RESUMO
PURPOSE: The purpose of this study was to explore the immediate effects of heavy isometric plantar flexor exercise on sensory output (pain during a functional task and mechanical pain sensitivity) and motor output (plantar flexor torque) in individuals with Achilles tendinopathy. METHODS: Sixteen subjects with Achilles tendinopathy participated in the study, mean (SD) age 48.6 (8.9) years and Victorian institute assessment-Achilles (VISA-A) score 61.3 (23.0). Sensory testing assessing pain during a functional task, mechanical pain sensitivity and motor output, and plantar flexor peak torque was completed prior to the intervention. All subjects completed a 45-s heavy isometric plantar flexor contraction and were then re-tested using the same sensory and motor tests. Motor output was assessed using isokinetic dynamometry at speeds previously identified as of interest in subjects with Achilles tendinopathy. RESULTS: Only 9 of the 16 subjects experienced pain during a functional task, self-reported pain was 4.2 (1.9) numerical rating scale (NRS) pre-intervention and 4.9 (3.2) NRS postintervention (n.s.). Mechanical pressure sensitivity was 446.5 (± 248.5) g/mm2 pre-intervention and 411.8 (± 211.8) g/mm2 post-intervention (n.s.). Mean concentric plantar flexor torque at 90 and 225°/s was 47.1 (14.5) and 33.6 (11.6) Nm, respectively, pre-intervention and 53.0 (18.5) and 33.4 (6.6) Nm post-intervention (p = 0.039 and n.s.). Eccentric torque at 90°/s was 98.5 (34.2) Nm preintervention versus 106.0 (41.4) Nm post-intervention (n.s.). CONCLUSION: In this exploratory study, patients with Achilles tendinopathy had a varied sensory and motor output response to heavy isometric contractions. Using the recommended approach of heavy 45-s isometric contractions did not offer a meaningful acute benefit for sensory or motor output for subjects with Achilles tendinopathy. Based on this study, heavy 45-s isometric contractions cannot be recommended for immediate pain relief or improved motor output for patients with Achilles tendinopathy. LEVEL OF EVIDENCE: IV, prospective cohort study.
Assuntos
Tendão do Calcâneo/fisiopatologia , Terapia por Exercício/métodos , Contração Isométrica , Dor/fisiopatologia , Tendinopatia/fisiopatologia , Tendinopatia/terapia , Adulto , Idoso , Estudos de Coortes , Feminino , Pé/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Medição da Dor , Modalidades de Fisioterapia , Estudos Prospectivos , Autorrelato , Inquéritos e Questionários , TorqueRESUMO
WHAT IS KNOWN AND OBJECTIVE: It is known that adverse drug reactions (ADRs) cause admission to hospital in adults and children. A recent adult study showed that ADRs are an important and frequent cause of hospital admission. The objective of this study is to develop methodology to ascertain the current burden of ADRs through a prospective analysis of all unplanned admissions to a paediatric hospital. METHODS: Prospective observational study over a 2-week period. RESULTS AND DISCUSSION: There were 19 admissions to the main hospital wards related to an ADR, giving an estimated incidence of 4%, with the ADR directly leading to the admission in 71% of cases. There were no deaths attributable to ADR. 33% of the reactions were possibly avoidable. The drugs most commonly implicated in causing admissions were anti-neoplastic agents. The most common reactions were neutropenia, vomiting and diarrhoea. The health burden of ADRs in the paediatric population is likely to be significant. This pilot study will be used to inform a much larger prospective study providing more detailed evidence of the burden of ill-health from ADRs in children. This larger study will add to a body of research aiming to identify drug-related problems within children to aid paediatric pharmacovigilance. WHAT IS NEW AND CONCLUSION: This study provides knowledge regarding the methodology to be used for a larger study investigating ADRs in children. The study will allow authors who wish to replicate the study in their own populations (internationally) to avoid some of the pitfalls in planning a large epidemiological study of paediatric ADRs. The study also provides an estimate of the incidence and problem of admissions caused by ADRs in a UK paediatric population.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hospitalização , Hospitais Pediátricos , Criança , Bases de Dados Factuais , Departamentos Hospitalares , Humanos , Incidência , Projetos Piloto , Estudos Prospectivos , Reino UnidoRESUMO
