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      Sex-specific reference intervals of hematologic and biochemical analytes in Sprague-Dawley rats using the nonparametric rank percentile method

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          Abstract

          Background

          Hematologic and biochemical analytes of Sprague-Dawley rats are commonly used to determine effects that were induced by treatment and to evaluate organ dysfunction in toxicological safety assessments, but reference intervals have not been well established for these analytes. Reference intervals as presently defined for these analytes in Sprague-Dawley rats have not used internationally recommended statistical method nor stratified by sex. Thus, we aimed to establish sex-specific reference intervals for hematologic and biochemical parameters in Sprague-Dawley rats according to Clinical and Laboratory Standards Institute C28-A3 and American Society for Veterinary Clinical Pathology guideline.

          Methods

          Hematology and biochemistry blood samples were collected from 500 healthy Sprague-Dawley rats (250 males and 250 females) in the control groups. We measured 24 hematologic analytes with the Sysmex XT-2100i analyzer, 9 biochemical analytes with the Olympus AU400 analyzer. We then determined statistically relevant sex partitions and calculated reference intervals, including corresponding 90% confidence intervals, using nonparametric rank percentile method.

          Results

          We observed that most hematologic and biochemical analytes of Sprague-Dawley rats were significantly influenced by sex. Males had higher hemoglobin, hematocrit, red blood cell count, red cell distribution width, mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, neutrophils, lymphocytes, monocytes, percentage of neutrophils, percentage of monocytes, alanine aminotransferase, aspartate aminotransferase, and triglycerides compared to females. Females had higher mean corpuscular hemoglobin concentration, plateletcrit, platelet count, eosinophils, percentage of lymphocytes, percentage of eosinophils, creatinine, glucose, total cholesterol and urea compared to males. Sex partition was required for most hematologic and biochemical analytes in Sprague-Dawley rats. We established sex-specific reference intervals, including corresponding 90% confidence intervals, for Sprague-Dawley rats.

          Conclusions

          Understanding the significant discrepancies in hematologic and biochemical analytes between male and female Sprague-Dawley rats provides important insight into physiological effects in test rats. Establishment of locally sex-specific reference intervals allows a more precise evaluation of animal quality and experimental results of Sprague-Dawley rats in our toxicology safety assessment.

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          The lung is a site of platelet biogenesis and a reservoir for hematopoietic progenitors

          Emma Lefrancais, Guadalupe Ortiz-Muñoz, Axelle Caudrillier … (2017)
          Platelets are critical for hemostasis, thrombosis, and inflammatory responses 1,2 , yet the events leading to mature platelet production remain incompletely understood 3 . The bone marrow (BM) is proposed to be a major site of platelet production although indirect evidence points towards a potential pulmonary contribution to platelet biogenesis 4-7 . By directly imaging the lung microcirculation in mice 8 , we discovered that a large number of megakaryocytes (MKs) circulate through the lungs where they dynamically release platelets. MKs releasing platelets in the lung are of extrapulmonary origin, such as the BM, where we observed large MKs migrating out of the BM space. The lung contribution to platelet biogenesis is substantial with approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature MKs along with hematopoietic progenitors that reside in the extravascular spaces of the lung. Under conditions of thrombocytopenia and relative stem cell deficiency in the BM 9 , these progenitors can migrate out of the lung, repopulate the BM, completely reconstitute blood platelet counts, and contribute to multiple hematopoietic lineages. These results position the lung as a primary site of terminal platelet production and an organ with considerable hematopoietic potential.
          Article 0 comments Cited 426 times – based on 0 reviews     Review now
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            ASVCP reference interval guidelines: determination of de novo reference intervals in veterinary species and other related topics.

            Kristen Friedrichs, Kendal E Harr, Kathy Freeman … (2012)
            Reference intervals (RI) are an integral component of laboratory diagnostic testing and clinical decision-making and represent estimated distributions of reference values (RV) from healthy populations of comparable individuals. Because decisions to pursue diagnoses or initiate treatment are often based on values falling outside RI, the collection and analysis of RV should be approached with diligence. This report is a condensation of the ASVCP 2011 consensus guidelines for determination of de novo RI in veterinary species, which mirror the 2008 Clinical Laboratory and Standards Institute (CLSI) recommendations, but with language and examples specific to veterinary species. Newer topics include robust methods for calculating RI from small sample sizes and procedures for outlier detection adapted to data quality. Because collecting sufficient reference samples is challenging, this document also provides recommendations for determining multicenter RI and for transference and validation of RI from other sources (eg, manufacturers). Advice for use and interpretation of subject-based RI is included, as these RI are an alternative to population-based RI when sample size or inter-individual variation is high. Finally, generation of decision limits, which distinguish between populations according to a predefined query (eg, diseased or non-diseased), is described. Adoption of these guidelines by the entire veterinary community will improve communication and dissemination of expected clinical laboratory values in a variety of animal species and will provide a template for publications on RI. This and other reports from the Quality Assurance and Laboratory Standards (QALS) committee are intended to promote quality laboratory practices in laboratories serving both clinical and research veterinarians. © 2012 American Society for Veterinary Clinical Pathology.
            Article 0 comments Cited 255 times – based on 0 reviews     Review now
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              Gender aspects in type 2 diabetes mellitus and cardiometabolic risk.

