RESUMO
The major histocompatibility complex (MHC) has repeatedly been found to influence mate choice of vertebrates, with MHC-dissimilar mates typically being preferred over MHC-similar mates. We used horses (Equus caballus) to test whether MHC matching also affects male investment into ejaculates after short exposure to a female. Semen characteristics varied much among stallions. Controlling for this variance with a full-factorial within-subject experimental design, we found that a short exposure to an MHC-dissimilar mare enhanced male plasma testosterone and led to ejaculates with elevated sperm numbers as compared to exposure to an MHC-similar mare. Sperm velocity seemed not affected by the treatment. Overall genetic similarity between stallions and mares (determined from polymorphic microsatellites on 20 different chromosomes) played no significant role here. The MHC type of the teaser mare also affected characteristics of cold-stored sperm after 24 and 48 hr. As expected from ejaculate economics, sperm viability was elevated after exposure to an MHC-dissimilar mare. However, oxidative stress and the percentage of sperm with a high DNA fragmentation were mostly increased after exposure to an MHC-dissimilar mare, depending also on whether the teaser mare was in oestrous or not. We conclude that males can quickly adjust ejaculate quality relative to a female's MHC, and that this male reaction to the social environment can also affect important characteristics of cold-stored semen.
Assuntos
Teste de Histocompatibilidade , Cavalos/genética , Complexo Principal de Histocompatibilidade/genética , Sêmen/metabolismo , Animais , Feminino , Masculino , Modelos BiológicosRESUMO
Multicellular organisms typically develop from a single fertilized egg and therefore consist of clonal cells. We report an extraordinary reproductive system in the yellow crazy ant. Males are chimeras of haploid cells from two divergent lineages: R and W. R cells are overrepresented in the males' somatic tissues, whereas W cells are overrepresented in their sperm. Chimerism occurs when parental nuclei bypass syngamy and divide separately within the same egg. When syngamy takes place, the diploid offspring either develops into a queen when the oocyte is fertilized by an R sperm or into a worker when fertilized by a W sperm. This study reveals a mode of reproduction that may be associated with a conflict between lineages to preferentially enter the germ line.
Assuntos
Formigas , Quimerismo , Reprodução , Animais , Masculino , Formigas/citologia , Formigas/genética , Formigas/crescimento & desenvolvimento , Diploide , Sêmen/citologia , Células Germinativas/citologiaRESUMO
Dendritic cells (DCs) are known to activate naive T cells to become effective helper cells. In addition, recent evidence suggests that DCs may influence naive B cells during the initial priming of antibody responses. In this study, using three-color confocal microscopy and three-dimensional immunohistograms, we have observed that in the first few days after a primary immunization, cells with dendritic morphology progressively localize within primary B cell follicles. These cells were identified by their ability to bind a fusion protein consisting of the terminal cysteine-rich portion of the mouse mannose receptor and the Fc portion of human immunoglobulin (Ig)G1 (CR-Fc). In situ, these CR-Fc binding cells express major histocompatibility complex class II, sialoadhesin, and CD11c and are negative for other markers identifying the myeloid DC lineage, such as (CD11b), macrophages (F4/80), follicular DCs (FDC-M2), B cells (B220), and T cells (CD4). Using CR-Fc binding capacity and flow cytometry, the cells were purified from the draining lymph nodes of mice 24 h after immunization. When injected into naive mice, these cells were able to prime T cells as well as induce production of antigen-specific IgM and IgG1. Furthermore, they produced significantly more of the lymphocyte chemoattractant, macrophage inflammatory protein (MIP)-1alpha, than isolated interdigitating cells. Taken together, these results provide evidence that a subset of DCs enters primary follicles, armed with the capacity to attract and provide antigenic stimulation for T and B lymphocytes.
