RESUMO
The terminology applied to canine prostatic epithelial lesions, especially carcinomas, is currently not standardized and this hampers the ability of pathologists to study the biological and clinical significance of these lesions. The aim of this review is to present the essential histomorphological diagnostic attributes of a wide spectrum of prostatic epithelial lesions in dogs. In addition to the traditionally recognized prostatic hyperplasia, hormonal atrophy, prostatitis, squamous metaplasia, adenocarcinoma and transitional cell (urothelial) carcinoma, new entities are described and discussed in order to provide veterinary pathologists with a basic atlas of common histological lesions of the canine prostate that is comprehensive and easy to use.
Assuntos
Doenças do Cão/patologia , Próstata/patologia , Hiperplasia Prostática/veterinária , Neoplasias da Próstata/veterinária , Terminologia como Assunto , Animais , Cães , Masculino , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologiaRESUMO
Companion animals may serve as valuable models for studying human cancers. Although KRAS is the most commonly mutated gene in human ductal pancreatic cancers (57%), with mutations frequently occurring at codons 12, 13 and 61, human pancreatic acinar cell carcinomas (ACCs) lack activating KRAS mutations. In the present study, 32 pancreatic ACC samples obtained from 14 dogs and 18 cats, including seven metastases, were analyzed for six common activating KRAS mutations located in codons 12 (n = 5) and 13 (n = 1) using Sequenom MassARRAY. No KRAS mutations were found, suggesting that, similar to human pancreatic ACC, KRAS mutations do not play a critical role in feline or canine pancreatic ACC. Due to the similarity of the clinical disease in dogs and cats to that of man, this study confirms that companion animals offer potential as a suitable model for investigating this rare subtype of pancreatic carcinoma.
Assuntos
Doenças do Gato/genética , Doenças do Cão/genética , Mutação , Neoplasias Pancreáticas/veterinária , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Gatos , Análise Mutacional de DNA , Cães , Reação em Cadeia da Polimerase Multiplex , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias PancreáticasRESUMO
The receptor tyrosine kinase (RTK) KIT is a major focus of current research into canine mast cell tumors (MCTs). Little is known about the role of other RTKs, such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs). These RTKs are dysregulated in many human and animal cancers and are key regulators of tumor angiogenesis. The aims of this study were to assess the expression and activation (phosphorylation) status of KIT, VEGFR2, and PDGFR (α and ß) in canine MCTs and to examine associations with various clinical outcomes. c-KITmutational status and KIT cellular localization pattern were also evaluated for these tumors. Twenty-seven MCTs, consisting of 5 subcutaneous and 22 cutaneous tumors, from 25 dogs were evaluated. MCT biopsies, cultured mast cells, and skin from the surgical margin were analyzed through Western blotting. MCT biopsies were also used for KIT immunohistochemical labeling and polymerase chain reaction for c-KITmutational analysis. MCT had heterogeneous expression profiles for all 3 RTKs, which varied in intensity and activation status. Statistical analyses showed phosphorylated KIT, VEGFR2, and KIT cellular localization to be predictive of decreased survival time, disease-free interval, and increased metastatic rate. Expression of VEGFR2 and KIT diffuse cytoplasmic labeling were also significantly associated with increased rate of local recurrence. The results of the study show that phosphorylated KIT, KIT, VEGFR2, and PDGFRß, in addition to KIT localization, may be valuable prognostic determinants in MCTs and should be further studied to improve diagnostic and therapeutic modalities.
