Days Of Levels Research Articles

ID: 1055 Adipose-derived stem cells and platelet rich plasma ameliorate liver cirrhotic circumstance in CCl4-induced mice: a new approach for liver cirrhosis treatment

Background: Stem cell therapy in liver cirrhosis treatment is attracting the attention of the scientific community. Adipose tissue-derived mesenchymal stem cells are a potential source of cells because they have self-renewal, high proliferation, and differentiation into a variety of cell types, including hepatocytes as potential cell sources for cirrhosis treatment. Platelet-rich plasma (PRP) growth factors contribute to regeneration and wound healing. We test the hypothesis that PRP co-administration enhances MSC treatment for mouse cirrhosis.
 Method: Male Swiss mice were treated orally with olive oil or CCl4 for 11 weeks. PRP was obtained from healthy mice. Mouse adipose-derived stem cells (mADSCs) from adipose tissue of 3 weeks CCl4 mice were cultured for three passages (P3-mADSCs) before the transfer by tail vein injection with or without PRP into 11 weeks CCl4 mice. Mice were divided into six groups (n=10 each group). 1) normal, 2) cirrhotic, 3) cirrhotic /PBS; 4) cirrhotic/PRP (0.2 ml/mice with PRP from healthy mice), 5) cirrhotic/mADSCs (5 x 105 cells/mice), and 6) cirrhotic/mADSC-PRP.
 
 Result: mADSCs were highly positive for CD44, CD90, and CD105. Relative to liver cells, P3-mADSCs highly expressed Alb, Ck18, Ck19, Tnf, c-met, Cyp1a1, Afp, Muc1, Ldl receptor. mADSCs were strongly positive for Cyp1a1 (98.21±1.57%) and Hgf (95.55±3.11%); moderately positive for alfa-fetoprotein (45.99±2.08%), Aat (44.43±7.79%), Alb (57.81±8.49%) and differentiated into hepatocyte-like cells under induction medium. After transplantation, CFDA-transplanted cells into CCl4-treated mice were found in the liver at day 21 st. Compared to mADSCs, mADSCs and PRP co-treatment most effectively improved serum AST/ALT/bilirubin and albumin levels in day seven cirrhotic mice (p<0.05); and significantly down-regulated procollagen (104-fold less) and TGF-beta 1 (10-fold less) in day 21 cirrhotic liver. Histology index and collagen deposition were improved in 100% of mADSC/PRP- and mADSCs- cirrhotic mice compared to 33.3% of PBS- or PRP- cirrhotic liver (p<0.05).
 Conclusion: Cultured mADSCs express hepatocyte enriched markers. PRP coadministration enhances mADSC effects to improve liver function further, and further reduce fibrosis.

Natural and artificial feeding management before weaning promote different rumen microbial colonization but not differences in gene expression levels at the rumen epithelium of newborn goats.

The aim of this work was to evaluate the effect of feeding management during the first month of life (natural with the mother, NAT, or artificial with milk replacer, ART) on the rumen microbial colonization and the host innate immune response. Thirty pregnant goats carrying two fetuses were used. At birth one kid was taken immediately away from the doe and fed milk replacer (ART) while the other remained with the mother (NAT). Kids from groups received colostrum during first 2 days of life. Groups of four kids (from ART and NAT experimental groups) were slaughtered at 1, 3, 7, 14, 21 and 28 days of life. On the sampling day, after slaughtering, the rumen content was sampled and epithelial rumen tissue was collected. Pyrosequencing analyses of the bacterial community structure on samples collected at 3, 7, 14 and 28 days showed that both systems promoted significantly different colonization patterns (P = 0.001). Diversity indices increased with age and were higher in NAT feeding system. Lower mRNA abundance was detected in TLR2, TLR8 and TLR10 in days 3 and 5 compared to the other days (7, 14, 21 and 28). Only TLR5 showed a significantly different level of expression according to the feeding system, presenting higher mRNA abundances in ART kids. PGLYRP1 showed significantly higher abundance levels in days 3, 5 and 7, and then experienced a decline independently of the feeding system. These observations confirmed a highly diverse microbial colonisation from the first day of life in the undeveloped rumen, and show that the colonization pattern substantially differs between pre-ruminants reared under natural or artificial milk feeding systems. However, the rumen epithelial immune development does not differentially respond to distinct microbial colonization patterns.

