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

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 (0.1 MU/cat rFeIFN-ω PO, SID, 90 days). 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.     

Dietary fish oil and flaxseed oil suppress inflammation and immunity in cats

Type-I interferons (IFNs) are cytokines that have non-specific antiviral activity, participating mostly in innate defense mechanisms. Their administration has been proposed to treat several viral and immunomediated diseases as an immunomodulatory therapy. Due to its availability, recombinant human interferon-alpha (rHuIFN-α) has been studied in relation to feline retrovirosis, both in vitro and in vivo. However, IFNs are species-specific and antibodies have been shown to develop in response to the high rHuIFN-α doses necessary for an effective therapy. A recombinant feline IFN has been developed, which has been characterized as interferon-omega (rFeIFN-ω), designed to overcome these problems. Nonetheless, very few studies have been undertaken to evaluate its efficacy in cats naturally infected with FIV or FeLV. In an initial study, we here demonstrated that rFeIFN-ω can dramatically improve the clinical condition of infected cats, and induce improvement of hematologic parameters. Minor changes or no change was observed for hypergammaglobulinemia, CD4/CD8 ratio, proviral load, viremia and RT activity, suggesting that the overall effect of IFN was on innate immunity. More studies are needed in order to better understand its in vivo mechanisms.     

Association of calicivirus infection with chronic gingivitis and pharyngitis in cats

Feline calicivirus was isolated from eight often cats with chronic stomatitis but not from 10 healthy cats kept under similar conditions. Tests for feline leukaemia viral antigen failed to detect evidence of this infection. The age of affected cats ranged from 1.5 to 11 years with a mean of 5.7 years. Treatment with corticosteroids, megestrol acetate and tooth extraction resulted in clinical improvement but in some cases the condition recurred when treatment was finished.     

Comparisons between cats with normal and increased fPLI concentrations in cats diagnosed with inflammatory bowel disease

Objectives : The aim of this study was to compare age, serum albumin and cobalamin concentrations, serum alanine amino transferase and alkaline phosphatase activities, feline inflammatory bowel disease clinical disease activity index, pancreatic ultrasound findings, intestinal histopathology scores, outcome, treatment and clinical response between cats diagnosed with inflammatory bowel disease with normal or increased serum feline pancreatic lipase immunoreactivity concentrations. Methods : Medical records for 23 cats diagnosed with inflammatory bowel disease and with serum feline pancreatic lipase immunoreactivity concentrations available were reviewed. Three groups were compared; cats with serum feline pancreatic lipase immunoreactivity concentrations 2·0 to 6·8 µg/l (group A), 6·9 to 11·9 µg/l (group B) and ≥12·0 µg/l (group C). Results : Sixteen of the 23 cats had increased serum feline pancreatic lipase immunoreactivity concentrations; 9 cats in group B and 7 cats in group C. The remaining seven cats were in group A. Cats with serum feline pancreatic lipase immunoreactivity concentrations ≥12·0 µg/l had significantly lower median serum albumin and cobalamin concentrations. No significant differences were identified between the three groups for age, serum alanine amino transferase and alkaline phosphatase activities, feline inflammatory bowel disease clinical disease activity index, pancreatic ultrasound findings, intestinal histopathology scores, clinical outcome, treatment or clinical response. Clinical Significance : Hypoalbuminaemia and hypocobalaminaemia were more frequently observed in cats with serum feline pancreatic lipase immunoreactivity concentrations ≥12·0 µg/l.     

Prevalence of feline calicivirus, feline leukaemia virus and antibodies to FIV in cats with chronic stomatitis

The prevalence of feline calicivirus (FCV), feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) antibodies were assessed in 78 British and 18 North American household cats with chronic stomatitis and in appropriate controls. In British cats, FCV was significantly (P less than 0.005) more prevalent in both hospital (92 per cent) and general practice (79 per cent) cases compared to their controls (19 per cent in both cases). A similar difference in prevalence of FCV was noted in North American cats where 50 per cent of cases were positive compared to 0 per cent of controls (P less than 0.01). FeLV prevalence was low in all chronic stomatitis populations. A significantly higher prevalence of antibody to FIV was found in British hospital cases (81 per cent) compared with time-matched controls (16 per cent) (P less than 0.001): a similar rate was found in the general practice cases (75 per cent) for which no controls were available. In the North American sample, FIV antibody status was similar in cases (54 per cent positive) and their age, sex and breed matched controls (50 per cent). The possible role of FCV and FIV in the pathogenesis of feline chronic stomatitis is discussed.     