Assuntos
Biomarcadores Tumorais/metabolismo , Doenças do Cão/diagnóstico , Mastócitos , Receptores Proteína Tirosina Quinases/metabolismo , Neoplasias Cutâneas/veterinária , Animais , Doenças do Cão/enzimologia , Doenças do Cão/patologia , Cães , Feminino , Masculino , Mastócitos/enzimologia , Mastócitos/patologia , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptores Proteína Tirosina Quinases/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Serum N-terminal pro-C-natriuretic peptide (NT-proCNP) concentration at hospital admission has sufficient sensitivity and specificity to differentiate naturally occurring sepsis from nonseptic systemic inflammatory response syndrome (SIRS). However, little is known about serum NT-proCNP concentrations in dogs during the course of sepsis. OBJECTIVE: To determine serum NT-proCNP and cytokine kinetics in dogs with endotoxemia, a model of canine sepsis. SAMPLES: Eighty canine serum samples. METHODS: Eight healthy adult Beagles were randomized to receive Escherichia coli lipopolysaccharide (LPS, 5 µg/kg) or placebo (0.9% NaCl) as a single IV dose in a randomized crossover study. Serum collected at 0, 1, 2, 4, and 24 hours was stored at -80°C for batch analysis. Serum NT-proCNP was measured by ELISA and 13 cytokines and chemokines by multiplex magnetic bead-based assay. RESULTS: Serum NT-proCNP concentrations did not differ significantly between LPS- and placebo-treated dogs at any time. When comparing serum cytokine concentrations, LPS-treated dogs had higher interleukin-6 (IL-6), IL-10, TNF-α and KC-like at 1, 2, and 4 hours; higher CCL2 at 1, 2, 4, and 24 hours; and higher IL-8 and CXCL10 at 4 hours compared to placebo-treated dogs. There were no differences in serum GM-CSF, IFN-γ, IL-2, IL-7, IL-15 or IL-18 between LPS- and placebo-treated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum NT-proCNP concentration does not change significantly in response to LPS administration in healthy dogs. Certain serum cytokine and chemokine concentrations are significantly increased within 1-4 hours after LPS administration and warrant further investigation as tools for the detection and management of sepsis in dogs.
Assuntos
Citocinas/sangue , Doenças do Cão/sangue , Endotoxemia/veterinária , Peptídeo Natriurético Tipo C/sangue , Animais , Quimiocina CCL2/sangue , Quimiocina CXCL10/sangue , Quimiocinas/sangue , Estudos Cross-Over , Doenças do Cão/metabolismo , Cães/sangue , Endotoxemia/sangue , Endotoxemia/metabolismo , Feminino , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Sepse/sangue , Sepse/metabolismo , Sepse/veterinária , Fator de Necrose Tumoral alfa/sangueRESUMO
Transmucosal fixation is a new strategy for the treatment of edentulous mandibular fractures using external fixation principles within the oral cavity. The component parts of this technique are not new. External fixation, locking plates and transmucosal implants represent the foundations of this technique; the authors' development has been to bring these established methods together as a transmucosal intra oral locking plate fixation technique. The first eight patients treated with this technique have achieved bony union, they have no long-term sensory deficit and all patients were able to eat a soft diet with minimal discomfort the day after surgery. The first five of eight patients on long-term review showed bony union confirmed radiographically. For the remainder and subsequent patients, radiographs have not been scheduled at review, in the absence of symptoms.
Assuntos
Fixação de Fratura/métodos , Arcada Edêntula/cirurgia , Fraturas Mandibulares/cirurgia , Placas Ósseas , Parafusos Ósseos , Fixadores Externos , Seguimentos , Fixação de Fratura/instrumentação , Consolidação da Fratura/fisiologia , Humanos , Estudos Longitudinais , Radiografia PanorâmicaRESUMO
BACKGROUND AND PURPOSE: Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. We previously showed that LCA activates the oxidative stress-responsive nuclear factor (erythroid-2 like), factor 2 (Nrf2) in cultured liver cells, triggering adaptive responses that reduce cell injury. In this study, we determined whether Nrf2 protects the liver against LCA-induced toxicity in vivo. EXPERIMENTAL APPROACH: Nrf2 disrupted (Nrf2(-/-) ) and wild-type mice were treated with LCA (125 mg·kg(-1) body weight) to induce liver injury. Levels of mRNA, protein and function of important Nrf2 target genes coupled with liver histology and injury biomarkers of mice were examined. KEY RESULTS: In 4 day LCA treatments, we observed a significantly higher hepatic induction of Nrf2 target, cytoprotective genes including thioredoxin reductase 1, glutamate cysteine ligase subunits, glutathione S-transferases, haeme oxygenase-1 and multidrug resistance-associated proteins 3 and 4 in the wild type as compared with the Nrf2(-/-) mice. Moreover, basal and LCA-induced hepatic glutathione and activities of glutathione S-transferases and thioredoxin reductases were higher in wild-type than in Nrf2(-/-) mice. This reduced production of cytoprotective genes against LCA toxicity rendered Nrf2(-/-) mice more susceptible to severe liver damage with the presence of multifocal liver necrosis, inflamed bile ducts and elevation of lipid peroxidation and liver injury biomarkers, such as alanine aminotransferase and alkaline phosphatase. CONCLUSIONS AND IMPLICATIONS: Nrf2 plays a crucial cytoprotective role against LCA-induced liver injury by orchestrating adaptive responses. The pharmacological potential of targeting liver Nrf2 in the management of cholestatic liver diseases is proposed.
