Hematology and clinical chemistry values in pregnant Wistar Hannover rats compared with nonmated controls

Liberati, Teresa A.; Sansone, Sandra R.; Feuston, Maureen H.

doi:10.1111/j.1939-165x.2004.tb00352.x

Cited by 43 publications

(34 citation statements)

References 22 publications

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“…As this article was being prepared, Mathur and colleagues reported similar results in their mouse polycythemia model with a pyridone containing tetracyclic JAK inhibitor (35), indicating that chronic therapy with JAK2 inhibitors might be useful in controlling RBC count and extramedullary hematopoiesis in patients suffering from PV. Of note, in both mice and rats, NVP-BSK805 treatment led to an elevation of platelet count beyond the upper limit of the reference interval (36). Although rhEpo administration on its own led to a slightly elevated platelet count in mice, in agreement with an earlier report (29), the increase in platelet count was also seen in animals that were given the JAK2 inhibitor without receiving rhEpo injections.…”

Section: Discussionsupporting

confidence: 79%

Potent and Selective Inhibition of Polycythemia by the Quinoxaline JAK2 Inhibitor NVP-BSK805

Baffert

Régnier²,

Pover³

et al. 2010

Molecular Cancer Therapeutics

109

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The recent discovery of an acquired activating point mutation in JAK2, substituting valine at amino acid position 617 for phenylalanine, has greatly improved our understanding of the molecular mechanism underlying chronic myeloproliferative neoplasms. Strikingly, the JAK2 V617F mutation is found in nearly all patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia and primary myelofibrosis. Thus, JAK2 represents a promising target for the treatment of myeloproliferative neoplasms and considerable efforts are ongoing to discover and develop inhibitors of the kinase. Here, we report potent inhibition of JAK2 V617F and JAK2 wild-type enzymes by a novel substituted quinoxaline, NVP-BSK805, which acts in an ATP-competitive manner. Within the JAK family, NVP-BSK805 displays more than 20-fold selectivity towards JAK2 in vitro, as well as excellent selectivity in broader kinase profiling. The compound blunts constitutive STAT5 phosphorylation in JAK2 V617F-bearing cells, with concomitant suppression of cell proliferation and induction of apoptosis. In vivo, NVP-BSK805 exhibited good oral bioavailability and a long half-life. The inhibitor was efficacious in suppressing leukemic cell spreading and splenomegaly in a Ba/F3 JAK2 V617F cell-driven mouse mechanistic model. Furthermore, NVP-BSK805 potently suppressed recombinant human erythropoietin-induced polycythemia and extramedullary erythropoiesis in mice and rats. Mol Cancer Ther; 9(7); 1945-55. ©2010 AACR.

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Section: Discussionsupporting

confidence: 79%

Potent and Selective Inhibition of Polycythemia by the Quinoxaline JAK2 Inhibitor NVP-BSK805

Baffert

Régnier²,

Pover³

et al. 2010

Molecular Cancer Therapeutics

109

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“…Among many reports concerning elevated glucose concentrations during gestation, there are some which demonstrate a progressive fall of glucose in the second half of rat pregnancy (Liberati et al, 2004). Similarly to the latter results, in our studies the serum glucose concentration during pregnancy was unchanged in early pregnancy but diminished on day 18 and slightly decreased after delivery.…”

Section: Discussionsupporting

confidence: 75%

The effect of a phytoestrogen, genistein, on the hormonal and metabolic status of pregnant rats

