Haemopoietic and Lymphatic Systems

Greaves, Peter

doi:10.1016/b978-044452771-4/50005-5

Cited by 8 publications

(5 citation statements)

References 345 publications

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“…High concentrations of radioactivity were also associated with EMH sites consistent with putative EPO receptor location (Juul et al 1998), which in the rat include spleen, adrenal gland, liver, lymph nodes, and kidney (Greaves and Faccini 1992; Elmore 2006). EMH, which appropriately occurs in the rat following increased demand or stimulation, is not a normal physiologic or pathophysiologic process that occurs in humans following birth.…”

Section: Discussionmentioning

confidence: 93%

“…The tissues that exhibited high concentrations at one or more time points included blood; the bone marrow (target tissue for pharmacologic effect); highly vascular-ized and lymphatic tissues such as the lung, liver, myocardium, spleen, and choroid plexus; sites of extramedullary hematopoiesis (EMH) in the rat, such as the spleen, adrenal gland, liver, kidney, and lymph nodes (Greaves and Faccini 1992; Elmore 2006); and organs/tissues associated with excretion of peginesatide including the kidney, bladder, and urine.…”

Section: Resultsmentioning

confidence: 99%

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Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats

et al. 2011

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The pharmacokinetics(PK) (absorption, distribution, metabolism, excretion) of peginesatide.a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA), was evaluated in rats. The PK profile was evaluated at 0.1-5 mg·kg−1 IV using unlabeled or [14C]-labeled peginesatide. Mass balance, tissue distribution and metabolism were evaluated following IV administration of 5 mg·kg−1 [14C]-peginesatide, with tissue distribution also evaluated by quantitative whole-body autoradiography (QWBA) following an IV dose of 17 mg·kg−1[14C]-peginesatide.Plasma clearance was slow and elimination was biphasic with unchanged peginesatide representing >90% of the total radioactivity of the total radioactive exposure. Slow uptake of the radiolabeled compound from the vascular compartment into the tissues was observed.Biodistribution to bone marrow and extramedullary hematopoietic sites, and to highly vascularized lymphatic and excretory tissues occurred.A predominant degradation event to occur in vivo was the loss of one PEG chain from the branched PEG moiety to generate mono-PEG.Renal excretion was the primary mechanism (41%) of elimination, with parent molecule (67%) the major moiety excreted.In conclusion, elimination of [14C]-peginesatide-derived radioactivity was extended, retention preferentially occurred at sites of erythropoiesis (bone marrow), and urinary excretion was the primary elimination route.

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Section: Discussionmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats

et al. 2011

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“…37,38 Lymphoid depletion of the thymus was observed in the high-dose females, and microscopic findings of cytoplasmic vacuolation of the adrenal cortex were noted in the males and high-dose group females. The lymphoid cortical depletion of the thymus and adrenal cortex vacuolation were considered to have been responses to stress, 39 although cytoplasmic vacuolation of the adrenal cortex can also occur spontaneously 40 or as the result of pharmacological effects. 41 The overall no effect level for all target organ effects was 100 mg/kg/d.…”

Section: Discussionmentioning

confidence: 99%

Toxicological Assessment of Refined Naphthenic Acids in a Repeated Dose/Developmental Toxicity Screening Test

et al. 2013

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Naphthenic acids (NAs) are primarily cycloaliphatic carboxylic acids with 10 to 16 carbons. To characterize the potential of refined NAs (>70% purity) to cause reproductive and/or developmental effects, Sprague-Dawley rats (12/group) were given oral doses of 100, 300, or 900 mg/kg/d, beginning 14 days prior to mating, then an additional 14 days for males or through lactation day 3 for females (up to 53 days) in a repeated dose/reproductive toxicity test (Organization for Economic Cooperation and Development [OECD] 422). Potential mutagenic effects were assessed using Salmonella (OECD 471) and in in vivo micronucleus tests (OECD 474) using bone marrow taken from treated animals in the screening study described previously. Systemic effects included reduced terminal body weights, increased liver weights, and changes in a number of blood cell parameters. The overall no effect level for all target organ effects was 100 mg/kg/d. In the reproductive/developmental toxicity assessment, there were significant reductions in numbers of live born offspring in groups exposed to 300 and 900 mg/kg/d. The overall no effect level for developmental effects was 100 mg/kg/d. The data from the Salmonella and micronucleus tests provide evidence that refined NAs are not genotoxic.

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“…This diagnosis should be used at the discretion of the pathologist, depending on the study requirements. 58,80 –86…”

Section: Enh Lymphocytes Increasedmentioning

confidence: 99%

Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System

Willard-Mack

Elmore

Hall³

et al. 2019

Toxicol Pathol

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The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative changes in rats and mice. The purpose of this publication is to provide a standardized nomenclature for classifying changes observed in the hematolymphoid organs, including the bone marrow, thymus, spleen, lymph nodes, mucosa-associated lymphoid tissues, and other lymphoid tissues (serosa-associated lymphoid clusters and tertiary lymphoid structures) with color photomicrographs illustrating examples of the lesions. Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. The nomenclature for these organs is divided into 3 terminologies: descriptive, conventional, and enhanced. Three terms are listed for each diagnosis. The rationale for this approach and guidance for its application to toxicologic pathology are described in detail below.

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Haemopoietic and Lymphatic Systems

Cited by 8 publications

References 345 publications

Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats

Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats

Toxicological Assessment of Refined Naphthenic Acids in a Repeated Dose/Developmental Toxicity Screening Test

Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System

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