Assuntos
Colestase Intra-Hepática/prevenção & controle , Ácido Litocólico/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Animais , Ductos Biliares/patologia , Biomarcadores/metabolismo , Colestase Intra-Hepática/patologia , Peroxidação de Lipídeos , Fígado/patologia , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Necrose , Índice de Gravidade de DoençaRESUMO
A 9-year-old female Golden Retriever was presented with an acute onset of progressive respiratory distress. Echocardiography revealed a left atrial mass that limited blood flow from the pulmonary veins. The pathological evaluation revealed a left atrial ossifying myxosarcoma, bilateral adrenocortical adenomas, multifocal pituitary hyperplasia with expression of adrenocorticotrophic hormone, and multiple pituitary Rathke's cleft cysts. These pathologic findings are similar to those described in Carney complex, a familial human syndrome characterized by cardiac myxoma and extracardiac tumors associated with mutations in the protein kinase A regulator gene PRKAR1A. Mutations were not detected in PRKAR1A exons in the present case.
Assuntos
Neoplasias do Córtex Suprarrenal/veterinária , Doenças do Cão/patologia , Neoplasias Cardíacas/veterinária , Mixossarcoma/veterinária , Neoplasias Hipofisárias/veterinária , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/patologia , Animais , Diagnóstico Diferencial , Doenças do Cão/diagnóstico , Cães , Evolução Fatal , Feminino , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/patologia , Mixossarcoma/diagnóstico , Mixossarcoma/patologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologiaRESUMO
The type-I insulin-like growth factor receptor (IGF-IR) is frequently overexpressed in breast cancer and therapeutic agents targeting IGF-IR are currently in development. The ultimate success of anti-IGF-IR therapies will depend on the extent to which established tumors remain dependent upon IGF-IR signaling for sustained growth. To investigate the potential benefits and pitfalls of targeting IGF-IR, we used a doxycycline inducible mouse model of IGF-IR initiated breast cancer. We found that downregulation of IGF-IR results in tumor-size-dependent regression to an undetectable state. Partially regressed tumors almost always resumed growth in the absence of doxycycline and a proportion of tumors that regressed to an undetectable state ultimately recurred. This re-emergence of tumor growth in the absence of doxycycline was facilitated by IGF-IR-dependent and IGF-IR-independent mechanisms. Tumor escape from IGF-IR dependence was associated with an epithelial to mesenchymal transition and upregulation of transcriptional repressors of E-cadherin. These results suggest that tumors initiated by IGF-IR have the ability to become independent of this initiating oncogene, and IGF-IR independence is associated with characteristics consistent with an epithelial to mesenchymal transition.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Receptor IGF Tipo 1/metabolismo , Animais , Neoplasias da Mama/genética , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Progressão da Doença , Doxiciclina/farmacologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos , Camundongos Transgênicos , Receptor IGF Tipo 1/genética , Recidiva , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
BACKGROUND: Successful thawing and orthotopic transplantation of ovarian tissue has produced live offspring in mice, but until now has only been successful for very young ovary donors. METHODS: Whole and half ovaries from adult C3H/HeNCrlBR (C3H) and whole ovaries from B6129SF1/J were frozen-thawed and then grafted orthotopically into B6C3F1/CrlBR (B6C3F1) and B6129SF1/J recipients, respectively. In bilateral transplant groups (bilateral), recipients underwent a bilateral ovariectomy, followed by orthotopic grafting. In unilateral groups recipients either underwent bilateral ovariectomy followed by unilateral grafting (unilateral(ovx)) or had only one ovary removed and replaced with a graft (unilateral) along with complete transection of the remaining oviduct. RESULTS: Ovary size and number of follicles decreased dramatically in grafted compared with control groups, but the loss in the unilateral(ovx) group was significantly less than in the unilateral group. Similar numbers of litters and litter size were obtained in bilateral and unilateral grafts of fresh ovary. However, a much lower number of litters and litter size were derived from unilateral grafts than from unilateral(ovx) grafts of frozen ovary. CONCLUSIONS: Normal fertility can be restored by orthotopic grafting of fresh or frozen adult mouse ovaries and no significant difference between fresh and frozen ovaries was found. Grafting of half ovaries does not alter the overall fertility rate. Unilateral(ovx) grafting is an efficient procedure to produce live pups and removes the negative effect of recipient native ovaries on post-grafting fertility.
