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1.
Exp Mol Pathol ; 100(2): 325-31, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26899552

ABSTRACT

Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70°C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70°C water was associated with N-nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells.


Subject(s)
Cell Proliferation/drug effects , Drinking Water/administration & dosage , Esophagus/pathology , Hot Temperature , Precancerous Conditions/pathology , Animals , Diethylnitrosamine/administration & dosage , Diethylnitrosamine/toxicity , Drinking Water/adverse effects , Drinking Water/chemistry , Esophagus/metabolism , Female , Immunohistochemistry , Ki-67 Antigen/metabolism , Mice, Inbred BALB C , Precancerous Conditions/etiology , Precancerous Conditions/metabolism , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Survival Analysis , Time Factors
2.
Braz. j. med. biol. res ; 44(10): 1048-1053, Oct. 2011. ilus
Article in English | LILACS | ID: lil-600686

ABSTRACT

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.


Subject(s)
Animals , Male , Rats , Antidepressive Agents, Tricyclic/administration & dosage , Anxiety/drug therapy , Behavior, Animal/drug effects , Corticosterone/administration & dosage , Imipramine/administration & dosage , Panic Disorder/drug therapy , Antidepressive Agents, Tricyclic/pharmacology , Corticosterone/pharmacology , Escape Reaction/drug effects , Imipramine/pharmacology , Maze Learning/drug effects , Motor Activity/drug effects , Rats, Wistar
3.
Braz J Med Biol Res ; 44(10): 1048-53, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21915474

ABSTRACT

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.


Subject(s)
Antidepressive Agents, Tricyclic/administration & dosage , Anxiety/drug therapy , Behavior, Animal/drug effects , Corticosterone/administration & dosage , Imipramine/administration & dosage , Panic Disorder/drug therapy , Animals , Antidepressive Agents, Tricyclic/pharmacology , Corticosterone/pharmacology , Escape Reaction/drug effects , Imipramine/pharmacology , Male , Maze Learning/drug effects , Motor Activity/drug effects , Rats , Rats, Wistar
4.
Pediatrics ; 106(3): 581-8, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10969106

ABSTRACT

OBJECTIVE: A prospective, double-blind, randomized, controlled trial was conducted to evaluate the growth and nutritional status of preterm infants receiving preterm human milk supplemented with a newly formulated powdered human milk fortifier (HMF), study fortifier (SF), or a powdered commercial HMF (CF). METHODS: Infants (n = 144) with a birth weight

Subject(s)
Dietary Supplements , Infant, Low Birth Weight , Infant, Premature/growth & development , Milk, Human , Anthropometry , Double-Blind Method , Evaluation Studies as Topic , Humans , Infant, Newborn , Nutritional Status , Prospective Studies
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