Biocides in the Hospital Environment: Application and Tolerance Development.

Hospital-acquired infections are a rising problem with consequences for patients, hospitals, and health care workers. Biocides can be employed to prevent these infections, contributing to eliminate or reduce microorganisms' concentrations at the hospital environment. These antimicrobials belong to several groups, each with distinct characteristics that need to be taken into account in their selection for specific applications. Moreover, their activity is influenced by many factors, such as compound concentration and the presence of organic matter. This article aims to review some of the chemical biocides available for hospital infection control, as well as the main factors that influence their efficacy and promote susceptibility decreases, with the purpose to contribute for reducing misusage and consequently for preventing the development of resistance to these antimicrobials.

Mechanisms of Antibiotic and Biocide Resistance That Contribute to Pseudomonas aeruginosa Persistence in the Hospital Environment.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for multiple hospital- and community-acquired infections, both in human and veterinary medicine. P. aeruginosa persistence in clinical settings is worrisome and is a result of its remarkable flexibility and adaptability. This species exhibits several characteristics that allow it to thrive under different environmental conditions, including the ability to colonize inert materials such as medical equipment and hospital surfaces. P. aeruginosa presents several intrinsic mechanisms of defense that allow it to survive external aggressions, but it is also able to develop strategies and evolve into multiple phenotypes to persevere, which include antimicrobial-tolerant strains, persister cells, and biofilms. Currently, these emergent pathogenic strains are a worldwide problem and a major concern. Biocides are frequently used as a complementary/combination strategy to control the dissemination of P. aeruginosa-resistant strains; however, tolerance to commonly used biocides has also already been reported, representing an impediment to the effective elimination of this important pathogen from clinical settings. This review focuses on the characteristics of P. aeruginosa responsible for its persistence in hospital environments, including those associated with its antibiotic and biocide resistance ability.

Epidemiologic Factors Supporting Triage of Infected Dog Patients Admitted to a Veterinary Hospital Biological Isolation and Containment Unit.

The teaching hospital of the Faculty of Veterinary Medicine at the University of Lisbon hosts a Biological Isolation and Containment Unit (BICU) for the hospitalization of both confirmed and suspected animals of an infectious disease. This study targets the BICU dog population to identify and characterize the most frequent infectious diseases recorded in a 7-year period. Several epidemiologic factors were analyzed for their significance to triage infected cases. During the study period, 534 dogs were admitted, of which 263 (49.3%) had a confirmed infectious disease diagnosis: parvovirosis (49.4%; n = 130); leptospirosis (21.7%; n = 57); multidrug-resistant (MDR) bacterial infection; (10.6%; n = 28), and canine distemper (9.9%; n = 26). Several potential risk factors for these diseases were identified: age under 2 years old (p < 0.001), incomplete vaccination for parvovirosis (p < 0.001), age ≥ 10 years old (p < 0.001), and the presence of concomitant disorders for MDR-infected cases (p = 0.03). Logistic regression models were constructed to classify cases and controls. The sensitivity and specificity estimates were very high (>0.83) for parvovirosis, MDR, and distemper infections. A lower sensitivity (0.77) was obtained for identifying cases with leptospirosis. In conclusion, infectious diseases are frequent, hence, it is essential to decrease their occurrence through effective preventive measures such as vaccination. The constructed logistic models can also help in triaging admitted dogs with a potential infectious disease.

Rabbit derived VL single-domains as promising scaffolds to generate antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not found in the human or mouse. Thus, to develop a new generation of ADCs, we explored the potential of rabbit-derived VL-single-domain antibody scaffolds (sdAbs) to selectively conjugate a payload to Cys80. Hence, a rabbit sdAb library directed towards canine non-Hodgkin lymphoma (cNHL) was subjected to in vitro and in vivo phage display. This allowed the identification of several highly specific VL-sdAbs, including C5, which specifically target cNHL cells in vitro and present promising in vivo tumor uptake. C5 was selected for SN-38 site-selective payload conjugation through its exposed free Cys80 to generate a stable and homogenous C5-DAB-SN-38. C5-DAB-SN-38 exhibited potent cytotoxicity activity against cNHL cells while inhibiting DNA-TopoI activity. Overall, our strategy validates a platform to develop a novel class of ADCs that combines the benefits of rabbit VL-sdAb scaffolds and the canine lymphoma model as a powerful framework for clinically translation of novel therapeutics for cancer.