Assuntos
Criopreservação , Fertilidade , Ovariectomia , Ovário/fisiopatologia , Ovário/transplante , Animais , Feminino , Tamanho da Ninhada de Vivíparos , Masculino , Camundongos , Camundongos Endogâmicos , Folículo Ovariano/patologia , Período Pós-Operatório , ReproduçãoRESUMO
Previously, we have shown that Copenhagen (Cop) rats are highly resistant to the induction of putative preneoplastic, glutathione S-transferase 7-7- (GST 7-7) positive liver lesions following treatment with a modified resistant hepatocyte (RH) protocol. The objective of this study was to determine if resistance is inherited in a dominant or recessive manner and to derive an estimate of the number of genetic loci involved. We crossed male and female Cop rats with F344 rats to produce F1 offspring. Backcross rats were generated using female F1 rats and either Cop or F344 males, resulting in B1c and B1f generations, respectively. The male rats from all these crosses were initiated with diethylnitrosamine (200 mg/kg) at 7 to 8 weeks of age and were promoted 3 weeks later with the RH protocol (2-acetylaminofluorene and a two-thirds partial hepatectomy). The rats were sacrificed 3 weeks after the partial hepatectomy and their livers were sectioned and stained for GST 7-7-positive lesions. The susceptibility of F1 rats was in between Cop and F344 rats, having 21.7% +/- 2.0% (mean +/- SEM) of their liver volume occupied by lesions versus 4.2% +/- 0.8% for Cop and 53.0% +/- 5.8% for F344 rats. As expected, B1c rats had a volume of liver occupied by lesions that was in between the F1 and Cop rats at 13.5% +/- 1.6%. Surprisingly, B1f rats were similar to B1c rats in their resistance (9.1% +/- 2.1%). These results point to a complex, polygenic inheritance pattern that can be explained by a minimum of four loci, one of which shows recessive epistasis.
Assuntos
Predisposição Genética para Doença , Neoplasias Hepáticas Experimentais/genética , Lesões Pré-Cancerosas/genética , Animais , Movimento Celular , Feminino , Glutationa Transferase/metabolismo , Hepatectomia , Masculino , Lesões Pré-Cancerosas/enzimologia , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Endogâmicos F344RESUMO
Matrix metalloproteinases- (MMPs) 2 and 9 (gelatinases A and B) have been implicated in tumor invasion and metastasis, and recent studies have shown increased levels of these enzymes during recovery from partial hepatectomy (PH) in rats. F344 rats are highly susceptible to the growth of glutathione S-transferase 7-7- (GST 7-7) positive preneoplastic liver lesions promoted using the modified resistant hepatocyte (RH) protocol. Since the RH protocol consists of 2-acetylaminofluorene (2-AAF) followed by a PH, we reasoned that MMP-2 and -9 might be critical for the growth of lesions. Using gelatin zymography, we examined the expression of these enzymes in the livers of F344 rats treated with the RH protocol and sacrificed on Days 2, 4, 7, 14, and 21 after 2-AAF/PH. We found increases in both pro- and active MMP-2 and -9 over baseline levels, with the highest levels occurring on Day 7 post-PH. Also, a 54-kDa band, likely to be proMMP-1, was elevated in a pattern similar to MMP-2 and -9. In contrast to F344 rats, identically treated Copenhagen rats that are highly resistant to promotion of liver lesion growth using the RH protocol had significantly lower levels of proMMP-1 and -2. To test the importance of these MMPs to the growth of liver lesions, F344 rats that had been initiated with diethylnitrosamine were treated using the RH protocol. They then received either the MMP inhibitor batimastat (30 mg/kg, intraperitoneally) or vehicle alone daily from Day 3 to 20 post-PH and were sacrificed on Day 21. There were no differences in the percentage of liver volume occupied by GST 7-7-positive lesions (19.1 +/- 4.84 vs 19.4 +/- 3.31, treated versus vehicle, mean +/- SEM) or liver weight as a percentage of body weight (4.11% +/- 0.15 vs 4.07% +/- 0.18, treated versus vehicle, mean +/- SEM) between the treated and control groups. Treatment of rats with batimastat clearly did not affect lesion growth or liver regeneration following the RH protocol. These results suggest that increases in gelatinase expression during the RH protocol are a result of the promotional stimulus rather than a mechanism by which 2-AAF/PH causes lesion growth.
