ABSTRACT
Given the predisposition of South American camelids to coccidioidomycosis, we sought to describe the disease presentation in alpacas and llamas and identify potential risk factors for these species. The records of 224 llamas and alpacas that were tested for Coccidioides infection using immunodiffusion serology at the Coccidioidomycosis Serology Laboratory of the University of California, Davis, between 1990 and 2016 were examined; of those, 46 alpacas and 42 llamas had positive test results. The remaining 99 alpacas and 37 llamas were used as control groups. We found that male llamas were at increased risk for Coccidioides infection when compared with female llamas and when compared with male alpacas. South American camelids living within California were at higher risk for infection than camelids living in other states. Alpacas were more likely than llamas to have subclinical infections. We documented five cases of abortion or neonatal mortality attributable to coccidioidomycosis in alpacas. Our study demonstrates that South American camelids are susceptible to Coccidioides infection in areas where the disease is endemic, lending support to the importance of vigilance for this disease in alpacas and llamas and suggesting a possible role for these animals as sentinel species. LAY SUMMARY: We examined cases of Valley Fever and described the disease and risk factors for llamas and alpacas. Male llamas were at increased risk for infection as were animals living within California. Five alpacas had miscarriages or neonatal deaths as a result of Valley Fever infections.
ABSTRACT
BACKGROUND: Cryptococcus spp. is a fungal pathogen with a predilection for the central nervous system (CNS). OBJECTIVES: To compare the clinical, advanced imaging, and neuropathologic findings in dogs and cats with CNS cryptococcosis, and to evaluate outcome of treatment in these animals. ANIMALS: Twenty-six cats and 21 dogs with CNS cryptococcosis. METHODS: Medical records were reviewed for clinical findings and results of CNS imaging. Archived cerebrospinal fluid and CNS tissue specimens were reviewed for pathology. Findings in cats were compared with those in dogs and the effects of variables on survival were determined by survival curve analysis. RESULTS: When present, pain was localized to the cervical region in dogs and was generalized or localized to the thoracolumbar spine or pelvic limbs in cats. Magnetic resonance imaging (MRI) findings were variable but correlated with CNS histopathological findings of meningitis, meningitis with gelatinous pseudocyst formation, and granulomatous mass lesions. Peripherally enhancing brain lesions were seen only in cats. Histopathologically, the inflammatory response was milder in cats compared with dogs. Remissions of ≥1 year occurred in 32% of treated animals. Altered mentation was associated with negative outcome. Glucocorticoid use after diagnosis was associated with improved survival in the first 10 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Lesions seen on MRI reflected neuropathological findings and were similar to those reported in human patients. The immune response to infection may differ between cats and dogs, or relate to the infecting cryptococcal species. Long-term (>6 month median survival time) survival may be possible in animals surviving ≥4 days after diagnosis.
Subject(s)
Cat Diseases/diagnosis , Central Nervous System Infections/veterinary , Cryptococcosis/veterinary , Dog Diseases/diagnosis , Animals , California/epidemiology , Cat Diseases/cerebrospinal fluid , Cat Diseases/epidemiology , Cat Diseases/pathology , Cats , Central Nervous System Infections/cerebrospinal fluid , Central Nervous System Infections/epidemiology , Central Nervous System Infections/pathology , Cryptococcosis/cerebrospinal fluid , Cryptococcosis/epidemiology , Cryptococcosis/pathology , Dog Diseases/cerebrospinal fluid , Dog Diseases/epidemiology , Dog Diseases/pathology , Dogs , Magnetic Resonance Imaging/veterinaryABSTRACT
BACKGROUND: Salmon poisoning disease (SPD) is a trematode-borne disease of dogs caused by Neorickettsia helminthoeca. OBJECTIVES: To determine risk factors and spatial epidemiology of SPD in dogs from northern California; to describe the clinicopathologic, microbiologic, and imaging findings of SPD in these dogs; and to evaluate treatments and outcomes for SPD. ANIMALS: Twenty-nine dogs with SPD based on the finding of trematode ova in the feces, or organisms consistent with N. helminthoeca in specimens submitted for microscopic examination. METHODS: Information regarding signalment, fish exposure, clinical signs, diagnostic evaluation, treatments, and outcomes was obtained for each dog. Archived lymph node aspirates and histopathology specimens were subjected to polymerase chain reaction (PCR) testing for Neorickettsia spp. RESULTS: Labrador Retrievers and intact male dogs were overrepresented. Exposure locations were often distant from the dogs' residence. Some dogs had neurologic signs, including twitching and seizures. Dogs lacking peripheral lymphadenomegaly had abdominal lymphadenomegaly on ultrasound examination. A combination of centrifugation fecal flotation and sedimentation had greatest sensitivity for finding fluke ova. N. helminthoeca DNA was amplified by PCR from 4/10 dogs. Penicillins, cephalosporins, and chloramphenicol did not appear to be effective treatments. Mortality rate was 4/29 (14%). CONCLUSIONS AND CLINICAL IMPORTANCE: SPD should be suspected in dogs with inappetence, gastrointestinal, or neurologic signs, with or without fever or peripheral lymphadenomegaly in the appropriate geographical setting. Diagnosis is facilitated by a combination of fecal sedimentation and centrifugal flotation, abdominal ultrasonography, and PCR-based assays on lymphoid tissue. The treatment of choice is tetracycline antimicrobials.
