Comparison of glomerular and mesangial prostaglandin synthesis and glomerular contraction in two rat models of diabetes mellitus

Enhanced prostaglandin production is postulated to contribute to altered vascular reactivity and glomerular hyperfiltration in early insulin-deficient diabetes mellitus. Rats with streptozocin-induced diabetes (STZ-D) show glomerular hyperfiltration and develop renal disease. BB rats with genetic diabetes (BB-D) also hyperfilter but have only minor renal lesions. We therefore compared glomerular and mesangial prostaglandin E2 (PGE2) production and glomerular contractility in response to pressors as a reflection of in vitro vascular reactivity in these models. Glomeruli isolated from rats with 3 wk of STZ-D produced significantly more PGE2 under basal and ionophore A23187-stimulated conditions than those from control rats. Glomeruli from BB-D rats under basal and stimulated conditions, however, generated amounts of PGE2 that were comparable to either those of nondiabetic littermates or of normal Wistar rats. Mesangial cells cultured from glomeruli of STZ-D, BB-D, and control rats all had identical prostaglandin profiles judged by conversion of [14 C]arachidonic acid. They also produced comparable amounts of PGE2 under basal conditions and after stimulation with angiotensin II or A23187, as determined by radioimmunoassay. Planar surface area of glomeruli isolated from control rats showed a dose-dependent decrease in response to angiotensin II (10(-11)-10(-9) M). This response to angiotensin II was at least as great in glomeruli from STZ-D rats. Contraction of glomeruli from control and STZ-D rats was also comparable after vasopressin or norepinephrine. Similarly, glomeruli from BB-D and BB control rats contracted in a comparable fashion to angiotensin II and norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventriculosubcutaneous shunt for temporary treatment of neonatal post-IVH hydrocephalus: a technical note

A technique for temporary ventricular drainage using a subcutaneous pouch is described for use in neonatal hydrocephalus after intraventricular hemorrhage. The advantages include continuous, valve-regulated ventricular decompression, no exposed tubing, avoidance of electrolyte imbalance and of the loss of CSF, obviation of the need for repeated tapping, and the ability to convert to a peritoneal shunt on an elective basis.     

Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.     

Effects of herbal medicine Dai-Kenchu-to on anorectal function in children with severe constipation.

AIM: We administered the herbal medicine Dai-Kenchu-To (DKT) to children with severe chronic constipation or with severe constipation after surgery for anorectal malformations. We then objectively assessed the effect of DKT on anorectal function by manometric study in addition to using a clinical scoring system. PATIENTS AND METHODS: Ten children with severe chronic constipation and 5 children with severe constipation after surgery for anorectal malformations were assessed. These 15 children received 0.3 g/kg/day of DKT for periods ranging from 3 months to 1 year. We objectively assessed their bowel function, sphincter function and rectal reservoir function by anorectal manometry and clinical scoring. RESULTS: In 10 children with severe chronic constipation, the clinical score after administration of DKT (7.2 +/- 0.8) improved significantly compared with that before administration of DKT (4.6 +/- 2.9) (p < 0.02). The threshold sensation volume and the maximum tolerable volume after administration of DKT significantly (p < 0.05; p < 0.01) decreased (128 +/- 63 ml vs. 69 +/- 18 ml; 229 +/- 99 ml vs. 144 +/- 47 ml), and rectal compliance after administration of DKT also significantly (p < 0.05) decreased (12.4 +/- 10.9 ml/cmH(2)O vs. 4.7 +/- 3.9 ml/cmH(2)O). CONCLUSION: The present study demonstrated that DKT had a favorable clinical effect on severe constipation in children, and anorectal manometry showed an improvement in their rectal reservoir functions. It appears that the results were secondary to DKT-stimulated peristalsis of the intestine, which promoted regular bowel habits.