Assuntos
Neoplasias Hepáticas/enzimologia , Metaloproteinase 2 da Matriz/fisiologia , Metaloproteinase 9 da Matriz/fisiologia , Lesões Pré-Cancerosas , Alquilantes/farmacologia , Animais , Densitometria , Dietilnitrosamina/farmacologia , Glutationa Transferase/metabolismo , Fígado/fisiologia , Ratos , Ratos Endogâmicos F344 , Fatores de TempoRESUMO
The aim of this study was to assess complications following various orthognathic surgical procedures that required early surgical intervention. This study was carried out on 821 patients who had undergone surgical treatment for correction of dentofacial deformities between 1985 and 2000. Only patients who required a second procedure to deal with immediate or early postoperative complications (i.e., those occurring within 4 weeks of surgery) were investigated in this study. Twelve patients underwent a second surgical procedure; 9 had undergone conventional osteotomy surgery, and 3 had undergone distraction osteogenesis. Three Le Fort I cases had to be further impacted and repositioned, and 4 vertical subsigmoid osteotomies had to be reexplored. The details of the complications are presented, and possible methods by which these problems could be reduced and/or prevented are discussed.
Assuntos
Anormalidades Craniofaciais/cirurgia , Anormalidades Maxilomandibulares/cirurgia , Complicações Pós-Operatórias/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Má Oclusão/cirurgia , Mandíbula/cirurgia , Maxila/cirurgia , Osteogênese por Distração/efeitos adversos , Osteotomia/efeitos adversos , Osteotomia de Le Fort/efeitos adversos , Complicações Pós-Operatórias/prevenção & controleRESUMO
This is a report from the first phase of a longitudinal study of the ways young adults imagine their future lives. The future possible selves of 223 18- and 19-year-old adults were examined using the Anticipated Life History measure (ALH), a psychological instrument prompting participants to describe their future life course from their 21st birthday until their death. When the ALH narratives were coded for presence/absence of life events, female participants were more likely to predict career choice, marriage, children, divorce, and death of spouse than their male counterparts; when coded for psychological qualities, female participants demonstrated greater psychological complexity and awareness of future life role choices and conflicts. Participants with lower SES wrote ALH narratives with fewer altruistic acts, less awareness of life role complexity, and fewer anticipated conflicts and their resolutions than those with higher SES.