Nogowski¹,

Szkudelska²,

Szkudelski³

et al. 2006

J. Anim. Feed Sci.

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Genistein, a plant-derived compound, is a phytoestrogen and has a quite well-documented effect on carbohydrate and lipid metabolism in animals. Data is lacking, however, about the influence of this compound when the level of endogenous oestrogens is high, for example in pregnancy. The aim of the performed experiment was to investigate the effect of dietary genistein (100 mg/kg of feed) on some blood hormone concentrations and metabolic parameters in pregnant rats. Two groups of pregnant Wistar rats were used: the animals in one group were fed a diet without genistein and in the other, a genistein-supplemented diet. Animals from both groups were sacrificed on day 13 or 18 of gestation or on the first day after delivery. Additionally, one group of control non-pregnant rats was fed a diet without genistein and used to compare with pregnant rats. The blood sera, livers and skeletal muscles of animals were collected and stored (-80 °C) until analysis.Genistein caused a substantial decrease of the serum leptin concentration on day 18 of gestation and of leptin and ACTH concentrations on the first day after delivery. The serum insulin, glucagon and corticosterone concentrations remained unaffected by genistein. The tested compound did not influence serum glucose, triglycerides, free fatty acids, cholesterol or liver and muscle glycogen, triglycerides and cholesterol. These results suggest that genistein, despite its well-described oestrogenic potency, can not manifest its action during pregnancy because of high levels of endogenous oestrogens.

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“…Increased reticulocyte concentrations have been observed in Sprague-Dawley (Papworth and Clubb 1995) and Wistar Hannover rats (Liberati, Sansone, and Feuston 2004). Similar observations have been reported in New Zealand white rabbits (Wells et al 1999).…”

Section: Anne Provencher Bolliger Pregnancy/gestationsupporting

confidence: 74%

“…Platelet reactivity may be increased in normal pregnant women, even if platelet number is decreased (Vincelot et al 2001). PLT are increased in pregnant rats (Liberati, Sansone, and Feuston 2004;Kim et al 2000) and at the beginning of gestation in New Zealand white rabbits, followed by a decrease at the end of the gestation period (Kim et al 2002;Wells et al 1999). Total white blood cell (WBC) concentrations are elevated, compared to prepregnancy levels in rats, rabbits, and dogs, as well as in women (Kim et al 2000;Kim et al 2002;Liberati, Sansone, and Feuston 2004;Mims and Prchal 2010;Weinberg et al 1983;Wells et al 1999).…”

Section: Anne Provencher Bolliger Pregnancy/gestationmentioning

confidence: 99%

“…Changes in RBC survival also appear during pregnancy, including reduced erythrocyte life span due to an ''emergency hematopoiesis'' response to elevated EPO levels (Lurie and Mamet 2000). The nonproportional increase of plasma volume versus RBC mass creates the characteristic ''relative physiological anemia of pregnancy'' observed in women and laboratory animals (Johnston, Kustritz, and Olson 2001;Kim et al 2000;Kim et al 2002;Liberati, Sansone, and Feuston 2004;Mims and Prchal 2010;Papworth and Clubb 1995;Weinberg et al 1983;Wells et al 1999;Yoshida, Ohtoh, Cho, Honjo, et al 1988).…”

Section: Anne Provencher Bolliger Pregnancy/gestationmentioning

confidence: 99%

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Nontraditional Applications in Clinical Pathology

Jordan

Tripathi

et al. 2014

Toxicol Pathol

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Most published reviews of preclinical toxicological clinical pathology focus on the fundamental aspects of hematology, clinical chemistry, coagulation, and urinalysis in routine toxicology animal species, for example, rats, mice, dogs, and nonhuman primates. The objective of this continuing education course was to present and discuss contemporary examples of nonroutine applications of clinical pathology endpoints used in the drug development setting. Area experts discussed bone turnover markers of laboratory animal species, clinical pathology of pregnant and growing laboratory animals, clinical pathology of nonroutine laboratory animal species, and unique applications of the Siemens Advia 1 hematology analyzer. This article is a summary based on a presentation given at the 31st Annual Symposium of the Society of Toxicologic Pathology, during the Continuing Education Course titled ''Nontraditional Applications of Clinical Pathology in Drug Discovery and Preclinical Toxicology.''

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Hematology and clinical chemistry values in pregnant Wistar Hannover rats compared with nonmated controls

Cited by 43 publications

References 22 publications

Potent and Selective Inhibition of Polycythemia by the Quinoxaline JAK2 Inhibitor NVP-BSK805

Potent and Selective Inhibition of Polycythemia by the Quinoxaline JAK2 Inhibitor NVP-BSK805

The effect of a phytoestrogen, genistein, on the hormonal and metabolic status of pregnant rats

Nontraditional Applications in Clinical Pathology

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