Increase In Erythrocyte Count Research Articles

Novel Anti-TMPRSS6 Monoclonal Antibody Provides a Potential Therapeutic Approach for the Treatment of Polycythemia Vera

Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) triggered by activating mutations in JAK2, an important kinase in the principal signaling pathway of the erythropoietin receptor. Most of the clinical manifestations of PV are caused by increased erythrocyte count, leading to increased risk of pulmonary hypertension and thrombosis. The mainstay of therapy for PV is therapeutic phlebotomy to reduce the hematocrit (HCT) level and minimize the risk of thrombosis, however, the effect of phlebotomy is transient until patients become iron deficient. Therefore, systemic iron restriction could be effective in treating PV patients. Transmembrane serine protease 6 (TMPRSS6) is a negative regulator hepcidin, the master regulator of iron homeostasis. Increasing genetic, preclinical and clinical evidence has demonstrated that inhibition of TMPRSS6 can potently elevated hepcidin levels, thereby achieving systemic iron restriction. Previously, we reported the generation of anti-TMPRSS6 antibody MWTx-003 and its efficacy in reducing iron overload and improving ineffective erythropoiesis in a mouse model of β-thalassemia. In this study, we explored therapeutic application of MWTx-003 in PV using a Jak2 V617F bone marrow transplantation mouse model. The mouse model exhibits typical PV phenotypes of erythrocytosis and elevated HCT levels. In the PV mice, treatment with MWTx-003 (2-10 mg/kg, i.p., every 4 days for 3 weeks) led to significantly reduced HCT levels, red blood cell (RBC) counts and hemoglobin (HGB) concentration that were comparable to that of wildtype control mice. These effects were evident in a dose-dependent manner and observed as early as two weeks into treatment. It is worth noting that in the 10 mg/kg dose group, a worsening splenomegaly and expansion of early erythroid progenitors were observed after 3 weeks of treatment, and these findings are typical of iron-restricted erythropoiesis in mice. Taken together, the anti-TMPRSS6 antibody offers a promising therapeutic approach in the management of PV, where erythrocytosis and high HCT levels are associated with poor outcomes. A Phase I clinical trial with MWTx-003 in healthy volunteers has been initiated in China.

ZAKα/P38 kinase signaling pathway regulates hematopoiesis by activating the NLRP1 inflammasome.

Chronic inflammatory diseases are associated with hematopoietic lineage bias, including neutrophilia and anemia. We have recently identified that the canonical inflammasome mediates the cleavage of the master erythroid transcription factor GATA1 in hematopoietic stem and progenitor cells (HSPCs). We report here that genetic inhibition of Nlrp1 resulted in reduced number of neutrophils and increased erythrocyte counts in zebrafish larvae. We also found that the NLRP1 inflammasome in human cells was inhibited by LRRFIP1 and FLII, independently of DPP9, and both inhibitors regulated hematopoiesis. Mechanistically, erythroid differentiation resulted in ribosomal stress-induced activation of the ZAKα/P38 kinase axis which, in turn, phosphorylated and promoted the assembly of NLRP1 in both zebrafish and human. Finally, inhibition of Zaka with the FDA/EMA-approved drug Nilotinib alleviated neutrophilia in a zebrafish model of neutrophilic inflammation and promoted erythroid differentiation and GATA1 accumulation in K562 cells. In conclusion, our results reveal that the NLRP1 inflammasome regulates hematopoiesis and pave the way to develop novel therapeutic strategies for the treatment of hematopoietic alterations associated with chronic inflammatory and rare diseases.