Correlation of arterial blood gas markers and lactate levels with outcomes in pediatric traumatic brain injury

Background: Various physical markers have been used to predict outcome of traumatic brain injury in children. However, the utility of metabolic alterations for prognostication has been poorly described. Thus, we aim to correlate arterial blood gas markers and lactate levels with outcomes in children with moderate to severe traumatic brain injury. Methods: This is a retrospective cohort study that included all patients <16 years old who presented to the Emergency Department with moderate to severe traumatic brain injury (Glasgow Coma Scale ⩽13). Serial arterial blood gas results and lactate levels in the first five days of admission to a pediatric intensive care unit (PICU) were reviewed. Primary outcome was in-hospital mortality. Secondary outcomes were 28-day ventilator-free and PICU-free days. A stepwise logistic regression analysis in conjunction with receiver operating characteristic analysis were used to identify variables that were associated with in-hospital mortality. Secondary outcomes were analyzed using multiple linear regression. Results: Among the 43 patients analyzed, more than half of the patients (60%) had severe traumatic brain injury (Glasgow Coma Scale 8). Twenty-seven of the 43 (65%) patients underwent neurosurgical intervention and overall mortality was 9/43 (20.9%). The worst base excess and lactate levels of Day 2 of PICU stay were found to be most predictive for mortality with maximal area-under-curve (95% confidence interval) of 0.967 (0.906, 1.000). Worst lactate level on day 2 of PICU stay was also found to be associated with ventilator-free days and PICU-free days. Conclusion: In children with moderate to severe traumatic brain injury, base excess and lactate on Day 2 of PICU stay were predictors of mortality, duration of mechanical ventilation and length of PICU stay.

Seasonal Changes of Some Reproductive Traits in Farafra Ewes under Egyptian Environmental Condition

AbstractThirty Egyptian Farafra ewes were used to study the effect of seasonal variations on reproductive cycleand ovarian activity. Estrus was detected twice daily throughout the year. Percentages of ewes showingestrus monthly, number of estrous cycle/ewe/season, estrous cycle length and heat duration weremeasured throughout different seasons of the year. Changes in ovarian activity were examined usingLaparoscopy technique. Percentage of ovulated ewes, ovulation rate and number of large and smallfollicles were recorded over different seasons. The obtained results revealed that the highest activecycles were observed in autumn and summer (87.1 and 84%), while the lowest was observed in spring(64.3%). Percentages of ewes that exhibited normal estrous cycle length during winter, spring; summerand autumn were 73.3, 47.0, 64.0, and 44.5%, respectively. While, the percentage of the short estrouscycle length was high in autumn (37.0%). During spring, summer and winter, the percentages of thelong cycle length were 25.0, 20.0 and 20.0 %, respectively. The percentages of ewes showed normalheat duration during autumn was 63.0%, summer (56.0%) and spring (46.4%), while the percentage ofewes exhibited short heat duration were in spring (53.6%) and winter (50%). During autumn, ewesrecorded the longest (p 3 mm3) in diameterwere significantly higher (P<0.05) in winter. Plasma progesterone concentration was always the lowestat the onset of estrous, increased gradually to a maximum level in day 8 and remained until day 14 (lutealphase), then declined in day 16 in winter, spring and summer and at day 18 in autumn. In conclusion,subtropical Farafra ewes were almost cyclic throughout the year. Reproductive performance of Farafraewes still need more studies to reveal the strength and potential of this breed.

Metabolic responses of the growing Daphnia similis to chronic AgNPs exposure as revealed by GC-Q-TOF/MS and LC-Q-TOF/MS

Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. Their fast-growing utilization has increased the occurrence of AgNPs in the environment, posing potential health and ecological risks. In this study, we conducted chronic toxicity tests and investigated the metabolic changes of the growing Daphna similis with exposure to 0, 0.02, and 1 ppb AgNPs, using non-targeted mass spectrometry-based metabolomics. To the best of our knowledge, this study is the first to report the baseline metabolite change of a common aquatic organism Daphnia crustacean through its life-cycle. The results show a dynamic kinetic pattern of the growing Daphnia's metabolome underwent a cycle from day 0 to day 21, with the level of metabolites gradually increasing from day 0 to day 13, before falling back to the baseline level of day 0 on day 21. As for the samples exposed to environmental concentrations of AgNPs, although without morphological or structural changes, numerous metabolite changes occurred abruptly during the first 10 days, and these changes reached steady state by day 13. The significant changes in certain metabolites, such as amino acids (serine, threonine and tyrosine), sugars (d-allose) and fatty acids (arachidonic acid) revealed new insights into how these metabolites in Daphnia respond to chronic AgNPs stress. These findings highlight the capability of metabolomics to discover early metabolic responses to environmental silver nanoparticles.

The role of HCG increment in the 48 h prior to methotrexate treatment as a predictor for treatment success

ObjectiveTo evaluate the role HCG change in the 48h prior to methotrexate treatment as a predictor for treatment success. Study designMedical records of all women who were diagnosed with ectopic pregnancy between January 2001 and June 2013 were reviewed. Four hundred and nine patients received methotrexate due to ectopic pregnancy. The “single dose” methotrexate protocol with 50mg/m2 was administered to patients with progressing ectopic pregnancy. HCG levels in days 1, 4 and 7 were used to evaluate methotrexate treatment success. The percentage of HCG change in the 48h prior to methotrexate treatment was compared between patients who were successfully treated and those who failed treatment with methotrexate. ResultsSingle dose methotrexate was successful in 309 patients (75.4%, success group). The medians of HCG change in the 48h prior to methotrexate administration were significantly higher in the “failure group” (21% vs. 4%, p<0.01). In a logistic regression analysis, the of HCG percent increment prior to methotrexate administration was shown to be an independent predictor for treatment outcome. Receiver operator characteristic curve for HCG percent change was 0.751, at a cutoff value of HCG increment <12% the positive predictive value for treatment success reached 86%. ConclusionsPercentage of HCG increment in the 48h prior to methotrexate administration is an independent predictor for methotrexate treatment success. HCG increment <12% prior to methotrexate treatment is a good predictor for treatment success.