We previously developed an immunohistochemical method for estimating cell cycle state and phase in tissue samples, including biopsies that are too small for flow cytometry. We have used our technique to examine whether primary abnormalities of the cell cycle exist in laryngeal neoplasia. Antibodies against the markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67, and putative markers of cell cycle phase, cyclin D1 (G1-phase), cyclin A (S-phase), cyclin B1 (G2-phase) and phosphohistone H3 (Mitosis) were applied to paraffin-embedded sections of normal larynx (n = 8), laryngeal dysplasia (n = 10) and laryngeal squamous cell carcinoma (n = 10). Cells expressing each marker were determined as a percentage of total cells, termed the labelling index (LI), and as a percentage of Mcm-2-positive cells, termed the labelling fraction (LF). The frequency of coexpression of each putative phase marker was investigated by confocal microscopy. There was a correlation between Mcm-2 and Ki67 LIs (rho = 0.93) but Mcm-2 LIs were consistently higher. All cells expressing a phase marker coexpressed Mcm-2, whereas Ki67 was not expressed in a proportion of these cells. The putative phase markers showed little coexpression. Labelling index values increased on progression from normal larynx through laryngeal dysplasia to squamous cell carcinoma for Mcm-2 (P = 0.001), Ki67 (P = 0.0002), cyclin D1 (P = 0.015), cyclin A (P = 0.0001) and cyclin B1 (P = 0.0004). There was no evidence of an increase in the LF for any phase marker. Immunohistochemistry can be used to estimate cell cycle state and phase in laryngeal biopsies. Our data argues against primary cell cycle phase abnormalities in laryngeal neoplasia.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/patologia , Biomarcadores Tumorais/biossíntese , Ciclo Celular , Proteínas de Ciclo Celular/biossíntese , Fase G1 , Fase G2 , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Microscopia Confocal/métodos , Componente 2 do Complexo de Manutenção de Minicromossomo , Mitose , Proteínas Nucleares/biossíntese , Inclusão em Parafina , Fase S , Sensibilidade e EspecificidadeRESUMO
We have investigated whether immunohistochemical markers can identify differences in cell cycle phase distribution in ovarian serous neoplasms, including borderline tumours of different grades. Sections of normal ovary (n=18), serous cystadenoma (n=21), borderline serous tumours (n=21) and serous cystadenocarcinoma (n=15) were analysed by immunohistochemistry using markers of cell cycle entry (Mcm-2) and cell cycle phase, including cyclin D1 (mid-to-late G1), cyclin A (S phase), cyclin B1 (G2 phase) and phosphohistone H3 (mitosis). Double-labelling confocal microscopy confirmed marker phase specificity and phase estimations were corroborated by flow cytometry. On progression from normal ovary through serous cystadenoma and borderline tumours to cystadenocarcinomas, expression of Mcm-2 (P<0.0001), cyclin D1 (P=0.002), cyclin A (P<0.0001), cyclin B1 (P<0.0001) and phosphohistone H3 (P<0.0001) increased, paralleled by an increase in the S-phase fraction (cyclin A : Mcm-2 ratio; P=0.002). Borderline tumours of increasing grade also showed increased Mcm-2 and cyclin A expression, together with an increase in the S-phase fraction. Immunohistochemistry can be used to estimate cell cycle phase distribution in ovarian serous neoplasms, giving results similar to flow cytometric analysis and enabling direct assessment of tumour heterogeneity. Immunohistochemical estimates of the S-phase fraction may identify serous borderline tumours likely to exhibit malignant progression and/or select serous cystadenocarcinomas likely to respond to adjuvant therapy.
