Decreased Mean Corpuscular Volume Research Articles

Evaluation of Hematological and Biochemical Effects of Kabuuti Herbal Cough Syrup: A Sub-acute Study in Wistar Rats

Herbal medicines, including Kabuuti cough syrup, have gained popularity in treating various ailments, yet their safety and efficacy require scientific scrutiny. This study aimed to evaluate the hematological and biochemical effects of Kabuuti herbal cough syrup after 28 days of oral administration in Wistar rats. The herbal extracts, containing secondary metabolites like terpenes, alkaloids, steroids, and phenols, were administered at different doses to rats, with distilled water as a control. Hematological and biochemical parameters were assessed, showing no statistically significant changes in most parameters. However, there were decreases in mean corpuscular volume (MCV) levels and lymphocyte percentage and increases in hemoglobin (HB) levels and gamma glutamyl transferase (GGT) levels observed in certain dosage groups. Despite these variations, the overall findings suggest that Kabuuti herbal cough syrup is safe for liver and kidney function in the short term, with no significant adverse effects observed. Keywords: Kabuuti Cough Herbal Preparation; Haematological Effects; Biochemical Effects; Oral Administration; Wistar Rats.

Correlation between Red Cell Distribution Width (RDW) and Mean Corpuscular Volume (MCV) as a Prognostic Biomarker for Diabetic Nephropathy Patients in a South Indian Hospital

Context: Diabetic nephropathy is one of the microvascular complications of diabetes mellitus, capable of leading to end-stage renal disease. Diabetic nephropathy could only be identified through renal biopsy testing, which is expensive and can impose a financial burden on patients. Therefore, there is a necessity to develop a cost-effective method for identifying diabetic nephropathy. Aim: To evaluate the correlation between RBC parameters, such as RDW and MCV values, as prognostic biomarkers for patients with diabetic nephropathy. Methods and Material: Study Design: Prospective comparative study. Study Site: Sudha Institute of Medical Science, Erode. Study Duration: Study was carried out over six-months. Sample Size: 101 diabetic nephropathy patients and 101 type 2 diabetes mellitus patients. Statistical Analysis: Pearson correlation. Results: The majority of diabetic nephropathy patients were 40 years old or older, and most of them were males. Among the study participants, a significant number of male participants had habits of smoking and alcohol consumption. The duration of diabetes and BMI exhibited a strong correlation with the occurrence of diabetic nephropathy. Furthermore, there were notable increases in urea, creatinine, FBS, RBS, PPBS, and HbA1C, alongside a decrease in MCV and eGFR as diabetic nephropathy progressed. Conclusions: Our research indicates a positive correlation between RDW and HbA1c, FBS, RBS, PPBS, urea, and creatinine. In contrast, negative correlation of RDW with MCV and eGFR. MCV is negatively correlated with HbA1c, FBS, RBS, PPBS, urea, creatinine. In contrast, positive correlation between MCV and eGFR.

Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase3 Roxadustat Trials in Japan.

Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase3 clinical trials in Japan. Thromboembolic events with onset before and after week12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36-37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95%CI 1.52-25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95%CI 1.23-15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150mg; unadjusted OR 5.95; 95%CI 1.07-33.16; vs < 50mg) over the previous 8weeks before the event onset were associated with thromboembolic events after week12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95%CI 1.82-33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< - 2fL; adjusted OR 5.55; 95%CI 1.73-17.83; vs ≥ 0fL) were associated with increased risk of thromboembolic events. In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. NCT02780726, NCT02952092, NCT02780141, NCT02779764.

Relationship between the Consumption of Fermented Red Beetroot Juice and Levels of Perfluoroalkyl Substances in the Human Body's Fluids and Blood Parameters.

Per- and polyfluoroalkyl substances (PFASs) are a group of fluorinated, organic, man-made chemicals; they do not occur naturally in the environment. This study aimed to determine the profile and content of PFASs in the volunteers' blood plasma and urine after the consumption of fermented red beetroot juice and then correlated it with the blood parameters. Over 42 days, 24 healthy volunteers ingested 200 mL/60 kg of body weight of fermented red beetroot juice. PFASs were analyzed using the micro-HPLC-MS/MS method. Five perfluoroalkyl substances were found in the volunteers' body fluids. After consuming the juice, it was discovered that regarding the perfluorocarboxylic acids, a downward trend was observed, while regarding the perfluoroalkane sulfonates, and their plasma content showed a statistically significant upward trend. Analysis of the hematology parameters indicated that the intake of fermented red beetroot juice showed a significant decrease in mean corpuscular volume (MCV), platelets concentration, mean platelet volume (MPV), platelet large cell ratio (P-LCR) at the significance level p < 0.01, and hematocrit (p < 0.05). On the other hand, the dietary intervention also indicated a significant (p < 0.01) increase in corpuscular/cellular hemoglobin concentration (MCHC). In the case of blood biochemistry, no significant change was observed in the blood samples after the intake of the fermented beetroot juice. However, a decreasing tendency of total cholesterol and low-density lipoprotein concentration (LDL-C) was observed. Based on the presented results, there is a need to analyze and monitor health-promoting food regarding undesirable substances and their impact on consumer health.

Efficacy of Carapa guianensis oil (Meliaceae) against monogeneans infestations: a potential antiparasitic for Colossoma macropomum and its effects in hematology and histopathology of gills.

