RESUMO
Residues of antineoplastic drugs in canine excretion products may represent exposure risks to veterinary personnel, owners of pet dogs and other animal care-takers. The aim of this study was to measure the extent and duration of platinum (Pt) excretion in pet dogs treated with carboplatin. Samples were collected before and up to 21 days after administration of carboplatin. We used validated, ultra-sensitive, inductively coupled plasma-mass spectrometry assays to measure Pt in canine urine, faeces, saliva, sebum and cerumen. Results showed that urine is the major route of elimination of Pt in dogs. In addition, excretion occurs via faeces and saliva, with the highest amounts eliminated during the first 5 days. The amount of excreted Pt decreased over time but was still quantifiable at 21 days after administration of carboplatin. In conclusion, increased Pt levels were found in all measured excretion products up to 21 days after administration of carboplatin to pet dogs, with urine as the main route of excretion. These findings may be used to further adapt current veterinary guidelines on safe handling of antineoplastic drugs and treated animals.
Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Neoplasias/veterinária , Platina/análise , Espectrofotometria Atômica/veterinária , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Carboplatina/administração & dosagem , Carboplatina/química , Carboplatina/farmacocinética , Cerume/química , Doenças do Cão/metabolismo , Cães , Relação Dose-Resposta a Droga , Fezes/química , Neoplasias/tratamento farmacológico , Platina/química , Platina/urina , Saliva/química , Sebo/químicaRESUMO
The objective of this study was to determine the surface contamination with platinum-containing antineoplastic drugs in veterinary and human oncology centres. Inductively coupled plasma mass spectrometry was used to measure platinum levels in surface samples. In veterinary and human oncology centres, 46.3 and 68.9% of the sampled surfaces demonstrated platinum contamination, respectively. Highest platinum levels were found in the preparation rooms (44.6 pg cm(-2)) in veterinary centres, while maximal levels in human centres were found in oncology patient-only toilets (725 pg cm(-2)). Transference of platinum by workers outside areas where antineoplastic drugs were handled was observed in veterinary and human oncology centres. In conclusion, only low levels of platinum contamination attributable to carboplatin were found in the sampled veterinary oncology centres. However, dispersion of platinum outside areas where antineoplastic drugs were handled was detected in veterinary and human oncology centres. Consequently, not only personnel, but also others may be exposed to platinum.
Assuntos
Antineoplásicos/análise , Carboplatina/análise , Monitoramento Ambiental/métodos , Espectrometria de Massas/métodos , Exposição Ocupacional/análise , Platina/análise , Animais , Institutos de Câncer , Contaminação de Equipamentos , Humanos , Espectrometria de Massas/veterinária , Países BaixosRESUMO
BACKGROUND: Peri-articular histiocytic sarcoma (PAHS) occurs in dogs, including Bernese Mountain Dogs (BMD). An etiologic relationship with previous joint disease has not been documented. HYPOTHESIS: Peri-articular histiocytic sarcoma in BMD will be more frequently encountered around previously diseased joints compared with normal joints. ANIMALS: 920 European BMD. METHODS: A retrospective study, in which data were obtained through an Internet questionnaire and from 2 veterinary pathology laboratories. Archived samples of hematoxylin-eosin (H&E) staining diagnosed PAHS and synovial cell sarcoma (SCS) were immunolabeled with CD18 and pancytokeratin. Descriptive, comparative, and actuarial statistics comprise the data analysis. RESULTS: All primary synovial tumors were identified as PAHS based on their morphology, positive CD18, and negative pancytokeratin labeling. Joint disease was diagnosed in 226 BMD, of which 15 developed PAHS in a previously diseased joint and 3 in a nondiseased joint. Of the remaining 694 BMD without joint disease, 9 developed PAHS. The odds ratio for a dog with previous joint disease developing PAHS is calculated as 5.4 (95% CI: 2.3-12.5; P < .0001) compared with no previous joint problem. A significant association between previous joint disease and PAHS in the same joint was demonstrated for the left elbow (P = .016), right elbow (P = .006), right shoulder (P = .047), left and right stifle (P < .001), and left carpal joint (P = .010). CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study suggest a relation between previous joint disease and the development of PAHS in the same joint of European BMD. Owners of BMD should monitor dogs for peri-articular swellings, particularly around previously diseased joints.
