thyroid hormone panel and triglyceride (TG) concentrations with non-invasively obtained measurements of anthropometric parameters of young women may provide preliminary knowledge about the homeostasis of metabolic processes and body composition and about the strategic role of the tested parameters as early screening tests for assessing the health status of apparently healthy women in the period preceding pregnancy. The study was conducted in 381 healthy female students (aged 18-26 years, mean ± SD = 22.1 ± 1.3). Anthropometric indices (BMI, waist-to-hip ratio, FAT%) were calculated and serum concentrations of thyroid hormones (TSH, fT3, fT4) were determined using electrochemiluminescence immunoassays and serum triglycerides (TG) with a commercially available test. No association was established between serum TSH and anthropometric indices in healthy young women. Increased serum concentrations of fT4, fT3 and TG were found in overweight subjects, i.e. BMI > 24.9 kg/m2 (p < 0.05). A significant negative association between fT3 and TG was found in underweight subjects (r = - 0.258, p = 0.049) and a significantly positive association in normal-weight subjects (r = 0.139, p = 0.019). In healthy young women differences in BMI are not related to thyroid function. The opposite directions between the associations fT3 vs TG in underweight compared to normal-weight young prepregnant females may suggest dependencies of fT3 and TG in the regulation of specific BMI-dependent metabolic processes.

Serum indoxyl sulphate and its relation to albumin and α1-acid glycoprotein as a potential biomarkers of maternal intestinal metabolism during pregnancy and postpartum.

BACKGROUND: Serum indoxyl sulfate (IS) levels depend on the production of indole in the gut. The biological effects of IS in the vascular bed could be confirmed by changes in the levels of individual serum proteins during normal pregnancy and in the postpartum period as compared with non-pregnant controls. Albumin (Alb) and α1-acid glycoprotein (AGP, orosomucoid) are the most abundant serum carrier proteins with potential interrelationships with serum levels of IS. METHODS: Serum levels of IS, Alb and AGP were measured in 84 pregnant women in the first, second and third trimester of pregnancy and in the postpartum period, as well as in non-pregnant controls (n = 20), using ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry (IS), colorimetric assay (Alb) and immunoturbidimetric assay (AGP). RESULTS: The postpartum serum levels [mg/L] of IS were lower (p = 0.027) than in the second trimester (mean±SD: 0.85±0.39 vs 0.58±0.32). There were no differences in the IS to ALB ratio calculated in the three trimesters of pregnancy, the postpartum period, and in the non-pregnant controls. The IS/AGP ratio increased from the first to the second trimester (p = 0.039), and decreased in the postpartum period (p<0.05), when it was lower than in the second and third trimester. CONCLUSIONS: The variability of the serum IS/AGP ratio during pregnancy and in the postpartum period may reflect shared involvement in the regulation of their intravascular relationships. The link between serum levels of IS derived from the gut and AGP could serve a potential biomarkers of maternal intestinal metabolism during pregnancy and postpartum.

Associations between the thyroid panel and serum protein concentrations across pregnancy.

Establishing any characteristic associations between the serum parameters of thyroid function and serum proteins in pregnancy may aid in elucidating the role of the thyroid gland in the regulation of pregnancy-specific metabolic processes and in selecting candidate biomarkers for use in their clinical assessment. Concentrations of thyroid stimulating hormone (TSH), free tri-iodothyronine (fT3) and free thyroxine (fT4), six electrophoretically separated protein fractions (albumin, alpha-1-, alpha2-, beta-1-, beta-2- and gamma-globulins), representative proteins-albumin (ALB), transferrin (TRF), alpha-2-macroglobulin (AMG) and ceruloplasmin (CER) were measured in 136 serum samples from 65 women in their consecutive trimesters of pregnancy. The concentrations of TSH, fT4 and fT3 were significantly correlated (p < 0.05) with the concentrations of the albumin, alpha-2- and beta-1 globulin fractions. Significant correlations (p < 0.05) which were positive between fT4 and ALB and negative between fT4 and TRF were established throughout pregnancy. Significant negative correlations (p < 0.05) were demonstrated for fT3 with alpha-2-globulin, AMG and CER. Changes in the serum concentrations of thyroid hormones seen between the trimesters were found to correlate with the concentrations of high-abundance serum proteins. Opposite directions of correlations between fT4 and ALB and fT4 and TRF observed throughout pregnancy may indicate the shared biological role of these parameters in maintaining maternal homeostasis and they suggest their potential use in the clinic as a simple biomarker panel. A negative correlation of fT3 with CER in the second trimester possibly reflects their involvement in the active regulation of metabolic processes.