This study evaluated the efficacy of therapeutic baths with Carapa guianensis (andiroba) oil against monogeneans of Colossoma macropomum (tambaqui), as well as the hematological and histological effects on fish. Among the fatty acids identified in C. guianensis oil, oleic acid (53.4%) and palmitic acid (28.7%) were the major compounds, and four limonoids were also identified. Therapeutic baths of 1 hour were performed for five consecutive days, and there was no fish mortality in any of the treatments. Therapeutic baths using 500 mg/L of C. guianensis oil had an anthelmintic efficacy of 91.4% against monogeneans. There was increase of total plasma protein and glucose, number of erythrocytes, thrombocytes, leukocytes, lymphocytes and number of monocytes and decrease in mean corpuscular volume. Histological changes such as epithelium detachment, hyperplasia, lamellar fusion and aneurysm were found in the gills of tambaqui from all treatments, including controls with water of culture tank and water of culture tank plus iso-propyl alcohol. Therapeutic baths with 500 mg/L of C. guianensis oil showed high efficacy and caused few physiological changes capable of compromising fish gill function. Results indicate that C. guianensis oil has an anthelmintic potential for control and treatment of infections by monogeneans in tambaqui.

Anemia Prevalence, Characteristics, and Hematological Profile among Stunted Children Under 2 Years Old in Bandung Regency, Indonesia

AbstractAnemia and stunted growth are major health problems with adverse consequences for children. This study aimed to determine the prevalence, characteristics, and hematological profile of anemia among stunted children under 2 years old. A nested cross-sectional study from a child cohort was conducted in Bandung Regency, West Java, Indonesia. Two hundred twenty-two children aged 6 to 24 months were randomly selected. These children were reexamined from November 2019 to March 2020 for anthropometric measurements and hematological assessment and interviewed for relevant risk factors of stunted growth and anemia. Ninety-eight stunted children were identified and distributed into stunted and severely stunted groups (47.96 vs. 52.04%). Around 85.4% of the children came from low-income families and 31.7% were severely underweight for age. Surprisingly most of these stunted children had normal birth weight and length and were born at term (68.3, 53.7, and 85.4%). The prevalence rate of anemia among stunted children was 41.8%, they had decreased mean corpuscular volume (56%), decreased mean corpuscular hemoglobin (73%), and normochromic mean corpuscular hemoglobin concentrations (51.2%). Leucocytosis was higher than leucopenia (10 vs. 3.7%) and thrombocytosis (n = 15, 36%) as compared to thrombocytopenia (n = 5, 12%). The prevalence of anemia was high among stunted children. The characteristics of stunted children with and without anemia were similar. The fact that these stunted children had few risk factors for stunting emphasizes the need to focus on improved postnatal care to prevent faltering. Based on the hematology profile, iron deficiency anemia was suspected to be the most etiology in these cases warranting further follow-up and management.

Clinical features and high-resolution chest computerized tomography findings of children infected by the B.1.617.2 variant of coronavirus disease 2019

Purpose To analyse the clinical symptoms, laboratory examinations and chest CT findings of children infected by the B.1.617.2 variant of COVID-19 and to compare the differences between clinical subtypes. Methods Fifty-three children (28 males, 25 females; age ranging from 4 months to 17 years) were included with B.1.617.2 variant infection in Nanjing, China, from July 21 to August 12 2021. Clinical data from patients were collected and analysed in groups of mild and common types. Imaging data were divided into three stages for evaluation: early, intermediate and late stages. Results In our study, fever (53%), cough (34%) and pharyngeal discomfort (28%) were the main symptoms. There were no differences in clinical symptoms between the mild and common type. The most common laboratory test items outside the normal range were decreased mean corpuscular volume (68%), lymphocyte percentage (64% elevated and 2% decreased) and decreased serum alkaline phosphatase concentration (66%). The differences in haemoglobin and monocyte percentages between the mild and common types were statistically significant (p = .037 and .033, respectively). No influencing factor was statistically significant in the regression analysis of both symptoms and clinical subtypes. The main CT findings were ground-glass opacity and consolidation located in the periphery and bilateral multilobed involvement. The mean CT score was 1.6. CT score correlated with packet cell volume, haemoglobin, mean erythrocyte volume, mean platelet volume and platelet distribution width. Conclusion The pathogenetic condition of children with B.1.617.2 variant infection is mild. Although there were intergroup differences in some blood cell analyses, T-lymphocyte counts, and comprehensive biochemical indicators, no factors had a significant effect on clinical typing and the presence or absence of symptoms. CT findings and CT scores reflect disease stage and pathological changes and correlate moderately with laboratory tests, making them of good value for disease diagnosis and monitoring. Key Messages Paediatric patients infected with B.1.617.2 variant have a milder clinical and imaging presentation than adults and are similar to the prototype infection. CT findings and scores which reflect disease stages and pathological changes. There is a correlation between chest CT and laboratory tests, which can be useful for the diagnosis and follow-up of the disease.