Plasma biomarker analysis of ramucirumab in Japanese patients with advanced gastric cancer: Preliminary results.

72 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use; however, no validated biomarker has been available until today. The aim of this study is 1) to reveal the dynamics of plasma biomarkers, 2) to assess the associations between these baseline levels or dynamics and efficacy. Methods: Plasma samples were collected at three points: base line, day 8, and after disease progression. Nine kinds of plasma biomarker involved in angiogenesis were measured by means of ELISA. Progression-free survival (PFS) was estimated using Kaplan-Meier methods and compared using the log-rank test. Comparisons of plasma biomarker levels were performed using Mann-Whitney-U test. Results: Samples were collected from 35 patients. Among them, 25 patients were evaluated when analyzed and 6 patients showed disease progression at the first evaluation. In VEGF-A and PlGF, plasma biomarker levels of day 8 were dramatically elevated in all patients; Day8/ baseline ratios were 18.1 folds in VEGF-A and 19.3 folds in PlGF. On the other hand, Day8/ baseline ratio of VEGFR1 and NRP1 were 0.7 and 0.8, respectively. The others appeared to show variable change at day 8. In survival analysis, lower than median Day8/ baseline ratios of VEGF-A were significantly associated with longer PFS with 6.3 months in &lt; median vs. 2.4 months in ≥ median (p = 0.004). In addition, patients with disease progression at the first evaluation by CT showed higher Day8/ baseline ratios of VEGF-C, Angiopoietin 1, and lower baseline NRP1 levels than those of patients with non-disease progression. Conclusions: Dramatic changes of biomarker levels at day 8 were observed among patients in each biomarker. These changes in VEGF-A, C, and Angiopoietin-1 may be candidate predictive marker of ramucirumab in Japanese patients with gastric cancer.

Follistatin and Endoglin: Potential Biomarkers of Endothelial Damage and Non-Relapse Mortality after Myeloablative Allogeneic Hematopoietic Cell Transplantation in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402

Introduction:Inflammation and angiogenesis are linked biologic processes influencing the onset and recovery of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT). In aGVHD, angiogenic factors (AF) contributing to tissue healing/repair (e.g. epidermal growth factor [EGF]) versus AF associated with tissue damage/inflammation (e.g. follistatin [FS]) exist in a dysregulated balance. Whether these AF are associated with, or predictive of, non-relapse mortality (NRM) in the absence of aGVHD, is not understood. Given that regimen-related tissue injury plays a role in NRM, we hypothesized that elevated levels of inflammation-associated AF early after HCT would be associated with NRM even in patients without aGVHD.Methods:We studied plasma samples from patients enrolled on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) aGVHD prophylaxis study 0402, a randomized trial of tacrolimus/methotrexate vs tacrolimus/sirolimus after matched sibling peripheral blood stem cell transplantation with myeloablative conditioning. Levels of AF (angiopoietin-2 [Ang2], EGF, FS, vascular endothelial growth factor [VEGF]-A and -B, endoglin [sEng], placental growth factor [PlGF], and soluble VEGF receptor [sVEGFR]-1 and -2) were quantified by MILLIPLEX magnetic bead panels.We analyzed factors associated with NRM in univariate analysis and used multivariate analysis to develop composite AF scores to predict NRM. In calculating the composite scores, we extrapolated the individual probabilities of NRM based upon regression models, and sorted the individual probabilities into 3 composite scores based on: 1) estimated probability of NRM <10%, 2) probability of NRM between 10-19%, 3) probability of NRM >20%.Results:221 patients from BMT CTN 0402 had pre-transplant plasma samples and samples at day +28 available for analysis. Univariate analysis showed associations of raw levels of Ang2, FS, sEng, and sVEGFR1 on day +28 with NRM. Of these, only higher levels of log-transformed FS (p=0.01) and of sEng (p=0.04) showed a correlation with NRM; these two AF were selected for the final model. In multivariate analysis, patients with the highest levels of day +28 FS and sEng (score 3, n=32, Figure) had a 4.6-fold higher relative risk (RR) of NRM (95% confidence interval 1.7-12.3, p<0.01, Table). The prognostic value of the composite score was stronger than either individual factor alone (RR log[FS]=2.1, p=0.03, and RR log[sEng]=2.3, p=0.07). Grade III-IV aGVHD and patient age>50 years were also independently associated with 1-year NRM. There was no effect of patient gender, disease status, CMV serostatus, or type of GVHD prophylaxis (tacrolimus/methotrexate versus tacrolimus/sirolimus) on NRM. There was no significant effect of the composite score, grade III-IV aGVHD, or age on the competing risk of relapse. FS and sEng measured before HCT were not associated with 1-year NRM (p=0.91 and p=0.62, respectively). There was only a weak correlation between the day 0 and day 28 FS and sEng (Spearman’s rho 0.36 and 0.38, respectively). Among the 221 cohort patients, there were 25 deaths due to NRM, including 5 deaths occurring prior to day 56. Death was more likely to be from organ toxicity in patients with composite score 3 (5/9, 56%) vs those with a composite score of 1 (1/8, 12%) or 2 (3/8, 37%).Conclusions:A composite score using day 28 plasma levels of FS and sEng predicts the risk of 1-year NRM after HCT, providing further evidence that endothelial dysfunction is a relevant biological problem in HCT. Pre-HCT measurements of FS and sEng were not associated with NRM, suggesting that elevations in these factors may reflect susceptibility to regimen-related toxicity. We have previously shown that elevated levels of FS and sEng at the onset of aGVHD are associated with poor survival. Here, we show that these factors are predictive of NRM independent of aGVHD. Follistatin modulates inflammatory responses following tissue injury via interaction with the transforming growth factor β superfamily and may reflect endothelial cell damage. sEng is upregulated in proliferating endothelial cells, in inflammation and tissue ischemia, and can influence leukocyte adhesion and endothelial transmigration. Measurement of these predictive AF may highlight prospective opportunities to intervene and prevent subsequent complications thereby limiting NRM after allogeneic HCT. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract 271: Animal Products Tend to Increase Hemoglobin A1c Among Depressed Individuals

