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JCI Insight Sep 2022Increased red cell distribution width (RDW), which measures erythrocyte mean corpuscular volume (MCV) variability (anisocytosis), has been linked to early mortality in...
Increased red cell distribution width (RDW), which measures erythrocyte mean corpuscular volume (MCV) variability (anisocytosis), has been linked to early mortality in many diseases and in older adults through unknown mechanisms. Hypoxic stress has been proposed as a potential mechanism. However, experimental models to investigate the link between increased RDW and reduced survival are lacking. Here, we show that lifelong hypobaric hypoxia (~10% O2) increased erythrocyte numbers, hemoglobin, and RDW, while reducing longevity in male mice. Compound heterozygous knockout (hKO) mutations in succinate dehydrogenase (Sdh; mitochondrial complex II) genes Sdhb, Sdhc, and Sdhd reduced Sdh subunit protein levels, reduced RDW, and increased healthy life span compared with WT mice in chronic hypoxia. RDW-SD, a direct measure of MCV variability, and the SD of MCV showed the most statistically significant reductions in Sdh hKO mice. Tissue metabolomic profiling of 147 common metabolites showed the largest increase in succinate with elevated succinate/fumarate and succinate/oxoglutarate (2-ketoglutarate) ratios in Sdh hKO mice. These results demonstrate that mitochondrial complex II level is an underlying determinant of both RDW and healthy life span in hypoxia and suggest that therapeutic targeting of Sdh might reduce high RDW-associated clinical mortality in hypoxic diseases.
Topics: Animals; Erythrocyte Indices; Hypoxia; Longevity; Male; Mice; Succinate Dehydrogenase; Succinates
PubMed: 35881479
DOI: 10.1172/jci.insight.158737 -
Journal of Clinical Medicine Jan 2023Hematocrit, a commonly used hematological indicator, is a simple and easily applicable test. As a marker of anisocytosis and anemia, it indicates the percentage of blood...
Hematocrit, a commonly used hematological indicator, is a simple and easily applicable test. As a marker of anisocytosis and anemia, it indicates the percentage of blood cells per unit volume of whole blood. This study aimed to evaluate the association between the level of the hematocrit at admission and preoperative deep vein thrombosis (DVT) in hip fractures of older people. We collected the demographic and clinical characteristics of patients with geriatric hip fractures between 1 January 2015, and 30 September 2019, at the largest trauma center in northwestern China. Doppler ultrasonography was used to diagnose DVT. The correlation between hematocrit levels at admission and preoperative DVT was assessed using linear and nonlinear multivariate logistic regression, according to the adjusted model. All analyzes were performed using EmpowerStats and R software. In total, 1840 patients were included in this study, of which 587 patients (32%) had preoperative DVT. The mean hematocrit level was 34.44 ± 5.64 vol%. Linear multivariate logistic regression models showed that admission hematocrit levels were associated with preoperative DVT (OR = 0.97, 95% CI: 0.95−0.99; p = 0.0019) after adjustment for confounding factors. However, the linear association was unstable, and nonlinearity was identified. An admission hematocrit level of 33.5 vol% was an inflection point for the prediction. Admission hematocrit levels <33.5 vol% were not associated with preoperative DVT (OR = 1.00, 95% CI: 0.97−1.04, p = 0.8230), whereas admission hematocrit levels >33.5 vol% were associated with preoperative DVT (OR = 0.94, 95% CI: 25 0.91−0.97, p = 0.0006). Hematocrit levels at admission were nonlinearly associated with preoperative DVT, and hematocrit at admission was a risk factor for preoperative DVT. However, the severity of a low hematocrit was not associated with preoperative DVT when the hematocrit was <33.5 vol%.
PubMed: 36615152
DOI: 10.3390/jcm12010353 -
Leukemia & Lymphoma Dec 2019
Comparative Study
Topics: Adult; Aged; Aged, 80 and over; Erythrocyte Indices; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Polycythemia; Polycythemia Vera; Prognosis; Retrospective Studies; Time Factors; Young Adult
PubMed: 31190587
DOI: 10.1080/10428194.2019.1622701 -
PLoS Pathogens May 2022Tick-borne Anaplasma species are obligate, intracellular, bacterial pathogens that cause important diseases globally in people, agricultural animals, and dogs. Targeted...