Relationship between the Hematological Indices and COVID-19

Background: Recently, the novel coronavirus disease-2019 (COVID-19) has a wide spread around the world. Clinically, it was responsible for respiratory illness ranged from mild to life-threatening infection. The study aimed to investigate the link of gender, age, ABO blood groups, and hematological indices with COVID-19 infection. Methods: One hindered COVID-19 cases, as confirmed using reverse transcription–polymerase chain reaction test, were checked for some sociodemographic features, blood group, and hematology parameters. A blood sample was collected from each person in an EDTA container and immediately tested for blood group using commercial antisera, in addition to complete blood count parameters using of a semiautomated hematology analyzer (Mindray BC-3200). Results: Of 100 COVID-19 patients, 52% were male and 48% were female. About 33% and 31% of the study participants were of age group 15–31 and 32–49 years, respectively. The majority (37%) of COVID-19 patients carried blood group O+ve, followed by A+ve (24%). A+ve blood group was significantly more reported in males (32.7%) than females (14.6%). Notably, 61% of participants showed low Hb level. Erythropenia was detected in 41% of the participants, while thrombocytopenia was observed only in 19% of the patients. Moreover, lymphocytopenia was detected in 82%, low packed cell volume in 66%, decreased mean corpuscular volume in 20%, and declined mean corpuscular hemoglobin concentration in 8% of the participants. In contrast, leukocytosis and neutrophilia were found in 69% and 73% of the participants, respectively. Conclusion: Taken together, the study findings highlighted the link of COVID-19 with age, gender, blood groups, and hematology parameters, which is important in diagnosis, prognosis, and management of illness.

Sublethal pulmonary toxicity screening of silica nanoparticles in rats after direct intratracheal instillation.

The present aimed to characterize the toxicity of silica nanoparticles in Sprague Dawley rats and determine the dose levels for a repeated-dose toxicity study. Silica nanoparticles (SiO2, 20nm and 50nm) were administered as a single intratracheal instillation of standardized SiO2 20nm (low dose, 200µg/mL; high dose, 400µg/mL) and 50nm (low dose, 200µg/mL; high dose, 400µg/mL). Each group consisted of five male rats. We documented the mortality rate, clinical signs, body weight, bronchoalveolar lavage fluid analysis, hematological values, serum chemistry values, organ weight, gross findings at necropsy, and histopathological assessments. Rats treated with 200µg/mL and 400µg/mL SiO2 50nm exhibited a decreased mean corpuscular volume, while those treated with 400µg/mL of SiO2 50nm showed increases in absolute monocyte and absolute lymphocyte count as well as prothrombin time. In addition, rats treated with 400µg/mL SiO2 20nm and 50nm presented reduced creatinine, alanine aminotransferase, and sodium levels. Therefore, a single intratracheal instillation of SiO2 20nm and 50nm elicited no toxicity up to a dose of 400µg/mL, and the approximate lethal dose of this test substance exceeded 400µg/mL in male Sprague Dawley rats under the present experimental conditions.

A novel ENU-induced Cpox mutation causes microcytic hypochromic anemia in mice.

Mouse models of red blood cell abnormalities are important for understanding the underlying molecular mechanisms of human erythrocytic diseases. DBA.B6-Mha (Microcytic hypochromic anemia) congenic mice were generated from the cross between N-ethyl-N-nitrosourea (ENU)-mutagenized male C57BL/6J and female DBA/2J mice as part of the RIKEN large-scale ENU mutagenesis project. The mice were established by backcrossing with DBA/2J mice for more than 20 generations. These mice showed autosomal-dominant microcytic hypochromic anemia with decreased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels and increased red blood cell distribution width (RDW) and plasma ferritin levels. Linkage analysis indicated that the Mha locus was located within an interval of approximately 1.95-Mb between D16Nut1 (58.35 Mb) and D16Mit185 (60.30 Mb) on mouse chromosome 16. Mutation analysis revealed that DBA.B6-Mha mice had a point mutation (c.921-2A>G) at the acceptor site of intron 4 in the coproporphyrinogen oxidase (Cpox) gene, a heme-synthesizing gene. RT-PCR revealed that the Cpox mRNA in DBA.B6-Mha mice caused splicing errors. Our results suggest that microcytic hypochromic anemia in DBA.B6-Mha mice is owing to impaired heme synthesis caused by splice mutations in Cpox. Therefore, the DBA.B6-Mha mice may be used to elucidate the molecular mechanisms underlying microcytic hypochromic anemia caused by mutations in Cpox. Although low MCV levels are known to confer malarial resistance to the host, there were no marked changes in the susceptibility of DBA.B6-Mha mice to rodent malarial (Plasmodium yoelii 17XL) infection.

Direct and Indirect Effects of Indoor Particulate Matter on Blood Indicators Related to Anemia.