Diagnostic approach and grading scheme for canine allergic conjunctivitis.

BACKGROUND: In humans, allergic conjunctivitis is a well described disease. In contrast, allergic conjunctivitis has not received much attention from the veterinary community so far. Canine allergic conjunctivitis (cAC) is one of the possible manifestations associated with canine atopic dermatitis (cAD), being often underdiagnosed and undertreated. Our aim is to contribute to disease characterization and clinical stagingfor cAC severity. RESULTS: A retrospective observational study including 122 dogs that underwent a complete ophthalmological and dermatological examinations and diagnosed with allergic conjunctivitis was conducted. A total of six ophthalmic clinical signs were considered for disease characterization and clinical staging: conjunctival hyperemia, chemosis, ocular pruritus, epiphora, seromucoid to mucopurulent discharge and keratitis, classified from 0 (absent) to 3 (severe). Scores comprised between 1-5 were considered mild, 6-10 moderate and 11-18 severe. The majority of dogs (64%) presented with moderate cAC followed by 24% of mild stages and only 12% of severe presentations. The severity of allergic conjunctivitis was not correlated to sex or age at the time of diagnosis and all presented with a bilateral form of the disease. Chemosis (84%), hyperemia (83%) and ocular pruritus (79%) was observed in 55% of the cases. Seromucoid to mucopurulent discharge (62%) and epiphora (69%) were less frequent, with keratitis being the least encountered clinical sign (15%). The degree of keratitis showed a positive correlation with both severity and chronicity of cAC (rho = 0.21-0.29, p ≤ 0.02)). Severity of cAD and cAD were not significantly correlated (p-value = 0.4). DISCUSSION AND CONCLUSION: The triad hyperemia, chemosis and ocular pruritus, already known in human medicine to be a reliable way of diagnosing human allergic conjunctivitis, also proved to be important in cAC Mild forms of the disease may pass unnoticed, ocular pruritus being hard to assess in canine patients.The proposed standardized diagnostic approach and novel grading scheme for cAC may be of value for both veterinary ophthalmologists and dermatologists, as well as general practitioners.

Enterococcus Virulence and Resistant Traits Associated with Its Permanence in the Hospital Environment.

Enterococcus are opportunistic pathogens that have been gaining importance in the clinical setting, especially in terms of hospital-acquired infections. This problem has mainly been associated with the fact that these bacteria are able to present intrinsic and extrinsic resistance to different classes of antibiotics, with a great deal of importance being attributed to vancomycin-resistant enterococci. However, other aspects, such as the expression of different virulence factors including biofilm-forming ability, and its capacity of trading genetic information, makes this bacterial genus more capable of surviving harsh environmental conditions. All these characteristics, associated with some reports of decreased susceptibility to some biocides, all described in this literary review, allow enterococci to present a longer survival ability in the hospital environment, consequently giving them more opportunities to disseminate in these settings and be responsible for difficult-to-treat infections.

Characterization of the canine CD20 as a therapeutic target for comparative passive immunotherapy.

Anti-CD20 therapies have revolutionized the treatment of B-cell malignancies. Despite these advances, relapsed and refractory disease remains a major treatment challenge. The optimization of CD20-targeted immunotherapies is considered a promising strategy to improve current therapies. However, research has been limited by the scarcity of preclinical models that recapitulate the complex interaction between the immune system and cancers. The addition of the canine lymphoma (cNHL) model in the development of anti-CD20 therapies may provide a clinically relevant approach for the translation of improved immunotherapies. Still, an anti-CD20 therapy for cNHL has not been established stressing the need of a comprehensive target characterization. Herein, we performed an in-depth characterization on canine CD20 mRNA transcript and protein expression in a cNHL biobank and demonstrated a canine CD20 overexpression in B-cell lymphoma samples. Moreover, CD20 gene sequencing analysis identified six amino acid differences in patient samples (C77Y, L147F, I159M, L198V, A201T and G273E). Finally, we reported the use of a novel strategy for the generation of anti-CD20 mAbs, with human and canine cross-reactivity, by exploring our rabbit derived single-domain antibody platform. Overall, these results support the rationale of using CD20 as a target for veterinary settings and the development of novel therapeutics and immunodiagnostics.

