Solange Gil

Relevance of feline interferon omega for clinical improvement and reduction of concurrent viral excretion in retrovirus infected cats from a rescue shelter.

Abstract Feline Immnunodeficiency (FIV) and Feline Leukemia (FeLV) viruses are common infectious agents in stray cats and shelter environments. Recombinant feline interferon-ω (rFeIFNω) has shown an antiviral action not only against FIV and FeLV but also against herpesvirus (FHV-1) and calicivirus (FCV). Sixteen naturally infected FIV/FeLV cats were followed during rFeIFNω therapy in order to monitor clinical signs and to correlate with excretion of concomitant viruses (FCV, FHV-1, feline coronavirus (FCoV) and parvovirus (FPV)). Cats were submitted to clinical evaluations and concomitant virus excretion assessement. Comparing D0–D65, 10/16 cats improved clinical scores. Of the 10 cats positive for FHV-1 on D0, 4 were negative and 6 reduced viral loads. Of the 11 FCoV positive cats, 9 reduced viral loads. The 13 FCV positive cats and the FPV positive cat were negative on D65. In conclusion, rFeIFNω improves clinical signs and reduces concurrent viral excretion in naturally infected retroviral cats.

Oral Recombinant Feline Interferon-Omega as an alternative immune modulation therapy in FIV positive cats : clinical and laboratory evaluation

Abstract Recombinant-Feline Interferon-Omega (rFeIFN-ω) is an immune-modulator licensed for use subcutaneously in Feline Immunodeficiency virus (FIV) therapy. Despite oral protocols have been suggested, little is known about such use in FIV-infected cats. This study aimed to evaluate the clinical improvement, laboratory findings, concurrent viral excretion and acute phase proteins (APPs) in naturally FIV-infected cats under oral rFeIFN-ω therapy (0.1MU/cat rFeIFN-ω PO, SID, 90days). 11 FIV-positive cats were treated with oral rFeIFN-ω (PO Group). Results were compared to previous data from 7 FIV-positive cats treated with the subcutaneous licensed protocol (SC Group). Initial clinical scores were similar in both groups. Independently of the protocol, rFeIFN-ω induced a significant clinical improvement of treated cats. Concurrent viral excretion and APP’s variation were not significant in the PO Group. Oral rFeIFN-ω can be an effective alternative therapy for FIV-infected cats, being also an option for treatment follow-up in cats submitted to the licensed protocol.

Evaluation of viremia, proviral load and cytokine profile in naturally feline immunodeficiency virus infected cats treated with two different protocols of recombinant feline interferon omega.

Abstract This study assesses viremia, provirus and blood cytokine profile in naturally FIV-infected cats treated with two distinct protocols of interferon omega (rFeIFN-ω). Samples from FIV-cats previously submitted to two single-arm studies were used: 7/18 received the licensed/subcutaneous protocol (SC) while 11/18 were treated orally (PO). Viremia, provirus and blood mRNA expression of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12p40, Interferon-γ and Tumor Necrosis Factor-α were monitored by Real-Time qPCR. Concurrent plasma levels of IL-6, IL-12p40 and IL-4 were assessed by ELISA. IL-6 plasma levels decreased in the SC group (p = 0.031). IL-6 mRNA expression (p = 0.037) decreased in the PO group, albeit not sufficiently to change concurrent plasma levels. Neither viremia nor other measured cytokines changed with therapy. Proviral load increased in the SC group (p = 0.031), which can be justified by a clinically irrelevant increase of lymphocyte count. Independently of the protocol, rFeIFN-ω seems to act on innate immunity by reducing pro-inflammatory stimulus.

Monitoring acute phase proteins in retrovirus infected cats undergoing feline interferon-ω therapy.

Objectives Recombinant feline interferon‐ω therapy is an immunomodulator currently used in the treatment of different retroviral diseases including feline immune deficiency virus and feline leukaemia virus. Although its mechanism of action remains unclear, this drug appears to potentiate the innate response. Acute phase proteins are one of the key components of innate immunity and studies describing their use as a monitoring tool for the immune system in animals undergoing interferon‐ω therapy are lacking. This study aimed to determine whether interferon‐ω therapy influences acute phase protein concentrations namely serum amyloid‐A, α‐1‐glycoprotein and C‐reactive protein. Methods A single‐arm study was performed using 16 cats, living in an animal shelter, naturally infected with retroviruses and subjected to the interferon‐ω therapy licensed protocol. Samples were collected before (D0), during (D10 and D30) and after therapy (D65). Serum amyloid‐A and C‐reactive protein were measured by specific enzyme‐linked immunosorbent assay kits and α‐1‐glycoprotein by single radial immunodiffusion. Results All the acute phase proteins significantly increased in cats undergoing interferon‐ω therapy (D0/D65: P<0·05) Clinical Significance Acute phase proteins appear to be reasonable predictors of innate‐immune stimulation and may be useful in the individual monitoring of naturally retroviral infected cats undergoing interferon‐ω therapy.