Exposure to indoor particulate matter (PM) is a potential risk factor that increases systemic inflammation and affects erythropoiesis. This study investigated the association between exposure to indoor PM and blood indicators related to anemia (BIRA) in housewives. Indoor PM and blood folate status are important factors in the risk of anemia. This was a housewife cohort study; we recruited 284 housewives in Seoul and Ulsan, Republic of Korea. Indoor exposure to PM2.5 and PM10 was measured by gravimetric analysis and sensors. We investigated the BIRA, such as hemoglobin (Hb), hematocrit, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), and mean corpuscular Hb concentration (MCHC). Statistical analysis was performed by multiple linear regression model and mediation analysis. The association between BIRA and PM was assessed by multiple linear regression models fitted by mediation analyses. The increase in the level of indoor PM2.5 was associated with a decrease in MCV (Beta coefficient (B): −0.069, Standard error (SE): 0.022) and MCH (B: −0.019, SE: 0.009) in gravimetric measurements. The increase in the level of indoor PM2.5 was associated with a decrease in Hb (B: −0.024, SE: 0.011), hematocrit (B: −0.059, SE: 0.033), and MCV (B: −0.081, SE: 0.037) and MCH (B: −0.037, SE: 0.012) in sensor measurements (PM2.5-Lag10). Further, we identified a serum folate-mediated PM effect. The indoor PM exposure was significantly associated with decreased Hb, MCV, and MCH in housewives. Taken together, our data show that exposure to indoor PM is a risk factor for anemia in housewives. Blood folate concentration can be a mediating factor in the effect of indoor PM on BIRA. Therefore, folate intake should be recommended to prevent anemia in housewives. Moreover, indoor PM exposure should be managed.

Effects of UGT1A1 Polymorphism, Glucose-6-Phosphate Dehydrogenase Deficiency and Deletional (-3.7кb) α-Thalassemia Among Young Nigerians with Sickle Cell Anemia

Several genetic factors modulate the clinical course of sickle cell anemia (SCA), such as the βs-haplotypes, 3.7кb α-globin gene deletions (-α3.7), glucose-6-phosphate dehydrogenase deficiency (G6PD), UGT1A1 polymorphism and influencers of fetal hemoglobin production. While many studies on these modifiers have been conducted among patients in the developed world, little is known about how they impact SCA among Nigerians.We hypothesized that these factors could modulate SCA in the Nigerian population. Hence, we set out to determine whether βs-haplotype, -α3.7deletion, G6PD, and UGT1A1 polymorphism influence the laboratory markers and clinical events in young Nigerians with SCA.The study was conducted among 101 hydroxyurea-naïve SCA patients aged 2-21years, (median 9 years) in steady state, on regular follow up at the pediatric hematology unit of the Ekiti State University Teaching Hospital (EKSUTH), Ado Ekiti, Southwest Nigeria.Molecular analysis were conducted to confirm the diagnosis of SCA by polymerase chain reaction (PCR) and direct sequencing; alpha thalassemia by GAP-PCR; to determine UGT1A1 genotypes by Fragment Analysis; and BS haplotypes and G6PD genotypes by TaqMan SNP genotyping assay at the Hemocentro - University of Campinas, Brazil. Automated analysers were used to carry out hematologic and biochemical analyses. Records of the patients were examined for clinical events and steady state laboratory parameters. Serial abdominal ultrasounds were done as clinically indicated to diagnose gallstones. Institutional review board approval was obtained and the study protocols followed the Declaration of Helsinki as revised in 2000.Four (TA)n alleles (5, 6, 7, and 8) were found with gene frequencies of 0.11, 0.44, 0.40, and 0.05, respectively, grouped into 11 genotypes: TA5/5, 5/6, 5/7, 5/8, 6/5, 6/6, 6/7, 6/8, 7/7, 7/8, 8/8. Low Activity UGT1A1 genotypes (TA7/7, 7/8, 8/8) were found in 25 (24.7%). The Benin/Benin βs-haplotype was found in 94 (93%), Benin/Cameroun 4 (4%), Benin/Bantu 2 (2%), and Benin/Arab 1(1%). Mutation for the African variant of G6PD deficiency (202G>A) was found in 21(20.8%). None had the Mediterranean (563C>T) mutation. The frequency of 3.7 κb α-globin gene deletion was 34 (33.6%) αα /-α3.7 as heterozygous, 7 (7%) -α3.7/-α3.7 homozygous. Additionally, we found one (1%) α-globin triplication (αααanti3.7/αα).There was significant difference in bilirubin levels of the patients when differentiated by the UGT1A1 genotypes according to expected enzyme activity (low > intermediate > high activity with median unconjugated bilirubin levels of 1.8, 0.8, and 0.6mg/dL, respectively, P <0.0001). The presence of either alpha thalassemia or G6PD deficiency or both did not alter this trimodal pattern of bilirubin levels. Asymptomatic gallstone was found in 6 (5.9%) patients aged 10 to 16 years. Five of them had the low UGT1A1 activity genotypes 4 (TA7/7) & 1(TA7/8). The low genotype was significantly associated with gallstone when compared to other genotype groups 5/25 vs 1/76, P=0.0033. Bilirubin levels of patients with gallstone was significantly higher than age & sex matched subjects without gallstone (4.7 vs 1.2mg/dl, p=0.002) suggesting that the pathway to developing hyperbilirubinemia and gallstone is primarily driven by the influence of UGT1A1 genotype of our study cohorts.When we evaluated the influence of -α3.7 deletion, we found that participants with alpha thalassemia had higher frequencies of pain crisis in the preceding one year of the study with median episodes of 3 (range 0-6) vs 0 (range 0-6), P <0.0001. The presence of alpha thalassemia was significantly associated with decreased mean corpuscular volume, mean corpuscular hemoglobin, reticulocyte count and with a higher hemoglobin concentration (P <0.05) However, none of the 6 participants with leg ulcers had alpha thalassemia 0/ 42 vs 6/59 (P=0.039). There were no significant associations of βs-haplotypes and G6PD deficiency with both laboratory parameters and clinical events.In conclusion, our findings confirmed that both alpha thalassemia and UGT1A1 polymorphism influence the laboratory markers and clinical events of young Nigerians with SCA. It appears the influence of UGT1A1 polymorphism outweighs the modest ameliorating effect of alpha thalassemia on hyperbilirubinemia and cholelithogenesis among the patients. DisclosuresFertrin:Alexion Pharmaceuticals: Consultancy.

