Lithium-induced malaise does not interfere with adaptation of the hypothalamic-pituitary-adrenal axis to stress.

We have recently demonstrated that adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated exposure to a stressor does not follow the rules of habituation and can be fully expressed after a single experience with severe stressors. In the present work we tested the hypothesis that adaptation could be impaired if animals experience malaise during initial exposure to the stressor. To this end, animals were allowed to drink saccharin for 30min before being exposed for 3h to immobilization on boards (IMO), a severe stressor; then they were given either saline or lithium ip after the first hour of IMO. Stress-naïve rats followed exactly the same procedure except IMO. Exposure to IMO caused a strong activation of the HPA axis whereas the effect of lithium was modest. Both IMO and lithium administration resulted in conditioned taste aversion to saccharin when evaluated 4days later. When all animals were exposed to IMO 6days later, reduced HPA response and less impact on body weight was observed in the two groups previously exposed to IMO as compared with stress-naïve rats. Therefore, lithium administration during the first IMO exposure did not affect adaptation of the HPA axis and weight gain. These results indicate that malaise per se only weakly activated the HPA axis and argue against the hypothesis that signs of physical malaise during exposure to the stressor could impair HPA adaptation.

The neuroendocrine response to stress under the effect of drugs: Negative synergy between amphetamine and stressors.

There have been numerous studies into the interaction between stress and addictive drugs, yet few have specifically addressed how the organism responds to stress when under the influence of psychostimulants. Thus, we studied the effects of different acute stressors (immobilization, interleukin-1ß and forced swimming) in young adult male rats simultaneously exposed to amphetamine (AMPH, 4 mg/kg SC), evaluating classic biological markers. AMPH administration itself augmented the plasma hypothalamic-pituitary-adrenal (HPA) hormones, adrenocorticotropin (ACTH) and corticosterone, without affecting plasma glucose levels. By contrast, this drug dampened the peripheral HPA axis, as well as the response of glucose to the three stressors. We also found that AMPH administration completely blocked the forced swim-induced expression of the corticotropin-releasing hormone (hnCRH) and it partially reduced c-fos expression in the paraventricular nucleus of the hypothalamus (PVN). Indeed, this negative synergy in the forced swim test could even be observed with a lower dose of AMPH (1mg/kg, SC), a dose that is usually received in self-administration experiments. In conclusion, when rats that receive AMPH are subjected to stress, a negative synergy occurs that dampens the prototypic peripheral physiological response to stress and activation of the PVN.

Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied.

Risk factors associated with colorectal flat adenoma detection.

OBJECTIVES: Colorectal flat adenomas have been associated with a higher risk of colorectal malignancy. We describe demographic characteristics and endoscopic findings in patients with colorectal flat adenomas. METHODS: In total, 1934 consecutive patients undergoing colonoscopy were prospectively included. Polyp shape was classified according to the Japanese classification. Chromoendoscopy was applied whenever a flat lesion was suspected. Indications for colonoscopy, demographic data, and characteristics of neoplastic lesions were recorded. Patients were classified as follows: group 1, no adenomas (n=1250); group 2, only protruding adenomas (n=427); group 3, protruding and flat adenomas (n=118); and group 4, only flat adenomas (n=139). RESULTS: Approximately one in every 10 patients (13.2%) had flat adenomas. Among them, concomitant protruding adenomas were identified in approximately half of the cases. In multivariate analysis, age older than 50 years [odds ratio (OR)=1.62; 95% confidence interval (CI)=1.08-2.43, P=0.02], protruding adenomas (OR=2.17; 95% CI=1.65-2.87, P<0.001), follow-up colonoscopy for polyps or cancer (OR=2.22; 95% CI=1.59-3.10, P<0.001), screening colonoscopy (OR=1.60, 95% CI=1.15-2.22, P=0.005), and specifically trained endoscopist (OR=2.02, 95% CI=1.53-2.68, P<0.001) were associated independently with flat adenoma detection. CONCLUSION: Flat adenomas have specific demographic factors that might help to improve detection. Particularly, age older than 50 years, colorectal neoplasia surveillance, and the presence of protruding adenomas should alert endoscopists to the possible presence of these lesions. Trained endoscopists may offer a greater chance of detecting these lesions.

Management of colonic Dieulafoy lesions with endoscopic mechanical techniques: report of two cases.

Although Dieulafoy lesion is generally located in the proximal stomach, other locations have been reported. We present two cases of bleeding colonic Dieulafoy in patients with chronic renal failure who were treated with mechanical methods. In the first case, an active arterial bleeding without mucosal defect was localized in the descending colon. In the second case, a protruding vessel with active bleeding was found in the transverse colon. The two patients were initially treated with epinephrine and hemostatic clips. In the second patient, an endoloop was attached to the base of the previously placed hemoclips because of rebleeding. To our knowledge, this is the first case of combined endoscopic approach with hemostatic clips and endoloop to treat a colonic Dieulafoy lesion. Colonic Dieulafoy lesions reported in the relevant literature and the hemostatic treatments used are reviewed.