Assuntos
Apresentação de Antígeno , Linfócitos B/imunologia , Células Dendríticas/imunologia , Imunidade , Lectinas Tipo C , Lectinas de Ligação a Manose , Receptores de Superfície Celular/imunologia , Receptores Fc/imunologia , Linfócitos T/imunologia , Animais , Antígenos CD/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Cooperação Linfocítica , Receptor de Manose , Camundongos , Camundongos Endogâmicos BALB C , Receptores de Superfície Celular/genética , Receptores Fc/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologiaRESUMO
BACKGROUND: Efficacy of inhaled fluticasone propionate (FP) for management of recurrent airway obstruction (RAO) has only been evaluated after several weeks' treatment. OBJECTIVES: To compare efficacy of (1) 3-day treatments with FP to dexamethasone (DEX) for management of RAO; and (2) FP and DEX to no treatment in prevention of acute RAO exacerbations. ANIMALS: Nine RAO affected horses. METHODS: Crossover studies in RAO-affected horses compared (a) 3-day treatment of RAO exacerbation with FP (3 and 6 mg q12h) and DEX (0.1 mg/kg q24h) and (b) FP (6 mg q12h) and DEX (0.1 mg/kg q24h) to no treatment for prevention of acute exacerbations of RAO. Treatment efficacy and unwanted effects were judged from maximal change in pleural pressure (DeltaPpl(max)), serum cortisol (COR), bronchoalveolar lavage (BAL) cytology, and subjective scores for respiratory distress and lameness. RESULTS: In treatment trial, DEX and FP (6 mg) significantly decreased DeltaPpl(max) by 48 and 72 hours, respectively; FP (3 mg) had no significant effect. DEX decreased COR more than did FP. In prevention trial, both DEX and FP (6 mg) prevented the increase in DeltaPpl(max) that occurred in untreated horses. Both treatments decreased COR to the same degree. FP and DEX had no effects on bronchoalveolar lavage fluid (BALF) cytology and there was no evidence of laminitis. CONCLUSIONS AND CLINICAL IMPORTANCE: FP (6 mg q12h) is as effective as DEX for prevention of acute exacerbations of RAO and lower doses should be evaluated. High-dose FP is not as effective as DEX for treatment of RAO exacerbations.
Assuntos
Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Pneumopatias Obstrutivas/veterinária , Aerossóis , Animais , Estudos Cross-Over , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Relação Dose-Resposta a Droga , Fluticasona , Cavalos , Pneumopatias Obstrutivas/tratamento farmacológicoRESUMO
Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroSpray Ionization, positive mode - Liquid Chromatography - Mass Spectrometry - Mass Spectrometry); with a Limit of Detection (LOD) estimated at 1 pg/mL. Following IV administration, TMQ plasma levels peaked at 1 min at 707 pg/mL, and at 9 min at 306 pg/mL following IT administration. Our results show that TMQ plasma concentrations decline rapidly following IV administration, which is consistent with the fast onset and short duration of TMQ effect that was observed in our previous studies. On the other hand, IT administration showed a very unique plasma concentration pattern. From a regulatory standpoint, the current available TMQ ELISA kit was also used in an attempt to detect TMQ from the plasma and urine samples. We report that the ELISA kit was unable to detect TMQ from any of the samples generated in these studies.
Assuntos
Obstrução das Vias Respiratórias/veterinária , Broncodilatadores/sangue , Tretoquinol/sangue , Obstrução das Vias Respiratórias/tratamento farmacológico , Animais , Broncodilatadores/uso terapêutico , Broncodilatadores/urina , Cromatografia Líquida , Feminino , Cavalos , Injeções Intravenosas , Intubação Intratraqueal , Masculino , Espectrometria de Massas/métodos , Tretoquinol/uso terapêutico , Tretoquinol/urinaRESUMO
REASON FOR PERFORMING STUDY: The bronchodilator effects of trimetoquinol (TMQ) have been studied when administered i.v. or intratracheally, but not in an aerosolised form. OBJECTIVES: To define the relationship between the therapeutic and adverse responses (therapeutic index) of TMQ when administered as an aerosol or by the oral route. METHODS: Increasing doses of TMQ were administered to horses with heaves as an aerosol and by the oral route. Dose ranged 100-1000 microg/horse for aerosolised TMQ and from 6-60 microg/kg bwt for the oral route. Airway and cardiac effects were assessed by measurement of maximal change in pleural pressure (deltaPplmax) and heart rate (HR), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action of aerosolised (1000 pg/horse) and oral (6-60 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Aerosol administration of TMQ caused dose-dependent bronchodilation but did not change HR or cause other observable side effects. When 1000 microg/horse was administered via aerosol, TMQ produced a 2-phase bronchodilation; an immediate effect lasting up to 30 min and a second phase between 2 and 4 h. Oral TMQ was therapeutically ineffective. CONCLUSION: Aerosol administration of TMQ is a safe and effective method of producing bronchodilation in horses.