Assuntos
Doenças do Cão/patologia , Sarcoma Histiocítico/veterinária , Cápsula Articular/patologia , Artropatias/veterinária , Animais , Distribuição de Qui-Quadrado , Cães , Feminino , Sarcoma Histiocítico/etiologia , Sarcoma Histiocítico/patologia , Histocitoquímica/veterinária , Artropatias/patologia , Masculino , Estudos RetrospectivosRESUMO
In preparing this document the Authors aimed to pool current information on canine and feline mast cell disease. The information was gathered from international studies and a emphasis was placed on material and opinion with a strong evidence base. We intend it to form the basis of our understanding in this disease at the current time and we anticipate that it will be particularly useful for the general practitioner. It should be emphasized that the authors are presenting this work from a European perspective.
Assuntos
Doenças do Gato/diagnóstico , Doenças do Cão/diagnóstico , Mastocitose/veterinária , Animais , Doenças do Gato/patologia , Doenças do Gato/terapia , Gatos , Doenças do Cão/patologia , Doenças do Cão/terapia , Cães , Mastócitos/patologia , Mastocitose/diagnóstico , Mastocitose/patologia , Mastocitose/terapia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/patologia , Síndromes Paraneoplásicas/terapia , Síndromes Paraneoplásicas/veterináriaAssuntos
Doenças do Cão/patologia , Mastocitoma Cutâneo/veterinária , Neoplasias Cutâneas/veterinária , Animais , Diagnóstico Diferencial , Cães , Feminino , Imuno-Histoquímica/veterinária , Masculino , Mastocitoma Cutâneo/patologia , Estadiamento de Neoplasias/veterinária , Neoplasias Cutâneas/patologiaRESUMO
Results of the treatment with a combination of carboplatin and piroxicam in seven dogs with advanced non-tonsillar oral squamous cell carcinoma (SCC) were retrospectively analysed. This multi-agent protocol was well tolerated by all dogs and resulted in a complete regression of the tumour without additional surgery in four of seven patients. Additional surgery was necessary to remove a metastatic lymph node in one dog and residual tumour in a second dog, which achieved a partial response following medical therapy. Median follow-up for all the dogs was 534 days, while the time-to-recurrence, time-to-progression and overall survival for this group of patients have not yet been reached. Our study, although limited in number of animals, suggests that this multiagent approach is a useful treatment option for oral non-tonsillar SCC in dogs and warrants wider application.
RESUMO
Six cats with an advanced stage squamous cell carcinoma (SCC) of the nasal planum were treated with a combination of superficial radiotherapy and intralesional carboplatin therapy. This multimodality protocol was well tolerated by the majority of cats and resulted in complete responses in all cats (100%). Median follow-up for all cats is 268 days, and the median time-to-recurrence, time-to-progression and overall survival have not yet been reached. Our study, although limited in number of animals and with a relatively short median follow-up compared to other studies for this disease, suggests that a combination of radiotherapy and intralesional carboplatin is a useful treatment option for an advanced stage SCC of the nasal planum in cats and warrants further application of the multimodality approach presented here.
RESUMO
BACKGROUND: cerebral hyperperfusion syndrome (HS), occurs in 0.5-1% of patients undergoing carotid endarterectomy (CEA), and may result in intracerebral haemorrhage and death. AIM: to diagnose HS by means of postoperative Transcranial Doppler (TCD). METHODS: between 1998 and 2001 nearly all 112 patients who underwent CEA were monitored for four days postoperatively by Transcranial Doppler. RESULTS: there were 3 patients with HS. All three showed TCD abnormalities hours before developing symptoms. One patient developed a full blown HS. Presumably, symptoms in the other two patients could be prevented by timely starting or restoring anti-hypertensive treatment. CONCLUSION: daily TCD investigation in all patients undergoing CEA seems an effective strategy for the presymptomatic detection of HS.