Immunotherapeutic Strategies for Canine Lymphoma: Changing the Odds Against Non-Hodgkin Lymphoma.

The new era of immune-oncology has brought complexities and challenges that emphasize the need to identify new strategies and models to develop successful and cost-effective therapies. The inclusion of a canine model in the drug development of cancer immunotherapies is being widely recognized as a valid solution to overcome several hurdles associated with conventional preclinical models. Driven by the success of immunotherapies in the treatment of human non-Hodgkin lymphoma (NHL) and by the remarkable similarities of canine NHL to its human counterpart, canine NHL has been one of the main focus of comparative research. Under the present review, we summarize a general overview of the challenges and prospects of today's cancer immunotherapies and the role that comparative medicine might play in solving the limitations brought by this rapidly expanding field. The state of art of both human and canine NHL and the rationale behind the use of the canine model to bridge the translational gap between murine preclinical studies and human clinical trials are addressed. Finally, a review of currently available immunotherapies for canine NHL is described, highlighting the potential of these therapeutic options.

Evaluation of a Biocide Used in the Biological Isolation and Containment Unit of a Veterinary Teaching Hospital.

Hospital-acquired infections (HAIs) are a rising problem worldwide, and the best way of coping with them is through infection tracking and surveillance systems, combined with prevention strategies, namely efficient disinfection protocols, that employ various biocides. However, increasing reports about reductions in biocide susceptibility and the development of cross-resistance to antimicrobials emphasize the need for identifying the factors influencing biocide efficiency. In this study, 29 bacterial isolates (n = 3 E. coli, n = 2 Pseudomonas spp., n = 23 Enterococcus spp., and n = 1 Staphylococcus pseudintermedius), obtained from environmental samples collected from the Biological Isolation and Containment Unit (BICU), of the Veterinary Teaching Hospital of the Faculty of Veterinary Medicine, University of Lisbon, were tested in order to determine their antimicrobial susceptibility to various antibiotics. Thirteen of these isolates were further selected in order to determine their antimicrobial susceptibility to Virkon™ S, with and without the presence of organic matter. Afterward, seven of these isolates were incubated in the presence of sub-lethal concentrations of this formulation and, subsequently, new susceptibility profiles were determined. Fourteen of the 29 isolates (48.3%) were classified as multidrug resistant, all previously identified as enterococci. Concerning Virkon™ S's susceptibility, the Minimal Bactericidal Concentration (MBC) of this biocide regarding all isolates was at least eight times lower than the concentration regularly used, when no organic matter was present. However, when organic matter was added, MBC values rose up to 23 times. After exposure to sub-lethal concentrations of Virkon™ S, four enterococci presented a phenotypical change regarding antimicrobial susceptibility towards gentamicin. Virkon™ S also resulted in higher MBC values, up to 1.5 times, in the presence of low concentrations of organic matter, but no rise in these values was observed in assays without interfering substance. Virkon™ S seemed to be an efficient formulation in eliminating all bacteria isolates isolated from the BICU. However, organic matter could represent a hindrance to this ability, which emphasizes the importance of sanitization before disinfection procedures. The changes seen in antimicrobial susceptibility could be explained by a general stress-induced response promoted by the sub-lethal levels of Virkon™ S. Additionally, when no organic matter was present, a decrease in susceptibility to this biocide seemed to be non-existent.

A 5-year retrospective study of canine and feline patients referred to an isolation unit for infectious diseases.

