Fumio Nanishi

Alpha Tocopherol Improves Focal Glomerulosclerosis in Rats with Adriamycin-lnduced Progressive Renal Failure

The effect of d-alpha-tocopherol on the progression of renal dysfunction was investigated in rats injected with adriamycin (ADR), a model of progressive glomerulosclerosis associated with the nephrotic syndrome. Treatment with d-alpha-tocopherol was started 1 day before or 1 day after ADR injections (BE-TOC or AF-TOC rats). When compared to rats without d-alpha-tocopherol treatment (ADR-CON rats), the serum total cholesterol and triglyceride levels were significantly lower in the BE-TOC and AF-TOC groups. In week 16, the LDL cholesterol level and the atherogenic index were both significantly lower in BE-TOC and AF-TOC rats than in ADR-CON rats. The urinary protein, serum creatinine, blood urea nitrogen, malondialdehyde, and systolic blood pressure levels as well as the glomerulosclerosis score were high in ADR-CON rats, and reduced in BE-TOC or AF-TOC rats. There were no significant differences in body weight and serum albumin between the three groups in week 16. It is concluded that d-alpha-tocopherol can improve hyperlipidemia and ameliorate glomerulosclerosis in rats with ADR-induced progressive renal failure. Thus, d-alpha-tocopherol may have the potential for clinical application to treat focal glomerulosclerosis.

Cerebral hemorrhage in patients on maintenance hemodialysis. CT analysis of 25 cases

Site of hematoma and clinical outcome in cerebral hemorrhage were analyzed in 25 maintenance hemodialysis (HD) patients and compared with those in 27 non-HD patients. Ganglionic-thalamic hemorrhage was found in 56% of HD and 74% of non-HD patients, lobar hemorrhage in 36% and 11%, respectively. Size of hematoma, expressed as a ratio (%) of hematoma area to entire brain on CT slice, was 6.5 +/- 4.2% (mean +/- SD) in HD, being significantly larger than that of 4.7 +/- 3.5% in non-HD patients (p less than 0.05). Mortality rate was 60% in HD patients, nearly twice as much as the 33% in non-HD patients. The hematomas were significantly larger in the death cases (8.4 +/- 3.7%) than the survivors on HD (3.6 +/- 3.1%, p less than 0.005). Likewise, the fatal cases in the non-HD group had bigger hematomas (6.9 +/- 4.3%) than the non-fatal ones (3.6 +/- 2.4%, p less than 0.05). Intraventricular hemorrhage (IVH) was found in 40% of HD and 44% of non-HD patients. Hematomas were significantly larger in HD patients with IVH (9.3 +/- 3.3%) than in those without IVH (4.6 +/- 3.7, p less than 0.005). Ninety percent of the HD patients with IVH but only 42% of non-HD patients died of hemorrhage. Hypertension was equally seen in HD (76%) and non-HD patients (74%). It is concluded that in HD patients cerebral hemorrhage is more severe in terms of hematoma size, association of IVH and clinical outcome. Chronic systemic heparinization might be responsible to the severity in HD patients.

Inhibitory effects of antihypertensive drugs on mesangial cell proliferation after anti-thymocyte serum (ATS) — induced mesangiolysis in spontaneously hypertensive rats

The effects of antihypertensive drugs on mesangial cell proliferation were studied in spontaneously hypertensive rats (SHR) with anti-thymocyte serum (ATS)-induced glomerulo-nephritis. Rats were treated with either enalapril (Group 1), nifedipine (Group 2), or reserpine + hydrochlorothiazide + hydralazine (Group 3), or were untreated (Group 4). The animals were sacrificed 2, 4 and 7 days after ATS injection and the glomerular cell number and degree of mesangial area expansion were examined. A marked, similar decrease in glomerular nuclear cell number (NC) due to severe mesangiolysis was observed in all of the groups on day 2. Thereafter, an increase in NC reflecting mesangial cell proliferation after mesangiolysis occurred in Group 4 on days 4 and 7. In Group 1 and 2, the NC was significantly smaller than that in Group 4 on days 4 and 7, indicating suppression of mesangial cell proliferation. In Group 3, however, the number of NCs did not differ from that in Group 4 on days 4 and 7, indicating a lack of such suppression by conventional antihypertensive drugs. The degree of mesangial area expansion (MS) showed the same pattern as mesangial cell proliferation. That is, the rapid increases in MS seen in Group 4 on days 4 and 7 were apparently suppressed in Groups 1 and 2, but not in Group 3. Our in vivo observations that both an angiotensin converting enzyme (ACE) inhibitor and a calcium channel blocker suppress mesangial cell proliferation and mesangial area expansion suggest that these agents have practical implications in the treatment of mesangial proliferative glomerular diseases through the suppression of excess mesangial cell proliferation.

