Does caffeine enhance bowel recovery after elective colorectal resection? A prospective double-blinded randomized clinical trial.

BACKGROUND: Postoperative ileus is a common condition following abdominal surgery. Previous studies have shown the positive effects of coffee on gastrointestinal motility. The aim of this study was to assess whether caffeine is the stimulatory agent in coffee that triggers bowel motility and thus may reduce the duration of postoperative ileus. METHODS: This was a single-centered, prospective, randomized controlled, double-blinded clinical trial. Patients scheduled to undergo elective laparoscopic colectomy between November 2017 and March 2019 were randomly assigned to receive either oral caffeine (100 mg three times daily) or placebo following the procedure. Primary endpoints were time to first flatus and time to first bowel movement. Secondary endpoints were time to tolerate a solid, low-residue diet and length of hospital stay. Registration number: NCT03097900. RESULTS: Seventy patients were included, [35 males, median age 56 years (range 19-79 years)]. After the exclusion of 12 patients, there were 30 patients in the caffeine group and 28 patients in the placebo group. The first passage of stool in the caffeine group occurred 18 h earlier than in the placebo group (p = 0.012); other endpoints did not reach statistical significance. No caffeine-related adverse events were observed. CONCLUSION: Caffeine consumption following colectomy is safe, leads to a significantly shorter time to first bowel movement, and may thus potentially lead to a shorter postoperative hospital stay.

Chronic brain cytochrome oxidase inhibition selectively alters hippocampal cholinergic innervation and impairs memory: prevention by ladostigil.

A 25-35% reduction of brain cytochrome oxidase (COx) activity found in Alzheimer's disease (AD) could contribute to neuronal dysfunction and cognitive impairment. The present study replicated the reduction in brain COx activity in rats by administering sodium azide (NaN(3)) for 4 weeks via Alzet minipumps at the rate of 1 mg/kg/h, and determined its effect on hippocampal cholinergic transmission, spatial and episodic memory. NaN(3) caused a selective reduction in choline acetyltransferase (ChAT) immunoreactivity in the diagonal band, a major source of cholinergic input to the hippocampus and cingulate cortex, without altering the number of cholinergic neurons. NaN(3) also induced a significant increase in vesicular acetylcholine transporter (VAChT)-immunoreactive varicosities, GAP-43 in the subgranular layer and of transferrin receptors (TfR) in the hilus of the dentate gyrus. These neurochemical changes were associated with impairment in spatial learning in the Morris water maze and in episodic memory in the object recognition test. Chronic treatment with ladostigil, a novel cholinesterase and monoamine oxidase inhibitor, prevented the decrease in ChAT in the diagonal band, the compensatory increase in synaptic plasticity and TfR and the memory deficits without restoring COx activity. Ladostigil had no significant effect on ChAT activity, synaptic plasticity or TfR in control rats. Ladostigil may have a beneficial effect on cognitive deficits in AD patients that have a reduction in cortical COx activity and cholinergic hypofunction.

Ladostigil, a novel multifunctional drug for the treatment of dementia co-morbid with depression.

Ladostigil is a novel drug that inhibits acetyl and butyrylcholinesterase, and monoamine oxidase (MAO) A and B selectively in the brain. It reverses memory deficits induced by chronic inhibition of cortical cytochrome oxidase in rats and has anxiolytic and antidepressant-like activity in prenatally-stressed rats. Ladostigil also prevents oxidative-nitrative stress induced in astrocytes in the hippocampal CA1 region following icv injection of STZ in rats which also impairs their episodic memory. The unique combination of ChE and MAO enzyme inhibition combined with neuroprotection makes ladostigil a potentially useful drug for the treatment of dementia in subjects that also have extrapyramidal dysfunction and depression.