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Measles and its neurological complications
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Benedikt Weissbrich, Jürgen Schneider-Schaulies
Measles virus (MV) is a member of the Mononegavirales group, which comprises the Rhabdo-, Filo-, and Paramyxoviridae [2]. As a paramyxovirus, MV possesses structural and biochemical features associated with this group, however it lacks a detectable virion-associated neuraminidase activity. Therefore, it has been grouped into a separate genus, the morbilliviruses. Other members of this group include rinderpest virus, which infects cattle; peste des petits ruminants, which infects sheep and goats; canine distemper virus, which infects various carnivores; phocine distemper virus; dolphin morbillivirus; and porpoise morbillivirus. All these viruses exhibit antigenic similarities, and produce similar diseases in their host species, but their neuroinvasiveness differs considerably. Whereas canine distemper virus causes neurological disease in approximately 50% of infected dogs, MV causes encephalomyelitis in about 0.1% of cases.
Autoimmunity and Immune Pathological Aspects of Virus Disease
Published in Irun R. Cohen, Perspectives on Autoimmunity, 2020
H. Wege, R. Dörries, P. Massa, R. Watanabe
Canine distemper virus (CDV) infections can develop into a chronic demyelinating disease which affects dogs and other canine species.43,54 Similar to measles, acute canine distemper is associated with signs of respiratory and gastrointestinal disease. Experimental infection of dogs with certain virus strains (Cornell A75-17 or Ohio R252) leads to diseases associated with predominant white matter lesions and variable neurological signs. Within 8 to 10 days, virus can enter the brain via infected lymphocytes, and demyelinative foci develop 14 to 16 days later. A severe involvement of lymph organs leads to lymphopenia, and, therefore, no pronounced inflammatory lesions are found in the brain in this stage of disease. A severe transient depression of the immune response is indicated by a reduced response of lymphocytes to lectins. The development of antiviral immunity influences the further course of disease.54-58 Inflammatory demyelinating CNS lesions are a typical finding in CDV infections which develop a chronic course.
Nervous System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Mark T. Butt, Alys Bradley, Robert Sills
There are several neuronal inclusions associated with infectious disease. The Negri body of rabies is a prime example. Inclusions are relatively common in cases of canine distemper and the various herpes infections. It might be possible to observe Cowdry Type A inclusions in monkeys infected with herpes viruses (including cytomegalovirus infection of immunosuppressed animals), but this would be unusual in the experience of the typical toxicologic pathologist. The toxicologic pathologist is going to encounter inclusions most often when evaluating animal models (typically transgenic models) of human disease.
Efficacy of HL036 versus Cyclosporine A in the Treatment of Naturally Occurring Canine Keratoconjunctivitis Sicca
Published in Current Eye Research, 2018
Han-Byul Lee, Hyun-Ji Choi, Sung-Min Cho, Suzie Kang, Hyea Kyung Ahn, Yeon Jung Song, Young Ju Kim, Woo-Chan Son
Animal models of spontaneous diseases have been shown to have practical advantages in comparative medicine.15–18 Dogs with naturally occurring KCS have proven to be suitable models for human KCS.19,20 Canine KCS, in particular, is considered an excellent animal model for human DED, owing to similarities in clinical features, histopathology, pathogenesis, treatment, and environmental conditions.15–18 DED (or KCS) is a relatively common spontaneous occurrence in dogs and humans.16 Canine KCS is a multifactorial disease with several known etiologic features, including neurogenic, iatrogenic (excision of the third eyelid), and endocrine disorders; infection (e.g., canine distemper, viral); trauma; and/or drug-related (sulfonamides, atropine, or anesthetic agents) conditions. However, the most common form of canine KCS is spontaneous and immune-mediated.17 Treatments for naturally occurring canine KCS include topical anti-inflammatory agents, antibiotics, artificial tears, and mucolytics. Immunosuppressive drugs, among them CsA, pimecrolimus, and tacrolimus, are the most common treatment agents owing to their considerable anti-inflammatory properties and effects on tear-production.19,21,22