Assuntos
Ego , Acontecimentos que Mudam a Vida , Adolescente , Adulto , Altruísmo , Conflito Psicológico , Feminino , Previsões , Humanos , Relações Interpessoais , Masculino , Satisfação Pessoal , Qualidade de Vida , Autoavaliação (Psicologia) , Fatores Sexuais , Ajustamento Social , Classe Social , Percepção SocialRESUMO
Previously, we have shown that Copenhagen (Cop) rats are highly resistant, compared with susceptible F344 rats, to the growth of glutathione S-transferase 7-7 (GST 7-7) positive preneoplastic liver lesions following treatment with a modified resistant hepatocyte (RH) protocol. Donryu rats, a strain with a level of susceptibility similar to F344, have a reduced T-cell response compared with the closely related, but highly resistant, DRH rat. Cop and DRH rats share several characteristics in their resistance to preneoplastic liver lesion growth and this study, therefore, was designed to examine whether T-cells play a role in Cop resistance. Cop rats were crossed with an athymic (nude) rat to produce F1s that were then interbred to produce F2 animals, some of which were nude with a partial Cop background. A comparison of the susceptibility of nude F2 animals and their euthymic (non-nude) littermates allowed us to determine what role, if any, T-cells play in Cop resistance. We treated 11 Cop, 11 F344, 19 nude F2s, and 18 non-nude F2s with diethylnitrosamine (DEN), followed 3 weeks later by a modified RH protocol. As expected, F344 rats were highly susceptible, having 41.9 +/- 3.3% (mean +/- SEM) of their liver section areas occupied by GST 7-7-positive lesions and Cop rats were highly resistant, having only 4.7 +/- 1.1% of their liver section areas occupied by lesions. Both nude and non-nude F2s were, like Cop rats, highly resistant (1.8 +/- 0.29 and 2.7 +/- 0.45%, respectively). These results show that T-cells are unnecessary for Cop rat resistance, or only play a minor role, and that the nude parental strain is also likely to be resistant to the growth of preneoplastic liver lesions.
Assuntos
Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas Experimentais/imunologia , Linfócitos T/imunologia , Animais , Carcinoma Hepatocelular/patologia , Cruzamentos Genéticos , Feminino , Glutationa Transferase/metabolismo , Imunidade , Imunidade Inata , Neoplasias Hepáticas Experimentais/patologia , Masculino , Fenótipo , Ratos , Ratos Endogâmicos F344 , Ratos NusRESUMO
The insulin-like growth factors (IGFs) are mitogenic polypeptides that have been linked to a variety of normal physiological processes as well as neoplasia. Overexpression of several components of the IGF system is associated with hepatocarcinogenesis in humans and rodents. In rat liver, diets rich in n-6 polyunsaturated fatty acid (PUFA) enhance the development of preneoplastic lesions and tumors. Therefore, the objective of this study was to determine the effect of these dietary fatty acids on the hepatic expression of the various components of the IGF system. The mRNA levels of IGF-1 and the type 1 receptor were not different in livers of rats fed a diet containing 20% corn oil (CO) compared with those fed 5% CO. Analysis of the IGF binding proteins revealed that insulin-like growth factor binding protein-1 (IGFBP-1) levels were altered by the amount and type of dietary fat. A 2.5-fold induction of IGFBP-1 mRNA occurred within 1 week after the animals were fed the 20% corn oil diet compared with those fed 5% CO and was further enhanced to over 6-fold after 1 month. Furthermore, IGFBP-1 protein was only detectable in the livers of animals fed the 20% CO diet. Induction of IGFBP-1 mRNA (4.5-fold) also occurred in rats fed a high-fat diet containing safflower (rich in n-6 PUFAs) compared with those fed a high-fat diet containing menhaden oil (rich in n-3 PUFAs). The induction of IGFBP-1 mRNA was independent of serum insulin levels and the development of insulin resistance. Since IGFBP-1 mRNA is upregulated in regenerating liver, we reasoned that the induction of IGFBP-1 mRNA may be associated with an increase in cell proliferation; however, no difference was observed in the hepatic labeling index of rats fed the 20% CO compared with the 5% CO diet. In summary, these studies show a striking induction by dietary n-6 PUFAs of hepatic IGFBP-1, a protein that has been implicated in liver cancer development.