Subject(s)
Animal Feed , Dog Diseases/parasitology , Food Parasitology , Foodborne Diseases/veterinary , Rickettsia Infections/veterinary , Salmon , Animals , Anthelmintics/therapeutic use , Anti-Bacterial Agents/therapeutic use , California , Dog Diseases/drug therapy , Dog Diseases/epidemiology , Dogs , Female , Male , Rickettsia Infections/drug therapy , Rickettsia Infections/epidemiology , Treatment Outcome , Trematoda/microbiology , Trematode Infections/drug therapy , Trematode Infections/parasitology , Trematode Infections/veterinaryABSTRACT
A commercial Aspergillus galactomannan antigen (GMA) enzyme linked immunosorbent assay (ELISA) is used to support a diagnosis of systemic aspergillosis in dogs. In human patients, false positive results have been associated with administration of medications derived from molds. We sought to determine the effect of administration of a commercially available oral probiotic nutraceutical that contained Aspergillus-derived ingredients on serum and urine Aspergillus GMA levels in dogs by conducting a prospective, cross-over study. Galactomannan index (GMI) was measured on the solubilized probiotic nutraceutical and was positive (GMI ≥ 0.5) with a mean of 7.91. Serum and urine galactomannan indices were measured in 10 healthy dogs before (day 0) and after 1 week (day 7) of probiotic nutraceutical administration, then again 2 weeks after the probiotic nutraceutical was discontinued (day 21). Median (range) serum GMI were 0.19 (0.08-0.62), 0.22 (0.07-1.15) and 0.17 (0.14-0.63) at day 0, 7 and 21, respectively. Two of 10 dogs developed positive GMI (≥0.5) results after probiotic nutraceutical administration; however, no significant changes were noted over the study period. Median (range) urine GMI results were 0.06 (0.04-0.22), 0.07 (0.05-0.41) and 0.06 (0.03-0.16) at day 0, 7 and 21, respectively. A trend towards an increase urine GMI was noted between day 0 and 7 (P = 0.18), and decrease was noted between day 7 and 21 (P = 0.09). Administration of probiotics containing Aspergillus-derived ingredients to dogs did not reliably result in elevated Aspergillus GMA levels.