Background: Development of a diabetic state has been correlated with the use of energy-rich foods. Depressed individuals are prone to have erroneous diet habits. Hypothesis: Animal products are energy-rich products. Intake of these products could affect glucose levels in depressed individuals. Methods: The study analyzed participants in a 10-day in-patient residential ,depression recovery program. A total of 309 participants that completed the program where studied: 106 men and 203 women. On day one, all participants completed a depression and anxiety assessment test, a validated 75-item self-report screening tool that determines (1) depression based on DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) criteria, (2) anxiety level, (3) mini EQ (Emotional Quotient), (4) demographic data, and (5) dietary intakes. The fact that meat, cheese and fish were part of each participant’s diet was determined dichotomously using their answers on the assessment test. A potential diabetic state was screened in each participant by analyzing hemoglobin A1c level in day one of the program. The participants’ dietary habits were correlated to the hemoglobin A1c level. SPSS software was used to process the data. An independent-samples t-Test was conducted to compare the intake of various energy rich foods with hemoglobin A1c level. Results: At baseline participants had a mean Beck Depression index II of 27.4 (SD = 10.1, min = 7, max = 53), corresponding with high moderate depression. Results exposed that consumption of meat at least twice a day (M=5.5, SD=.68, SEM=.4) compared to no meat intake (M=5.7, SD=1.15,SEM=.17), was related with higher levels of hemoglobin A1c, t(286)=-2, p = 0.041. This association was not found for cheese t(286)=0.45, p = 0.65 or fish t(286)=0.9, p = 0.368 intake. Conclusion: It seems meat intake, excluding fish or chicken, has a negative effect in the level of hemoglobin A1c in a clinically depressed population. To further confirm these results, prospective studies are required, as to determine its mechanisms.

