Biomedical subjects

Alessandra Sfacteria

Publications and source records attributed to Alessandra Sfacteria.

10 recordsLinked to original sources

PubMed2005

Carcinoma of the submandibular salivary glands with multiple metastases in a cat.

A 9-year-old neutered male domestic shorthair cat was presented because of coughing, dysphagia, and prostration. Examination revealed firm bilateral anterocervical swellings extensively adhered to the surrounding tissues. Anisocoria with left-side miosis was also evident. X-ray and ultrasound examinations along with a fine-needle aspiration biopsy were performed. Slides were stained with May-Grünwald Giemsa, and a diagnosis of salivary gland carcinoma was made. At surgery, the tumor was found to involve both submandibular salivary glands as well as adjacent lymph nodes and surrounding tissues. The cat was euthanized and necropsy was performed. The majority of tissues and organs examined histologically, including mandibular and retropharyngeal lymph nodes, soft palate, laryngopharynx and lungs, contained neoplastic cells whose appearance was consistent with adenocarcinoma. Bilateral salivary adenocarcinoma has not previously been reported in cats, and extensive metastases are rare.

Animals↗

PubMed2005

Erythropoietin and erythropoietin receptor expression after experimental spinal cord injury encourages therapy by exogenous erythropoietin.

OBJECTIVE: Erythropoietin (EPO) is a pleiotropic cytokine originally identified for its role in erythropoiesis. Recent studies have demonstrated that EPO and its receptor (EPO-R) are expressed in the central nervous system, where EPO exerts neuroprotective functions. Because the expression of the EPO and EPO-R network is poorly investigated in the central nervous system, the aim of the present study was to investigate whether the resident EPO and EPO-R network is activated in the injured nervous system. METHODS: A well-standardized model of compressive spinal cord injury in rats was used. EPO and EPO-R expression was determined by immunohistochemical analysis at 8 hours and at 2, 8, and 14 days in the spinal cord of injured and noninjured rats. RESULTS: In noninjured spinal cord, weak immunohistochemical expression of EPO and EPO-R was observed in neuronal and glial cells as well as in endothelial and ependymal cells. In injured rats, a marked increase of expression of EPO and EPO-R was observed in neurons, vascular endothelium, and glial cells at 8 hours after injury, peaking at 8 days, after which it gradually decreased. Two weeks after injury, EPO immunoreactivity was scarcely detected in neurons, whereas glial cells and vascular endothelium expressed strong EPO-R immunoreactivity. CONCLUSION: These observations suggest that the local EPO and EPO-R system is markedly engaged in the early stages after nervous tissue injury. The reduction in EPO immunoexpression and the increase in EPO-R staining strongly support the possible usefulness of a therapeutic approach based on exogenous EPO administration.

Aneurysm↗

PubMed2004

Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor.

The cytokine erythropoietin (Epo) is tissue-protective in preclinical models of ischemic, traumatic, toxic, and inflammatory injuries. We have recently characterized Epo derivatives that do not bind to the Epo receptor (EpoR) yet are tissue-protective. For example, carbamylated Epo (CEpo) does not stimulate erythropoiesis, yet it prevents tissue injury in a wide variety of in vivo and in vitro models. These observations suggest that another receptor is responsible for the tissue-protective actions of Epo. Notably, prior investigation suggests that EpoR physically interacts with the common beta receptor (betacR), the signal-transducing subunit shared by the granulocyte-macrophage colony stimulating factor, and the IL-3 and IL-5 receptors. However, because betacR knockout mice exhibit normal erythrocyte maturation, betacR is not required for erythropoiesis. We hypothesized that betacR in combination with the EpoR expressed by nonhematopoietic cells constitutes a tissue-protective receptor. In support of this hypothesis, membrane proteins prepared from rat brain, heart, liver, or kidney were greatly enriched in EpoR after passage over either Epo or CEpo columns but covalently bound in a complex with betacR. Further, antibodies against EpoR coimmunoprecipitated betacR from membranes prepared from neuronal-like P-19 cells that respond to Epo-induced tissue protection. Immunocytochemical studies of spinal cord neurons and cardiomyocytes protected by Epo demonstrated cellular colocalization of Epo betacR and EpoR. Finally, as predicted by the hypothesis, neither Epo nor CEpo was active in cardiomyocyte or spinal cord injury models performed in the betacR knockout mouse. These data support the concept that EpoR and betacR comprise a tissue-protective heteroreceptor.