Tick-borne Anaplasma species are obligate, intracellular, bacterial pathogens that cause important diseases globally in people, agricultural animals, and dogs. Targeted mutagenesis methods are yet to be developed to define genes essential for these pathogens. In addition, vaccines conferring protection against diseases caused by Anaplasma species are not available. Here, we describe a targeted mutagenesis method for deletion of the phage head-to-tail connector protein (phtcp) gene in Anaplasma marginale. The mutant did not cause disease and exhibited attenuated growth in its natural host (cattle). We then assessed its ability to confer protection against wild-type A. marginale infection challenge. Additionally, we compared vaccine protection with the mutant to that of whole cell A. marginale inactivated antigens as a vaccine (WCAV) candidate. Upon infection challenge, non-vaccinated control cattle developed severe disease, with an average 57% drop in packed cell volume (PCV) between days 26-31 post infection, an 11% peak in erythrocytic infection, and apparent anisocytosis. Conversely, following challenge, all animals receiving the live mutant did not develop clinical signs or anemia, or erythrocyte infection. In contrast, the WCAV vaccinees developed similar disease as the non-vaccinees following A. marginale infection, though the peak erythrocyte infection reduced to 6% and the PCV dropped 43%. This is the first study describing targeted mutagenesis and its application in determining in vivo virulence and vaccine development for an Anaplasma species pathogen. This study will pave the way for similar research in related Anaplasma pathogens impacting multiple hosts.
Topics: Anaplasma; Anaplasma marginale; Anaplasmosis; Animals; Cattle; Cattle Diseases; Dogs; Humans; Mutagenesis; Vaccine Development; Virulence
PubMed: 35576225
DOI: 10.1371/journal.ppat.1010540 -
Biomeditsinskaia Khimiia Nov 2023Hypoxia is accompanied by changes in metabolism and cell functioning. Erythrocyte hemoglobin can be involved in adaptation to hypoxia by acting as an oxygen sensor,...
Hypoxia is accompanied by changes in metabolism and cell functioning. Erythrocyte hemoglobin can be involved in adaptation to hypoxia by acting as an oxygen sensor, providing a link between oxygen content and blood circulation. The mechanisms providing this function have not been completely established. The purpose of this study was to evaluate the effect of the gasotransmitter nitric oxide on the structural and functional organization of erythrocytes under conditions of hypoxia/reoxygenation. NO participated in adaptive reactions under hypoxia/reoxygenation conditions by changing hemoglobin conformation, followed by changes in hemoprotein spectral characteristics and hemoglobin affinity to oxygen together with increasing anisocytosis, volume and cell surface. The increase in intracellular NO concentrations under hypoxic conditions was provided by extracellular fluid nitrites. Molsidomine (a NO donor) induced a higher NO increase without involvement of the nitrite reductase mechanism, it caused an increase in the average erythrocyte volume, anisocytosis, and an increase in the cell surface.
Topics: Humans; Nitric Oxide; Gasotransmitters; Erythrocytes; Hypoxia; Hemoglobins; Nitrites; Oxygen
PubMed: 37937434
DOI: 10.18097/PBMC20236905315 -
Journal of Veterinary Research Jun 2020Although peripheral blood analysis has become increasingly automated, microscopy is the only available method for the diagnosis of anisocytosis and poikilocytosis. The...
INTRODUCTION
Although peripheral blood analysis has become increasingly automated, microscopy is the only available method for the diagnosis of anisocytosis and poikilocytosis. The aims of the study were to compare RBC volume data obtained with two different analysers and by manual assessment of smears and to compare this data between dogs in various stages of heart failure secondary to degenerative mitral valvular (DMV) disease. The impact of diuretic administration on RBC morphology was also assessed.
MATERIAL AND METHODS
Sixty-eight dogs, 56 in different stages of DMV disease and 12 as healthy controls, were studied. Impedance and flow cytometry haematological analyses were performed for each animal. Additionally, two smears were prepared for manual analysis. RBC structure, staining, and size differences were recorded.
RESULTS
There were no significant differences between the blood morphological parameters assessed using haematological analysers nor between dogs receiving diuretic treatment and those not treated. Based on the manual smear, significantly higher erythrocyte anisocytosis was observed in the dogs with symptomatic DMV disease than in the control group.
CONCLUSION
Haematological analysers based on impedance and flow cytometry provide reliable and comparable morphological results in dogs with heart failure. However, microscopic assessment of blood smears is a more reliable tool to detect erythrocyte anisocytosis.
PubMed: 32587922
DOI: 10.2478/jvetres-2020-0043 -
Annals of Medicine and Surgery (2012) Dec 2022Secondary thrombocytosis, also known as reactive thrombocytosis, is defined as an abnormal increase in platelet count as a result of another underlying medical or...