PD50-08 IMPROVEMENT OF ARTERIAL ENDOTHELIAL FUNCTION FOLLOWING INITIATION OF TESTOSTERONE REPLACEMENT THERAPY

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II1 Apr 2016PD50-08 IMPROVEMENT OF ARTERIAL ENDOTHELIAL FUNCTION FOLLOWING INITIATION OF TESTOSTERONE REPLACEMENT THERAPY Daniel Shoskes, Kathryn Dunlap, and Barbara Tucky Daniel ShoskesDaniel Shoskes More articles by this author , Kathryn DunlapKathryn Dunlap More articles by this author , and Barbara TuckyBarbara Tucky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2798AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Isolated recent studies have suggested an increased risk of heart attack as early as 3 months following testosterone replacement therapy (TRT) initiation. Such a rapid risk increase would likely require rapid deterioration of arterial endothelial function since atherosclerosis would be unlikely to develop so quickly de novo. Our goal was to assess arterial endothelial function in hypogonadal men prior to and at least 3 months after initiation of TRT METHODS Adult men were consented for the study if they had symptoms of hypogonadism, a total testosterone < 350 ng/dl, and planned to begin TRT. Endothelial function was non-invasively assessed using the Endo-PAT2000 machine, an FDA approved test of cardiac risk. We measured the Augmentation Index (AI) (normal < 3%), a measure of arterial stiffness and Reactive Hyperemia Index (RHI), a measure of endothelial vasodilation (normal > 1.69). Prior studies suggest that a 10% level of day to day test variability is expected. Topical gels or Testopel were used for TRT and target testosterone confirmed post therapy. Endothelial function was reassessed at the next clinic visit, between 3 and 6 months after treatment started if the patients were compliant with therapy. Changes in continuous variables were assessed with the paired t test and significance set at p<0.05 RESULTS 23 patients were consented with a mean age of 52.7 (range 34-68) and starting testosterone 196.9 ng/dl (range 35-339). There was a history of diabetes in 4, hypertension in 10 and coronary artery disease in 5 men. Mean RHI was 1.67+/-0.37 (70% were abnormal) and mean AI was 2.57%+/-14.0 (39% were abnormal). No patient subsequently developed a clinical cardiac event. At follow up 20 patients were compliant with therapy and retested. Mean total testosterone increased from 203 to 511 (p<0.0001). Mean RHI improved from 1.70 to 2.14 (p=0.01). Mean AI improved from 2.9% to -1.75% (p=0.01). In 4 men RHI was unchanged and any lower values were within the 10% error of the test (1.3-6.3%). No man had worsening of AI. CONCLUSIONS Men with symptomatic hypogonadism often have abnormal arterial endothelial function. Following TRT, this endothelial function either remains unchanged or improves. This improvement would be expected to reduce the risk of subsequent cardiac events. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1188 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Daniel Shoskes More articles by this author Kathryn Dunlap More articles by this author Barbara Tucky More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Exhaled nitric oxide and carbon monoxide in mechanically ventilated brain-injured patients

The inflammatory influence and biological markers of prolonged mechanical-ventilation in uninjured human lungs remains controversial. We investigated exhaled nitric oxide (NO) and carbon monoxide (CO) in mechanically-ventilated, brain-injured patients in the absence of lung injury or sepsis at two different levels of positive end-expiratory pressure (PEEP).Exhaled NO and CO were assessed in 27 patients, without lung injury or sepsis, who were ventilated with 8ml kg−1 tidal volumes under zero end-expiratory pressure (ZEEP group, n = 12) or 8 cm H2O PEEP (PEEP group, n = 15). Exhaled NO and CO was analysed on days 1, 3 and 5 of mechanical ventilation and correlated with previously reported markers of inflammation and gas exchange.Exhaled NO was higher on day 3 and 5 in both patient groups compared to day 1: (PEEP group: 5.8 (4.4–9.7) versus 11.7 (6.9–13.9) versus 10.7 (5.6–16.6) ppb (p < 0.05); ZEEP group: 5.3 (3.8–8.8) versus 9.8 (5.3–12.4) versus 9.6 (6.2–13.5) ppb NO peak levels for days 1, 3 and 5, respectively, p < 0.05). Exhaled CO remained stable on day 3 but significantly decreased by day 5 in the ZEEP group only (6.3 (4.3–9.0) versus 8.1 (5.8–12.1) ppm CO peak levels for day 5 versus 1, p < 0.05). The change scores for peak exhaled CO over day 1 and 5 showed significant correlations with arterial blood pH and plasma TNF levels (rs = 0.49, p = 0.02 and rs = −0.51 p = 0.02, respectively). Exhaled NO correlated with blood pH in the ZEEP group and with plasma levels of IL-6 in the PEEP group.We observed differential changes in exhaled NO and CO in mechanically-ventilated patients even in the absence of manifest lung injury or sepsis. These may suggest subtle pulmonary inflammation and support application of real time breath analysis for molecular monitoring in critically ill patients.

Platelets regulate vascular endothelial stability: assessing the storage lesion and donor variability of apheresis platelets.

In current blood banking practices, platelets (PLTs) are stored in plasma at 22°C, with gentle agitation for up to 5 days. To date, the effects of storage and donor variability on PLT regulation of vascular integrity are not known. In this study, we examined the donor variability of leukoreduced fresh (Day 1) or stored (Day 5) PLTs on vascular endothelial barrier function in vitro and in vivo. In vitro, PLT effects on endothelial cell (EC) monolayer permeability were assessed by analyzing transendothelial electrical resistances (TEER). PLT aggregation, a measure of hemostatic potential, was analyzed by impedance aggregometry. In vivo, PLTs were investigated in a vascular endothelial growth factor A (VEGF-A)-induced vascular permeability model in NSG mice, and PLT circulation was measured by flow cytometry. Treatment of endothelial monolayers with fresh Day 1 PLTs resulted in an increase in EC barrier resistance and decreased permeability in a dose-dependent manner. Subsequent treatment of EC monolayers with Day 5 PLTs demonstrated diminished vasculoprotective effects. Donor variability was noted in all measures of PLT function. Day 1 PLT donors were more variable in their effects on TEER than Day 5 PLTs. In mice, while all PLTs regardless of storage time demonstrated significant protection against VEGF-A-induced vascular leakage, Day 5 PLTs exhibited reduced protection when compared to Day 1 PLTs. Day 1 PLTs demonstrated significant donor variability against VEGF-A-challenged vascular leakage in vivo. Systemic circulating levels of Day 1 PLTs were higher than those of Day 5 PLTs In vitro and in vivo, Day 1 PLTs are protective in measures of vascular endothelial permeability. Donor variability is most prominent in Day 1 PLTs. A decrease in the protective effects is found with storage of the PLT units between Day 1 and Day 5 at 22°C, thereby suggesting that Day 5 PLTs are diminished in their ability to attenuate vascular endothelial permeability.