Assuntos
Gorduras Insaturadas na Dieta/toxicidade , Ácidos Graxos Insaturados/toxicidade , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Fígado/efeitos dos fármacos , Fígado/metabolismo , Animais , Divisão Celular/efeitos dos fármacos , Ácidos Graxos Ômega-6 , Feminino , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Insulina/sangue , Resistência à Insulina , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like II/genética , Neoplasias Hepáticas Experimentais/etiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Previously, we have shown that Copenhagen (Cop) rats are highly resistant to the induction of putative preneoplastic, glutathione S-transferase 7-7 (GST 7-7)-positive liver lesions following treatment with a modified resistant hepatocyte protocol. The objective of the current study was to establish the time course for the development of resistance and examine potential resistance mechanisms in Cop rats using F344 rats as susceptible controls. Male Cop and F344 rats (n = 25), 7-8 weeks of age, were initiated with diethylnitrosamine (200 mg/kg) and promoted 3 weeks later with four doses of 2-acetylaminofluorene (20 mg/kg) and a 2/3 partial hepatectomy (PH). Groups of rats from each strain were killed on days 2, 4, 7, 14 and 21 post-PH, 2 h after receiving bromodeoxyuridine. Cop livers contained similar numbers of GST 7-7-positive lesions to F344 livers on days 2 and 4 post-PH. The percent volume of liver occupied by these lesions did not differ between the strains on days 2, 4 and 7 post-PH. On day 14, however, approximately 29% of the liver volume in F344 rats was occupied by lesions, whereas in Cop rats this was significantly less (approximately 9%, P < 0.001). On day 21, lesions occupied approximately 58% of F344 rat livers and only approximately 6% of Cop livers. Despite these differences, the labeling index of hepatocytes was not significantly different between the strains at any time point, either within lesions or within surrounding normal liver. Furthermore, the apoptotic indices were not different between the strains at any time. However, differences were found in the extent of lesion remodeling (redifferentiation) and in the pattern of oval cell response following PH in Cop livers. By day 14 post-PH, approximately 76% of Cop liver lesions showed evidence of remodeling, compared with only approximately 14% of F344 lesions. The oval cell response to PH was equivalent in the two strains up to day 4 post-PH but by day 7, in F344 livers there was extensive migration of these cells into the liver parenchyma, whereas in Cop livers, the response remained localized to the portal regions. These results suggest that Cop resistance occurs at the promotion stage and not the initiation stage of carcinogenesis. Resistance appears not to be due to a lower proliferation rate nor to a higher apoptotic rate within Cop lesions. Precocious remodeling and/or a diminished oval cell response, however, may contribute to the resistance of Cop rats to the growth of GST 7-7-positive hepatic lesions.
Assuntos
Glutationa Transferase/metabolismo , Neoplasias Hepáticas Experimentais/enzimologia , Lesões Pré-Cancerosas/enzimologia , 2-Acetilaminofluoreno , Animais , Apoptose , Bromodesoxiuridina , Divisão Celular , Dietilnitrosamina , Hepatectomia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos , Especificidade da Espécie , Fatores de TempoRESUMO
PURPOSE: It was the purpose of the present study to examine the possibility of increased muscle coordination after anterior cruciate ligament (ACL) reconstruction through the wearing of a compression sleeve. METHODS: Thirty-six patients were studied who had undergone unilateral ACL reconstruction at least 12 months previously. All subjects were required to perform a 10-cm standing drop jump from an elevated platform onto a force plate, to land on one leg, and thereafter maintain a one-legged balance for 25 s. This task was repeated three times without and three times with an elastic compression sleeve worn on the reconstructed limb. For analysis, the task was partitioned into a landing phase (150 ms), an adjusting phase (10s), and a balancing phase (10s). The peak impact loadings were measured in each direction (Fx, Fy, and Fz) during landing, while force-time integrals (intFz, intFy, and intFz) and root mean square (RMS) error of these forces were calculated for the adjusting and balancing phases. The path length and RMS of the center of pressure coordinates (Ax and Ay) were obtained for the adjusting and balancing phases combined. RESULTS: Drop landings with the bandage produced significantly larger (P < 0.001) peak ground reaction forces in the vertical and anteroposterior direction, suggesting increased subject confidence in their knee. Wearing the knee bandage also enabled the patients to reduce all measured parameters in the anteroposterior direction (rmsFx, intFx, rmsAx) during both the adjusting and balancing phases (P < 0.001 ). A significant reduction in the center of pressure path length further indicated an enhanced steadiness during the one-legged stance. CONCLUSIONS: It was concluded that a compression sleeve improved the total integration of the balance control system and muscle coordination.