Assuntos
Transtornos Cerebrovasculares/etiologia , Endarterectomia das Carótidas/efeitos adversos , Ultrassonografia Doppler Transcraniana , Idoso , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Circulação Cerebrovascular , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Transtornos Cerebrovasculares/terapia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , SíndromeRESUMO
In most cell types the major pathway of sphingomyelin synthesis is the direct transfer of the phosphocholine head group from phosphatidylcholine to ceramide catalyzed by the enzyme L-acylsphingosine:phosphatidylcholine phosphocholinetransferase (SM synthase; EC 2.7.8.-). Although this pathway has been demonstrated in brain tissue, its quantitative importance has been questioned. An alternative biosynthetic pathway for sphingomyelin synthesis in brain tissue has been proposed, viz., the direct transfer of phosphoethanolamine from phosphatidylethanolamine to ceramide, followed by methylation of the ethanolamine moiety to a choline group. We have evaluated various possible biosynthetic pathways of sphingomyelin synthesis in rat spinal cord oligodendrocytes, the myelin-forming cells of the CNS, by labeling cells in culture with radiolabeled choline, ethanolamine, or serine. Our results indicate that, in oligodendrocytes, most of the phosphocholine for the biosynthesis of sphingomyelin is provided by phosphatidylcholine, which is predominantly derived from de novo synthesis. No evidence was found for the operation of the alternative pathway via ceramide-phosphoethanolamine. Furthermore, our results indicate that a small pool of phosphatidylcholine is provided by methylation of phosphatidylethanolamine, which in turn is formed preferentially by decarboxylation of phosphatidylserine.
Assuntos
Oligodendroglia/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Esfingomielinas/metabolismo , Animais , Células Cultivadas , Senescência Celular , Etanolamina , Etanolaminas/metabolismo , Feminino , Metilação , Fosfatidilserinas/metabolismo , Ratos , Ratos Wistar , Especificidade por SubstratoRESUMO
Sphingomyelin (SM) biosynthesis in cultured oligodendrocytes (OC) was evaluated: (i) with [14C] tracers (choline, ethanolamine, serine) to pinpoint the major metabolic routes; (ii) with fluorescent and truncated, radiolabeled ceramide analogs to determine the relative activities of SM-synthase in intra-and extra-Golgi compartments of OC. In contrast to a general contention in the literature that SM synthase is absent from the brain, our data show that (choline-->CDP-choline-->phosphatidylcholine (PC)-->SM) is the major anabolic route with only a minor contribution to PC via methylation of phosphatidylethanolamine (PE). SM synthase activity was found to be equally divided between intra- and extra-Golgi compartments of OC. Moreover, significant SM-synthase activity was recovered in purified myelin preparations. Our results shed new light on the possible involvement of sphingolipid-derived mediators in myelination.
Assuntos
Oligodendroglia/metabolismo , Esfingomielinas/biossíntese , Medula Espinal/metabolismo , Animais , Compartimento Celular , Oligodendroglia/ultraestrutura , Ratos , Ratos Wistar , Medula Espinal/ultraestruturaRESUMO
The regulation and maintenance of developmental lineages by trophic factors, both cell-mediated and soluble, is a key aspect of cellular differentiation in the nervous system. In this review we focus on oligodendrocytes and their progenitors and how differentiation and survival are regulated by four neuropoietic cytokines: ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin M, and interleukin-6 (IL-6). We discuss how these cytokines act as "broad spectrum" factors. That is, how, even within a specific cell lineage, a given cytokine may have different effects on the target cells at various stages of differentiation.
Assuntos
Inibidores do Crescimento/fisiologia , Interleucina-6/fisiologia , Linfocinas/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Oligodendroglia/citologia , Peptídeos/fisiologia , Animais , Diferenciação Celular , Sobrevivência Celular , Fator Neurotrófico Ciliar , Citocinas/fisiologia , Humanos , Fator Inibidor de Leucemia , Modelos Neurológicos , Fatores de Crescimento Neural/fisiologia , Sistema Nervoso/citologia , Oligodendroglia/fisiologia , Oncostatina M , Células-Tronco/citologia , Células-Tronco/fisiologiaRESUMO
In most cell types sphingomyelin is synthesized predominantly in the cis-medial compartments of the Golgi stacks whereas the contribution of the plasma membrane is much lower. The aim of this study was to assess the contribution of both compartments to the synthesis of sphingomyelin in myelinating cells. Therefore, oligodendrocytes from rat spinal cord were incubated in culture with fluorescently- or radiolabelled ceramides, and the effects of a block in the vesicular flow (monensin, brefeldin A, low temperature) on surface synthesis of sphingomyelin were evaluated. The results indicate that approximately 50% of the sphingomyelin synthase is present at the plasma and myelin membranes of oligodendrocytes.