#3178 EFFECTS OF SGLT-2 INHIBITORS VERSUS DPP-4 INHIBITORS ON ANEMIA IN PATIENTS WITH TYPE 2 DIABETES

Abstract Background and Aims The number of people suffering from diabetes has exceeded 400 million worldwide. The incidence of anemia in type 2 diabetes mellitus (T2D) patients is about twice that of non-diabetic patients. Moreover, patients with T2D who have chronic kidney disease are at higher risk of developing anemia and it also occurs earlier. Therefore it is worth investigating the problem of anemia in T2D patients. This study was conducted to compare the effects of the new oral hypoglycemic agents (sodium-glucose cotransporter-2 inhibitors, SGLT-2i and dipeptidyl peptidase-4 inhibitors, DPP-4i) on anemia in patients with T2D. Method This study was designed as a retrospective cohort study and analyzed using the Kaohsiung Medical University Hospital Research Database (KMUHRD). Study inclusion criteria: (1) patients start using SGLT-2i or DPP-4i from January 1, 2015 to December 31, 2020 (first prescription is defined as not used within 180 days prior to the activation date, and cases are screened from the year prior to the starting intake date), and (2) patients with T2D who meet the diagnosis of anemia (according to the World Health Organization definition of hemoglobin <13 g/ dL in men and <12 g/ dL in women) at the time of initial dosing. Patients without hemoglobin data within 180 days before and after treatment were excluded. The outcome will evaluate the effect of SGLT-2i and DPP-4i on erythropoietic parameters including erythrocyte, reticulocyte count, hemoglobin, and hematocrit. Results In total 4,555 patients were enrolled in this study. Of these patients, 4,251 were treated with DPP-4i and 304 with SGLT-2i. Using propensity score matching, 303 patients each from the DPP-4i and SGLT-2i groups were selected based on patient characteristics. There were no difference in hemoglobin values (Median: 11.30 vs. 11.20 g/ dL, P = 0.328) and renal function (expressed as eGFR, 83.30 vs. 81.84 mL/min, P = 0.255) between the DPP-4i and SGLT-2i groups before treatment. After six months of follow-up, only the SGLT-2i group showed a statistically significant increase in erythrocyte count (3.88 to 4.19 × 10^6/uL, P < 0.001), hemoglobin (11.20 to 11.70 g/ dL, P < 0.001), and hematocrit values (34.4 to 36.5%, P < 0.001). However, the same changes were not observed in the DPP-4i group: erythrocyte count (3.87 to 3.91 × 10^6/uL, P = 0.051), hemoglobin (11.30 to 11.40 g/ dL, P = 0.315), and hematocrit values (34.4 to 34.7%, P = 0.102). The Δhemoglobin showed a significant correlation with the SGLT-2i use, metformin use, erythrocyte count, hematocrit, hemoglobin and eGFR levels at baseline. Multiple regression analyses showed that use of SGLT-2i might be the main influencing factor. Conclusion Our study compared the effects of SGLT-2i and DPP-4i on erythropoietic parameters in T2D patients, and only the SGLT-2i group showed significant increase in erythrocyte count, hemoglobin, and hematocrit. The use of SGLT-2i may be the major factor affecting the improvement of erythropoietic parameters. Therefore the hypoglycemic effect of SGLT-2i may be accompanied by the improvement of anemia.

Analysis of Changes in the Selected Nutritional Parameters of Patients within a Year from the Admission to the Enteral Nutrition Clinic.

(1) The following research question was formulated: What are the relationships between enteral nutrition and selected anthropometric and blood biochemical parameters? The aim of this study was to provide an assessment of the nutritional status of patients within one year from their admission to the Enteral Nutrition Clinic. (2) The study group included 103 participants. For the purpose of analysing their nutritional status, the Subjective Global Assessment (SGA) and Nutritional Risk Score (NRS) scales were used, anthropometric measurements were taken, and blood laboratory tests were performed. The assessment of changes in the indicated parameters was conducted at three time intervals: upon admission (T0) and 6 and 12 months after admission (T6 and T12, respectively). (3) The study group showed a significant improvement in the circumference of their upper and lower limbs. Nutrition therapy had an effect on the levels of erythrocytes, iron concentration, the activity of liver enzymes, and C-reactive protein levels. (4) The enrolment of patients into the Nutritional Therapy Programme had a positive effect on the selected results. 1. Twelve months after the introduction of nutritional intervention, an increase in erythrocyte count was particularly marked, and there was a decrease in the CRP (C Reactive Protein) level as well as the activity of liver enzymes. There was no significant effect of enteral nutrition on albumin and protein values. 2. To ensure the greatest efficiency of enteral nutritional therapy, it is to be continued for more than six months. 3. Nutritional interventions resulted in a significant increase in upper and lower limb circumferences among the study group. 4. For the purpose of identifying patients at risk of malnutrition, medical personnel should systematically raise their qualifications, and educational measures on this issue should be implemented at the stage of medical training at medical universities.