Molecular and serological surveillance of canine enteric viruses in stray dogs from Vila do Maio, Cape Verde

BackgroundInfections caused by canine parvovirus, canine distemper virus and canine coronavirus are an important cause of mortality and morbidity in dogs worldwide. Prior to this study, no information was available concerning the incidence and prevalence of these viruses in Cape Verde archipelago.ResultsTo provide information regarding the health status of the canine population in Vila do Maio, Maio Island, Cape Verde, 53 rectal swabs were collected from 53 stray dogs during 2010 and 93 rectal swabs and 88 blood samples were collected from 125 stray dogs in 2011. All rectal swabs (2010 n = 53; 2011 n = 93) were analysed for the presence of canine parvovirus, canine distemper virus and canine coronavirus nucleic acids by quantitative PCR methods. Specific antibodies against canine distemper virus and canine parvovirus were also assessed (2011 n = 88).From the 2010 sampling, 43.3% (23/53) were positive for canine parvovirus DNA, 11.3% (6/53) for canine distemper virus RNA and 1.9% (1/53) for canine coronavirus RNA. In 2011, the prevalence values for canine parvovirus and canine coronavirus were quite similar to those from the previous year, respectively 44.1% (41/93), and 1.1% (1/93), but canine distemper virus was not detected in any of the samples analysed (0%, 0/93). Antibodies against canine parvovirus were detected in 71.6% (63/88) blood samples and the seroprevalence found for canine distemper virus was 51.1% (45/88).ConclusionsThis study discloses the data obtained in a molecular and serological epidemiological surveillance carried out in urban populations of stray and domestic animals. Virus transmission and spreading occurs easily in large dog populations leading to high mortality rates particularly in unvaccinated susceptible animals. In addition, these animals can act as disease reservoirs for wild animal populations by occasional contact. Identification of susceptible wildlife of Maio Island is of upmost importance to evaluate the risk of pathogen spill over from domestic to wild animals in Cape Verde and to evaluate the associated threat to the wild susceptible species.

Effects of etomidate in the adrenal and cytokine responses to hemorrhagic shock in rats

Hemorrhagic shock (HS) induces a compensatory endocrine and cytokine response which aims to restore homeostasis. This response can be modulated by general anesthetics. To our knowledge, no studies have evaluated if etomidate modulates this response in experimental HS. After being premedicated with buprenorphine (0.05 mg/kg subcutaneously), male Wistar rats were anaesthetized with 5% isoflurane and divided into three groups: G1 (control, n = 16), G2 (n = 13), and G3 (n = 14). G2 and G3 were subjected to HS by collecting 30% of their blood volume and resuscitated 90 min later with the collected blood and normal saline, in a 1:3 ratio, respectively. G3 received etomidate (1 mg/kg IV) before HS. Blood gas analysis, adrenocorticotropic hormone (ACTH), corticosterone, and plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and of TNF-α, IL-6, and IL-10 mRNA obtained through real-time polymerase chain reaction (RT-PCR) were measured at 0, 90, 150, and 240 min after HS induction. Compared with G2, etomidate-treated animals had significantly lower corticosterone, PO2, PO2/FiO2, base excess and HCO3, and higher TNF-α, IL-6, IL-10, and TNF-α mRNA levels (P <0.05). Etomidate-treated rats showed impaired adrenal and increased cytokine response to HS and evidence of worse tissue oxygenation and lung dysfunction. Based on these results, and until further studies are performed to confirm if these findings occur in clinical patients, we suggest that etomidate should be used cautiously in HS.

The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives

Type I interferons (IFNs) are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). In HIV infection, it has been shown that IFN therapy limits early viral replication, particularly useful on post-exposure prophylaxis. In veterinary medicine, recombinant feline interferon omega (rFeIFN-ω) was the first interferon licensed for use in cats. Several studies have recently shown that this compound seems to stimulate the innate immunity, decreasing clinical signs and co-infections in naturally FIV-infected cats. More than summarizing the main conclusions about rFeIFN-ω in cats, this review emphasizes the immune-modulation properties of IFN therapy, opening new perspectives for its use in retroviral infections. Either in FIV-infected cats or in HIV individuals, type I IFNs seem to induce an innate immune-modulation and should not be overlooked as a therapeutic option in retroviral infections.

The histone deacetylase inhibitor panobinostat is a potent antitumor agent in canine diffuse large B-cell lymphoma

Non-Hodgkin lymphoma (NHL) is one of the most common causes of cancer-related death in the United States and Europe. Although the outcome of NHL patients has improved over the last years with current therapies, the rate of mortality is still high. A plethora of new drugs is entering clinical development for NHL treatment; however, the approval of new treatments remains low due in part to the paucity of clinically relevant models for validation. Canine lymphoma shares remarkable similarities with its human counterpart, making the dog an excellent animal model to explore novel therapeutic molecules and approaches. Histone deacetylase inhibitors (HDACis) have emerged as a powerful new class of anti-cancer drugs for human therapy. To investigate HDACi antitumor properties on canine diffuse large B-cell lymphoma, a panel of seven HDACi compounds (CI-994, panobinostat, SBHA, SAHA, scriptaid, trichostatin A and tubacin) was screened on CLBL-1 canine B-cell lymphoma cell line. Our results demonstrated that all HDACis tested exhibited dose-dependent inhibitory effects on proliferation of CLBL-1 cells, while promoting increased H3 histone acetylation. Amongst all HDACis studied, panobinostat proved to be the most promising compound and was selected for further in vitro and in vivo evaluation. Panobinostat cytotoxicity was linked to H3 histone and α-tubulin acetylation, and to apoptosis induction. Importantly, panobinostat efficiently inhibited CLBL-1 xenograft tumor growth, and strongly induced acetylation of H3 histone and apoptosis in vivo. In conclusion, these results provide new data validating HDACis and, especially, panobinostat as a novel anti-cancer therapy for veterinary applications, while contributing to comparative oncology.