Assuntos
Membrana Celular/metabolismo , Ceramidas/metabolismo , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Esfingomielinas/biossíntese , Animais , Transporte Biológico/efeitos dos fármacos , Brefeldina A , Células Cultivadas , Temperatura Baixa , Ciclopentanos/farmacologia , Corantes Fluorescentes , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Monensin/farmacologia , Fosfatidilcolinas , Ratos , Ratos Wistar , Medula EspinalRESUMO
A clustering of generalized malignant lymphoma is reported in a single household of Rottweiler dogs (both parents and three of the four sibling in one litter) and in a breeding pair of unrelated Scottish terriers. In addition, malignant lymphoma of the myocardium was found in three directly related otterhounds (the sire and two sibling offspring). Possible genetic and viral factors in the aetiology of canine malignant lymphoma are discussed.
Assuntos
Doenças do Cão/genética , Linfoma/veterinária , Animais , Análise por Conglomerados , Cães , Feminino , Linfoma/complicações , Linfoma/genética , Masculino , LinhagemAssuntos
Glicolipídeos/fisiologia , Lipídeos/fisiologia , Animais , Transporte Biológico , Galactolipídeos , Glicolipídeos/química , Humanos , Lipídeos/química , Masculino , Estrutura Molecular , Bainha de Mielina/química , Bainha de Mielina/fisiologia , Espermatozoides/química , Espermatozoides/metabolismoRESUMO
We studied the metabolism of sphingolipids by oligodendrocytes derived from rat spinal cord by providing lipid vesicles with either N-lissamine-rhodaminyl-ceramide (LRh-Cer) or N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-ceramide (NBD-Cer) to the cells cultured in a chemically-defined medium. With both probes the major fluorescent product turned out to be sphingomyelin (SM). Most of LRh-SM was not cell-associated but recovered from the culture medium, probably due to back-exchange to the lipid vesicles. The accumulation of LRh-SM, both in the cells and in the medium, was inhibited in the presence of monensin or brefeldin A, whereas the production of NBD-SM was much less affected by these Golgi perturbing drugs. With LRh-Cer as substrate, LRh-labelled fatty acid (FA), galactosyl- and sulfogalactosyl-ceramides (GalCer and SGalCer) were also formed. NBD-Cer, however, was metabolized to glucosylceramide (GlcCer) and GalCer but not to SGalCer or NBD-FA. These data demonstrate that chemical modifications of ceramide alter its metabolism in oligodendrocytes and that the metabolites of LRh-Cer reflect the glycolipid composition of myelin more closely than those of NBD-Cer.
Assuntos
Ceramidas/metabolismo , Oligodendroglia/metabolismo , Animais , Células Cultivadas , Cromatografia em Camada Fina , Feminino , Fluorescência , Cinética , Oligodendroglia/citologia , Ratos , Ratos WistarRESUMO
It has been suggested that oligodendrocytes can actively phagocytose myelin debris during active myelination or after injury and experimental demyelination. Therefore, we have used a fluorescent analogue (N-lissamine rhodaminyl-(12-aminododecanoyl) cerebroside 3-sulphate) to study the metabolic fate of sulphatide, a galactosphingolipid that is highly enriched in myelin membranes. The fluorescent sulphatide was incorporated in small unilamellar vesicles and administered to cultured oligodendrocytes. The association of the lipid probe to the cells in culture was saturable in time and with the concentration of the probe. The processes of association, internalization and subcellular distribution were followed by confocal scanning laser microscopy and appeared to be very rapid. Within 20 min a marked perinuclear staining was seen. After prolonged incubation the fluorescence distributed gradually over the cytoplasm and into cellular branches along structures suggestive of cytoskeletal elements. Lipid analysis demonstrated that ceramide was the major metabolite present in the cells but galactosylceramide, sphingomyelin and free fatty acid were also detected. In the culture medium only free fatty acid and sphingomyelin were found. Monensin did not affect the cellular association and internalization of the fluorescent sulphatide but markedly reduced its conversion to metabolic products. These results indicate that exogenous sulphatide is targeted to the Golgi apparatus prior to its lysosomal degradation.