Dietary supplementation of Spirulina platensis and Saccharomyces cerevisiae on egg quality, physiological condition and ammonia emission of hens at the late laying period

The study was aimed to evaluate the effect of Spirulina platensis and Saccharomyces cerevisiae or its combination on egg quality, physiological condition and ammonia excretion of hens at the late lay-ing period. At 81 weeks old, 144 Lohmann Brown layer chickens were divided into four treatment groups included CON (hens fed basal feed), SP (basal feed + 0.3% S. platensis), SC (basal feed + 0.2% S. cerevisiae), and SPSC (basal feed + 0.3% S. platensis + 0.2% S. cerevisiae). At the end of the study, eggs, intestinal mucosa, digesta, excreta and blood sample were collected. Results showed that albumin index was higher (P<0.05) in SPSC group than in CON, SP and SC. The yolk index and yolk colour were greater (P<0.05) in SP and SPSC groups than in CON and SC. The erythrocyte values were high-er (P<0.05) in SP group compared to CON, SC and SPSC groups. The ileum pH was higher (P<0.05) in SP than in CON, SC and SPSC. Lactic acid bacteria counts were lower (P<0.05) in the caecum of SC and SPSC than in CON and SP groups. The lower (P<0.05) counts of lactose-negative Enterobacte-riaceae were shown in SC and SPSC than in CON. The excreta pH was lower (P<0.05) in SC group compared to CON, SP and SPSC groups. There were better (P<0.05) protein digestibility coefficient and nitrogen retention in SPSC group than others. Faecal ammonia decreased (P<0.05) in SP, SC and SPSC groups. In conclusion, S. platensis improved egg yolk index and colour, increased erythrocyte counts and played an important role in maintaining the balance of bacteria in the intestine resulting in reduced ammonia excretion. Dietary inclusion of S. cerevisiae reduced ammonia excretion of laying hens during the late laying period.

EFFECTS OF DRUG BETAMETHASONE ON HEMATOLOGICAL PARAMETERS OF RATTUS NORVEGICUS (BERKENHOUT 1769) IN VIVO CONDITIONS

Glucocorticoids prevent or suppress the full inflammatory response to the infectious, immunological or physical agents by inhibiting early inflammatory events such as edema or cell exudation. The main effect of glucocorticoids on the inflammatory process is the inhibition or recruitment of neutrophils and monocytes. In this study, the effect of the glucocorticoid betamethasone on the hematological parameters of rats of the species Rattus norvegicus Berkenhout 1769 was examined in vivo. Betamethasone has been shown to affect the values of hematological parameters four hours after application and leads to a significant decrease in the prevalence of lymphocytes and monocytes, but also leads to a statistically significant increase in erythrocyte count, hemoglobin concentration and hematocrit values.