Hematological and Immunological Characterizations of Experimental Ulcerative Colitis Rats: The Impact of Alcohol Consumption Pattern

BACKGROUND: Studies have documented the contributions of alcohol to ulcerative colitis (UC) development. The present study sought to determine the specific pattern of hematological and immunological indices in experimental ulcerative colitis rats exposed to different alcohol intervention schedules. METHODS: 28 female Wistar rats weighing between 150-200 g were randomly divided into control, non-alcohol colitis (NAC), low-frequency alcohol colitis (LAC) and high-frequency alcohol colitis (HAC) groups. Experimental UC was induced through a single intra-colic instillation of 1 ml/100g of 7% acetic acid and rats were administered 20% v/v of ethanol ad libitum. RESULTS: When compared with NAC group, LAC elicited a significant increase (P&lt;0.05) in white blood cells (WBC), neutrophils, eosinophils, basophils, and myeloperoxidase while monocytes, lymphocytes, platelet, superoxide dismutase (SOD), catalase and glutathione decreased. Also, HAC caused an increase in myeloperoxidase and a decrease in Mean Corpuscular Volume (MCV), neutrophils, platelet, SOD, catalase, glutathione and tumor necrosis factor (α-TNF) when compared with NAC group. On the other hand, LAC raised WBC, neutrophils, eosinophils, basophils, platelet, MCV and α-TNF but decreased lymphocyte and monocyte when compared with HAC group. Histological analyses also revealed disruption of normal colonic integrity in NAC, LAC, and HAC. CONCLUSION: Low-frequency alcohol intake was relatively more granulocytic, inflammatory, thrombocytic, macrocytic and agranulopenic in colitis female rats than high-frequency alcohol intake.

Mechanism of Systemic Iron Regulation and Hematocrit Control By Hepcidin Peptidomimetics in Pre-Clinical Models

In polycythemia vera (PV), point mutation in JAK2 kinase (V617F) confers constitutive intracellular activity to JAK2 leading to a condition with excessive erythropoiesis that is independent of erythropoietin. Elevated hematocrit (HCT) and hyper-viscosity in the blood are risk factors for thrombosis and other symptoms. There is an increased iron demand required to support excessive erythropoiesis in the bone marrow. Hence, regulation of systemic iron in PV provides a mechanism for erythropoiesis control with potential disease modifying effects (Ginzburg YZ, Leukemia 2018). PTG-300 is an injectable hepcidin peptidomimetic drug currently in Phase 2 clinical studies for polycythemia vera and hereditary hemochromatosis. Pharmacodynamic (PD) effects of PTG-300 are reductions in serum iron and transferrin-saturation due to reduced expression on cells of ferroportin which exports iron into the peripheral circulation. Splenic red pulp macrophages that recycle iron from senescent RBCs are the primary source of serum iron for erythropoiesis. PTG-300 administration in cynomolgus monkey resulted in dose dependent reduction in serum iron (Fig. 1). Single subcutaneous (SC) dose of 0.3 mg/kg achieved a maximum of ~54.9% reduction in serum iron at 24 hr post-dose, serum iron returned to baseline in &amp;lt; 60 hr. Maximum PTG-300 concentration of 171.6±31.2 nM was observed at 8 hr, and concentration had reduced to 25.5±3.9 nM by 72 hr. SC dose of 1 mg/kg achieved ~75.8% reduction in serum iron at 24 hr post-dose (from baseline 31.3±2.3 µM to 7.6±0.9 µM). This dose exhibited a more sustained PD, with serum iron returning to baseline at ~108 hr. For 1 mg/kg, maximum PTG-300 concentration was 472.5±47.2 nM at 6 hr, and concentration reduced to 70.9±13.7 nM by 72 hr. At both doses a delay of 16-18 hr was observed between the maximum PTG-300 concentration and the maximum PD response. In a dose limiting GLP toxicity study in monkeys (over 13 weeks), weekly SC dosing of PTG-300 resulted in dose-dependent reductions in HCT (Fig. 2). In 2 mg/kg dose group, HCT reduction from baseline was 2.5% on Day 27 and 5.3% on Day 90 in males, and 3.5% on Day 27 and 6.8% on Day 90 in females. There were no decreases in mean corpuscular volume as is otherwise observed in phlebotomy dependent PV patients who are iron-deficient, indicating that PTG-300 may not create an iron deficient state but rather restricts iron availability to the bone marrow thereby reducing RBC levels. At higher dose of 6 mg/kg, HCT reduction was 14.2% at Day 27 and 19% at Day 90 in males, and 12.4% at Day 27 and 14.5% at Day 90 in females. In concurrence with HCT, dose dependent reductions were observed in hemoglobin (HGB). 0.6 mg/kg dose did not show significant reductions in HCT or HGB, albeit only marginal reductions at Day 90 (data not shown). HCT and HGB returned to baseline after a recovery period of 30 days post-last dose for all groups. In a mouse model for acquired secondary erythrocytosis, wild type mice were administered with daily injections of exogenous erythropoietin (EPO; 50 units/dose) for 7 days(Wang J, Haematologica 2018), resulting in elevated HCT. Concurrent treatment with peptide A (hepcidin mimetic with in vitro and in vivo potencies similar to PTG-300) on alternate days showed dose dependent reductions in HCT, RBCs and reticulocytes (Fig. 3). 5 mg/kg dose was able to normalize all three parameters to levels similar to control group that did not receive any EPO. Dose dependent reductions in spleen weight indicate that peptide A was effective in lowering extra medullary stress erythropoiesis in the spleen. The desired end points for PTG-300 as a therapy for PV are sustained reduction of HCT to circumvent the need for chronic phlebotomy and prevent the exacerbation of systemic iron deficiency. Our pre-clinical data support the efficacy of our hepcidin mimetics in limiting erythrocytosis with sustained control of hematocrit through iron redistribution. In addition to lowering hematocrit and reducing the need for phlebotomy treatment, we believe that PTG-300 has the potential to reduce debilitating symptoms associated with chronic iron deficiency by restoring tissue iron to meet the needs of critical/normal cellular functions (Krayenbuehl PA, Blood 2011). PTG-300 would potentially provide a novel mechanism for selective hematocrit control while maintaining adequate body iron levels in polycythemia vera and other congenital and acquired erythropoietic disorders. Disclosures Mattheakis: Protagonist Therapeutics: Current Employment, Current equity holder in private company. Zhao:Protagonist Therapeutics: Current Employment, Other: shareholder. Lee:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Tovera:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Zhao:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Cheng:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Liu:Protagonist Therapeutics: Current Employment, Current equity holder in private company.