Assuntos
Monensin/farmacologia , Oligodendroglia/metabolismo , Sulfoglicoesfingolipídeos/metabolismo , Animais , Células Cultivadas , Cromatografia em Camada Fina , Feminino , Corantes Fluorescentes , Galactosilceramidas , Cinética , Microscopia de Fluorescência , Oligodendroglia/citologia , Gravidez , Ratos , Ratos Endogâmicos , RodaminasRESUMO
Spinal cords and cerebra from 7-day-old rat pups were compared as tissue sources for the isolation of oligodendrocytes and for studies on the development of these cells in culture. After 1 day in culture the serum-containing medium was replaced by a chemically-defined medium, which contained a cocktail of hormones that stimulated oligodendrocyte development. The cultures were characterized with various immunocytochemical markers; monoclonal A2B5 for bipotential glial progenitor cells, anti-galactocerebroside (GC) serum for oligodendrocytes, and anti-glial fibrillary acidic protein (GFAP) serum for astrocytes. The number of positive cells was counted and expressed as a percentage of total cells. At 1 day in culture the cell cultures from spinal cord contained 30% GC+ cells, increasing to 90% after 7 days in culture. In cultures derived from cerebra the percentage of GC+ cells was always lower than in cultures from spinal cord. In cerebral cultures GFAP+ cells increased from 15% at 1 day in culture to 30% at 7 days in culture, whereas it remained low in spinal cord cultures. The activity of oligodendroglial marker enzyme 2',3'-cyclic-nucleotide 3'-phosphodiesterase was followed during development in culture. The specific activity increased rapidly in both types of culture but was more than threefold higher in cultures derived from spinal cord. This procedure yields, within one week and without subculture, primary glial cultures from rat spinal cord, that are highly enriched in oligodendrocytes (greater than or equal to 90%; 3.10(5) oligodendrocytes per rat pup).
Assuntos
Dendritos , Medula Espinal/citologia , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/análise , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Células Cultivadas , Dendritos/enzimologia , Feminino , Imunofluorescência , Galactosilceramidas/análise , Gravidez , Ratos , Ratos Endogâmicos , Medula Espinal/metabolismoRESUMO
Recently it has been shown that B-50 is identical to the neuron-specific, growth-associated protein GAP43. The present study reports on the fate of B-50/GAP43 mRNA and B-50/GAP43 protein, determined by radioimmunoassay, in a rat model of peripheral nerve regeneration (sciatic nerve crush) over a period of 37 and 312 d, respectively. Moreover, the effects of repeated subcutaneous injection of the neurotrophic peptide Org.2766 (an ACTH4-9 analog) and of a conditioning lesion on B-50/GAP43 protein levels in the regenerating nerve and dorsal root ganglia (DRG) were investigated. Both treatments enhanced the functional recovery as evidenced by a foot-flick withdrawal test. Immunocytochemical analysis using antineurofilament antibodies revealed a peptide-induced increase in the number of outgrowing sprouts in the sciatic nerve. Both the peptide and the conditioning lesion amplified the crush lesion-induced increase in B-50 protein content in the nerve as determined by radioimmunoassay. B-50 protein levels seem to correlate proportionally with the number of sprouts. In the DRG of the crushed sciatic nerve, the time course of B-50 expression was studied. B-50 mRNA was quantified from Northern blots. A linear increase up to 10 times the basal level of B-50 mRNA was observed 2 d postsurgery, followed by a gradual decline to normal levels at day 37. The first significant rise in B-50 mRNA level became apparent between 8 and 16 hr after placement of the crush lesion. The first significant rise in B-50 protein level occurred 40 hr after the crush lesion, reaching a plateau of 3 times the basal level between day 6 and 20. B-50 protein levels in DRG cell bodies remained elevated up to 60 d after crush, a period much longer than that observed for B-50 mRNA. Thus, during a later phase of peripheral axonal regeneration, the presence of B-50 appears to be prolonged, probably by an increase in half-life and not so much by enhanced transcription. Treatment with Org.2766 did not affect the B-50/GAP43 levels in DRG cell bodies during the first 6 d following crush. Conditioning lesion resulted in a DRG B-50/GAP43 protein amount at the same level as in rats 14 d after the test lesion. B-50/GAP43 levels in DRG are probably influenced by the rapid axonal transport of the protein, as has been reported by others.
Assuntos
Gânglios Espinais/metabolismo , Proteínas de Membrana/metabolismo , Regeneração Nervosa , Proteínas do Tecido Nervoso/metabolismo , Nervo Isquiático/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Feminino , Proteína GAP-43 , Substâncias de Crescimento/metabolismo , Proteínas de Membrana/genética , Atividade Motora/fisiologia , Compressão Nervosa , Proteínas do Tecido Nervoso/genética , Fragmentos de Peptídeos/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Sensação , Nervo Tibial/fisiologia , Fatores de TempoRESUMO
A case of infection with the fur mite of domestic rabbits, Listrophorus gibbus, is reported. Possible methods of treatment of individual rabbits as well as of colonies of rabbits are reviewed. The presence of Listrophorus gibbus in conjunction with Cheyletiella parasitivorax is also discussed.