Assuntos
Obstrução das Vias Respiratórias/veterinária , Broncodilatadores/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Tretoquinol/uso terapêutico , Administração por Inalação , Administração Oral , Obstrução das Vias Respiratórias/tratamento farmacológico , Animais , Broncodilatadores/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Cavalos , Masculino , Recidiva , Resultado do Tratamento , Tretoquinol/efeitos adversosRESUMO
REASONS FOR PERFORMING STUDY: Exercise-induced pulmonary haemorrhage (EIPH) occurs in the majority of horses performing strenuous exercise. Associated pulmonary lesions include alveolar and airway wall fibrosis, which may enhance the severity of EIPH. Further work is required to understand the pulmonary response to blood in the equine airways. OBJECTIVES: To confirm that a single instillation of autologous blood into horse airways is associated with alveolar wall fibrosis, and to determine if blood in the airways is also associated with peribronchiolar fibrosis. METHODS: Paired regions of each lung were inoculated with blood or saline at 14 and 7 days, and 48, 24 and 6 h before euthanasia. Resulting lesions were described histologically and alveolar and airway wall collagen was quantified. RESULTS: The main lesion observed on histology was hypertrophy and hyperplasia of type II pneumocytes at 7 days after blood instillation. This lesion was no longer present at 14 days. There were no significant effects of lung region, treatment (saline or autologous blood instillation), nor significant treatment-time interactions in the amount of collagen in the interstitium or in the peribronchial regions. CONCLUSION: A single instillation of autologous blood in lung regions is not associated with pulmonary fibrosis. POTENTIAL RELEVANCE: Pulmonary fibrosis and lung remodelling, characteristic of EIPH, are important because these lesions may enhance the severity of bleeding during exercise. A single instillation of autologous blood in the airspaces of the lung is not associated with pulmonary fibrosis. Therefore the pulmonary fibrosis described in EIPH must have other causes, such as repetitive bleeds, or the presence of blood in the pulmonary interstitium in addition to the airspaces. Prevention of pulmonary fibrosis through therapeutic intervention requires a better understanding of these mechanisms.
Assuntos
Hemorragia/veterinária , Doenças dos Cavalos/patologia , Pneumopatias/veterinária , Esforço Físico , Fibrose Pulmonar/veterinária , Animais , Feminino , Hemorragia/complicações , Hemorragia/patologia , Cavalos , Pulmão/patologia , Pneumopatias/complicações , Pneumopatias/patologia , Masculino , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , Índice de Gravidade de DoençaRESUMO
PURPOSE: Indirect inguinal hernia related to the presence of a patent processus vaginalis (PPV) in adult is estimated to be around 15%. Most surgeons would favor a standard anterior hernioplasty to minimize the potential risk of damaging the spermatic cord structures that are always intimately fused to the congenital peritoneal sac. This also means overlooking the potential benefit of alternative posterior techniques such as endoscopic totally extraperitoneal (TEP) repair that is known to offer faster recovery with reduced risk of developing chronic groin pain. The aim of this study was to evaluate the safety of TEP approach for repair of adult inguinoscrotal hernias associated with completely PPV and to compare those results with a corresponding group of male patients undergoing an identical procedure, but with no demonstrated PPV. METHODS: This is a prospective study of consecutive male patients diagnosed with inguinal hernia during a 10-year period and eligible for endoscopic TEP repair. Every recognized completely PPV were systematically divided taking care not to damage the attached cord structures and the proximal end closed with a pre-tied Endoloop of PDS. In both groups, all meshes were secured with fibrin sealant only. Patients were reviewed in clinic 2 and 6 weeks after the operation. Further follow-up was scheduled if deemed necessary. The primary post-operative outcome parameter was spermatic cord injury; secondary outcome parameters included groin pain, surgical complications, and recurrence. RESULTS: Nine hundred and thirty-nine hernia repairs were prospectively recorded during this period. All procedures were carried out endoscopically. A total of 41 patients with a median age of 27 years presented with 43 inguinoscrotal hernias (two bilateral) related to the presence of a congenital completely PPV. 72% of them were right-sided. No injury to the cord structures was recorded and only one complication (2.4%) occurred at 1 week post-operatively that was unrelated to the PPV. There was no report of chronic groin or testicular pain, symptomatic seroma formation, or hernia recurrence. By comparison, out of the 608 patients representing the no PPV group, there were 35 complications out of 33 patients (5.4%), one of those requiring subsequent laparoscopic revision. Only one early post-operative recurrence was recorded in this group (0.15%). CONCLUSIONS: In the presence of a completely PPV, the recognized benefit of a posterior approach, such as endoscopic TEP inguinal hernia repair, outweighs the theoretical risk of damaging the spermatic cord structures when dissecting and dividing the congenital hernia sac. This technique should be the preferred option among expert laparoscopic surgeons.
Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Adesivo Tecidual de Fibrina , Hérnia Inguinal/congênito , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cordão Espermático/cirurgia , Telas Cirúrgicas , Adulto JovemRESUMO
REASONS FOR PERFORMING STUDY: In vitro, glucocorticoids potentiate vasoconstriction of equine digital vessels to catecholamines and this has been implicated as a mechanism of glucocorticoid-induced laminitis. This observation has never been confirmed in vivo. OBJECTIVES: To study the effects of glucocorticoid therapy on vasoconstrictor responsiveness in the horse in vivo. METHODS: In a blinded, randomised cross-over experiment, 9 horses were treated with either dexamethasone (0.1 mg/kg bwt i.v. q. 24 h) or saline i.v. for 6 days. The changes in local average skin temperature before (baseline) and after intradermal injections of the alpha1-adrenoceptor agonist phenylephrine (PHE; 10(-4), 10(-5), 10(-6), 10(-7) and 10(-8) mol/l), endothelin-1 (ET-1; 10(-5), 10(-6), 10(-7), 10(-8) and 10(-9) mol/l) or ET-1 plus a blocker (BQ-123 10(-6) mol/l; RES-701 10(-6) mol/l; and L-NAME 10(-4) mol/l) were investigated with a thermograph. RESULTS: Dexamethasone (DEX) decreased baseline skin temperatures, suggesting reduced blood flow as a consequence of an increase in vasomotor tone. This was accompanied by potentiation of the response to PHE as demonstrated by a left shift in the dose-response curve and a decrease in the EC50. Dexamethasone did not potentiate ET-1, but the interplay with the lower baseline temperature resulted in a significantly lower skin temperature for this vasoconstrictor after DEX. The different ET-1 blockers had no effect on ET-1 modulated skin temperatures. CONCLUSIONS: Dexamethasone decreases skin perfusion. This is accompanied by a potentiated alpha1-adrenoceptor agonist response and a greater response to ET-1. POTENTIAL RELEVANCE: Glucocorticoid therapy probably decreases perfusion of the equine hoof. During disease states that already are characterised by hypoperfusion and/or increased levels of circulating catecholamines, glucocorticoid therapy could, according to the vascular model of laminitis, tilt the balance in favour of laminitis.
