Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the  common receptor. In the present work, we have delimited tissueprotective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58 -82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.cognition ͉ cytoprotection ͉ excitotoxicity ͉ ischemia-reperfusion injury ͉ wound healing
Dirofilaria immitis is the causative agent of heartworm disease in North America. The adult nematodes are typically found in the pulmonary arteries leading to respiratory, cardiac and systemic illness. In this report, the authors describe an aberrant migration of adult D immitis associated with fibrinous lesions in the peritoneum of a dog. The nematode was recovered during routine ovariohysterectomy. Examination of the organism revealed that the anterior end of the nematode contained several insignificant cranial papillae and no lips while the caudal region contained two rows of papillae. Histological examination demonstrated coelomyarian musculature and prominent lateral internal cuticular ridges. Subsequent amplification of a region of the 16S rRNA gene confirmed the authors’ diagnosis of D immitis. Diagnosis of nematode parasites often heavily relies on the location of the worm and the identity of the host. This case highlights the use of integrating morphological, histopathological and molecular data in order to identify an aberrantly migrating nematode which is important for diagnostic, public health and epidemiological purposes.
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