RESUMO
The prognostic value of phosphatase and tensin homolog (PTEN) loss in prostate cancer has primarily been evaluated by either fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). Previously, we found that PTEN loss by IHC was associated with increased risk of upgrading from biopsy (Gleason 3 + 3) to prostatectomy (Gleason 7+). Now, using an evaluable subset of 111 patients with adjacent biopsy sections, we analyzed the association between PTEN deletion in cancer and the odds of upgrading by a highly sensitive and specific four-color FISH assay. We also compared the concordance of PTEN loss by IHC and PTEN deletion by FISH. PTEN deletion was found in 27 % (12/45) of upgraded cases compared with 11 % (7/66) of controls (P = 0.03). Cancers with PTEN deletions were more likely to be upgraded than those without deletions (adjusting for age odds ratio = 3.40, 95 % confidence interval 1.14-10.11). With respect to concordance, of 93 biopsies with PTEN protein detected by IHC, 89 (96 %) had no PTEN deletion by FISH, and of 18 biopsies without PTEN protein by IHC, 15 had homozygous or hemizygous PTEN deletion by FISH. Only 4 biopsies of the 93 (4 %) with PTEN protein intact had PTEN deletion by FISH. When the regions of uncertainty in these biopsies were systematically studied by FISH, intra-tumoral variation of PTEN deletion was found, which could account for variation in immunoreactivity. Thus, FISH provides a different approach to determining PTEN loss when IHC is uncertain. Both FISH and IHC are concordant, showing consistent positive associations between PTEN loss and upgrading.
Assuntos
Biomarcadores Tumorais/análise , Hibridização in Situ Fluorescente , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias da Próstata/química , Neoplasias da Próstata/patologia , Idoso , Biópsia por Agulha , Humanos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodosRESUMO
To evaluate the endoscopic and histologic aspects of the esophageal mucosa in patients who underwent the Serra Dória operation for advanced megaesophagus. Thirty patients with advanced megaesophagus underwent the Serra Dória operation (operated group) and 15 patients were not submitted to surgery (non-operated group). The esophageal mucosa was evaluated by macroscopy and histologic examinations. In the operated group, 21, five and four patients with mild, moderate and severe esophagitis, respectively, were identified by endoscopy. In the non-operated group, 4 and 11 patients had moderate and severe esophagitis, respectively. The histologic examinations identified 19, six and five specimens with mild, moderate and severe esophagitis, respectively, in the operated group as opposed to one, three and 11 specimens with mild, moderate and severe esophagitis, respectively, in the non-operated group. The prevalence of severe esophagitis was high in the non-operated group while, after the Serra Dória operation, mild esophagitis was prevalent.
Assuntos
Acalasia Esofágica/patologia , Acalasia Esofágica/cirurgia , Esôfago/patologia , Adulto , Idoso , Anastomose em-Y de Roux , Endoscopia do Sistema Digestório , Esofagite/diagnóstico , Esofagite/etiologia , Esofagite/prevenção & controle , Esofagoplastia , Estudos de Avaliação como Assunto , Feminino , Gastrostomia/métodos , Humanos , Jejunostomia/métodos , Masculino , Pessoa de Meia-Idade , Mucosa/patologia , Período Pós-Operatório , VagotomiaRESUMO
In the present study we investigated the effect of acute fluoxetine administration on the expression of c-Fos in the rat brain under two different metabolic conditions: fed and fasting states. Wistar male rats, weighing 220+/-30g, received i.p. injections of saline solution or fluoxetine (10mg/kg), and were killed 2 h later. The brains were removed after transcardiac perfusion with phosphate-buffered saline followed by paraformaldehyde, and were then processed for immunohistochemistry. Fos-like immunoreactivity was quantified by a computerized system. Fasted animals faced an 18-h suppression of food intake, while fed groups were submitted to an initial 14-h period of fast followed by a 4-h period in which food was freely available. Both in fasting and fed states, fluoxetine-treated animals presented a significant increase in c-Fos expression in hypothalamic areas, limbic structures, circumventricular areas, and in mesencephalic and rhomboencephalic regions, as compared with saline-treated controls. The quantitative comparison of data obtained from fasted and fed animals showed that fasted rats treated with fluoxetine presented a higher c-Fos expression in the ventromedial hypothalamus and the paraventricular nuclei compared with the fed group, while in fluoxetine-treated fed rats c-Fos expression was higher in the arcuate nuclei, medial amygdala, locus coeruleus and dorsal raphe nuclei, as compared with fasted, fluoxetine-treated animals. These data indicate that the metabolic condition of the animals significantly modifies fluoxetine-induced brain c-Fos expression, suggesting that visceral and behavioral fluoxetine effects may be influenced by the metabolic state of the individual.