INTRODUCTION
Secondary thrombocytosis, also known as reactive thrombocytosis, is defined as an abnormal increase in platelet count as a result of another underlying medical or surgical condition. Once the medical cause of reactive thrombocytosis was determined, it could be treated. In this case, supportive treatment with no iron supplements for anemia and infection improved the case condition rapidly.
CASE PRESENTATION
we report a 20 years old Sudanese female who presented with high-grade fever, right iliac fossa pain, hyper pigmented macules on the tongue and a past history of undiagnosed anemia. Laboratory results showed platelets = 1007 × 10^3/μl, hemoglobin = 3.5 g/dl with low MCV, total WBC was also high = 14.9 × 10^3/μl. Peripheral blood picture showed anisocytosis and poikilocytosis, microcytic hypochromic RBCs associated with target cells, pencil cells, teardrops cells and polychromies cells and with leukocytosis and very high platelets in the film. Abdominal ultrasound showed evidence of pelvic inflammatory disease. After receiving supportive treatment, antibiotics and 3 units of blood the patient showed remarkable improvement and reduction in platelet count.
DISCUSSION
We discuss the mechanism of the reactive thrombocytosis state and the variable treatment options when accompanied with iron deficiency anemia.
CONCLUSION
Reactive thrombocytosis with extreme platelet count should always be considered in patients presented with severe iron deficiency anemia and infection. In this case report the high platelet count was reversed successfully after commencing antibiotics and blood transfusion although of the poor patient compliance and the poor investigations were obtained from the patient.
PubMed: 36582913
DOI: 10.1016/j.amsu.2022.104927 -
BMC Veterinary Research Jul 2021Serious disease outbreaks in cattle are usually associated with blood pathogens. This study aims to detect blood pathogens namely Theileria species, Anaplasma species,...
Molecular detection of Theileria species, Anaplasma species, Candidatus Mycoplasma haemobos, Trypanosoma evansi and first evidence of Theileria sinensis-associated bovine anaemia in crossbred Kedah-Kelantan x Brahman cattle.
BACKGROUND
Serious disease outbreaks in cattle are usually associated with blood pathogens. This study aims to detect blood pathogens namely Theileria species, Anaplasma species, Candidatus Mycoplasma haemobos and Trypanosoma evansi, and determine their phylogenetic relationships and haemato-biochemical abnormalities in naturally infected cattle.
METHODS
Molecular analysis was achieved by PCR amplification and sequencing of PCR amplicons of 18SrRNA gene of Theileria species, 16SrRNA genes of Anaplasma and Mycoplasma species, MPSP genes of T. orientalis and T. sinensis, MSP4 gene of A. marginale, 16SrRNA gene of Candidatus Mycoplasma haemobos, and RoTat1.2 VSG gene of Trypanosoma evansi, in sixty-one (61) clinically ill Kedah-Kelantan x Brahman cattle in Pahang, Malaysia.
RESULTS
A total of 44 (72.13%) cattle were infected with more than one blood pathogen. Theileria species was the blood pathogen with the highest molecular detection rate (72.13, 95% CI 59.83-81.81%). Nucleotide blast analyses of all sequences demonstrated high degree of molecular similarity (98-100%) in comparison with their respective reference sequences. Analysis of 18SrRNA gene sequences of Theileria species and 16SrRNA gene sequences of Anaplasma species revealed Theileria sinensis and Anaplasma platys respectively as additional species detected in these cattle. MPSP-PCR analysis was conducted for further confirmation of T. sinensis. The blood picture of eight infected cattle groups revealed poikilocytosis, anisocytosis, rouleaux formation and degenerative left shift. High mean erythrocyte fragility values were common in infected cattle groups. Anaemia of the macrocytic normochromic type and spherocytes were observed in the T. evansi and Anaplasma platys + Theileria sinensis double species co-infected cattle group. Normocytic normochromic anaemia was observed in the T. sinensis infected cattle group. Significant (p < 0.05) increases in serum liver and kidney parameters, total protein, globulin, total and unconjugated bilirubin and decreased albumin values were observed in the T. evansi infected cattle when compared to clinically healthy cattle.
CONCLUSION
We present the first evidence of Theileria sinensis-associated bovine anaemia (TSABA) in Malaysian cattle. Because of the high occurrence of bovine theileriosis and detection of A. platys, there is an urgent need for appropriate preventive and control measures against these blood pathogens.