              Naveed Sattar (2013)
              Men are well known to have a higher risk than women for cardiovascular disease. In recent years, however, studies show adult men also have higher risk for type 2 diabetes, an observation which has important clinical implications, particularly in the public health arena. This chapter explores the relevant data underlying this observation, examines potential mechanisms including life course changes in insulin resistance and role of adiposity, and discusses relevant clinical implications and solutions. Copyright © 2013. Published by Elsevier Ltd.
              Article 0 comments Cited 81 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Qili He: Role: Data curationRole: Formal analysisRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Guoming Su: Role: Formal analysisRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Keliang Liu:
                ORCID: http://orcid.org/0000-0002-6628-104X
                Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Fangcheng Zhang: Role: InvestigationRole: Methodology
                Yong Jiang: Role: InvestigationRole: Validation
                Jun Gao: Role: InvestigationRole: Resources
                Lida Liu: Role: InvestigationRole: Validation
                Zhongren Jiang: Role: InvestigationRole: Resources
                Minwu Jin: Role: InvestigationRole: Methodology
                Huiping Xie: Role: InvestigationRole: Resources
                Colin Johnson: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 20 December 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 12
                Electronic Location Identifier: e0189837
                Affiliations
                [1 ] Institute of Toxicological Detection, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan, China
                [2 ] Department of Pharmacy and Laboratory, Sichuan Nursing Vocational College, Chengdu, Sichuan, China
                [3 ] Department of Ultrastructural Pathology Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
                Oregon State University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-6628-104X
                Article
                Publisher ID: PONE-D-17-25053
                DOI: 10.1371/journal.pone.0189837
                PMC ID: 5738108
                PubMed ID: 29261747
                SO-VID: edb5e1ce-2147-4a57-a140-f56cda54edd5
                Copyright © © 2017 He et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 3 July 2017
                Date accepted : 1 December 2017
                Page count
                Figures: 6, Tables: 3, Pages: 18
                Funding
                The authors received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Research and analysis methods
                Subject: Experimental organism systems
                Subject: Model organisms
                Subject: Rats
                Subject: Sprague-Dawley rats
                Subject: Research and analysis methods
                Subject: Model organisms
                Subject: Rats
                Subject: Sprague-Dawley rats
                Subject: Research and analysis methods
                Subject: Experimental organism systems
                Subject: Animal models
                Subject: Rats
                Subject: Sprague-Dawley rats
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Eukaryota
                Subject: Animals
                Subject: Vertebrates
                Subject: Amniotes
                Subject: Mammals
                Subject: Rodents
                Subject: Rats
                Subject: Sprague-Dawley rats
                Subject: Medicine and Health Sciences
                Subject: Hematology
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Eukaryota
                Subject: Animals
                Subject: Vertebrates
                Subject: Amniotes
                Subject: Mammals
                Subject: Rodents
                Subject: Research and Analysis Methods
                Subject: Bioassays and Physiological Analysis
                Subject: Biochemical Analysis
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Body Fluids
                Subject: Blood
                Subject: Platelets
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Body Fluids
                Subject: Blood
                Subject: Platelets
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Body Fluids
                Subject: Blood
                Subject: Platelets
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Body Fluids
                Subject: Blood
                Subject: Platelets
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Blood Cells
                Subject: Platelets
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Biomarkers
                Subject: Creatinine
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Blood Cells
                Subject: White Blood Cells
                Subject: Lymphocytes
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Lymphocytes
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Lymphocytes
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Lymphocytes
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Blood Cells
                Subject: White Blood Cells
                Subject: Neutrophils
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Neutrophils
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Neutrophils
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Immune Cells
                Subject: White Blood Cells
                Subject: Neutrophils
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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