Assuntos
Biomarcadores Tumorais/análise , Proteínas de Ciclo Celular/análise , Ciclo Celular , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/patologia , Proteínas de Ciclo Celular/biossíntese , Transformação Celular Neoplásica , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica/métodos , Microscopia Confocal , Lesões Pré-Cancerosas , Manejo de EspécimesRESUMO
OBJECTIVE: Minichromosome maintenance protein 2 (Mcm2) is an accurate indicator of cell cycle entry in tissue samples, but its expression in inflammatory bowel disease (IBD) has not previously been investigated. We have used immunohistochemistry to assess the expression of Mcm2, in comparison to the existing proliferation marker Ki-67, in active IBD and IBD without inflammatory activity. MATERIALS AND METHODS: For this experimental study, sections from colonic biopsy and resection specimens of 48 patients with IBD (5 inactive/quiescent Crohn's disease (CD), 13 active CD, 19 inactive/quiescent ulcerative colitis (UC) and 11 active UC) and 15 normal controls were immunostained with antibodies to Mcm2 and Ki-67. The percentage of immunopositive epithelial nuclei was determined by calculating a labelling index (LI) for entire glands and for gland thirds (superficial, middle and basal). RESULTS: The Mcm2 LI was significantly increased in the superficial third of glands in active vs. inactive/quiescent UC (P < 0.0001) and active vs. inactive/quiescent CD (P = 0.001). The Mcm2 LI was significantly greater than the Ki-67 LI in active IBD, both in entire glands (P < 0.0001) and in the superficial third of glands (UC, P = 0.001; CD, P = 0.0002). Mcm2 LIs for entire glands were significantly higher in UC (all cases) compared to CD (all cases) (P = 0.032). CONCLUSIONS: There is increased cell cycle entry, as indicated by expression of Mcm2 and to a lesser extent Ki-67, in the superficial third of colonic glands in active IBD compared to inactive/quiescent IBD. Detection of Mcm2 may contribute to improved histological assessment of small tissue biopsies and may enable the development of a direct stool-based test for detection of active IBD and potentially for assessment of disease activity.
Assuntos
Proteínas de Ciclo Celular/biossíntese , Colo/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Colite Ulcerativa/metabolismo , Doença de Crohn/metabolismo , Humanos , Antígeno Ki-67/biossínteseRESUMO
Histological classification of laryngeal epithelial lesions is highly subjective, and methods of cytological detection are not well developed. Improved determination of aberrant cell cycle entry may allow increased objectivity in histological assessment and enable the development of less invasive diagnostic cytology tests. Sections of normal larynx (n=10), laryngeal dysplasia (n=20) and laryngeal squamous cell carcinoma (SCC) (n=10) were classified according to the Ljubljana classification and stained for markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67. Expression patterns were compared using double labelling confocal microscopy. There was a correlation between Mcm-2 and Ki67 labelling indices (rho=0.93; 95% CI [0.84, 0.97]) and both markers showed increased expression from normal epithelium to SCC (Mcm-2, P=0.001; Ki67, P=0.0002). Importantly, there was minimal expression of Mcm-2 or Ki67 in the most superficial layers of normal larynx and abnormal or atypical hyperplasia, in contrast to carcinoma in situ and SCC. Clusters of Mcm-2/5-positive cells were present in cytological preparations from SCC, but not from those showing atypical hyperplasia or inflammation in non-neoplastic tissue. Minichromosome maintenance protein-2 staining may increase the objectivity and reliability of histological grading of laryngeal epithelial lesions. Laryngeal brushings, combined with immuno-enhanced liquid-based cytology, could be useful, as a less invasive approach, to the detection of laryngeal malignant and premalignant lesions.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Laríngeas/metabolismo , Proteínas Nucleares/metabolismo , Antígenos de Neoplasias/metabolismo , Biópsia , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Ciclo Celular , Replicação do DNA , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Técnicas Imunoenzimáticas , Neoplasias Laríngeas/patologia , Componente 2 do Complexo de Manutenção de Minicromossomo , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologiaRESUMO
Vulval intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. To investigate the functional properties of VIN, the expression of several proteins involved in the regulation of the cell cycle as well as in situ DNA replication competence was analysed by immunohistochemistry. Snap-frozen vulval biopsies were graded as normal squamous epithelium (n=6), undifferentiated HPV positive VIN 1 (n=3), VIN 2 (n=8) and VIN 3 (n=20). Immunohistochemistry was performed using the following markers: cyclin D1 (expressed in middle/late G1), cyclin B1 (expressed in G2/early M), phosphorylated histone H3 (expressed during mitosis) and minichromosome maintenance (Mcm) proteins 2 and 5 (expressed during the cell cycle, but not in differentiated or quiescent cells). In situ DNA replication competence was used to identify S-phase cells. The percentage of positively stained nuclei in three representative microscopic fields was calculated per biopsy. In normal vulva, the expression of all markers was restricted to the proliferative compartment of the basal layer of the epithelium. In contrast in high-grade VIN, the majority of epithelial cells expressed the Mcm proteins from basal to superficial layer. The detection of cyclins B1 and D1, phospho-histone H3 and in situ DNA replication was also found through the full thickness of these lesions but by a lower proportion of the cells. This is consistent with these markers providing a series of 'snapshots' of the cell cycle status of individual cells. The low-grade VIN showed reduced expression of the cell cycle markers in relation to the level of dysplasia. The combination of these analyses establishes that the majority of VIN cells remain in a functional replicative or prereplicative state of the cell cycle. Clinical application of these analyses may provide a basis for improved diagnosis of VIN.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/genética , Carcinoma in Situ/metabolismo , Replicação do DNA , DNA de Neoplasias/metabolismo , Neoplasias Vulvares/genética , Neoplasias Vulvares/metabolismo , Biópsia , Carcinoma in Situ/patologia , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Ciclina B/metabolismo , Ciclina B1 , Ciclina D1/genética , Ciclina D1/metabolismo , Proteínas de Ligação a DNA , Feminino , Histonas/genética , Humanos , Técnicas Imunoenzimáticas , Componente 2 do Complexo de Manutenção de Minicromossomo , Proteínas Nucleares/metabolismo , Proteínas de Schizosaccharomyces pombe , Neoplasias Vulvares/patologiaRESUMO
We have investigated the potential utility of monoclonal antibodies against mini-chromosome maintenance-2 protein (Mcm2) in predicting meningioma recurrence. MCM proteins are members of the DNA-binding prereplicative complex and are essential for eukaryotic DNA replication. They are present throughout the cell cycle, but are down-regulated in quiescence and cell differentiation, making them specific markers of proliferating cells. We analysed 10 benign meningiomas that subsequently recurred within a 5-year period, together with 20 matched non-recurrent benign meningiomas. There was no significant correlation between histological subtype, mitotic count or Ki-67 labelling index and tumour recurrence. We observed that whilst the average Mcm2 labelling index (LI) of the tumour section as a whole (LI(Ave)) is not significantly different between recurrent and nonrecurrent meningiomas, the Mcm2 labelling index in the area of highest proliferative activity within the tumour section (LI(Max)) is significantly higher in recurrent meningiomas (p < 0.0001). Seven out of the 10 recurrent meningiomas displayed a Mcm2 LI((Max) greater than 30%, compared to 0 out of 20 for non-recurrent tumours. In conclusion, these results suggest that analysis of Mcm2 expression may facilitate identification of patients with a high risk of meningioma recurrence, for whom adjuvant radiotherapy may be of benefit.