Studies on the role of feline calicivirus in chronic stomatitis in cats.

Two groups of cats were inoculated oro-nasally with one of two isolates of feline calicivirus (FCV) from clinical cases of chronic stomatitis. All cats developed signs typical of acute FCV infection; namely, ocular and nasal discharge, conjunctivitis, and marked oral ulceration. None of the cats shed virus beyond 28 days. Seronegative control cats were then infected with a lower dose of one isolate, but again only acute signs were seen and no carriers produced. The original cats were then re-infected with the heterologous isolate. As before, only signs of acute disease were seen, but the range of clinical signs and severity was reduced. Virus shedding patterns in one group were similar to those seen originally, but in the other the duration was reduced. No chronic stomatitis developed over the 10 months of the study. Serum virus neutralising and serum and salivary class specific immunoglobulin responses were investigated. Although long-term carriers were not induced, no relationship between cessation of virus shedding in an individual animal and systemic and local antibody responses was seen.     

The use of oral cyclosporin to treat feline dermatoses: a retrospective analysis of 23 cases

Limited information is available regarding the use of cyclosporin A (CsA) for the treatment of feline dermatoses. The aim of this retrospective study was therefore to describe the efficacy of CsA for the therapy of eosinophilic granuloma (EG), eosinophilic plaque, indolent ulcer, linear granulomas, idiopathic pruritus and stomatitis. A computer search for feline dermatological cases treated with CsA between 1999 and 2004 was performed. Based on history, clinical signs and laboratory diagnostic tests, it was then possible to divide cases into three groups and to select 23 cats. Seven cats had one or more of the following conditions: EG, eosinophilic plaque, indolent ulcer and/or linear granuloma (group A); eight cats had idiopathic pruritus (group B) and eight cats had plasmacytic stomatitis (group C). Doses ranged from 5.8 to 13.3 mg kg(-1) oral CsA. All cats were monitored, with complete serum blood analysis and physical examination, monthly for a minimum of 6 months. Response to therapy was scored (severity of lesions and pruritus) with a 0-10 visual analogue scale at each visit (day 0, day, 30, day 60, day 90). All cats in groups A and B were cured and were maintained on alternate day therapy. In group C, 4/8 patients went into remission, while remaining cats have a fair to good improvement. Routine haematological and biochemical examination failed to reveal abnormalities related to CsA administration.     

Tissue distribution of virus replication in cats experimentally infected with distinct feline calicivirus isolates.

Four specific pathogen-free (SPF) cats were each inoculated with one of two genetically and antigenically well characterized feline caliciviruses originally isolated from cats with acute respiratory disease (FCV-KS100/2), or with chronic stomatitis (FCV-KS20). Two cats of each group were euthanized at day 10 post infection and two cats at day 28. No clear differences between the clinical disease induced by the two isolates could be observed, and no apparent differences in the tissue spectrum were seen between day 10 and 28. No persistent virus shedding was observed over the 4-week period of this experiment.     

Prevalence of feline leukaemia virus and antibodies to feline immunodeficiency virus in cats in the United Kingdom

A representative sample of the pet cat population of the United Kingdom was surveyed. Blood samples from 1204 sick and 1007 healthy cats of known breed, age and sex were tested for antibodies to feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). The prevalence of FIV was 19 per cent in sick cats and 6 per cent in healthy cats, and the prevalence of FeLV was 18 per cent in sick cats and 5 per cent in healthy cats; both infections were more common in domestic cats than in pedigree cats. Feline immunodeficiency virus was more prevalent in older cats but FeLV was more prevalent in younger cats. There was no difference between the prevalence of FeLV in male and female cats but male cats were more likely to be infected with FIV than female cats. No interaction was demonstrated between FIV and FeLV infections. Of the cats which were in contact with FIV in households with more than one cat, 21 per cent had seroconverted. The prevalence of FeLV viraemia in cats in contact with FeLV was 14 per cent. The clinical signs associated with FIV were pyrexia, gingivitis/stomatitis and respiratory signs, and with FeLV, pyrexia and anaemia. It was concluded that both viruses were significant causes of disease, and that the cats most likely to be infected with FIV were older, free-roaming male cats and for FeLV, younger, free-roaming cats.     

