piperidines and Cat-Diseases

Non-Helicobacter pylori species (NHPS) are newly emerging bacteria that naturally inhabit birds and mammals apart from humans and rarely cause diseases in humans. In recent years, a rise in the number of cases associated with NHPS infections in humans has been observed. Among them, infections with Helicobacter (H.) canis are sporadic and challenging to recognise clinically. To date, ten cases of H. canis infections in mainly immunocompromised humans have been reported in the literature. Transmission pathway is most likely zoonotic via the faecal-oral route during close contacts with dogs and cats or may result from a contaminated sheep milk intake. No clear guidelines for successful antibiotic regimen are known. Important additional risk factor for infection might be biologic agents and Janus kinase inhibitors (JAKi) used in the treatment of rheumatoid arthritis (RA) and other conditions. Herein we present the first case of H. canis bacteraemia in a RA patient treated with novel JAKi tofacitinib.. A 65-year-old female patient with RA and rituximab-induced hypogammaglobulinemia treated with tofacitinib, methotrexate, and methylprednisolone came to a planned visit in our outpatient rheumatology clinic. She presented with a history of back pain that significantly worsened 2 days before visit. She had numbness and tingling sensation in both legs and muscle weakness. Neurological examination was within a normal range. The patient was afebrile, had no chills, and was haemodynamically stable. She was in close contact with her pet dogs. Laboratory examination showed increased markers of inflammation. She was found to have H. canis bacteraemia with underlying multilevel degenerative lumbar spinal stenosis. Identification of H. canis was performed by MALDI-TOF MS and 16 S rRNA gene sequence analysis of isolate from subcultured positive aerobic blood culture bottles. Antimicrobial susceptibility testing showed low minimum inhibitory concentrations to amoxicillin-clavulanate, cefotaxime, ceftriaxone, meropenem, and gentamicin. She was treated with combined antibiotic regimen (ceftriaxone, doxycycline) for 14 days, which resulted in total remission of the infection.. Clinicians should recognise H. canis infection risk in patients with recent pet exposure and predisposing factors such as immunodeficiency disorders or diseases that demand immunosuppressive drug therapy. A minimum of two weeks of antibiotic therapy is suggested.

Topics: Aged; Animals; Arthritis, Rheumatoid; Bacteremia; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Helicobacter; Humans; Methotrexate; Methylprednisolone; Piperidines; Pyrimidines; Sheep; Treatment Outcome

Recent advances in molecular biology have permitted the identification and characterization of specific abnormalities regarding cell signaling and function in cancer cells. Proteins that are found to be dysregulated in cancer cells can serve as relevant targets for therapeutic intervention. Although there are several approaches to block proteins that contribute to cellular dysfunction, the one most commonly used involves a class of therapeutics called small molecule inhibitors. Such inhibitors work by disrupting critical pathways/processes in cancer cells, thereby preventing their ability to grow and survive.

Topics: Animals; Benzamides; Cat Diseases; Cats; Dog Diseases; Dogs; Indoles; Neoplasms; Piperidines; Protein Kinase Inhibitors; Pyridines; Pyrroles; Thiazoles

Capromorelin is a ghrelin receptor agonist that is FDA approved for appetite stimulation in dogs. The objective of this study was to evaluate the safety of daily oral administration of capromorelin to cats over a range of doses and for an extended period. Two randomized, controlled studies were conducted: in Study 1, cats (n = 6 per group) received placebo or capromorelin at a dose of 9, 15, 30 or 60 mg/kg once daily for 14 days; and in Study 2, cats received capromorelin at 6 mg/kg (n = 8) or placebo (n = 4) once daily for 91 days. Cats were evaluated using clinical observations and clinical pathology test results for both studies, with the addition of postmortem examination in Study 1 and measurements of growth hormone and insulin-like growth factor 1 in Study 2. Abnormal clinical observations were limited to emesis, hypersalivation, lethargy/depression, head shaking and lip smacking, which occurred more frequently in the capromorelin-treated groups than in the placebo group. There were no clinically relevant differences in clinical pathology test results between the capromorelin and placebo groups in either study.

Topics: Administration, Oral; Animals; Cat Diseases; Cats; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Growth Hormone; Insulin-Like Growth Factor I; Lethargy; Male; Piperidines; Pyrazoles; Sialorrhea; Vomiting

To determine the dose of naltrexone necessary to fully antagonize a high dose of remifentanil in cats.. Prospective experimental study.. Six healthy adult cats weighing 4.9 ± 0.7 kg.. In a first phase, remifentanil (200 μg kg(-1) followed by 60 μg kg(-1) minute(-1) ) was administered intravenously to two cats, causing an increase in locomotor activity. Naltrexone (100 μg kg(-1) ) was then administered intravenously every minute until the increase in locomotor activity had been reversed. In a second phase, six cats were used. Baseline thermal threshold was determined, naltrexone (600 μg kg(-1) ) was administered intravenously and 30 minutes later thermal threshold determination repeated. Remifentanil (200 μg kg(-1) followed by 60 μg kg(-1) minute(-1) ) was administered intravenously and thermal threshold determination repeated at 60, 120, 180, and/or 240 minutes after naltrexone administration. Thermal threshold determinations were started shortly after the start of the continuous rate infusion (CRI) of remifentanil and this CRI was discontinued immediately after thermal threshold determination. If an increase in thermal threshold was found, naltrexone administration was repeated at decreasing intervals in the next experiment (all cats were not used for all dosing intervals). Experiments were repeated until a naltrexone dosing interval was found that prevented increases in thermal threshold for 4 hours in all six cats.. In the first phase, both cats became severely dysphoric following remifentanil administration. A cumulative naltrexone dose of 300 μg kg(-1) was necessary to restore normal behavior in both cats. In the second phase, hourly administration of naltrexone (600 μg kg(-1) ) prevented increases in thermal threshold associated with hourly administration of remifentanil for 4 hours. Less frequent administration did not prevent increases in thermal threshold consistently.. Hourly administration of naltrexone (600 μg kg(-1) ) antagonizes the behavioral and antinociceptive effects of a high dose of remifentanil in cats.. Naltrexone may be useful for the treatment of opioid overdose in cats.