Assuntos
Biomarcadores Tumorais/análise , Meningioma/química , Proteínas de Neoplasias/análise , Recidiva Local de Neoplasia/química , Proteínas Nucleares/análise , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Replicação do DNA , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Meningioma/patologia , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo , Índice Mitótico , Recidiva Local de Neoplasia/patologia , Proteínas Nucleares/imunologia , PrognósticoRESUMO
OBJECTIVE: To evaluate plasma taurine concentrations (PTC), whole blood taurine concentrations (WBTC), and echocardiographic findings in dogs fed 1 of 3 protein-restricted diets that varied in fat and L-carnitine content. ANIMALS: 17 healthy Beagles. DESIGN: Baseline PTC and WBTC were determined, and echocardiography was performed in all dogs consuming a maintenance diet. Dogs were then fed 1 of 3 protein-restricted diets for 48 months: a low-fat (LF) diet, a high-fat and L-carnitine supplemented (HF + C) diet, or a high-fat (HF) diet. All diets contained methionine and cystine concentrations at or above recommended Association of American Feed Control Officials (AAFCO) minimum requirements. Echocardiographic findings, PTC, and WBTC were evaluated every 6 months. RESULTS: The PTC and WBTC were not significantly different among the 3 groups after 12 months. All groups had significant decreases in WBTC from baseline concentrations, and the HF group also had a significant decrease in PTC. One dog with PT and WBT deficiency developed dilated cardiomyopathy (DCM). Taurine supplementation resulted in significant improvement in cardiac function. Another dog with decreased WBTC developed changes compatible with early DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Results revealed that dogs fed protein-restricted diets can develop decreased taurine concentrations; therefore, protein-restricted diets should be supplemented with taurine. Dietary methionine and cystine concentrations at or above AAFCO recommended minimum requirements did not prevent decreased taurine concentrations. The possibility exists that AAFCO recommended minimum requirements are not adequate for dogs consuming protein-restricted diets. Our results also revealed that, similar to cats, dogs can develop DCM secondary to taurine deficiency, and taurine supplementation can result in substantial improvement in cardiac function.
Assuntos
Carnitina/farmacologia , Dieta com Restrição de Proteínas/veterinária , Gorduras na Dieta/farmacologia , Cães/sangue , Coração/efeitos dos fármacos , Taurina/sangue , Animais , Biópsia/veterinária , Carnitina/sangue , Carnitina/metabolismo , Dieta com Restrição de Proteínas/efeitos adversos , Gorduras na Dieta/metabolismo , Cães/fisiologia , Ecocardiografia/efeitos dos fármacos , Eletrocardiografia/veterinária , Feminino , Coração/fisiologia , Masculino , Distribuição Aleatória , Análise de Regressão , Taurina/biossínteseRESUMO
Five client owned dogs with cystinuria were diagnosed with carnitine and taurine deficiency while participating in a clinical trial that used dietary management of their urolithiasis. Stored 24-hour urine samples collected from the cystinuric dogs before enrollment in the clinical diet trial were quantitatively evaluated for carnitine and taurine. These results were compared to those obtained from 18 healthy Beagles. Both groups of dogs were fed the same maintenance diet for a minimum of 2 weeks before 24-hour urine collection. The protocol used for 24-hour urine collections was the same for cystinuric dogs and healthy Beagles except that cystinuric dogs were catheterized at baseline, 8 hours, 12 hours, and at the end of the collection, whereas Beagles were catheterized at baseline, 8 hours, and at the end of the collection. Three of 5 dogs with cystinuria had increased renal excretion of carnitine. None of the cystinuric dogs had increased renal excretion of taurine, but cystinuric dogs excreted significantly less (P < .05) taurine in their urine than the healthy Beagles. Carnitinuria has not been recognized previously in either humans or dogs with cystinuria, and it may be 1 risk factor for developing carnitine deficiency. Cystinuric dogs in this study were not taurinuric; however, cystine is a precursor amino acid for taurine synthesis. Therefore, cystinuria may be 1 risk factor for developing taurine deficiency in dogs. We suggest that dogs with cystinuria be monitored for carnitine and taurine deficiency or supplemented with carnitine and taurine.
