CORRELATION BETWEEN URIC ACID LEVEL WITH BODY MASS INDEX AND HEMATOLOGY PARAMETERS AMONG HYPERURICEMIA PATIENTS

Hyperuricemia has became the public health issue worldwide. Hematology parameters abnormality is considered to be one of the factors relating the disease such as hyperuricemia. Current study suggest that body mass index (BMI) related to uric acid (UA) levels. The aim of the study was to examine the association between uric acid levels and hematological parameters and BMI among hyperuricemia patients. This was cross sectional study with 50 hyperuricemia patients in Hortus Medicus clinic. Results demonstrate that of the participants, 54% were women but the mean of UA levels was higher in the men (8,41 + 0,80 mg/dL) than in women (7,38 + 0,97 mg/dL). In BMI classified, the mean BMI for men was normoweight, and the women was overweight. The mean of hematology parameters in both of sex were normal range. No significant association were testified between uric acid levels and hemoglobin, hematocrit, erythrocyte, trombocyt, leukocyte and BMI. This study indicate that uric acid has no apparent association with hematology parameters and BMI

Discovering the Potent Inhibitors Against Babesia bovis in vitro and Babesia microti in vivo by Repurposing the Natural Product Compounds

In the present study, we screened 502 natural product compounds against the in vitro growth of Babesia (B.) bovis. Then, the novel and potent identified compounds were further evaluated for their in vitro efficacies using viability and cytotoxicity assays. The in vivo inhibitory effects of the selected compounds were evaluated using B. microti “rodent strain” in mice model. Three potent compounds, namely, Rottlerin (RL), Narasin (NR), Lasalocid acid (LA), exhibited the lowest IC50 (half-maximal inhibitory concentration) as follows: 5.45 ± 1.20 μM for RL, 1.86 ± 0.66 μM for NR, and 3.56 ± 1.41 μM for LA. The viability result revealed the ability of RL and LA to prevent the regrowth of treated parasite at 4 × IC50 and 2 × IC50, respectively, while 4 × IC50 of NR was sufficient to stop the regrowth of parasite. The hematology parameters of B. microti in vivo were different in the NR-treated groups as compared to the infected/untreated group. Interestingly, intraperitoneal administration of NR exhibiting inhibition in the growth of B. microti in mice was similar to that observed after administration of the commonly used antibabesial drug, diminazene aceturate (DA) (76.57% for DA, 74.73% for NR). Our findings indicate the richness of natural product compounds by novel potent antibabesial candidates, and the identified potent compounds, especially NR, might be used for the treatment of animal babesiosis.

Regulation of Iron Homeostasis and Efficacy of Rusfertide Analog Peptide in a Mouse Model for Polycythemia Vera