Assuntos
Temperatura Corporal/efeitos dos fármacos , Endotelina-1/farmacologia , Cavalos/fisiologia , Fenilefrina/farmacologia , Pele/irrigação sanguínea , Termografia/veterinária , Vasoconstritores/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Área Sob a Curva , Estudos Cross-Over , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Feminino , Termografia/métodosRESUMO
REASONS FOR PERFORMING STUDY: Guidelines for administration of oxygen to standing horses are unavailable because previous investigations of the efficacy of oxygen administration to increase arterial oxygenation in standing horses have produced equivocal results. OBJECTIVE: To determine the effect of nasal oxygen supplementation on inspired and arterial blood gas tensions in control horses and those with moderate to severe recurrent airway obstruction (RAO). METHODS: Normal horses (n = 6) and horses during an attack of RAO induced by stabling (n = 6) were studied. Oxygen was administered through either one or 2 cannulae, passed via the nares into the nasopharynx to the level of the medial canthus of each eye. Intratracheal inspired oxygen and carbon dioxide concentration and arterial blood gas tensions were measured at baseline and during delivery of 5, 10, 15, 20 and 30 l/min oxygen. RESULTS: Nasal cannulae and all but the highest oxygen flow rates were well tolerated. Fractional inspired oxygen concentration (F(I)O2) increased with flow but was significantly lower at all flow rates in horses with RAO compared with controls. Arterial oxygen tension (PaO2) was significantly increased (P < 0.001) by all flow rates, but was always lower in RAO-affected animals. At 30 l/min, PaO2 increased to 319 +/- 31 mmHg in control horses and 264 +/- 69 mmHg in horses with RAO. Additionally, a large arterial to end-tidal gradient for CO2 in RAO-affected horses was observed, indicating increased alveolar deadspace ventilation in these animals. CONCLUSIONS: The use of nasal cannulae to deliver oxygen effectively increases both F(I)O2 and PaO2 in horses with moderate to severe RAO. Oxygen flow rates up to 20 l/min are well tolerated, but flow rates of 30 l/min produce occasional coughing or gagging. POTENTIAL RELEVANCE: Oxygen therapy delivered by means of an intranasal cannula is a highly effective means of increasing arterial oxygen tension in horses with respiratory disease. Generally, flows of 10-20 l/min should be effective. If higher flows (20-30 l/min) are necessary, they should be delivered by means of 2 cannulae.
Assuntos
Doenças dos Cavalos/terapia , Pneumopatias Obstrutivas/veterinária , Oxigenoterapia/veterinária , Animais , Gasometria/veterinária , Feminino , Cavalos , Cinética , Pneumopatias Obstrutivas/terapia , Masculino , Consumo de Oxigênio , Oxigenoterapia/métodos , Pressão Parcial , Resultado do TratamentoRESUMO
REASON FOR PERFORMING STUDY: Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. OBJECTIVES: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. METHODS: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (deltaPplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 microg/kg bwt) and i.t. (2 microg/kg bwt) TMQ was evaluated over 6 h. RESULTS: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 microg/kg bwt, and was still increasing after administration of highest dose, 0.2 microg/kg bwt. Airway bronchodilation, measured as a decrease in deltaPplmax, also commenced at 0.01 microg/kg bwt. By the i.t. route, TMQ was 50-100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. CONCLUSION: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with 'heaves'. Further studies of TMQ by oral and aerosol routes are necessary. POTENTIAL RELEVANCE: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of 'heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other beta-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of 'heaves'.
Assuntos
Broncopatias/veterinária , Broncodilatadores/farmacocinética , Sistemas de Liberação de Medicamentos/veterinária , Doenças dos Cavalos/tratamento farmacológico , Tretoquinol/farmacocinética , Animais , Broncopatias/tratamento farmacológico , Broncodilatadores/uso terapêutico , Estudos Cross-Over , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos/efeitos adversos , Sistemas de Liberação de Medicamentos/métodos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Cavalos , Injeções Intravenosas/efeitos adversos , Injeções Intravenosas/métodos , Injeções Intravenosas/veterinária , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Intubação Intratraqueal/veterinária , Masculino , Pressão Propulsora Pulmonar/efeitos dos fármacos , Segurança , Resultado do Tratamento , Tretoquinol/uso terapêuticoRESUMO
Reduction 'en masse' of inguinal hernia is a rare entity defined as manual reduction of an external hernia sac back through the abdominal wall but where its content still remains incarcerated or strangulated into a displaced position, most often in the pre-peritoneal space. Small bowel obstruction habitually follows requiring urgent repair, preferentially via a trans-abdominal approach. Pre-operative clinical diagnosis is difficult and abdominal CT-scan imaging is the investigation of choice.