Bioavailability of morphine,methadone, hydromorphone,and oxymorphone following buccal administration in cats

Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time–concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean ± SE (range) bioavailability was 36.6 ± 5.2 (12.7–49.5), 44.2 ± 7.9 (18.7–70.5), 22.4 ± 6.9 (6.4–43.4), and 18.8 ± 2.0 (12.9–23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone.     

Effect of glipizide on serum insulin and glucose concentrations in healthy cats.

With the recent identification of non-insulin-dependent diabetes mellitus (NIDDM) in cats, new possibilities arise for the use of oral hypoglycaemic agents in the treatment of feline NIDDM, similar to their use in humans. To identify the future applicability of the oral hypoglycaemic agent, glipizide, in the treatment of feline NIDDM, its effects on serum insulin and glucose concentrations in healthy cats was examined. In addition, adverse effects seen clinically or on bloodwork following short-term use of the drug were looked for. Serum insulin and glucose concentrations were evaluated after the oral administration of 2.5, 5.0 and 10.0 mg glipizide and placebo in 10 healthy cats. For each drug trial, blood was obtained five minutes before, immediately before, and 7.5, 15, 30, 45, 60, 90 and 120 minutes after glipizide or placebo administration. Mean serum insulin concentration increased after glipizide administration, with peak mean serum insulin concentration occurring 15 minutes after administration and declining to baseline by 60 minutes. There was no significant difference in peak mean serum insulin concentration, mean serum insulin concentration at 60 minutes after glipizide administration, or mean total insulin secretion between the three glipizide dosages. Mean serum glucose concentration decreased within 15 minutes of glipizide administration, with the glucose nadir occurring 60 minutes after glipizide administration. Placebo trials showed no significant change in mean serum insulin or glucose concentrations from baseline concentrations.     

Use of two virustatica (AZT, PMEA) in the treatment of FIV and of FeLV seropositive cats with clinical symptoms.

In the present study the therapeutic efficacy and the side effects of two antiretroviral compounds used in human acquired immunodeficiency syndrome (AIDS) research, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine, Retrovir) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), were investigated in the treatment of cats naturally infected with feline immunodeficiency virus (FIV) and cats naturally infected with feline leukemia virus (FeLV). AZT was administered subcutaneously at a dose of 5 mg kg-1 body weight every 12 h and PMEA was administered subcutaneously at a dose of 2.5 mg kg-1 body weight every 12 h during a 3 week hospitalization. The therapeutic efficacy of both compounds was investigated. There was a stronger potency of PMEA than of AZT on the regression of stomatitis in FIV and in FeLV infected cats. In addition, in FIV infection PMEA had a stronger effect on the improvement of the general clinical status. Both antiretroviral compounds were potent agents to improve the immunologic status of FIV infected cats by raising the CD4/CD8 ratio. In FeLV infection PMEA and AZT appeared to reduce antigenemia. The hematological side effects caused by PMEA were severe and stronger than those of AZT. Therefore the advantage of PMEA in clinical and immunologic improvement was diminished by the hematologic disorders, which do not allow long term treatment with this drug in the dose used.     

Determination of serum fPLI concentrations in cats with diabetes mellitus

Diabetes mellitus (DM) is one of the most common feline endocrinopathies. Pancreatitis is a reported cause for poor control of DM in cats; however, its prevalence in diabetic cats is unknown. Measurement of serum feline pancreatic lipase immunoreactivity (fPLI) has been proposed as a sensitive and specific test for the detection of pancreatitis in cats. The aim of this study was to assess fPLI concentrations in diabetic cats and compare these with non-diabetic cats of similar age. Samples from 29 cats with DM and 23 non-diabetic cats were analysed. Serum fPLI concentrations were significantly higher in samples from diabetic cats (P<0.01). A weak association was found between serum fructosamine and fPLI concentrations (R(2)=0.355, P=0.015), but there was no association between fPLI concentrations and the degree of diabetic control. There were no significant differences in reported clinical signs between cats with or without DM regardless of serum fPLI concentration. This is the first study to demonstrate elevated serum fPLI concentrations in cats with DM, suggesting that pancreatitis could be a significant comorbidity in these cats.     