Correlation Between Peripheral Blood Counts and Day 14 Bone Marrow Biopsy in Acute Myeloid Leukemia during Induction Chemotherapy

BackgroundCurrent NCCN guideline recommends that a bone marrow sample be performed 7-10 days (day 14 bone marrow) after completion of induction therapy in newly diagnosed acute myeloid leukemia (AML). However, the value of day 14 bone marrow has been questioned due to the invasive nature of the procedure and lack of specificity pertaining to complete remission in cases of borderline blasts count and cellularity. We examined peripheral blood count and bone marrow from day 0 to day 14, to see if a reduction of peripheral blood correlated and predicted the day 14 bone marrow morphologic changes and complete remission (mCR).MethodsWe did 10 years retrospective review between year 2004 and 2013 at the Henry Ford Hospital, on patients who had newly diagnosed AML and day 14 bone marrow biopsy. The majority of patients underwent "7+3" or a "7+3"-like regimen for induction chemotherapy. Firstly, we evaluated the relationship of change of peripheral blood count from day 0 to day 14 with blast percentage and cellularity of bone marrow. Spearman correlations coefficients were computed for each pair of characteristics. Peripheral blood count includes neutrophil (ANC), monocyte, white blood cells (WBC), blast, hemoglobin and platelet. Secondly, we investigated the possible correlation of mCR to peripheral blood and bone marrow changes, using binary univariate logistic regression. mCR as defined by blast percentage <5, absolute neutrophil (ANC) >1000/mm3, platelets>100,000/mm3. Thirdly, we explored differences in peripheral blood counts on day 14 among three bone marrow groups, those with blast percentage <5, 5-20, >20.ResultsA total of 200 patients were reviewed and 56 patients met the inclusion criteria. Decrease of ANC/WBC correlated with decrease of bone marrow blast/cellularity from day 0 to day 14 (ANC: Blast P ≤ 0.05; ANC: cellularity P ≤ 0.05; WBC: blast P ≤ 0.001, WBC: cellularity P ≤ 0.01). In other words, a larger reduction in ANC/WBC correlated with larger reduction in both blast and cellularity in bone marrow. However, this correlation with bone marrow change was not found in peripheral blast, monocyte, hemoglobin and platelet. We also found that with increasing age, there was less reduction from day 0 to day 14 in bone marrow blast and cellularity.Bone marrow blast and cellularity on day 14 is strongly associated with mCR (P<0.01), the reduction of blast (43.7 +/- 22.86, Odds ratio 1.03 (1.01, 1.06), P=0.012) and cellularity (66.21 +/- 29.98, Odds ratio 1.03 (1.01, 1.05), P=0.003) from day 0 to 14 is also predictive for mCR. Interestingly, there is a trending effect that the reduction of ANC from day 0 to 14 may predict mCR, but it is not statistically significant (Odds ratio 1.22 (1.02, 1.66), P=0.097). The reduction of WBC is not associated with mCR.Furthermore, peripheral blood counts on day 14 are similar among 3 bone marrow groups, those of blast percentage <5, 5-20, and >20% on day 14.ConclusionANC/WBC decrease from day 0 to day 14 correlated with the decrease in bone marrow blast count and cellularity, and can be used as a predictor for bone marrow change on day 14, but the level of day 14 peripheral blood findings are similar among 3 bone marrow groups (blast percentage <5, 5-20, and >20% on day 14), so it could not be used to predict the level of bone marrow change. Our data confirmed that the significant decrease of bone marrow blast percentage and cellularity from day 0 to 14 predicts mCR. Decrease of ANC from day 0 to 14 may also predict mCR although it is not statistically significant. A larger sample size can be studied in the future to further explore the possibility of using peripheral blood to predict bone marrow changes and mCR.SummaryOur data demonstrates a significant reduction of ANC on day 14 after induction therapy in newly diagnosed AML, which correlates with a decrease in bone marrow cellularity and blast percentage. However, a statistically significant association with blast percentage pertaining to mCR was not obtained. In conclusion, while the current findings do not justify replacement of day 14 bone marrow for predicting mCR, further large scale studies are indicated. DisclosuresNo relevant conflicts of interest to declare.

Neuroprotective properties of dehydroepiandrosterone-sulfate and its relationship to interleukin 6 after aneurysmal subarachnoid hemorrhage: a prospective cohort study.