Assuntos
Carnitina/deficiência , Carnitina/urina , Cistinúria/veterinária , Doenças do Cão/urina , Taurina/deficiência , Taurina/urina , Animais , Estudos de Casos e Controles , Cistinúria/urina , Cães , Feminino , MasculinoRESUMO
PURPOSE: Heparin binds to human platelets and can cause activation and aggregation, although the mechanisms are unknown. To determine how heparin alters platelet function, we identified platelet-binding sites for heparin and measured heparin's influence on the function of platelet integrin alpha(IIb)beta(3) (glycoprotein IIb/IIIa). METHODS: Photoaffinity cross-linking and affinity chromatography experiments were performed to identify platelet membrane proteins that bind heparin. Heparin's effect on fibrinogen binding to platelets was measured with a radioligand-binding assay. The translocation to the cytoskeleton of Rap2, a guanosine triphosphate-binding protein, was measured from platelets aggregating in response to heparin and other agonists. RESULTS: Cross-linking and affinity chromatographic experiments positively identified the integrin alpha(IIb)beta(3) as a heparin-binding site. Heparin aggregation was calcium dependent. Low concentrations of unfractionated porcine mucosal heparin (2-5 U/mL) significantly increased fibrinogen I 125 binding to activated platelets, whereas higher doses did not. Heparin-mediated platelet aggregation was completely blocked by GRGDS peptide (5 mmol/L), a competitive inhibitor of fibrinogen binding, and was blocked by EDTA (2 mmol/L), which dissociates the functional integrin complex. Aggregation was associated with Rap2 translocation to the cytoskeleton, a sign of outside-in signaling. CONCLUSIONS: Heparin binds to the alpha(IIb)beta(3) integrin in vitro and ex vivo, and heparin increases fibrinogen binding to the integrin. Heparin-mediated aggregation requires an intact integrin and ligand and leads to Rap2 translocation to the cytoskeleton-an outside-in signal of ligand engagement. Heparin may directly modulate platelet integrin function, most likely through direct binding and modulation of integrin function.
Assuntos
Plaquetas/efeitos dos fármacos , Heparina/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Sítios de Ligação , Células Cultivadas , Fibrinogênio/metabolismo , Humanos , Receptores de Superfície Celular/metabolismoRESUMO
Turnover of carnitine in the body is primarily the result of renal excretion, and high-fat (HF) diets have been shown to increase urine carnitine excretion in healthy people. Recently, increased renal excretion of carnitine was observed in dogs diagnosed with cystinuria and carnitine deficiency. Carnitine deficiency has been linked to dilated cardiomyopathy and lipid storage myopathies in dogs and humans, and low-fat (LF) diets have been beneficial in some human patients with carnitine deficiency. In addition, HF, protein-restricted diets are often recommended for management of cystinuria in dogs. However, whether HF diets increase renal carnitine excretion in dogs or whether dogs with carnitine deficiency would benefit from LF diets remains unknown. Therefore, the purpose of this study was to determine the influence of dietary fat and carnitine on renal carnitine excretion in healthy dogs. Results from this study revealed that an HF diet increased urine carnitine excretion in dogs; however, carnitine excretion with the HF diet was not significantly different from that in dogs consuming an LF diet. Nonetheless, these results raise the possibility that increased renal carnitine excretion associated with HF diets could be one risk factor for development of carnitine deficiency in dogs with an underlying disorder in carnitine metabolism, and some dogs with carnitine deficiency may benefit from an LF diet. Another important observation in this study was that renal excretion of carnitine exceeded dietary intake in all diet groups, confirming previous reports that concluded that canine renal tubular cells reabsorb carnitine poorly when compared with those of humans.