Assuntos
Encéfalo/efeitos dos fármacos , Fluoxetina/administração & dosagem , Privação de Alimentos/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Análise de Variância , Animais , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Imuno-Histoquímica/métodos , Masculino , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagemRESUMO
The aim of the present study was to investigate the effect of acute third ventricle injections of two different 5-HT(4) receptor antagonists, GR 113808 and SB 204070, on water intake in different situations. Injections of 80 nmol/rat of both GR 113808 and SB 204070 were unable to modify water intake in normohydrated rats. Pretreatment with GR 113808 (40 and 80 nmol/rat) and SB 204070 (80 and 160 nmol/rat) blunted water intake after third ventricle injections of angiotensin II (9.6 pmol/rat) compared to saline-pretreated controls. Pretreatment with 80 nmol/rat of both antagonists potentiated drinking induced by third ventricle injections of carbachol (11.0 nmol/rat) compared to saline-pretreated control. In all doses employed, none of the compounds was able to modify water intake in dehydrated rats. A separate control test using one-bottle taste aversion paradigm indicated that the reduction in water intake observed in some of the present experiments could not be attributed to a drug-induced malaise. It is suggested that central 5-HT(4) receptors exert a dualistic role on the control of water intake potentiating angiotensin II-induced drinking and inhibiting thirst induced by central cholinergic activation
Assuntos
Comportamento de Ingestão de Líquido/fisiologia , Receptores de Serotonina/fisiologia , Animais , Dioxanos/administração & dosagem , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Indóis/administração & dosagem , Injeções Intraventriculares , Masculino , Piperidinas/administração & dosagem , Ratos , Ratos Wistar , Receptores 5-HT4 de Serotonina , Antagonistas da Serotonina/administração & dosagem , Sulfonamidas/administração & dosagem , Sede/efeitos dos fármacos , Sede/fisiologia , Privação de Água/fisiologiaRESUMO
We have demonstrated that central administration of zinc in minute amounts induces a significant antidipsogenic action in dehydrated rats as well as in rats under central cholinergic and angiotensinergic stimulation. Here we show that acute third ventricle injections of zinc also block water intake induced by central ss-adrenergic stimulation in Wistar rats (190-250 g). Central inhibition of opioid pathways by naloxone reverses the zinc-induced antidipsogenic effect in dehydrated rats. After 120 min, rats receiving third ventricle injections of isoproterenol (160 nmol/rat) exhibited a significant increase in water intake (5.78 +/- 0.54 ml/100 g body weight) compared to saline-treated controls (0.15 +/- 0.07 ml/100 g body weight). Pretreatment with zinc (3.0, 30.0 and 300.0 pmol/rat, 45 min before isoproterenol injection) blocked water intake in a dose-dependent way. At the highest dose employed a complete blockade was demonstrable (0.54 +/- 0.2 ml/100 g body weight). After 120 min, control (NaAc-treated) dehydrated rats, as expected, exhibited a high water intake (7.36 +/- 0.39 ml/100 g body weight). Central administration of zinc blocked this response (2.5 +/- 0.77 ml/100 g body weight). Naloxone pretreatment (82.5 nmol/rat, 30 min before zinc administration) reverted the water intake to the high levels observed in zinc-free dehydrated animals (7.04 +/- 0.56 ml/100 g body weight). These data indicate that zinc is able to block water intake induced by central ss-adrenergic stimulation and that zinc-induced blockade of water intake in dehydrated rats may be, at least in part, due to stimulation of central opioid peptides.
Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Ingestão de Líquidos/efeitos dos fármacos , Isoproterenol/administração & dosagem , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Zinco/administração & dosagem , Agonistas Adrenérgicos beta/farmacologia , Animais , Desidratação/fisiopatologia , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Isoproterenol/farmacologia , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Peptídeos Opioides/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/efeitos dos fármacos , Sede/efeitos dos fármacos , Fatores de Tempo , Zinco/farmacologiaRESUMO
We have demonstrated that acute third ventricle injections of lead acetate (PbAc) exert a powerful antidipsogenic effect and induce a significant increase in renal sodium excretion. In the present study we confirm the antidipsogenic effect of lead and demonstrate that central administration of this metal, in minute amounts, significantly reduces salt intake both during dehydration and after central angiotensinergic stimulation. Adult male Wistar rats had the third ventricle cannulated seven days before the experiments. During this period they had free access to distilled water and hypertonic saline solution (1.5%). After a 24-h period of fluid deprivation, experimental animals received third ventricle injections of PbAc (0.3, N = 8 and 3.0 nmol/rat, N = 14) while controls received sodium acetate (NaAc; 3.0 nmol/rat, N = 10). Rats treated with PbAc at the highest dose showed a significant reduction (P<0.05) both in water and hypertonic saline intake when compared to controls. When the effect of lead administration on angiotensin II-induced water and salt intake was studied, normohydrated animals received third ventricle injections of angiotensin II (9.6 nmol/rat) after pretreatment with 3.0 nmol/rat of PbAc (experimental group, N = 10) or NaAc (controls, N = 8). The group pretreated with PbAc presented a significant reduction (P<0.05) in both water and salt intake compared to controls. Thus, this study confirms the antidipsogenic effect of central lead injections and demonstrates that the presence of lead in the brain exerts a significant inhibition of sodium appetite.