Topics: Anaplasma; Anaplasmosis; Anemia; Animals; Cattle; Cattle Diseases; Female; Malaysia; Male; Mycoplasma; Mycoplasma Infections; Theileria; Theileriasis; Trypanosoma; Trypanosomiasis
PubMed: 34275459
DOI: 10.1186/s12917-021-02902-0 -
Veterinary and Comparative Oncology Sep 2019A cell line named FB-LCH01, derived from a dog diagnosed with Langerhans cell histiocytosis (LCH), was established and characterized. FB-LCH01 had C-shaped nucleoli,...
A cell line named FB-LCH01, derived from a dog diagnosed with Langerhans cell histiocytosis (LCH), was established and characterized. FB-LCH01 had C-shaped nucleoli, characterized by modal chromosome aberrations. The original tumour cells as well as established FB-LCH01 cells were immunopositive for human leukocyte antigen-DR, Iba-1 and E-cadherin, and immunonegative for CD163 and CD204, suggesting Langerhans cell origin. Furthermore, the characteristics of FB-LCH01 were compared with those of two canine histiocytic sarcoma cell lines (PWC-HS01 and FCR-HS02) established previously. Expression of E-cadherin was detected only in FB-LCH01, but not in PWC-HS01 and FCR-HS02. All (n = 9) the severe combined immunodeficiency mice inoculated with the FB-LCH01 cells developed subcutaneous tumour masses after 3 weeks. Eight of nine mice also developed metastatic lesions in the lymph nodes (8/8; 100%), lung (5/8; 62.5%), stomach (5/8; 62.5%), heart (4/8; 50%), pancreas (4/8; 50%), kidney (3/8; 37.5%), skin (3/8; 37.5%) and bone marrow (1/8; 12.5%). Tumour cells were pleomorphic and round- to polygonal-shaped with prominent anisocytosis and anisokaryosis. The xenotransplanted tumour cells maintained the immunohistochemical features of the original tumour with persistent E-cadherin expression at injection site and some visceral organs. In conclusion, the established cell line as well as the mice xenotransplant model in this study reflect the nature of canine LCH and may serve as promising models for investigating the patho-tumorigenesis and therapy of the disease.
Topics: Animals; Cell Culture Techniques; Cell Line, Tumor; Disease Models, Animal; Dog Diseases; Dogs; Female; Histiocytosis, Langerhans-Cell; Mice; Mice, SCID; Neoplasms, Experimental; Organizational Case Studies
PubMed: 30884050
DOI: 10.1111/vco.12476 -
Scientific Reports Nov 2020Tilapia lake virus (TiLV) causes high mortality and high economic losses in tilapines. We describe an experimental challenge study focusing on early post challenge...
Tilapia lake virus (TiLV) causes high mortality and high economic losses in tilapines. We describe an experimental challenge study focusing on early post challenge innate immune responses. Nile tilapia (Oreochromis niloticus) were infected with 10 TCID/mL TiLV intraperitoneally, followed by virus quantification, histopathology and gene expression analysis in target (brain/liver) and lymphoid (spleen/headkidney) organs at 3, 7, 12, 17, and 34 days post challenge (dpc). Onset of mortality was from 21 dpc, and cumulative mortality was 38.5% by 34 dpc. Liver and kidney histopathology developed over the period 3-17 dpc, characterized by anisocytosis, anisokaryocytosis, and formation of multinucleated hepatocytes. Viral loads were highest at early time (3 dpc) in liver, spleen and kidney, declining towards 34 dpc. In brain, viral titer peaked 17 dpc. Innate sensors, TLRs 3/7 were inversely correlated with virus titer in brain and headkidney, and IFN-ß and Mx showed a similar pattern. All organs showed increased mRNA IgM expression over the course of infection. Overall, high virus titers downplay innate responses, and an increase is seen when viral titers decline. In silico modeling found that TiLV segments 4, 5 and 10 carry nucleolar localization signals. Anti-viral effects of TiLV facilitate production of virus at early stage of infection.
Topics: Animals; Antibodies, Viral; Brain; Cichlids; Fish Diseases; Gene Expression Regulation; Hepatocytes; Host-Pathogen Interactions; Immunity, Innate; Immunoglobulin M; Interferon-beta; Kidney; Liver; Negative-Sense RNA Viruses; Spleen; Survival Analysis; Time Factors; Toll-Like Receptor 3; Toll-Like Receptor 7
PubMed: 33230226
DOI: 10.1038/s41598-020-73781-y