Acute intracerebroventricular inositol does not reverse the effect of chronic lithium treatment in the forced swim test.

BACKGROUND: Lithium has numerous biochemical effects but it is difficult to dissect which of these is responsible for its therapeutic action in bipolar disorder. In the current study we aimed to address one of the major hypotheses, the inositol depletion hypothesis. This hypothesis postulates that lithium's mood-stabilizing effect is mediated by the depletion of brain inositol levels and the subsequent effect on cellular signaling. METHODS: We studied whether acute intracerebroventricular (ICV) administration of myo-inositol could reverse the antidepressant-like effect of chronic lithium treatment in the forced swim test (FST). RESULTS: In contrast with our prediction, acute myo-inositol administration did not reverse the effect of chronic lithium to decrease immobility in the FST. CONCLUSIONS: The results of the present study are limited due to the following: (1) inositol was given acutely while possible events downstream of inositol depletion might require a longer period and (2) ICV inositol may not have reached those areas of the brain involved in the FST.

Antidepressive-like effects of rapamycin in animal models: Implications for mTOR inhibition as a new target for treatment of affective disorders.

Lithium, the prototypic mood stabilizer, was recently demonstrated to enhance autophagy in cells. Recent hypotheses regarding the source of therapeutic effects of lithium as well as other mood stabilizers and antidepressants suggest that they may stem from increased neuroprotection, cellular plasticity and resilience. Hence it is clearly a possibility that enhanced autophagy may be involved in the therapeutic action by contributing to increased cellular resilience. A well-documented mechanism to induce autophagy is by inhibition of mTOR, a negative modulator of autophagy and rapamycin (sirolimus) is a commonly used inhibitor of mTOR. Accordingly, the present study was designed to evaluate the effects of rapamycin in animal models of antidepressant activity. A dose-response experiment in the mice forced swim test was performed and followed by additional testing of mice and rats in an open field, the forced swim test and the tail suspension test. Results show that sub-chronic, but not acute, administration of rapamycin doses of 10mg/kg and above, have an antidepressant-like effect in both mice and rats and in both the forced swim and the tail suspension tests with no effects on the amount or distribution of activity in the open field. Whereas it is tempting to conclude that the antidepressant-like effects are related to mTOR inhibition, they may also be the consequences of interactions with other intracellular pathways. Additional studies are now planned to further explore the behavioral range of rapamycin's effects as well as the biological mechanisms underlying these effects.

Small bowel phytobezoars: detection with radiography.

The authors reviewed the radiographic findings in 19 patients with phytobezoars of the small bowel. The most common predisposing causes were previous gastric outlet surgery and persimmon ingestion. Twelve patients underwent contrast material-enhanced studies of the upper gastrointestinal tract, and one patient underwent a barium enema study. These examinations revealed four gastric, two duodenal, and eight small bowel phytobezoars in 10 patients. The obstruction caused by small bowel phytobezoars frequently occurred in the jejunum or proximal ileum, more proximally than has been reported in previous series. Barium studies are useful in differentiating obstruction due to postoperative adhesions from obstruction caused by bezoars. In addition, barium studies enable the detection of residual gastric bezoars. This information has important implications in patient treatment because bezoar obstruction is unlikely to respond to conservative treatment, and concurrent gastric bezoars must be removed to prevent recurrent bowel obstruction.

Destructive bone lesions in primary amyloidosis.

We describe a patient with primary amyloidosis in whom multiple osteolytic lesions caused by amyloid bone tumours developed, and review the clinical features of the 18 cases with primary amyloidosis in whom destructive bone lesions have been reported. In contrast to amyloidosis associated with multiple myeloma, destructive lesions in the primary disease are mainly located to long bones; joint involvement is common, and radionuclide bone scan shows pronounced uptake of 99mTc-PP by the destructive bone lesions. Despite the superficial similarity between the destructive bone lesions associated with primary amyloidosis and multiple myeloma, distinction between these entities on clinical grounds is possible and may be easily confirmed by direct aspiration of the osteolytic infiltrates.