Assuntos
Carnitina/farmacologia , Carnitina/urina , Dieta/veterinária , Gorduras na Dieta/farmacologia , Cães/urina , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Carnitina/administração & dosagem , Gorduras na Dieta/administração & dosagem , Quimioterapia Combinada , Feminino , MasculinoRESUMO
Most chicken strains are highly susceptible to avian leukosis virus (ALV) induction of bursal lymphoma, involving proviral integration within the c-myc proto-oncogene, while certain strains are genetically resistant to lymphomagenesis. A nested PCR assay was developed to analyse the appearance of proviral c-myc integrations after ALV infection of lymphoma-susceptible birds, and to determine whether these integrations arise in lymphoma-resistant birds. Proviral c-myc integrations are detected in bursa and other tissues from 6 day-old lymphoma-susceptible birds infected as embryos. The abundance of bursal cells carrying these integrations increases roughly 40-fold by 35 days of age, indicating that these cells hyperproliferate within the bursal environment. Bursal cells with proviral c-myc integrations also arise soon after infection of lymphoma-resistant embryos. However, these cells expand much more slowly than cells from lymphoma-susceptible birds. Both strains show the same rate of viral infection, so that resistance to lymphomagenesis occurs at a step subsequent to proviral c-myc integration. Proviral c-erbB gene integrations arise at the same frequency in bursa and other tissues of both strains, and they do not increase in abundance during development. These findings indicate that the mechanism of resistance to lymphomagenesis involves specific inhibition of cells with proviral c-myc integrations within the bursa.
Assuntos
Vírus da Leucose Aviária/genética , Genes myc , Integração Viral , Animais , Aves , Suscetibilidade a Doenças , Hematopoese , Imunidade Inata , Linfoma , Provírus/genética , Receptor ErbB-2/genética , Células Tumorais CultivadasRESUMO
Of the hundreds of minerals that are found in the earth, most canine uroliths are comprised of only six types: (1) magnesium ammonium phosphate, (2) calcium oxalate, (3) calcium phosphates, (4) ammonium urate and other salts or uric acid, (5) cystine, or (6) silica. Each type has characteristics that allow its identification. During the past two decades, the prevalence of calcium oxalate canine uroliths has dramatically increased, while struvite has decreased. The most effective treatment and prevention protocols are based on knowledge of the primary mineral type comprising the urolith.
Assuntos
Doenças do Cão/diagnóstico , Cálculos Urinários/veterinária , Distribuição por Idade , Animais , Oxalato de Cálcio/análise , Fosfatos de Cálcio/análise , Cistina/análise , Doenças do Cão/epidemiologia , Cães , Compostos de Magnésio/análise , Fosfatos/análise , Prevalência , Dióxido de Silício/análise , Estruvita , Ácido Úrico/análise , Cálculos Urinários/química , Cálculos Urinários/diagnósticoRESUMO
Cystine uroliths are a sequela to cystinuria, an inherited renal tubular defect in reabsorption of cystine and some other amino acids. At the Minnesota Urolith Center, 67 breeds of dogs were identified, including English Bulldogs, Dachshunds, Mastiffs, and Newfoundlands. In some dogs, the severity of cystinuria may decline with advancing age. Current recommendations for dissolution of cystine uroliths include various combinations of diet modification, diuresis administration of 2-MPG, and alkalinization of urine.
Assuntos
Cistinúria/veterinária , Doenças do Cão/etiologia , Cálculos Urinários/veterinária , Animais , Cistina/química , Cistinúria/complicações , Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Cães , Cálculos Urinários/diagnóstico , Cálculos Urinários/etiologia , Cálculos Urinários/terapiaRESUMO
Uroliths containing 70% or greater silica comprise approximately 1% of the canine uroliths submitted to the Minnesota Urolith Center. Male dogs are far more commonly affected than females. In our series, 84 different breeds were affected. Currently available data suggest dietary factors play a role in their formation. Diagnosis is facilitated by the characteristic jackstone configuration of silica uroliths, but must be confirmed by quantitative analysis. Voiding urohydropropulsion or surgery are currently the most practical methods of removal of silica uroliths.
Assuntos
Doenças do Cão/etiologia , Cálculos Urinários/veterinária , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Cães , Dióxido de Silício/química , Cálculos Urinários/diagnóstico , Cálculos Urinários/etiologia , Cálculos Urinários/terapiaRESUMO
Calcium oxalate (39%) and struvite (33%) were the predominant mineral types in canine nephroliths submitted to the Minnesota Urolith Center. Urate salts (12%) and calcium phosphate (2%) occurred less frequently. Provided they are not causing obstruction, struvite nephroliths may be dissolved with medical protocols. Although there are no dissolution protocols for nephroliths containing calcium, risk-benefit ratios should be considered before proceeding with surgery.