Animals↗

PubMed2004

Derivatives of erythropoietin that are tissue protective but not erythropoietic.

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

Animals↗

PubMed2004

Early correction of cell cycle perturbations predicts the immunological response to therapy in HIV-infected patients.

OBJECTIVE: To determine whether changes in the indices of HIV-associated cell cycle dysregulation (i.e., increased expression of cyclin B1 and abnormal nucleolar structure) may predict the level of immunological reconstitution in HIV-infected patients treated with highly active antiretroviral therapy (HAART). METHODS: Cross-sectional and longitudinal analysis of viral load, CD4 T cell counts, cyclin B1 expression, and AgNOR number and area of distribution in 30 HIV-infected patients who were studied before and up to 6 months after initiation of HAART. RESULTS: In HIV-infected individuals, the level of cell cycle dysregulation correlated with the type of response to HAART. While low levels of dysregulation were present in patients with complete (both virological and immunological) response to HAART, high levels were present in HAART-treated patients with limited CD4 T cell increases despite persistent viral suppression (immunological non-responders). Importantly, the level of correction of cell cycle dysregulation after 60 days of therapy predicted the level of immune reconstitution after 6 months. CONCLUSION: These observations suggest that correction of cell cycle dysregulation predicts a good immunological response to HAART and that sequential analysis of cell cycle dysregulation might help to identify patients that could benefit from alternative, immune-based interventions in addition to standard HAART.

Antiretroviral Therapy, Highly Active↗

PubMed2004

Erythropoietin as a tissue-protective cytokine in brain injury: what do we know and where do we go?

In the 10 years since neurotrophic activity was first reported for erythropoietin (EPO), a broad understanding of its multiple paracrine/autocrine functions has emerged. Recent studies firmly establish EPO as a multifunctional molecule, typical of the pliotrophic cytokine superfamily of which it is a member. The realization that EPO activates neuroprotection by multiple mechanisms has identified a generalized system of local tissue protection with EPO as a critical component. Here, the authors characterize the biology of the local tissue-protective system, review data that support this concept, and suggest why non-hematopoietic analogues of EPO may be better choices as therapeutics.

Animals↗

PubMed2004

A new computed-assisted technique for experimental sciatic nerve function analysis.

BACKGROUND: Peripheral nerve injury is a well-known experimental tool to evaluate the effect of various neurotrophic substances. Besides histological and electrophysiological techniques, nerve functional status has been assessed by means of the sciatic function index (SFI) and the static sciatic index (SSI). However, these techniques are still based on a complex and old-fashioned apparatus requiring a relatively long time of execution. This study aimed to assess a novel, rapid, computerized method for assessment of SSI in a rat model of sciatic nerve injury. MATERIAL/METHODS: Fourteen rats were used in this study. The left sciatic nerve was exposed and compressed for 2 minutes with an aneurysm clip. Functional evaluation was performed by analysing the footprints of standing rats, comparing the injured to the uninjured limb with the static sciatic index (SSI). For this purpose the rats were placed on a digital scanner and the resulting images were acquired on a personal computer. Analysis was carried out every day after surgery for 21 consecutive days. RESULTS: Two-minute compression of the sciatic nerve produced a major reduction in motor function as assessed by SSI. Improvement was observed by day 7. By day 20, SSI was completely restored. CONCLUSIONS: This technique is simple to use, quick, without expensive technical equipment. It provides good accuracy and precise quantification of the extent of functional loss and recovery after sciatic nerve injury.

Animals↗

PubMed2003

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo.