Показники еритрограми та їх констеляції у хворих на цироз печінки різної етіології з остеопенією й остеопорозом: їх зміни і діагностична цінність

Introduction. There is a need to search for new publicly available methods for screening and diagnosing bone lesions in patients with liver cirrhosis (LC), one of which the detection of changes in individual parameters of the erythrogram and their combination in a routine general blood test could be. The aim of the study. To characterize the parameters of erythrogram and their constellation in patients with liver cirrhosis of various etiologies with osteopenia and osteoporosis, to find out their diagnostic value. Materials and methods. The study involved 79 patients with LC (women - 22; men - 57 aged 18 to 66 years) with bone mineral density (BMD) disorders (experimental group) (62 (78.48 %) , which is divided into 2 subgroups: patients with LC with osteopenia (38 (48.10 %) and osteoporosis (24 (30.38%)) and without it (comparison group (17 (21.52 %)). The control group consisted of 25 healthy individuals of the same gender and age. We studied the characteristics of changes in individual erythrogram parameters and their constellations: sensitivity (Se), specificity (Sp), accuracy (Ac), positive and negative predicted values (PPV and NPV), the likelihood ratios of positive and negative result (LR + and LR-), post-test probability of bone damage, the difference between the frequency of cases. The relationship between individual erythrogram parameter or constellation and bone damage was considered statistically confirmed at the modulus of G. U. Yule's coefficient of association (YCA) more than 0.5 or contingency coefficient (CC) more than 0.3. Results. We found the confirmed inverse stochastic relationship between the constellation «normal hemoglobin (HGB) + normal mean cell hemoglobin (MCH) + increase in red cell distribution width in percent (RDWC)», which may be combined with normal red blood cells (RBC) and/or normal mean corpuscular hemoglobin concentration (MCHC), and each of the bone lesions (with osteopenia: YCA = -0.69; CC = -0.33, with osteoporosis: YCA = -1.00, CC = -0.39), which most likely indicates BMD within normal limits. The individual erythrogram parameters and their constellations diagnostically valuable for osteopenia were not identified. We found such changes of the individual erythrogram parameters: revealed highly sensitive decrease in RBC, as the the most valuable (Se = 95.83 %; NPV = 83.33 %; LR- = 0.14; post-test probability of osteoporosis in its absence - 5.82%), decrease in HGB, decrease in hematocrit (HCT), moderately sensitive increase in red cell distribution width standard deviation in femtoliters (RDWS) (Se = 87.50-95.83%; NPV = 66.67-80.00 %; LR- = 0.17-0.35) and highly specific decrease in MCH (Sp = 94.12 %; PPV = 80.00 %; LR + = 2.83), between which and osteoporosis the direct stochastic relationship was confirmed (YCA = 0.52-0.81), being characteristic for the diagnosis of osteoporosis. Among the constellations, «normal RBC + normal mean corpuscular volume (MCV) + normal MCHC» and «normal RBC + normal MCH + normal MCHC + normal RDWS» were found indicating the absence of osteoporosis, as evidenced by the presence of an inverse stochastic relationship between constellations and osteoporosis (YCA = -1.00; CC = -0.33). Also the moderately sensitive constellation «decrease in RBC + increase in RDWS» (Se = 83.33 %; LR- = 0.35) and constellations - highly specific «decrease in MCV + increase in RDWS» and the most specific (most valuable) «decrease in RBC + decrease in MCV + increase in RDWS» were found which can be combined with a decrease in HGB, and/or a decrease in HCT, and/or an increase in RDWC, and/or normal MCHC (Sp = 94.12-100.00 %; PPV = 88.89-100,00 %; LR + = 5.67 - tends to infinity), between which there and osteoporosis there is a confirmed direct stochastic relationship (YCA = 0.63-1.00; SS = 0.33-0.38). Conclusions. The presence of the constellation «normal HGB + normal MCH + increase in RDWC», which may be combined with normal RBC and/or normal MCHC, indicates the absence of bone damage in a patient with liver cirrhosis. The individual erythrogram parameters or their constellations diagnostically valuable for osteopenia were not identified. The absence of such highly sensitive changes of erythrogram parameters as decrease in RBC being of the greatest diagnostic value, or decrease in HGB content, HCT, or moderately sensitive increase in RDWS, or constellation «decrease in RBC + increase in RDWS», or presence of constellations «normal RBC + normal MCV + normal MCHC» or «normal RBC + normal MCH + normal MCHC + normal RDWS» most likely indicates the absence of osteoporosis in patients with liver cirrhosis. The presence of highly specific decrease in MCH and/or constellations - highly specific «decrease in MCV + increase in RDWS», or the most specific and most valuable «decrease in RBC + decrease in MCV + increase in RDWS» which can be combined with decrease in HGB and/or decrease in HCT, and/or increase in RDWC, and/or normal MCHC, indicates that patients with liver cirrhosis have osteoporosis.