Effects of age and allergen-induced airway inflammation in cats: radiographic and cytologic correlation

Thoracic radiography is an important diagnostic tool for feline respiratory medicine. The aim of this study was (1) to assess age-related changes of thoracic radiographic views in healthy young cats and (2) to test if experimentally-induced bronchial inflammation by inhaling Ascaris suum (AS) allergens leads to radiographic changes after single or repeated exposures. Healthy cats (n=15-30) aged between 6 and 30 months were evaluated. Eight healthy cats and eight AS-sensitised cats, respectively, inhaled sterile saline or allergen. Radiographs were taken 24h before, and 6, 24 and 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed after the last radiographic examination. AS-sensitised cats underwent three further allergen challenges at 3-month intervals. The radiographic evaluation was based on a scoring system considering bronchial, interstitial and alveolar patterns. A significant age-related increase in interstitial and total radiographic score was detected in healthy cats older than 18 months and in healthy cats older than 24 months. Whilst saline inhalation did not affect radiographic scores, a single AS challenge induced significant changes of all scores within 6-24h. A significant positive correlation between radiographic scores and BAL neutrophils and eosinophils was found. Repeated AS challenges did not induce irreversible changes in radiographic scores.     

Humoral immunity in cats infected with feline immunodeficiency virus or leukaemia virus

The humoral antibody responses of 82 domestic cats to the common commensal bacteria Pasteurella multocida and Staphylococcus aureus were measured by an indirect immunofluorescence assay to give a subjective quantification of specific IgG in serum. There was no significant difference in specific serum IgG levels between sick cats which tested antibody-positive to feline immunodeficiency virus or antigen-positive to feline leukaemia virus and sick, virus-negative cats. This finding suggested that there was no change in immune status, as measured by this method, in both feline leukemia and feline immunodeficiency virus infections, although, based on clinical signs shown by the virus-positive cats, overall immunosuppression was indicated. Feline immunodeficiency virus and feline leukemia virus infection may have an effect on cellular immunity, as is the case with human immunodeficiency virus.     

Analgesic efficacy of preoperative administration of meloxicam or butorphanol in onychectomized cats

OBJECTIVE: To determine analgesic efficacy and adverse effects of preemptive administration of meloxicam or butorphanol in cats undergoing onychectomy or onychectomy and neutering. DESIGN: Randomized controlled study. ANIMALS: 64 female and 74 male cats that were 4 to 192 months old and weighed 1.09 to 705 kg (2.4 to 15.5 lb). PROCEDURE: Cats received meloxicam (0.3 mg/kg [0.14 mg/lb], s.c.) or butorphanol (0.4 mg/kg [0.18 mg/lb], s.c.) 15 minutes after premedication and prior to anesthesia. A single blinded observer measured physiologic variables, assigned analgesia and lameness scores, and withdrew blood samples for each cat at baseline and throughout the 24 hours after surgery. Rescue analgesia (butorphanol, 0.4 mg/kg, i.v. or s.c.) or administration of acepromazine (0.025 to 0.05 mg/kg [0.011 to 0.023 mg/lb], i.v.) was allowed. RESULTS: Meloxicam-treated cats were less lame and had lower pain scores. Cortisol concentration was higher at extubation and lower at 1, 5, and 12 hours in the meloxicam-treated cats. Fewer meloxicam-treated cats required rescue analgesia at 3, 5, 12, and 24 hours after extubation. General impression scores were excellent or good in 75% of meloxicam-treated cats and 44% of butorphanol-treated cats. There was no treatment effect on buccal bleeding time; PCV and BUN concentration decreased in both groups, and glucose concentration decreased in meloxicam-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of meloxicam improved analgesia for 24 hours without clinically relevant adverse effects in cats that underwent onychectomy or onychectomy and neutering and provided safe, extended analgesia, compared with butorphanol.     

Iatrogenic hyperadrenocorticism in a cat following a short therapeutic course of methylprednisolone acetate

Iatrogenic hyperadrenocorticism (or iatrogenic Cushing's syndrome) is an adrenal disorder that may result from long-term administration of glucocorticoids for therapeutic purposes, most often given to treat allergic or immune-mediated disorders. Prolonged treatment with synthetic glucocorticoids can suppress hypothalamic corticotrophin releasing hormone and plasma adrenocorticotrophic hormone (ACTH), thus causing a functional inactivity of the adrenal cortex. The result is a clinical syndrome of hyperadrenocorticism but with basal and ACTH-stimulated plasma cortisol concentrations that are consistent with spontaneous hypoadrenocorticism (Addison's disease).Whilst iatrogenic hyperadrenocorticism is relatively frequent in dogs, the diagnosis of iatrogenic hyperadrenocorticism in cats is very uncommon because this species has been found to be remarkably resistant to prolonged administration of glucocorticoids. To the author's knowledge, there are only two published clinical cases of feline iatrogenic Cushing's syndrome. This report describes a case of iatrogenic hyperadrenocorticism in a cat, and shows how normalisation of the adrenal function was achieved with supportive treatment and withdrawal of glucocorticoid administration.     

