Induction of NGF synthesis in astrocytes by onjisaponins of Polygala tenuifolia, constituents of kampo (Japanese herbal) medicine, Ninjin-yoei-to.

The effect of a kampo medicine, Ninjin-yoei-to (NYT; Ren-shen-yang-rong-tang in Chinese) on nerve growth factor (NGF) secretion from the cultured rat astrocytes was examined in vitro. When rat embryo astrocytes were cultured in the presence of NYT for 24 h, the amount of NGF in the medium was significantly increased in a dose dependent manner. Among 14 kinds of component herbs in NYT, the roots of Polygala tenuifolia and roots of Panax ginseng extracts increased NGF levels from the astrocytes. Saponin fraction from the roots of P. tenuifolia enhanced the production of NGF, however phenolic glycoside fraction showed no effect. Onjisaponins A, B, E, F and G as major saponins of the root of P. tenuifolia strongly increased the NGF level, whereas ginsenosides Rb1 and Rg1 did not affect the NGF level. Onjisaponin F also induced ChAT mRNA level in rat basal forebrain cells. These results indicate the possibility that NYT and/or onjisaponins in P. tenuifolia may have potential therapeutic effects for the treatment of Alzheimer disease patients.

[A case of primary antiphospholipid antibody syndrome with severe nephrotic syndrome showing remarkable endothelial cell damage in the capillary lumen].

A 25-year-old woman complained of anasarca and was admitted to Sakura National hospital on the presumptive diagnosis of nephrotic syndrome with 10.7 g of 24-hour urinary protein. At first, lupus nephritis with antiphospholipid antibody syndrome was suspected because of prolongation of APTT, existence of lupus anticoagulant and elevation of serum anticardiolipin antibody titer (IgM) in addition to positive ANA, lymphocytopenia and the biologically false positive test for syphilis (BFPTS). On day 28 of hospitalization, renal biopsy findings revealed severe endocapillary cell damage, such as swelling and proliferation of endothelial cells, fragmentation and double contour of the basement membrane walls, which were located only in the capillary lumens with a few thrombi. Immunofluorescent micrography revealed the absence of specific immunoglobulin or complement deposit. Therefore, the diagnosis of lupus nephritis was negated as these findings were suggestive of characteristic glomerulopathy due to primary antiphospholipid antibody syndrome. She was treated initially with oral prednisolone 60 mg and intravenous infusion of heparin 20,000 units daily. Moreover, cyclophosphamide 750 mg was administered intravenously as pulse therapy on day 13 as her serum level of CH50 had fallen suddenly, and hemodialysis was necessary because her renal function had deteriorated and she was suffering from cough and orthopnea with overhydratin. After the combined therapy, BFPTS disappeared and APTT returned to the normal range: dialysis treatment was not required further after the 4th hemodialysis. Thereafter, renal function improved and complete remission of nephrotic syndrome was obtained. This patient was a case of primary antiphospholipid antibody syndrome in which endothelial cell damage was located exclusively in the capillary lumens and pulse cyclophosphamide therapy in addition to prednisolone and anticoagulant was effective. We present this instructive case to promote understanding of the pathogenesis of primary antiphospholipid antibody syndrome.

[Effect of hypercholesteremia on vascular endothelial function and albumin excretion rate in patients with diabetes mellitus].

Tissue-type plasminogen activator (tPA) is an endothelium-derived vasoactive substance which is released to the blood stream by exercise, blood occlusion, and desmopressin (DDAVP). The increased capacity of the plasma tPA level raised by these factors is thought to reflect in vivo endothelial function. On the other hand, endothelial dysfunction has been reported in patients with hypercholesteremia as well as in those with diabetes mellitus. Therefore, diabetic patients with hypercholesteremia were administered 5 mg of simvastatin daily for one month and plasma tPA responses evoked by DDAVP were examined before and after treatment for hypercholesteremia. While the treatment of simvastatin for one month significantly reduced serum cholesterol levels from 257 +/- 12 mg to 206 +/- 10 mg (no change in HbA1c was observed during the study), plasma tPA levels and % delta vWF (von Willebrand factor) following DDAVP infusion significantly increased from 11.4 +/- 1.2 ng/ml to 13.4 +/- 1.4 ng/ml and from 69.3 +/- 23.4% to 126.5 +/- 47.4%, respectively. However, neither increase in plasma levels of guanosine 3', 5'-cyclic monophosphate (cGMP) nor change in the depressive response of blood pressure was observed following DDAVP infusion after the treatment of simvastatin. In addition, no change in urinary albumin excretion rate was observed with the treatment of hypercholesteremia. Therefore, it was suggested that improvement in hypercholesteremia may ameliorate vascular endothelial dysfunction in diabetic patients with hypercholesteremia and that hypercholesteremia may enhance endothelial dysfunction in these patients.

