Takuya Hanada

Effects of N-hexacosanol on nitric oxide synthase system in diabetic rat nephropathy.

We attempted to clarify the effects of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on nitric oxide synthase (NOS) in streptozotocin-induced diabetic nephropathy. After induction of experimental diabetes with streptozotocin, rats were maintained for 8 weeks with or without treatment by N-hexacosanol (8 mg/kg i.p. every day). Urinary albumin excretion, blood chemistry, immunoblot analysis, and real-time polymerase chain reactions (real-time PCR) of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were investigated. Although N-hexacosanol had no effects on serum glucose or insulin level, it normalized serum creatinine and urinary albumin excretion. N-hexacosanol was found to improve the diabetes-induced alterations in the eNOS, iNOS, and nNOS protein and their mRNA levels. Histologically, N-hexacosanol inhibited the progression to glomerular sclerosis. Our data suggest that N-hexacosanol improves diabetes-induced NOS alterations in the kidney, resulting in the amelioration of diabetic nephropathy.

Treatment with modified intravesical oxybutynin chloride for neurogenic bladder in children

OBJECTIVE We have previously reported that intravesical oxybutynin chloride with hydroxypropylcellulose (modified intravesical oxybutynin) is an effective therapeutic agent for patients with detrusor overactivity. In this study, we report on the efficacy, safety and side effects of modified intravesical oxybutynin administration in children with neurogenic bladder. PATIENTS Modified intravesical oxybutynin (1.25mg/5 mL, twice a day) was administered to four children (three males and one female) with neurogenic bladder (detrusor overactivity and/or low compliance bladder), who were previously unresponsive to or experienced intolerable side effects from oral medications. A cystometrogram was obtained before, 1 week after, and 1 year after the first intravesical instillation of modified oxybutynin. We also carefully observed anticholinergic side effects, occurrence of urinary tract infection and degree of incontinence during this treatment. RESULTS After 1 week, both cystometric bladder capacity and compliance were improved in all patients, and detrusor overactivity was undetectable in three of four patients. At 1 year, there was further improvement in bladder compliance in three patients, and detrusor overactivity was not observed in two patients. Significant improvement in the degree of incontinence was achieved. No systemic anticholinergic side effects were observed in any of the patients. One patient with vesicoureteral reflux discontinued the therapy after 2 months due to upper urinary tract infections. CONCLUSION Modified intravesical oxybutynin is an effective and relatively safe therapeutic option for children with neurogenic bladders.

Castleman disease in a child with short stature.

We report a 14‐year‐old boy with Castleman disease in this article. He complained of short stature, and his body height was 133.8 cm (<3rd percentile; z score −4.5). There was marked delay in the appearance of secondary sexual characteristics. He was found to have a remittent fever and a lower mid‐abdominal tumor. Blood test revealed microcytic hypochromic anemia, thrombocytosis, polyclonal hypergammaglobulinemia, hyperfibrinogenemia, and elevated erythrocyte sedimentation rate. The serum IL‐6 and C‐reactive protein levels were increased. The mass was found to be mixed hyaline vascular and plasma cell type of Castleman disease through a pathological examination. Lymph nodes affected by Castleman disease cause overproduction of IL‐6. It decreases IGF‐1, IGFBP‐3 and serum testosterone levels. As a result of tumorectomy, his short stature and delay in the development of secondary sexual characteristics were improved.

Treatment with Cyclohexenonic Long-Chain Fatty Alcohol Reverses Diabetes-Induced Tracheal Dysfunction in the Rat

In this study, we tried to elucidate the effect of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on tracheal dysfunction in diabetic rats. Diabetes was induced in 8-week-old male Sprague-Dawley rats by administering an intraperitoneal injection of 50 mg/kg streptozotocin. Non-diabetic control rats received an injection of citrate-phosphate buffer alone. Four weeks after the induction of diabetes, rats were randomly divided into 5 groups: age-matched non-diabetic control rats (group A); 4-week diabetic rats without N-hexacosanol treatment (group B); diabetic rats treated with vehicle (group C), and diabetic rats treated with N-hexacosanol at a dose of 2 or 8 mg/kg i.p. every day for the following 4 weeks (group D and group E, respectively; n = 6–8 animals in each group). Serum glucose and insulin levels were determined, as were the contractile responses induced by carbachol and 100 mmol/l KCl. The participation of M2 and M3 receptors was investigated in the trachea by real-time polymerase chain reaction (PCR), hematoxylin and eosin (HE) and immunohistochemical staining. Hypertrophy of airway smooth muscle was observed in diabetic rats, and was ameliorated by treatment with N-hexacosanol. Treatment with either 2 or 8 mg/kg N-hexacosanol did not alter diabetic rat status, i.e., body weight, serum glucose or serum insulin levels, but it significantly reversed the decrease in tracheal wall thickness and diabetes-induced hypercontractility in the rat trachea. In the immunohistochemical studies, muscarinic M2 and M3 receptors were expressed in the airway smooth muscle, the elastic fibers, the fibroblast and the surface of epithelium, and these expressions were not altered by either induction of diabetes or N-hexacosanol treatment. The expression of M3 muscarinic receptor mRNAs in the trachea tended to be increased by the induction of diabetes and normalized when treated with N-hexacosanol. Our data indicate that N-hexacosanol could reverse diabetes-induced hypercontractility in the rat trachea.

Mizoribine oral pulse therapy for a patient with polyarticular juvenile idiopathic arthritis

Mizoribine (MZR) is a novel immunosuppressive agent developed in Japan. It has been used in patients with renal transplantation, lupus nephritis, nephrotic syndrome and rheumatoid arthritis. 1 There are several reports on the effi cacy of MZR in patients with juvenile idiopathic arthritis (JIA). However, the clinical application of MZR for JIA remains low compared with that of methotrexate (MTX) or other disease-modifying antirheumatic drugs. Recently, some studies have shown that MZR oral pulse therapy may be of benefi t to a proportion of patients with fl areup of lupus nephritis as an alternative to an increased dose of corticosteroids. 2 The authors speculated that the mild clinical effi cacy of MZR may be attributable to low peak blood levels and that oral pulse therapy may achieve a suffi ciently high peak blood concentration of MZR. The authors of the present report, therefore, attempted MZR oral pulse therapy for a patient with JIA, and assessed its effi cacy and safety.