Subject(s)
Antigens, Fungal/analysis , Aspergillosis/veterinary , Aspergillus/immunology , Dog Diseases/microbiology , Mannans/immunology , Probiotics/administration & dosage , Animals , Antigens, Fungal/blood , Antigens, Fungal/urine , Aspergillosis/diagnosis , Dietary Supplements/microbiology , Dog Diseases/diagnosis , Dogs , Enzyme-Linked Immunosorbent Assay/veterinary , Female , Galactose/analogs & derivatives , MaleABSTRACT
Anaplasma phagocytophilum is an emerging pathogen of humans, horses, and dogs worldwide that is transmitted by Ixodid ticks and maintained in a variety of small wild mammal species. Recent studies suggest that multiple strains of A. phagocytophilum may be circulating in wild and domestic animal populations, and these strains may have differential host tropisms and pathogenicity. The organism infects and survives within neutrophils by disabling key neutrophil functions, including neutrophil motility, phagocytosis, the oxidative burst mechanism, and neutrophil-endothelial cell interactions, as well as interfering with neutrophil apoptosis. Coinfections with other tick-borne pathogens may occur, especially Borrelia burgdorferi. A. phagocytophilum causes an acute febrile illness in dogs with lethargy and inappetence. Less frequent signs include lameness, coughing, polydipsia, intermittent vomiting, and hemorrhages. Diagnosis is based on finding morulae within granulocytes in the peripheral blood, the combination of acute and convalescent serology using immunofluorescent antibody techniques, and detection of the DNA of A. phagocytophilum using specific polymerase chain reaction assays. Whether persistent infection or reinfection with A. phagocytophilum occurs after natural infection requires additional study, with most reports suggesting that anaplasmosis is a self-limiting disease in dogs that responds well to a 2-week course of doxycycline therapy.
Subject(s)
Anaplasmosis/microbiology , Dog Diseases/microbiology , Anaplasma/classification , Anaplasma/genetics , Anaplasma/isolation & purification , Animals , Dogs , PhylogenyABSTRACT
BACKGROUND: Serial arthrocentesis and synovial fluid examination can be used to monitor treatment efficacy in immune-mediated polyarthritis (IMPA), but whether this procedure induces inflammation that interferes with test result interpretation is unknown. OBJECTIVES: The aim of this study was to determine the effect of repeated arthrocentesis on synovial fluid cytology in healthy dogs. ANIMALS: Nine healthy client-owned dogs. METHODS: Prospective study. Arthrocentesis was performed under sedation on 4 joints (both carpi, 1 tarsus, 1 stifle) on each dog every 3 weeks, a total of 4 times. Automated cell counts were done on stifle fluid, smears were made, and differential cell counts done on smears from all joints. Slides were evaluated microscopically for erythrocyte numbers, total nucleated cell count, differential cell count, and cell morphology. Data were analyzed by 2-way analysis of variance. RESULTS: A total of 144 synovial fluid samples were examined. Repeated arthrocentesis was not associated with increases in synovial fluid neutrophil numbers. Mild mononuclear inflammation was detected in 13 samples from 6 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Serial arthrocentesis at 3-week intervals can rarely be associated with mild mononuclear joint inflammation, but does not appear to induce neutrophilic inflammation, at least in healthy dogs, and can be useful to monitor treatment response in canine IMPA.
Subject(s)
Arthritis/veterinary , Dog Diseases/diagnosis , Paracentesis/veterinary , Synovial Fluid/cytology , Animals , Arthritis/diagnosis , Arthritis/immunology , Dogs , Female , Male , Neutrophils/cytology , Paracentesis/adverse effectsABSTRACT
BACKGROUND: Systemic aspergillosis is a serious disease of dogs for which the clinical characteristics are poorly described. OBJECTIVE: To describe the clinical and diagnostic imaging characteristics of dogs with systemic aspergillosis. ANIMALS: Thirty dogs with systemic aspergillosis. METHODS: Retrospective case review. Medical records were reviewed for signalment, clinical features, and results of clinicopathologic testing and diagnostic imaging. Diagnosis was confirmed by culture of Aspergillus terreus (n = 13), Aspergillus deflectus (n = 11), or other Aspergillus spp. (n = 6). RESULTS: Compared with the background hospital population, German Shepherd dogs and female dogs were overrepresented (odds ratio [OR] 43, 95% confidence interval [CI] 20-91, P < .0001, and OR 2.9, 95% CI 1.2-6.7, P= .02), respectively, with 20 of the 30 dogs being German Shepherd dogs and 77% (23 of 30) of the dogs being female. The median age was 4.5 years (range 2-8 years). Anemia, leukocytosis, hyperglobulinemia, azotemia, hypercalcemia, and hypoalbuminemia were present in 8, 21, 12, 9, 8, and 6 dogs, respectively. Diskospondylitis, osteomyelitis and thoracic lymphadenomegaly were present in 16, 10, and 5 dogs, respectively. Sonographic findings were enlarged hypoechoic lymph nodes (n = 12), mottled and irregular kidneys with or without masses (n = 12), pyelectasia, and an aggregate of echogenic material in the renal pelvis (n = 9). Thirteen dogs were treated with antifungal drugs, with survival times ranging from 0 to 25 months after diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic aspergillosis typically involves young to middle-age female German Shepherd dogs, and there are characteristic abdominal ultrasound findings with the disease process. Infection with A. deflectus was as common as A. terreus, and in rare cases, long-term survival was associated with antifungal therapy.