BACKGROUND: Referral of cases is becoming more and more frequent in companion animal practice. The Infectious Diseases Isolation Unit (IDIU) admits first opinion, second opinion and referred patients with a confirmed infectious disease (ID) or a clinically suspected ID that is awaiting laboratory diagnosis. The primary aims of this study were to describe the annual number and characteristics of patients referred to the IDIU and identify the most frequent IDs in referred dogs and cats. A secondary aim was to investigate possible differences in the length of the hospitalisation and the clinical outcome among referred cases and those admitted to the IDIU after first and second opinion appointments. METHODS: A retrospective study was carried out on patients hospitalised at the unit over 5 years from 9th October 2013 to 31st December 2018. RESULTS: The study population consisted of 365 dogs and 515 cats to give a total of 880 patients hospitalised at the IDIU from October 2013 to December 2018. Among the 96 referred dogs, parvovirosis (37.7%) and leptospirosis (31.1%) were the most frequent IDs. Feline upper respiratory tract infection (38.2%) and feline leukaemia virus infections (36.4%) were the main causes in the 80 referred cats. Worrying noncompliance rates of dog (51.0%) and cat (52.5%) vaccination schedules were identified. The analysis of the length of hospitalisation in the three groups of patients was not statistically different. In both animal species there were statistically significant higher clinical discharge rates on the first opinion patients' group in comparison to referred patients and the second opinion group. CONCLUSIONS: Parvovirosis and leptospirosis in dogs and upper respiratory disease and feline leukaemia virus infection in cats were the most common diagnoses for patients admitted to the IDIU, reinforcing the need for accurate vaccination. Discharge rates results pinpoint the need for timely accurate reference.

Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance.

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug's encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

Detection and modeling of anti-Leptospira IgG prevalence in cats from Lisbon area and its correlation to retroviral infections, lifestyle, clinical and hematologic changes.

Leptospirosis is a zoonosis of global importance caused by Leptospira species. Rodents are the main reservoirs, known to shed the bacteria in urine, thus contaminating water and soil and infecting other animals and people. Leptospirosis has been re-emerging in both developing and developed countries including Europe. It has been hypothesized that cats could be asymptomatic carriers of Leptospira. This study aims to evaluate cats' exposure to Leptospira in Lisbon, Portugal, by measuring IgG titres and correlating them with possible factors that may increase the risk of exposure in urban cats. Two hundred and forty-three samples were collected from the biobank. An ELISA test followed by a seroprevalence analysis using a finite mixture model was performed to detect and measure anti-Leptospira IgG antibodies titres. In parallel, a survey was conducted to identify possible risk factors for seropositivity. According to the ELISA test protocol, only twenty-three cats (9.5%; 95% CI =(6.1%;13.9%)) could be considered as seropositive to Leptospira antigens. However, when the same data were analysed by the best different mixture models, one hundred and forty-four cats (59.3%; 95%CI = (52.8%; 65.5%)) could be classified as intermediate and high antibody responders to Leptospira antigens. Seropositivity to Feline Immunodeficiency Virus infection (FIV) was found to be the only significant risk factor associated with anti-Leptospira IgG antibodies. In conclusion, the present studies raises the possibility of a higher exposure of cats to Leptospira than previously thought due to the identification of a subpopulation of cats with intermediate antibody levels.

Selected cytokine expression in dogs with alergic conjunctivitis: Correlation with disease activity.

INTRODUCTION: Canine allergic conjunctivitis (cAC) is described as the most frequent ocular manifestation associated with canine atopic dermatitis (cAD). OBJECTIVES: Clinical and immunological characterization of cAD through IL-6, TNF-α and IL-12 mRNA expression quantification in canine conjunctivae. PROCEDURES: Twenty client-owned dogs with both cAC and cAD and twenty-one healthy controls were enrolled and clinician assessed CADESI-04 and grade of ocular signs were calculated. Conjunctival biopsies were performed on all animals and relative quantification of the interleukins mRNA expression performed by qRT-PCR. The correlation between cytokine gene expression and cAC score was evaluated, as well as CADESI-04 values. RESULTS: The qRT-PCR showed a significant gene upregulation of respectively 291.48 (p = 1.306e-09) and 4.85 (p = .00033) folds on IL-6 and IL-12 in dogs with allergic conjunctivitis compared to the control group. Regarding the average expression of TNF-α there were no statistical significant differences between both groups (p = .18). Higher cAC scores were associated with enhanced gene expression of TNF-α and IL-12. No correlation was found between the cytokine gene expression levels and the CADESI-04 values. CONCLUSION: An increase of IL6 and IL12 in cAC was found in the studied population. These two cytokines may be potential immunotherapy targets cAC classification.