Immunohistochemical study of human advanced glycosylation end-products (AGE) in chronic renal failure.

In patients with diabetic renal failure plasma advanced glycosylation end-products (AGE) levels are reported to be elevated and dialyzer of continuous ambulatory peritoneal dialysis (CAPD) is usually used with a high glucose concentration. Here, an immunohistochemical study on human AGE accumulation in vascular beds and peritonea of patients with chronic renal failure (CRF) or those on CAPD was undertaken. Further, the influence of aging was studied using AGE-specific monoclonal antibody. 1. AGE accumulation was observed in radial arterial walls (from vascular intima to smooth muscle layer) of diabetic patients with CRF. Even in some non-diabetic patients with CRF (n = 3/6), especially in those with a long history of CRF and dialysis treatment, similar positive staining was seen in vascular walls. No AGE staining was observed in any renal tissue of age-matched control subjects including tissue from patients with acute renal failure. 2. Although AGE accumulation was not seen in the peritonea of CRF patients with no prior CAPD therapy, it was seen in the mesothelial layers and in adjacent coarse connective tissues of peritonea from patients on CAPD (n = 6), even from as early as only 3 months of CAPD therapy. 3. AGE accumulation was observed in the vascular bed of the non-diabetic aged kidney with normal function, but not in that of the young kidney. Thus, AGE accumulation in the vascular bed may depend on the degree and term of renal impairment and on aging in addition to diabetes. AGE accumulation in the peritonea became positive following CAPD treatment, indicating that it might affect the efficiency of CAPD.

[Effects of methylprednisolone on functional recovery of stunned myocardium in dogs].

We investigated the effects of methylprednisolone (MP) on the time course of functional recovery of myocardium following 15 min of coronary artery occlusion and 1 h reperfusion (stunned myocardium) in morphine-urethane-alpha-chloralose-anesthetized dogs. Myocardial segmental shortening (%SS) in the subendocardium of ischemic areas was measured by sonomicrometry. MP (30 mg.kg-1 iv) was administrated 90 min before the occlusion period. Compared with the control group, %SS in the ischemic region was significantly (P < 0.05) greater in the MP-treated group during 15 to 60 min of the reperfusion period. There were no significant differences in other hemodynamic data between the control and MP-treated groups. In conclusion, it was shown that MP enhances the functional recovery of stunned myocardium.

[Clinico-pathological evaluation of mesangial IgA deposition of minimal change with nephrotic syndrome].

The case of IgA glomerulonephritis that shows minimal change with nephrotic syndrome is unusual. Thirteen patients of mesangial IgA deposition of minimal change with nephrotic syndrome (IgAMCNS) are discussed in comparison with twenty patients of non IgA deposition of minimal change with nephrotic syndrome (MCNS). On a common basis of hematuria, two groups are undistinguished. On a reaction pattern to steroid treatment, the former is based on IgA nephritis and the latter is based on minimal change with nephrotic syndrome. There is no difference in light microscopical findings between the two groups. Electron microscopically, the former suggests IgA nephritis and the latter suggests minimal change with nephrotic syndrome. In immunofluorescence, the former group is rare to show typical IgA glomerulonephritis. In conclusion, IgAMCNS is considered to be nephrotic syndrome with asymptomatic IgA deposit in mesangium.

Strong association of idiopathic membranous nephropathy with HLA-DR2 and MT1 in Japanese.

HLA-A, B, DR, and MT antigens were examined in 50 patients with idiopathic membranous nephropathy (IMN) by the standard microlymphocytotoxicity technique. The frequency of HLA-DR2 was significantly increased in the patients in comparison to the controls. Significant decreases in the frequencies were seen for HLA-DR4, DRw8 and DRw9 in the patients. The linkage disequilibrium between HLA-Bw52 and DR2 was noted in the controls, but it was significantly weaker in the patients. The frequency of MT1 was significantly higher, and that of MT3 was significantly lower in the patients as compared with the controls. The findings suggest that an immunological disturbance under the influence of genetic factors may confer a susceptibility to IMN.

Strong association between IgA nephropathy and HLA-DR4 antigen.

Although the etiology and pathogenesis of IgA nephropathy is not fully understood, it has been classified as an immune-complex induced glomerulonephritis caused by an immunological mechanism. Forty-two patients with primary IgA nephropathy underwent tissue typing for HLA-A, B, and DR antigens by the standard method using a microlymphocytotoxicity test. There was no significant correlation between HLA-A and B antigens and this disease. However, the frequency of HLA-DR4 was 57.1% in the patients with normal renal function, 85.7% in those with decreased renal function, 100% in dialysis patients, and 39.2% in the control group. It is statistically significant in the patients with renal dysfunction (corrected P less than 0.05). Our results suggest that the HLA system may play an important role in the occurrence and exacerbation of IgA nephropathy in the Japanese population.