Subject(s)
Aspergillosis/veterinary , Dog Diseases/diagnosis , Animals , Antifungal Agents/therapeutic use , Aspergillosis/diagnosis , Aspergillosis/diagnostic imaging , Central Nervous System Infections/diagnosis , Central Nervous System Infections/veterinary , Dogs , Female , Magnetic Resonance Imaging/veterinary , Male , Ultrasonography/veterinaryABSTRACT
A 5-year-old male castrated Lhasa Apso cross was evaluated for a 1-month history of inappetence, lethargy, gagging, and progressive right thoracic limb lameness. Synovial fluid analysis revealed nonseptic suppurative inflammation, and a diagnosis of immune-mediated polyarthritis (IMPA) was made. After 3 months of treatment with prednisone and later cyclosporine, the dog developed multiple firm cutaneous and subcutaneous masses and a focal mass within the jejunum. Cultures of blood, urine, skin lesions, and the jejunal mass identified Nocardia veterana by matrix-absorption laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and allowed for earlier identification of the organism compared to more traditional secA1 gene sequencing. Immunosuppressive drug treatment was discontinued, and the dog was treated for 3 months by administration of trimethoprim-sulfamethoxazole (TMS). No recurrence of clinical signs was reported 1 year later. This case report highlights the clinical utility of MALDI-TOF MS, particularly for the rapid identification of slow-growing, fastidious organisms.
Subject(s)
Nocardia Infections/veterinary , Nocardia/isolation & purification , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Animals , Arthritis/drug therapy , Arthritis/immunology , Arthritis/veterinary , Cyclosporine/therapeutic use , Dog Diseases/drug therapy , Dog Diseases/microbiology , Dogs , Immunosuppressive Agents/therapeutic use , Male , Nocardia Infections/diagnosis , Nocardia Infections/drug therapy , Prednisone/therapeutic use , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/veterinaryABSTRACT
BACKGROUND: Antimicrobial resistance is an emerging problem. HYPOTHESIS/OBJECTIVE: To investigate the safety and efficacy of a live biotherapeutic product, ASB E. coli 2-12 for UTI treatment. ANIMALS: Six healthy research dogs; nine client-owned dogs with recurrent UTI. METHODS: Prospective noncontrolled clinical trial. For safety data, research dogs were sedated, a urinary catheter was inserted into the bladder; 1010 CFU/mL of ASB E. coli 2-12 was instilled. Urine was cultured on days 1, 3, and 8 post-instillation and dogs were observed for lower urinary tract signs (LUTS). For client-owned dogs, ASB E. coli 2-12 was instilled similarly and urine cultures analyzed on days 1, 7, and 14 days postinstillation. RESULTS: No LUTS were noted in any of the 6 research dogs after ASB E. coli 2-12 infusion. Pulse field gel electrophoresis (PFGE) studies confirmed the bacterial strains isolated matched that ASB E. coli 2-12 strain. Four of the nine client-owned dogs had complete or nearly complete clinical cures by day 14. Of these four dogs, 3 also had microbiologic cures at day 14; one of these dogs had subclinical bacteriuria (in addition to ASB E. coli 2-12). Three of these four dogs had ASB E. coli 2-12 isolated from their urine at day 14. With the exception of mild, temporary, self-limiting, hyporexia in two dogs on the day of biotherapeutic administration, there were no major adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest ASB E. coli 2-12 is safe and should be investigated in a larger controlled study evaluating clinical UTI in dogs.