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin (rhEPO) as a potential neuroprotective therapeutic must be tempered, however, by the knowledge it also enlarges circulating red cell mass and increases platelet aggregability. Here we examined whether erythropoietic and tissue-protective activities of rhEPO might be dissociated by a variation of the molecule. We demonstrate that asialoerythropoietin (asialoEPO), generated by total enzymatic desialylation of rhEPO, possesses a very short plasma half-life and is fully neuroprotective. In marked contrast with rhEPO, this molecule at doses and frequencies at which rhEPO exhibited erythropoiesis, did not increase the hematocrit of mice or rats. AsialoEPO appeared promptly within the cerebrospinal fluid after i.v. administration; intravenously administered radioiodine-labeled asialoEPO bound to neurons within the hippocampus and cortex in a pattern corresponding to the distribution of the EPO receptor. Most importantly, asialoEPO exhibits a broad spectrum of neuroprotective activities, as demonstrated in models of cerebral ischemia, spinal cord compression, and sciatic nerve crush. These data suggest that nonerythropoietic variants of rhEPO can cross the blood-brain barrier and provide neuroprotection.

Animals↗

PubMed2002

Beneficial effects of systemic administration of recombinant human erythropoietin in rabbits subjected to subarachnoid hemorrhage.

Cerebral vasospasm and ischemic damage are important causes of mortality and morbidity in patients affected by aneurysmal subarachnoid hemorrhage (SAH). Recently, i.p. administration of recombinant human erythropoietin (r-Hu-EPO) has been shown to exert a neuroprotective effect during experimental SAH. The present study was conducted to evaluate further the effect of r-Hu-EPO administration after SAH in rabbits on neurological outcome, degree of basilar artery spasm, and magnitude of neuronal ischemic damage. Experimental animals were divided into six groups: group 1 (n = 8), control; group 2 (n = 8), control plus placebo; group 3 (n = 8), control plus r-Hu-EPO; group 4 (n = 8), SAH; group 5 (n = 8), SAH plus placebo; group 6 (n = 8), SAH plus r-Hu-EPO. r-Hu-EPO, at a dose of 1,000 units/kg, and placebo were injected i.p. starting 5 min after inducing SAH and followed by clinical and pathological assessment 72 h later. Systemic administration of r-Hu-EPO produced significant increases in cerebrospinal fluid EPO concentrations (P < 0.001), and reduced vasoconstriction of the basilar artery (P < 0.05), ischemic neuronal damage (P < 0.001), and subsequent neurological deterioration (P < 0.05). These observations suggest that r-Hu-EPO may provide an effective treatment to reduce the post-SAH morbidity.

Animals↗

PubMed2002

Does administration of recombinant human erythropoietin attenuate the increase of S-100 protein observed in cerebrospinal fluid after experimental subarachnoid hemorrhage?

OBJECT: Results of recent studies indicate that erythropoietin (EPO) produces a neuroprotective effect on experimental subarachnoid hemorrhage (SAH). It has been reported that S-100 protein levels increase in cerebrospinal fluid (CSF) after SAH, providing a highly prognostic indication of unfavorable outcome. This study was conducted to validate further the findings of S-100 protein as an index of brain damage and to assess whether treatment with recombinant human EPO (rhEPO) would limit the increase of S-100 protein level in CSF following experimental SAH. METHODS: Thirty-two rabbits were each assigned to one of four groups: Group 1, control; Group 2, SAH; Group 3, SAH plus placebo; and Group 4, SAH plus rhEPO (each group consisted of eight rabbits). The rhEPO and placebo were administered to the rabbits after SAH had been induced, and S-100 protein levels in the CSF of these animals were measured at 24, 48, and 72 hours after the experimental procedure. In each group of animals levels of S-100 protein were compared with the mortality rate, neurological outcome, and neuronal ischemic damage. High S-100 protein levels were found in rabbits in Groups 2 and 3, which exhibited poor neurological status and harbored a high number of damaged cortical neurons. Favorable neurological outcome and significant reductions in total numbers of damaged neurons were observed in animals in Group 4 in which there were significantly lower S-100 protein concentrations compared with animals in Groups 2 and 3 (p < 0.001). CONCLUSIONS: The results of this study support the concept that determination of the S-100 protein level in CSF has prognostic value after SAH. The findings also confirm that rhEPO acts as a neuroprotective agent during experimental SAH.

Animals↗