Effectiveness of treatment regimens for cows with seous mastitis using zinc chelate complex

The article presents the therapeutic efficacy of Biozinc in the treatment of cattle with serous mastitis. The authors revealed a decrease in the number of somatic cells in milk in the experimental group of cows to 170 thousand, which corresponds to the milk from a healthy animal. Cows in the experimental group showed a positive trend in milk quality. Five cows had watery milk. Positive changes in milk quality were evident 12 hours after the first injection in the form of a reduction in flake secretion from the affected quarters. Milk was watery in all cows of the experimental group by the third day, without flakes and white color. The authors note a positive trend during disease treatment by the end of the first day of treatment in both test groups. Complete recovery was noted in ten animals, which was 100%, in the experimental group, which were treated with Biozinc. Complete recovery occurred after 3.00±0.15 days. The therapeutic efficacy was 100%. In the control group, seven cows (70%) recovered. A hematological examination revealed a 15.52 g/l (18.1 %) increase in hemoglobin level in the experimental group of animals and a 0.88 x 1012/l (P<0.05) increase in erythrocyte count. Through serum biochemical studies, the authors found that cows with serous mastitis showed changes in such parameters as protein, bilirubin, alanine aminotransferase (ALAT), and aspartate aminotransferase (ASAT). Cows in the experimental group showed a 21.5% (P<0.01) decrease in protein content after treatment. The values of ASAT in the control group decreased by 35.2%, and in the experimental group - by 42.6%. The values of ALAT also tended to decrease by 38.7% in the control group and by 48.6% in the experimental group (P<0.001).

Filterability of Erythrocytes in Patients with COVID-19.

For the first time, the influence of COVID-19 on blood microrheology was studied. For this, the method of filtering erythrocytes through filters with pores of 3.5 μm was used. Filterability was shown to significantly decrease with the increasing severity of the patient’s condition, as well as with a decrease in the ratio of hemoglobin oxygen saturation to the oxygen fraction in the inhaled air (SpO2/FiO2). The filterability of ≤ 0.65, or its fast decrease during treatment, were indicators of a poor prognosis. Filterability increased significantly with an increase in erythrocyte count, hematocrit and blood concentrations of hemoglobin, albumin, and total protein. The effect of these parameters on the erythrocyte filterability is directly opposite to their effect on blood macrorheology, where they all increase blood viscosity, worsening the erythrocyte deformability. The erythrocyte filterability decreased with increasing oxygen supply rate, especially in patients on mechanical ventilation, apparently not due to the oxygen supplied, but to the deterioration of the patients’ condition. Filterability significantly correlates with the C-reactive protein, which indicates that inflammation affects the blood microrheology in the capillaries. Thus, the filterability of erythrocytes is a good tool for studying the severity of the patient’s condition and his prognosis in COVID-19.

Co-administration of morphine and levamisole increases death risk, produces neutropenia and modifies antinociception in mice.

Levamisole is a veterinary anthelmintic drug and a common adulterant of misused drugs. This study analyses the lethal, antinociceptive and haematological effects produced by acute or repeated levamisole administration by itself or combined with morphine. Independent groups of male Swiss Webster mice were i.p. injected with 100 mg/kg morphine, 31.6mg/kg levamisole (lethal doses at 10%, LD10 ) or the same doses combined. Naloxone pretreatment (10mg/kg, i.p.) prevented morphine-induced death, as did 2.5mg/kg, i.p. mecamylamine with levamisole. Co-administration of levamisole and morphine (Lvm + Mor) increased lethality from 10% to 80%. This augmented effect was prevented by 30 mg/kg, i.p. naloxone and reduced with 10mg/kg naloxone plus 2.5mg/kg, i.p. mecamylamine. In independent groups of mice, 17.7mg/kg, i.p. levamisole antagonized the acute morphine's antinociceptive effect evaluated in the tail-flick test. Repeated 17.7mg/kg levamisole administration (2×/day/3weeks) did not affect tolerance development to morphine (10mg/kg, 3×/day/1week). Blood samples obtained from mice repeatedly treated with levamisole showed leukopenia and neutropenia. Morphine also produced neutropenia, increased erythrocyte count and other related parameters (e.g. haemoglobin). Lvm + Mor had similar effects on leukocyte and neutrophil counts to those seen with levamisole only, but no erythrocyte-related alterations were evident. Blood chemistry analysis did not indicate liver damage but suggested some degree of electrolyte balance impairment. In conclusion, Lvm + Mor increased death risk, altered morphine-induced antinociceptive effects and produced haematologic abnormalities. The importance of studying combinations of drugs of abuse lies in the fact that drug users frequently combine drugs, which are commonly adulterated.