Polycythemia Vera (PV) is a rare blood disease where mutations in JAK2 kinase confer constitutive JAK2 activity leading to abnormally elevated erythropoiesis that is independent of erythropoietin. PV patients present with iron deficiency at diagnosis due to increased iron utilization for erythropoiesis (Ginzburg YZ, Leukemia 2018) which worsens after repeated therapeutic phlebotomy (TP) performed to maintain hematocrit below 45%. The resulting suppression of hepcidin, the body's main negative regulator of iron metabolism, fuels expanded erythropoiesis resulting in a continued need for TP and thereby exacerbating patients' iron deficiency. Rusfertide targets iron exporter membrane protein ferroportin to trigger its degradation, preventing iron export from cells responsible for dietary iron absorption and cells that store and recycle iron. The resulting pharmacodynamic effect of lowered serum iron has disease-modifying effects in PV (Ginzburg YZ, Leukemia 2018). Rusfertide essentially eliminated the need for therapeutic phlebotomy in all PV patients (Kremyanskaya M, Blood 2020 136 Suppl 1: 33). Rusfertide also reversed iron deficiency, as indicated by increased serum ferritin, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in these patients. We present results from studies in a mouse PV model with JAK2-V617F mutation as in human PV (Mullaly A, Cancer Cell 2010; JAX stock #031658). We show that rusfertide analog Peptide A is efficacious in lowering hematocrit (HCT) while modulating other hematological parameters. Further, we show redistribution of iron away from erythropoiesis and renormalization of iron homeostasis as evidenced by ferrokinetic parameters. PV mice were treated over 6-weeks (thrice per week) with Vehicle or Peptide A at 2.5 or 7.5 mg/kg. At the end of 6 weeks, hematology parameters HCT, hemoglobin, RBC counts, were elevated in the PV-Vehicle group as compared to wild type (WT-Vehicle) mice (Table 1). Hematology parameters in PV-2.5 mg/kg group were lowered to WT-Vehicle values. In PV-7.5 mg/kg group, these parameters were lower than WT-Vehicle values, indicating that excessive iron restriction (EIR) leads to the expected anemic conditions. MCH and mean corpuscular hemoglobin concentration (MCHC) in PV-Vehicle group and PV-2.5 mg/kg treated were comparable to WT-Vehicle, indicating a lack of EIR. For the PV-7.5 mg/kg treated group, MCH and MCHC were significantly lower than WT-Vehicle, suggesting EIR at a high dose impacts hemoglobin concentration of RBC. To investigate the impact of iron restriction with Peptide A on erythroblast precursor cells in bone marrow, we conducted flow-cytometry analysis by gating on CD71 and TER-119 expression, and measuring intracellular iron using Ferro Far Red (FFR) dye. The CD71 + early precursor cell population did not change with Peptide A treatment however, the CD71 -/TER-119 + late precursor cell population was significantly lowered (~4-fold and 7.5-fold, in 2.5 and 7.5 mg/kg Peptide A treated PV groups respectively). Iron levels of CD71 + cells were dose-dependently and statistically significantly reduced in the Peptide A treated groups as compared to PV-Vehicle group. Iron levels of CD71 - cells were marginally lowered only in the PV-7.5 mg/kg group. We investigated the nature of iron redistribution induced by Peptide A, by using flow assay to assess iron concentration in splenic macrophages (F4/80 +/CD11b +). Iron was ~2-fold higher in the PV-7.5 mg/kg group as compared to PV-vehicle, and marginally higher in PV-2.5 mg/kg group. Total tissue iron concentration in the spleen was elevated in a dose-related manner in Peptide A treated groups compared to PV-Vehicle group, and in commensuration serum ferritin was increased. Serum iron was ~2-fold lower in PV-Vehicle group as compared to WT-Vehicle indicating iron depletion due to increased iron utilization for erythropoiesis. Serum iron measured after clearance of Peptide A from circulation (48 hr post-dose), was marginally increased for both Peptide A treated groups compared to PV-Vehicle. These data demonstrate that treatment with rusfertide and analogs, restricts iron from erythropoiesis by sequestering it in macrophage storage compartments. These effects along with normalization of iron homeostasis contribute to usefulness of rusfertide dose titration treatment in maintaining HCT <45% and improving symptoms related to iron deficiency in human PV. Figure 1 Figure 1. Disclosures Taranath: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Zhao: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Vengalam: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lee: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Tang: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Dion: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Su: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Tovera: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Bhandari: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Cheng: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Mattheakis: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company. Liu: Protagonist Therapeutics: Current Employment, Current equity holder in publicly-traded company.

Hematology parameters as potential indicators of feed efficiency in pigs

The identification of an inexpensive, indirect measure of feed efficiency in swine could be a useful tool to help identify animals with improved phenotypes to supplement expensive phenotypes including individual feed intakes. The purpose of this study was to determine whether hematology parameters in pigs at the beginning and end of a feed efficiency study, or changes in those values over the study, were associated with average daily gain (ADG), average daily feed intake (ADFI), or gain-to-feed (G:F). Whole blood samples were taken at days 0 and 42 from pigs (n = 178) that were monitored for individual feed intakes and body weight gain during a 6-week study. Blood samples were analyzed for blood cell parameters including white blood cell (WBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts, red blood cell (RBC) counts, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC), platelet count, and mean platelet volume (MPV). Feed efficiency parameters were predicted using an ANOVA model including fixed effects of farrowing group and pen (sex constant) and individual hematology parameters at day 0, day 42 or their change as covariates. At day 0, platelet count was positively associated with ADFI (P < 0.05) and negatively associated with G:F (P < 0.1), and lymphocyte count was positively associated with ADFI (P < 0.05). At day 42, neutrophil, RBC counts, hemoglobin and hematocrit were associated with ADFI (P < 10−3). Over the course of the study, changes in RBC measurements including RBC, hemoglobin, MCV, MCH, and MCHC (P < 10−4) which may improve oxygen carrying capacity, were associated with ADG and ADFI. The change in hematocrit over the course of the study was the only parameter that was associated with all three measures of feed efficiency (P < 0.05). Changes in RBC parameters, especially hematocrit, may be useful measurements to supplement feed efficiency phenotypes in swine.

Evaluasi Analitik Hematology Analyzer Diatron Abacus 3 Pada Parameter Hematologi Rutin Di Laboratorium Hematologi Poltekkes Kemenkes Kalimantan Timur

