Supplementation of pancreatic digestive enzymes alters the composition of intestinal microbiota in mice.

Although pancreatic enzyme replacement therapy (PERT) is effective in the alleviation of pancreatic exocrine insufficiency (PEI)-related symptoms in patients with chronic pancreatitis, its mechanism of action is poorly understood. Recent studies suggest that the intestinal microbiota is associated with the pathogenesis of chronic pancreatitis. Therefore, we hypothesized that PERT exerts its effect by modifying the intestinal microbiota in addition to its presumed role in promoting fat and protein absorption. To explore the mechanism of action of PERT, we analyzed the intestinal microbiotas of two groups of mice treated with either pancrelipase or tap water by using 16S rRNA amplicon sequencing. The results revealed that the bacterial compositions of the pancrelipase-treated mice were significantly different from those of the control samples. Akkermansia muciniphila, a key beneficial bacterium in the intestinal tract, showed a higher relative abundance in the pancrelipase-treated samples than in the control samples. Lactobacillus reuteri, a widely used probiotic bacterium known to relieve intestinal inflammation, also showed a higher relative abundance in the pancrelipase-treated samples. These results suggested that PERT induces the colonization of beneficial bacteria, thereby contributing to the attenuation of PEI-associated symptoms in addition to improvement of the nutritional state.

Effect of the cholinesterase inhibitor donepezil on cardiac remodeling and autonomic balance in rats with heart failure.

In an earlier study we demonstrated the beneficial effect of direct vagal electrical stimulation on cardiac remodeling and survival. In the study reported here, we attempted to reproduce the effect of vagal enhancement through the administration of an acetylcholinesterase inhibitor, donepezil. A rat model of heart failure following extensive healed myocardial infarction was used. Compared to their nontreated counterparts, rats given donepezil (5 mg/kg/day) in their drinking water had a smaller biventricular weight (3.40 +/- 0.13 vs. 3.02 +/- 0.21 g/kg body weight, P < 0.05), and maximal rate of rise (3256 +/- 955 vs. 3822 +/- 389 mmHg/s, P < 0.05) and the end-diastolic value (30.1 +/- 5.6 vs. 23.2 +/- 5.7 mmHg, P < 0.05) of left ventricular pressure were improved. Neurohumoral factors were suppressed in donepezil-treated rats (norepinephrine 1885 +/- 1423 vs. 316 +/- 248 pg/ml, P < 0.01; brain natriuretic peptide 457 +/- 68 vs. 362 +/- 80 ng/ml, P < 0.05), and the high-frequency component of heart rate variability showed a nocturnal increase. These findings indicated that donepezil reproduced the anti-remodeling effect of electrical vagal stimulation. Further studies are warranted to evaluate the clinical usefulness of donepezil in heart failure.

Tranexamic acid-induced visual impairment in a hemodialysis patient.

We report a case of overdosage of tranexamic acid (TNA), which was suggested as the cause of visual impairment in a 56-year-old man. He had been undergoing chronic hemodialysis for 1 year, following 10 years of peritoneal dialysis. He had been hospitalized for an emergency operation for a bleeding ulcer of the stomach and duodenum. After the operation, he experienced a gradual loss of sight over about 1 week, although his general condition was good. He received intravenous injections of TNA as a hemostat during hospitalization for the operation. Two weeks after the operation he became blind. Retinography was flat and his visual field had become narrowed. On fluorescein angiography, microgranular hyperfluorescence, which indicated malfunction of the pigmented layer of the retina, was observed. No abnormality of the brain or the optic nerve was shown by magnetic resonance imaging. Concentrations of vitamins and trace minerals in the blood were within the normal ranges. Administration of vitamins A and B(12) did not improve his sight. However, discontinuation of TNA rapidly restored his sight, within a few days. He had received TNA once before because of bleeding ulcer, and his sight had been impaired at that time. Based on the repeated episodes, it was strongly suggested that an overdose of TNA in this dialysis patient caused the sight disturbance. Because TNA is metabolized by the kidney, caution is necessary when prescribing TNA for patients with renal failure.