Assuntos
Angiotensinas/farmacologia , Apetite/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Compostos Organometálicos/administração & dosagem , Sódio na Dieta/administração & dosagem , Animais , Líquidos Corporais/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Compostos Organometálicos/farmacologia , Ratos , Ratos WistarRESUMO
We have demonstrated that central administration of zinc in minute amounts induces a significant antidipsogenic action in dehydrated rats as well as in rats under central cholinergic and angiotensinergic stimulation. Here we show that acute third ventricle injections of zinc also block water intake induced by central ß-adrenergic stimulation in Wistar rats (190-250 g). Central inhibition of opioid pathways by naloxone reverses the zinc-induced antidipsogenic effect in dehydrated rats. After 120 min, rats receiving third ventricle injections of isoproterenol (160 nmol/rat) exhibited a significant increase in water intake (5.78 ± 0.54 ml/100 g body weight) compared to saline-treated controls (0.15 ± 0.07 ml/100 g body weight). Pretreatment with zinc (3.0, 30.0 and 300.0 pmol/rat, 45 min before isoproterenol injection) blocked water intake in a dose-dependent way. At the highest dose employed a complete blockade was demonstrable (0.54 ± 0.2 ml/100 g body weight). After 120 min, control (NaAc-treated) dehydrated rats, as expected, exhibited a high water intake (7.36 ± 0.39 ml/100 g body weight). Central administration of zinc blocked this response (2.5 ± 0.77 ml/100 g body weight). Naloxone pretreatment (82.5 nmol/rat, 30 min before zinc administration) reverted the water intake to the high levels observed in zinc-free dehydrated animals (7.04 ± 0.56 ml/100 g body weight). These data indicate that zinc is able to block water intake induced by central ß-adrenergic stimulation and that zinc-induced blockade of water intake in dehydrated rats may be, at least in part, due to stimulation of central opioid peptides
Assuntos
Animais , Masculino , Ratos , Desidratação , Ingestão de Líquidos/efeitos dos fármacos , Isoproterenol/farmacologia , Naloxona/farmacologia , Neurotransmissores/administração & dosagem , Receptores Adrenérgicos beta/efeitos dos fármacos , Sede/efeitos dos fármacos , Zinco/administração & dosagem , Análise de Variância , Injeções Intraventriculares , Neurotransmissores/farmacologia , Peptídeos Opioides/efeitos dos fármacos , Ratos Wistar , Fatores de Tempo , Zinco/farmacologiaRESUMO
We have demonstrated that acute third ventricle injections of lead acetate (PbAc) exert a powerful antidipsogenic effect and induce a significant increase in renal sodium excretion. In the present study we confirm the antidipsogenic effect of lead and demonstrate that central administration of this metal, in minute amounts, significantly reduces salt intake both during dehydration and after central angiotensinergic stimulation. Adult male Wistar rats had the third ventricle cannulated seven days before the experiments. During this period they had free access to distilled water and hypertonic saline solution (1.5 percent). After a 24-h period of fluid deprivation, experimental animals received third ventricle injections of PbAc (0.3, N = 8 and 3.0 nmol/rat, N = 14) while controls received sodium acetate (NaAc; 3.0 nmol/rat, N = 10). Rats treated with PbAc at the highest dose showed a significant reduction both in water and hypertonic saline intake when compared to controls. When the effect of lead administration on angiotensin II-induced water and salt intake was studied, normohydrated animals received third ventricle injections of angiotensin II (9.6 nmol/rat) after pretreatment with 3.0 nmol/rat of PbAc (experimental group, N = 10) or NaAc (controls, N = 8). The group pretreated with PbAc presented a significant reduction in both water and salt intake compared to controls. Thus, this study confirms the antidipsogenic effect of central lead injections and demonstrates that the presence of lead in the brain exerts a significant inhibition of sodium appetite