Subject(s)
Bacteriuria/veterinary , Biological Therapy/veterinary , Dog Diseases/therapy , Escherichia coli , Urinary Tract Infections/veterinary , Animals , Asymptomatic Diseases , Bacteriuria/microbiology , Biological Therapy/methods , Dog Diseases/microbiology , Dogs , Female , Male , Recurrence , Urinary Tract Infections/microbiology , Urinary Tract Infections/therapyABSTRACT
Given the predisposition of dogs to coccidioidomycosis, identification of high-risk regions for coccidioidomycosis in dogs may improve early recognition of emerging human disease. We sought to identify risk factors for canine coccidioidomycosis and to produce a risk map for coccidioidomycosis occurrence. Forty-one dogs seen at the Veterinary Medical Teaching Hospital at the University of California, Davis, between 2005 and 2013 with coccidioidomycosis were identified together with a control population of 79 dogs. Owners were surveyed about potential risk factors including younger age, digging behaviour, and travel to Arizona or the California central valley. Risk factors were analysed using logistic regression analysis. Outcomes were used to generate a risk map for coccidioidomycosis in California. There was a significant correlation between the reported rate of coccidioidomycosis in humans and our risk map for canine coccidioidomycosis in California, supporting the idea of dogs as sentinels for emerging geographic areas for coccidioidomycosis in humans.
Subject(s)
Coccidioidomycosis/veterinary , Dog Diseases/epidemiology , Animals , California/epidemiology , Case-Control Studies , Coccidioides/isolation & purification , Coccidioidomycosis/epidemiology , Coccidioidomycosis/microbiology , Dog Diseases/microbiology , Dogs , Female , Geographic Mapping , Male , Risk Factors , Spatial AnalysisABSTRACT
Respiratory tract disease can be associated with primary or secondary bacterial infections in dogs and cats and is a common reason for use and potential misuse, improper use, and overuse of antimicrobials. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, the International Society for Companion Animal Infectious Diseases convened a Working Group of clinical microbiologists, pharmacologists, and internists to share experiences, examine scientific data, review clinical trials, and develop these guidelines to assist veterinarians in making antimicrobial treatment choices for use in the management of bacterial respiratory diseases in dogs and cats.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/veterinary , Cat Diseases/drug therapy , Dog Diseases/drug therapy , Respiratory Tract Diseases/veterinary , Animals , Bacterial Infections/drug therapy , Cats , Dogs , Respiratory Tract Diseases/drug therapyABSTRACT
BACKGROUND: We observed evidence of protein-losing nephropathy in some dogs with coccidioidomycosis, suggestive of immune complex glomerulonephritis (ICGN). The goal of this study was to understand the prevalence of renal histopathologic lesions and proteinuria in dogs with coccidioidomycosis. HYPOTHESIS: Biochemical and histopathological evidence of glomerular lesions is present in dogs with coccidioidomycosis. ANIMALS: Hundred and fifty-six dogs with naturally occurring coccidioidomycosis. METHODS: Retrospective case series. Clinical information and results of clinicopathologic testing were retrieved from the University of California, Davis Veterinary Medical Teaching Hospital (VMTH). Microscopic sections of renal tissue procured from necropsy of dogs with coccidioidomycosis were examined to evaluate the nature and distribution of lesions. RESULTS: A total of 156 dogs with coccidioidomycosis were identified; 87 dogs had serum biochemistry and a urinalysis performed, 17 had urine protein:creatinine ratios (UPCs), and 24 had renal tissue available for histopathology. Eleven (13%) of the 87 dogs were azotemic, 55 (63%) were proteinuric (of which 14 [25%] had clinically relevant proteinuria defined as ≥3+ or ≥500 mg/dL), and 14 dogs had UPC ≥0.5 (range, 0.5-21.5, median 4.2). Thirteen (54%) of 24 dogs had renal histopathologic lesions suggestive of ICGN. Seven of these dogs had urinalyses performed; 5 (71%) had clinically relevant proteinuria as described above. Two dogs (33%) with normal glomeruli had granulomatous nephritis, 1 of which had intralesional Coccidioides spherules. CONCLUSIONS AND CLINICAL IMPORTANCE: Coccidioidomycosis should be considered as a possible contributor to glomerular disease in dogs. Whether similar lesions occur in other mammalian hosts, including humans, warrants further investigation.