Assuntos
Ligamento Cruzado Anterior/cirurgia , Braquetes , Traumatismos do Joelho/cirurgia , Equilíbrio Postural , Adulto , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Período Pós-Operatório , Pressão , Ruptura , Análise e Desempenho de TarefasRESUMO
BACKGROUND: Resistance to mammary tumorigenesis in Copenhagen rats is associated with loss of early preneoplastic lesions known as intraductal proliferations. The cause of this disappearance, however, is unknown. RESULTS: There were no differences in the numbers of lesions in mammary whole-mounts prepared from Copenhagen or Wistar-Furth rats at 20 or 30 days after N-methyl-N-nitrosourea treatment, but at 37 days there were significantly fewer lesions in Copenhagen glands. Furthermore, lesions in Copenhagen glands were exclusively intraductal proliferations, whereas in Wistar-Furth glands more advanced lesions were also present. Immunohistochemical staining showed frequent cyclin D1 overexpression in Wistar-Furth lesions at 37 days, but not in Copenhagen lesions. There were, however, no differences in p16INK4a protein expression, bromodeoxyuridine labeling and apoptotic indices, or mast cell infiltration between Copenhagen and Wistar-Furth lesions at any time. CONCLUSIONS: Overexpression of cyclin D1 in preneoplastic lesions may be important in the development of mammary tumors in susceptible rats, although this overexpression does not appear to cause significant changes in cell kinetics. Furthermore, the low levels of cyclin D1 expression in Copenhagen intraductal proliferations may play a role in the resistance of these rats to mammary tumorigenesis.
Assuntos
Ciclina D1/biossíntese , Neoplasias Mamárias Experimentais/metabolismo , Animais , Bromodesoxiuridina/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma Ductal de Mama/metabolismo , Ciclina D1/análise , Inibidor p16 de Quinase Dependente de Ciclina/análise , Feminino , Imuno-Histoquímica , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/prevenção & controle , Metilnitrosoureia , Lesões Pré-Cancerosas/metabolismo , Ratos , Ratos Endogâmicos WFRESUMO
OBJECTIVE: To determine whether the distension of bowel-augmented bladders during filling and urine storage stimulates gastrointestinal peristalsis, resulting in diarrhoea and increased bowel frequency. PATIENTS AND METHODS: Five patients with symptomatic diarrhoea occurring after enterocystoplasty were studied; all had undergone bladder augmentation using ileum or colon at least 6 months previously. Using bowel frequency charts and colonic transit-time studies, their bowel function was assessed over 6 days while patients self-catheterized 4-hourly. This was repeated when the patient's bladders were decompressed with an indwelling catheter, and the results before and after bladder decompression compared. RESULTS: One patient showed a significant increase in colonic transit time, from 44.4 to 57.6 h, a decrease in the percentage of liquid motions from 50% to 42.8% and a corresponding small decrease in bowel frequency with bladder decompression. One patient reported an increase in liquid stools, but there was a minor decrease in colonic transit time. The remaining three patients showed no improvement with bladder decompression. When data were combined and analysed using Student's paired t-test, there were no significant changes in colonic transit time, bowel frequency and diarrhoea stools with bladder decompression. CONCLUSIONS: Eliminating bladder distension and hence distension of the incorporated bowel segment in reconstructed bladders has no impact on bowel motility.
Assuntos
Ceco/transplante , Diarreia/etiologia , Íleo/transplante , Complicações Pós-Operatórias/etiologia , Bexiga Urinaria Neurogênica/cirurgia , Adulto , Feminino , Motilidade Gastrointestinal/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/complicações , Disrafismo Espinal/complicações , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/fisiopatologiaRESUMO
A yellows disease of strawberry plants was identified in propagation beds in New Zealand. Affected plants were flatter to the ground, showed purpling of older leaves, reduced leaf size, yellowing of younger leaves, and sometimes plant death. A phytoplasma was observed in the phloem of affected plants. The 16S rRNA gene of the phytoplasma was amplified by polymerase chain reaction from symptomatic plants and from one asymptomatic plant, but not from 36 other asymptomatic plants. Nucleotide sequence analysis of the 16S rRNA gene showed that the phytoplasma is closely related or identical to the phytoplasma associated with the yellow leaf disease of New Zealand flax (Phormium tenax).