Topics: Analgesics, Opioid; Animals; Cat Diseases; Cats; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Overdose; Female; Hyperkinesis; Naltrexone; Narcotic Antagonists; Piperidines; Prospective Studies; Remifentanil

Coronaviruses (CoVs) are major human and animal pathogens and antiviral drugs are pursued as a complementary strategy, chiefly if vaccines are not available. Feline infectious peritonitis (FIP) is a fatal systemic disease of felids caused by FIP virus (FIPV), a virulent pathotype of feline enteric coronavirus (FeCoV). Some antiviral drugs active on FIPV have been identified, but they are not available in veterinary medicine. ERDRP-0519 (ERDRP) is a non-nucleoside inhibitor, targeting viral RNA polymerase, effective against morbilliviruses in vitro and in vivo.. The antiviral efficacy of ERDRP against a type II FIPV was evaluated in vitro in Crandell Reese Feline Kidney (CRFK) cells. ERDRP significantly inhibited replication of FIPV in a dose-dependent manner. Viral infectivity was decreased by up to 3.00 logarithms in cell cultures whilst viral load, estimated by quantification of nucleic acids, was reduced by nearly 3.11 logaritms.. These findings confirm that ERDRP is highly effective against a CoV. Experiments will be necessary to assess whether ERDRP is suitable for treatment of FIPV in vivo.

Topics: Animals; Antiviral Agents; Cat Diseases; Cats; Cell Line; Coronavirus, Feline; Feline Infectious Peritonitis; Morpholines; Piperidines; Pyrazoles

Heart rate (HR) is often elevated in cats with cardiomyopathies (CMPs). Pharmacologic modulation of HR may reduce cardiac morbidity and mortality.. To investigate the effects of cilobradine vs. placebo, regarding time to cardiac mortality or morbidity in cats with first episode of congestive heart failure (CHF) due to primary CMP.. Three hundred and sixty-seven client-owned cats with primary CMP that had presented with a first episode of CHF at 50 centers in Europe. Per-protocol population comprised 193 cats (n = 89 cilobradine, n = 104 placebo). An interim analysis for futility was planned.. Prospective, randomized, placebo-controlled, double-blinded, multicenter clinical trial. Primary outcome variable was the time to a composite of cardiac mortality or cardiac morbidity.. Median time to primary outcome was 84 days (95% confidence interval [CI]: 63-219 days) in the cilobradine group (CG) and 203 days in the placebo group (95% CI: 145-377 days) with observed hazard ratio of 1.44, indicating a higher hazard for the CG (P = 0.057). Mean HR was 28 beats per minute (bpm) lower at Day 7 (P < 0.0001) and remained 29 bpm lower at Day 360 (P = 0.026) in the CG than that in the placebo group. Although the number of adverse events did not differ, there were more serious adverse events in the CG.. Heart rate reduction by cilobradine in cats with a first episode of CHF due to primary CMP did not reduce cardiac mortality and morbidity.

Topics: Animals; Benzazepines; Cardiomyopathies; Cat Diseases; Cats; Heart Failure; Piperidines; Prospective Studies

Masitinib, a selective tyrosine kinase inhibitor, was investigated as a radiosensitizer in three primary feline injection-site sarcoma (ISS) cell lines. Sensitivity to masitinib was previously assessed via cell growth inhibition assays with mean IC50 values of 5.5-8.6μM. Clonogenic assays were performed to determine the effect of masitinib and radiation on cell survival. Single dose radiation (0-12Gy) experiments were carried out under normal growth conditions in control ISS cells and in cells incubated with 1 or 6μM masitinib for 72h prior to irradiation. Radiation administered either alone or in combination with masitinib induced a dose-dependent reduction in clonogenic survival. Survival from the combined masitinib and radiation treatment was not significantly different from that of radiation alone. Results suggest that masitinib does not directly enhance ISS cell radiosensitivity under normal in vitro conditions, although this does not preclude the utility of further investigations to assess sensitization properties under altered conditions.

Topics: Animals; Benzamides; Cat Diseases; Cats; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Piperidines; Protein Kinase Inhibitors; Pyridines; Radiation-Sensitizing Agents; Sarcoma; Thiazoles

Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease. The in vitro effects of masitinib on growth, apoptosis and PDGFR signalling in two novel ISS cell lines were investigated. PDGFR expression was confirmed by Western blot in cell lines derived from a primary ISS tumour (JB) and a corresponding, histologically confirmed ISS lung metastasis (JBLM). Masitinib inhibited cell growth and PDGFR phosphorylation in both cell lines. Higher drug concentrations were required to inhibit growth than to modulate ligand-induced autophosphorylation of PDGFR. These in vitro data suggest that masitinib displays activity against both primary and metastatic ISS cell line and may aid in the clinical management of ISS.

Topics: Animals; Antineoplastic Agents; Benzamides; Cat Diseases; Cats; Cell Line, Tumor; Dose-Response Relationship, Drug; Flow Cytometry; Gene Expression Regulation, Neoplastic; Piperidines; Platelet-Derived Growth Factor; Pyridines; Receptors, Platelet-Derived Growth Factor; Sarcoma; Soft Tissue Neoplasms; Thiazoles; Vaccines, Inactivated

Topics: Animals; Cat Diseases; Cats; Cisapride; Constipation; Female; Parasympathomimetics; Piperidines