IntroductionThe established neuroprotective property of the sex steroid precursor dehydroepiandrosterone-sulfate (DHEAS) has not yet been investigated in the context of aneurysmal subarachnoid hemorrhage (aSAH). The influence of DHEAS on inflammatory response resulting in modulation of interleukin 6 (IL-6) synthesis has been shown. Here, we evaluate DHEAS serum levels after aSAH (day 0–14) and levels of IL-6 related to functional outcome at discharge and at six months.MethodsA complete data set (DHEAS and IL-6 serum levels for days 0, 1, 4, 7, 10 and 14 after aSAH) and outcome assessment at discharge according to modified Rankin Scale score (mRS) was available for 53 patients of the initially screened cohort (n = 109). Outcome assessment six months after aSAH was obtained from 41 patients. Logarithmized levels of DHEAS and IL-6 were related to dichotomized functional outcome either assessed at discharge or at six months. A mixed between-within subjects ANOVA was applied for statistical analysis (SPSS 21.0).ResultsDHEAS and IL-6 levels across time were related to functional outcome. Regarding outcome assessment at discharge and at six months after aSAH, DHEAS levels (transformed to square root for statistical purposes) were considerably higher in patients with favorable outcome (mRS 0–2) (p = .001; p = .020). Inversely, in patients with favorable outcome either at discharge or six months after aSAH, lower IL-6 levels (logarithmized for statistical purposes) were observed across time (both p < .001).ConclusionWe provide new evidence that DHEAS is associated with protective properties resulting in improvement of functional outcome after aSAH, possibly by influencing the inflammatory response after aSAH shown in the decreasing IL-6 serum levels. But the results for outcome six months after SAH are limited due to a high drop-out rate.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0954-1) contains supplementary material, which is available to authorized users.

The impact of the presence of antithyroid antibodies on pregnancy outcome following intracytoplasmatic sperm injection-ICSI and embryo transfer in women with normal thyreotropine levels.

The aim of our study was to investigate the impact of anti-thyroid peroxidase antibodies (Anti-TPO) on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET) in general groups and in subgroups divided according to AMH level and age. A total of 114 patients positive for anti-thyroid peroxidase antibodies (Anti-TPO+ group) and 495 infertile women negative for anti-thyroid peroxidase antibodies (Anti-TPO- group) undergoing IVF with ICSI from April 2010 to April 2012 were analyzed retrospectively. There were no significant differences in age, BMI, basal FSH, LH, AMH levels and duration of infertility between the two main groups. No significant differences in terms of the days of ovarian stimulation, estradiol level in day 8, total gonadotropin dose, number of oocytes retrieved, available embryos and blastocysts, number of embryos transferred nor in rates of fertilization, implantation, clinical pregnancy, live birth and abortion rate between two main groups were found. The only statistically significant difference among the groups with different anti-TPO antibodies levels was found in basal FSH concentration and BMI. Among the clinical outcomes of IVF with respect to the different anti-TPO levels, the only significant difference was found for the number of oocytes retrieved. Analysis of the baseline parameters in relationship to age categories and AMH levels found significant differences between women positive and negative for thyroid antibodies with respect to basal FSH and LH levels for women >37 years and for basal FSH in AMH <0.6 subgroup. The present study reveals that patients with anti-TPO antibodies showed no significant differences in fertilization, implantation, pregnancy rates, live birth rates and no higher risk for miscarriage following IVF-ET when compared with those negative for anti-thyroid antibodies.

Efficacy of Fixed Low Dose Rasburicase in the Prevention and Treatment of Tumor Lysis Syndrome

Tumour Lysis Syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Hyperuricaemia is one of the prominent features of TLS which if not adequately prevented or treated can lead to renal failure requiring dialysis. Rasburicase is the most recent agent indicated for treating TLS which is a recombinant urate oxidase enzyme that will oxidize uric acid to allantoin, a metabolite with 5-10 fold greater solubility than uric acid and reduces serum uric acid (SUA) levels within four hours of administration. The recommended dose according to US Food and Drug Administration is 0.15 to 0.2 mg/kg/d for 5 days. This retrospective study was aimed to evaluate the clinical efficacy of fixed low dose Rasburicase (1.5mg) in hyperuricemic patients who was admitted under Medical Oncology, Department in Amrita Institute of Medical Sciences And Research Centre, Kochi. 55 patient received Rasburicase during the study period of approximately 3years (July 2012 - June2015). 52 patients (94.54%) showed reduction in serum uric acid level in day 1 and by day 3.All patients (100%) had significant reduction in SUA after administration. In this study we found that Rasburicase significantly lowered the serum uric acid level. Single dose of 1.5mg of rasburicase was found to be effective in rapidly correcting the hyperuricemia in all these patients. This can lead to considerable cost saving in the treatment and prevention of TLS occurring in patients with both solid tumors and hematological malignancies. The advantage of Rasburicase over Allopurinol is its rapid onset of action, efficacy in patients with renal dysfunction and is well tolerated with very few side effects.