Antigen-specific augmentation of delayed-type hypersensitivity by immune serum factor in mice

The serum from C3H/He mice immunized with chicken erythrocytes (CRBC) in complete Freunds adjuvant contained a factor able to augment delayed-type hypersensitivity (DTH) antigen specifically, when transferred into naive syngeneic recipient mice before their sensitization with CRBC. This activity in immune serum appeared on Day 4 and reached a peak on Day 8 after immunization, and was enhanced when donor mice were treated with cyclophosphamide (CY) 2 days before immunization. The ability of recipient mice to respond to this factor was enhanced by CY treatment of these mice 4 days before being transferred. This factor could be discriminated from conventional antibodies. Production of this factor in the serum donor and the expression of its activity in transferred recipient was mediated by a T-cell subset which showed a low degree of thymus dependency in ontogenic development.

Correction of serious iron overload in a chronic hemodialysis patient by recombinant human erythropoietin and removal of red blood cells: confirmation by follow-up liver biopsy.

A chronic hemodialysis case, a 46-year-old woman with secondary hemosiderosis induced by parenteral iron and blood transfusion due to a refractory anemia, was effectively treated with recombinant human erythropoietin and the removal of red blood cells. The cumulative dose of the iron removed was 5,712 mg. Plasma ferritin decreased from 8,290 to 2,203 micrograms/l during 18 months. Concomitantly, liver histology performed before and after the therapy revealed a prominent regression of the deposited iron.

Effects of fish oil rich in eicosapentaenoic acid on focal glomerulosclerosis of adriamycin-induced nephropathy in rats

Abstract The effects of fish oil rich in eicosapentaenoic acid (EPA) and those of purified EPA on the progression of focal glomerulosclerosis were investigated in adriamycin (ADR)-injected rats, a model of progressive chronic renal failure. Fish oil and purified EPA were administered through a gastric tube 1 week after the ADR injections. When compared with the control rats (ADR-CON), total cholesterol was significantly lower in the rats receiving fish oil (ADR-FO) or purified EPA (ADR-EPA) at week 8 ( P

Importance of early initiation of antihyperlipidemic treatment for the prevention of experimental progressive renal failure

Abstract This study was conducted to clarify the appropriate time to initiate antihyperlipidemic treatment in adriamycin (ADR)-induced progressive glomerular sclerosis in rats. Glomerular sclerosis was induced by ADR intravenous injection 2 mg/kg, twice, at a 20-day interval. The treatment of hyperlipidemia with lovastatin (subcutaneous injection 4 mg/d, 6 times a week) was started either 1 week (ADR-1W; 10 rats) or 8 weeks (ADR-8W; 10 rats) after the second ADR injection. The mean serum cholesterol levels were significantly reduced in both ADR-1W and ADR-8W rats compared with rats without any antihyperlipidemic treatment (ADR-CON; 10 rats). The urinary protein and serum creatinine values, blood pressure, and glomerular sclerosis score, which markedly increased in ADR-CON rats, decreased significantly in the ADR-1W rats at week 22. Blood pressure, urinary protein excretion, and the glomerular sclerosis score were significantly lower in the ADR-1W rats than in the ADR-8W rats at week 22. These results indicate that treatment of hyperlipidemia weakens the progress of glomerular sclerosis and that such treatment is more effective when begun in the early stages of glomerular disease.

A case of chronic renal failure with ruptured aneurysm of the sinus of Valsalva treated by open heart surgery

Valsalva洞動脈瘤破裂は大動脈基部のValsalva洞が下外方に拡大突出し破綻する比較的稀な疾患である. 我々は本症を合併した慢性腎不全症例を経験した. 患者は44歳男, 昭和55年IgA腎症と診断され, 腎機能が低下傾向にあった. 昭和61年4月突然胸部圧迫感・労作時呼吸困難が出現, 連続性心雑音も認められ, 腎機能も急激に低下したため, 当科に入院した. クレアチニンクリアランスは6-8ml/minと比較的保たれていたが, 腎機能低下による心不全の増悪, ならびに心臓カテーテル検査・大動脈造影・開心術による腎不全の増悪の可能性を考慮し, 早期に血液透析に導入し, 根治術を施行し良好な結果を得た.

A case of neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure.

経過中rhabdomyolysisを発症し,急性腎不全をきたした悪性症候群の1例を報告した.症例は精神分裂病に対して向精神薬にて長期治療中の48才,男性.胃潰瘍に対して,抗潰瘍薬(H2受容体阻害薬)を投与したところ3週後に下肢を中心とした筋強直と黒褐色尿が出現し,乏尿が持続したため当科に転院した.入院時, BUN, creatinine, CPK,血中ミオグロブリン,尿中ミオグロブリンの異常高値を認め, rhabdomyolysisによる急性腎不全と診断した.臨床経過からcalpipramine系の向精神薬に抗潰瘍薬のH2受容体阻害薬を併用したことが本症発症の誘因と考えられた.向精神薬で治療中の患者に対するH2受容体作動性抗潰瘍薬の使用には十分注意すべきである.