Increased urethral resistance by periurethral injection of low serum cultured adipose-derived mesenchymal stromal cells in rats.

OBJECTIVES: To evaluate the effects of a periurethral injection of low serum cultured adipose tissue-derived mesenchymal stromal cells (LASC) and to develop a new autologous cell therapy for stress urinary incontinence. METHODS: F344 rats were divided into three groups as based on the periurethral injection of LASC, GAX collagen or vehicle (control). At 2 and 4 weeks after injection, leak point pressure (LPP) was measured before and after transection of the pelvic nerves. For cell tracking, LASC of green fluorescent protein transgenic rats were injected into nude rats. RESULTS: At 2 weeks, both the LASC and collagen groups showed significantly higher LPP than the control group. At 4 weeks, the increase in LPP in the LASC group remained, whereas LPP in the collagen group decreased to baseline levels. In the absence of the urethral closure reflex after transection of the pelvic nerves, LPP in the LASC group was significantly higher than that in the other two groups. Histologically, the size of the urethral lumen was smaller in the LASC group than the collagen group. At 4 weeks, most of the LASC were positive for myogenic antigens including α-smooth muscle actin, desmin and calponin I. CONCLUSIONS: Periurethral injection of autologous LASC capable of myogenic differentiation made a greater contribution to the increase in urethral resistance than did the conventional collagen bulk injection. Thus, its use for treatment of stress urinary incontinence can be postulated.

Myoclonus after dextromethorphan administration in peritoneal dialysis.

OBJECTIVE: To report a case of myoclonus that developed after administration of dextromethorphan. CASE SUMMARY: A 64-year-old man was diagnosed with chronic renal failure due to diabetic nephropathy. The patient started on peritoneal dialysis 6 months before he was hospitalized. Two days before hospitalization, he developed cough and sputum and he visited an outpatient clinic, where dextromethorphan was prescribed. After taking a total of 30 mg of dextromethorphan, the patient developed myoclonus, tremor, agitation, slurred speech, and diaphoresis, which continued after he stopped taking the prescribed medicine. He visited an emergency department and was hospitalized for examination and treatment of myoclonus. DISCUSSION: As the patient's dialysis schedule was adequate, these symptoms were likely not due to uremia. The blood concentration of dextromethorphan (2.68 ng/mL) 60 hours after the 30-mg dose was higher than expected, and the blood concentration of dextrorphan, a metabolite, was lower than expected. We suspected that myoclonus was due to dextromethorphan-related symptoms induced by CYP2D6, which primarily metabolizes dextromethorphan. We analyzed the CYP2D6 gene for polymorphisms and identified CYP2D6 (*)1/(*)10. The patient had been taking metoprolol 40 mg/day for 2 years. The blood concentration of metoprolol 6 hours after administration was 13 ng/mL, which suggests that it was metabolized normally. Metoprolol has another metabolic pathway, via CYP2C19, and this may have led to its lack of accumulation. Moreover, metoprolol may have bound to active CYP2D6. Thus, affinity for CYP2D6, protein-binding rate, and lipid solubility may influence these drug interactions. Total scores for the Adverse Drug Reaction (ADR) probability scale and the Drug Interaction Probability Scale (DIPS) were 9 (highly probable) and 3 (possible), respectively. CONCLUSIONS: Myoclonus and other symptoms in this patient may have been caused by a prolonged high concentration of dextromethorphan due to CYP2D6 polymorphisms and drug interactions.