Effects of trichothecene mycotoxin T-2 toxin on haematological and immunological parameters of rainbow trout (Oncorhynchus mykiss).

The aim of this study was to assess the effects of T-2 toxin-contaminated feed (at concentrations of 1.0 and 1.8 mg/kg) on the rainbow trout immune system by studying non-specific cellular and humoral immune responses and its effect on red and white blood cells. Consumption of T-2 toxin at both concentrations resulted in significantly increased erythrocyte counts and a decrease in mean corpuscular volume. While a significant decrease in mean corpuscular haemoglobin was observed at both experimental concentrations, the decrease in plasma haemoglobin was only significant at the higher T-2 toxin concentration. Higher T-2 toxin concentrations resulted in a significant increase in leukocyte and lymphocyte count, while absolute phagocyte count and counts of less mature neutrophil granulocyte forms remained unchanged at both concentrations. Non-specific humoral immunity (bactericidal activity measured as complement activation) decreased significantly in both experimental groups when compared with the control. The results of this study show that T-2 toxin in feed at a concentration range of 1.0-1.8 mg/kg influences the immunological defence mechanisms of rainbow trout.Trial registration number, MSMT-3876/2014-14; date of registration, 31/1/2014.

Effect of β-glucan in water on growth performance, blood status and intestinal microbiota in tilapia under hypoxia

In the present study, the effects of β-glucan administration in water on growth performance and blood status (hematological indexes, immunological and biochemical parameters) were evaluated in Nile tilapia fingerlings (Oreochromis niloticus) under hypoxia-induced stress. In parallel, effect of this prebiotic (beta-glucan) was evaluated on gut microbiota diversity (16S rRNA gene) under normal oxygenation condition. Three treatments were implemented according to beta-glucan water supplementation: 0 (control), 0.1 and 0.3 mg L−1. Blood was collected before hypoxic challenge (BHC) and 9 h after hypoxic challenge (AHC). No significant differences were observed according to growh performance parameters. A significant increase in erythrocyte number and decrease in mean corpuscular volume (P < 0.05) were identified in control group when were under hypoxia. The plasma glucose level was higher in the 0.3 group than in the 0.1 group BHC; however, for all groups, the glucose level increased markedly AHC, and then receded seven days AHC (7AHC, P < 0.05). Total protein, serum lysozyme, plasma lactate, triglyceride, and cholesterol concentrations did not differ between groups. Comparison of the two β-glucan concentrations indicated that the 0.3 mg L−1 concentration promoted an increase in lymphocyte count. The 0.1 group showed the highest survival rate 7 days after hypoxia. Metagenomic analysis revealed a greater number of operational taxonomic units (OTUs) in the 0.1 and 0.3 groups. The Chao richness value was higher in the 0.1 group than in the control group (P < 0.05), with a greater abundance observed for members of the Vibrionaceae family. It is concluded that the concentration of 0.1 mg L−1 was able to increase tolerance to hypoxia, increasing the survival rate and regulating glucose levels. The concentration of 0.3 mg L−1 modulated hematological responses under stress and increased the lymphocyte count before hypoxic challenge.

Effects of Self-Care for Older PErsons (SCOPE) on Functional and Physiological Measures: A Cluster Randomized Controlled Trial.