Balance of saccharolysis and proteolysis underpins improvements in stool quality induced by adding a fiber bundle containing bound polyphenols to either hydrolyzed meat or grain-rich foods
Published in Gut Microbes, 2019
Matthew I. Jackson, Dennis E. Jewell
All study protocols and this study were reviewed and approved by the Institutional Animal Care and Use Committee, Hill’s Pet Nutrition, Inc., Topeka, KS, USA, and complied with the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978). Studies were conducted using dogs from a colony of beagles (Table S2). Inclusion criteria for dogs with chronic enteritis/gastroenteritis were diagnosis following endoscopy and histopathologic analysis of excised tissues confirming plasmacytic/lymphocytic inflammation. In a few cases, the research veterinarian deemed that the endoscopic procedure was not in the best interest of the dog’s health, and observation of chronic symptomology sufficed. Healthy dogs were matched to chronic enteritis dogs by sex, reproductive status, and approximate age and weight. Dogs were considered healthy when there was no evidence of chronic systemic disease from physical examination, complete blood count, serum biochemical analyses, urinalysis, or fecal examination for parasites; exclusion criteria were recorded instances of gastrointestinal upset (vomiting, diarrhea) or abnormally low appetite. All dogs were pair-housed in spacious indoor rooms with natural light. Dogs received behavioral enrichment by interacting with each other, as well as through play time with caretakers, daily opportunities to run outside, and access to toys. Dogs were fed once daily and had ad libitum access to water. All dogs were immunized against canine distemper, adenovirus, parvovirus, Bordetella, and rabies, were monitored for parasites, and received routine heartworm preventative. Symptoms of dogs with chronic enteritis/gastroenteritis were managed with bismuth subsalicylate, prednisolone, cobalamin, omeprazole, and prednisone as needed to maintain their quality of life (Table S2).
In vivo nose-to-brain delivery of the hydrophilic antiviral ribavirin by microparticle agglomerates
Published in Drug Delivery, 2018
Alessandro Giuliani, Anna Giulia Balducci, Elisa Zironi, Gaia Colombo, Fabrizio Bortolotti, Luca Lorenzini, Viola Galligioni, Giampiero Pagliuca, Alessandra Scagliarini, Laura Calzà, Fabio Sonvico
The nasal route has been extensively studied for the administration of drugs directly to the CNS (Landis et al., 2012). In fact, this route exploits the olfactory region and the trigeminal nerve pathway to enable drugs’ entry into the CNS bypassing the BBB (Hanson & Frey, 2008). This delivery approach was explored for the administration of ribavirin (RBV), in view of an innovative treatment of the encephalitis associated with canine distemper virus, a major veterinary infection that could serve as a proof of concept of the approach. This virus belongs to the Morbillivirus genus as the measles virus and primarily infects dogs (Elia et al., 2008; Dal Pozzo et al., 2010). RBV is a synthetic guanosine antiviral analog. It has a broad-spectrum antiviral activity, being clinically effective against several viruses and successfully tested in vitro against several RNA and DNA virus infections (Beaucourt & Vignuzzi, 2014). The drug is currently marketed in oral dosage forms; however, it has been clinically administered as pulmonary aerosol in the treatment of respiratory syncytial virus (Li et al., 2012) and for the therapy of measles pneumonia (Safdar et al., 2009) as well as intravenously and intraventricularly for subacute sclerosing panencephalitis (Tomoda et al., 2003; Garg, 2008). However, the latter two approaches are plagued by adverse effects and exploit a highly invasive, risky, and infection-prone administration route, remarkably fostering the development of an alternative delivery route such as nasal administration. Our group showed that measurable brain concentrations of RBV can be obtained in rats after intranasal administration of a RBV aqueous solution. In particular, it was evidenced that 20 min after nasal administration, RBV was highly concentrated in the olfactory bulb and in other brain structures after nasal administration (Colombo et al., 2011).