Canine multicentric lymphoma exhibits systemic and intratumoral cytokine dysregulation.

Non-Hodgkin Lymphoma (NHL) is among the most common neoplasias in dogs and humans. Owing to remarkable similarities with its human counterpart, the canine lymphoma (cNHL) model has been proposed as a powerful framework for rapid and clinically relevant translation of novel immunotherapies. However, the establishment of cNHL as a predictive preclinical model has been hampered by the limited characterization of the canine immune system. Cytokines are key players of the interaction between tumor and its microenvironment. In human NHL, multiple cytokines have been linked to the development of lymphoma and are relevant biomarkers for treatment response and prognosis. In contrast, few studies have investigated cytokines in cNHL. Within this context, this study aimed to investigate cytokine regulation in cNHL. A multicentric cNHL biobank was successfully constructed. Cytokine mRNA profiles in tumor tissue and circulating PBMC were analyzed by qRT-PCR and compared to a healthy control group. Specific primers were used to evaluate Th1, Th2 and Th17 responses. Systemic cytokine concentrations were measured using a commercial canine multiplex assay which included IL-2, IL6, IL-10 and TNF-α, and compared to a healthy control group. Our results demonstrated a dysregulation of cytokine mRNA expression, representative of the tumor microenvironment and systemic response in cNHL. Intratumoral cytokine response revealed a significant downregulation of humoral and Th1 responses. The systemic response demonstrated a distinct mRNA pattern, however immunosuppression also prevailed. Cytokine serum quantification showed a significant increase of IL-10 concentration in cNHL. Significant differences in hematological parameters were described and a correlation between IL-6 protein serum levels and neutrophil count was shown. Finally, data analysis demonstrated that baseline pretreatment IFN-γ tissue mRNA levels were correlated to survival outcome, predicting a favorable response to chemotherapy. Altogether, these results revealed that cNHL presents a local and systemic dysregulation in cytokine response. By confirming and extending previous research, our work contributed for the evaluation of potential cytokine candidates for diagnostic, prognostic purposes and therapeutic intervention, therefore adding value to comparative oncology.

Establishment of a bioluminescent canine B-cell lymphoma xenograft model for monitoring tumor progression and treatment response in preclinical studies.

Canine diffuse large B-cell lymphoma (DLBCL) is one of the most common cancers in dogs which shares remarkable similarities with its human counterpart, making the dog an excellent model for the investigation of novel therapeutic agents. However, the integration of canine lymphoma in comparative studies has been limited due in part to the lack of suitable xenograft mouse models for preclinical studies. To overcome these limitations, we established and characterized a localized subcutaneous bioluminescent canine DLBCL xenograft mouse model. The canine CLBL-1 cell line stably expressing the luciferase and green fluorescent protein reporters was generated and used to establish the xenograft tumor model. A pilot study was first conducted with three different cell densities (0.1×10(6), 0.5×10(6) and 1×10(6) cells) in SCID mice. All mice presented homogeneous tumor induction within eight days after subcutaneous injection, with a 100% engraftment efficiency and no significant differences were observed among groups. The tumors were highly aggressive and localized at the site of inoculation and reproduced histological features and immunophenotype consistent with canine DLBCL. Importantly, xenograft tumors were detected and quantified by bioluminescent imaging. To assess response to therapy, a therapeutic study with a histone deacetylase inhibitor, panobinostat, was performed. The results demonstrated that panobinostat (20 mg/kg) efficiently inhibited tumor growth and that bioluminescent imaging allowed the monitorization and quantification of tumor response to therapy. In summary, this study provides a bioluminescence canine DLBCL model that offers high engraftment efficiency, preservation of tumor features, and noninvasive monitoring of tumor progression, validating the model as a promising preclinical tool for both veterinary and human medicine.