Background: Population aging poses unprecedented demands on the healthcare system. There is also a scarcity of evidence on self-care intervention to improve objective measures of morbidity and aging-associated functional and physiological measures in a low-income multi-ethnic population setting. Methods: We conducted a cluster randomized controlled trial (ClinicalTrials.gov Identifier: NCT01672177) to examine the effects of the Self-Care for Older PErsons (SCOPE) program. We randomized 14 Senior Activity Centers and randomly selected older adults within these centers. Functional and physiological measurements were performed at baseline, 10-month, and 18-month periods. The primary outcome was a composite of three morbidity-specific measures, which include hemoglobin A1c (HbA1C), peak expiratory flow, and systolic blood pressure. Aging-associated functional and physiological measures were examined as secondary outcomes. Repeated-measure mixed models were employed to examine the effects of SCOPE on these measures. Results: 378 community-dwelling older adults participated in either the treatment (n= 164) or the control arm (n = 214). The primary outcome was not significantly improved. For the secondary outcomes, SCOPE participants demonstrated slower oxygen desaturation at an 18-month period (p = 0.001), improved time to complete the chair-stand test (p < 0.001) at a 10-month period with the effect persisting at the 18-month period (p < 0.001). SCOPE participants also had significantly improved vitamin B12 levels at the 18-month period (p < 0.001), increased hemoglobin concentration (p < 0.001), decreased mean corpuscular volume (p = 0.001), and decreased creatinine (p = 0.002) at the 10-month period. Conclusions: SCOPE did not improve morbidity-specific measures. However, it improved several aging-associated measures implicated in geriatric syndromes. This study highlights the potential of a self-care program in the prevention of geriatric syndromes in community-dwelling older adults, while emphasizing self-management to manage existing morbidities.

Changes of the erythrocyte phenotype and blood biochemistry in dairy calves during the first ten weeks of age.

BackgroundBovine erythrocytes undergo important changes in their morphology and chemical composition during the first weeks of age, which must be understood to accurately interpret hematology results in calves. The objectives of this prospective cohort study were to describe physiological changes of calf erythrocytes and to investigate mechanisms potentially causing these changes.MethodsBlood samples from 30 clinically healthy dairy calves were obtained from birth to the tenth week of age in weekly intervals. Hematological and plasma biochemical parameters as well as the mineral electrolyte content of erythrocytes were determined and followed over time. The changes of parameters characterizing the erythrocyte phenotype over time were compared to the changes of plasma and erythrocyte biochemical parameters and possible associations were investigated using correlation and stepwise regression analyses.ResultsAlthough the erythrocyte mean corpuscular volume (MCV) declined from 43.6 ± 3.7 fL to 35.6 ± 3.2 fL between the first and seventh week, the red blood cell count (RBC) increased from 7.2 ± 1.1 × 1012/L to 9.3 ± 1.0 × 1012/L until the fifth week of age. The blood hemoglobin (Hb) concentration increased from 0.96 ± 0.16 g/L to 1.16 ± 0.11 g/L in the first three weeks of age and remained at this level until the end of the study. Changes in MCV were accompanied by a decline of the erythrocyte potassium content (KERY) from 91.9 ± 13.5 to 24.6 ± 7.2 mmol/L and a concomitant increase of the erythrocyte sodium content from 45.0 ± 32.0 to 102.7 ± 26.5 mmol/L. MCV was found to be associated with KERY, the primary determinant of the intra-erythrocyte osmotic pressure from the sixth week of age and with blood hemoglobin, the primary determinant of the intra-erythrocyte oncotic pressure from the eighth week of age, when KERY, blood Hb and MCV already had reached or approached normal levels of adult cattle. The plasma iron concentration was not found to be associated to any of the studied hematological parameters.ConclusionA volume reduction of 20% in bovine neonatal erythrocytes is a physiological change occurring during the first weeks of age and is neither associated with sideropenia nor with anemia in healthy calves. The mechanism driving the observed erythrocyte volume change could not be identified. Results of the correlation and regression analyses indicate that changes in intra-erythrocyte osmotic or oncotic pressure are improbable underlying causes. Results reported here show that KERY is an unreliable indicator for the K homeostasis of the intracellular space in neonatal calves and that a decrease in MCV in early life per-se is an unreliable indicator for the development of microcytic anemia.

The effect of atorvastatin on haemostatic parameters in apparently healthy dogs.

To determine the effect of atorvastatin on haemostatic parameters as measured by prothrombin time, activated partial thromboplastin time and thromboelastography in apparently healthy dogs administered 2mg/kg orally once daily for 1week. Prospective study of 20 apparently healthy client-owned dogs at a small animal specialty hospital. Dogs had a baseline complete blood count, serum chemistry profile, fibrinogen, platelet count, prothrombin time, activated partial thromboplastin time and thromboelastography performed. Each dog was then administered approximately 2mg/kg of atorvastatin orally once daily for 1 week, and the laboratory tests were repeated. Adverse effects attributed to atorvastatin were recorded. All 20 enrolled dogs completed the study. Dogs received a median dose of 2.06 mg/kg (range 1.94 to 2.44 mg/kg) atorvastatin once daily, which was associated with a significant increase in pulse rate, mean corpuscular haemoglobin concentration, albumin and a significant decrease in mean corpuscular volume, cholesterol and lipase values compared with baseline. On thromboelastography, there was a significant increase in maximum amplitude, G, coagulation index, amplitude at 30 minutes, amplitude at 60minutes and significant decrease in percentage of clot lysed at 30 minutes and percentage of clot lysed at 60 minutes values compared with baseline. Six dogs had a noticeable increase in appetite. The results of this study suggest that atorvastatin may produce a procoagulant effect in dogs, although the clinical significance is unclear. Polyphagia was the most commonly reported adverse effect.