Assuntos
Hérnia Inguinal/complicações , Hérnia Inguinal/cirurgia , Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Progressão da Doença , Hérnia Inguinal/diagnóstico , Humanos , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Remissão Espontânea , Tomografia Computadorizada por Raios XRESUMO
Airway responsiveness was studied in cats 3 or 6 days after exposure to feline herpesvirus I. Control cats were sham inoculated with tissue culture media. Intrathoracic airway caliber was evaluated by pulmonary resistance (RL) and dynamic compliance (Cdyn). Trachealis shortening was quantitated with microfoil strain gauges, which measured the external diameter of tracheal ring 4. Airway smooth muscle contraction was produced using vagal stimulation and local infusion of acetylcholine. The diameter of tracheal ring 4 decreased with increasing frequency of vagal stimulation, and there was more constriction at 3 (PID3) than at 6 days postinfection (PID6) or in control cats. RL increased and Cdyn tended to decrease with increasing frequency of stimulation, but there was no difference between control and infected cats. Infected and control cats did not differ in their response to locally infused acetylcholine. Virus was consistently cultured from conjunctival, nasal, and oral mucous membranes, trachea, and main stem bronchi at PID3 but not from the trachea and main stem bronchi at PID6. Virus was never isolated distal to the main stem bronchi. Tracheal hyperresponsiveness to vagal stimulation correlates with the presence of virus at PID3 and is apparently presynaptic in origin.
Assuntos
Acetilcolina/farmacologia , Infecções por Herpesviridae/fisiopatologia , Pulmão/fisiopatologia , Músculo Liso/fisiopatologia , Traqueia/fisiopatologia , Animais , Gatos , Estimulação Elétrica , Herpesviridae/isolamento & purificação , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Valores de Referência , Sistema Respiratório/microbiologia , Traqueia/efeitos dos fármacos , Traqueia/fisiologia , Nervo Vago/fisiologia , Nervo Vago/fisiopatologiaRESUMO
We undertook a study to analyze the expression of urokinase-type plasminogen activator (u-PA) protein in colorectal cancer (CRC) and to compare it with c-erbB-2 (HER2/neu) and nm23 protein expression. Paraffin-embedded specimens from 58 patients with CRC were retrospectively collected. Immunohistochemical staining of u-PA, c-erbB-2, and nm23 was quantitatively evaluated using a color video image analysis (color VIA) technique. No correlation was found between u-PA expression and tumor stage, age, sex, or tumor site. Although there was no evidence from our data that the level of u-PA in the primary tumors could predict risk of liver metastasis or survival duration, CRC showing overexpression of u-PA (above 85 pixels) had a worse prognosis (P = 0.013). There were significant positive correlations among all three u-PA, c-erbB-2, and nm23 proteins (u-PA vs. c-erbB-2, P = 0.003; u-PA vs. nm23, P < 0.001; c-erbB-2 vs. nm23, P = 0.001), suggesting that, in vivo, all proteins interact or are similarly regulated.
Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Proteínas Monoméricas de Ligação ao GTP , Núcleosídeo-Difosfato Quinase , Receptor ErbB-2/biossíntese , Fatores de Transcrição/biossíntese , Ativador de Plasminogênio Tipo Uroquinase/biossíntese , Biomarcadores Tumorais/análise , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Nucleosídeo NM23 Difosfato Quinases , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Receptor ErbB-2/análise , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Fatores de Tempo , Fatores de Transcrição/análise , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/análiseRESUMO
We undertook a retrospective study to investigate the correlation between the expression of vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (u-PA) proteins with progression of colorectal carcinoma (CRC). Immunohistochemical analyses using antibodies against VEGF and u-PA were carried out on archival specimens of 58 human colon carcinomas, 30 liver secondaries and 20 adenomas. Expression of VEGF was significantly reduced in the metastatic liver tumours compared with primary ones (Wilcoxon test, P = 0.002), suggesting VEGF activity to be secondarily down-regulated once the tumour cells reach the hepatic parenchyma. There was no strong evidence from our data that the level of VEGF or u-PA in the primary tumour could predict risk of liver metastasis or survival duration. VEGF and u-PA expression were positively correlated in primary CRC suggesting that both proteins may interact in vivo (chi-square test, P = 0.019) in tumour progression.