Cyclooxygenases 1 and 2 inhibition and analgesic efficacy of dipyrone at different doses or meloxicam in cats after ovariohysterectomy

ObjectiveTo evaluate the cyclooxygenases (COX) inhibition, adverse effects and analgesic efficacy of dipyrone or meloxicam in cats undergoing elective ovariohysterectomy.Study designProspective, blinded, randomized, clinical study.AnimalsA total of 30 healthy young cats.MethodsThe cats were randomly assigned to three postoperative groups: D25 (dipyrone 25 mg kg^?1 every 24 hours), D12.5 (dipyrone 12.5 mg kg^?1 every 12 hours) and M (meloxicam 0.1 mg kg^?1 every 24 hours). In the first 24 hours, the drugs were administered intravenously (IV), and then orally for 6 (dipyrone) or 3 days (meloxicam). Prostanoids thromboxane B₂ and prostaglandin E₂ concentrations served as indicators of COX activity and, with physiological variables and pain and sedation scores, were measured for 24 hours after first analgesic administration. Rescue analgesia (tramadol, 2 mg kg^?1 IV) was provided if Glasgow feline composite measure pain scale (CMPS-Feline) ≥5. Laboratory tests included symmetric dimethylarginine and adverse effects were evaluated regularly up to 7 and 10 days after surgery, respectively. Parametric and nonparametric data were analyzed with two-way anova and Kruskal-Wallis tests, respectively (p < 0.05).ResultsIn the first half hour after analgesic administration, COX-1 activity was close to zero and remained significantly lower than before drug administration for 24 hours in all groups. The inhibition of COX-2 activity was significant for 30 minutes in all groups and up to 4 hours in group M. No alterations in laboratory tests or significant adverse effects were observed. Pain scores and need for rescue analgesia did not differ statistically among groups.ConclusionsDipyrone at both doses and meloxicam provided a nonselective inhibition of COX-1 and -2 activities and effective analgesia without causing significant adverse effects or laboratory tests alterations.Clinical relevanceDipyrone at both doses provides equally effective analgesia without causing adverse effects in cats undergoing ovariohysterectomy.     

Use of nociceptive threshold testing in cats in experimental and clinical settings: a qualitative review

ObjectiveThe objective of this study was to review the scientific articles on the use of nociceptive threshold testing (NTT) in cats and to summarize the clinical and experimental applications in this species.Databases usedPertinent literature was searched with PubMed, Scopus, Web of Science, Universitätsbibliothek Basel (swissbib Basel Bern) and Google Scholar. The search was then refined manually based first on article titles and abstracts, and subsequently on full texts.ConclusionsOf the four classical acute nociceptive models used for NTT, thermal and mechanical are most commonly used in cats. Thermal stimulation is applicable in experimental settings and has been used in pharmacodynamics studies assessing feline antinociception. Although mechanical stimulation is currently less used in cats, in the future it might play a role in the evaluation of clinical feline pain. However, the low response reliability after stimulus repetition within a narrow time interval represents a major limitation for the clinical use of mechanical thresholds in this species. Challenges remain when thermal thresholds are used to investigate analgesics that have the potential to affect skin temperature, such as opioids and α2-adrenergic agonists, and when a model of inflammatory pain is reproduced in experimental cats with the purpose of evaluating non-steroidal anti-inflammatory drugs as analgesics.     

Clinical, hematologic, and survival data from cats infected with feline immunodeficiency virus: 42 cases (1983-1988).

A retrospective study of stored feline serum samples was done to determine the infection rate of feline immunodeficiency virus in cats in central Missouri. Infected cats were compared with uninfected cats subjected to the same selection criteria on the basis of signalment, clinical signs, and CBC abnormalities. A significant incidence of virus infection was found in male cats. Neither age nor breed predilection could be identified. Infected cats were more likely to be anemic and leukopenic because of neutropenia. Cellulitis and neoplasia were more common in infected cats. A spectrum of disease severity was seen in infected cats ranging from no clinical signs to signs of severe chronic inflammatory disease. Infected cats were more likely to have clinical disease. Mean survival of infected cats was 24.4 months from the time of diagnosis.