PGF2α levels in Day 8 blood plasma are increased by the presence of one or more embryos in the uterus

In cattle, the detection of very early endometrial responses is considered to be hampered by the presence of only a single embryo. Therefore, we have previously developed a model of multiple embryo transfer to circumvent this hindrance. In this work, we analysed embryo–maternal interactions in the bovine uterus on day 8 of development while comparing the presence of multiple v. single embryos using embryo transfer and artificial insemination, respectively. Concentration of proteins (β-actin, NFkB, clusterin and immunoproteosome 20S β5i subunit–i20S), by western blot, and hexoses (glucose and fructose) were measured in paired samples of uterine fluid (UF) from the same animal with and without embryos in the uterus and were compared with UF obtained after artificial insemination. Prostaglandin (PG) F2α and PGE2 concentrations were also analysed in blood plasma. The four proteins analysed and hexoses were unaffected by the presence of one or more embryos in the uterus. However, blood PGF2α showed similar, significant increases with one or more embryos over cyclic animals; such changes were not observed in blood PGE2. Although multiple embryo transfer may appear to be non-physiological, we showed that the uterus, at the very early embryonic stages, does exhibit physiological reactions. Multiple embryo transfer can, therefore, be used for studies of very early embryo–maternal interactions in vivo in monotocous species.

Quantitative Trait Analysis of Polymorphisms in Two Bilirubin Metabolism Enzymes to Physiologic Bilirubin Levels in Chinese Newborns

To explore the effects of variants in Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) and Heme Oxygenase-1 (HMOX1) on daily physiological bilirubin levels and bilirubin changes during the first week after birth in Chinese newborns. Both UGT1A1 and HMOX1 code rate-limiting enzymes in the bilirubin metabolism pathway. We conducted a retrospective quantitative trait study to analyze 4154 daily bilirubin values, 3129 bilirubin changes, and 11 polymorphisms of 988 newborns during the natural course of physiological hyperbilirubinemia. For UGT1A1, we found minor allele A of rs4148323 (G211A, UGT1A1*6) contributed to higher daily bilirubin levels on days 4-6 (with contributions to variations increasing from 4.8% to 12.3%), minor allele T of rs887829 (c-364t) contributed to lower daily bilirubin levels for days 6 and 7 (with contributions to variations increasing from 7.0% to 10.2%) (P < .03 for all). In addition, minor alleles of rs887829 and (TA)n repeat (UGT1A1*28), and haplotype T-long-G at rs887829-(TA)n-rs4148323 were associated with a decrease in bilirubin levels from day 5 to day 6 (P < .01 for all). No contribution from HMOX1 was found. Bilirubin levels and changes during the middle and late parts of the first week were attributed to variants and haplotypes in UGT1A1. This quantitative trait study may provide a more robust statistical method for determining the association of genetic factors and bilirubin kinetics to predict the development of neonatal bilirubin in early postnatal life.

Second dose methotrexate in ectopic pregnancies- the role of beta human chorionic gonadotropin

Second dose methotrexate in ectopic pregnancies- the role of beta human chorionic gonadotropin

Highlights of This Issue

Arsenic poses a significant human cancer risk and millions worldwide are exposed to naturally occurring arsenic in grains, vegetables, meats and fish, and through food processed with water containing arsenic. Oberoi and colleagues estimated the global burdens of bladder, lung, and skin cancers due to inorganic arsenic in food using World Health Organization estimates of food consumption and reported arsenic levels in different foods. Worldwide, thousands of additional cases of bladder, lung, and skin cancers are attributable to inorganic arsenic in food. These findings warrant policy changes to help reduce arsenic in food.Exposure to light-at-night has been shown to disrupt melatonin production, but this effect has only partly been confirmed in studies of night shift workers. Papantoniou and colleagues examined the variation of urinary 6-sulfatoxymelatonin levels in day or night shift workers while continuously monitoring light exposure. 6-sulfatoxymelatonin levels were lower in night compared to day workers and the lowest 6-sulfatoxymelatonin levels were observed in night workers. These findings may relate to future cancer risks in these worker populations.Infections in early childhood may protect against pediatric acute lymphoblastic leukemia (ALL). Marcotte and colleagues selected pediatric ALL cases from the California Cancer Registry and investigated markers of exposure to infections, including date of birth, and the timing of influenza and respiratory syncytial virus (RSV) seasons. The authors observed an increased risk of ALL for spring and summer births and for those first exposed to an influenza or RSV season at nine to twelve months compared to those exposed during the first three months of life. These results support the hypothesis that infections in early childhood decrease risk of ALL.Inflammation influences cancer development and progression and an elevated platelet/lymphocyte ratio (PLR) has been linked to poor prognosis in several malignancies. Templeton and colleagues conducted a systematic review to explore the association of blood PLR and overall survival from various solid tumors. A significant association between blood PLR and survival was observed for colorectal, hepatocellular, gastroesophageal, ovarian, and pancreatic carcinoma. PLR represents an inexpensive biomarker with prognostic value in solid tumors.