Evaluation of the humoral immune response induced by vaccination for canine distemper and parvovirus: a pilot study.

BACKGROUND: Canine Distemper Virus (CDV) and Canine Parvovirus (CPV) lead to infections with high mortality rates in dogs. These viruses affect unvaccinated dogs or dogs with incomplete vaccination protocols. Vaccination plays an important role in reducing death rates, preventing clinical cases and controlling the spread of virus However, the efficacy of vaccination might be affected by different factors including vaccine scheduling and the neutralization of the vaccine targets by maternal antibodies. In face of these factors, the main goals of this study are (i) to investigate the antibody responses of puppies undergoing different primary vaccination protocols against CPV and CDV and (ii) to estimate the time until seroreversion in adult dogs unvaccinated for at least 3 years. RESULTS: Antibody protection against CDV and CPV was evaluated in a total of 20 dogs: 5 puppies that initiated immunization at 6 weeks after birth (group A), 8 animals that started vaccination between 8 and 12 weeks of age (group B), and 7 adult dogs that have not been vaccinated for at least 3 years (group C). Blood samples were collected from each animal, with 3 to 4 weeks apart. Antibody responses were measured using indirect ELISA. In the second immunization point, no significant differences were found between the seroconversion of groups A and B for each viral infection (p = 0.81 and 0.20 for CDV and CPV, respectively). In the third immunization, there was evidence for a shorter time to achieve a protective titer against CPV in group B when compared to group A (p = 0.015). Similar evidence was not found for CDV (p-value = 0.41). In Group C, the average time until seroveversion was estimated at 2.86 years and 7.63 years for CDV and CPV, respectively. CONCLUSION: Vaccine response to CDV and CPV is specific in each individual. Effective immune protection in primary vaccination depends mainly on the initial titer of maternal antibodies acquired by the neonate. Other factors such as environmental exposure, immunization schedules and immune system activity influence the duration of immunity in adult dogs. The variability found reinforces the need to determine individual humoral immunity levels in order to assess vaccine efficacy.

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.

Effects of buprenorphine in the adrenal, thyroid, and cytokine intra-operative responses in a rat model (Rattus norvegicus): a preliminary study.

OBJECTIVES: Buprenorphine is a common analgesic in experimental research, due to effectiveness and having few side-effects, including a limited influence in the immune and endocrine systems. However, how buprenorphine affects cytokine levels and the adrenal and thyroid response during general anesthesia and surgery is incompletely understood. This study aimed to assess whether buprenorphine modulated significantly those responses in rats submitted to general anesthesia, mechanical ventilation, and surgical insertion of intravascular catheters. MATERIALS AND METHODS: Animals were anesthetized with isoflurane, mechanically ventilated, and surgically instrumented for carotid artery and the femoral vein catheter placement. The test group (n=16), received buprenorphine subcutaneously before surgery, whereas the control group (n=16) received normal saline. Blood sampling to determine plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CS), total thyroxine (TT4), total triiodothyronine (TT3), thyroid-stimulating hormone (TSH), TNF-α, IL6, IL10, TNF-α, IL6, and IL10 mRNA was performed at 10 min after completion of all surgical procedures and at 90, 150, 240, and 300 min thereafter, with the animals still anesthetized and with mechanical ventilation. RESULTS: Buprenorphine-treated animals had higher levels of ACTH, CS, and TT4 at several time points (P<0.05) and TSH and TT3 at all-time points (P<0.05). They also had increased IL10, TNF-α, and IL10 mRNA levels. CONCLUSION: In this model, buprenorphine significantly modulated the intra-operative cytokine and endocrine response to anesthesia, mechanical ventilation, and surgical placement of intravascular catheters. The mechanism and significance of these findings remain undetermined. Researchers should be aware of these effects when considering the use of buprenorphine for analgesic purposes.

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.