Seasonal variation of human physiology does not influence the harvest of peripheral blood CD34+ cells from unrelated hematopoietic stem cell donors.

There are many reports on factors predicting the outcome of PBSC (peripheral blood stem cell) mobilization, such as the donor's gender, age, weight, white blood cell count, platelets pre apheresis, LDH and iron status. Although there are reports of seasonal variation in the physiology of the human immune system and hematopoiesis there are no data that such differences play a role in the response to G-CSF in healthy hematopoietic stem cell donors. The response to G-CSF could also impact the collection results during different seasons. To assess the possible impact of seasonal variation we performed a retrospective, single-center analysis of mobilization and harvest of PBSC in 330 healthy unrelated donors. We found no significant differences in the number of CD34+ cells in peripheral blood after G-CSF mobilization and in collection results when all donors were analyzed. In the subgroup of male donors the number of CD34+ stem cells after G-CSF mobilization was higher than average in summer and autumn (p = 0.036), however, it did not translate into clinically relevant differences in stem cell harvest. We conclude that although there is possible seasonal variation in the response to G-CSF in male donors there is no impact on PBSC harvest in healthy unrelated donors.

Can variability of serum electrophoretic fractions during pregnancy provide knowledge about maternal and fetal health.

AIM: Characteristics of variability of concentrations total protein and its electrophoretic fractions in serum of healthy pregnant women between successive trimesters and post-partum for initial classification of proteins involved in specific metabolic processes associated with pregnancy. METHODS: Total serum protein concentrations were measured by biuret method and serum protein fractions were electrophoretically separated in 166 serum samples collected from healthy pregnant women in three trimesters of pregnancy (1st, n = 55; 2nd, n = 42; 3rd, n = 39) and in post-partum (n = 30), and in 20 samples from nonpregnant controls. RESULTS: Across pregnancy, there were gradual, but occurring at different rates, decreases over time in serum total protein, albumin and gamma globulins compared to controls (P < 0.05). In 1st trimester, serum concentrations of total protein, albumin and gamma globulins were <10% lower than in nonpregnant state, with further decreases in 2nd and 3rd trimesters and in post-partum. The concentrations of alpha-1-, alpha-2-, beta-1- and beta-2-globulins were elevated compared to controls (P < 0.05) with different dynamics of change and with the highest percentage increase for alpha-1-globulin. CONCLUSION: Pregnancy-associated alterations in the serum concentrations of total protein and in its individual electrophoretic protein fractions in each trimester of pregnancy and differences versus normal ranges in nonpregnant healthy females could be a simple screening method for classification useful laboratory parameters that help obstetricians and gynecologists to make multidirectional judgments about the state of health of pregnant women.

Negative Impact of Borderline Creatinine Concentration and Glomerular Filtration Rate at Baseline on the Outcome of Patients With Multiple Myeloma Treated With Autologous Stem Cell Transplant.

BACKGROUND: Renal impairment (RI) is one of the multiple myeloma (MM)-defining events for initiating therapy. After induction therapy, high-dose chemotherapy followed by autologous peripheral blood stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients with MM. According to the International Myeloma Working Group (IMWG), the organ criterion for kidney damage is defined by a serum creatinine concentration (CrC) > 2 mg/dL or estimated glomerular filtration rate (eGFR) < 40 mL/min. In this long-term study, we evaluated the impact of CrC and eGFR calculated by the Modification of Diet in Renal Disease equation on progression-free and overall survival using a lower threshold than the IMWG criteria. PATIENTS AND METHODS: We studied the longitudinal outcomes as measured by progression-free survival and overall survival in 59 transplant-eligible patients with MM: 38 patients with normal renal function and 21 patients with RI defined as a CrC higher than upper limit of normal (≥ 1.1 mg/dL), eGFR < 60 mL/min, treated with ASCT from 1998 to 2004. RESULTS: The risk of disease progression and death following ASCT increased by 16.5% (P = .005) and 19% (P < .0009) per 1 mg/dL of CrC, respectively. The thresholds for the association of renal insufficiency and negative outcomes were CrC > 1.4 mg/dL and eGFR < 55mL/min. CONCLUSIONS: We observed a negative correlation between minimal renal insufficiency and long-term outcomes. Management of patients with even marginally increased CrC and/or decreased eGFR not fulfilling IMWG RI criteria requires more concentrated effort to reverse even minimal renal insufficiency.