Changes in morphological composition of blood in rats under intragastric load with walnut meal

The basis for the existence of all living organisms is homeostasis. Any living organism is an open dynamic self-regulating system and self-regulation is based on the feedback principle. The use of biologically active substances, for example, plant meal, opens up great possibilities for modulation of physiological processes in the body. Walnut fruit meal also has a rich composition, contains almost all microelements, large amounts of protein as well as carotene, quinones, lecithin, water-soluble vitamins and flavonoids. The aim of the work was to study the adaptive changes in the morphological composition of rat blood to intragastric loading with walnut meal in the form of suspension on distilled water. The experiment was carried out on 60 white laboratory rats. Conclusion: intragastric loading with distilled water suspension of walnut meal in a concentration of 15 mg/100 g body weight of clinically healthy rats was accompanied by an increase in erythrocyte count, hemoglobin concentration and leukocyte count by 6.8%, 7.0% and 9.6%, respectively, compared with the control group animals.

English

Helminths have been a serious trouble for the farmers due to their adverse effects on small ruminant production. Hemonchus contortus (H. contortus) and Fasciola hepatica (F. hepatica) are highly pathogenic and pose serious threat in co-existence. Because of increasing threat of anthelmintic resistance, alternative methods are being investigated and the herbal remedies stand the most prominent due to their efficacy and availability. Anthelmintic activity of the herbal mixture was evaluated in goats. Adult goats were selected at Livestock Production and Research Centre (LPRI) Bahadarnagar, Okara and were examined for helminth eggs in their feces. Twenty-four goats having almost similar egg per gram (EPG) of feces values of H. contortus and F. hepatica were selected and allocated to four groups of equal size. Herbal mixture was administered at dose rate of 1400, 1200 and 1000 mg/kg to each member of groups G1, G2 and G3, respectively on day 0, 7, 14 and 21 of the trials, while group G4 served as negative control receiving no medicine/herbal mixture. Trials continued for 30 days and data about EPG, fecal egg count reduction, complete blood count and serum biochemistry were collected before administration of herbal mixture at day 15 and day 30 of trial while animals were weighed before initiation of trial (day 0) and at the end of trial (day 30). All treatments showed a significant reduction in fecal egg count as compared to control group. Maximum fecal egg count reduction was observed in animals of group G1, which is 91.35% for H. contortus and 82.35% for F. hepatica. There was a slight increase in weight gain ratio of the treated animals in respective decreasing order with G1 having highest weight gain. An increase in erythrocyte count, pack cell volume and hemoglobin concentration was recorded while non-significant effect was observed on serum parameters. The results of this trial suggested that herbal dewormer is effective and can be an option for integrated management strategies for nematodes and trematodes control in the goats

Electrolyte and Electrocardiogram Changes in Dehydrated Male Bovine Calves

Background: Since many electrolytes are invariably lost in the diarrheal fluid, their serum alterations would have a profound bearing on the ECG. Methods: The study was conducted on twelve diarrhoeic and dehydrated male bovine calves of 2-5 months of age. Electrocardiogram and some haemato-biochemical parameters were compared between dehydrated and hydrated animals after supportive treatment. Result: Heart rate was found to be increased from 90.33 ± 9.71 bpm to 104.33 ± 9.03 bpm with considerable cardiac arrhythmias in dehydrated animals. Significantly (P less than 0.05) decreased QRS amplitudes and ST intervals were seen in dehydrated animals, whereas QRS durations were significantly increased. P waves were sometimes flattened or not visible, while T waves often were tall and peaked in diarrhoeic calves. No other significant changes in ECG parameters including cardiac axis were noticed. Non-significant increase in erythrocyte count and haematocrit associated with haemoconcentration was found. There was however a significant increase in lymphocyte and eosinophil count, together with increase in osmotic fragility in dehydrated animals. Electrolytes sodium and magnesium decreased significantly, while potassium increased amongst dehydrated calves. Based on observable ECG changes, alterations were indifferent from those of hyperkalemia, hyponatremia and hypomagnesemia. It is hoped that the present communication would be a helpful guide for the clinical veterinarian or those electrocardiographically monitoring supportive therapy of dehydrated animals.