Entering the era of globalization, manual tools in clinical laboratories have been replaced by full automatic devices. One of them is the Diatron Abacus Hematology analyzer 3. A relatively new hematology analyzer is required for analytical evaluation. Analytical evaluation is an evaluation of Diatron Abacus 3 on Sysmex KX 21 as a standard in RSUD I.A Moeis Samarinda, and it is very important to do this to assess the performance of the tool. Analytical evaluation is done by determining the value of accuracy, precision, and total error and linearity of measurement results from routine hematological examination parameters, which are erythrocytes, leukocytes, platelets, hemoglobin, and hematocrit. To determine the results of the hematology analyzer evaluation of Abacus 3 Diatron Analyzers on Routine Hematology Parameters in the Hematology Laboratory of the Health Ministry of Health, East Kalimantan. This type of research is observational descriptive, using a total sampling technique, and a sample of 40 complete K3EDTA blood specimens. Data processing using Microsoft Excel and SPSS 20 applications, analyzed using descriptive statistics. The observations were still included in the criteria for acceptance, accuracy or inaccuracy (d%) in erythrocytes 1.8%, leukocytes 8.0%, platelets -5.3%, hemoglobin 2.3% and hematocrit -1.7%; Precision or impression (CV%) in erythrocytes 4.2%, leukocytes 11.1%, platelets 6%, hemoglobin 3.9% and hematocrit 4.5%; Total errors in erythrocytes were 8.7%, leukocytes 17.9%, platelets 23.6%, hemoglobin 8.8% and hematocrit 9.1; Linearity of the measurement results against the routine hematological cell count values performed using Abacus 3 and Sysmex KX 21 has a positive relationship. Acceptance values are still included in the LOA on all parameters examined and still meet the criteria; the accuracy/bias value is smaller than the true value of the parameter being examined, except for leukocytes, which is greater; the precision on the five parameters is greater than the CV% Abacus 3 insert kit; The total error obtained by the TE value is greater than the TEA in the parameters examined, except for smaller platelets; Linearity of the measurement results against the calculated hematology cell routine values performed using Abacus 3 and Sysmex KX 21 have a positive relationship, meaning an increase in measurement values using Abacus 3 is followed by an increase in measurement values using Sysmex KX 21.

The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib

Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. Methods: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. Results: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. Conclusions: The results increase our understanding of the role of acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification.

A Nomogram Based on Clinicopathologic Features and Preoperative Hematology Parameters to Predict Occult Peritoneal Metastasis of Gastric Cancer: A Single-Center Retrospective Study

Background. In patients with gastric cancer (GC), peritoneal metastasis is an indication of the end stage and often indicates a poor outcome. The diagnosis of peritoneal metastasis, especially occult peritoneal metastasis (OPM), remains a challenge for surgeons. This study was designed to explore the relationship between OPM and clinicopathological characteristics and preoperative hematological parameters in patients with GC and to develop a nomogram to predict the probability of OPM before surgery. Methods. A total of 672 patients with GC from our center were included, including 583 OPM-negative and 89 OPM-positive patients. These patients were divided into training and validation groups based on when they received treatment. OPM was diagnosed during surgery in patients without any signs of metastasis through imaging examination. Predictive factors were screened by least absolute shrinkage and selection operator logistic regression of all 18 characteristics. The nomogram of OPM was constructed based on these filtered variables. The discriminative and calibration performance of the model were simultaneously evaluated. Results. A total of six variables, including tumor size, degree of differentiation, depth of invasion, Glasgow prognosis score, and plasma levels of CA125 and fibrinogen, were selected for integration into the final predictive nomogram. The area under curve (AUC) of the nomogram with six factors was 0.906 (95% confidence interval (CI): 0.872-0.941) and 0.889 (95% CI: 0.795-0.984) in the training and validation groups, respectively. Calibration plots of the nomogram in the two sets revealed a good consistency between predicted and actual probabilities. Decision curve analysis showed that the nomogram had a positive net benefit among all threshold probabilities between 0% and 82%. This nomogram was superior to models incorporating only clinicopathologic or hematologic features. Conclusion. Both clinicopathological and preoperative hematological parameters are significantly associated with OPM. The nomogram constructed with six factors could be used to calculate the probability of OPM and identify the high-risk population in GC. This may be helpful for early detection of OPM in patients with GC.

Effects of Prazosin in Hematology Parameters and Lipid Profile in Rats (Rattus Norvegicus)

Alpha blockers are characterize as one of the most therapies that used for treatment of several condition such as Raynaud's disease, hypertension, scleroderma , and one of the most treatments for treated continuing pelvic pain syndrome- continuing prostatitis and also be used to treat anxiety and panic disorder such as generalized anxiety, posttraumatic stress disorder (Raskind, et al.,2003) . This study was conducted at the laboratory of department of biology, faculty of science/university of Kufa , 40 male rats that was used. The present study was conducted to investigate the effect of Prazosin hydrochloride on some organs in male rats (Rattus norvegicus), after administration of prazosin hydrochloride at three doses (25,50,75) mg/kg b.wt. for eight-weeks, prazosin revealed significant decreased at (p ˂0.05) the hemoglobin concentration, red blood cell account, packed cell volume , and erythropoietin hormone but a significant increased at (P˂0.05) in the levels of erythrocyte sedimentation rate of the blood, when compred with control group,the levels of HDL showed significant increment at (P˂0.05) in group that gives low dose (50 and 75)mg/kg b.wt. when compared with control, but significant decline at (P˂0.05) in the levels of very low density lipoprotein in group that gives low dose of prazosin (25)mg/kg b.wt. when equaled with control group, the levels of LDL and VLDL revealed significant decreased at (P˂0.05) in groups that gives moderate and high doses.