Subject(s)
Coccidioidomycosis/veterinary , Dog Diseases/etiology , Kidney Diseases/veterinary , Animals , Coccidioidomycosis/etiology , Coccidioidomycosis/pathology , Dog Diseases/pathology , Dogs , Female , Kidney Diseases/etiology , Kidney Diseases/pathology , Male , Retrospective StudiesABSTRACT
We studied the effect of sodium 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA), a potent inhibitor of mitochondrial carnitine palmitoyltransferase I, on fatty acid oxidation by rat brain cells. In cultured glial cells as well as in dissociated brain cells from adult rats palmitic acid (16:0) oxidation was inhibited by about 85% of control values when 25 microM POCA was added to the medium, whereas no inhibition of cerotic acid (26:0) oxidation was observed. Furthermore, omission of carnitine from the culture medium resulted in a 57.7% decrease in palmitic acid oxidation in cultured glial cells, whereas cerotic acid oxidation was not influenced. These results indicate that rat brain peroxisomes contribute only little (about 15%) to palmitic acid oxidation and provide conclusive evidence that cerotic acid is oxidized exclusively in rat brain peroxisomes.
Subject(s)
Brain/metabolism , Fatty Acids/metabolism , Microbodies/metabolism , Animals , Brain/drug effects , Carnitine/pharmacology , Carnitine O-Palmitoyltransferase/antagonists & inhibitors , Cells, Cultured , Epoxy Compounds/pharmacology , Microbodies/drug effects , Mitochondria/metabolism , Neuroglia/drug effects , Neuroglia/metabolism , Oxidation-Reduction , RatsSubject(s)
Corynebacterium Infections/veterinary , Corynebacterium/classification , Pneumonia, Bacterial/veterinary , Animals , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use , Corynebacterium Infections/microbiology , Dogs , Itraconazole/therapeutic use , Male , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Pulmonary Aspergillosis/drug therapy , Pulmonary Aspergillosis/microbiology , Pulmonary Aspergillosis/veterinaryABSTRACT
The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/veterinary , Societies, Scientific/organization & administration , Veterinary Drugs , Veterinary Medicine/organization & administration , Animal Husbandry/methods , Animals , Anti-Bacterial Agents/administration & dosage , Bacterial Infections/drug therapy , Drug Resistance, Bacterial , United States , Veterinary Medicine/standardsABSTRACT
The genome of the avian pathogen Mycoplasma gallisepticum contains a number of related genes for putative adhesion molecules (pMGA). Cloning and sequence analysis of several pMGA genes suggested that all of them might be transcriptionally and translationally functional. Analysis of the gene sequence encoding the sole pMGA variant expressed in vitro in the S6 strain (pMGA1.1) revealed no unambiguous feature that could account for its unique expression. It is estimated that the pMGA gene family may contain up to 50 members, and its possible role is discussed herein.
Subject(s)
Bacterial Proteins/genetics , Genes, Bacterial , Multigene Family , Mycoplasma/genetics , Amino Acid Sequence , Base Sequence , Blotting, Southern , Cloning, Molecular , Conserved Sequence , DNA, Bacterial/chemistry , DNA, Bacterial/metabolism , Gene Expression , Genetic Variation , Hemagglutinins/genetics , Introns , Molecular Sequence Data , Mycoplasma/metabolism , Restriction Mapping , Sequence Homology, Amino Acid , Sequence Homology, Nucleic AcidABSTRACT
Glial cells were isolated from the cerebra of 7-day old rats and the effect of serum on the development of these cells in culture was studied. The activities of the oligodendrocyte marker-enzymes, 2?3?-cyclic nucleotide 3?-phosphodiesterase and glycerol 3-phosphate dehydrogenase and the synthesis of the myelin-associated sulpholipid, sulphatide, were used to monitor the differentiation of these cells in vitro. The results indicate that serum: (i) represses lipogenesis, cholesterogenesis and sulphatide synthesis, (ii) lowers the expression of 2?3?-cyclic nucleotide 3? phosphodiesterase and glycerol 3-phosphate dehydrogenase but not of lactate dehydrogenase and (iii) thus impairs the differentiation of oligodendrocytes.