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.

Novel Therapies in Polycythemia Vera.

Polycythemia vera is a myeloproliferative neoplasm characterized by increased erythrocyte count, thrombotic potential, and transformation to myelofibrosis. Older patients and those who have a history of thrombosis require cytoreductive therapy, most commonly with hydroxyurea. Other currently available therapies include pegylated interferon alfa-2a and the JAK1/2 inhibitor ruxolitinib. However, there are limitations to these agents, including potential detrimental adverse effects. In this review, we will describe current therapeutic options for the treatment of PV and then detail new agents with available clinical trial data. A number of novel investigational therapies including MDM2 inhibitors, histone deacetylase inhibitors, and long-acting pegylated interferon alfa-2b are in various stages of clinical development with encouraging efficacy data. The therapeutic landscape for patients with PV is expanding. Novel agents are in development that not only reduce the thrombotic potential but also act directly on the malignant PV clone with the intention of significantly modifying disease progression.

The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice.

The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2-3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.

Oxidative status of growing West African dwarf goat kids fed diets containing different nutrient density

Nutritional manipulation is the best option against parasitic infection in ruminants, as it has no residual effect on the animal. Nutrition improves the resilience and resistance of the infected animals and eliminates the resultant clinical anaemia. Twenty-four growing intensively raised West African dwarf (WAD) goats (10.2 + 0.78) were used to assess the effect of incremental levels of protein and energy on the performance characteristics and oxidative status of the WAD goats. The animals were individually housed and allotted to diets containing varying levels of crude protein and energy levels: high-energy high-protein (HH), medium-energy medium-protein (MM) and low-energy low-protein (LL) diets in a completely randomised design. Data were collected for changes in weight gain, haematogical and serum constituents, oxidative stress biomarkers and faecal egg count. Higher levels of energy and protein in the diets increased (P < 0.05) metabolic weight gain (kgBW^0.75) and average daily gain (g/day). Increased levels of crude protein and energy significantly (P < 0.05) increased packed cell volume, haemoglobin concentration and red blood cell count of the goats. Thiol concentration was increased (P < 0.05) with increased level of protein and energy in the diets. The observed reductions in egg per gram of the faeces were similar among the treatment groups. Therefore, increased levels of protein and energy in the diets improve the dry matter intake and daily weight gain with increased erythrocyte count and antioxidant status (through increased thiol concentration) in goats fed MM and HH diets.

Extension of 2016 World Health Organization (WHO) Classification into a New Set of Clinical, Laboratory, Molecular, and Pathological Criteria for the Diagnosis of Myeloproliferative Neoplasms: From Dameshek to Vainchenker, Green, and Kralovics

Improved Clinical, Laboratory, Molecular, and Pathological (CLMP) 2017 criteria for myeloproliferative neoplasms (MPN) define the JAK2V617F trilinear MPNs as a broad continuum of essential thrombocythaemia (ET), polycythaemia vera (PV), masked PV, and post-ET or post-PV myelofibrosis (MF). Normal versus increased erythrocyte counts (5.8×1012/L) on top of bone marrow histology separate JAK2V617F ET and prodromal PV from early and classical PV. Bone marrow histology of the JAK2V617F trilinear MPNs show variable degrees of normocellular megakaryocytic, erythrocytic megakaryocytic and erythrocytic megakaryocytic granulocytic (EMG) myeloproliferation, peripheral cytoses, and splenomegaly related to JAK2V617F allele burden. MPL515 thrombocythaemia displays predominantly normocellular megakaryocytic proliferation. CALR thrombocythaemia intially presents with megakaryocytic followed by dual granulocytic and megakaryocytic myeloproliferation without features of PV. The megakaryocytes are large, mature, and pleomorphic with hyperlobulated nuclei in JAK2V617F ET and prodromal, classical, and masked PV. The megakaryocytes are large to giant with hyperlobulated staghorn-like nuclei in MPL515 thrombocythaemia. The megakaryocytes are densely clustered, large, and immature dysmorphic with bulky (bulbous) hyperchromatic nuclei in CALR thrombocythaemia and MF.