Assuntos
Doenças do Gato/terapia , Doenças do Cão/terapia , Cálculos Renais/veterinária , Animais , Doenças do Gato/diagnóstico , Doenças do Gato/epidemiologia , Gatos , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Cães , Feminino , Cálculos Renais/diagnóstico , Cálculos Renais/epidemiologia , Cálculos Renais/terapia , Fatores de RiscoRESUMO
Diagnostic and therapeutic drugs may enhance urolithiasis in one or a combination of ways, including: (1) alteration of urine pH in such fashion as to create an environment that increases the solubility of some lithogenic substances, (2) alteration of glomerular filtration rate, tubular reabsorption, and tubular secretion of drugs of endogenous substances so as to enhance promoters or impair inhibitors of urolithiasis, and (3) precipitation (e.g., drugs or their metabolites) to form a portion or all of a urolith.
Assuntos
Doenças do Gato/induzido quimicamente , Doenças do Cão/induzido quimicamente , Cálculos Urinários/veterinária , Alopurinol/efeitos adversos , Animais , Antibacterianos/efeitos adversos , Anti-Infecciosos/efeitos adversos , Anticonvulsivantes/efeitos adversos , Gatos , Cães , Inibidores Enzimáticos/efeitos adversos , Fluoroquinolonas , Primidona/efeitos adversos , Sulfonamidas/efeitos adversos , Tetraciclina/efeitos adversos , Cálculos Urinários/induzido quimicamente , Xantina Oxidase/antagonistas & inibidoresRESUMO
Voiding urohydropropulsion is a nonsurgical method of removing uroliths from the urinary bladder. Any urocystolith of sufficient size to pass through the distended urethral lumen can be safely and effectively removed by this technique. Compared to cystotomy, voiding urohydropropulsion offers several advantages: urolith removal can be performed in minutes, anesthetic period is shorter, postprocedural dysuria and hematuria are less severe, and it provides greater success for complete removal of small urocystoliths. This technique is not suitable for removal of large urocystoliths or uroliths that become lodged in the urethral lumen.
Assuntos
Doenças do Cão/terapia , Cálculos Urinários/veterinária , Micção , Animais , Cães , Tamanho da Partícula , Obstrução Uretral/etiologia , Obstrução Uretral/terapia , Obstrução Uretral/veterinária , Cálculos Urinários/complicações , Cálculos Urinários/terapiaRESUMO
Avian leukosis virus (ALV) infection induces bursal lymphomas in chickens after proviral integration within the c-myc proto-oncogene and induces erythroblastosis after integration within the c-erbB proto-oncogene. A nested PCR assay was used to analyze the appearance of these integrations at an early stage of tumor induction after infection of embryos. Five to eight distinct proviral c-myc integration events were amplified from bursas of infected 35-day-old birds, in good agreement with the number of transformed bursal follicles arising with these integrations. Cells containing these integrations are remarkably common, with an estimated 1 in 350 bursal cells having proviral c-myc integrations. These integrations were clustered within the 3' half of c-myc intron 1, in a pattern similar to that observed in bursal lymphomas. Bone marrow and spleen showed a similar number and pattern of integrations clustered within 3' c-myc intron 1, indicating that this region is a common integration target whether or not that tissue undergoes tumor induction. While all tissues showed equivalent levels of viral infection, cells with c-myc integrations were much more abundant in the bursa than in other tissues, indicating that cells with proviral c-myc integrations are preferentially expanded within the bursal environment. Proviral integration within the c-erbB gene was also analyzed, to detect clustered c-erbB intron 14 integrations associated with erythroblastosis. Proviral c-erbB integrations were equally abundant in the bone marrow, spleen, and bursa. These integrations were randomly situated upstream of c-erbB exon 15, indicating that cells carrying 3' intron 14 integrations must be selected during induction of erythroblastosis.