Variations in serum concentrations of C-reactive protein, ceruloplasmin, lactoferrin and myeloperoxidase and their interactions during normal human pregnancy and postpartum period.

BACKGROUND: Serum proteins may provide information about homeostasis of redox status and inflammatory processes also during pregnancy. The aim of the study was to assess the dynamics of changes in serum concentrations of C-reactive protein (CRP), ceruloplasmin (CP), lactoferrin (LF) and myeloperoxidase (MPO) and their interactions during normal pregnancy and the postpartum period. METHODS: The concentrations of proteins were measured in serum (n=113) from pregnant in consecutive trimesters and in postpartum period (n=28) and in non-pregnant women (n=17), using immunoturbidimetric assays (CRP, CP) and ELISA Kits (LF, MPO). RESULTS: The concentrations [mg/dl] CP and CRP (mean±SD respectively): second trimester (43.1±6.2; 0.49±0.57), third trimester (44.5±5.8; 0.41±0.37), postpartum (42.39±6.4; 4.15±3.6) were higher than in the first trimester (33.0.5±8.7; 0.31±0.36) or non-pregnant women (24.12±7.4; 0.12±0.13). The increases in concentrations of CP and CRP between the first and the second trimesters were by approximately 35% and 50% respectively and the correlation coefficients in the first trimester and in non-pregnant women were twice higher than in the second trimester and the postpartum period. The concentrations [µg/ml] LF and MPO were no significant differences (mean±SD respectively): first (6.19±4.54; 0.17±0.12), second (5.68±4.4; 0.14±0.08), third (6.34±6.98; 0.17±0.14), the postpartum (4.86±3.64; 0.25±0.4), and non-pregnant (3.9±2.56; 3.2; 0.14±0.05). However, significant correlations were established (p<0.05) between MPO and LF in all groups and between the following ratios CRP/LF vs CP/MPO and CRP/MPO vs CP/LF. CONCLUSIONS: The concentrations of proteins synthesized by the liver (CP, CRP) dynamically increase during consecutive trimesters of pregnancy unlike neutrophil-derived proteins (LF, MPO). Statistically significant correlations between the proportions of the serum proteins may suggest their combined role for the maintenance of homeostasis during pregnancy.

Biosimilar G-CSF versus filgrastim and lenograstim in healthy unrelated volunteer hematopoietic stem cell donors.

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 µg/kg for lenograstim, 9.8 µg/kg for biosimilar filgrastim, and 9.3 µg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 106, 7.6 × 106, and 7.3 × 106, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF.

Relevance of male-to-female sex mismatch in liver transplantation for primary biliary cirrhosis.

BACKGROUND: Because male-to-female transplantations are related to exposure to H-Y antigen, sex matching may influence the outcomes after liver transplantation for autoimmune diseases. The purpose of this retrospective study was to evaluate the relevance of male-to-female mismatch in liver transplantation for primary biliary cirrhosis (PBC). MATERIAL AND METHODS: This retrospective study was based on the data of 82 female liver transplant recipients with PBC from a single institution. The primary outcome measure was graft survival at 10 years. The negative effects of well-known risk factors for poor outcomes were evaluated separately and compared between the female-to-female and male-to-female transplantations. RESULTS: Graft survival was similar after female-to-female and male-to-female transplantations (74.7% versus 73.1% at 10 years, respectively, p=0.676). Regarding the differential impact of other risk factors, prolonged cold ischemia and increased amount of blood transfusions adversely influenced outcomes after male-to-female transplantation (p=0.039 and p=0.039, respectively) but not after female-to-female transplantation (p=0.843 and p=0.110, respectively). Sex mismatched transplantations were associated with lower 10-year graft survival in subgroups of patients with blood transfusions >4 units (61.4% versus 100.0%, p=0.063) and >8 hours of cold ischemia (54.7% versus 75.8%, p=0.418). CONCLUSIONS: Although male-to-female sex mismatch does not seem to yield a direct negative impact on outcomes following liver transplantation for PBC, it can aggravate the negative effects of prolonged cold ischemia and blood transfusions.

Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post-transplant year.

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long-term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post-transplant year (p = 0.655) but worse during the five subsequent years among the five-yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post-transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post-transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non-ALD recipients up to the fifth post-transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre-transplant diagnosis of ALD yields negative effects on post-transplant outcomes beyond the fifth post-transplant year, not attributable to recidivism.