Assuntos
Fatores de Crescimento Endotelial/análise , Neoplasias Hepáticas/secundário , Linfocinas/análise , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Idoso , Neoplasias Colorretais , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
We have previously shown that c-erbB-2 oncoprotein encoded by the erbB-2 gene is overexpressed in human colorectal cancers that metastasis compared to those that are cured by surgery. To determine whether c-erbB-2 is also differentially expressed in vivo in metastasising and non-metastasising tumours, we developed models of colorectal cancer growth in nude mice. Human colon cancer cell lines, HCT116, KM12SM, LIM1215 and SW480, were injected into the caecum after characterising their morphology, doubling time, DNA flow-cytometry and expression of c-erbB-2. Six weeks later, xenografted tissues were fixed for histological analysis and detection of c-erbB-2 by immunohistochemistry, 78% (21/27) of mice developed caecal cancers. The caecal tumours derived from HCT116, KM12SM or LIM1215 were highly metastatic; 67 to 100% of them had liver metastases and lymph node involvement and 33 to 75% had lung tumours. Most of the tumours were c-erbB-2-positive. In contrast SW480 caecal tumours had only 33% lymph node involvement, but not liver or lung metastases. Only one SW480 caecal tumour and one lymph node metastasis expressed c-erbB-2. C-erB-2 was more frequently expressed in xenografted tissues in colon cancer primaries and secondaries of the highly metastatic cells (HCT116, KM12SM and LIM1215) compared to the cells (SW480) giving predominantly local growth. Our results suggest that c-erbB-2 gene may play an important role in the development of metastasis from colorectal cancer.
Assuntos
Neoplasias do Colo/genética , Receptor ErbB-2/metabolismo , Animais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica , Células Tumorais CultivadasRESUMO
PURPOSE: To report spontaneous visual improvement in a patient with unilateral optic neuropathy due to pituitary metastasis. METHODS: Report of a case. RESULTS: A 54-year-old woman with a history of breast carcinoma lost vision in her right eye to 20/70 without any other symptoms. Six days later, vision spontaneously improved to 20/30. A pituitary mass compressing the right intracranial optic nerve was found on magnetic resonance imaging and the diagnosis of metastatic breast carcinoma was confirmed by biopsy. CONCLUSIONS: Spontaneous visual improvement can occur in the setting of compressive optic neuropathy by a solid mass.
Assuntos
Neoplasias da Mama/patologia , Neoplasias Hipofisárias/secundário , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia , Evolução Fatal , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Doenças do Nervo Óptico/etiologia , Remissão Espontânea , Transtornos da Visão/etiologia , Campos VisuaisRESUMO
The dose of aerosol pirbuterol that could be administered safely to ponies (weight approximately 200 kg) was determined by observation for sweating, trembling and excitement and measurement of heart and respiratory rates during cumulative administration of the drug. Sweating, trembling and excitement were first observed following a dose of 2,400 micrograms and became more severe at 3,200 micrograms. These effects were accompanied by an increase in heart rate but not a change in respiratory rate. When 3200 micrograms was administered without prior administration of lower doses, side effects were trivial. This dose was therefore tested for its bronchodilator activity. Pulmonary function was evaluated in ponies that developed airway obstruction ('heaves') when housed in a barn and fed hay. Measurements were made when ponies were in clinical remission (Period A) and during an acute attack of airway obstruction (Period B). At Period A, pirbuterol had no effect on pulmonary function. Barn housing increased pulmonary resistance and decreased dynamic compliance. At Measurement Period B, pirbuterol administration significantly reduced pulmonary resistance and increased dynamic compliance and minute ventilation. These changes were significant 5 min after drug administration and lasted for the 30 min duration of the study. Vehicle administration had no effect on pulmonary function. It was concluded that aerosol pirbuterol has few undesirable side effects and is an effective bronchodilator in ponies with recurrent airway obstruction.
Assuntos
Obstrução das Vias Respiratórias/veterinária , Broncodilatadores/uso terapêutico , Etanolaminas/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Cavalos/fisiologia , Aerossóis , Obstrução das Vias Respiratórias/tratamento farmacológico , Animais , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Relação Dose-Resposta a Droga , Etanolaminas/administração & dosagem , Etanolaminas/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Recidiva , Respiração/efeitos dos fármacosRESUMO
Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function.