ABSTRACT
The metabolism of oligodendrocytes has been studied using cultures of oligodendrocyte-enriched glial cells isolated from cerebra of 5-8-day old rats. Cultures containing 60-80% oligodendrocytes were incubated for 16h with [3-(14)C]acetoacetate, d-[3-(14)C]3-hydroxybutyrate, [U-(14)C]glucose, l-[U-(14)C]glutamine and [1-(14)C]pyruvate or [2-(14)C]pyruvate in the presence or absence of other oxidizable substrates. Labelled CO(2) was collected as an index of oxidative metabolism and the incorporation of label into total lipids, fatty acids and cholesterol was used as an index of the de novo synthesis of lipids. Glucose, acetoacetate, D-3-hydroxybutyrate, pyruvate and l-lactate were measured to determine substrate utilization and product formation under various conditions. Our results indicate that glucose is rapidly converted to lactate and is a relatively poor substrate for oxidative metabolism and lipid synthesis. Ketone bodies were used as an energy source and as precursors for the synthesis of fatty acids and cholesterol. Preferential incorporation of acetoacetate into cholesterol was not observed. Exogenous pyruvate was incorporated into both the glycerol skeleton of complex lipids and into cholesterol and fatty acids. l-Glutamine appeared to be an important substrate for the energy metabolism of these cells.
ABSTRACT
This study focuses on the activity of the pentose-phosphate pathway and its relationship to de novo synthesis of fatty acids and cholesterol in oligodendrocyte-enriched glial cell cultures derived from 1-week old rat brain. The proportion of glucose that was metabolized along the pentose-phosphate pathway was estimated by measuring (14)CO(2) production from [1-(14)C]-, [2-(14)C]- and [6-(14)C]glucose, the utilization of glucose and the production of lactate. Incorporation of (14)C from [(14)C]glucose and from [3-(14)C]acetoacetate into lipids was analysed. The pentose- phosphate pathway produced much more CO(2) from glucose than the Krebs cycle, although it accounted for only a small part of the consumption of glucose (< 3%). The higher (14)CO(2) production from [2-(14)C]glucose than from [6-(14)C]glucose indicated that recycling of the products of the pentose-phosphate pathway takes place in these cells. Gradual inhibition of the pathway with increasing concentrations of 6-aminonicotinamide resulted in a parallel inhibition of the conversion of acetoacetate and of glucose into fatty acids and into cholesterol. Glycolysis was also strongly inhibited in the presence of 6-aminonicotinamide whereas the activity of the Krebs cycle was not affected. These results suggest that de novo synthesis of fatty acids and cholesterol by oligodendrocytes of neonatal rats is closely geared to the activity of the pentose-phosphate pathway in these cells.
ABSTRACT
Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated the effects of hydrocortisone on the development of oligodendrocytes, on the activities of oligodendrocyte-specific enzymes and on glucose- and lipid-metabolism of the glial cells. Hydrocortisone greatly enhanced the survival of glial cells in culture. The development of galactocerebroside-positive cells and the specific activity of 2',3'-cyclic-nucleotide 3'-phosphodiesterase were stimulated by 50 nM hydrocortisone, whereas these effects were partly reversed at higher concentrations of the hormone. The specific activity of glycerol-3-phosphate dehydrogenase was markedly stimulated by hydrocortisone; 1 microM or higher concentrations of hydrocortisone were required for an optimal effect. The consumption of glucose and the production of lactate were lowered by hydrocortisone whereas the oxidation of [6-14C]glucose to 14CO2 was not affected. Incorporation of [35S]sulfate into sulfolipids was greatly enhanced by hydrocortisone and [14C]incorporation from [1-14C]acetate into cholesterol and fatty acids was also stimulated but to a smaller extent. These results show that hydrocortisone exerts a general trophic function on glial cells in our culture system; enhances the ratio of oligodendrocytes over astrocytes, possibly by directing bipotential progenitor cells to develop into oligodendrocytes; specifically induces glycerol-3-phosphate dehydrogenase in oligodendrocytes.