Effects of gossypol from cottonseed cake on the blood profile in sheep.

Cottonseed cake contains gossypol, a potentially toxic compound that, when consumed by sheep, can affect reproduction, the immune system, and the liver. Changes in hematologic and serum biochemical parameters were monitored for 63days in 12 Santa Inês ewes, six of which received ration containing 400gkg(-1) of cottonseed cake. Blood samples were collected at the start of the experiment and weekly thereafter for hematologic assessment and determination of serum urea, creatinine, total protein, and albumin concentrations and for measurement of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase activities. No clinical signs of toxicity were observed. Evaluation of the erythron showed that sheep consuming cottonseed cake had an increased packed cell volume (p < 0.05) and increased erythrocyte counts and hemoglobin concentrations (p < 0.05) in the leukogram and serum biochemistry panel. In conclusion, consumption of 400gkg(-1) cottonseed cake by sheep for 63days may induce changes in the erythron but no consistent changes in serum biochemical parameters, indicating no damage to the liver or kidneys.

Monitoring recovery from iron deficiency using total hemoglobin mass.

Using hemoglobin concentration ([Hb]) to diagnose borderline iron deficiency and monitor the progress of its treatment is difficult because of the confounding effects of plasma volume. Because hemoglobin mass (Hbmass) is not affected by plasma volume, it may be a more sensitive parameter. The aim of this study was to monitor Hbmass, iron storage, and maximal oxygen consumption (V˙O2max) during and after oral iron therapy in subjects with severe and moderate iron deficiency. Three groups of female recreational athletes were monitored for at least 22 wk, as follows: 1) severe iron deficiency group (SID) (n = 8; ferritin, ≤12 ng·mL), 2) moderate iron deficiency group (MID) (n = 14; ferritin, ≤25 ng·mL), and 3) control group (n = 8; ferritin, >25 ng·mL). Hbmass and iron status were determined before, during, and up to 12 wk after at least 10 wk of oral iron supplementation. In total, five V˙O2max tests were performed before, during, and after the supplementation period. Hbmass increased markedly in the SID group (15.6% ± 11.0%, P < 0.001) and slightly in the MID group (2.2% ± 3.7%, P < 0.05) by the end of the supplementation period and remained at this level for the following 12 wk. [Hb] and Hbmass were similarly affected, but Hbmass was more closely related to mean corpuscular volume and mean corpuscular hemoglobin than [Hb]. The SID group incorporated 534 ± 127 mg of iron into ferritin and hemoglobin, whereas the MID group incorporated 282 ± 68 mg of iron. V˙O2max increased only in the SID group by 0.20 ± 0.18 L·min (P < 0.05) and was closely related to Hbmass (P < 0.01). Hbmass is a sensitive tool for monitoring recovery from iron deficiency anemia and assessing the effectiveness of iron supplementation in individuals with severe or moderate iron deficiency.

Increased Erythrocyte Count on Top of Bone Marrow Histology but not Serum EPO Level or JAK2 Mutation Load Discriminates between JAK2V617F Mutated Essential Thrombocythemia and Polycythemia Vera

Increased Erythrocyte Count on Top of Bone Marrow Histology but not Serum EPO Level or JAK2 Mutation Load Discriminates between JAK2V617F Mutated Essential Thrombocythemia and Polycythemia Vera